ANSWERS FOR STATE EXAM:

INTERNAL MEDICINE

ANSWERED BY:
Mariyam Aalaa
F. Fahudha Sayd
Ahmed Shabin M.S.
A. Anaa Hifaz L.
Hussein Abdikadir H.
A. Layal Mausoom
M. Baneen Waheed
Uqd Alzahraa Dawood

BATCH OF 2022
1. Pneumonia: definition, classification, etiology, pathogenesis. Main clinical presentations of
pneumonia. Treatment.
Infection of the lung parenchyma, in which consolidation of the affected part and a filling of the
alveolar air spaces with exudate, inflammatory cells, and fibrin is characteristic.
Definition: Lower respiratory tract infection - An acute illness (present for 21 days or less), usually
with cough as the main symptom, and with at least 1 other LRT symptom (fever, sputum
production, breathlessness, wheeze or chest discomfort or pain) and no alternative explanation (such
as sinusitis or asthma) (include pneumonia, acute bronchitis and exacerbation of chronic obstructive
airways disease)
Classification and etiology:
o Community Acquired:
• Usually Gram-Positive – (Strep pneumonia [90%])
• Occasionally Gram-Negative – (H.Influenzae)

o Hospital Acquired (Nosocomial - >48hrs POST Admission):

• Usually Gram-Negative – (Pseudomonas.aeruginosa, E.coli, Klebsiella)

o Atypical/Interstitial Pneumonia (“Walking Pneumonia”):

• Intracellular Bacteria – (Mycoplasma, Chlamydia, Legionella, Coxiella Burnetii)

o In Immunocompromised:
• Cytomegalovirus
• Pneumocystis jirovecii
• Fungal (Candida/Aspergillus)

Aspiration pneumonias more commonly manifest as infiltrates in the right middle or lower lobes
due to the larger calibre and more vertical orientation of the right bronchus

Types of Pneumonias - Based on Morphology:

o LOBAR-PNEUMONIA (Well Defined; One Lobe):
Aetiology:
• Typically Strep Pneumoniae (Gram Positive Diplococci)
• (Or Klebsiella in Aged)
Pathogenesis:
• Whole Lobe Involvement
• Exudate Within Alveolar SpacesàAlveolar Consolidation

Clinical Features:
• Symptoms:
o Abrupt onset High Fever + Chills
o Productive Cough (Occasionally Rusty Sputum &/or Haemoptysis)
o Pleuritic Chest pain + Pleural Rub.
• Signs:
o Usually Unilateral
o Exudation – Entire Lobe Consolidation
o Cardinal Pneumonia Signs –(Fever, Tachycardia, Tachypnoea)
BRONCHO-PNEUMONIA (Patchy; Multiple Lobes):
Aetiology:
• Secondary to Debilitating Diseases, Extremes of Age, or Post-Surgery: o Gram Pos - Strep
Pneumoniae, Staph Aureus Or Gram Neg - H. Influenzae
Pathogenesis:
• Patchy Areas of Acute Suppurative InflammationàPatchy Consolidation
• Basal Lower Lobes Common (Due to gravity – bacteria settle in the lower lungs)

*Clinical features same as lobar pneumonia

o ATYPICAL, INTERSTITIAL PNEUMONIA (“Walking Pneumonia”):

Aetiology:
• Typically Intracellular Bacteria:
o Mycoplasma, Chlamydia pneumonia, Legionella, Q-Fever (Coxiella burnetii)
• Or Viral:
o Influenza A/B, RSV – Respiratory Syncytial Virus, Corona Virus (SARS)
Pathogenesis:
• Interstitial Inflammation (NOT within the Alveolar Spaces)
• NB: 2o Bacterial Pneumonia (Typically Strep/Staph) may follow.
Clinical Features:
• Symptoms:
o Initial URTI ! SLOW Onset (Days-Weeks) o Symptoms more General & ‘Flu-like’.
o Few Localizing Symptoms:
" Often NO Cough
" Wheezing (Not seen in other pneumonias)
• Signs:
o No Physical Signs of Consolidation
o Unresponsive to Common Antibiotics

- Management:
- Admit to ICU? - CURB 65 (score <3 —> ICU)
- Confusion
- Uraemia
- Resp rate >30
- BP <90/60
- >65 yrs old
- Abx:
- Empirical
- Gram +ve- Amoxicillin/ Benz- Penicillin V/ Doxycycline/ Clarythromycin
- Gram -ve- Gentamicin/ Ceftriaxone
- Severe: + Meropenem/ Imipenem
- Fluids
- O2 if Sats <92%
- +/- ventilation
2. Differentiated antibiotic therapy for lung disease. Clinical pharmacology of antibacterial
drugs.
drugs adult doses indication side effects
3. Pneumonia: complications and their treatment. Outcomes. Periodic health examination of
patients with acute pneumonia. Prophylaxis.
o ARDS – Acute Respiratory Distress Syndrome:
Severely Impaired Gas ExchangeàHypoxia & Confusion.
Rx. Mechanical Ventilation and ICU.
o Lung Abscesses
o Pleuritis/Pleural Effusion/Empyema
Inflammation of the pleura (Strep Pneumoniae)
Blood Rich Exudate/Pus in Pleural Space
Rx. Drainage + MCS -> IV Antibiotics
o Septicemia, Meningitis
o Fibrosis, Scarring, Adhesions o Rarely Adenocarcinoma

Prevention
■ vaccine for influenza A and B annually for all ages ≥6 mo
■ pneumococcal polysaccharide vaccine (Pneumovax®) for all adults >65 yr and in younger
patients 24 mo of age and older at high risk for invasive pneumococcal disease (e.g. functional or
anatomic asplenia, congenital or acquired immunodeficiency)
■ pneumococcal conjugate vaccine (Prevnar-13®) for all children <5 yr, and for children and
adolescents at high risk for invasive pneumococcal disease who are 5-17 yr and who have not
previously received Prevnar-13® (CDC recommends giving Prevnar-13® to all adults at high risk
for invasive pneumococcal disease)
4. Atypical pneumonia: epidemiology, clinical picture, differential diagnostics, approaches to
treatment, antiepidemic measures, prophylaxis.
• Caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae & Legionella pneumophila.
• Atypical pneumonia typically has an indolent course (slow onset) and commonly manifests with
extrapulmonary symptoms.

Mycoplasma pneumonia
• Epidemiology:
◦ One of the most common causes of atypical pneumonia
◦ More common in school-aged children and adolescents
◦ Outbreaks most commonly occur in schools, colleges, prisons, and military facilities.
• Clinical features: Generalized papular rash, erythema multiforme, Nonproductive, dry
cough, dyspnea, auscultation often unremarkable. Common extrapulmonary features include
fatigue, headaches, sore throat, myalgias, and malaise.
• Diagnostics:
◦ Subclinical hemolytic anemia: associated with elevated cold agglutinin titers (IgM)
◦ Interstitial pneumonia, often with a reticulonodular pattern on chest x-ray
◦ Chest x-ray can show extensive pulmonary involvement in patients with mild
pneumonia.
• Treatment: macrolides, doxycycline, or fluoroquinolones

• Legionnaires' disease
• Incubation period: 2–10 days
• Clinical features:
◦ Fever, chills, headache
◦ Severe pneumonia:
◦ Unilateral lobar pneumonia
◦ Atypical pneumonia: dry cough which can become productive, shortness of
breath, bilateral crackles
◦ Relative bradycardia (uncommon)
◦ Diarrhea
◦ Neurological features, especially confusion, agitation, and stupor
◦ Failure to respond to beta-lactam monotherapy
• Imaging:
◦ Chest x-ray: Diffuse reticular opacities are commonly seen
◦ Chest CT: Bilateral or unilateral consolidative changes and/or ground-glass opacities.
• Treatment:
• If legionellosis is verified:
• Drug of choice: uoroquinolones (preferably levofloxacin, alternatively moxifloxacin) for 7–
10 days
• Initial parenteral treatment is recommended for all patients to avoid possibly poor
gastrointestinal absorption
• 2nd-line: macrolides (e.g., erythromycin/ azithromycin) for 3 weeks (IV at first, later orally)
• If patients are unresponsive to monotherapy, consider adding rifampin or tigecycline.
• Prophylaxis: Legionellosis is a noti able disease.
Course of action when contaminated water sources are detected in medical facilities:
Contaminated water systems should be disinfected . Use terminal tap water filters, especially for
high-risk patients (e.g., immunocompromised or the elderly).
fl
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Chlamydophila pneumoniae
• Transmission: person-to-person transmission of respiratory secretions via aerosols • Incubation
period: 3–4 weeks
• Clinical features:
- Sometimes asymptomatic
- General symptoms of atypical pneumonia
- Fever
- Non-productive cough Headache
- Myalgias
- Sometimes associated with pharyngitis and hoarseness
• Diagnostics:
- Chlamydia IgG and IgM serology
- NAAT: performed on the patient's nasopharyngeal swab or sputum
• Treatment:
- First-line treatment: oral azithromycin, clarithromycin
- Second-line treatment: oral doxycycline
• Complications:
- Asthma exacerbation Myocarditis Encephalitis
5. Acute bronchitis. Definition, etiology, pathogenesis, clinical features. Diagnosis and
differential diagnosis, treatment and prevention.
Acute bronchitis is inflammation of the tracheobronchial tree, commonly following an upper
respiratory infection that occurs in patients without chronic lung disorders
• Etiology
• 80% viral: rhinovirus, corona virus, adenovirus, influenza, parainfluenza, RSV
• 20% bacterial: S. pneumoniae
• Pathogenesis:
Acute Infection Of The Tracheobronchial Tree!Inflammation With Resultant Bronchial Edema
And Mucus Formation!Airway Obstruction!Cough/Wheeze
• Clinical Features:
• URTI Symptoms
• Productive Cough (Esp. @ Night)
• Wheezing
Subjective dyspnea results from chest pain or tightness with breathing, not from hypoxia.
Signs are often absent but may include scattered rhonchi and wheezing. Sputum may be clear,
purulent, or occasionally contain streaks of blood. Sputum characteristics do not correspond with a
particular etiology (ie, viral vs bacterial). Mild fever may be present, but high or prolonged fever is
unusual and suggests influenza, pneumonia, or COVID-19.
• Investigations
• Typically a Clinical Diagnosis
• CXR – (Rule out Pneumonia/CHF – if cough >3 weeks, abnormal vital signs,
localized chest findings)
• Spirometry + Bronchodilatory – (Rule out Asthma)
• Differential Diagnosis
• URTI/Asthma/Exac.COPD/Sinusitis/Pneumonia/Bronchiolitis/Pertussis
• Others: reflux esophagitis, CHF, bronchogenic CA, aspiration syndromes, CF,
foreign body
• Bacterial? - Higher Fevers + Excessive Purulent Sputum.
• Management
• Symptomatic Relief: Paracetamol, Rest, Fluids (3-4 L/ Day When Febrile),
Humidified O2.
• Bronchodilators [Salbutamol] – (May ↓Symptoms)
• Antibiotics [Doxycycline / Erythromycin] If: Elderly/Comorbidities/Suspected
Pneumonia.
7. Chronic obstructive pulmonary disease. Definition. Etiology, pathogenesis.
Classification.Clinical variants (emphysematous and bronchitical).Complications. Therapy,
depending on stages (basic therapy with bronchodilators, corticosteroids). Preventing
exacerbations.
Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease
that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway
and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.

Aetiology: significant exposure to noxious particles or gases and influenced by host factors
including genetics, airway hyper responsiveness and poor lung growth during childhood.
RISK factors: tobacco smokes, indoor/outdoor air pollution, occupational exposures, genetic
factors, age and sex ( older and female> ), socioeconomic status, chronic bronchitis, frequency of
respiratory infections in childhood.
1. Conditions With The Lumen - (Eg. Excessive Mucous)
2. Conditions Within The Wall of the Airway:
" Inflammation & Oedema (Chronic Bronchitis or Asthma)
" Bronchoconstriction (Asthma)
3. Conditions Outside The Airway:
" Destruction of Lung Parenchyma (eg. Emphysema)
" Localised Compression of Airway
" Peribronchial Oedema

- Clinical Features:
o Type A – Pinker ‘Puffer’ – (Emphysema):
" Normal Blood Gasses
" Little/No Cough
" Breathless
" Quiet Breath Sounds
" No Peripheral Oedema
o Type B – Blue ‘Bloater’ (Chronic Bronchitis):
" Low O2 + High CO2 + Cyanosis!Blue (hence name)
" Chronic Productive Cough
" Breathless
" Loud, Abnormal ‘Crackling’ Breath Sounds (“Crepitations”/”Rales”)
" May Have Peripheral Oedema
- Complications of COPD:
o Acute Infective Exacerbations
o
o Cor Pulmonale – (RV-Failure 2 to Pulmonary HTN):
o Polycythaemia (Due to Hypoxia) ! high Hb
o Bronchiectasis
o End Stage Lung Disease (due to extensive lung fibrosis) ! Palliative O2 Therapy. o Lung
Cancer (Indirectly – due to smoking)
8. Multiple bronchiectasis: etiology, pathogenesis, clinical picture, complications. Diagnostics
and treatment.
Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and
inflammation.
Diffuse bronchiectasis develops most often in patients with genetic, immunologic, or anatomic
defects that affect the airways.
A Result of Chronic or Severe Necrotizing Lung Infections : o Often seen in:
" Cystic Fibrosis
" Post-infectious Conditions
" Bronchial Obstruction (Eg tumour/foreign bodies)
" HIV
Pathogenesis:
o Chronic AND/OR Severe Bacterial Lung Infections!
" !Bronchial Inflammation, (Often with Necrosis)
" !Damage to Airway Walls (Destruction of Supporting Smooth Muscle & Elastic Tissues)
" !Fibrosis & Eventually Dilation of Airways.
!Irregular, Permanently Dilated Bronchus filled with Pus.

Signs and Symptoms:

• chronic cough,copious purulent sputum (but 10-20% have dry cough), dyspnea, fatigue, chronic
rhinosinusitis, hemoptysis (can be massive), recurrent pneumonia, local crackles (inspiratory and
expiratory), rhonchi, wheezes
• maybe difficult to differentiate from chronic bronchitis

Dyspnea and wheezing are common, and pleuritic chest pain can develop. In advanced cases,
hypoxemia and right-sided heart failure due to pulmonary hypertension may increase dyspnea.

Acute exacerbations are common and frequently result from new or worsened infection.
Exacerbations are marked by a worsening cough and increases in dyspnea and the volume and
purulence of sputum. Low-grade fever and constitutional symptoms (eg, fatigue, malaise) may also
be present.

Complications:
" Pneumonias (Staph/Strep/Enterococci/Haemophilus/Pseudomonas)
" Empyema
" Septicaemia
" Meningitis
As the disease progresses, chronic inflammation and hypoxemia cause neovascularization of the
bronchial (not the pulmonary) arteries. Bronchial artery walls rupture easily, leading to hemoptysis,
which can be massive and life threatening. Other vascular complications include pulmonary
hypertension due to vasoconstriction, arteritis, and sometimes shunt from bronchial to pulmonary
vessels.
Colonization with multidrug-resistant organisms can lead to chronic, low grade airway
inflammation. This inflammation can progress, causing recurrent exacerbations and worsen airflow
limitation on pulmonary function tests.
Dx:
• History and physical examination
• Chest x-ray (Bronchial Markings out towards Periphery)
• High-resolution chest CT
• Pulmonary function tests for baseline evaluation and monitoring disease progression
• Sputum culture for bacteria and mycobacteria to determine colonizing organisms
• Specific tests for suspected causes
Chronic bronchitis may mimic bronchiectasis clinically, but bronchiectasis is distinguished by
increased purulence and volume of daily sputum and by dilated airways shown on imaging studies.

Treatment:
Physiotherapy – (Postural Drainage & Cupping)
o If Sx of Infection – Anti-Pseudomonal Antibiotics ( Tobramycin)
- Prevention of exacerbations with regular vaccinations and sometimes suppressive antibiotics
- Measures to help clear airway secretions
- Bronchodilators and sometimes inhaled corticosteroids if reversible airway obstruction is present
- Antibiotics and bronchodilators for acute exacerbations
- Sometimes surgical resection for localized disease with intractable symptoms or bleeding
- Lung transplantation in carefully selected patients who have advanced disease despite maximal
therapy
9. Bronchial asthma: definition, etiology, pathogenesis, classification, clinical picture.
Diagnostics. Rapid relief of asthma of different levels of severity.
Asthma is a common and potentially chronic disease that causes symptoms such as wheezing, SOB,
chest tightness and cough that vary overtime in their occurrence, frequency and intensity. These
symptoms are associated with variable expiratory airflow, i.e. difficulty breathing air out of lungs
due to bronchoconstriction, airway wall thickening and increased mucus.

Factors affecting the risk of BA can be divided into factors that cause the development of the
disease (mainly internal factors, primarily heredity), and factors that provoke symptoms (mainly
external factors).
The main factors affecting the development and manifestation of BA:

(a) Internal factors:

1. genetic (genes predisposing to atopy - increased production of allergen-specific IgE antibodies
and genes predisposing to bronchial hyperreactivity)
2. obesity (increased production of the leptin mediator increases the likelihood of BA)
3. gender (up to 14 years old, the prevalence of BA in boys is twice as high, in adult BA is more
common in women).

b) external factors:
1. allergens: indoors (home dust mites, pet hair, cockroach allergens, mold and yeast mushrooms)
and external (plant pollen, etc.)
2. infections (mainly respiratory viral, less often parasitic)
3. professional sensitizers
4. tobacco smoking (both active and passive)
5. indoor and outdoor air pollution
6. nutrition - in breastfed children, the frequency is lower than in children on artificial feeding

The main factors provoking the exacerbation of AD: 1) domestic and external allergens; 2) indoor
pollutants and external pollutants; 3) respiratory infections; 4) physical activity and
hyperventilation; 5) changes in weather conditions; 6) sulfur dioxide; 7) food, food additives; 8)
some medicines; 9) excessive emotional stress;

Narrowing of the airways is often caused by abnormal sensitivity of cholinergic receptors, which
cause the muscles of the airways to contract when they should not. Certain cells in the airways,
particularly mast cells, are thought to be responsible for initiating the response. Mast cells
throughout the bronchi release substances such as histamine and leukotrienes, which cause the
following:
Smooth muscle to contract
Mucus secretion to increase
Certain white blood cells to move to the area
Eosinophils, release additional substances, contributing to airway narrowing.
Classification:
Asthma severity:
Intermittent: The person's symptoms occur two days per week or less and do not interfere
with activities of daily life
Mild persistent: The person's symptoms occur more than twice per week but only slightly
limit activities of daily life
Moderate persistent: The person's symptoms occur daily and limit some activities of daily
life
Severe persistent: The person's symptoms occur throughout the day and interfere
excessively with activities of daily life.
Most severe form is status asthmaticus

Control is classified as
Well controlled: Symptoms occur twice per week or less often
Not well controlled: Symptoms occur more than twice per week but not every day
Very poorly controlled: Symptoms occur daily

Clinical picture and diagnosis:

Typical symptoms are wheeze, shortness of breath, chest tightness, cough:
• People with asthma generally have more than one of these symptoms,
• The symptoms often occur or are worse at night or on waking,
• Symptoms are often triggered by exercise, laughter, allergens or cold air,
• Symptoms often occur with or worsen with viral infections.

Evidence of variable expiratory airflow limitation

• At least once during the diagnostic process (e.g. when FEV1 is low), document that the FEV1/
FVC ratio is below the lower limit of normal.
• Document that variation in expiratory lung function is greater than in healthy people. For example,
excess variability is recorded if:
o FEV1 increases after inhaling a bronchodilator by >200 mL and >12% of the pre-bronchodilator
value (or in children, increases from the pre-bronchodilator value by >12% of the predicted value).
This is called significant bronchodilator responsiveness or reversibility.
o Average daily diurnal PEF variability* is >10% (in children, >13%)
o FEV1 increases by more than 12% and 200 mL from baseline (in children, by >12% of the
predicted value) after 4 weeks of anti-inflammatory treatment (outside respiratory infections).
• The greater the variation, or the more times excess variation is seen, the more confident you can
be of the diagnosis of asthma.
• Testing may need to be repeated during symptoms, in the early morning, or after withholding
bronchodilator medications.
• Significant bronchodilator reversibility may be absent during severe exacerbations or viral
infections. If significant bronchodilator reversibility is not present when it is first tested, the next
step depends on the clinical urgency and the availability of other tests.
10. Pleurisy: etiology, pathogenesis, classification, main clinical presentations according to the
character of effusion, diagnostics. Treatment.
Pleurisy is an inflammation of pleura with the formation of fibrin on their surface and/or
accumulation of exudate of various nature in the pleural cavity.

Etiology of pleurisy:
1. Infectious agents: a) mycobacteria tuberculosis b) bacteria (pneumococcus, streptococcus,
staphylococcus, hemophilic bacillus, clebsiella, etc.); c) rickettsia; d) mycoplasma; e
2. Non-communicable causes: tumors (acute leukemia, lymphogranulomatosis, lymphosarcoma);
rheumatic diseases (SLE, dermatomyositis, scleroderma); closed chest injuries; TELA infarctions;
Dressler syndrome in myocardial infarction; acute pancreatitis; uremia, etc.

Pathogenesis of infectious pleurisy.

1. Penetration of the pathogen into the pleural cavity in one of the following ways:
a) directly from infectious foci in pulmonary tissue
b) lymphogenic
c) hematogenically
e) directly from the external environment in case of chest injuries and operations

2. The pathogen causes the development of an inflammatory process in the pleura —> dilation of
lymphatic capillaries, increased vascular permeability, moderate effusion into the pleural cavity.

3. the liquid part of the effusion is absorbed and fibrin (fibrinose pleurisy) that fell out of the
exudate remains on the surface of the pleural leaves.

4. With a high intensity of the inflammatory process, exudative pleurisy develops:

5. With the reverse development of the pathological process, the resorption rate begins to gradually
prevail over the exudation rate and the liquid part of the exudate dissolves. Fibrinous overlays on
the pleura are scarred, mooring is formed that can cause more or less significant obliteration of the
pleural cavity.

Pathogenesis of some non-communicable pleurisy.

a) carcinomatous pleurisy: impaired lymph circulation
b) aseptic traumatic pleurisy: pleura's reaction to spilled blood, as well as its direct damage in
injury pleural effusion
c) uremic pleurisy: irritation of the pleura by secreting uremic toxins
d) enzymatic pleurisy: damaging effect on pleuropancreatic enzymes entering the pleural cavity
through lymphatic vessels through the diaphragm pleural effusion, etc.
Classification of pleurisy:
1. By etiology: infectious and non-communicable

2. By the nature of the pathological process: dry (fibrinous) pleurisy and exudative pleurisy

3. According to the nature of effusion in exudative pleurisy: a) serous b) serous-fibrinous c)

purulent d) rotting e) hemorrhagic, etc.

4. Downstream: acute, subacute, chronic

5. By distribution and localization: diffuse and sump (upper, paracostal, bone diapragm, diaphragm,
paramediastinal, intershared).

The main clinical manifestations of dry pleurisy.

1. Subjectively, complaints about:
a) chest pain on the side of the lesion, which is more often localized in the anterior and lower lateral
parts, appears with deep inhalation, sharply increases with coughing, when the torso is tilted to a
healthy side (Shepelman-Degio symptom), laughter, sneezing.
b) for increased body temperature, general weakness, transient low-intensity pain in muscles, joints,
headache (intoxication syndrome).

2. Objectively:
a) forced position: the patient lies on the sore side (immobilization of the chest reduces irritation of
the parietal pleura), less often on a healthy
b) rapid superficial breathing (with such breathing, less pain is expressed)
c) the affected half of the chest lags behind in breathing due to pain
d) palpation: at the location of inflammation at hand when breathing, there is a crunch of snow
(noise of friction of the pleura)
e) percussion - clear pulmonary sound
f) auscultation: in the projection of the localization of inflammation - the noise of friction of the
pleura, which is heard when inhaling and exhaling and resembles the crunch of snow under your
feet, the creaking of new skin or the rustle of paper, silk.

Diagnosis of dry pleurisy:

1. Lung radiography: high standing of the diaphragm dome on the affected side and its remaining in
deep breathing; restriction of mobility of the lower pulmonary edge; slight clouding of part of the
pulmonary field.
2. Ultrasound examination: thickening of the pleura with an uneven, wavy contour, increased
echogenicity, homogeneous structure.
3. Laboratory data: inflammatory changes in UAC, LHC.
The main clinical manifestations of exudative pleurisy.
1. Subjectively, complaints about:
a) pain acute, intense in fibrinous pleurisy, weaken or completely disappears as exudative pleurisy
develops
b) feeling of heaviness in the chest, shortness of breath (with a significant amount of exudate)
c) dry cough of reflex genesis
e) increased body temperature, sweating, headache, anorexia, etc. (intoxication syndrome)

2. Objectively:
a) forced position - patients lie on the sore side, which limits the displacement of the mediastinum
in a healthy direction, and allows the healthy lung to participate more actively in breathing, with
very large effusions, patients occupy a half-sitting position
b) cyanosis and swelling of cervical veins (a large amount of fluid in the pleural cavity complicates
the outflow of blood from the cervical veins)
c) shortness of breath (inspiration rapid and superficial)
d) increase in chest volume on the side of the lesion, smoothness or swelling of intercostal spaces
e) restriction of breathing excursions of the chest on the side of the lesion
e) swelling and thicker skin fold in the lower chest on the side of the lesion compared to the healthy
side (Wintrich symptom)
g) percussion symptoms of fluid presence in the pleural cavity:
1. blunt percussion sound above the effusion zone (an increase in the level of dulling by one edge
corresponds to an increase in the amount of liquid by 500 ml).

2. dulling of the percussion sound on a healthy side in the form of a rectangular Raufus triangle.
3. Clear pulmonary sound in the Garland right triangle zone on the sore side. The hypotenuse of this
triangle is the part of the Sokolov-Ellis-Damuazo line starting from the spine, one leg is the spine,
and the other is a line connecting the top of the Sokolov-Ellis-Damousoiso line with the spine
4. tympanic sound zone (Skoda zone) - located above the upper border of the exudate, has a height
of 4-5 cm. In this zone, the lung is subjected to some compression, the walls of the alveoli subside
and relax, their elasticity and ability to oscillate decreases, as a result, during lung percussion in this
zone, air oscillations in the alveoli begin to prevail over the oscillations of their walls and the
percutor sound
5. in left-sided exudative pleurisy, the Traube space disappears (tympanitis zone in the lower parts
of the left half of the chest caused by the gas bubble of the stomach)
6. shifting the boundaries of the heart to a healthy direction
h) voice jitter over the effusion area is sharply weakened
i) auscultatively vesicular breathing over the exudate area is sharply weakened or not listened to;
with a large effusion and severe compression of the lung, muted bronchial breathing begins to be
heard.
Diagnosis of exudative pleurisy.
1) Lung radiography reveals an amount of fluid of at least 300-400 ml, and in lateraloscopy
(radiography performed in a horizontal position on the sore side) - at least 100 ml; characterized by
intense homogeneous darkening with an oblique upper boundary going down and inside;
displacement of mediastinum in a healthy direction.
2) Ultrasound examination: a small amount of effusion looks in video-shaped ekhonegative areas;
as the amount of liquid increases, the echonegative space expands, maintaining its wedge-shaped
shape, pleural leaves are extended by accumulated liquid, pulmonary tissue (homogeneous
echogenic formation) shifts to the root.
3) Pleural puncture: assess the physical, chemical properties of the resulting liquid, perform its
cytological, biochemical, bacteriological examination.
4) Laboratory data: inflammatory changes in UAC, LHC

Principles of treatment.
1. Etiological treatment (effects to the underlying disease): in case of pleuriitis, which complicates
the course of pneumonia, abscesses, - AB taking into account the sensitivity of infectious agents; in
tuberculosis pleurisy - long-term anti-tuberculosis drugs (isoniazid, pyrazinamide, rifampicin,
streptomycin, ethambutol); in case of allergic etiology or in the presence of systemic diseases -
prednisolone oral 20-30 mg/day with a subsequent reduction in the daily dose and withdrawal of the
drug.
2. Pathogenetic therapy: NSAIDs, desensitizing drugs (10% calcium chloride 1 tablespoon 4-5
times/day).
3. In exudative pleurisy - evacuation of exudate according to indications (a large number of
effusions that causes shortness of breath; displacement of the mediastinum; dulling of the
percustoon sound to the 2nd rib along the anterior chest wall). No more than 1.5 liters are evacuated
at a time to avoid collapse. After the evacuation of the exudate, AB, GCS, proteolytic enzymes are
injected into the pleural cavity.
4. Diet therapy (rich in vitamins and proteins, restriction of salt and water), general tonic treatment,
after the subsidence of acute phenomena - chest massage, breathing gymnastics.
11. Alveolitis. Idiopathic pulmonary fibrosis, exogenous (toxic) alveolitis. The clinical picture,
diagnosis, treatment.
Alveolitis is inflammation of the alveoli, the small air sacs of the lungs responsible for breathing

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing
interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs,
and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia
(UIP). It causes lung scarring, which, over time, results in reduced oxygen intake.

Most patients present with a gradual onset (often >6 mo) of exertional dyspnea and/or a
nonproductive cough. Approximately 5% of patients have no presenting symptoms when idiopathic
pulmonary fibrosis is serendipitously diagnosed.
Associated systemic symptoms that can occur but are not common in idiopathic pulmonary fibrosis
include the following:
• Weight loss
• Low-grade fevers
• Fatigue
• Arthralgias
• Myalgias
The diagnosis of IPF requires the following [3] :
• Exclusion of known causes of interstitial lung disease
• Presence of the high-resolution computed tomography (HRCT) pattern of UIP
• Specific combinations of HRCT patterns and histopathology patterns in patients subjected to
lung tissue sampling

Physical examination in patients with idiopathic pulmonary fibrosis may reveal the following:
• Fine bibasilar inspiratory crackles (Velcro crackles): Noted in most patients
• Digital clubbing (25-50%)
• Pulmonary hypertension at rest (20-40%) [4] : Loud P2 component of the second heart sound,
a fixed split S2, a holosystolic tricuspid regurgitation murmur, pedal edema
• High-resolution computed tomography (HRCT) scanning: Sensitive, specific, and essential
for the diagnosis of idiopathic pulmonary fibrosis. Demonstrates patchy, peripheral,
subpleural, and bibasilar reticular opacities.

• Chest radiography: Abnormal findings but lacks diagnostic specificity. Demonstrate

peripheral reticular opacities (netlike linear and curvilinear densities) predominantly at the
lung bases, honeycombing (coarse reticular pattern), and lower lobe volume loss
• Surgical lung biopsy (via open lung biopsy or video-assisted thoracoscopic surgery [VATS]
[preferred]): Best sample for distinguishing usual interstitial pneumonia from other idiopathic
interstitial pneumonias.

management strategies include the following:

• Encourage tobacco users to quit and offer pharmacotherapy as needed.
• Prescribe oxygen therapy in patients with hypoxemia at rest or with exercise (partial pressure
of oxygen [PaO2] < 55 mmHg or an oxygen saturation by pulse oximetry [SpO2] < 88%). The
goal is to maintain an oxygen saturation of at least 90% at rest, with sleep, and with exertion.
• Vaccinate patients against influenza and pneumococcal infection.
Surgery
• Lung transplantation: Refer all patients with diagnosed or probable idiopathic pulmonary
fibrosis for lung transplantation evaluation regardless of the vital capacity, unless there are
contraindications. [9]
Pharmacotherapy
• Tyrosine kinase inhibitors (eg, nintedanib)

• Antifibrotic agents (eg, pirfenidone)

• Treatment of idiopathic pulmonary fibrosis exacerbation

Hypersensitivity pneumonitis is a type of inflammation in and around the tiny air sacs (alveoli) and
smallest airways (bronchioles) of the lung caused by a hypersensitivity reaction to inhaled organic
dusts or, less commonly, chemicals.
Many substances can cause hypersensitivity reactions in the lungs. Organic dusts that contain
microorganisms or proteins, and chemicals, such as isocyanates, may cause hypersensitivity
pneumonitis. Farmer's lung, which results from repeated inhalation of heat-loving (thermophilic)
bacteria in moldy hay, is a well-known example of hypersensitivity pneumonitis. Bird fancier's lung
is another example. It occurs when dust from the feathers of birds (either on living birds or in
pillows and comforters) is inhaled.

The diagnosis of hypersensitivity pneumonitis is based partly on symptoms, the clinical features,
identification (if possible) of the dust or other substance causing the problem, as determined by
what the person says, an analysis of the workplace by industrial hygiene specialists, the presence of
antibodies on a blood test, or a combination.

may suspect the diagnosis based on chest x-ray findings.

computed tomography (CT) of the chest is needed to help confirm the diagnosis.
Results of pulmonary function tests—which measure the lungs' capacity to hold air and their ability
to move air in and out and to exchange oxygen and carbon dioxide—are used to assess how well the
lungs work and may help support a diagnosis of hypersensitivity pneumonitis.

Treatment: Corticosteroids or immunosuppressants

People who have an acute episode of hypersensitivity pneumonitis usually recover if further contact
with the substance is avoided. If the episode is severe, corticosteroids, such as prednisone, reduce
symptoms and may help reduce severe inflammation. Prolonged or recurring episodes may lead to
irreversible disease and progressive disability and requires long-term immunosuppression
12. Acute and chronic purulent destruction of the lungs, lung abscess, lung gangrene. Features
of pathogenesis, course, clinical manifestations. Diagnostic approach. Choosing the place of
treatment of patients, features of treatment.
Lung abscess is a limited purulent-destructive process accompanied by the formation of single or
multiple purulent cavities in pulmonary tissue.

Lung gangrene is a common purulent-necrotic process in pulmonary tissue that has no clear
boundaries.

Classification of lung abscesses:

I. Purulent abscesses
a) on pathogenesis: aerogenic aspiration, hematogenic-embolic, traumatic, septic
b) downstream: acute, chronic
c) by localization: central; peripheral (single, multiple with an indication of the share and segment)
d) due to the presence of complications: uncomplicated and complicated (empyema,
pionneumothorax, bleeding, acute respiratory distress syndrome of the lungs, sepsis, chest
phlegmon, etc.)

II. Gangrenous abscesses (with distribution along the flow, localization and complications, like
purulent abscesses) are an intermediate form of infectious lung destruction, which differs from
gangrene by less extensive and more prone to detimitation by pulmonary tissue death.

III. Common gangrene.

Etiology of lung abscesses.

1. Bacteria (in 60-65% - non-spore-forming obligate anaerobes: bacteroids, fusobacteria, anaerobic
cocci, in 30-40% - Staphylococcus aureus, streptococcus, clebsiella, blue bacillus, etc.)

2. Mushrooms, protozoa and other infectious agents (in very rare cases).
Predisposing factors: smoking, chronic bronchitis, bronchial asthma, diabetes mellitus, epidemic
flu, alcoholism, maxillofacial trauma, long stay in the cold, etc.

Pathogenesis of lung abscesses:

Penetration of the pathogen into the pulmonary parenchyma is transbronchial, less often
hematogenic, lymphogenic, by spreading from neighboring organs and tissues, directly from the
external environment in penetrating chest injuries with the development of:

a) abscess - limited inflammatory infiltration with purulent melting of pulmonary tissue and the
formation of a decay cavity surrounded by a granulation shaft; after 2-3 weeks, the purulent focus
breaks into the bronchi (drained), and the walls of the cavity subside to form a scar

b) gangrene - against the background of inflammatory infiltration of the lung parenchyma, exposure
to microorganism products and vascular thrombosis, extensive necrosis develops without clear
boundaries; many foci of decay are formed in necrotized tissue, which are partially drained through
the bronchus
Clinical manifestations of lung abscess.
a) before the breakthrough of pus in the bronchi:
1. Subjectively:
- pronounced toxication syndrome: high body temperature, chills, pouring sweats
- dry cough with chest pain on the side of the lesion
- difficulty breathing or shortness of breath (due to the impossibility of deep breath or early
respiratory failure)
2. Objectively:
- pale skin, sometimes cyanotic blush on the face, more pronounced on the side of the lesion
- forced position (more often on the sick side)
- pulse is faster, sometimes arrhythmic; heart tones are muted; BP with a tendency of hypotension
- percustotor - intensive shortening of sound over the focus of lesion
- auscultative - vesicular breathing weakened with a hard tint, sometimes bronchial breathing

b) after a breakthrough in the bronchus:

1. Subjectively:
- cough attack with the release of a large amount of purulent, often sting, wet (100-500 ml)
- with good drainage of the abscess, well-being improves, temperature and other signs of
intoxication decrease; with poor drainage - body temperature remains high, characterized by chills,
sweats, cough with poor separation of stinking sputum, shortness of breath, loss of appetite, etc.
2. Objectively:
- percuteurous - shortening of pulmonary sound over the focus of lesion, restrictive shade (due to
the presence of air in the cavity)
- auscultative - fine-bubble wheezing
After bronchi breakout, the symptoms of the abscess are reduced within 6-8 weeks. In an
unfavorable course, there is no tendency to cleanse the inflammatory necrotic focus, and various
complications appear: pionneumothorax, pleura empyema, respiratory distress syndrome, infectious
and toxic shock, sepsis,
pulmonary bleeding.

Diagnosis of lung abscess.

1. Lung radiography: before the breakthrough of the abscess in the bronchi - infiltration of
pulmonary tissue, more often in segments II, VI, X of the right lung, after a breakthrough in the
bronchi - enlightenment with a horizontal level of liquid.

2. Laboratory data:
a) leukocytosis, rod-nuclear shift, toxic neutrophil granularity, significant increase in ESR
b) moderate albuminuria, cylindrulum, microhematuria.
c) increase in the content of sialic acids, seromukoid, fibrin, haptoglobin, 2- and -globulins, in the
chronic course of abscess - a decrease in albumin levels.
d) general analysis of sputum: purulent sputum with an unpleasant smell, when standing it is
divided into two layers, in microscopy - leukocytes in large quantities, elastic fibers, hematoidin
crystals, fatty acids.
Clinical manifestations of lung gangrene.
a) before breaking through the bronchi:
- severe general condition of the patient: hectic body temperature, chills, weight loss, lack of
appetite, tachycardia, shortness of breath
- chest pain on the side of the lesion, increasing when coughing
- percutorously over the affected area, blunt sound and soreness (Kryukov-Sauerbruh symptom),
when pressed by a stethoscope on the intercostal, a cough appears in this area (Kassling's
symptom); with the rapid decay of necrotized tissue, the dulling zone increases,
- auscultative breathing over the affected area is weakened vesicular or bronchial.

b) after a breakthrough in the bronchus:

- symptoms of intoxication remain quite pronounced
- there is a cough with the departure of sting sputum of dirty gray color in large quantities (up to 1 l
and more)
- auscultatively over the focus of lesion - wet wheezing

Diagnosis of lung gangrene.

1. Radiography of the lungs: before breaking through the bronchi - massive infiltration of fuzzy
boundaries, occupying one or two lobes, and sometimes all lungs; after a breakthrough in the
bronchi - against the background of massive darkening, multiple, more often small, enlightenments
of irregular shape, sometimes with liquid levels, are determined.
2. Laboratory data:
a) signs of anemia, leukocytosis, rod nuclear shift, toxic graininess of neutrophils, pronounced
increase in ESR.
b) proteinuria, cylindrical.
c) increase in the content of sialic acids, fibrin, seromukoid, haptoglobin
d) general analysis of sputum: color - dirty gray, three layers are formed during sedimentation:
upper - liquid, foamy, whitish color, medium - serous, lower - purulent detritus and fragments of
molten pulmonary tissue; elastic fibers, many neutrophils are determined in sputum.

Treatment.
1. Rational diet (energy value up to 3000 kcal/day, increased protein content: 110-120 g/day,
moderate fat restriction: 80-90 g/day, vitamin-rich foods).

2. Rational antimicrobial therapy (in the ulcer cavity, intrabronchial, parenterally): cepim 1-2 g 2
times/day in combination with amoxiclav 625 mg 2 times/day or levofloxacin 0.5 g 1 time/day in/in
before clinical and radiological recovery (6-8 weeks).

3. Improvement of drainage conditions of the purulent cavity and bronchial tree: expectorant,
proteolytic enzymes, bronchoscopy, pus puncture, external drainage with fine drainage,
pneumotomy, positional drainage, breathing gymnastics
4. Immunotherapy (antistaphylococcal plasma, staphylococcal anatoxin, etc.)
5. Symptomatic treatment - as in pneumonia.

6. In case of ineffective conservative treatment - surgical treatment (always indicated in the

following cases: multiple abscesses; tissue sequesters; abscesses of lower lobe localization;
formations with a cavity diameter of more than 5 cm): lung resection, lobectomy, pulmonectomy,
pleuropulmonectomy.
13.Pulmonary hypertension. Causes, classification, diagnostic methods. The main principle in
the treatment of pulmonary hypertension.
Pulmonary hypertension is increased pressure in the pulmonary circulation.
The most common overall causes of pulmonary hypertension are:
Left heart failure, including diastolic dysfunction
Parenchymal lung disease with hypoxia
Miscellaneous: Sleep apnea, connective tissue disorders, and recurrent pulmonary embolism
The World Health Organization (WHO) has divided pulmonary hypertension into five groups on the
basis of similarities in pathophysiology, clinical presentation, and therapeutic options.
• Group 1 - Pulmonary arterial hypertension (PAH)
• Group 2 - Pulmonary hypertension due to left-sided heart disease
• Group 3 - Pulmonary hypertension due to lung diseases and/or hypoxia
• Group 4 - Chronic thromboembolic pulmonary hypertension (CTEPH)
• Group 5 - Pulmonary hypertension with unclear or multifactorial etiologies, including
hematologic disorders (eg, myeloproliferative disorders), systemic disorders (eg, sarcoidosis,
pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis,
vasculitis), metabolic disorders (eg, glycogen storage disease, Gaucher disease, thyroid
disorders), and miscellaneous conditions (eg, tumor obstruction, mediastinal fibrosis, chronic
renal failure on dialysis)

Diagnosis
• Findings from the history, physical examination, chest radiography, and electrocardiography
(ECG) may suggest the presence of pulmonary hypertension and right ventricular dysfunction.
• Two-dimensional transthoracic echocardiography (TTE) with Doppler analysis should be used as
an initial screening measure to estimate the pulmonary artery pressure and assess ventricular
function.
• Right-sided cardiac catheterization is recommended as the confirmatory test for pulmonary
hypertension. This can also be useful for assessment of the reversibility of pulmonary arterial
hypertension (PAH) with vasodilatory therapy.

Treatment
• Avoidance of activities that may exacerbate the condition (eg, cigarette smoking, high altitude,
pregnancy, use of sympathomimetics)
• Idiopathic and familial pulmonary arterial hypertension: IV epoprostenol; inhaled, oral, sc, or IV
prostacyclin analogs; oral endothelin-receptor antagonists; oral phosphodiesterase 5 inhibitors,
oral soluble guanylate cyclase stimulators; oral prostacyclin (IP2) receptor agonists
• Secondary pulmonary arterial hypertension: Treatment of the underlying disorder
• Lung transplantation
• Adjunctive therapy: Supplemental oxygen, diuretics, and/or anticoagulants
14.Pulmonary heart disease: classification, etiology, pathogenesis. The main clinical
manifestations of compensated and decompensated pulmonary heart disease, diagnosis,
course and treatment.
The pulmonary heart is a complex of hemodynamic disorders in the small circle of blood
circulation, developing as a result of diseases of the bronchopulmonary apparatus, chest deformity
or primary lesions of pulmonary arteries, manifested at the end stage by hypertrophy and dilatation
of the right ventricle and progressive circulatory insufficiency.

Etiology of the pulmonary heart:

a) acute (develops in minutes, hours or days): massive PE, valve pneumothorax, severe attack BA,
common pneumonia
b) subacute (developing within weeks, months): repeated small PE, nodular periarteritis,
pulmonary carcinomatosis, repeated attacks of severe BA, botulism, myasthenia, polio
c) chronic (developed within a few years):

1. diseases affecting the airways and alveoli: chronic obstructive bronchitis, pulmonary emphysema,
bronchial asthma, pneumoconiosis, bronchiectasis, pulmonary polycystosis, sarcoidosis,
pneumosclerosis, etc.
2. diseases affecting the chest with reduced mobility: kyphoscoliosis and other chest deformities,
Bekhterev's disease, condition after thoracoplasty, pleural fibrosis, neuromuscular diseases
(polyomyelitis), diaphragm paresis, Pikvik syndrome in obesity, etc.
3. diseases affecting pulmonary vessels: primary pulmonary hypertension, repeated
thromboembolism in the pulmonary artery system, vasculitis (allergic, obliterating, nodular, lupus,
etc.), atherosclerosis of the pulmonary artery, compression of the pulmonary artery trunk and
pulmonary veins by mediastinal tumors, etc.

Classification of the pulmonary heart (according to the Votchaly):

1. Downstream: acute pulmonary heart, subacute pulmonary heart, chronic pulmonary heart
2. Depending on the level of compensation: compensated, decompensated
3. Depending on the genesis: vascular, bronchial, toracodiaphragmal

The main pathogenetic factor is pulmonary hypertension, which occurs due to a number of reasons:
1) in diseases with hypoventilation of pulmonary alveoli in alveolar air, the partial pressure of
oxygen decreases and partial pressure of carbon dioxide increases; the advancing alveolar hypoxia
causes spasm of pulmonary arterioles and increased pressure in the small circle (alveolo-capillary
reflex
2) hypoxia causes erythrocytosis with subsequent increase in blood viscosity; increased blood
viscosity contributes to increased platelet aggregation, the formation of microaggregates in the
microcirculation system and increased pressure in small branches of the pulmonary artery
3) reducing the oxygen tension in the blood causes irritation of the chemoreceptors of the aortic
carotid zone, as a result, the minute volume of blood increases; its passage through spasmodic
pulmonary arterioles leads to a further increase in pulmonary hypertension
4) in case of hypoxia, a number of biologically active substances (histamine, serotonin, etc.) are
released in tissues, which also contribute to pulmonary arteriole spasm
5) atrophy of alveolar walls, their rupture with thrombing and obliteration of part of arterioles and
capillaries due to various lung diseases leads to anatomical reduction of the vascular bed of the
pulmonary artery, which also contributes to pulmonary hypertension.
Under the influence of all the above factors, hypertrophy and dilatation of the right parts of the heart
occur with the development of progressive circulatory insufficiency.

Initially, cor pulmonale is asymptomatic, although patients usually have significant symptoms (eg,
dyspnea, exertional fatigue) due to the underlying lung disorder.
Later, as RV pressures increase, physical signs commonly include a left parasternal systolic lift, a
loud pulmonic component of the 2nd heart sound (S2), and murmurs of functional tricuspid and
pulmonic insufficiency.
Later, an RV gallop rhythm (3rd [S3] and 4th [S4] heart sounds) augmented during inspiration,
distended jugular veins (with a dominant a wave unless tricuspid regurgitation is present),
hepatomegaly, and lower-extremity edema may occur.

Clinical signs of a decompensated pulmonary heart:

- orthopnea
- cold acrocyanosis
- swelling of cervical veins, not decreasing when inhaling
- liver enlargement
- Plesh symptom (pressure on the enlarged painful liver causes swelling of the cervical veins);
- in case of severe heart failure, it is possible to develop swelling, ascites, hydrothorax

Diagnostics of CLS.
1. Echocardiography - signs of right ventricular hypertrophy: increase in the thickness of its wall
(normally 2-3 mm), expansion of its cavity (right ventricle index - the size of its cavity in terms of
the body surface - normal 0.9 cm/m2); signs of pulmonary hypertension: increase in the

2. Electrocardiography - signs of right ventricular hypertrophy (increase of RIII, aVF, V1,V2;

depression of the ST segment and changes in tooth T in leads V1, V2,aVF, III; plaving;
displacement of the transition zone in V4/V5; complete or incomplete blockade of the right leg of
the Geese beam; increase in the internal deviation interval > 0.03 in V1, V2).

3. Chest X-ray - enlargement of the right ventricle and atrium; swelling of the cone and trunk of the
pulmonary artery; significant expansion of root vessels with depleted peripheral vascular pattern;
"chopping" of lung roots, etc.

4. Investigation of external respiratory function (to identify disorders of the restrictive or obstructive
type).

5. Laboratory data: UAC is characterized by erythrocytosis, high hemoglobin content, delayed ESR,
tendency to hypercoagulation.
Principles of CLS treatment.
1. Etiological treatment - aimed at the treatment of the underlying disease that led to CLS (AB in
bronchopulmonary infection, bronchodilators of bronchobstructive processes, thrombolytics and
anticoagulants in TELA, etc.)

2. Pathogenetic treatment is aimed at reducing the severity of pulmonary hypertension:

a) long-term oxygen therapy - reduces pulmonary hypertension and significantly increases
life expectancy
b) improvement of bronchial patency - xanthins: euphyllin (2.4% p-p 5-10 ml w/in 2-3
times/day), theophyllin (in tab. 0.3 g 2 times/day) in repeated courses of 7-10 days, 2 -
adrenomimetics: salbutamol (in tab. 8 mg 2 times/day)
c) reduction of vascular resistance - peripheral vasodilators: prolonged nitrates (sustaple 2.6
mg 3 times a day), calcium channel blockers (nifedipine 10-20 mg 3 times/day, amlodipine,
isradipine - have increased affinity for MMC of pulmonary vessels),
d) improvement of microcirculation - courses of heparin of 5000 IU 2-3 times/day p/c
increase in APTT by 1.5-1.7 times compared to control, low molecular weight heparins (fraxiparin),
with pronounced erythrocytosis - bloodletting with subsequent injection of low viscosity solutions
(reopolyglukin).

3. Symptomatic treatment: to reduce the severity of right ventricular insufficiency - loop diuretics:
furosemide 20-40 mg/day (carefully, as they can cause hypovolemia, polycytemia and thrombosis),
when combined with MA - cardiac glycosides, to improve myocardial function - metabolic agents
(mildronate orally 0.25 g 2 times/day in combination with potassium orothate or panangin), etc.

4. Physiotherapy (breathing gymnastics, chest massage, hyperbaric oxygenation, exercise therapy)

5. Ineffective conservative treatment shows lung or lung-heart transplantation.

 II. Cardiovascular diseases

1. Epidemiology and classification of coronary heart disease. The concept of "ischemic

cascade." Basic approaches to cardiovascular risk stratification.

Epidemiology :CAD is the leading cause of death in the US and worldwide. The lifetime risk of
coronary artery disease at age 50 is approx. 50% for men and 40% for women.

1.Sudden cardiac death.

2.Angina pectoris:

 stable angina pectoris;

 vasospastic angina (Princmetala's);
 unstable angina.

3. Myocardial infarction (Ml):

 acute Q-wave Ml;

 acute non-Q-wave MI;
 -subendocardial MI;
 acute MI (undetected);
 recurrent MI (3-28 days);
 repeated MI (after 28 days).

4. Postinfarction cardiosclerosis faction.

 Cardiac arrhythmia.
 Painless form of the IHD.

IHD is an acute or chronic myocardial dysfunction due to a relative or absolute decrease in the
supply of myocardium with arterial blood, most often associated with a pathological process in
the coronary artery (CA) system.

Etiology of IHD:

1. Atherosclerosis of the CA - the anterior descending branch of the left CA is more often
affected, less often - the circumflex branch of the left CA and the right CA.
2. Congenital anomalies of the CA (divergence of the circumflex artery from the right
coronary sinus or right coronary artery, etc.)
3. Dissection of the coronary artery (spontaneous or due to dissection of an aortic
aneurysm)
4. Inflammatory lesions of the CA (with systemic vasculitis)
5. Syphilitic aortitis with spread of the process to the coronary artery
 6. Radiation fibrosis of the coronary artery (after irradiation of the mediastinum with
lymphogranulomatosis and other tumors)
7. CA embolism (more often with IE, MA, less often with rheumatic defects)

Currently, CAD is considered to be myocardial ischemia caused only by an atherosclerotic

process in the coronary artery.

Risk factors for coronary artery disease:

a. Modifiable : 1) cigarette smoking 2) arterial hypertension 3) diabetes mellitus 4) low HDL

cholesterol, high LDL cholesterol, total cholesterol above 6.5 mmol / l 5) obesity

b. Non-modifiable : 1) age: 55 years and older for men, 65 years and older for women 2) male
gender 3) family history of coronary artery disease

The main ones are also distinguished (age over 65 years for women and over 55 years for men,
smoking, total cholesterol > 6.5 mmol / l, family history of coronary artery disease)
and others (low HDL cholesterol, high LDL cholesterol, impaired glucose tolerance, obesity,
microalbuminuria in DM, sedentary lifestyle, elevated fibrinogen levels) are risk factors for
coronary artery disease.

IBS pathogenesis.

Normally, there is a clear correspondence between the delivery of oxygen to cardiomyocytes and
the need for it, which ensures normal metabolism and functions of heart cells. Coronary
atherosclerosis causes:

a) mechanical obstruction of the CA with a decrease in cell perfusion

b) dynamic obstruction of the coronary artery - coronary spasm - due to increased reactivity
of the coronary arteries affected by atherosclerosis to the action of vasoconstrictors
(catecholamines, serotonin, endothelin, thromboxane) and reduced reactivity to the action of
vasodilators (endothelial relaxing factor, prostacyclin)

c) violation of microcirculation - due to the tendency to form unstable platelet aggregates in the
affected CA during the release of a number of biologically active substances (thromboxane A 2 ,
etc.), which often undergo spontaneous disaggregation

d) coronary thrombosis - in the area of damage to the atherosclerotic plaque on the

thrombogenic subendothelium, thrombi are formed that potentiate ischemia

All of the above leads to an imbalance between myocardial oxygen demand and its delivery,
impaired cardiac perfusion and the development of ischemia with subsequent clinical
manifestations in the form of anginal pain, myocardial infarction, etc.

IHD classification:
 1. Sudden coronary death (primary circulatory arrest).
2. Angina:
a. angina pectoris: 1) for the first time (up to 1 month); 2) stable (more than 1
month); 3) progressive
b. spontaneous (vasospastic, special, variant, Prinzmetal's angina)
3. Myocardial infarction: a) with a Q-wave (large-focal - transmural and non-transmural) b)
without a Q-wave (small-focal)
4. Postinfarction cardiosclerosis (2 months after MI)
5. Heart rhythm disorders
6. Heart failure
7. +7. Painless (“silent”) ischemia
8. Microvascular (distal) CAD
9. New ischemic syndromes (myocardial stunning, myocardial hibernation, myocardial
ischemic preconditioning)

Some clinical forms of CAD - new onset angina, progressive angina, rest angina, and early
postinfarction angina (first 14 days after MI) - are forms of unstable angina .

The ischaemic cascade is the concept that progressive myocardial oxygen supply–demand
mismatch causes a consistent sequence of events, starting with metabolic alterations and
followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG
changes, and angina.

Myocardial ischemia

 Reversible ischemia: Tissue is ischemic but not irreversibly dead and, therefore, still
potentially salvageable.
 Myocardial stunning: acutely ischemic Myocardial segments with transiently impaired but
completely reversible contractility
 Hibernating myocardium: a state in which myocardial tissue has persistently impaired
contractility due to repetitive or persistent ischemia
 Partially or completely reversible when adequate oxygen supply is restored (e.g., after
angioplasty or coronary artery bypass grafting)
 Irreversible ischemia: tissue necrosis (myocardial scars)

2. Classification, diagnosis and treatment of stable angina. Relief of pain attack.

Stable angina: a type of angina that occurs upon exertion, mental stress, and/or exposure to cold
and usually subsides within 20 minutes of rest or after administration of nitroglycerin

Clinical features

The main parameters of pain in patients with stable angina are: location, character, intensity,
duration, frequency, radiation, associated symptoms and cause of onset, aggravating and
relieving factors.
  The typical location of angina is mid or lower part of sternum. Less typically, discomfort
may occur in the epigastric area.
 The discomfort is usually described as pressure, tightness, heaviness, strangling,
constricting, burning, squeezing, suffocating and crushing.
 The severity of the discomfort varies greatly.
 The pain may radiate in arm to the wrist and fingers, lower jaw or teeth, throat, between
the shoulder blades.
 The duration of the discomfort is brief, not more than 10 min in the majority of cases and
more commonly even less.
 Angina equivalents are common and include dyspnea, faintness, and syncope.
 Chest discomfort may be accompanied by less specific symptoms such as nausea,
burping, restlessness, or a sense impending doom.
 Frequency of the pain may be different.
 An important characteristic is the relation to exercise, specific activities, or emotional
stress.
 Symptoms classically triggered by increased levels of exertion, such as walking up an
incline or against a breeze, and rapidly disappear within a few minutes, when these causal
factors abate.
 Exacerbations of symptoms after a heavy meal or work are classical features of angina.
 Buccal or sublingual nitrates rapidly relieve angina.

Clinical signs of angina pectoris:

 the nature of the pain sensations - squeezing, burning, pressing;

 localization - retrosternal region or atrial region to the left of the sternum;
 conditions of occurrence - physical activity or emotional stress;
 duration of painful sensations - 2-3 minutes (no more than 10 minutes);
 irradiation - in the shoulder, lower jaw, in the interscapular region;
 fast and complete stopping effect of nitroglycerin .

Functional classes:

1. Class I. Seizures occur at high intensity loads, coronary blood flow (CC) can increase by
7 times, the power attainable at EEP 750 kg * m / min or more, DP - 278 or more, where:
DP (double product) = (SBP * HR / 100) .
2. Class II. Seizures occur when walking on a flat surface for a distance of more than 500
meters, when climbing more than one floor, CC - 4-6 times, VEP - 450 kg * m / min or
more, DP - 218-277.
3. III class. Seizures occur when walking at a distance of 100-500 meters, when climbing
one floor, CC - 2-3 times, VEP - less than 300 kg * m / min, DP - 151-217.
 4. IV class. Angina pectoris occurs with small physical exertion, when walking at a distance
of less than 100 meters, CC - less than 2 times, VEP most often cannot be performed, DP
- less than 150.

Diagnosis:

1.Clinical blood analysis is without change.

Biochemical analysis in patients with stable angina may show

 elevated level of cholesterol, triglycerides

 decreased high density lipoprotein cholesterol
 increased low density lipoprotein cholesterol.
 Biochemical markers of myocardial damage in stable angina are in a normal range.

2. X-ray examination in stable angina does not provide specific information for diagnosis.

3. Resting ECG may show evidence of previous myocardial infarction, left ventricular
hyperthrophy, bundle branch block, preexcitation, arrhythmias, or conduction defects, but is
normal in most patients.

 Since 12-lead ECG is normal in 50 % of patients with chronic stable angina it cannot
exclude 1HD.
 During chest pain the ECG becomes abnormal in half of the angina patients with a normal
resting ECG. ST-segment and T-wave depression or inversion on the resting ECG and their
pseudo normalization during pain are observed.
 Sinus tachycardia is common, bradyarrhythmia less go.
 These findings indicate that resting ECG should be performed during episode of chest pain.
 Exercise ECG is more sensitive and specific than the resting ECG for detecting myocardial
ischemia.
 Exercise tolerance test is usually performed using a standard treadmill or bicycle ergometer
protocol to ensure a progressive and reproducible increase in work load while monitoring the
patient's ECG, blood pressure and general condition.
 Planar and down sloping ST-segment depression of 1 mm or more is indicative of ischemia;
up sloping ST-depression is less specific and often occurs in normal individuals.
 An exercise test should be carried out only after careful clinical evaluation of symptoms and
a physical examination including resting ECG.
 Exercise ECG testing is not of diagnostic value in the presence of left bundle branch block,
paced rhythm, and Wolff-Parkinson-White syndrome in which cases the ECG changes
cannot be evaluated.
 Additionally, false positive results are more frequent in patients with abnormal resting ECG
in the presence of left ventricular hypertrophy, electrolyte imbalance, intraventricular
 conduction abnormalities, and use of digitalis. Exercise ECG testing is also less sensitive and
specific in women.
 Resting two-dimensional and Doppler echocardiography is useful to detect or rule out the
possibility of other disorders such as heart valve disease or hypertrophic cardiomyopathy as a
cause of symptoms and to evaluate ventricular function.
 For diagnostic purposes, Echo-CG is useful in patients with clinically detected murmurs,
history and ECG changes compatible with hypertrophic cardiomyopathy or previous
myocardial infarction and symptoms or signs of heart failure.
 Tissue Doppler imaging allows regional quantification of myocardial motion and strain rate,
imaging allows determination of regional deformation thus improve to detect ischemia earlier
in the ischemic cascade.
 Stress testing in combination with imaging are used in the diagnosis of stable angina.
 The most well-established stress imaging techniques are echocardiography and perfusion
scintigraphy.
 Both may be used in combination with either exercise stress.
 Exercise stress echocardiography has been developed as an alternative to "classica"
exercisetesting with ECG and as an additional investigation to establish the presence or
location and extent of myocardial ischaemia during stress.
 A resting echocardiogram is acquired before a symptom-limited exercise test is performed,
most frequently using a bicycle ergometer, with further images acquired where possible
during each stage of exercise and at peak exercise.
 Exercise testing with myocardial perfusion scintigraphy is required.
 Thallium-201 and technetium-99m radiopharmaceuticals are the most commonly used
tracers, employed with single-photon emission computed tomography in association with a
symptom-limited exercise test on either a bicycle ergometer or a treadmill.
 With this technique myocardial hypoperfusion in patients with stable angina is characterized
by reduced tracer uptake during stress in comparison with uptake at rest.
 Pharmacological stress testing with imaging techniques.
 Pharmacological stress testing with either perfusion scintigraphy or echocardiography is
indicated in patients who are unable to exercise adequately or may be used as an alternative
to exercise stress.
 Two approaches may be used to achieve this: infusion of short-acting sympathomimetic
drugs such as dobutamine in an incremental dose protocol which increases myocardial
oxygen consumption and mimics the effect of physical exercise or infusion of coronary
vasodilators (adenosine and dipyridamole).
 Cardiac magnetic resonance stress testing in conjunction with a dobutamine infusion can be
used to detect wall motion abnormalities induced by ischemia or perfusion abnormalities

Characteristics of therapeutic measures.

Lifestyle recommendations:

 weight loss if you are obese;

 giving up bad habits - smoking, alcohol abuse;
 do not eat before bedtime;
 limit the intake of fats, salty foods;
 conducting physical therapy classes.

Principles of drug treatment for angina pectoris:

 antianginal agents: nitric oxide donors - nitrates (nitroglycerin, isosorbide dinitrate,

isosorbide-5- mononitrate), sydnonimines (molsidomin, korvaton, sidnopharm);
 β-blockers (atenolol, bisoprolol, propranolol, etc.);
 antiplatelet drugs (aspirin, tiklid);
 calcium antagonists (verapamil, diltiazem, etc.);
 ACE inhibitors (in the presence of arterial hypertension or a decrease in the left ventricular
ejection fraction of less than 40%);
 anti-atherosclerotic (lipid-lowering) agents (simvastatin, pravastatin, etc.);
 metabolic agents (trimetazidine, trimetazidine MB)

Tactics of treatment of patients with angina pectoris.

 In FC I, drug treatment is not carried out, non-drug measures are recommended, exposure to
risk factors, prophylactic administration of small doses of aspirin (100 mg / day), sublingual
nitroglycerin or in the form of a spray on demand.
 In FC II, additional therapy with long-acting nitrates, beta-blockers, or calcium antagonists is
indicated
 In FC III, one of the previously unused antianginal drugs is added (long-acting nitrate with a
beta-blocker or calcium antagonist is more often used)
 In FC IV, all three main antianginal drugs are indicated (long-acting nitrate, calcium
antagonist, beta-blocker), metabolic therapy, ACE inhibitors, and the question of surgical
treatment is raised.
 With the ineffectiveness of conservative treatment at all stages, the question of surgical
treatment is decided!
 ITU : with FC I, patients do not need drug therapy, with FC II, the duration of VN for
inpatient treatment with stable angina is 5-7 days, with FC III - 7-10 days, with FC IV,
patients are disabled, with unstable angina, the duration of VN for inpatient treatment 8-12
days.
 Rehabilitation : lifestyle improvement and correction of risk factors (reduction of excess
body weight, smoking cessation, correction of concomitant hypertension and other diseases),
regular dosed physical activity (walking, skiing, swimming, etc.), psychological
rehabilitation (rational and group psychotherapy, autogenic training), rational employment,
dispensary observation, adequate drug therapy.
3. Modern methods of treatment of chronic ischemic heart disease.
Principles of treatment :

1. Recommendations for lifestyle changes : weight loss in obesity; giving up bad habits
(smoking, alcohol abuse); stabilization of hypertension and diabetesrational diet (restriction
of fatty and salty foods, do not eat before bedtime); physiotherapy exercises
2. Drug treatment - the main groups of drugs:

a) antianginal agents (nitric oxide donators) - nitrates (nitroglycerin, isosorbide dinitrate,

isosorbide-5-mononitrate), sydnonimines (molsidomine, corvaton, sydnopharm).

1) nitroglycerin preparations : sublingual forms (nitroglycerin tab. 0.5 mg), oral aerosols
(nitromint), depot preparations (nitrong-forte: single dose 6.5 mg, daily 13.0-26.0 mg, sustak
mite / forte, nitrogranulong: single dose 5.3 mg, daily 10.6-15.9 mg, nitro-time), ointments
and patches for cutaneous application (nitroderm, deponit-5.10: single dose 1 patch, a day up
to 3 patches, nitro ointment 2%: single dose 1 g, daily 2 g), infusion forms (perlinganite,
nitroglycerin for infusion)
2) preparations of isosorbide dinitrate : oral forms (kardiket retard: single dose 20-120 mg,
daily 60-120 mg, isosorb retard, isolong, nitrosorbide: single dose 10-20 mg, daily 40-80
mg), oral aerosols (isoket , aerosonite, iso-mic), infusion forms (isoket, isolong), buccal
forms (trinitrolong, dinitrosorbilong)
3) isosorbide mononitrate : oral forms (mononite: single dose 20-40 mg, daily 80-120 mg,
olicard: single dose 40 mg, daily 40-80 mg, monocinque: single dose 50 mg, daily 50 mg).

b) β-blockers :

1) without vasodilating properties:

 non-selective (propranolol / obzidan 120-240 mg / day, nadolol, oxprenolol, sotalol, timolol)

 β 1 -selective (atenolol / tenormin - 100-150 mg / day, bisoprolol / concor 2.5-10 mg / day,
metoprolol / egilok 100-200 mg / day)

2) with vasodilating properties:

 non-selective (carvedilol / dilatrend 12.5-50 mg / day, pindolol, labetalol)

 β 1 -selective (nebivolol / nebilet 5-10 mg / day, acebutolol / sektral 200-800 mg / day).

Contraindicated in :

 PQ interval more than 0.24 s;

 heart rate less than 50 in 1 minute; c) the level of systolic blood pressure is less than 90
mm. rt. Art.; d) AV block II-III degree (with no pacemaker); e) BA, COPD; e) severe heart
failure.
 calcium antagonists (verapamil, diltiazem, etc.): increasing the pulse (dihydropyridine -
nifedipine 30-60 mg / day, amlodipine 5-10 mg / day, isradipine) and slowing down the pulse
(verapamil 240-480 mg / day, diltiazem 90 -120 mg/day); drug of choice for vasospastic
angina
 antiplatelet drugs : aspirin - significantly reduces mortality in patients with MI, therefore,
with MI, all patients who have not taken aspirin during the last day are immediately
prescribed at a dose of 0.160-0.325 mg orally to chew
 ACE inhibitors (in the presence of hypertension or a decrease in left ventricular EF less than
40%)
 anti-atherosclerotic (lipipidemic) drugs (simvastatin, pravastatin, etc.)
 metabolic agents (trimetazidine, trimetazidine MB / preductal 40-60 mg / day).

Significantly prolong the life of patients with angina pectoris: β-blockers; ACE inhibitors (in the
presence of LV insufficiency); aspirin; amiodarone (PAS III, not possible simultaneously with β-
blockers).

3. Additional treatments :

b) psychopharmacological effects
c) physical training
d) surgical treatment : coronary angioplasty (indicated for: damage to one or two coronary
vessels; angina pectoris refractory to drug therapy; proven ischemia at rest or during
exercise; proven ischemia with a high risk of surgery; repeated angina pectoris after
myocardial infarction or ventricular tachycardia) and aorto -coronary bypass
grafting (indicated for: angina pectoris refractory to drug therapy, unstable angina pectoris,
variant angina pectoris; critical stenosis (more than 50%) of the trunk of the left coronary
artery or 2nd, 3rd vascular lesion (more than 75%); acute myocardial infarction , sudden
death syndrome; congestive heart failure; recurrent ventricular arrhythmias, ventricular
tachycardia associated with LV aneurysm).

4. Non-invasive diagnosis of ischemic heart disease. Indications for routine and diagnostic
coronary angiography.

1. Data of anamnesis (conditions for the onset of pain) and a characteristic clinical picture.
2. ECG: at rest and during an attack, Holter monitoring - specific for angina is the dislocation of
the ST segment by 1 mm down (subendocardial ischemia) or up (transmural ischemia) from
the isoline, most often recorded at the time of an attack
3. Stress tests: VEP, treadmill, transesophageal pacing (in response to an increase in heart rate,
ischemic damage occurs on the ECG), pharmacological tests with dobutamine and isadrine
(cause an increase in myocardial oxygen demand), dipyridamole and adenosine (cause steal
syndrome, expanding primarily intact vessels) - allow to detect myocardial ischemia, not
determined at rest, to establish the severity of coronary insufficiency.
Signs of myocardial ischemia during stress testing:

 an attack of angina pectoris

 depression or elevation of the ST segment of the horizontal or oblique descending type by
1 mm or more lasting at least 0.8 seconds from point j
 an increase in the amplitude of the R wave in combination with depression of the ST
segment

4.Radionuclide scintigraphy of the myocardium with 201 Tl (absorbed by the normal

myocardium in proportion to coronary perfusion) or 99 m Tc (selectively accumulates in areas of
myocardial necrosis)

5.Echo-KG (including stress-Echo-KG, Echo-KG with pharmacological tests) - allows you to

assess local and greater myocardial contractility (violation of local contractility corresponds to
the focus of ischemia)

6.Coronary angiography - the "gold standard" for the diagnosis of coronary artery disease;
performed more frequently to determine the appropriateness of surgical treatment

7.Electrocardiotopography - 60-lead ECG mapping

8.Positron emission tomography - allows you to get information about coronary blood flow and
myocardial viability

9.Mandatory laboratory examinations: KLA, OAM, blood sugar, BAC (lipidogram, electrolytes,
cardiospecific enzymes: CPK, AST, LDH, myoglobin, troponin T), coagulogram.

Functional classes of angina pectoris make it possible to assess the functional state of patients
with coronary artery disease and their tolerance to physical activity:
5. Silent myocardial ischemia, medical and social significance, diagnosis and therapeutic
tactics.

Silent myocardial ischemia is defined as the presence of objective evidence of myocardial

ischemia in the absence of chest discomfort or another anginal equivalent symptom (eg, dyspnea,
nausea, diaphoresis, etc). Objective evidence of silent myocardial ischemia may be obtained in
several ways:

 ●ST segment changes consistent with ischemia seen during exercise treadmill testing or
ambulatory monitoring.
 ●Reversible myocardial perfusion defects noted during radionuclide myocardial perfusion
imaging.

According to the Cohn classification, 4 patients with silent ischemia are stratified into types I, II,
or III:

 •Type I silent ischemia is the least common form. It occurs in asymptomatic patients with
obstructive CAD who do not experience anginal symptoms at any time.
 •Type II silent ischemia most commonly occurs in patients with a documented previous
myocardial infarction (MI).
 •Type III is the most common form; it occurs in patients with chronic stable angina, unstable
angina, or variant angina.

DIAGNOSTIC STUDIES

Several diagnostic tools can detect SMI. The most frequently used tests in clinical practice are
ETT and ambulatory ECG, or Holter, monitoring. The Algorithm shows the patient populations
for whom noninvasive testing for ischemic heart disease is recommended.

 Exercise treadmill testing. This is the preferred tool to identify silent ischemia in patients
with either symptomatic or asymptomatic disease. A diagnosis of CAD in asymptomatic
patients, however, must be confirmed with radionuclide imaging (thallium perfusion
scintigraphy or exercise ventriculography) because of the high rate of false-positive results
with ETT.17,18 False-positive results are seen most often in patients with hypertension and
are caused by ECG repolarization abnormalities that become evident during exercise in
patients with LV hypertrophy. False-positive results are also commonly seen in women.
 False-negative results on treadmill testing are particularly common among patients with
diabetes and among those with physical disabilities that limit the extent to which they can
exercise.
 No large randomized controlled trials have demonstrated a clinical benefit of ETT in this
asymptomatic population. Because of insufficient evidence, the US Preventive Services Task
Force (USPSTF), the American Heart Association, and the American College of Cardiology
have recommended against using ETT as a screening tool.
 However, the USPSTF and American Diabetes Association guidelines recognize the possible
usefulness of ETT for patients with diabetes who are contemplating starting an exercise
program, for persons with multiple CAD risk factors, for men older than 45 and women older
than 55 years who plan to start a vigorous exercise program, and for those involved in high-
risk occupations who are at risk for CAD.20 Furthermore, they found that ETT had no value
in low-risk patients and recommended against routine screening in these patients.21
 Ambulatory monitoring. This study is recommended to confirm or refute the presence of SMI
in patients with a positive exercise test result.22 For initial diagnosis, however, reserve
ambulatory monitoring for patients with ischemia following an acute coronary event and for
patients with chronic stable angina who exhibit exerciseinducible ischemia.1 Unlike
treadmill testing, ambulatory monitoring assesses ECG changes while patients engage in
routine daily activities.

TREATMENT

Because SMI increases the risk of cardiovascular events, it is reasonable to use pharmacological
therapy in an attempt to decrease the patient’s total ischemic burden.

β-Blockers. These seem to be the most effective agents; they reduce the incidence, frequency,
duration, and severity of silent ischemia. 23-25 The Atenolol Silent Ischemia Study (ASIST)
evaluated the effects of atenolol in asymptomatic or mildly symptomatic patients who had
abnormal results on exercise thallium testing and silent ischemia documented by ambulatory
ECG monitoring.26 Treatment with atenolol, 100 mg/d, reduced daily ischemia, as well as the
risk of future adverse cardiac events at 1 year. Another effective treatment is to combine a
longacting β-blocker with a long-acting nitrate.

Anti-ischemic efficacy can be evaluated by repeated Holter monitoring and titrating drug doses
until the ischemic burden is suppressed by at least 50% or the maximum tolerated dose of a β-
blocker is attained.

Calcium channel blockers. These agents, specifically amlodipine, long-acting nifedipine, and
short- or long-acting diltiazem, have been shown to reduce ischemic episodes by 13% to 69%,
and to decrease the duration of episodes by 6% to 68%. Combining a long-acting
dihydropyridine calcium channel blocker (CCB) with a β-blocker has proved superior to either
agent alone in reducing ischemia.27-29 If β-blocker therapy is not an option because of adverse
effects or contraindications, consider combining a long-acting dihydropyridine CCB and a long-
acting nitrate.

Revascularization. This is achieved with either percutaneous coronary interventions or coronary

artery bypass grafting (CABG). Revascularization, regardless of the method, has not
conclusively reduced the risk of MI or cardiovascular death in patients with chronic stable angina
and preserved LV systolic function. Consider revascularization for patients with unacceptably
frequent or severe angina that has not responded to optimized medical therapy, and for patients
with such high-risk features as symptomatic multivessel disease, proximal left anterior
descending or left main artery disease, LV systolic dysfunction, diabetes, a large area of
myocardium at jeopardy on nuclear or echocardiographic stress testing, early onset of ischemia
on stress testing, or STsegment depression of 2 mm or more.

Revascularization currently is not recommended for patients without anginal symptoms unless
they meet the above criteria.30,31 Focus instead on steps to modify risk factors, such as blood
pressure control, lipid lowering, smoking cessation, and lifestyle modifications including diet
and exercise.

6. Acute coronary syndrome with ST segment elevation. Definition, diagnosis,

organizational tactics in the prehospital and hospital stage. Emergency care, differentiated
approach. Methods of reperfusion therapy. Medicine therapy

STE-ACS: acute coronary syndrome manifesting with ST-elevations on ECG

Patients with STEMI require immediate revascularization and should be identified as soon as
possible. ECG findings can change over time and with fluctuations in symptoms, which is why
the diagnosis of STEMI should not be excluded based on a single ECG. Percutaneous coronary
intervention (PCI) within 90 minutes of first medical contact (FMC) is the treatment of choice.
Intravenous fibrinolytics are an alternative if PCI can not be performed within 120 minutes and
no contraindications are present.

ECG changes in STEMI : significant ST elevation in two contiguous leads

Specific criteria: elevation measured at the J point in reference to the onset of the Q wave

 In all leads except V2 and V3: ≥ 1 mm (≥ 0.1 mV)

 In V2 and V3: depends on patient's sex and age
 Men < 40 years: ≥ 2.5 mm (≥ 0.25 mV)
 Men ≥ 40 years: ≥ 2.0 mm (≥ 0.2 mV)
 Women of any age: ≥ 1.5 mm (≥ 0.15 mV)
 The criteria are valid only in the absence of left ventricular hypertrophy and LBBB.

Additional considerations

 ECG findings may change over time (see “Timeline of ECG changes in STEMI”)
 Hyperacute T waves can be present without ST elevations in the very early stages of
ischemia.
 If inferior myocardial infarction is suspected, investigate for signs of right ventricular
involvement

Classical timeline of ECG changes in STEMI

Acute stage: myocardial damage ongoing

 Hyperacute T waves (peaked T wave)

 ST elevations in two contiguous leads with reciprocal ST depressions

Intermediate stage: myocardial necrosis present

 Absence of R wave
 T-wave inversions
 Pathological Q waves
 Duration ≥ 0.04 seconds
 Amplitude ≥ ¼ of the R wave or ≥ 0.1 mV
 Any Q wave in leads V1–3

Chronic stage: permanent scarring

 Persistent, broad, and deep Q waves

 Often incomplete recovery of R waves
 Permanent T-wave inversion is possible.

STEMI-equivalent ECG findings :Presence of any of the following findings requires immediate
evaluation for revascularization therapy (i.e., management is the same as that for STEMI).

Posterior myocardial infarction

 ST depression ≥ 0.5 mm in leads V1–V4

 ST elevations ≥ 0.5 mm in leads V7–V9

Left main-vessel occlusion or three-vessel diseas

 ST depression ≥ 1 mm in ≥ 6 leads
 Combined with ST elevation in leads aVR and/or V1

New or presumably new LBBB or RBBB with strong suspicion for myocardial ischemia

Modified Sgarbossa criteria for suspected STEMI in patients with LBBB

 Can help assess the need for emergency revascularization in patients with ACS and
LBBB.
 The criteria can also be used in right-ventricular pacing with LBBB configuration but are
less specific in this scenario.
 Presence of any of the following indicate a high risk for acute myocardial ischemia
requiring immediate revascularization:
 Concordant ST elevation of ≥ 1 mm in any lead
  Concordant ST depression of ≥ 1 mm in any of leads V1–V3
 Discordant ST elevation ≥ 1 mm and ≥ 25% of preceding S wave

Treatment:

Immediate revascularization [1]

 Emergency coronary angiography with PCI

 Indication: : preferred method of revascularization in patients suspected of having
STEMI
 STEMI and STEMI equivalents
 LBBB with positive modified Sgarbossa criteria
 LBBB or RBBB with strong clinical suspicion of myocardial ischemia
 Procedure: balloon dilatation with stent implantation (see “Cardiac catheterization”)
 First medical contact (FMC) to PCI time
 Ideally ≤ 90 minutes.

Should not exceed 120 minutes

Fibrinolytic therapy in STEMI

 Indications (in STEMI and STEMI equivalents, if all of the following apply):
 PCI cannot be performed ≤ 120 minutes after FMC.
 Symptom onset ≤ 12 hours
 OR 12–24 hours with clinical signs of ongoing ischemia (PCI is even more preferable in
this context)
 No contraindications to fibrinolysis present
 Timing: within < 30 minutes of patient arrival at the hospital
 If > 24 hours after symptom onset

Regimens (one of the following)

 Tenecteplase
 Alteplase
 Reteplase
 Streptokinase

Postfibrinolysis: Check TIMI coronary grade flow and transfer to a facility with PCI capabilities.

Coronary artery bypass grafting: Not routinely recommended for acute STEMI

 Consider in the following cases:

 Coronary anatomy poorly suited to PCI
  After unsuccessful PCI
 STEMI occurring at the time of surgical repair of a mechanical defect
 Antiplatelet therapy and anticoagulation in STEMI [1]

Timing: Therapy should be initiated without delaying revascularization.

7. Acute coronary syndrome without ST segment elevation. Definition, diagnosis,

organizational tactics in the prehospital and hospital stage. Risk stratification scale
GRACE. Emergency care, differentiated approach. Methods of reperfusion therapy.
Medicine therapy.

Acute coronary syndrome (ACS): the suspicion or confirmed presence of acute myocardial
ischemia

Acute coronary syndrome may be further classified into the following categories:

 NSTEMI: positive myocardial injury biomarkers

Patients with NSTE-ACS are classified based on the presence (NSTEMI) or absence (UA) of
significantly elevated cardiac troponin (cTn) levels. A key element of management is to assess
the necessity for and timing of PCI (fibrinolytics are not indicated in NSTE-ACS).
Hemodynamically unstable patients and those with intractable angina require immediate PCI
(i.e., they are managed like STEMI patients). Multiple risk scores (e.g., HEART, TIMI, GRACE)
can help to determine an adequate strategy but are no substitute for individual clinical judgment.
Dual antiplatelet therapy and anticoagulation is indicated initially and the preferred regimens
vary based on patient risk factors and timing of revascularization.Some low-risk NSTE-ACS
patients can be managed conservatively.

8. Myocardial infarction: etiology, pathogenesis, clinical variants (typical and atypical),

severity classes. ECG diagnosis and laboratory diagnosis. Thrombolytic and anticoagulant
therapy. Indications for percutaneous coronary intervention and cardiac surgery
treatment.

Myocardial infarction (MI) is an ischemic necrosis of a part of the heart, resulting from an
acute discrepancy between myocardial oxygen demand and its delivery through the coronary
arteries.

Epidemiology : MI is one of the most common causes of death in developed countries; in the
USA every year in 1 million patients, 1/3 of them die, ½ of them within the first hour; incidence
of 500 men and 100 women per 100 thousand population; up to 70 years, men get sick more
often, then - equally with women.
Etiology of MI: thrombosis of the coronary artery in the area of atherosclerotic plaque (90%),
less often - spasm of the coronary artery (9%), thromboembolism and other causes (embolism of
the coronary arteries, congenital defects of the coronary arteries, coagulopathy - 1%).

Pathogenesis of MI : violation of the integrity of the endothelium, erosion or rupture of an

atherosclerotic plaque  platelet adhesion, the formation of a "platelet plug"  stratification of
erythrocytes, fibrin, platelets with rapid growth of a parietal thrombus and complete occlusion of
the arterial lumen  ischemic damage to the myocardial region supplied by this CA (15-20 min,
reversible state)  myocardial necrosis (irreversible state).

Clinical picture and course of MI.In the clinical course of a typical MI, 5 periods are
distinguished:

1. Prodromal, or pre-infarction, period (from several minutes to 1-1.5 months) - clinically

manifested by the clinic of unstable angina pectoris with transient ischemic changes on the
ECG.
2. The most acute period (from 2-3 hours to 2-3 days) - often occurs suddenly, is determined
by the appearance of signs of necrosis on the ECG, various variants of the course are
characteristic:
a) anginal variant (status anginosus, typical variant) - extremely intense, undulating, pressing
(“hoop, iron tongs squeezing the chest”), burning (“fire in the chest, feeling of boiling
water”), squeezing, bursting, sharp (“ dagger") pain behind the sternum, increases very
quickly, widely radiates to the shoulders, forearms, collarbones, neck, lower jaw on the left,
left shoulder blade, interscapular space, lasts from several hours to 2-3 days, accompanied
by excitement, fear, motor restlessness , vegetative reactions, is not stopped by
nitroglycerin.
b) asthmatic variant (ALZHN) - manifested by a clinic of cardiac asthma or alveolar
pulmonary edema; more common in patients with repeated MI, severe hypertension, in the
elderly, with papillary muscle dysfunction with the development of relative mitral valve
insufficiency
c) arrhythmic variant - manifested by paroxysmal tachycardia, ventricular fibrillation,
complete AV block with loss of consciousness, etc.
d) abdominal (gastralgic) variant - suddenly there is pain in the epigastric region,
accompanied by nausea, vomiting, paresis of the gastrointestinal tract with a sharp bloating,
muscle tension of the abdominal wall; more common with lower localization of necrosis
e) cerebral variant - may begin with clinical manifestations of a dynamic violation of
cerebral circulation (headache, dizziness, motor and sensory disorders).
f) peripheral with atypical localization of pain (left-handed, left-scapular, laryngeal-
pharyngeal, upper-vertebral, mandibular)
g) erased (oligosymptomatic)

Other rare atypical variants of MI: collaptoid; hydropic

3. Acute period (up to 10-12 days) - the boundaries of necrosis are finally determined,
myomalacia occurs in it; pain disappears, resorption-necrotic syndrome is characteristic
(increased body temperature to subfebrile, neutrophilic leukocytosis, increased ESR from 2-3
days for 4-5 days, increased activity of a number of cardiospecific enzymes in the BAC: AsAT,
LDH and LDH1, CK, CK- MB, myoglobin, TnT, TnI).

4. Subacute period (up to 1 month) - a scar is formed; soften and disappear manifestations of
resorption-necrotic syndrome, heart failure.

5. Postinfarction cardiosclerosis : early (up to 6 months) and late (after 6 months) -

consolidation of the resulting scar.

Diagnosis of IM.:According to WHO recommendations, the diagnosis of MI is made if at least

two of the three criteria are met :

1. Characteristic pain syndrome (status anginosus), not relieved by nitroglycerin

2. ECG changes typical of myocardial necrosis or ischemia

According to Bayley , ECG in MI is formed by the influence of three

zones : necrosis zone - located in the center of the lesion (Q
wave), damage zone - located on the periphery of the necrosis zone (ST
segment), ischemia zone - located on the periphery of the damage zone ( T wave)

Typical changes characteristic of Q -myocardial infarction :

1) the most acute period - at first, a high pointed T wave (there is only an
ischemia zone), then a dome-shaped elevation of the ST segment appears and its
merger with the T wave (a zone of damage appears); in the assignments
characterizing zones of a myocardium, opposite to an infarction, reciprocal
depression of the ST segment can be registered.

2) acute period - a zone of necrosis appears (pathological Q wave: duration of more than 0.03 s,
amplitude of more than ¼ of the R wave in leads I, aVL, V1-V6 or more than ½ of the R wave in
leads II, III, aVF), R wave may decrease or disappear; the formation of a negative T wave
begins.

3) subacute period - the ST segment returns to the isoline, a negative T wave is formed (the
presence of only zones of necrosis and ischemia is typical).

4) post-infarction cardiosclerosis - the pathological Q wave persists, the amplitude of the

negative T wave may decrease, over time it may become smoothed or even positive.

For nonQ-myocardial infarction, changes on the ECG will occur depending on the stage only
with the ST segment and the T wave. In addition to the typical changes on the ECG, MI may be
indicated by the first complete blockade of the left bundle branch block.
 Topical diagnosis of MI according to ECG data: anterior septal - V 1 -V 3 ; anterior apical - V 3 ,
V 4 ; anterolateral - I, aVL, V 3 -V 6 ; anterior extensive (common) - I, II, aVL, V 1 -
V 6 ; anteroposterior - I, II, III, aVL, aVF, V 1 -V 6 ; lateral deep - I, II, aVL, V 5 -V 6 ; lateral
high - I, II, aVL; posterior diaphragmatic (lower) - II, III, aVF.

With little information content of the standard ECG, you can take an ECG in additional leads
(according to the Sky, etc.) or do a cardiotopographic study (60 leads).

Indicators Terms of increase in blood

Start Maximum Duration

myoglobin 2-3 h 6-10 h 24-32 hours

Troponin-T 3-4 h 12-72 h 10-15 days

Troponin-I 4-6 h 24 hours 5-10 days

Creatine phosphokinase 3-8 h 24-36 hours 3-6 days

(CPK)

Creatine phosphokinase-MB 3-8 h 12-24 h 2-3 days

Aspartate aminotransferase 6-8 h 24-36 hours 5-6 days

Lactate dehydrogenase 8-10 h 48-72 h 10-14 days

isoform 1 (LDH 1)

3. Characteristic dynamics of serum enzymes.

Other research methods for MI:

a) non-invasive : scintigraphy with 99 m Tc-pyrophosphate (accumulates in the infarction zone,

forming a "hot" focus) and with 201 Tl (accumulates in a viable myocardium, forming a
"cold" focus in the infarct zone); radionuclide ventriculography; two-dimensional
echocardiography (reveals local violations of myocardial contractility, ruptures of the
 myocardium of the ventricles and papillary muscles, true and false aneurysms, intracardiac
thrombi, fluid in the pericardium, etc.)
b) invasive : ventriculography (allows to clarify the presence and localization of pathological
movements of the heart wall in patients with refractory pain syndrome and non-informative
ECG), coronary angiography (allows to detect coronary artery occlusion and decide whether
CABG or balloon angioplasty is appropriate).

Tactics of management and treatment of uncomplicated MI.

1. Resuscitation measures (at least 30 minutes): cardiac monitoring, chest compressions and
mechanical ventilation; defibrillation as early as possible (I category - 200 J, II - 300 J; III -
360 J, and so on), in the absence of effect - adrenaline (in / in, under the tongue,
intracardiac), in the absence of effect - antiarrhythmic therapy (lidocaine with repeated
defibrillation); 4% NaHCO 3 50-100 ml IV (due to metabolic acidosis).
2. Pain relief : neuroleptanalgesia (1-2 ml of 0.005% fentanyl solution + 2-4 ml of 0.25%
droperidol solution IV slowly in 10 ml of physical solution), ataralgesia (especially with
severe arousal , feeling of fear; 1 ml of 2% solution of promedol + 2 ml of diazepam IV
slowly in 10 ml of physical solution), morphine 2-5 mg intravenously every 5-15 minutes
until the pain is completely eliminated ( in case of its overdose: nalorfin 1-2 ml 0.5% solution
IV), clonidine 1 ml 0.01% solution IV slowly, nitrous oxide, sodium hydroxybutyrate.

a) restoration of coronary blood flow :

1) oxygen therapy (through nasal cannulas, 2-4 l/min).

2) thrombolytic therapy : streptokinase 1.5 million units in 100 ml of physical. intravenous drip
for 30 minutes + aspirin 325 mg chew (to prevent allergic reactions, prednisolone 90-120 mg or
hydrocortisone 75-150 mg IV) OR tissue plasminogen activator / alteplase IV bolus 10 mg , then
50 mg during the 1st hour and 20 mg each during the 2nd and 3rd hour

Indications for thrombolysis : ischemic chest pain lasting at least 30 minutes, not relieved by
repeated administration of nitroglycerin; elevation of the ST segment by 1-2 mm or more in at
least two adjacent chest leads (if anterior myocardial infarction is suspected) or in two of the
three "lower" limb leads - II, III, aVF (if inferior myocardial infarction is suspected ); the
appearance of a blockade of one of the legs of the bundle of His or idioventricular rhythm; the
ability to start thrombolytic therapy no later than 12 hours from the onset of the disease (but
better in the first 6 hours!)

Absolute contraindications to thrombolysis : acute bleeding; recent (less than 10 days) bleeding
from the gastrointestinal tract or urinary tract; surgical interventions, injuries, cardiopulmonary
resuscitation up to 10 days old; trauma or surgery to the brain or spinal cord within the last 2
months; hemorrhagic stroke in history; hemorrhagic diathesis, including thrombocytopenia
(platelets less than 100,000 in 1 mm 3 ); uncontrolled hypertension (BP above 200/120 mm Hg);
suspected dissecting aortic aneurysm; malignant neoplasms; allergic reactions to thrombolysis in
history (with the introduction of streptokinase and APSAK); streptokinase use in the last 6
months

Thrombolysis is effective if : a) the pain stopped or decreased; b) the ST segment decreased to

the isoline;

After the patient is delivered to the hospital : ECG every 3 hours (permanent cardiac monitoring
is better) + once a complete list of all cardiospecific enzymes (reference point), followed by a
study of those enzymes that should appear at the time of the study (depending on the dynamics
of MI).

3) antithrombotic therapy :

 aspirin 160-325 mg once chewed, then 75-160 mg / day daily or if intolerance and
contraindications ticlopidine / ticlid 250 mg 2 times / day, clopidogrel / plavix 75 mg 1 time
/ day
 heparin therapy (6-12 hours after thrombolysis): heparin 5,000 IU IV bolus, then 1,000 IU /
hour for 48-72 hours IV under the control of APTT (should increase 1.5-2 times from the
original ) OR low molecular weight heparins (nadroparin/fraxiparin 85-100 IU/kg 2
times/day, dalteparin/fragmin 100-120 IU/kg 2 times/day, enoxaparin/clexan 1 mg/kg 2
times/day)

4) invasive manipulations (balloon angioplasty with stenting, coronary artery bypass grafting)

b) hemodynamic unloading of the myocardium:

1) ACE inhibitors : captopril 12.5-100 mg / day, enalapril / berlipril / renitek 2.5-20 mg / day,
lisinopril / diroton 5-10 mg / day
2) beta-blockers : propranolol / obzidan IV bolus 1-2 mg every 5 minutes to a total dose of 10
mg or decrease in heart rate to 55 beats / min, followed by oral administration of 20-80 mg
every 6 hours
3) nitrates : nitroglycerin (2-4 ml 1% solution), perlinganite (20-40 ml 0.1% solution) or
isosorbide dinitrate / isoket (20-40 ml 0.1% solution) in / in drip in physical. solution with an
initial rate of 10 µg/min followed by an increase of 5 µg/min every 5-10 minutes for 48-72
hours min)

c) metabolic cardioprotection : alpha-tocopherol 2 ml 20-30% solution IM 2 times a day for the

first 3 days and 1 time a day for the next 10-12 days + phosphocreatinine / neoton 8 g / day iv 5
days + trimetazidine / preductal 20 mg orally 3 times / day + polarizing mixture (400 ml of 20%
glucose solution, 2-3 g of potassium chloride, 4-5 g of magnesium sulfate, 32 IU of insulin) IV
drip
4. Prevention of complications .ITU : general disability with small focal MI - 55-65 days (of
which in the hospital - 3-4 weeks), with large focal - 60-80 days (of which in the hospital - 4-5
weeks).

9. Complications of myocardial infarction (cardiogenic shock, pulmonary edema),

diagnosis and treatment.

1. Complications of the most acute period:

a) heart rhythm disturbances - all ventricular arrhythmias (ventricular paroxysmal tachycardia,

polytopic ventricular extrasystoles, etc.) are especially dangerous, which can lead to ventricular
fibrillation and cardiac arrest.

b) violations of AV conduction - more often occurs in the anterior and posterior septal forms of
MI

c) acute left ventricular failure : cardiac asthma, pulmonary edema

d) cardiogenic shock - a clinical syndrome caused by a sharp drop in the pumping function of
the heart, vascular insufficiency and severe disorganization of the microcirculation system.

Diagnostic criteria for cardiogenic shock :

4) symptoms of peripheral circulatory insufficiency: pale cyanotic, "marble", moist

skin; acrocyanosis; collapsed veins; cold hands and feet; decrease in body
temperature; prolongation of the disappearance of the white spot after pressing on the nail >
2 sec
5) impaired consciousness (lethargy, confusion, less often - arousal)
6) oliguria < 20 ml/h or anuria
7) SBP at two measurements < 90 mm Hg. Art. (with pre-existing hypertension < 100 mmHg)
8) decrease in pulse blood pressure to 20 mm Hg. and below
9) decrease in mean blood pressure < 60 mm Hg.
10) hemodynamic criteria: cardiac index < 2.5 l/min/m 2 ; "jamming" pressure in the pulmonary
artery> 15 mm Hg; increase in OPSS; decrease in stroke and minute volumes

The relief of cardiogenic shock is carried out in stages, but depending on the form of CABG,
these or other measures are performed in the first place:

1. In the absence of pronounced stagnation in the lungs, lay down with the lower limbs raised
at an angle of 20, in case of stagnation in the lungs - a position with a raised headboard
2. Oxygen therapy with 100% oxygen
3. With a pronounced anginal attack ( reflex form of KSh ): 1-2 ml of 0.005% fentanyl
solution OR 1 ml of 1% morphine solution OR 1 ml of 2% promedol solution intravenously
 slowly to eliminate pain impulses + 90-150 mg prednisolone or 150-300 mg hydrocortisone
IV slow bolus to stabilize blood pressure
4. In the case of an arrhythmic form of CABG with supraventricular and ventricular
tachyarrhythmias - 5-10 ml of 10% solution of novocainamide in combination with 0.2-0.3
ml of 1% solution of mezaton IV for 5 minutes --> no effect 6-10 ml of 2% lidocaine
(trimecaine) solution IV for 5 minutes --> no effect --> anesthesia with sodium thiopental,
sodium oxybutyrate + EIT, in acute bradyarrhythmia - 1-2 ml 0.1 % atropine solution IV
slowly AND / OR 1 ml of 0.05% solution of isadrin or alupent in 200 ml of 5% glucose
solution (or saline) IV drip under the control of blood pressure and heart rate.
5. In case of hypovolemia (CVD < 80-90 mm of water column - hypovolemic form of KSh ):
400 ml of dextran / sodium chloride / 5% glucose solution in / in drip with a gradual
increase in infusion rate until the signs of shock or CVP disappear until 120-140 mm w.c.
6. With a sharp decrease in the pumping function of the left ventricle ( the true form of KSh ):
 dopamine 200 mg in 400 ml of 5% glucose solution (saline) intravenously, the initial rate
of administration is 15-20 drops / min +
 1-2 ml of 0.2% norepinephrine solution in 200-400 ml of 5% glucose solution (saline)
intravenously under the control of blood pressure, the initial rate of administration is 15-
20 drops / min OR
 dobutamine / dobutrex 250 mg per 250 ml of saline IV drip, the initial rate of
administration is 15-20 drops / min

e) lesions of the gastrointestinal tract: paresis of the stomach and intestines (more often with
cardiogenic shock), stress-induced gastric bleeding

2. Complications of the acute period - all previous complications are possible +:

a) pericarditis - occurs when necrosis develops on the pericardium, usually 2-3 days from the
onset of the disease, while chest pains intensify or reappear, which are of a constant
pulsating nature, aggravated by inhalation, changing with changes in body position and
movements, auscultatory - pericardial rub
b) parietal thromboendocarditis - occurs with transmural MI with involvement of the
endocardium in the necrotic process; signs of inflammation persist for a long time or they
reappear after a certain calm period; the outcome of the process is thromboembolism in the
vessels of the brain, limbs and other vessels of the systemic circulation; diagnostics:
ventriculography, myocardial scintigraphy
c) myocardial ruptures:
1) external with cardiac tamponade - before the rupture, there is usually a period of
precursors in the form of recurrent pains that are not amenable to narcotic analgesics; the
moment of rupture is accompanied by severe pain with loss of consciousness, severe
cyanosis, the development of cardiogenic shock associated with cardiac tamponade
 2) internal rupture - in the form of a detachment of the papillary muscle (with MI of the
posterior wall) with the subsequent development of acute valvular insufficiency (often
mitral); characterized by severe pain, signs of cardiogenic shock, pulmonary edema,
palpation systolic tremor at the apex, percussion sharp increase in the boundaries of the
heart to the left, auscultatory rough systolic murmur with an epicenter at the apex of the
heart, conducted in the axillary region; in the form of a rupture of the interatrial and
interventricular septa

d) acute aneurysm of the heart - occurs during myomalacia with transmural MI, most often
located in the anterior wall and apex of the left ventricle; clinically - increasing left ventricular
failure, an increase in the boundaries of the heart and its volume, supraapical pulsation or rocker
symptom (supraapical pulsation + apical beat), if an aneurysm is formed on the anterior wall of
the heart; protodiastolic gallop rhythm, additional III tone, systolic murmur; discrepancy
between a strong pulsation of the heart and a weak filling of the pulse; "Frozen" ECG with signs
of MI without characteristic dynamics; ventriculography is indicated to verify the
diagnosis; surgical treatment

3. Complications of the subacute period:

a) chronic aneurysm of the heart - occurs as a result of stretching of the post-infarction

scar; signs of inflammation appear or persist for a long time, an increase in the size of the
heart, supraapical pulsation, double systolic or diastolic murmur are characteristic; on the
ECG - a frozen form of the curve of the acute phase
b) Dressler's syndrome (post-infarction syndrome) - associated with sensitization of the
body by autolysis products of necrotic masses, appears no earlier than 2-6 weeks. from the
onset of the disease; there are generalized lesions of the serous membranes (polyserositis),
sometimes with the involvement of the synovial membranes, clinically manifested by
pericarditis, pleurisy, joint damage (most often the left shoulder); pericarditis is initially
dry, then exudative, characterized by pain behind the sternum and in the side (associated
with lesions of the pericardium and pleura), undulating fever, soreness and swelling in the
sternocostal and sternoclavicular joints, in the KLA - accelerated ESR, leukocytosis,
eosinophilia; when prescribing GCS, all symptoms quickly disappear
c) thromboembolic complications - more often in the pulmonary circulation, where emboli
from the veins enter in case of thrombophlebitis of the lower extremities, pelvic veins (see
PE - question 151).

d) post-infarction angina pectoris

4. Complications of the chronic period: postinfarction cardiosclerosis - the outcome of

myocardial infarction associated with scar formation; manifested by disturbances in rhythm,
conduction, myocardial contractility
10. Arterial hypertension: etiology, pathogenesis, classification, risk stratification, clinical
picture, treatment.

Arterial hypertension is a stable increase in blood pressure - systolic to a value of  140 mm

Hg. and / or diastolic to a value of  90 mm Hg. according to the data of at least two
measurements according to the Korotkoff method at two or more consecutive visits of the patient
with an interval of at least 1 week.

Media and arterial hypertension are distinguished:

a) primary hypertension (essential, hypertension, 80% of all hypertension) - an increase

in blood pressure is the main, sometimes the only, symptom of the disease, not associated
with organic damage to the organs and systems that regulate blood pressure.
b) secondary hypertension ( symptomatic, 20% of all hypertension) - an increase in blood
pressure due to renal, endocrine, hemodynamic, neurogenic and other causes.

Epidemiology: AH is registered in 15-20% of adults; with age, the frequency increases (at 50-55
years old - in 50-60%);

The main etiological factors of essential hypertension.

a) hereditary predisposition (mutations in the genes of angiotensinogen, aldosterone synthetase,

sodium channels of the renal epithelium, endothelin, etc.)
b) acute and chronic psycho-emotional overstrain
c) excessive salt intake
d) insufficient intake of calcium and magnesium with food
e) bad habits (smoking, alcohol abuse)
f) obesity
g) low physical activity, hypodynamia

The main factors and mechanisms of the pathogenesis of essential hypertension .

1. Polygenic hereditary predisposition  defect in the plasma membrane of a number of cells

with a violation of its structure and ion transport function --> dysfunction of Na + /K + -
ATPase, calcium pumps  retention of Na + and fluid in the vascular wall, an increase in the
intracellular content of Ca 2 +  hypertonicity and hyperreactivity of SMC vessels.
2. Disbalance between pressor (catecholamines, RAAS factors, ADH) and depressor (atrial
natriuretic hormone, endothelial relaxing factor - nitric oxide, prostacyclins) factors.
3. Psycho-emotional overstrain --> formation of a focus of congestive excitation in the cerebral
cortex  disruption of the activity of vascular tone centers in the hypothalamus and medulla
oblongata  release of catecholamines 
a) an excessive increase in sympathetic vasoconstrictor effects on α 1 -adrenergic receptors of
resistive vessels --> an increase in OPSS (trigger).
b) increased protein synthesis, growth of cardiomyocytes and SMC and their hypertrophy
c) narrowing of the renal arteries  renal tissue ischemia --> hyperproduction of renin by cells
of the juxtaglomerular apparatus --> activation of the renin-angiotensin system  production
of angiotensin II  vasoconstriction, myocardial hypertrophy, stimulation of aldosterone
production (in turn, aldosterone promotes sodium and water retention in the body and
secretion of ADH with further accumulation of fluid in the vascular bed)

The above mechanisms cause an increase in blood pressure , which leads to:

1. hypertrophy of the walls of arteries and myocardium  development of relative coronary

insufficiency (because the growth of myocardial capillaries does not keep pace with the
growth of cardiomyocytes)  chronic ischemia --> growth of connective tissue -->
diffuse cardiosclerosis.
2. prolonged spasm of the renal vessels  hyalinosis, arteriolosclerosis --> primary wrinkled
kidney  CRF
3. chronic cerebrovascular insufficiency --> encephalopathy, etc.

Classification of essential hypertension:

Categories SBP mmHg Art. DBP mmHg Art.

Optimal blood pressure < 120 < 80 (up to 60)

Normal BP < 130 < 85

High normal BP < 130-139 < 85-89

Arterial hypertension:

Grade I (mild) 140-159 90-99

Grade II (moderate) 160-179 100-109

Grade III (severe) > 180 > 110

Isolated systolic hypertension > 140 < 90

Notes : 1) with different SBP and DBP, they are guided by a higher value 2) against the
background of antihypertensive therapy, the degree of AH increases by 1 level.
Risk stratification - the probability of developing cardiovascular complications in a given patient
in the next 10 years (risk 1 - up to 15%, risk 2 - 15-20%, risk 3 - 20-30%, risk 4 - more than
30%).

Determining the degree of risk:

Other risk factors (except for

hypertension), target organ damage Grade I Grade II Grade III
(POM), comorbidities:

1. No low risk Medium risk high risk

2. 1-2 risk factors Medium risk Medium risk Very high risk

3. 3 or more risk factors or POM high risk high risk Very high risk

4. Associated clinical conditions Very high risk Very high risk Very high risk

NB! The diagnosis of hypertension indicates its degree (I, II or III) and risk (1, 2, 3, 4).

Clinical manifestations of arterial hypertension.

1. Subjectively - complaints about:

 headaches - occur mainly in the morning, of varying intensity (from mild, perceived as a
feeling of heaviness in the head, to significant, strong stabbing or squeezing), localization
(more often in the back of the head, less often in the temporal region, forehead, crown); more
often the pain increases with increasing pressure and decreases with its decrease; may be
accompanied by dizziness, staggering when walking, a feeling of congestion or tinnitus, etc.
 flickering of flies, the appearance of circles, spots, a feeling of a veil, fog before the eyes,
with a severe course of the disease - progressive loss of vision
 unstable mood, irritability, tearfulness, sometimes depression, fatigue (neurotic disorders,
detected in half of patients with hypertension)
 pain in the heart area - moderately intense, more often in the apex of the heart, appear after
emotional stress and are not associated with physical stress; may be long-term, unresponsive
to nitrates, but decreasing after sedation
 palpitations (more often as a result of sinus tachycardia, less often - paroxysmal), a feeling of
interruptions in the region of the heart (due to extrasystole)

2. Objectively :
a) examination - increased body weight can be detected, with the development of CHF -
acrocyanosis, shortness of breath, peripheral edema
b) palpation of the peripheral arteries (common carotid, temporal, subclavian, brachial) -
suggests the development of an atherosclerotic process in them: the arteries are well palpable,
dense, tortuous, beaded, the pulsation is reduced, tense, difficult to compress.
c) percussion of the borders of the heart - their expansion to the left with myocardial
hypertrophy.
d) auscultation of the carotid, subclavian arteries, abdominal aorta, renal and iliac arteries
(systolic murmur in stenosing lesions), heart (accent of the II tone over the aorta, with aortic
atherosclerosis - systolic ejection murmur at the base of the heart on the right).

In the diagnosis of hypertension , there are two levels of examination of the patient:

a) outpatient - examination plan:

1) laboratory methods : KLA, OAM, BAC (total lipids, cholesterol, glucose, urea, creatinine,
proteinogram, electrolytes - potassium, sodium, calcium)

2) instrumental methods :

 ECG (to assess the degree of myocardial hypertrophy, determine ischemic changes)
 rheoencephalography (to determine the type of cerebral hemodynamics)
 chest x-ray
 Examination of the fundus by an ophthalmologist
 load tests
 if possible, it is also desirable to perform: Echo-KG, ultrasound of the kidneys, examination
of the thyroid gland, tetrapolar replethysmography (to determine the type of hemodynamic
disorder)

b) stationary : the patient is additionally examined by all possible methods in order to confirm
hypertension and establish its stability, exclude its secondary origin, identify risk factors, damage
to target organs, concomitant clinical conditions.

Principles of treatment of hypertension.

1. Goals of primary hypertension treatment:

1) the maximum tolerated by the patient decrease in SBP and DBP with the help of non-drug
measures and drugs
2) prevention of target organ damage, and if present, their stabilization and regression
3) reduced risk of cardiovascular complications and mortality
4) increasing the duration and quality of life of the patient.

The reduction in blood pressure is achieved by the following activities:

a) non- medical measures, the benefits of which have been proven:

 increase in dosed physical activity (up to 30-45 minutes daily)

 reduction of excess body weight
 reduction of the daily calorie content of the diet to 1200 kcal
 limiting the intake of animal fats, cholesterol
 restriction of sodium intake from food to 5-6 g of table salt per day
 increase in potassium intake with food up to 1.5 g / day
 limiting alcohol consumption to 168 ml of 100% alcohol per week for men (30 ml/day of
alcohol = 60 ml/day of vodka = 240 ml/day of wine = 700 ml/day of beer) and to 112 ml per
week for women
 regular isotonic outdoor exercise of moderate intensity and duration of at least 30-60
minutes, 3-4 times a week (metered brisk walking, swimming, cycling);
 to give up smoking

Activities that are recommended, although their benefits have not been proven: the use of
nutritional supplements containing calcium, magnesium; the use of fish oil; limiting caffeine
intake (tea, coffee); - use of relaxation methods, normalization of sleep.

b) long-term pharmacotherapy - basic principles:

1) the beginning of treatment with the minimum doses of one drug, selected taking into account
indications and contraindications
2) transition to drugs of another class with insufficient effect (after increasing the dose of the
first) or poor tolerance
3) the use of long-acting drugs (24-hour effect with a single dose)
4) a combination of drugs for maximum hypotensive effect and reduction of undesirable
manifestations

The main groups of antihypertensive drugs:

a) drugs of the first line

1) thiazides and thiazide-like diuretics: hydrochlorothiazide, cyclomethiazide, clopamide,

brinaldix, indapamide - are used in small doses, the effect occurs after 3-4 weeks: indapamide
(arifon) 2.5 mg 1 time per day

2) beta blockers :

- non-cardioselective:

a) without sympathomimetic activity: propranolol, sotalol

b) with sympathomimetic activity: trazikor, pindolol (whisken), alprenolol, betapressin,
labetalol.
- cardioselective beta-1-blockers:

 without sympathomimetic activity: metaprolol (specicor), atenolol (tenormin), bisoprolol,

carvedilol, nebivalol.
 with sympathomimetic activity: acebutalol (sectral), talinolol (cordanum), epanolol.

Average daily doses: atenolol 25-100 mg/day in 1-2 doses, bisoprolol 2.5-10 mg/day in 1 dose,
propranolol 40-240 mg/day in 2-3 doses, pindolol 14-40 mg/day in 2-3 doses.

3) calcium channel blockers :

a) L-type (by chemical structure):

-phenylalkylamine derivatives: verapamil, gallopamil

benzothiazepine derivatives: diltiazem, klentiazem

- dihydropyridine derivatives: nifedipine, amlodipine, nisoldipine, nitrendipine, relodipine

b) T-type: mibephradil

Average daily doses: amlodipine 5–10 mg/day, verapamil retard 120–480 mg/day, diltiazem
retard 120–360 mg/day, isradipine 5–10 mg/day, isradipine retard 5–10 mg/day, nifedipine -
retard 30-60 mg/day, felodipine-retard 5-10 mg/day.

4) ACE inhibitors

Class I - lipophilic drugs: captopril, alacepril, altiopril

Class II - lipophilic prodrugs:

subclass IIA - drugs whose active metabolites are excreted mainly through the kidneys:
benazepril, quinapril, perindopril, cilazapril, enalapril

subclass IIB - drugs whose active metabolites are excreted both through the kidneys and with
bile and feces: moexipril, ramipril, spirapril, trandolapril, fosinopril

Class III - hydrophilic drugs: lisinopril, ceronapril

Average daily doses: captopril 50-100 mg/day, berlipril 5-15 mg/day, ramipril 5-10 mg/day,
fosinopril 20-40 mg/day, cilazapril 2.5-5 mg/day, enalapril 10-24 mg /day

5) angiotensin II receptor antagonists : losartan, valsartan, irbesartan

6) alpha-blockers : prazosin, cardura.

b) drugs of the second line - are used mainly for the relief of crises
 1) potassium-sparing : spironolactone, triamterene and loop : furosemide diuretics
2) direct vasodilators : hydralazine, diazoxide.
3) neurotropic agents of central action : clonidine, dopegyt, reserpine
4) ganglionic blockers : hexamethonium, benzohexonium, pentaminewith an unknown
mechanism of action : magnesium sulfate, dibazol

Factors affecting the prognosis and used for risk stratification:

Risk factors for cardiovascular disease Target organ damage Concomitant (associated) clinical
conditions

A. Used for risk stratification: - left ventricular hypertrophy Cerebrovascular diseases:

(ECG, radiography,
- age: men > 55 years old, women > 65 echocardiography) - ischemic stroke
years old
- proteinuria and / or a slight - hemorrhagic stroke
- smoking increase in plasma creatinine (1.2- - transient ischemic attack.
- total blood cholesterol > 5.0 mmol/l 2.0 mg / dl)
Heart disease:
- SD (immediate risk 4) - ultrasound or radiological signs of
atherosclerotic plaque (carotid, iliac - myocardial infarction
- family history of early development and femoral arteries, aorta)
of cardiovascular disease - angina pectoris
- generalized or focal narrowing of
(under 55 for men, under 65 for - revascularization of the coronary
the retinal arteries
women) arteries

- congestive heart failure

B. Other factors that adversely affect
Vascular diseases:
the prognosis:
- dissecting aortic aneurysm
- reduced HDL cholesterol
- clinically manifested peripheral
- increased LDL cholesterol
arterial disease
- microalbuminuria (30-300 mg/day) in
Severe hypertensive retinopathy
diabetes
- hemorrhages or exudates
- Impaired glucose tolerance
- swelling of the optic nerve
- obesity
Kidney diseases:
- sedentary lifestyle
- elevated fibrinogen levels - diabetic nephropathy

- high-risk socio-economic factors - renal failure (plasma creatinine >

2.0 mg/dl)
- high risk ethnic group

- geographic region of high risk.

11. Symptomatic arterial hypertension. Differential diagnosis, treatment features.

Symptomatic hypertension (SAH) is arterial hypertension with an established cause (5-10% of

all hypertension).

Classification of symptomatic hypertension:

1. Renal hypertension is the most common cause of SAH:

a) acquired kidney diseases (chronic glomerulonephritis, chronic pyelonephritis, diabetic

glomerulosclerosis, tumors, etc.)
b) congenital anomalies of the kidneys (hypoplasia, polycystosis, horseshoe kidney, etc.)
c) lesions of the renal arteries - renovascular hypertension (fibromuscular dysplasia of the renal
artery, atherosclerotic stenosis of the renal artery, etc.)

2. Endocrine Ag:

a) Itsenko-Cushing's disease and syndrome

b) pheochromocytoma
c) primary hyperaldosteronism (Conn's syndrome)
d) toxic goiter
e) acromegaly
f) menopausal hypertension

3. Hemodynamic (cardiovascular) hypertension:

a) coarctation of the aorta

b) aortic atherosclerosis
c) aortic valve insufficiency
d) stenotic lesion of the carotid and vertebrobasilar arteries
e) complete atrioventricular blockade
f) nonspecific aortoartery

4. Neurogenic or hypertension in diseases of the central nervous system:

a) hypothalamic syndrome
b) subarachnoid hemorrhage
c) brain tumors and cysts
d) trauma, brain abscesses
e) meningitis, meningoencephalitis

5. Hypertension associated with taking medications, alcohol and drugs:

a) taking GCS (patients with bronchial asthma, rheumatological diseases, etc.)

b) taking NSAIDs (patients with rheumatological, nervous diseases)
c) taking sympathomimetics (patients with bronchial asthma, when taking anorexants to
reduce appetite for weight loss)
d) taking MAO inhibitors and tricyclic antidepressants in patients with CNS diseases
e) taking oral contraceptives
f) use of alcohol, cocaine, etc.

6. Combined arterial hypertension: diabetic glomerulosclerosis + chronic pyeloneuritis, aortic

atherosclerosis + renal artery atherosclerosis, etc.

Signs that can be suspected of SAG:

1) onset before the age of 20 and after 50-55 years

2) rapidly progressive or malignant hypertension (constantly high blood pressure  220/130,
severe damage to the fundus, rapidly progressive renal failure, frequent attacks of acute left
ventricular failure, hypertensive encephalopathy, repeated cerebrovascular accidents)
3) target organ damage (retinopathy grade 2 or higher, serum creatinine more than 0.15 mg/l,
left ventricular hypertrophy or cardiomegaly according to echocardiography)
4) ineffectiveness of combined (three- or even four-component) antihypertensive therapy
5) exacerbation of hypertension, initially treatable
6) anamnestic, physical and laboratory data indicating SAH (AGN; the presence of crises
suspected of pheochromocytoma; bulging eyes and enlargement of the thyroid gland with
toxic goiter, changes in urine tests, etc.)

Clinical and diagnostic features of certain types of SAH and approaches to their treatment:

a) renal SAH:

1. chronic glomerulonephritis : young age of patients; connection of the disease with

streptococcal or viral infection, hypothermia; change in the color of urine such as "meat
slops" in history; the presence of edema; in urine tests, proteinuria, often  1 g / l,
erythrocyturia, cylindruria; in the presence of chronic renal failure - an increase in the
content of urea, creatinine in the blood; decrease in glomerular filtration and specific gravity
of urine; changes in the echogenicity of the parenchyma of both kidneys on the sonogram of
 the kidneys, lengthening of the secretory segments on the RRG; morphological diagnosis
according to kidney biopsy.
2. chronic pyelonephritis : more common in women; connection of the disease with
pregnancy, gynecological diseases, hypothermia, urolithiasis, kidney anomalies; in the
clinical picture - fever, chills, dysuric phenomena, cloudy urine, back pain, pain on palpation
of the kidneys; in OAM - pyuria, bacteriuria; growth of pathogenic microflora in urine
culture; in the event of chronic renal failure - an increase in urea and creatinine, a decrease in
GFR; characteristic changes on the intravenous urogram and sonogram (atony and deformity
of the calyces and pelvis), elongation of the excretory segment of the RRG on the side of the
lesion
3. diabetic glomerulosclerosis : a long history of diabetes; inadequate treatment of
diabetes; edematous syndrome, hypoproteinemia, proteinuria, cylindruria; rapid increase in
CKD
4. polycystic kidney disease : average age of patients; burdened family history; on palpation of
the abdominal cavity, large tuberous kidneys are determined; typical picture of numerous
cysts on sonogram, intravenous urogram, angiogram
5. renal artery stenosis : young women (fibromuscular dysplasia), elderly men (atherosclerotic
stenosis); severe, often malignant hypertension; in 40% of patients, a systolic murmur is
heard near the navel and in the lateral sections of the abdomen; no or minimal changes in
urine tests; on RWG there is a decrease in the vascular segment on the affected
side; acceleration of blood flow and slowing down of reaching the peak velocity in the
Doppler spectroscopy of the renal artery blood flow on the side of the lesion

Treatment of renal hypertension:

a) conservative:Restriction of salt and protein intake (especially in diabetic glomerulosclerosis

and CRF) + loop diuretics (especially in CRF)  no effect  calcium antagonists (nifedipine,
isradipine, amlodipine)  no effect  ACE inhibitors (especially indicated in diabetic
glomerulosclerosis, because slow down further progression of kidney damage in diabetes;
contraindicated in bilateral renal artery stenosis or renal artery stenosis of a single kidney,
because in these cases lead to a sharp decrease in GFR)  no effect   -adrenergic blocker
(prazosin) or - adrenoblocker (labetalol)  no effect  potassium channel activator, direct
vasodilator minoxidil 10-25 mg/day in 2 doses (reserve drug for the treatment of severe
hypertension)

b) surgical:

1. Reconstructive surgery on the renal arteries (balloon angioplasty, resection of the stenosis
site and end-to-end anastomosis, endarterioectomy, aorto-renal bypass grafting)
2. Unilateral nephrectomy with wrinkling of one of the kidneys, impossibility of reconstructive
surgery on the renal vessel with unilateral lesion
3. Bilateral nephrectomy for bilateral lesion with end-stage renal failure and malignant course
of hypertension followed by hemodialysis and donor kidney transplantation

b) endocrine SAG:

1. disease (pituitary adenoma, excessively producing ACTH, causing hyperplasia of the adrenal
glands and the release of an increased amount of corticosteroids into the blood)
and syndrome (corticosteroma, corticoblastoma - tumors of the adrenal cortex, causing
increased secretion of corticosteroids into the blood) Itsenko-Cushing : obesity of the upper half
of the body, moon-shaped face; striae on the abdomen, thighs; hirsutism, dry skin, multiple
acne; dystrophy of the nail phalanges; steroid ulcers; polycythemia; bone pain due to
osteoporosis; secondary SD; dysfunction of the reproductive system; daily urinary excretion of
free cortisol  100 mcg; visualization of the tumor on CT scan of the brain or adrenal glands

Treatment: surgical (transsphenoidal removal of pituitary adenoma, adrenalectomy, destruction

of the adrenal gland with the introduction of ethanol); gamma irradiation of the pituitary
gland; adjuvant therapy therapy: parlodel and peritol (reduce the secretion of corticotropic
hormones); chlorditan, aminoglutethimide and ketoconazole (block steroidogenesis in the
adrenal glands).

2. pheochromocytoma (a hormone-active tumor from mature cells of the chromaffin tissue of

the adrenal medulla, causing excessive secretion of adrenaline, norepinephrine and dopamine,
less often - a tumor of the paraganglia of the aorta, sympathetic ganglions and plexuses) -
periodic release of catecholamines into the blood  sudden, within a few minutes, increase in
blood pressure above 300 mm Hg, accompanied by pronounced autonomic disorders
(palpitations, trembling, sweating, fear, anxiety, skin manifestations, increased blood glucose
with thirst during a crisis, polyuria after it, a tendency to orthostatic pressure drop); weight loss
(due to increased basal metabolism); excretion of adrenaline and norepinephrine above 100 mcg
/ day in daily urine; test with alpha-adrenergic blockers: phentolamine 0.5% - 1 ml intravenously
or intramuscularly than by 80 mm Hg, and DBP by 60 mm Hg. after 1-2 minutes - a positive test
for pheochromocytoma; CT scan of the adrenal glands; hyperglycemia and leukocytosis during a
crisis

Treatment: surgical - removal of the tumor, conservative treatment for crisis and persistent
hypertension - -blockers (phentolamine, prazosin)

3. primary hyperaldosteronism (Kohn's syndrome, caused by aldosterone-producing adenoma

of the adrenal cortex or bilateral hyperplasia of the adrenal cortex)

At the heart of pathogenesis : increased intake of aldosterone, which enhances tubular

reabsorption of Na + --> replacement of intracellular K + with Na + --> accumulation of sodium
and water inside cells, including in the vascular wall --> narrowing of the lumen of the vessels,
increase sensitivity of SMC to humoral pressor substances --> AG.
Clinical and diagnostic features : stable and steady increase in hypertension, resistant to
conventional antihypertensive drugs, except for veroshpiron / spironolactone, an aldosterone
antagonist; signs of severe hypokalemia: muscle disorders (muscle weakness, adynamia,
parasthesia, there may be paresis, functional paralysis); changes in the CCC (tachycardia,
extrasystole, other rhythm disturbances); LHC: increased sodium, decreased potassium; OAM:
isohypostenuria, alkaline urine reaction; ECG: electrolyte disturbances (arrhythmias, ST-segment
depression, T-wave inversion, abnormal U-wave, prolongation of electrical systole, prolongation
of the QT interval); visualization of the tumor by CT and ultrasound

Treatment: surgical - resection of the adrenal gland, conservative - aldosterone antagonists

(spironolactone), salt restriction, diet rich in potassium + potassium preparations (panangin); in
the absence of effect - calcium channel blockers or ACE inhibitors.

4. toxic goiter - a hereditary autoimmune disease leading to the appearance of IgG, which
stimulate the thyroid gland, causing an increased release of T 3 and T 4 into the blood , increased
and increased heart contractions and hypertension: increased mental excitability and
irritability; thickening of the neck; weight loss sweating, feeling hot; palpitations, extrasystole,
atrial fibrillation; hand tremor, muscle weakness, shortness of breath; bulging eyes, typical eye
symptoms; an increase in the content of T 3 and T 4 in the blood; an increase in the thyroid gland
and a decrease in the echogenicity of the parenchyma during sonography; increased absorption
of radioactive iodine during isotopic examination of the thyroid gland.

Treatment : thyreostatics (mercasolil, potassium perchlorate, lithium carbonate, microiodine

preparations); -blockers; radioactive iodine treatment; surgical - subtotal resection of the
thyroid gland

c) hemodynamic SAG:

1. coarctation of the aorta - congenital narrowing of the aorta below the place of origin of the
left subclavian artery, leading to a sharp increase in resistance to blood flow in the area of
narrowing and impaired blood circulation in the kidneys, because. renal arteries depart distal to
the site of narrowing: the predominant development of the upper half of the body over the
lower; Blood pressure on the arms is higher than on the legs (normally vice versa); cold feet and
intermittent claudication; systolic trembling over the notch of the sternum; systolic murmur
heard better on the back of the chest on the left; lack of pulse on the femoral artery; on a plain
chest radiograph: rib usuration due to increased collateral blood flow through the intercostal
arteries, deformity of the aortic arch in the form of the number “3”; visualization of stenosis with
Echo-KG and angiography

Treatment: surgical correction; ACE inhibitors, calcium antagonists.

2. atherosclerosis of the aorta - hypertension occurs due to the impossibility of adequate

stretching of the aorta during the ejection of blood: increased SBP, normal DBP; systolic
murmur in the 2nd intercostal space on the right; induration of the aortic wall on a plain chest x-
ray

Treatment: small doses (because there is a high risk of cerebral ischemia in the elderly) calcium
antagonists, ACE inhibitors, diuretics.

3. complete AV blockade - leads to lengthening of the diastole and an increase in the end
diastolic volume of the left ventricle, while a larger stroke volume of blood enters the aorta
during systole, causing a compensatory increase in vascular resistance: shortness of breath,
palpitations; dizziness, fainting, Morgagni-Adams-Stokes attacks; bradycardia  40 beats per
minute, “cannon” 1st tone at the top during auscultation; complete A-V blockade on the ECG.

Treatment: surgical (implantation of a permanent pacemaker with physiological heart rate), ACE
inhibitors, diuretics

+4. aortic valve insufficiency - the return of blood back to the left ventricle in diastole leads to
an increase in the end diastolic volume of the left ventricle and an increase in stroke output in
systole: SBP is increased, DBP is sharply reduced, in some cases even to zero; shortness of
breath, palpitations, dizziness, pallor of the skin; protodiastolic murmur in the 2nd intercostal
space on the right and at the Botkin point, weakening of the 2nd tone on the aorta; tendency to
tachycardia; an increase in the size of the heart to the left during percussion and on a plain chest
radiograph (aortic configuration); direct signs of aortic malformation by Echo-KG

Treatment : surgical: aortic valve replacement, ACE inhibitors.

12. Plan and algorithm evaluation of patients with elevated blood pressure. Differentiated
approach to treatment.

13. Etiology, pathogenesis, clinical picture, treatment of acute rheumatic fever.

Toxic-immunological systemic inflammatory disease of connective tissue with a predominant

localization of process in CVS, that occurs as a delayed sequel to group A streptococcal infection

EPIDEMIOLOGY: Mostly affect children (7-15 years), from lower socio-economic class living
in crowded conditions

ETIOLOGY: Highly virulent strain (beta hemolytic group A streptococcus)

PATHOGENESIS: Toxic-immunological theory. Streptococcus produces substances with a

pronounced cardiotoxic effect and capable of suppressing phagocytosis, damage lysosomal
membranes, main substance of connective tissue (M-protein, peptidoglycan, streptolysin-O and
S, hyaluronidase, streptokinase, deoxy ribonuclease, etc.). There is certain immunological
relationship between streptococcal antigen and myocardial tissues. Streptococcal toxins cause
inflammation in body tissues, CVS. Presence of antigenic commonality between streptococcus
and heart leads to an activation of an autoimmune mechanisms – appearance of autoantibodies to
myocardium, antigenic components of connective tissues, formation of immune complexes and
aggravation of inflammation. Immune inflammatory process cause disorganization of connective
tissue, which occur in successive stages

 Mucoid swelling (disorganization of collagen fibers) – reversible, last 1-2 months

 Fibrinoid changes (irreversible fibrinoid necrosis)
 Proliferative changed (granulomatosis) – cells (histocytes, lymphoid, plasma and mast
cells) accumulate around the vessels, in myocardium, endocardium and form
AschoffTalalaev granuloma
 Sclerosis – granuloma turns into fibroblasts and scar develops (heart defect formed)

Favorite location is the mitral valve, less often aortic ant tricuspid

CLINICAL MANIFESTATIONS

 Main clinical signs are carditis, polyarthritis, minor chorea, EM, s/c rheumatic nodules
 First attack begins in almost every 2nd child 1-2 weeks after and acute or exacerbation of
chronic streptococcal infection – increase temperature to febrile, symmetrical migrating
arthritis (mostly knee) and signs of carditis (pain in heart, SOB, palpitation)
 Rest of the children have monosyndromic course with a preponderance of signs or arthritis or
carditis, or rarely chorea
 Acute, but the type of “outbreak” developsin middle school children and soldiers wo have
suffered from angina
 For adolescence and young people, gradual onset – after clinical manifestation of angina
subside, sub febrile fever, pain in large joints or moderate signs of carditis
 A repeat attack is a new episode, not a relapse – carditis, less carditis and polyarthritis, rarely
chorea

Carditis (mostly endomyocarditis) : SOB, palpitations, chest pain , Tachycardia, cardiomegaly,

new/changes murmur

 Systolic murmur of mitral regurgitation – long lasting, different intensity, doesn’t change
with changes in position and breathing, associated with 1st tone and occupies most systole
with epicenter at top of hears, radiate to left axillary region
 Mesodiatolic murmur in acute carditis w/ MR – often after 3rd tone or drowns it out, heard at
top of heart in patient position on left side while holding breath on exhalation
 Protodiastolic murmur of AR – immediately after 2nd tone, high frequency blowing
decreasing character, best heard along left edge of sternum after deep exhalation when
patient leans forward, combined with systolic murmur
 MS – all 3 of the above
Migratory large-joint polyarthritis : Large joints (mainly knee, then ankle, elbow or wrist) ,
Red, warm and swollen, asymmetric, not deformed

Subcutaneous nodules : Mainly over bony surfaces, joint prominence and tendons , Lasts 1-2
weeks , Small (0.5-2cm), firm and painless , Occur after >3 weeks of onset

Erythema marginatum : Red macule, late fade in center but red at edges , Mainly on trunk and
proximal extremities, NOT face , Exacerbated by heart. Fades and reappear in hours

Sydenham’s chorea : Mostly in women, late neurological manifestation after 3 months .

Emotional lability , Followed by purposeless, involuntary, choreiform movement of hand, feet
and face , Explosive or halting speech , OCD

DIAGNOSTICS

 Blood test – Leukocytosis with left shift, increased ESR (>30mm/hr.) and positive CRP
 Bacteriological – detect BHSA in smear from pharynx
 Rapid Ag testing
 Serological – increased or increasing tires of anti-streptolysin O (>200 U), anti
streptohyalurondase and anti-deoxyribonuclease
 ECG – ST and T wave change, AV block – syncope
 Echocardiography – diagnosis of valvular heart disease and detection of pericarditis, cardiac
dilation
 CXR – cardiomegaly, pulmonary congestion

DIAGNOSTIC CRITERIA:

 Major : Carditis , Polyarthritis , Chorea , EM , S/C rheumatoid nodules

 Minor : Arthralgia , Fever , Prolonged PR , Increased ESR and CPR
 Evidence of Group A B-streptococcal pharyngitis (+ve throat/rapid Ag or increase Ab titer)
Evidence + 2 major or 1 major 2 minor = Acute Rheumatic Fever
 Special cases o Isolated chorea in absence of other causes o Late carditis – >2 months of
clinic and instrumental symptoms of vasculitis

TREATMENT

• Etiotropic (anti-streptococcal) therapy

 Benzylpenicillin 0.5-1mU QDS IM for 10 days (adults), 100,000-150,000 U QDS

(children)
 Penicillin allergic – Erythromycin PO 1 hours before meals for 10 days

• Anti-inflammatory:
  Glucocorticosteroids – prednisone 15-20mg/day in morning after meals – 2 weeks then
decrease reduced 2.5mg/week until complete withdrawal (total maybe 4 months)
 Used in acute respiratory viral infections with severe carditis and/or polyserositis.
NSAIDs – diclofenac 25-50 mg TDS until normalization of inflammatory activity (2
months)
 Mild vasculitis, rheumatic arthritis with valvulitis, minimal activity of process, after high
activity subsides and withdrawal, repeated ARF on background of heart disease Aspirin
PO 4-8g daily until ESR and ERP normalize

• Treatment of Heart failure

 Diuretics, Beta blockers, long acting calcium channel blockers

 ACE inhibitors might weaken the action of NSAID as they both effect prostaglandin
synthesis

• Surgical: Indications: pronounced clinical manifestations of heart disease or its complications

14. Mitral valve disease: etiology, pathogenesis, clinical picture, treatment.

Mitral regurgitation

ETIOLOGY

 Expansion of LV cavity and stretching of fibrous mitral annulus

 Mitral valve prolapse due to chord lengthening in connective tissue dysplasia
 Dysfunction of papillary muscles
 Rupture of chords or papillary muscles in acute MI, IE, ARF, osteogenesis imperfecta, heart
injuries – spontaneous rupture of tendon chords
 Primary idiopathic calcification of annulus fibrosus, chorda, papillary muscles
 Displacement of anterior cusps of mitral valve to interventricular septum during systole in
obstructive form of hypertrophic cardiomyopathy

PATHOGENESIS OF HEMODYNAMIC DISTURBANCES : During LV systole, some

blood returns to LA, increase blood volume and pressure in LA by beginning of diastole
stretching and dilation of LA during diastole LV overfilled due to regurgitated blood increases
stroke volume LV undergoes volume overload LV hypertrophy hyperdynamic LV over time,
contractile capacity LV decreases increase diastolic pressure in LV (stage I defect compensation)
increase pressure in LA (stage II compensation) increase pressure in pulmonary vein pulmonary
HTN RV pressure increases (sage III compensation) RV hypertrophy left and right HF

CLINICAL PRESENTATION

 Complaints absent for a long time

 First manifestations are due to decrease in SV and increase in pulmonary circulation pressure
–Rapid fatigue, muscle weakness, heaviness in legs, palpitations, SOB, only with PE
 As disease progresses, SOB at rest, reaching orthopnea
 Pulse become rapid, reflects decrease in SV and reflex activation of sympatho-adrenal
system
 In severe cases – cardiac asthma, dry cough with small mucosal sputum, sometime with
blood

Inspection With a small degree – no external manifestation of heart defect, Hemodynamically

significant valve defect with pHTN and decrease in effective cardiac output – acrocyanosis,
facies mitralis (bright cyanotic blush on cheeks), With RV insufficiency – edema of legs,
swelling of cervical veins, increasing volume of abdomen due to ascites

Palpation : Apical impulse amplified, diffused, shifts to left ,Systolic tremor, as a low frequency
equivalent of systolic murmur , In severe cases – increased heart pulse, localized in III-IV
intercostal space to left of sternum, as well as epigastric pulsation

Percussion : Displacement of left border of relative heart dullness due to LV dilation , Upper
border of relative heart dullness is shifted up only with pronounced dilation of RA

Auscultation : Weakening of S1 at top or even disappearance (valve doesn’t close) , Increased

S2 on pulmonary artery in late stages, with occurrence of LVF and pHTN , S3 caused by volume
overload of LV , Systolic murmur – follows or merges with S1, ribbon or fusiform shape,
occupying 2/3rd or entire systole (pansystolic). Heard at apex and radiate to left axilla ,
Functional diastolic murmur (Coombs noise) – appears with significant dilation of LV and LA in
absence of expansion of fibrous ring of valve

PROGNOSIS

 Asymptomatic for many years.

 Sudden deterioration (chord rupture, infectious endocarditis).
 Survival rate for 5 years-more than 80%, during 10 years - more than 60%.
 If severe mitral insufficiency is caused by myocardial ischemia, the prognosis is worse
(survival rate for 5 years - 30%).

INDICATIONS FOR SURGERY

 Severe clinical manifestations caused by mitral insufficiency (acute or chronic).

 The presence of atrial fibrillation.
 Pulmonary hypertension (pulmonary artery pressure greater than 50 mmHg at rest or greater
than 60 mmHg at exertion).
 The presence of pronounced LV systolic dysfunction (LV EF less than 30%, of course, the
LV systolic size is more than 55 mm) with a high probability of chord preservation.
Mitral stenosis

ETIOLOGY

o Main cause is rheumatic fever (99%)

o Other causes
 Infective endocarditis
 Chronic valvulitis
 LA myxoma
 Round valvular thrombus
 Mucopolysaccharidosis
 Atherosclerosis with damage to mitral valve flaps (fibrosis, calcinosis)

• Stenosis occurs as 3 levels

 Chorda (fuse, thicken and shorten)

 Cusps (thicken and calcify)
 Commissures (fuse with cusps)

PATHOGENESIS OF HEMODYNAMIC DISTURBANCES

 Normal opening 4-6cm2, <2cm2 increase LA pressure, <1cm2 critical (change in

hemodynamics)
 Due to narrowing, decrease blood flow in to LV during diastole , increase in volume and
pressure in LA , dilation and hypertrophy of LA (enlargement protects lung microcirculation
beds resulting in increase in pressure) , increase pressure in pulmonary circulation and RV
(Kitaev’s reflex) , right sided HF with dilation of right ventricle and secondary tricuspid and
pulmonary regurgitation
 With severe stenosis, less blood flows into LV than normal , decrease systolic BP

CLINICAL PRESENTATIONS

 SOB is an early symptom – first with PE or psychoemotional stress, later at rest or orthopnea
 Attack of suffocation and hemoptysis (pink frothy in capillary rupture, large hemorrhagic in
bronchial vein rupture, blood stained in chronic bronchitis), cardiac asthma
 Palpitations, tachycardia
 Cardialgia (dull, pressing, prolonged not associated with exercise. In acute – stabbing, short
term, nitroglycerine doesn’t relieve pain
 Late stage – pain in right hypochondrium, dyspeptic disorders

Inspections

 Asthenic, fragile constitution, thin limbs and cold to touch, poorly developed muscles
 Acrocyanosis and facial cyanosis (facies mitralis, cyanotic lips, nose ears with bright
cyanotic cheeks ‘mitral butterfly’)
 Orthopnea position
 Edema of legs, lower back and neck vein swelling – RV insufficiency
 RV insufficiency – hepatomegaly and ascites

Palpation

 Increased and diffused pulsation of precardial region to left of sternum, extending to

epigastric region. Apical impulse not changed
 At apex, low-frequency diastolic tremor (cat purr)
 In childhood or adolescence – bulge of left pericardial region (heart hump – gibbus
cordis)

Percussion: Right borders shift to right and upper borders shift to up (mitral configuration)

• Auscultation

 Increased ‘flapping’ S1 – rapid closing and sharp tension of valve during LV contraction
 Accentuation and splitting of S2 on pulmonary artery – increase pulmonary artery
pressure
 Opening snap – 0.1 sec after start of S2 (greater the stenosis, higher pressure in LA, faster
 valve opens and short interval between S2 and OS. With significant narrowing, OS may
not be heard)

 Diastolic murmur at apex
 Separated from S2, starting after OS
 Decreasing nature, with tendency to presystolic increase due to acceleration of blood
flow during LA systole
 Better heard at apex in horizontal position, especially in position on left side
 With severe pulmonary arterial HTN, soft blowing diastolic murmur (Graham Still
murmur) heard at 2nd intercostal space left of sternum, caused by expansion of
pulmonary trunk and relative insufficiency off pulmonary valve. Occurs immediately
after 2nd tone
 Lung – moist, small bubble wheezes in lower part (interstitial pulmonary edema), medium
and large bubble non-ringing wet wheezes over entire chest against the background of
vesicular respiration
 Botkin’s auscultation phenomenon – when auscultating lungs in mitral stenosis patients –
crepitation or small bubble wet wheezes along upper and left boarder of hearts

MITRAL INSUFFICIENCY
• Conservative

 Mild – no special treatment

 Moderate or severe – careful administration of ACE-I (reduce the amount of post-load)
 In LVF use diuretics and drugs that reduce blood flow to heart like nitrates (remember
aboutthe possible decrease in CO when using high doses)
 RV insufficiency – Diuretics and aldosterone antagonists
 Permanent form of AF – digoxin and B-blockers
 In later stages – anticoagulants to prevent thromboembolic complications

• Surgical

 Replacement of mitral valve

 Replacement of mitral valve with preservation of part or all of mitral structures
 Replacement of mitral valve with removal of mitral structures

MITRAL STENOSIS

• Conservative

o Drugs that restricts blood flow to pulmonary artery

 Diuretics (dichlorothiazide 50-100mg/day, furosemide 40-60mg/day)

 Nitrates (nitrosorbide, isoket, cardiket 20-40mg/day, Monchique-retard 50mg/day)
 Excessive diuresis when using diuretics or significant blood deposition when using
nitrates can lead to s sharp decrease in pressure gradient between LA and LV which leads
to an undesirable drop in cardiac output

o Use of cardiac glycoside is contraindicated, since increase in impact volume of RV increases

the flow and stagnation of blood in pulmonary circulation

 Digoxin 0.25-0.375mg/day indicated only in tachysystole form of AF

 In sinus tachycardia – B blockers (atenolol 25-50mg/day, metoprolol 50-100mg/day,
carvedilol 12.5-50mg/day)
 Severe cases require continued therapy with diuretics, to which aldosterone antagonists are
added (aldactone, veroshpiron 200-300mg/day)
 ACE-I (enalapril 10mg/day, perindopril 2mg/day) should be used with caution, since sharp
decrease in HR and BP can lead to decrease in CO and reflex tachycardia
 For thromboembolic complications – heparin.
 Warfarin indicated for at least 1 year with maintenance of INR level at 2-3 units.
 With repeated thromboembolism – increase warfarin to maintain INR at 3.0-4.5 units, while
adding aspirin (100mg/day)

• Surgical
 Catheter balloon valvuloplasty
 Commissurotomy (valvulotomy)
 Mitral valve replacement

15. Etiology, pathogenesis, clinical picture, treatment of aortal valvular heart disease.

Aortic regurgitation

ETIOLOGY

 Most common cause – Rheumatic fever (70%) and Infective endocarditis

 Less common – atherosclerosis, syphilis, lupus endocarditis Liebman-Sachs, rheumatoid
arthritis, etc.
 I – Congenital abnormality (Congenital bivalve aortic valve – incomplete closure or
prolapse)
 II – Inflammatory process (RF, IE – destruction of valves, perforation, prolapse, non-closure
due to vegetations)
 III – Degenerative processes (Myxomatous degeneration – violation of mechanical properties
of valves with prolapse and dilation of aortic root)
 IV – Aortic root lesions (Arterial HTN, blunt chest trauma, syphilis, aortoarteritis, ankylosing
spondylitis, Marfan syndrome – Aortic dilation, damage to valve flaps by hydraulic shock
during diastole, medionecrosis with dilated fibrous ring)

CLINICAL PRESENTATIONS

 First clinical manifestation – unpleasant sensation of increased pulsation in the neck, head,
tachycardia
 With significant defect – cardialgia, dizziness, sudden nausea, tendency to faint, especially
with PE or rapid change in body position
 Decompensation period – LVF – SOB first with PE, then at rest. Rapid fatigue, weakness
 Blood stagnation in systemic circulation – edema, heaviness in RUQ, dyspepsia – rare

Inspection

 Pallor of skin
 Strong pulsation of carotid arteries (dance of carotid), visible pulsation in all s/f arteries
 Symptoms de Musset – rhythmic sway of head forward and backward according to phases of
heart
 Quincke’s symptoms (capillary pulse) – redness (in systole) and paleness (in diastole) of nail
bed at base of nail with sufficient intense pressure on top.
 Landolfi’s symptoms – pulsation of pupil in form of constriction and expansion
 Mueller’s symptoms – pulsation of soft palate

Palpation

 Apical impulse is enhanced, diffuse, shifted to left and downs

 Systolic tremor along left and right edges of sternum, in jugular notch, on carotid arteries

Percussion

 Sharp shift of left border of relative heart dullness to left

 Aortic configuration – accentuated waist of the heart

Auscultation

 S1 – a top is weakened as result of sharp volume overload of LV

 S2 – weakening on aorta or its disappearance (valve pathology), normal or loud (root
pathology)
 Syphilitic aortic lesion – enhanced S2 with a metallic tinge (ringing S2)
 Pathological S3 – volume overload of LV and decreasing in its connective capacity
 Diastolic murmur – 2nd IC space to right of sternum and 3rd-4th IC space at left
 Functional diastolic murmur ‘Flint’ – presystolic murmur of relative mitral stenosis
 Function systolic murmur – relative stenosis of aortic stenosis
 Durosier’s sign – auscultation heard above femoral when compressed
 Traube sign – loud noise with auscultation of large artery

• BP –

INDICATIONS FOR SURGERY

 Severe aortic insufficiency (the volume of regurgitation is more than 50%) with clinical
manifestations of the defect
 Severe aortic insufficiency (regurgitation volume greater than 50%) with objective signs of
LV systolic dysfunction, regardless of the presence or absence of clinical manifestations of
the disease

Aortic stenosis:
ETIOLOGY

 Valvular – narrowing of aortic valve formed due to fusion of aortic flaps with each other –
Aortic stenosis
 Subavalvular – valves are intact, an obstacle to blood flow is created by pronounced
hypertrophy of output tract of LV – subaortic stenosis
 Supravalvular – caused by circular cord or membrane located further than valve of coronary
arteries – supravalvular stenosis
 Moas common cause of aortic stenosis in adults – calcification of the valve (senile
degeneration)or congenital bicuspid valve
 Less common – rheumatic fever
 Other – IE, Paget’s disease, rheumatoid arthritis SLE, atherosclerosis

CLINICAL PRESENTATIONS

 First complains arise when stenosis is about 50% - syncope during PE

 Angina attacks – during period of compensation, which appears or worsens during PE,
behind sternum, radiates to left am and shoulder and is stopped by nitroglycerine
 SOB is transient, appears with PE or tachycardia, over time it progresses
 Complaints of edema, heaviness of RUQ and other signs of RVF are NOT TYPICAL
 Sudden cardiac death in 5-10%

Inspection

 Pallor of skin
 Acrocyanosis at later stage due to mitral heart disease

Palpation and percussion

 In compensation stage – increased concentrated and slighlt displaced apical impulse. Limits
of relative dullness unchanged
 In decompensation – enhanced apical impulses, left border shift to left, “aortic configuration”
 Systolic tremor at base and jugular notch

Auscultation

 S1 – weakened at top of the heart

 S2 – weakened
 S3 – in decompensation stage, protodiastolic rhythm of gallop
 S4 – in compensation stage
 Systolic murmur – ejection, best in aortic arch in full expiration and radiate to carotid

Arterial pulse and BP: Initially unchanged but as narrowing becomes severe, pulse become
small, low and rare (pulsus parvus, tardus et rarus). Decrease in SBP and pulse pressure

AORTIC INSUFFICIENCY

• Conservative

 ACE inhibitors reduce volume of regurgitation and contributes to development of LV

myocardial hypertrophy
 Cardiac glucoside – with development of decompensation and decrease in LV systolic
function (EF <40-50%), as well as AF
 Diuretics – decrease stagnation in pulmonary circulation
 Venous vasodilators – decrease amount of preload
 B-blockers are used with caution, since elimination of tachycardia prolongs the diastole
and increase reverse diastolic blood flow from aorta to LV

• Surgical

 Performed as early as possible, before development of LVF or appearance of objective

sings
 of LV systolic dysfunction
 Prosthetics of aortic valve

AORTIC STENOSIS

 With compensated – drug treatment not carried out

 Symptomatic therapy performed in patient with clinics, for whom radical treatment is
contraindicated
 In compensation stage
 Treatment of stable angina (nitrated and Beta blockers in minimal dose)
 Correction of LV dysfunction (B-blockers in small, individually selected dose, ACEI) –
under control of blood pressure and heart rate
 AF (digoxin 250mg/day and B-blockers in small doses)
• In decompensation stage

 Cardiac glycoside
 Diuretics (avoid massive diuresis)
 Intra-aortic balloon conterpulsation (stabilize hemodynamics before surgery)

• Medication used to treat CHF may cause deterioration in AS patients

 Massive diuretics or use of nitr

cardiac output and BP
 Use of B-blockers or slow Ca-channel blockers may exacerbate signs of decompensation and
contribute to bradycardia and AV block
 Cardiac glycoside contributes to impaired diastolic function of hypertrophied myocardium,
as well as restrict coronary blood flow

• Surgical – only type of treatment in presence of clinics

 Aortic valve replacement

 Aortic balloon valvuloplasty

INDICATIONS FOR SURGERIES – refer to previous questions

16. Etiology, pathogenesis, clinical picture, diagnostic criteria and treatment of infective
endocarditis.

ETIOLOGY

 Polyetiological with wide and dynamic spectrum of microbial flora

 Main significance
 Gram-positive cocci (staphylococcus, streptococcus, enterococcus),
 Gram negative (Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)
 Fungi (Candida, Aspergillus)

• Recently, main agents – Staphylococcus aureus (primary) and S. epidermis (secondary)

PATHOGENESIS

• Endocardial damage

 Mechanical damage to endocardium by turbulent blood flow in congenital and acquired

heart defects, electrodes and catheters, with formation of non-bacterial trombendocarditis
 Inflammation of endocardium without previous damage to valve by highly virulent
microorganism with increased adhesive properties

• Bacteremia
  Foci of chronic infection, invasive medical procedures, surgical interventions, procedure
in oral cavity
o Adhesion and multiplication of pathogenic bacteria on the valves
 Change in natural resistance (elderly, alcoholism, drug addictions), disorders in HLA
histocompatibility system during treatment with immunosuppresses
 Morphological changes in valvular apparatus of hearts, disorders of intracardiac
hemodynamics and microcirculation
 S. aureus – increased adhesion and binding by peptidoglycan of endocardium of these
bacteria, registered in 10-15 mins after manipulation, persists for 1-1.5 hours, fixation of
microbe on vale after 6 hours, formation of platelet-fibrin layer 18-24 hours

• Weakening of anti-infective protection of microorganism: DM, HIV, solid tumors, DIC,

transplantation, infected skin disease, hemodialysis, etc.

• Development of heart failure

• Formation of systemic inflammatory reaction of body

 Release of endogenous mediators of acute phase of inflammations and launch of

immunopathological mechanisms of inflammation
 Emboli, thrombo-hemorrhagic and immunocomplex lesions of internal organs and tissues

Pathogenetic Stages

 Infectious-toxic (transient bacteremia, “sowing of microbes on prepared soil”, formation of

microbial-thrombotic vegetation)
 Immune-inflammatory (internal organ damage: vasculitis, myocarditis, GN)
 Dystrophic (severe and irreversible damages to internal organs)

Clinical picture consists of

 Infectious-toxic syndrome
 Heart failure
 Embolic complications
 Immunological complications with sign of damage to various organs and systems

• Fever (90-95%) is an early symptom

 Sub febrile can be undulating, accompanied by inadequate profuse sweats, chills, rising
for days or hours
 2-3-week fever waves up to 38-39 C, alternating with 1-2 week of apyrexy or subfebrility
Fever may be permanent, remitting, intermittent, hectic or inverted
• Heart Failure – significance is not so much the pathological signs that are recorded once, as the
change in their character over a certain period of time

• Heart murmurs (85%)

o Aortic valve – systolic murmurs and left edge of sternum and at 5th IC point

 After 1.5-2 weeks – gentle diastolic murmur at 5th IC point and above aorta, which
increases when patient is upright or in left side. With destruction of valve flabs, noise
increases in intensity and duration, acquires a musical character (‘sawing’), zone of
auscultation expands. 2nd heart sound of aorta weakens, diastolic BP decreases
 Development of ulcer and valve
murmur at base of heart

Noise of musical hue (bird’s squeak, “cry of seagulls) – perforation of valve flaps,
interventricular septum, ruptures of papillary muscle chord

o Mitral valve – increase in systolic noise in intensity, change in nature with simultaneous
weakening of 1st heart sound

o Tricuspid valves – common in drug addict

 Increase in dynamic of systolic noise over xiphoid process, which increases at height of
inspiration – 50% of patient in later stage
 Repeated thromboembolism in small branches of pulmonary artery, often with
development of infarct-pneumonia

o Pulmonary artery valves are rarely affected, mainly in congenital heart defect patients

 Myocardial damage in every second patient – increase in heart cavities, increasing nature of
cardiac decompensation with predominance of right ventricular or total circulatory failure
 Due to occlusion of coronary arteries by microbial vegetations from aortic valve, embolic
necrosis develops – pronounced anginous syndrome, intermuscular intracardiac abscesses
 Thromboembolic complications – observed in 1/3 patient in vessels with formation of
infarcts of affected organs
 Vascular damaged – endovasculitis, septic aneurism
 Glomerulonephritis (diffuse, focal, mesingocapillary, extracapillary), tubulointerstitial
nephritis, renal artery thromboembolism, renal infarction, mycotic aneurysm of renal artery,
kidney abscessor secondary kidney amyloidosis
 Skin and mucosa are often pale, pale gray or yellowish-earth with a hint of “coffee milks”.
Jaundice appears later due to hemolytic anemia of toxic hepatitis
 Short-lived petechial rashes on transitional fold of eyelid mucosa (Lukin’s spot),
conjunctiva, hard and soft palate, neck, chest, forearms, hands and legs
 o 1-2mm with a center of gray or white color pale though 2-4 days and disappears
• Intense hemorrhagic rash – wave like character ad a symmetrical arrangement

 Extremities, face and other skin and mucosa

 Ca be accompanied by necrosis and leave scar

• Janeway spot – macular or papular erythematous spots or painless bruises with diameter 1-
1.5cm on palms, soles, distal phalanges and increasing with lifting of the limb. (mostly in acute)

• Osler nodules – reddish nodular painful skin formation with diameter 1.5cm on palms, soles,
fingers, under nails. Disappear without a trace after few days or hours, rarely necrosis and
suppuration

• Bone and joint changes (20%) – polyarthralgia or polyarthritis. Small joints of hand and feet,
but large joints are more common

• Splenomegaly (40-45%) – due to hypertrophy in response to septic infection and formation of

heart attacks and abscesses of spleen

• Hepatomegaly – without jaundice with signs of pronounced dysproteinemia in early stages

 Rarely, jaundice with liver failures

 Progressive heart failure exacerbates diffuse liver damage and development of cirrhosis
 Complications of thromboembolism, liver abscess

• Pulmonary – Pulmonary embolism or local inflammatory changes

 Loss of voice, hoarseness and stridor due to edema of vocal cords during blockage of a.
laryngeal cranalis et caudalis
 Lung damage is manifested by heart attacks, pneumonia, and edema of LV
 Pulmonary infarctions due to vascular thrombosis and embolism of endocarditis in right
heart, with thrombophlebitis and peripheral vein thrombosis

• CNS – general cerebral and neurological symptoms up to violation of consciousness.

Meningeal symptoms. Diffuse meningoencephalitis

• Acute

 High fever (39-400C)

 Tachycardia
 Fatigue
 Rapid and extensive heart valve damage
o Subacute
 Fatigue, mild fever (37-38 c)
 Moderately fast heart rate, weight loss
  Sweating, anemia
 Thromboembolism

DIAGNOSTIC CRITERIA – Modified Dukes criteria

Major criteria

• Positive blood culture

o Typical microorganism consistent with IE from 2 separate blood cultures

 T. viridians, S. bovis, HACEK group, S. aureus, or

 Community acquired enterococci in absence of primary foci

o Microorganisms consistent with IE from persistently positive blood cultures

 More than 2 cultures drawn more than 12 hours apart, or

 All 3 or majority of >4 separate cultures (first and last drawn >1 hour apart)

o Single positive culture for Coxiella burnetti or phase I IgG Ab titer >1:800

• Positive imaging

o Echo positive for

 Vegetations
 Abscess, pseudoaneurysm, intracardiac fistulas
 Valvular perforation or aneurysm
 Few partial dehiscence of prosthetic valve

o Abnormal activity around site of prosthetic valve implantation detected by 18F-FDG PET/CT
(only is planted for >3 months) or radioleucocytes SPECT/CT

o Definitive paravalvular lesion by cardiac CT

Minor criteria

 Predispositions such as heart conditions, or drug injections use

 Fever >38C
 Vascular phenomenon: major arterial emboli, septic pulmonary infarcts, infectious aneurysm,
intracranial hemorrhage, conjunctival hemorrhage and Janeway’s lesions
 Immunological phenomena: GN, Osler’s node, Roth’s spots and rheumatoid factors
 Microbiological evidence: positive culture but does not meet major criteria OR serological
evidence of active infection with organism consistent with IE

Treatment:
Antibiotic therapy

• Principles

 Early start (delay in appointment from 2-8 weeks from onset reduces survival by 2 times)
 Use maximum daily dose of 2-3 Abx with parenteral administration
 Perform at least 4-6 weeks with timely treatment and 8-10 weeks with late treatment
 Consider the sensitivity of microorganisms
 Determine in vitro sensitivity of pathogens to Abx, detect minimum suppressive
concentration
 Correction of dose and interval of administration, depending on excretory function of kidney
 Replacement in event of resistance within 3-4 days
 Average duration of treatment of strept – 4 weeks, staph and gram negative – 6-8 weeks

• Abx for streptococcal

o Penicillin sensitive and/or resistant oral streptococcal and group D streptococci

o S. pneumonia and group A, B, C and G streptococci – same regimen except 2 weeks

o Regimen:

 Penicillin G (12-18 mU), amoxicillin (100-200 mg/kg/day) or ceftriaxone (2g/day)– 4

weeks, or
 Same + gentamycin (2mg/kg/day) or netilmicin (4-5mg/kg/day) – 2 weeks

• Abx for staphylococcal

 S. aureus and coagulase negative staphylococci

 MRSA and VRSA – same except gentamycin for 4-6 weeks in native
 Native valves
 Cloxacillin or Oxacillin (4-6 weeks) + Gentamicin (3-5 days)
 Prosthetic valves
 Cloxacillin or Oxacillin + rifampicin + gentamicin (2 weeks) – 6 weeks
 MRSA – Vancomycin (30mg/kg/d), rifampicin (6 weeks) and gentamicin (2 weeks)
 Abx for enterococcal
 Slow response to therapy and presence of multiple mechanisms for formation of resistant
 Penicillin or ampicillin or amoxicillin + gentamicin (with ceftriaxone resistance)

• Abx for gram negative

 Ceftriaxone 2g/day – 4 weeks

 Alternative – co-trimoxazole and fluoroquinolones
• Antifungal

 Amphotericin B (1mg/kg/day) monotherapy or in combination with azole (fluconazole 200-

400mg/kg/day)

• Empirical

 Native valve and late prosthetic valve (>1 year) – 4-6 weeks
 Ampicillin (12g/day) or amoxicillin (12g/day) + Gentamicin
 Vancomycin + Gentamicin + Ciprofloxacin (800mg/day in 2 doses)
 Prosthetic valve (early) – Vancomycin (6 weeks) + Gentamycin + Rifampin (1.2g/d PO) – 2
weeks

Criteria of cure rate

• Persistent normalization of body temperature; negative repeated blood tests to identify the
pathogen; absence of fresh petechiae and embolism; absence of enlarged spleen; absence of
hematuria and albuminuria; absence of anemia; normalization of ESR; normalization of
biochemical markers of inflammation

Indications for surgery

• Heart failure – IE of aortic and/or mitral valve with active regurgitation or valve obstruction
causing refractory pulmonary edema (or cardiogenic shock)

• Uncontrolled infection

 local uncontrolled infections (abscess, false aneurysm, fistula, increase in vegetation);

persistent fever and positive blood culture for more than 7-10 days; infection caused by
fungi or polyresistant microorganisms

• Preventions of embolism

 IE of aortic and/or mitral valve with large vegetation (>10mm) + 1 or more episodes of
embolism, despite adequate Abx or + predictors of thromboembolic complications (HF,
persistent infections, abscess)
 Isolated very large (>15mm) vegetations

17. Etiology, pathogenesis, clinical picture of chronic heart failure. Classification of heart
failure. Modern approaches to therapy. Surgical treatment of chronic heart failure .

Etiology of CHF:

1. Myocardial damage:

a) primary myocardial insufficiency (myocarditis, idiopathic dilated cardiomyopathy)

b) secondary myocardial insufficiency (post-infarction cardiosclerosis, specific
cardiomyopathy: metabolic, with systemic connective tissue diseases, alcohol, toxic-allergic,
etc.)

2. Hemodynamic myocardial overload:

a) overload due to increased resistance to ejection (pressure overload): hypertension, pulmonary

hypertension, aortic stenosis, pulmonary artery stenosis
b) overload with increased filling of the heart chambers (volume overload): heart valve
insufficiency, CHD with blood shunt from left to right (VSD, etc.)
c) combined overload (by volume and pressure): combined heart defects

3. Violation of diastolic filling of the ventricles : stenosis of the left or right atrioventricular
orifice, exudative and constrictive pericarditis, restrictive cardiomyopathy)

4. Increased metabolic needs of tissues (HF with high minute volume): anemia, thyrotoxicosis.

Pathogenesis.

1. The main trigger of CHF is a decrease in myocardial contractility and a drop in cardiac
output , which causes a decrease in perfusion of a number of organs and activation of
compensatory mechanisms (sympathetic-adrenal system, renin-angiotensin-aldosterone
system, etc.).
2. Catecholamines (norepinephrine) cause peripheral vasoconstriction of arterioles and venules,
increase venous return to the heart, and equalize reduced cardiac output to normal
(compensatory response). However, further activation of the sympathetic-adrenal system
leads to the progression of CHF (catecholamines activate the RAAS, tachycardia worsens the
filling of the heart in diastole, and other decompensation reactions).
3. Spasm of renal arterioles + hypoperfusion of the kidneys against the background of CHF 
activation of the RAAS  hyperproduction of angiotensin II (a powerful vasopressor;
potentiates myocardial hypertrophy and remodeling) and aldosterone (increases sodium
reabsorption and plasma osmolality, activates the production of ADH, which retains
water). An increase in BCC, on the one hand, normalizes cardiac output (compensation), on
the other hand, it potentiates dilation and damage to the heart (decompensation).
4. An important role in the development of CHF also belongs to endothelial vascular
dysfunction (decrease in the production of endothelial vasorelaxant factor), hyperproduction
of a number of cytokines: IL, TNF- (impairs the transport of calcium ions into cells, inhibits
PVK dehydrogenase, leading to ATP deficiency, triggers apoptosis of cardiomyocytes ).

CHF classification.

1. By origin : due to volume overload, due to pressure overload, primary myocardial

2. According to the cardiac cycle : systolic form, diastolic form, mixed form
 3. According to the clinical variant : left ventricular, right ventricular, biventricular (total)
4. According to the magnitude of cardiac output : with low cardiac output, with high
cardiac output

According to Vasilenko-Strazhesko

 Stage I (initial) - latent HF, manifested only during physical exertion (shortness of breath,
tachycardia, fatigue).
 II stage (expressed) - expressed violations of hemodynamics, organ function and
metabolism
 II A - moderately pronounced signs of heart failure with hemodynamic disturbances in only
one circle
 IIB - strongly pronounced signs of heart failure with hemodynamic disturbances in a large
and small circle
 Stage III (final, dystrophic) - severe hemodynamic disorders, persistent changes in
metabolism and functions of all organs, irreversible changes in the structure of tissues and
organs, complete disability.

By nyha:

1. Class I (lack of restrictions on physical activity) - ordinary (habitual) physical activity does
not cause severe fatigue, shortness of breath or palpitations (but there is heart
disease!); distance of a 6-minute walk 426-550 m.
2. Class II (mild, slight limitation of physical activity) - satisfactory state of health at rest, but
habitual physical activity causes fatigue, palpitations, shortness of breath or pain; distance of
a 6-minute walk 301-425 m.
3. Class III (pronounced, noticeable limitation of physical activity) - satisfactory state of health
at rest, but the load is less than usual leads to the appearance of symptoms; 6-minute walk
distance 151-300 m.
4. Class IV (complete limitation of physical activity) - the inability to perform any physical
activity without deterioration of health; HF symptoms are present even at rest and are
aggravated by any physical activity; the distance of a 6-minute walk is less than 150 m.

The main clinical manifestations of biventricular CHF:

1. Subjective manifestations:

 shortness of breath - the most frequent and early symptom of CHF, initially appears only
during physical exertion, as the disease progresses and at rest; shortness of breath often
occurs when lying down and disappears when sitting
 rapid fatigue, severe general and muscle weakness (due to a decrease in muscle perfusion and
their oxygen starvation); weight loss (due to the activation of TNF-α and the development of
malabsorption syndrome)
 palpitations (more often due to sinus tachycardia) - at first they disturb patients during
exercise or with a rapid rise in blood pressure, as CHF progresses - and at rest
 attacks of suffocation at night (cardiac asthma) - attacks of pronounced shortness of breath
that occur at night, accompanied by a feeling of lack of air, a feeling of fear of death
 cough - usually dry, appears after or during exercise (due to venous congestion in the lungs,
swelling of the bronchial mucosa and irritation of cough receptors); in severe cases, there
may be a wet cough with a large amount of frothy, pink sputum (with the development of
pulmonary edema)
 peripheral edema - at first there is a slight pastiness and local swelling in the area of the feet
and legs, mainly in the evening, by the morning the edema disappears; as CHF progresses,
edema becomes widespread, localized not only in the feet, ankles, legs, but also in the thighs,
scrotum, anterior abdominal wall, in the lumbar region; extreme degree of edematous
syndrome - anasarca - massive, widespread edema with ascites and hydrothorax
 violation of urine separation (oliguria, nocturia - the predominance of nighttime diuresis over
daytime)
 pain, feeling of heaviness and fullness in the right hypochondrium - appear with an increase
in the liver, due to stretching of the Glisson capsule

2. Objectively :

a) inspection :

 forced sitting or semi-sitting position of patients with their legs down or a horizontal position
with a high headboard
 acrocyanosis of the skin and visible mucous membranes, most pronounced in the distal parts
of the extremities, on the lips, tip of the nose, auricles, subungual spaces, accompanied by
cooling of the skin of the extremities, trophic disorders of the skin (dryness, peeling) and
nails (brittleness, dullness) (due to decrease in perfusion of peripheral tissues, increased
oxygen extraction by tissues and an increase in reduced hemoglobin)
 peripheral edema (up to ascites and hydrothorax): located symmetrically, leaving a deep hole
after pressing with a finger, which then gradually smoothes out; the skin in the area of edema
is smooth, shiny, initially soft, and with prolonged edema it becomes dense; blisters may
form at the site of edema, which open and fluid flows out of them, foci of necrosis, skin tears
 swelling and pulsation of the cervical veins (with the development of right ventricular
failure)
 a positive symptom of Plesha (hepato-jugular test) - with calm breathing of the patient,
pressure is made with the palm of the hand on the enlarged liver, which causes increased
swelling of the jugular veins
 atrophy of skeletal muscles (biceps, thenar and hypothenar muscles, temporal and
masticatory muscles), weight loss, a pronounced decrease in subcutaneous fat ("cardiac
cachexia").
b) physical examination :

1) respiratory organs : inspiratory tachypnea; percussion: dullness behind in the lower parts of
the lungs; auscultatory: crepitus and moist small bubbling rales against the background of
hard or weakened vesicular breathing in the lower parts
2) cardiovascular system : the pulse is quickened, small filling and tension, often arrhythmic;
BP is reduced (SBP is greater than DBP); palpation apical impulse spilled, shifted to the left
and down; percussion borders of the heart expanded to the left; auscultatory tachycardia and
various arrhythmias, often protodiastolic gallop rhythm
3) abdominal organs : bloating (flatulence), palpation - pain in the right hypochondrium; the
liver is enlarged, painful on palpation, its surface is smooth, the edge is rounded, with a large
stagnation - systolic pulsation (bulging in systole and decreasing in diastole); ascites

The goals of treatment of patients with CHF: 1) elimination of symptoms of the disease
(shortness of breath, palpitations, increased fatigue, fluid retention in the body); 2) slowing down
the progression of the disease by protecting target organs (heart, kidneys, brain, blood vessels,
muscles); 3) improving the quality of life 4) reducing the number of hospitalizations; 5)
prolongation of the patient's life.

1. General activities:

 exclusion of alcohol consumption (because ethanol retains water and is a powerful inducer of
apoptosis)
 weight loss in obese patients
 correction of hypertension, hyperlipidemia and diabetes
 restriction of salt and liquid intake (up to 1-1.5 l / day)
 daily weighing to detect hidden edema
 regular moderate exercise (walking is best)
 avoid taking PAS (cardiodepressive effect), most calcium antagonists (verapamil -
cardiodepressive effect, dihydropyridines - activation of the SNS), NSAIDs (retain fluid,
increase blood pressure, reduce the activity of ACE inhibitors and β-AB).

2. Drug therapy for CHF:

a) the main drugs - 5 groups, the effectiveness has been reliably proven:

1) ACE inhibitors - drugs No. 1 in the treatment of CHF; improve the clinical course of the
disease, reduce the risk of death, slow down the progression of the disease and the onset of
decompensation.

2) β-adrenergic blockers (BAB) - with long-term administration, they reduce the risk of
decompensation and significantly prolong the life of patients (more than ACE inhibitors!), lead
to an increase in EF and pumping function of the heart, inhibit and cause regression of
pathological myocardial remodeling, reduce electrical instability, indirectly reduce the activity of
the RAAS.

Use: metoprolol-SR (initial dose 5-12.5 mg / day, optimal - up to 100 mg / day); bisoprolol
(initial dose 1.25 mg/day, optimal - up to 10 mg/day); carvedilol (initial dose - 3.125 mg / day,
optimal - up to 50 mg / day - the most optimal, is a non- - -blocker ,
antioxidant)

3) diuretics - are indicated only for clinical signs and symptoms of fluid retention in the body
(i.e. with congestive heart failure) mainly together with ACE inhibitors; the criterion for a
sufficient dose is a decrease in body weight by 0.5-1 kg / day; loop diuretics increase sodium
excretion by 20-25% and excretion of free water, thiazide diuretics increase sodium excretion by
5-10%, do not increase free water clearance.

Use: thiazide diuretics (hydrochlorothiazide orally in the morning 25-75 mg), with insufficient
effectiveness - loop diuretics (furosemide orally in the morning 20-500 mg)

4) cardiac glycosides (only digoxin 0.125 mg 1-2 times / day) - indicated in the presence of atrial
fibrillation, in sinus rhythm - the fourth drug (after ACE inhibitors, BAB, diuretics); the use in
patients with sinus rhythms in low doses does not improve the prognosis and does not slow down
the progression of CHF, but improves the quality of life; it is inappropriate to prescribe in
patients with HF in violation of LV diastolic filling, HF with high ejection, cor pulmonale.

5) oral spironolactone 25-50 mg once in the morning or in 2 doses in the morning - reduces the
risk of overall mortality by 30%, is used

b) additional drugs - drugs, the effectiveness and safety of which require clarification:

1) AT II antagonists - used for intolerance to ACE inhibitors (valsartan orally at an initial dose of
40 mg 2 times / day, gradually increasing to a maximum of 160 mg 2 times / day, losartan,
irbesartan)

2) cardioprotectors - used in short courses to enhance the contractility of the heart (mildronate -
limits the transport of long-chain fatty acids through the mitochondrial membranes, while short-
chain fatty acids can freely penetrate and oxidize; trimetazidine / preductal inside 20 mg 3 times /
day - inhibits beta in mitochondria -oxidation of all fatty acids, which contributes to the
accumulation of activated fatty acids in mitochondria).

c) auxiliary drugs:

1. peripheral vasodilators (nitrates) - only with concomitant angina and pulmonary edema
2. calcium channel blockers (only amlodipine) - "on top" on ACE inhibitors with severe
valvular regurgitation, high arterial and / or pulmonary hypertension
3. antiarrhythmics (only group III) - only for life-threatening arrhythmias
4. GCS (prednisolone, methylprednisolone) - with persistent hypotension and as a "treatment of
despair" with the ineffectiveness of other drugs
5. non-glycoside inotropic stimulants (dopamine, dobutamine) - short courses during
exacerbation and CHF with persistent hypotension
6. acetylsalicylic acid - used by patients after myocardial infarction
7. indirect anticoagulants (only warfarin) - with dilatation of the heart, intracardiac thrombus,
atrial fibrillation, after operations on the heart valves.

Patients with CHF are at risk of sudden cardiac death (SCD) from arrhythmias such as
ventricular tachycardia (VT) or ventricular fibrillation (VF) and heart failure may be worsened
by cardiac dyssynchrony. Devices may only pace or have both pacing and defibrillator
functions. [47]

 Implantable cardioverter defibrillator (ICD): consist of a pulse generator and leads that
can sense VF or VT and deliver a shock to restore sinus rhythm. ; [48]

Patients with CHF are at risk of sudden cardiac death (SCD) from arrhythmias such as
ventricular tachycardia (VT) or ventricular fibrillation (VF).

Indications in heart failure :HFrEF with expected survival of > 1 year if, despite receiving
optimized medical therapy for 3–6 months, the following criteria are still met:,Stage B with
ischemic cardiomyopathy if LVEF is ≤ 30%,Stage C with dilated cardiomyopathy (DCM) or
ischemic heart disease with an LVEF ≤ 35% and NYHA class II–III symptoms,Patients who
have previously had sustained VT or a cardiac arrest secondary to VF or VT [49]

 Cardiac resynchronization therapy (CRT): leads in the RA, RV, and coronary sinus
(which lies adjacent to the LV) pace the heart in a coordinated manner.

Benefits include:Improved ventricular function ,Reversal of ventricular remodeling,Reduction

of secondary mitral regurgitation

Indications: The criteria below apply to patients with stage C HFrEF with an LVEF ≤ 35% on
optimized medical therapy and an expected survival of > 1 year. ,NYHA class I–IV symptoms in
sinus rhythm with QRS duration of > 150 ms; (can be either left bundle branch block (LBBB)
pattern or non-LBBB pattern) ,Patients with LVEF ≤ 35% who require pacing for other purposes,
e.g., atrial fibrillation, replacement of existing pacemaker

18. Etiology, pathogenesis, classification, clinic, treatment of pericarditis.

Pericarditis is a serous-fibrinous, fibrinous, hemorrhagic, purulent or putrefactive inflammation

of the pericardial cavity (cardiac shirt, pericardial sac).

NB! Before establishing the cause of the appearance of fluid in the pericardial cavity and its
nature, the diagnosis should sound like "effusion syndrome in the pericardial cavity."
Epidemiology : Pericarditis accounts for 3-5% of all autopsies, with 70-80% of them not
diagnosed during their lifetime; according to a complete clinical examination, pericarditis is
detected in 0.25-0.5% of inpatient therapeutic patients.

Classification of pericarditis:

a) by etiology:

I. Infectious or infectious-allergic pericarditis:

1. tuberculosis
2. other bacterial:
a) non-specific (streptococcal, staphylococcal (pyopericarditis), pneumococcal, meningococcal,
caused by anaerobic infection, Escherichia coli and other gram-negative flora)
b) specific (for typhoid fever, relapsing fever, dysentery, cholera, plague, anthrax, brucellosis,
tularemia, syphilis, gonorrhea)
3. viral (adenoviruses, influenza viruses, infectious mononucleosis‚ Coxsackie, HIV, hepatitis B
virus)
4. rickettsial (with typhus, fever Q)
5. chlamydia (with ornithosis, urogenital pathology)
6. mycoplasma (against the background of acute respiratory infections, pneumonia)
7. fungal (against the background of candidiasis, actinomycosis, histoplasmosis,
coccidioidomycosis, etc.)
8. caused by protozoa (malarial, amoebic).

II . Aseptic pericarditis:with rheumatic diseases (rheumatism, DBST, systemic vasculitis,

gout); with myocardial infarction (local, fibrinous - with transmural myocardial infarction,
autoimmune - Dressler's syndrome); with dissecting aortic aneurysm; in diseases of organs
adjacent to the heart (pneumonia, pleurisy, lung abscess, mediastinitis, perforation of the
esophagus, pancreatic-pericardial fistula); uremic; post-traumatic; postoperative (installation of
an artificial pacemaker, invasive diagnostic procedures in cardiology, pericardiotomy); with
blood diseases (leukemia, LGM, lymphoma); with malignant tumors (cancer of the lung,
breast); with radiation sickness and as a consequence of local radiation
therapy; allergic; medicinal (hydralazine, procainamide, isoniazid, phenylbutazone, etc.); with
sarcoidosis; with amyloidosis; with myxedema.

III. Idiopathic pericarditis.

According to the frequency of the causes of acute pericarditis :

rheumatism; THEM; tuberculosis; pneumonia; tumors; kidney disease, causes of chronic
pericarditis : tuberculosis; tumors; DBST.
b) clinical classification (according to the course, the nature of the exudate or the productive
process)

I. Acute pericarditis:

a) dry (fibrinous)
b) exudative (exudative) with or without cardiac tamponade
c) pyopericardium (with purulent or putrefactive effusion) with or without cardiac tamponade

II. Chronic pericarditis:

a) effusion (exudative)
b) adhesive (adhesive): asymptomatic, with functional disorders of cardiac activity, with lime
deposits ("armored heart"), with intrapericardial adhesions (nodules), incl. and compressive
(constrictive) pericarditis, with extrapericardial adhesions (acretions).

The pathogenesis is due to the following mechanisms:

1) direct impact of the pathological process on the pericardium

2) hematogenous or lymphogenous spread of infection
3) allergic mechanism (autoaggression - "antibody" and immunocomplex mechanisms of
myocardial damage, immune inflammation according to the DTH mechanism)

Schematically, the pathogenesis of pericarditis : the impact of etiological factors  damage

and "exposure" of its arterial hypertension  autoimmune reactions of the type of GND or HTH,
non-immune inflammation of the pericardium  increased permeability of vascular membranes
 fluid leakage into the pericardial cavity  release of fibrinogen with fluid  absorption of
fluid by pericardial sheets, transformation fibrin into fibrin (under the influence of thrombin),
deposited on the sheets of the pericardium (dry pericarditis)  reduced absorption of fluid from
the pericardial cavity, the predominance of exudation processes  effusion  thickening of the
fluid, partial resorption of fibrin deposits, the transformation of granulations into dense scar
tissue, the formation of fibrinous strands ( adhesions)  adhesive adhesive pericarditis (with the
severity of the adhesive process.

Clinic of dry (fibrinous) pericarditis.

1. Subjectively complaints about:

a) pain in the region of the heart , which has a number of features:

 gradual onset, builds up over several hours

 intensity is pronounced (although it can be from slight to unbearable)
 the nature of the pain is aching, stabbing, burning, scratching, less often pressing,
squeezing
  localization of pain depends on the localization of overlays, most often in the precordial
region, less often - in the region of the heart, in the epigastrium, behind the sternum
 radiates to the neck, right hypochondrium, epigastric region (without irradiation to the
left shoulder and arm, as in IHD)
 may be aggravated by swallowing, breathing, coughing, turning the torso, changing body
position, clearly not related to physical activity
 when exudate appears, it decreases and disappears, when it is resorbed, it may appear
again
 a forced position is characteristic: the pain decreases when leaning forward, in the
position on the right side with the knees pressed to the chest
 stopped by analgesics, NSAIDs. No effect from nitrates
c) weakness, sweating, fever, headache, chilling ( general intoxication syndrome )
d) persistent hiccups, sometimes nausea and vomiting that does not bring relief; on soreness at
the points between the legs of the left sternocleidomastoid muscle, between the xiphoid
process and the costal cartilages (often on the left); for tachypnea, tachycardia, extrasystole
and other reflex manifestations of dry pericarditis

2. Objectively during auscultation :

a) pericardial friction rub :

 localized in the region of the left edge of the sternum, in its lower part (in the zone of
absolute dullness of the heart), is not carried out anywhere
 synchronous with heart contractions, does not disappear when breathing
 aggravated by pressure with a stethoscope, changeable: may be heard for several hours and
disappear (when fluid appears)
 by nature gentle, rough, scraping (sometimes felt by palpation); more often two-component
(1 - due to ventricular systole, 2 - due to rapid filling of the left ventricle at the beginning and
middle of diastole), in 50% of patients, a three-membered Traube murmur is heard (in 50%
of patients), which occurs during atrial contraction (phase III) - "locomotive rhythm" ; in
some patients - a rough continuous systolic-diastolic murmur of a scraping nature.

b) pleuropericardial murmur : auscultated along the edge of relative cardiac dullness, in the
area of the cardiac notch; due to pleural friction noise, a sign of limited pleurisy.

Diagnosis of dry pericarditis:

1. Echo-KG, chest x-ray : to exclude the presence of effusion

2. ECG : concordant ST rise with a downward convexity of no more than 7 mm, turning into
high T in two or three standard leads (especially in III), not accompanied by reciprocal
depression of the ST segment in other leads; with diffuse dry pericarditis within 1-2 days, the
rise of the segment can cover all standard leads with a maximum in standard lead II; with
 limited dry pericarditis, ST segment elevation is noted in two or one standard lead; if dry
pericarditis develops against the background of MI, there is no pathological Q wave; with
pericarditis in the atrial region, the P wave may be distorted and shifted downward from the
PQ isoline.

Clinic of exudative (effusion) pericarditis.

1. Subjectively : the pain is replaced by increasing shortness of breath (because dry pericarditis
turns into exudative), which decreases in a sitting position with an inclination forward,
persistent barking cough, aphonia, dysphagia, vomiting and other symptoms of compression
appear (due to exudate pressure on trachea, recurrent nerve, esophagus, phrenic nerve,
superior and inferior vena cava, etc.)
2. Objectively :
a) on examination : restriction of diaphragm mobility; the abdomen is not involved in the act of
breathing
b) percussion can detect the presence of fluid in its amount of 500 ml or more; percussion is
carried out in two positions of the patient (vertical and horizontal), while the outlines of the
dullness of the heart change
c) auscultatory : distinct heart sounds (the heart is adjacent to the chest wall); if the disease lasts
more than 1 month, the tone of the vascular bundle, on which the heart rests, decreases, the
heart "sinks", the tones become deaf.

Early symptoms of a hemodynamically significant effusion : swelling of the jugular veins,

deafness of heart tones, disappearance of pericardial rub.

If the volume of fluid reaches 2.5-3 liters, cardiac tamponade occurs : fear of death; cyanosis,
cold sweat; neck veins swell and do not collapse on inspiration, CVP increases sharply
(measured by the Waldmann apparatus, the cannula of which is inserted into the cubital vein,
norm = 60-120 mm of water column); severe swelling of the neck ("Stokes' collar") and face,
increasing in the supine position, swelling can spread to the anterior wall of the chest; a rapid
increase in the liver, an increase in ascites and edema (ascites is more pronounced than
edema); severe shortness of breath (more than 20) and tachycardia (more than 100); paradoxical
pulse (decrease in filling at the height of inhalation due to a decrease in blood flow to the left
heart), alternating (+, -) or threadlike; decrease in blood pressure until collapse

Diagnosis of exudative pericarditis .

1. X-ray of the chest : at first, the heart is rounded, the waist is smoothed, the pulsation along
the arcs is preserved, the vascular bundle is not shortened; further, the length of the
cardiovascular bundle decreases, the diameter increases in relation to the length, the pulsation
along the arcs and the aorta are not visible, accretions can be seen (blurring, fuzzy contours
of the heart at the sites of adhesions); with chronic exudative pericarditis - a triangular shape
of the heart.
2. Echo-KG : 2-dimensional (parasternal access): echo-free space between the pericardium and
epicardium in the region of the posterior LV wall, if there is more fluid, then along the
anterior contour; 1-dimensional: increase in the distance between the sheets of the
pericardium; assessment of the volume of fluid in the pericardial cavity (resolution threshold
50-100 ml):
 if the value of the echo-free space in the region of the posterior wall of the left ventricle is
less than 1 cm and there is no echo-free space above the anterior wall of the right ventricle,
the amount of fluid is not more than 150 ml
 when the amount of fluid is 150-400 ml, the size of the echo-free space in the region of the
posterior wall of the left ventricle is more than 1 cm, but there is no fluid in front
 with an amount of 500 to 2000 ml, the value of the echo-free space behind the posterior wall
of the left ventricle is 2-3 cm, while the echo-free space is also determined in front, but its
value is less.
3. Puncture of the pericardium with cytological, biochemical, immunological, bacteriological
examination of the effusion.
4. Additional methods for diagnosing pericarditis : tuberculin skin test; blood culture for
sterility; virological, serological studies; antinuclear antibodies; titer ASL-O; cold
agglutinins; thyroid hormones; creatinine and blood urea, etc.

Treatment of acute pericarditis.

1. Mode: strict bed for 1-2 weeks, then 2-3 weeks - depending on the dynamics.
2. Diet number 10 or 10a
3. Etiotropic therapy (if the genesis of pericarditis is established): AB, antiparasitic,
antituberculous, antifungal agents, surgical treatment, etc.
4. Pathogenetic anti-inflammatory therapy:
a) NSAIDs - anti-inflammatory, analgesic, mild immunosuppressive effect (diclofenac / ortofen
/ voltaren 0.05 g 3 times / day; ibuprofen / brufen 0.4 g 3 times / day; meloxicam / movalis
0.015 g 2 times / day
b) GCS - a pronounced anti-inflammatory, anti-shock, immunosuppressive effect: with MCTD,
depending on the activity of the process - 30-90 mg per day for prednisolone; with rheumatic
pancarditis (and ARF) - 25-30 mg / day; with Dressler's syndrome - 15-30 mg / day; with
persistent exudative pericarditis of tuberculous etiology - 45-60 mg / day together with anti-
tuberculosis drugs; with idiopathic exudative pericarditis - 30-60 mg / day; are never
prescribed for purulent and tumor pericarditis!
5. Posyndromic therapy (heart failure, arrhythmias, etc.)
6. Puncture of the pericardial cavity (pericardiocentesis) - indications:
a. absolute: 1. threat of tamponade 2. purulent pericarditis
b. relative: rapidly progressive exudative pericarditis of unknown etiology
The puncture is more often performed at the Larrey point (between the xiphoid process and the
costocartilaginous angle).

As an outcome of purulent pericarditis, tuberculous pericarditis, hemorrhagic pericarditis,

hemopericardium, constrictive pericarditis with severe accretion phenomena can form, which is
characterized by Beck's diagnostic triad: 1) high venous pressure (swelling of the cervical
veins) 2) ascites 3) small, "quiet" heart ( due to gluing of pericardial sheets, diastole is disturbed
and cardiac output decreases) + negative apex beat + foci of calcification along the outer contour
of the heart. Treatment of constrictive pericarditis is operative (percutaneous balloon
pericardiotomy; partial pericardectomy ("fenestration"); subtotal pericardectomy).

19. Etiology, pathogenesis, classification, clinical picture, diagnostics of myocarditis.

Treatment of myocarditis.

Etiology of myocarditis:

1) infectious agents (viruses: Coxsackie A and B, influenza, ECHO, hepatitis B, CMV, herpes,
etc., bacteria: staphylococcus aureus, pneumococcus, spirochetes, chlamydia, myocaplasma,
fungi: actinomycetes, aspergillus, protozoa: leishmania, trypanosomes, helminths:
echinococcus, trichinella)
2) allergic or immunological factors (during treatment with various sera, vaccines, allergic
diseases - BA, food allergies, etc.)
3) toxic substances and effects (uremia, burn disease, a number of drugs: cytostatics,
novocainamide, anti-tuberculosis drugs with many months of chemotherapy, radiation
therapy of the chest organs)
4) systemic connective tissue diseases and systemic vasculitis (SLE, primary dermatomyositis,
rheumatoid arthritis, nonspecific aortoarteritis, etc.)
5) idiopathic myocarditis (Abramov-Fiedler).

The pathogenesis of myocarditis ::Cytopathic effect of the pathogen on the cardiomyocyte,

exposure to its toxins  infectious-toxic damage to the myocardium (non-immune
inflammation)  release of AG (“unmasking”)  formation of antimyocardial antibodies,
immune complexes (HNT), proliferation of T-lymphocytes, blast transformation (HRT) 
immune myocardial inflammation.

Pathomorphology : inflammatory process of the myocardium with a predominance of

exudative, proliferative or productive component; myocardial infiltrates, myofibril dystrophy,
vasculitis.

Classification of non-rheumatic myocarditis:

b) by etiology : infectious, allergic, toxic, radiation, idiopathic

c) by prevalence : focal and diffuse
d) by pathogenesis : infectious-toxic, allergic, toxic-allergic
e) downstream : acute, subacute, recurrent
f) by severity : mild (heart size is not changed, subjective sensations in the patient are not
expressed, there is no dilatation of cavities and signs of congestive heart failure, recovery
after 1-2 months, recovery may remain, a focus of cardiosclerosis may remain), medium
(increased heart size, no congestive HF at rest, duration of the disease - 2 or more months,
outcome - cardiosclerosis), severe (increased heart size, congestive HF, poor prognosis).

Clinical manifestations of myocarditis.

1. Anamnesis data - signs of an infectious disease 1-2 weeks before the onset of cardiac
symptoms (fever, sneezing, cough with mucous sputum, runny nose, myalgia, general
weakness, etc.)
2. Subjectively :

a) pain syndrome - pain in the region of the heart, arising from edema of the stroma and
compression of the nerve endings of the myocardium:

 localized in the apex or precordial region

 irradiation of pain is not typical
 diverse in nature, but more often dull, aching or stabbing, low- or medium-intensity pain
 pain is gradual (in the first days of the disease it is short-term, then after a few hours or days
it becomes constant, persistent, prolonged - up to several weeks)
 the pain increases with a deep breath, lifting up the left hand (especially with
myopericarditis)
c) angina pectoris syndrome (in 10%) - due to the involvement of the coronary
arteries; nitrglycerin does not help
d) arthralgia and myalgia (especially leg muscles)
e) signs of heart failure: shortness of breath during physical exertion (with Fiedler-Abramov
myocarditis - and at rest), sharply increasing with small movements, swelling of the jugular
veins.
f) palpitations, sensation of interruptions in the work of the heart with extrasystole, paroxysmal
tachycardia with paroxysmal tachycardia, dizziness, darkening of the eyes, severe weakness
and fainting with bradycardia due to sinoatrial or complete AV blockade
g) astheno-vegetative syndrome: weakness, fatigue, decreased performance, fever, not
associated with inflammation in cardiomyocytes.

Affected heart syndrome is a concept that combines the signs of heart failure and rhythm and
conduction disturbances.

2. Objectively :
g) examination : shortness of breath at rest, orthopnea, acrocyanosis, swelling of the jugular
veins, pronounced edema in the legs and feet (with pronounced heart failure)
h) percussion : expansion of the borders of the heart to the left or in all directions (with
significant cardiomegaly)
i) auscultation : weakening of the heart tones, especially the I tone; pathological III tone,
“gallop rhythm” (with large dilated ventricles), pendulum rhythm (the same systole and
diastole leads to the fact that heart sounds are perceived the same) or embryocardia (like a
pendulum rhythm, but with an increase in heart rate); systolic murmur at the apex of muscle
genesis; systolic murmurs of mitral regurgitation and relative tricuspid valve insufficiency
j) when examining the pulse - persistent tachycardia even at rest, not corresponding to the level
of fever.

Abramov-Fiedler myocarditis - affects only men, more often young, severe prognosis - always
ends in death, clinically manifested by progressive heart failure, complex arrhythmias
(paroxysms, blockades), myocardial infarction-like changes, thromboembolic complications.

Diagnosis of myocarditis:

1. ECG: decrease in the voltage of the teeth, arrhythmia (more often AV block or ventricular
extrasystole, sinus tachycardia), flattening of the T wave up to negative in all leads,
depression of the ST segment
2. X-ray of the chest organs: an increase in the size of the heart, a deviation of the mediastinal
organs
3. EchoCG: dilatation of the heart cavities; systolic myocardial dysfunction (decrease in EF),
diastolic myocardial dysfunction (due to myocardial edema), parietal thrombi (with severe
myocarditis)
4. Subendomyocardial biopsy of the myocardium (according to the Dalas criteria for
myocarditis, there is an inflammatory cell infiltration of the myocardium in combination
with necrosis and degenerative changes in cardiomyocytes, which is not characteristic of
IHD)
5. Laboratory data: KLA: increased ESR, leukocytosis with a shift to the left or
leukopenia; BAC: biochemical inflammation syndrome - an increase in blood fibrin,
haptoglobin, seromucoid, cerruloplasmin, sialic acids,  2 - and -globulins with a decrease in
albumin levels, an increase in C-reactive protein), in severe cases - the appearance of markers
of myocardial destruction (increase in ASAT , LDH 1 , CPK and CPK-MB, TnI and TnT;
serological studies: virus-neutralizing antibodies (titer increased by more than 4 times, etc.)

Complications of myocarditis : acute HF during the course of the disease, CHF at the
end; arrhythmias (up to fibrillation), thromboembolic complications, etc.

Principles of treatment of myocarditis:

6. Only bed rest, even with mild forms (mild course - up to 1 month, moderate course - 1.5-2
months, severe course - 4-6 months or until the temperature returns to normal), physical
activity is limited, if there are signs of congestive heart failure – diet low in salt, restricted
fluid intake
7. Etiotropic therapy: antiviral drugs are not used; in infectious diseases - antibiotic therapy up
to 2 weeks (depending on the intended agent)
8. Anti-inflammatory drugs:
k) NSAIDs (diclofenac 50-150 mg / day, indomethacin 25 mg 3-4 times / day - up to 4-5 weeks)
l) GCS (prednisolone 20-40 mg/day) - indicated: for patients with severe myocardial dilatation
(severe and moderate course); patients with exudative pericarditis (myopericarditis), with
autoimmune signs (skin syndrome, articular syndrome); with the ineffectiveness of NSAIDs
m) aminoquinoline preparations (delagil, plaquenil, 0.5 g each for 6-8 months) are indicated for
severe cases; have anti-inflammatory, weak immunosuppressive, antiarrhythmic actions
9. Symptomatic therapy: SG - very carefully, even ordinary doses can cause glycoside
intoxication; shown only with atrial fibrillation and very low EF; anticoagulants of indirect
action; metabolic therapy (mildronate, preductal) - in the presence of dystrophic changes and
at the end of treatment; antiarrhythmic drugs; antihistamines

20. Cardiomyopathy: definition of this disoders group, classification, clinical types and
their diagnostics. Treatment.

Cardiomyopathy (CMP) is a myocardial disease of unknown or unclear etiology, the dominant

features of which are cardiomegaly and / or HF, the processes of damage to the valves, coronary
arteries, systemic and pulmonary vessels (WHO) are excluded.

Classification of CMP by clinical variants and their characteristics:

CLASSIFICATION

• Primary

 Genetic
 Hypertrophic.
 Arrhythmogenic / right ventricular dysplasia.
 Non-compact left ventricle ("spongy" myocardium).
 Disorders of the conducting system of the heart (Lenegre syndrome).
 Glycogenoses (types PRKAG, and Danone).
 Mitochondrial myopathies.
 Disorders of ion channel function:
 long QT syndrome; Brugada syndrome;
 catecholaminergic polymorphic ventricular tachycardia;
 short QT interval syndrome;
• south Asian sudden unexplained sleep death syndrome

o Acquired

 Myocarditis (inflammatory).
 caused by sudden emotional stress. Takotsubo.
 Peripartial
 induced by tachycardia.
 in children whose mothers suffer from type 1 diabetes.
 Mixed
 Dilated
 Primary restrictive hypertrophic

• Secondary – part of a secondary systemic diseas

1. Dilated cardiomyopathy - a disease with impaired systolic function of the heart,

insufficiency of cardiac output, dilatation of the ventricles and cardiac arrhythmias.

Etiology of DCMP : not known for certain, a number of hypotheses - hereditary

predisposition; autoimmune disorders (AT to myosin heavy chains, connection with HLA-
DR4); violation of metabolic processes (carnitine deficiency); subclinical viral
infection; apoptosis of cardiomyocytes.

Clinical picture of DCMP:

 young men are more often affected; symptoms develop gradually, nothing bothers the patient
for a long time, and DCM is detected by chance during preventive examinations
 the first signs of the disease are increased fatigue, weakness, then shortness of breath (first
with exercise, then at rest), cardiac asthma, orthopnea, peripheral edema, hepatomegaly
(clinic of congestive biventricular HF)
 often there is cardialgia, less often - angina pectoris
 thromboembolic complications

Objectively : huge cardiomegaly and dilatation of the heart; deaf 1 tone, accent 2 tones over the
pulmonary artery, 3 and 4 tones, gallop rhythm, systolic murmur at the apex and in the area of
the tricuspid valve (relative insufficiency), cardiac rhythm and conduction disturbances

Diagnosis of DCMP:

1. EchoCG: dilatation of all chambers of the heart with unchanged or slightly changed wall
thickness; increase in systolic and end-diastolic dimensions of the left ventricle; diffuse
hypokinesis of the LV walls; decrease in contractile function; mitral and tricuspid
regurgitation; parietal thrombi; decrease in left ventricular EF
2. ECG: change in the end part of the ventricular complex; may be pathological Q
3. X-ray of the chest organs: pronounced expansion of the cardiac shadow, in the later stages -
signs of stagnation in the pulmonary circulation.

Principles of treatment of DCMP:

1. Limitation of physical activity (bed rest is indicated only for severe decompensated HF), diet
(restriction of fluid intake to 1.5 l / day, sodium chloride), prohibition of smoking and alcohol
2. ACE inhibitors - increase the life expectancy of patients with DCMP, reduce myocardial
remodeling and fibrosis (enalapril 2.5-40 mg / day - individual dose selection) + diuretics
(thiazide, loop) and digoxin (with severe heart failure and MA)
3. Beta-blockers (preferably carvedilol) in small doses - to stabilize neurohumoral regulation in
DCM.
4. Antiplatelet and anticoagulant therapy (since thromboembolic complications are frequent):
small doses of ASA, with bed rest during the entire period - direct anticoagulants (heparin s /
c 1 ml (5000 IU) 2 times / day or enoxaparin sodium p / to 0.2-0.4 ml (20-40 mg) 1 time /
day under the control of platelet count), in the presence of MA, episodes of
thromboembolism in history - indirect anticoagulants (warfarin with dose selection according
to INR up to 2.0- 3.0 and subsequent monitoring of its stability every 4-6 weeks)
5. Antiarrhythmic therapy - preferably PAS III (amiodarone and sotalex)
6. Metabolic therapy (phosphaden, cytochrome-C, neoton)
7. With refractoriness to drug therapy - surgical treatment (heart transplantation)
1. Prognosis : severe, characteristically progressive deterioration of ventricular functions, up
to 70% of patients die within 5 years.

2. Hypertrophic cardiomyopathy - a disease characterized by a significant increase in the

thickness of the wall of the left ventricle (in 90% - with hypertrophy of the interventricular
septum) without dilatation of its cavity.

Variants of HCM: subaortic stenosis (most common); apical variant; asymmetric septal
hypertrophy; symmetrical myocardial hypertrophy (concentric hypertrophy - obstructive and
non-obstructive types).

Etiology : more than 50% - hereditary diseases of an autosomal dominant type, in other cases,
sporadic mutations of genes encoding proteins of the myofibrillar apparatus play a role (-
myosin heavy chain, TnT, -tropomyosin, etc.)

Clinical picture of HCM:

 can proceed from asymptomatic forms accidentally detected during examination to severe
clinical manifestations and sudden death (more often in young people)
 a variety of cardialgia - common, variable - from rare stabbing pains to typical angina attacks
(with relative coronary insufficiency; nitroglycerin aggravates the patient's condition !!!)
 a feeling of palpitations, interruptions in the region of the heart (arrhythmic syndrome) -
more often AV conduction disturbances, ventricular arrhythmias of various gradations, less
often - MA
 dizziness, syncope (both due to arrhythmias and due to low cardiac output syndrome) from
multiple daily to single during life
 shortness of breath, less often peripheral edema and hepatomegaly as signs of heart failure -
rare

Objectively : an increase in the size of the heart; systolic ejection murmur at the apex (relative
mitral valve insufficiency); BP is normal or low.

Diagnosis of HCM:

1. Echocardiography: "unexplained" hypertrophy of one or more LV segments (usually the

anterior part of the IVS) without dilatation of the ventricular cavity; decrease in the volume
of the LV cavity; increase in myocardial contractility; violation of LV diastolic
function; signs of LV outflow tract obstruction
2. ECG: a characteristic feature is the presence of a pathological Q wave (more often in II, III,
aVF and left chest leads; at the same time, the R wave does not grow in the right chest
leads); with the apical form of HCM - giant negative T waves in the chest leads; with
asymmetric hypertrophy of the interventricular septum - a pathological Q wave or QS
complex in the right chest leads.

Principles of HCM treatment:

1. Limitation of heavy physical exertion (due to the risk of sudden death).

2. -blockers (propranolol 120-160 mg / day), verapamil 240-480 mg / day - prescribed from
the moment of diagnosis, because they stop the progression of the disease by reducing the
intraventricular pressure gradient and improving diastolic function of the heart
3. When indicating dangerous cardiac arrhythmias - amiodarone orally 200 mg 3-4 times / day
for 3-10 days under ECG control, then a maintenance dose of 100-400 mg 1 time / day with
periodic ECG control, with MA + anticoagulants. If there is a risk of sudden death - a
defibrillator-cardioverter.
4. Symptomatic therapy for heart failure. But! do not prescribe nitrates and vasodilators (due to
the risk of increasing left ventricular obstruction), SG and diuretics.
5. Surgical treatment: partial muscle resection in the basal part of the interventricular septum
(myotomy-myectomy), heart transplantation.

Prognosis : the most favorable in comparison with other cardiomyopathies, the disease can
proceed for decades, patients remain able-bodied for a long time.
3. Restrictive cardiomyopathy - a disease with a violation of the diastolic function of the heart
as a result of fibrotic changes in the endocardium, subendocardium and myocardium, normal or
reduced heart size, the development of total heart failure.

Etiology : in addition to the idiopathic variant, a number of other diseases (amyloidosis,

hemochromatosis, sarcoidosis, etc.) can lead to RCMP.

Clinical picture of RCMP:

 The first signs are nonspecific: weakness, shortness of breath, decreased exercise
tolerance, rarely - pain in the heart area, further HF progresses (but even with
biventricular HF, right ventricular symptoms predominate): recurrent ascites, effusion in
the pleural and pericardial cavities, hepatomegaly, severe cyanosis of the face and
swelling of the jugular veins, less often - peripheral edema.
 Heart rhythm disturbances and various thromboembolic complications are often detected.
 Objectively, the heart tones are muffled, the murmur of mitral insufficiency is heard, the
gallop rhythm; tachycardia, decrease in blood pressure is recorded.

Diagnosis of RCMP:

1. Echo-KG: diastolic ventricular dysfunction; dilatation and hypertrophy of the myocardium is

absent; contractility is not changed.
2. ECG: low volts QRS and T (especially with pericardial effusion), various rhythm and
conduction disturbances.

Principles of treatment of RCMP:

1. Limiting physical activity and salt intake

2. In the initial stage - GCS (reduce myocardial fibrosis), if they are ineffective - cytostatics
3. Pathogenetic and symptomatic treatment of HF, arrhythmias (amiodoron), prevention of
thromboembolism (anticoagulant and antiplatelet therapy)
4. Surgical treatment - heart transplantation - is ineffective due to the possibility of recurrence
of the process in the transplanted heart.

Prognosis : serious, 5-year mortality up to 70%.

21. Primary cardiomyopathy: differential diagnostics. Treatment.

• Primary

 Genetic

 Hypertrophic.
 Arrhythmogenic / right ventricular dysplasia.
 Non-compact left ventricle ("spongy" myocardium).
  Disorders of the conducting system of the heart (Lenegre syndrome).
 Glycogenoses (types PRKAG, and Danone).
 Mitochondrial myopathies.
 Disorders of ion channel function:
 long QT syndrome; Brugada syndrome;
 catecholaminergic polymorphic ventricular tachycardia;
 short QT interval syndrome;
 south Asian sudden unexplained sleep death syndrome

o Acquired

 Myocarditis (inflammatory).
 caused by sudden emotional stress. Takotsubo.
 Peripartial
 induced by tachycardia.
 in children whose mothers suffer from type 1 diabetes.
 Mixed
 Dilated
 Primary restrictive hypertrophic

Arrhythmogenic right ventricular cardiomyopathy (ARVC):

Etiology

 Mutations of various genes (e.g., JUP gene)

 Autosomal recessive or autosomal dominant inheritance

Pathophysiology

 Right ventricular myocardial cell death (due to myocyte apoptosis, inflammation, and
fatty/fibrotic tissue replacement) → thinning of the right ventricular wall → dilation of the
ventricle → ventricular arrhythmia and dysfunction [6]
 The left ventricle can also be affected, but consequences are usually less severe.

Clinical features

 Highly variable
 Many patients remain asymptomatic.
 Angina pectoris
 Dyspnea
 Peripheral edema, ascites, hepatic and splenic congestion
  Palpitations, syncope, possibly sudden cardiac death (particularly during or after
exercise)

Diagnostics :

 ARVC is diagnosed based on the AHA criteria which include the following features:
 Dysfunction and structural abnormalities of RV (can be revealed by echocardiography,
MRI, or RV angiography)
 Histological characteristics (require myocardial biopsy)
 Abnormal repolarization (diagnosed with ECG)
 Depolarization/conduction abnormalities (diagnosed with ECG)
 Arrhythmias (diagnosed with ECG)
 Family history (confirmation of ARVC in a relative either by criteria, pathological
examination in surgery or autopsy, or by genetic testing)

ECG

 Repolarization disturbances in the right precordial leads (V1-3)

 Possibly epsilon wave (at the end of a widened QRS complex)
 Highly specific for ARVC but only occurs in ∼ ⅓ of patients
 Increased QRS duration
 Ventricular tachycardia
 Ventricular extrasystoles
 Echocardiography and cardiac MRI
 RV enlargement
 RV wall motion abnormalities
 ↓ RV EF
 Localized RV aneurysms
 Endomyocardial biopsy: fibrofatty replacement of myocardial tissue
 Genetic testing: Multiple genetic abnormalities that can cause ARVC have been
identified (e.g., plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2),
desmoglein-2 (DSG2), desmocollin (DSC2)).

Management :

 Avoid intense physical exertion.

 Antiarrhythmic treatment
 Pharmacologic: beta blockers (e.g., sotalol), amiodarone, calcium channel blockers
 Invasive
 AICD implantation (in high-risk patients, e.g., patients with left ventricular involvement)
 Radiofrequency ablation (only as ancillary treatment)
 Heart transplant (in severe cases that are refractory to all other treatments)
  Screening and genetic counseling for first-degree relatives

Left ventricular noncompaction : rare inherited cardiomyopathy which is associated with

structural abnormalities of the left ventricular myocardium (prominent trabeculations and deep
intertrabecular recesses)

Clinical findings:Signs of heart failure and arrhythmia (e.g., dyspnea, edema, chest pain,
palpitations, syncope),Thromboembolisms

Diagnostics: echocardiography and/or cardiac MRI: LV wall thickening, prominent trabecular

meshwork, detection of abnormal flow (within the deep intertrabecular recesses)

Treatment: no causal treatment available

 Avoid intense physical exertion

 Symptomatic treatment of complications (e.g., heart failure)
 Prevention of thromboembolism
 \AICD
 Heart transplant
 Family and genetic counseling

Arrhythmia-induced cardiomyopathy : recurring or persistent atrial or ventricular arrhythmias

causing structural cardiac changes and left ventricular dysfunction (potentially reversible)

Etiology

 Supraventricular tachyarrhythmias (i.e., tachycardia, atrial fibrillation, atrial flutter,

supraventricular reentry tachycardia)
 Ventricular tachyarrhythmia (less commonly than supraventricular tachyarrhythmias)
 Atrial or ventricular ectopy (with or without tachycardia)

Clinical features:Signs of underlying arrhythmia (e.g., palpitations, syncope),Signs of left heart

failure (e.g., dyspnea, chest pain, pulmonary edema)

Diagnostics

 ECG: tachyarrhythmia, ectopic foci

 Cardiac monitoring (e.g., Holter monitor)
 Echocardiography and/or cardiac MRI: to evaluate cardiac structure and function (e.g.,
LVEF measurement)
 To exclude other causes (e.g., coronary heart disease via coronary angiograph)

Treatment
  Beta blockers: management of CHF, rate control in tachyarrhythmias
 Antiarrhythmics (e.g., amiodarone): rhythm control in tachyarrhythmias
 Catheter ablation: rhythm control in tachyarrhythmias, ectopic foci

22. Paroxysmal arrhythmias: clinical picture, ECG -diagnostics, treatment.

Classification of rhythm disturbances :

I. Violation of the formation of an impulse.

A. Violation of the automatism of the SA node (nomotopic arrhythmias) :

1) sinus tachycardia
2) sinus bradycardia
3) sinus arrhythmia
4) sick sinus syndrome

B. Ectopic (heterotopic) rhythms due to the predominance of automatism of ectopic

centers (passive rhythms - the main driver does not work, ectopic drivers turn on):

1) slow (replacement) escape complexes and rhythms: atrial, from the AV connection,
ventricular
2) accelerated ectopic rhythms (non-paroxysmal tachycardia): atrial, from the AV connection,
ventricular
3) migration of the pacemaker source

B. Ectopic (heterotopic) rhythms due to the re - entry mechanism (active rhythms - both the main
pacemaker and ectopic ones work)

1) extrasystole: atrial, from the AV connection, ventricular, polytopic

2) paroxysmal tachycardia: atrial, from the AV junction, ventricular, polytopic
3) atrial flutter
4) atrial fibrillation (fibrillation)
5) flutter and flicker (fibrillation) of the ventricles.

II. Conduction disorders:

1) sinoatrial (sinoauricular) blockade

2) intra-atrial (inter-atrial) blockade
3) atrioventricular block: I degree, II degree (Mobitz type I and II), III degree (complete block)
4) intraventricular blockade (blockade of the branches of the His bundle): one branch, two
branches or three branches (mono-, bi-, trifascicular)
5) ventricular asystole
6) premature ventricular excitation syndrome (PVZh): Wolf-Parkinson-White (WPW) and
shortened P-Q interval (CLC).

III. Combined arrhythmias: parasystole, ectopic rhythms with exit block, AV dissociation

Clinic of arrhythmias:Symptoms of arrhythmia are nonspecific and often absent; in the presence
of complaints, two main groups are distinguished:

1) due to the actual violation of the heart rhythm: a feeling of palpitations and interruptions in
the form of jolts, "fading", "turning over"
2) due to the effect on hemodynamics (due to reduced cardiac output) : dizziness, loss of
consciousness, shortness of breath, angina pectoris, sudden cardiac arrest

Diagnosis of arrhythmias:

1. ECG at rest (including long-term ECG recording in leads II, aVF, double voltage ECG,
ECG with stress tests - medication, exercise, ECG recording at a speed of 100 mm / s)
2. 24 hour Holter ECG monitoring
3. Esophageal ECG
4. Electrophysiological examination (registration of intracardiac ECG and programmed
pacing) is an invasive research method in which catheters with electrodes are inserted
through the femoral vein into various parts of the heart, then ECG is recorded at rest and
during stimulation, etc.

The prognosis of arrhythmias is determined by their:

1) influence on cardiohemodynamics, cerebral, coronary and renal blood flow

2) the ability to transform or serve as triggers for potentially fatal electrical instability of the
ventricular myocardium (persistent ventricular tachycardia, ventricular fibrillation)

Arrhythmias that usually do not require treatment: sinus bradycardia, tachycardia, arrhythmia,
pacemaker migration, accelerated rhythm from the AV junction, 1st degree AV block, rare atrial
and ventricular extrasystoles.

Arrhythmias requiring intensive care : sinoatrial block, ventricular tachycardia, Mobitz II degree
AV block, ventricular flutter and fibrillation, complete AV block, accelerated idioventricular
rhythm, two- or three-beam block, frequent (more than 6 per minute) atrial extrasystoles, atrial or
nodal tachycardia, flutter and atrial fibrillation, frequent (more than 5 per minute) ventricular
extrasystoles.

The main types of arrhythmias and their clinical and diagnostic features:

I. Violation of the automatism of the sa node (nomotopic arrhythmias):

a) sinus tachycardia - an asymptomatic course is characteristic, less often - signs of circulatory
disorders (more often with concomitant pathology); ECG: increase in heart rate up to 100-
160 beats / min; correct sinus rhythm. Treatment: with hemodynamically significant
tachycardia, propranolol orally 10-40 mg 2-4 times / day or verapamil orally 40-80 mg 3-4
times / day.
b) sinus bradycardia - more often asymptomatic, less often - signs of impaired blood supply to
organs (more often in the elderly: fatigue, low exercise tolerance, dizziness, fainting); ECG:
decrease in heart rate to 40-59 beats / min; correct sinus rhythm. Treatment: with
hemodynamically significant bradycardia, atropine IV or s / c 0.6-2.0 mg up to 2-3 times /
day or isoprenaline inside 2.5-5 mg up to 3-4 times / day.
c) sinus arrhythmia is characterized by an asymptomatic course; ECG: fluctuations in the
duration of RR intervals exceeding 0.16 s ( 10%); sinus rhythm. Treatment: not required.
d) with SA node weakness syndrome - most often a rare heart rhythm (complaints of dizziness,
fainting), its insufficient increase during exercise; bradycardia is associated with
tachyarrhythmia (complaints of palpitations, dizziness, fainting, angina pectoris, poor
tolerance to vagotropic effects and PAS due to tachycardia); ECG - complex of arrhythmias:
sinus bradycardia, sinus node arrest (sinus arrest), SA blockade, alternation of brady- and
tachyarrhythmias (tachybrady syndrome), MA paroxysms against the background of sinus
bradycardia. Treatment: with severe bradycardia or episodes of asystole - pacemaker
implantation, with hemodynamically significant bradycardia - atropine intravenously or s / c
at 0.6-2.0 mg up to 2-3 times / day or isoprenaline inside at 2.5-5 mg up to 3-4 times / day.

II. Ectopic rhythms due to the predominance of automatism of ectopic centers:

a) slow escape rhythm:

1. lower atrial - asymptomatic; ECG: negative P waves in leads II, III, aVF; unchanged
QRS complex.
2. from the AV connection - asymptomatic course; ECG: negative P wave before the QRS
complex (with premature excitation of the atria), the P wave is superimposed on the QRS
complex (with simultaneous excitation of the atria and ventricles), negative P wave after
the QRS complex (with premature excitation of the ventricles)
3. ventricular rhythm (idioventricular) - asymptomatic course; ECG: no P wave; rare
ventricular rhythm; widening and deformation of the QRS complex.

b) non-paroxysmal tachycardia - asymptomatic course; ECG: different from corresponding slow

escape rhythms of higher heart rate (120-130/min).

III. Ectopic rhythms due to the re-entry mechanism:

a) extrasystole - clinically more often asymptomatic, less often complaints of "interruptions in

work" or periods of "cardiac arrest"
1. atrial - ECG: premature extraordinary appearance of the P wave and the QRS
complex; deformation or change in the polarity of the P wave of the
extrasystole; extrasystolic QRS complex in shape as normal; incomplete compensatory pause
(the distance from the R wave of the QRS complex of sinus origin before extrasystole to the
R wave of the QRS complex of sinus origin after extrasystole is less than 2 RR intervals of
sinus origin)
2. atrioventricular - ECG: extrasystole from the upper third of the AV node - QRS ≤ 0.10 sec,
extrasystolic P positive or negative; incomplete compensatory pause; from the middle third
of the AV node - QRS ≤ 0.10 s, extrasystolic P is absent or negative after the post-QRS
complex; incomplete CP; from the lower third of the AV node: QRS ≤ 0.10 s; extrasystolic P
is absent or negative after QRS; incomplete CP.

Treatment of supraventricular extrasystoles:

1. In the absence of a clinic, no treatment is required. Therapy of the underlying disease.

2. If the patient's condition worsens and there is no organic pathology of the heart - beta-
blockers (metoprolol orally 50-100 mg 2 times / day) or if there are contraindications to
them - calcium antagonists (verapamil orally 40-80 mg 3-4 times / day )
3. If extrasystoles cause episodes of supraventricular tachycardia or atrial fibrillation - PAS
IA (quinidine sulfate orally 200-300 mg 3-4 times / day), less often IC (etacizin orally 50
mg 3-4 times / day) classes.

3. ventricular - ECG: premature extraordinary appearance of an extended (> 0.12 s) and

deformed extrasystolic QRS complex; absence of a P wave before ventricular extrasystole; the T
wave is discordant (opposite) to the main wave of the ventricular extrasystolic
complex; complete compensatory pause (the distance from the R wave of the QRS complex of
sinus origin before extrasystole to the R wave of the QRS complex of sinus origin after
extrasystole is equal to 2 RR intervals of sinus origin). With right ventricular extrasystole, high
extrasystolic R I and deep S III , with left ventricular: high R III and deep S I.

Treatment of ventricular extrasystoles:

1. In the absence of a clinic, no treatment is required. Therapy of the underlying

disease. Refusal of alcohol, smoking, excessive consumption of coffee.
2. If the patient's condition worsens in the absence of an organic pathology of the heart -
PAS IA (quinidine sulfate orally at 200-300 mg 3-4 times / day), less often - IC (etacizin
orally 50 mg 3-4 times / day)
3. With high-grade ventricular extrasystoles (III-V according to B.Lown) - additionally
lidocaine or phenytoin, and in the presence of an organic heart disease - amiodarone (200
mg orally 3 times / day in the 1st week, then 200 mg 2 times / day in the 2nd week, then
200 mg 1 time / day from the 3rd week for a long time under ECG control every 4-6
weeks)
b) paroxysmal tachycardia: clinically occurs suddenly and ends abruptly; complaints of an attack
of palpitations, which began with a sharp push behind the sternum; the patient is frightened,
worried; there may be dizziness up to syncope; with a sharp increase in heart rate, acute left
ventricular failure, myocardial infarction is possible; auscultatory leveling of I and II heart
sounds, the pauses between them become the same ("pendulum mode"), over the area of the
aorta and pulmonary artery - systolic murmur (due to accelerated turbulent blood flow)

1. supraventricular (atrial and atrioventricular) - ECG: suddenly starting and suddenly ending
attack of increased heart rate up to 160-220 / min; reduced, biphasic, deformed P wave before
each QRS complex; normal unchanged QRS complexes.

Treatment of supraventricular paroxysmal tachycardia.

1. Relief of an attack : vagal techniques  no effect  ATP 1% - 2-4 ml IV quickly (but only
in a hospital, because asystole is possible)  no effect  ATP 1% - 2-4 ml IV / c quickly
repeatedly  no effect  verapamil 0.25% - 4 ml IV  no effect 5-10 min  procainamide
500-1000 mg iv for 10 min or amiodarone 300 mg (5 mg/kg) for 20 min, then in/in drip up to
1000-1200 mg/day
2. Seizure prevention : verapamil 120-240 mg/day or propranolol 30-120 mg/day or
amiodarone 100-600 mg/day under QT control (not higher than 25% of baseline) + treatment
of the underlying disease

2. ventricular - ECG: suddenly starting and suddenly ending attack of increased heart rate up to
160-220 / min; deformation and expansion of the QRS complex (> 0.12 s); discordant
arrangement of R and T waves; P wave and QRS complex are located independently of each
other (atrioventricular dissociation).

Treatment of ventricular paroxysmal tachycardia.

1. Relief of paroxysm :

a) if systemic blood pressure < 90/60 mm Hg.  EIT 200-360 J

b) with stable hemodynamics: lidocaine 2% 10-20 ml IV or 10% 2-5 ml IV or amiodarone 300
mg (5 mg/kg) for 20 minutes, then IV drip up to 1000-1200 mg/day (amiodorone is
preferred).

2. Prevention of paroxysms : propranolol 40-120 mg / day or amiodarone 100-600 mg / day

under QT control (not higher than 25% of the initial value) + treatment of the underlying disease

3 . atrial fibrillation - patients are often worried about shortness of breath, palpitations,
sometimes pain behind the sternum, fatigue, dizziness, fainting; signs of heart failure may
increase; episodes of thromboembolism are characteristic (especially at the time of rhythm
recovery); ECG: P wave is absent in all leads; there are frequent waves of atrial fibrillation f in
leads II, III, aVF, V1, V2 (up to 350-700/min); RR intervals are different in duration (the
difference is more than 0.16 seconds). Depending on the frequency of contraction of the
ventricles, there may be a tachy-, normo- and bradyarrhythmic form.

4. atrial flutter - complaints as with atrial fibrillation, but thromboembolic complications are
rare; ECG: frequent (250-300/min) regular similar sawtooth atrial waves F in II, III, aVF, V1,
V2; correct regular ventricular rhythm with equal RR intervals; the presence of unchanged
ventricular complexes, each of which is preceded by a certain number of atrial waves F.

Treatment of fibrillation and atrial flutter:

1. Relief of an attack :

a) with atrial flutter with impaired hemodynamics - EIT

b) with atrial fibrillation, rhythm restoration is not carried out in cases of severe organic heart
damage, frequent paroxysms of MA (more than 3 per year), concomitant pathology that
determines an unfavorable prognosis for life, in other cases, drugs can be used to restore the
rhythm (but not more than 2- x immediately!):
1) verapamil 0.25% - 4 ml IV (caution with WPW)
2) procainamide 10% - 5-10 ml IV (careful - causes significant hypotension)
3) quinidine sulfate orally 200 mg every 2-3 hours up to a total dose of 1000 mg or until the
relief of paroxysm (only with persistent MA for at least 3 days)
4) amiodarone 1200 mg/day, of which 600 mg IV for several hours, the rest of the IV dose at a
rate of 0.5 mg/min for the rest of the day

If the paroxysm lasted more than 48-72 hours, at least 6 hours before the rhythm is restored,
anticoagulant therapy is performed.

2. Prevention of paroxysms :

a) if there is CHF II and above - cardiac glycosides

b) if there is no CHF, beta-blockers (propranolol 30-120 mg/day) or amiodarone (100-600
mg/day, once a year - chest x-ray and thyroid control)
c) if one drug is not effective: beta-blocker + cardiac glycoside or beta-blocker + amiodarone.

For the prevention of thromboembolic complications, constantly acetylsalicylic acid 150 mg /

day orally.

5. flutter and flicker (fibrillation) of the ventricles - clinically incompatible with life,
because with them, hemodynamics is sharply disturbed, which leads to clinical death (since the
onset of flutter or ventricular fibrillation, the pulse disappears, heart sounds are not heard, blood
pressure is not detected, the skin becomes pale with a bluish tinge; the patient loses
consciousness, convulsions may appear, pupils dilate breathing becomes noisy and
frequent); ECG: with flutter - a frequent rhythm of 160-300 beats / min; QRS complex and T
wave indistinguishable, diastole absent; regular sinusoidal flutter waves; with flickering -
continuously changing in shape, duration, height and direction of the wave with a frequency of
300-500 per minute (usually large at first, as hypoxia increases, their amplitude decreases down
to zero - cardiac asystole)

Treating flutter and ventricular fibrillation:

1. Within 10 seconds, assess the presence of breathing, pulsation, restore airway patency and
proceed to cardiopulmonary resuscitation
2. Artificial ventilation of the lungs and indirect heart massage (mode: 15 breaths per 2 clicks, if
there is one resuscitator and 5 breaths per 1 click, if there are two resuscitators, the frequency
of pressure on the sternum during heart massage is 100 / min)
3. Adrenaline 1 mg IV every 3-5 minutes until the end of resuscitation (with endotracheal
administration, the doses are doubled)
4. A series of defibrillations (200 - 300 - 360 J for biphasic defibrillators, 300 - 360 - 360 J for
monophasic), each subsequent defibrillation - as close as possible to the previous one. Before
the third defibrillation - amiodarone 300 mg into the central vein by jet, then 1 minute - chest
compressions, then - defibrillation.
5. Amiodarone 150 mg IV, followed by chest compressions for 1 minute, followed by shock.
6. Continuation of the defibrillation complex with artificial respiration and chest compressions
for at least 30 minutes. If resuscitation lasts more than 10 minutes, sodium bicarbonate 4% -
100 ml IV can be administered to prevent acidosis.
7. When restoring cardiac activity: amiodarone 1 mg / min for 6 hours, then 0.5 mg / min for
the remainder of the day to a total dose of 1200 mg; on the second day amiodarone IV 1200
mg.

With asystole + 3 times, atropine is added every 3-5 minutes, 1 mg IV.

23. Heart blocks: clinical picture, ECG-diagnostics, treatment.

Etiology of heart block:

1. Organic heart disease (cardiosclerosis, MI, all myocarditis, especially rheumatic origin,
syphilis, congenital heart disease, heart injury, especially surgical)
2. Changes in the tone of the autonomic nervous system (neurosis, vagotonia of athletes,
brain tumors)
3. Overdose of drugs (cardiac glycosides, beta-blockers)
4. Electrolyte disorders (especially potassium imbalance)

The pathogenesis of heart block:

The conduction of impulses along the conduction system of the heart is determined by a number
of factors, with a pathological change in which blockades occur:
1. the ratio between the parasympathetic mediator acetylcholine (slows down the conduction of
an impulse) and the sympathetic mediator norepinephrine (accelerates the conduction of an
impulse)
2. the presence of local acidosis due to myocardial ischemia (slows down the conduction of the
impulse)
3. the level of a number of hormones (catecholamines, corticosteroids)
4. the concentration of potassium in the blood (hyperkalemia slows down conduction,
hypokalemia speeds it up)

Clinical and diagnostic features of various heart blocks:

1) Sinoatrial (sinoauricular) blockade - slowing down or stopping the conduction of an

impulse from the sinus node through the sinoatrial connection; clinically asymptomatic or
manifested by dizziness, fainting, a feeling of irregular heart activity; ECG: periodic loss of
individual cardiac cycles (P waves and QRS complexes); an increase at the time of the loss of
cardiac cycles of the pause between two adjacent RR teeth by almost 2 times compared to the
usual interval between them.

Treatment of SA: in the presence of clinical manifestations - atropine in / in or s / c at 0.6-2.0 mg

up to 2-3 times / day or isoprenaline inside at 2.5-5 mg up to 3-4 times / day.

2) Intra-atrial (inter-atrial) blockade - a violation of the conduction of an impulse through the

conduction system of the atria; clinically asymptomatic; ECG: increase in the duration of the P
wave more than 0.11 sec; splitting of the R wave. Does not need treatment.

3) Atrioventricular block - slowing down or stopping the impulse from the atria to the
ventricles.

a) I degree - slowing down the conduction of impulses from the atria to the ventricles; clinically
not manifested; ECG: prolongation of the PQ interval more than 0.2 sec
b) II degree - is divided into two types; patients may not feel anything or feel moments of
cardiac arrest, in which dizziness appears, blackout in the eyes (clinical symptoms increase
with the loss of several ventricular complexes in a row)
1. Mobitz type I (proximal blockade) - ECG: a gradual increase in the PQ interval, followed by
prolapse of the ventricular complex (Samoilov-Wenckebach periods); QRS not changed
2. Mobitz type II (distal block) - ECG: regular or random prolapse of individual ventricular
complexes without prolongation of the PQ interval

c) III degree (complete blockade) - lack of impulse conduction to the ventricles, while in the
ventricles there is its own heterotopic focus of idioventricular rhythm, the lower its automatism,
the more difficult the clinic; clinically: progressive heart failure during exercise (associated with
low heart rate), Morgagni-Adams-Stokes syndrome with the transition of incomplete blockade to
complete and progression of AV conduction disorders (sudden pallor, loss of consciousness,
pulse is not detected, heart sounds are not audible; then the patient blue, convulsions appear,
there may be involuntary urination and defecation; the attack ends for 1-2 minutes with the
appearance of an idioventricular rhythm or for 3-4 minutes with the death of the
patient); characteristic slow pulse; ECG: P waves without connection with QRS
complexes; correct alternation of atrial complexes (independent atrial rhythm); correct
alternation of ventricular complexes (correct ventricular rhythm); P waves may overlap with
ventricular complexes.

Treatment : AV blockade of the 1st degree does not need treatment, only periodic examinations
are necessary; AV blockade II Mobitz I - atropine IV or s / c 0.6 mg up to 2-3 times / day; with
AV blockade II Mobitz II and complete AV blockade, pacemaker implantation is indicated.

4) Intraventricular blockade (blockade of the branches of the bundle of His): one branch,
two branches or three branches (mono-, bi-, trifascicular) - most often do not manifest
themselves clinically.

a) blockade of the right leg of the bundle of His - ECG: ventricular QRS complexes in V 1 ,
V 2 in the form of RsR (M-shaped); in the right chest leads, ST segment depression, negative
or biphasic T wave; in I, aVL, V 5 , V 6 - broadened serrated tooth S; J>0.02 in V 1 ,
V 2 ; rightgram (not always); the QRS complex is more than 0.12 sec with complete blockade
of RBBB and less than 0.12 sec with incomplete blockade of RBBB.
b) blockade of the left leg of the bundle of His - ECG: ventricular QRS complexes in V 5 ,
V 6 in the form of RsR or R with a split or wide top; in the left chest leads, ST segment
depression, negative or biphasic T wave; in V 1 , V 2 , III, aVF broadened deformed
ventricular complexes such as QS or rS; J>0.05 sec in V 5 , V 6 , levogram; QRS complex >
0.12 sec with complete blockade of LBBB.

With the blockade of the posterior branch of the LBPH: angle  >
120; rightgram; R II >S II , with blockade of the anterior branch of the LBB : angle  < -
30; levogram; S II > R II .

Treatment : Stable, long-standing bundle branch block does not require special treatment; bi- and
trifascicular blockade is an indication for pacemaker implantation.

24. Rehabilitation of patients with acute myocardial infarction.

Rehabilitation for MI 3-stage:

1) stationary stage - physical (timely and adequate activation of patients, early appointment of
therapeutic exercises and exercise therapy under the supervision of a doctor - are carried out
differentiated depending on the severity class of MI) and psychological (creating a favorable
psycho-emotional environment around the patient, maintaining an optimistic mood, instilling
confidence in a favorable prognosis, etc.) rehabilitation
2) sanatorium stage - depending on the severity class of MI, therapeutic exercises, dosed
walking, training walking up the stairs with a gradual increase in the intensity of physical
activity are used
3) dispensary-polyclinic stage - the amount of physical activity is determined taking into
account the functional classes of coronary artery disease (FC I - therapeutic exercises in
training mode, participation in sports games: badminton, volleyball, table tennis, swimming,
skiing, housework, etc. , FC II - therapeutic exercises in a gentle training mode, short-term
(up to 10 minutes) non-competitive sports games, housework, FC III - exercise therapy in a
gentle training mode, light types of housework, sports games are contraindicated, sexual
activity is limited, FC IV - active rehabilitation is contraindicated)

25. Algorithm for the diagnosis and treatment of syncope

Clinical featurestoggle arrow icon

Prodrome

 Vasovagal: impairment of senses; , nausea, pallor, warmth, diaphoresis, lightheadedness,

and hyperventilation
 Orthostatic: lightheadedness, nausea, and dizziness

Rapid onset loss of consciousness

 Accompanied by complete loss of muscle tone

 Last seconds to minutes followed by spontaneous recovery
 Convulsive syncope: common form in which loss of consciousness is accompanied by
myoclonic movements

The following recommendations are consistent with the 2017 American Heart Association
(AHA) syncope guidelines.

Initial management :Syncope and presyncope can be multifactorial, with widely varying
etiologies and diagnostic approaches. Focus on identifying the possible etiology of syncope
while excluding differential diagnoses of syncope. [

Stabilization (as needed)

 Consider stabilizing measures for acutely syncopal patients, e.g., ABCDE survey, POC
glucose, supine positioning, IV access, cardiac monitoring, fluid resuscitation.
 Identify and treat life-threatening causes of syncope concurrently.

Initial evaluation: Perform a detailed clinical assessment with select routine investigations.

 Obtain medication, medical, and family history

  Determine triggers and ask witnesses (if available) for details about the event.
 Conduct a thorough physical examination.
 Obtain ECG and orthostatic vital signs
 Consider basic laboratory studies
 Risk stratification: Consider performing on all patients based on clinical features,
historical factors, and results of the initial evaluation to help guide disposition and need
for further investigations.

Next steps

 Detailed diagnostics: Consider as guided by clinical suspicion, especially in patients

without a clear cause of syncope identified on initial evaluation.
 Definitive management: Depends on underlying etiology, risk stratification, and disease
severity.
 Manage complications: e.g., fall injuries

Routine investigations :Adding an ECG and orthostatic vital signs to a thorough clinical
evaluation can help identify the etiology of syncope in up to 50% of patients. [12]

ECG

 Indicated in all patients

 Potential findings
 Arrhythmias and conduction abnormalities
 Brugada syndrome
 Ischemic changes
 Ventricular hypertrophy

Orthostatic vital signs :Method

 Measure blood pressure and heart rate after the patient has been in a supine position for 5
minutes.
 Ask the patient to stand up and retake vital signs after 1 minute and 3 minutes (a third
measurement after 10 minutes is optional).
 Document any symptoms that the patient experiences.

Findings

 Normal: Minimal or no variation in blood pressure or heart rate

 Abnormal
 Significant drop in systolic and/or diastolic BP
 Significant increase in heart rate
Laboratory studies: These are commonly requested as part of the initial workup. See “Further
investigations” for more detailed diagnostics.

 Glucose (may detect hypoglycemia)

 CBC (may show ↓ serum hemoglobin)
 BMP (e.g., ↑ BUN/creatinine ratio may suggest dehydration)
 Pregnancy test

Disposition

Disposition decisions should take into account individual patient factors and follow local hospital
policy .

Admission: e.g., for further investigations (e.g., provocation studies, cardiovascular imaging),
continuous cardiac monitoring, and targeted management

Typically indicated for patients with cardiac syncope: e.g., structural heart disease, pulmonary
embolism, shock, SAH

In patients with noncardiac syncope (i.e., reflex syncope or orthostatic syncope) OR syncope of
unclear origin after initial evaluation, consider admission if there is a high risk of serious adverse
events following syncope.

Consider critical care unit admission for patients with immediately life-threatening causes of
syncope.

Discharge

 In patients with noncardiac syncope OR syncope of unclear origin, consider discharge

with reassurance and instructions if there is a low risk of serious adverse events following
syncope.
 Consider outpatient cardiac monitoring (e.g., loop recorder, Holter monitoring) for
recurrent or frequent syncopal episodes of unclear origin.
 Consultations: as guided by suspected underlying cause and severity (e.g., cardiology,
ICU).
26. Features of the treatment of arterial hypertension, acquired valvular heart disease in
pregnant women.

Treatment of hypertension in pregnancy

 Initial treatment options: labetalol, hydralazine, nifedipine, or methyldopa

 Additional treatment options: thiazides or clonidine
 Contraindicated: ACEIs, ARBs, renin inhibitors (e.g., aliskiren), or atenolol

Gestational hypertension and preeclampsia without severe features

Hospitalization and delivery indicated if:

 Pregnancy ≥ 37 0/7 weeks' gestation

 Suspected placental abruption
 Pregnancy ≥ 34 0/7 weeks' gestation plus one of the following:
 Labor or rupture of membranes
 Fetal weight < 5th percentile
 Oligohydramnios
  Abnormal maternal or fetal test results

In all other cases, continue outpatient monitoring

 Maternal monitoring: (1–2 x/week): blood pressure, urine dipsticks, blood analysis
(platelet count, liver enzymes, renal function)
 Fetal monitoring: ultrasound every 3 weeks and NST 1–2 x/week
 Patient education
 Recognize signs of severe preeclampsia or fetal distress (e.g., reduced fetal movement,
vaginal bleeding).
 Avoid physical exertion .
 Antihypertensive drug therapy for severe hypertension (systolic BP ≥ 160 mmHg or
diastolic BP ≥ 110 mmHg)
 Hydralazine
 Labetalol
 Methyldopa
 Nifedipine
III. GASTROINTESTINAL DISEASES
1. Diagnostic capabilities and value of instrumental methods in gastroenterology: endoscopic,
ultrasound, electrometric (Ph-metry),radiological, radioisotope, magnetic resonance imaging.
Indications and contraindications for instrumental studies.
ENDOSCOPY
Esophagoscopy → can be performed diagnostically to evaluate pain or dysphagia, to identify
structural abnormalities or bleeding sites, or to obtain biopsy specimens. Therapeutic procedures
include removal of foreign bodies, hemostasis by coagulation or variceal banding, debulking of
tumors by laser or bipolar electrocoagulation, and dilation of webs or strictures. There is no absolute
contraindication, and esophagoscopy can easily be performed on an outpatient basis.
Upper GI endoscopy → An upper GI endoscopy or EGD (esophagogastroduodenoscopy) is a
procedure to diagnose and treat problems in the upper GI (gastrointestinal) tract.
This procedure is done using a long, flexible tube called an endoscope. The tube has a tiny light and
video camera on one end. The tube is put into the mouth and throat. Then it is slowly pushed Through
the esophagus and stomach, and into the duodenum. Video images from the tube are seen on a
monitor.

Small tools may also be inserted into the endoscope. These tools can be used to:

• Take tissue samples for a biopsy

• Remove things such as food that may be stuck in the upper GI tract
• Inject air or fluid
• Stop bleeding
• Do procedures such as endoscopic surgery, laser therapy, or open (dilate) a narrowed area

Indications

It is often used to find the cause of unexplained symptoms such as:

− Trouble swallowing (dysphagia) -Unexplained weight loss

− Upper belly pain or chest pain that is not heart-related
− Continuous vomiting for an unknown reason (intractable vomiting)
− Dyspepsia over 55 years of age or with alarm symptoms
− Atypical chest pain -Dysphagia
− Vomiting -Weight loss
− Acute or chronic gastrointestinal bleeding -Suspicious barium meal
− Duodenal biopsies in the investigation of malabsorption

Contraindications

Absolute contraindications

- Shock. -acute MI. -Peritonitis -Acute perforation. -fulminant colitis

Relative contraindications →Include poor patient cooperation, coma (unless the patient is intubated),
and cardiac arrhythmias or recent myocardial ischemia.
Proctoscopy and sigmoidoscopy →. Proctoscopy visualizes the anal canal and only 2-3 cm of the
rectum. Sigmoidoscopy examines the rectum and the lower few centimeters of the pelvic colon.
Digital examination of the rectum should always precede endoscopy. Patient preparation involves
taking cathartics and enemas or drinking an intestinal lavage solution (polyethylene glycol
electrolyte). Proctoscopy is used for demonstration of haemorrhoids. Sigmoidoscopy is used to
diagnosis of polyps, cancer of rectum, ulcerative colitis, Crohn&#39;s disease. Biopsy of mucosa or
lesion may be taken.
Colonoscopy → Digital examination of the rectum should always precede endoscopy. Patient
preparation involves taking cathartics and enemas or drinking an intestinal lavage solution
(polyethylene glycol electrolyte). Colonoscopy is used diagnostically to screen for colonic polyps or
cancer in high-risk individuals (those with a family history of colon cancer); to evaluate an
abnormality seen on barium enema; to determine the source of occult or active gastrointestinal
bleeding or unexplained (microcytic) anemia; to evaluate patients with colon cancer for other lesions
during pre - or postoperative assessment; and to determine the extent of inflammatory bowel disease.
Therapeutic indications include removal of polyps, coagulation of bleeding sites, reduction of
volvulus or intussusception, and decompression of acute or subacute colonic dilatation.
ULTRASOUND , CT , MRI
These are increasingly used in the evaluation of intraabdominal disease. They are non-invasive and
offer detailed images of the abdominal contents.
US CT MRI PET CT
Indications Abdominal Assessment of Hepatic tumour staging Detection of
masses, e.g. pancreatic Magnetic resonance metastases
cysts, tumours, disease Hepatic cholangiopancreatography not seen on
abscesses tumour (MRCP) Pelvic/perianal ultrasound or
Organomegaly deposits CT disease Crohn’s fistulas CT Images
Ascites Biliary colonography Small bowel visualisation can be fused
tract dilatation (‘virtual with CT to
Gallstones colonoscopy’) form
Guided biopsy Tumour staging composite
of lesions Assessment of image
vascularity of
lesions
Abscesses and
collections
Limitations/ Low sensitivity Contraindicated in
Contraindications for small presence of metallic
lesions Little prostheses, cardiac
functional pacemaker, cochlear
information implants
Operator-
dependent Gas
and obesity may
obscure view
RADIOISOTOPE TESTS →Many different radioisotope tests are used .In some, structural
information is obtained, e.g. localisation of a Meckel’s diverticulum. Others use radioisotopes for
functional information, e.g. rates of gastric emptying or ability to reabsorb bile acids. Yet others are
tests of infection and rely on the presence of bacteria to hydrolyse a radio-labelled test substance
followed by detection of the radioisotope in expired air (e.g. urea breath test for H. pylori).
Commonly used radioisotope tests in gastroenterology
- Gastric emptying study → Used in assessment of gastric emptying, particularly for possible
gastroparesis
- Urea breath test → Used in non-invasive diagnosis of H. pylori. Bacterial urease enzyme
splits urea to ammonia and CO2 which is detected in expired air
- Meckel’s scan → Diagnosis of Meckel’s diverticulum in cases of obscure gastrointestinal
bleeding. Isotope is injected i.v. and localises in ectopic parietal mucosa within diverticulum
- Somatostatin receptor scan (SRS) → Labelled somatostatin analogue binds to cell surface
somatostatin receptors on pancreatic neuroendocrine tumours
Indications
to assess for gastroparesis in patients with post-prandial symptoms of nausea, vomiting, abdominal
pain, and/or early satiety.
Contraindications
• Allergies to the recommended meal
• Hyperglycemia in diabetics (blood glucose greater than 250 to 275 mg/dL)

RADIOLOGICAL STUDIES
Plain X-rays → Plain X-rays of the abdomen are useful in the diagnosis of intestinal obstruction or
paralytic ileus where dilated loops of bowel and (in the erect position) fluid levels may be seen.
Calcified lymph nodes, gallstones and renal stones can also be detected. Chest X-ray is useful in the
diagnosis of suspected perforation as it shows subdiaphragmatic free air.
PH-METRY. → Oesophageal pH-metry consists of a continuous recording of pH in the distal
oesophagus. Detection of periods of oesophageal acidification allows for a direct diagnosis of
episodes of gastro-oesophageal reflux and quantification of the exposure of the distal oesophagus to
acid.
Indication :
• Persistence of symptoms while taking adequate antisecretory therapy, such as PPI therapy
• Recurrence of symptoms after discontinuation of acid-reducing medications
• Investigation of atypical symptoms, such as chest pain or asthma, in patients without
esophagitis
• Confirmation of the diagnosis in preparation for antireflux surgery
 2. Diseases of esophagus. Etiology. Clinical picture and diagnostics of esophagitis, achalasia of
esophagus, cancer of esophagus. Therapeutic aspects of treatment.
ESOPHAGITIS
Def : inflammation of the esophageal mucosa that is secondary to direct mucosal injury or to
inflammatory infiltrates due to a systemic inflammatory disorder
Etiology :
Mechanism Possible causes
Mucosal injury • Gastroesophageal reflux disease (GERD)
• Infections
o Candida spp.
o Herpes simplex virus (HSV)
o Cytomegalovirus (CMV)
• Substance-induced esophagitis
• Radiotherapy
• Drugs (Potassium supplements and NSAIDs may cause oesophageal ulcers when
the tablets are trapped above an oesophageal stricture. Liquid preparations of
these drugs should be used in such patients. Bisphosphonates, especially
alendronate, cause oesophageal ulceration and should be used with caution in
patients with known oesophageal disorders.)

Specific • Eosinophilic esophagitis

infiltrates • Lymphocytic esophagitis

Others • Immune-mediated disorders, including:

o Crohn disease
o Autoimmune diseases (e.g., scleroderma, Behcet disease, systemic
lupus erythematosus, Sjogren syndrome)
o Graft-versus-host disease
• Anatomical causes (e.g., hiatal hernia, esophageal rings, webs, diverticula)
• Motility disorders (e.g., achalasia, muscular dystrophy)

Clinical picture
• Retrosternal burning chest pain (heartburn)
• May be associated with dyspepsia, dysphagia, regurgitation, belching, and globus sensation
• Features of the underlying etiology, e.g.:
o Heartburn that worsens on lying down or bending forward: GERD
o Retrosternal chest pain, dysphagia, and reflux of undigested food
particles: achalasia cardia
o Dysphagia, weight loss, hematemesis: esophageal cancer

Diagnosis

• Endoscopy
 • Biopsy: A small sample of the esophageal tissue is removed and sent to a laboratory to be
examined under a microscope.
• Barium X-ray: X-rays are taken of the esophagus after the patient drinks a barium solution.
Barium coats the lining of the esophagus and is visible on X-ray. This enables doctors to view
abnormalities of the esophagus.
• Laboratory tests : Small tissue samples removed (biopsy) during an endoscopic exam are sent
to the lab for testing. Depending on the suspected cause of the disorder, tests may be used to:

o Diagnose a bacterial, viral or fungal infection

o Determine the concentration of allergy-related white blood cells (eosinophils)

o Identify abnormal cells that would indicate esophageal cancer or precancerous changes

Treatment
Treatment for esophagitis depends on its cause.
Reflex esophagitis
• Pharmacological treatment : antacids , h2 receptor blockers ( cimetidine) , PPI ( pantaprazole
, omeprazole) , prokinetics (bethanechol , metoclopramide).
• Surgery : Fundoplication may be used to improve the condition of the esophagus if other
interventions don't work. A portion of the stomach is wrapped around the valve separating the
esophagus and stomach (lower esophageal sphincter). This strengthens the sphincter and
prevents acid from backing up into the esophagus.
Eosinophilic esophagitis
• Treatment for eosinophilic esophagitis is primarily avoiding the allergen and reducing the
allergic reaction with medications.
• Medications : PPI ( pantaprazole , esmoprazole) , steroids (fluticasone , budesonide) ,
elimination and elemental diet (A response to a food allergen is likely the cause of eosinophilic
esophagitis. Therefore, elimination of the culprit food may be an effective treatment strategy)
• Esophageal dilation: Consider for patients with a narrow stricture or diffuse narrowing of
the esophagus.

Drug induced esophagitis

Treatment for drug-induced esophagitis is primarily avoiding the problem drug when possible and
reducing the risk with better pill-taking habits
• Discontinuethe medication or substance causing esophagitis.
• Ensure nutrition and hydration.
• Consider antacids, sucralfate, or PPIs to ameliorate symptoms.
• Some patients may develop strictures that require esophageal dilations.
Infectious esophagitis
a medication to treat a bacterial, viral, fungal or parasitic infection causing infectious esophagitis.
ACHALASIA
Def : Achalasia is a failure of the lower esophageal sphincter (LES) to relax that is caused by the
degeneration of inhibitory neurons within the esophageal wall. It is classified as either primary
(idiopathic) or secondary (in the context of another disease).
Etiology
• Primary achalasia (most common): cause is unknown
• Secondary achalasia (pseudoachalasia): the presentation and manometric findings of a
mechanical cause of obstruction (e.g., a malignancy) that mimics achalasia
o Esophageal cancer
o Stomach cancer and other extraesophageal cancers (symptoms may be due to mass
effect or paraneoplasia)
o Chagas disease
o Amyloidosis
o Neurofibromatosis type I
o Sarcoidosis
Clinical features
• Dysphagia to solids and liquids; can be progressive or paradoxical
dysphagia (difficulty swallowing liquids, while solids are easily swallowed)
• Regurgitation
• Retrosternal pain and cramps
• Weight loss

Diagnostics
• Approach
o In general, all patients with suspected achalasia should initially undergo upper
endoscopy and/or esophageal barium swallow; findings may support the diagnosis.
o Esophageal manometry is indicated to establish the diagnosis (confirmatory test of
choice), irrespective of the initial imaging findings.
o If manometry is inconclusive and an esophageal barium swallow was not obtained
initially, esophagram can also play a confirmatory role.
o Endoscopy should be performed to rule out pseudoachalasia because the
presentation and manometric findings of a mechanical cause of obstruction (e.g.,
a malignancy) may mimic achalasia.
• Esophageal barium swallow: supportive and/or confirmatory test [8]
o Bird-beak sign: dilation of the proximal esophagus with stenosis of
the gastroesophageal junction
o Delayed barium emptying or barium retention
• Upper endoscopy: to rule out pseudoachalasia
o Usually normal
o May show retained food in esophagus or increased resistance of LES during
passage with endoscope [8]
o If malignancy is suspected, biopsy and endoscopic ultrasound are indicated
 • Esophageal manometry: confirmatory test of choice
o Peristalsis is absent or uncoordinated in the lower two-thirds of the esophagus.
o Incomplete or absent LES relaxation
o High LES resting pressure
o No evidence of mechanical obstruction
• Chest x-ray
o Widened mediastinum
o Air-fluid level on lateral view
o Possible absence of gastric air bubble
Treatment
If a low surgical risk [8]
The preferred treatment often depends on the surgeon and the patient's situation. However,
attempting pneumatic dilation before myotomy is gaining popularity because it is less invasive and
the time of recovery is faster. This approach is already more popular in Europe.
• Pneumatic dilation
o Endoscope-guided graded dilation of the LES that tears the surrounding muscle
fibers with the help of a balloon
o The success rate at one month is ∼ 85%; perforation risk is ∼ 2%.
• LES myotomy (Heller myotomy): a surgical procedure in which the lower esophageal
sphincter is incised longitudinally to re-enable passage of food or liquids to the stomach.
• Peroral endoscopic myotomy
o An endoscopy-guided myotomy of the inner circular muscular layer of the lower
esophageal sphincter (the longitudinal muscle layer is preserved)
o May be considered in other esophageal motility disorders (e.g., diffuse esophageal
spasm) as well, in which case the myotomy incision may need to be extended into
the esophageal body
If a high surgical risk
• Botulinum toxin injection in the LES
o A good choice for patients who are poor surgical candidates
o More than 50% of patients require treatment again within 6–12 months.
• If other measures are unsuccessful: nitrates or calcium channel blockers

CANCER OF ESOPHAGUS
Benign tumours → The most common is a gastrointestinal stromal tumour (GIST). This is usually
asymptomatic but may cause bleeding or dysphagia.
Carcinoma of the oesophagus → Squamous oesophageal cancer is relatively rare in Caucasians
whilst in Iran, parts of Africa and China it is much more common
Etiology
• Smoking • Alcohol excess • Chewing betel nuts or tobacco • Coeliac disease
• Achalasia of the oesophagus • Post-cricoid web • Post-caustic stricture
• Tylosis (familial hyperkeratosis of palms and soles)
Clinical features
Early stages [10]
• Oftenasymptomatic
• May manifest with swallowing difficulties or retrosternal discomfort

Advanced stages [10]

• General signs
o Weight loss
o Dyspepsia
o Signs of anemia
• Signs of advanced disease
o Progressive dysphagia (from solids to liquids) with possible odynophagia
o Retrosternal chest or back pain
o Cervical adenopathy
o Hoarseness and/or persistent cough
o Horner syndrome
• Signs of upper gastrointestinal bleeding
o Hematemesis
o Melena
Diagnostics
Esophagogastroduodenoscopy
• Best initial and confirmatory test [11]
• Direct visualization of the tumor
• Allows biopsy of any suspicious lesions

Barium swallow
• Overview
o Sensitive, but does not allow confirmation or staging of a malignancy
o Inferior to endoscopy
• Indications
o Severe stricture that inhibits endoscopic evaluation
o Suspected tracheoesophageal fistula
• Findings: asymmetrical and irregular borders of the esophagus with characteristic stenosis
and proximal dilatation (apple core lesion)

Treatment
The treatment of choice is surgery if the patient presents at a point at which resection is possible.
Curative
• Indication
o Locally invasive disease that has not invaded surrounding structures
o High-grade metaplasia in Barrett syndrome
 • Methods
o Neoadjuvant chemoradiation: as definitive treatment in patients with
proven complete response (e.g., during endoscopy)
o Surgical resection
▪ Endoscopic submucosal resection for removal
[14][15]
of superficial, epithelial lesions
▪ Subtotal or total esophagectomy with gastric pull-through procedure
or colonic interposition
Palliative
• Indication: patients with advanced disease (majority of patients)
• Methods
o Chemoradiation
o Stent placement
o Other endoscopic treatments (e.g., laser therapy)
3. Gastroesophageal reflux disease: causes, differential diagnosis, treatment.
Def : Gastroesophageal reflux disease (GERD) is a chronic condition in which stomach contents flow
back into the esophagus, causing irritation to the mucosa.
CAUSES
• Gastroesophageal junction dysfunction can occur because of the following factors:
o Increased frequency of transient lower esophageal sphincter relaxations (TLESRs)
o Imbalance between intragastric and lower esophageal sphincter (LES) pressures
o Anatomic abnormalities of gastroesophageal junction (e.g., hiatal hernia, tumors)
• Impaired esophageal acid clearance

RISK FACTORS
• Smoking, caffeine and alcohol consumption
• Stress
• Obesity
• Pregnancy
• Angle of His enlargement (> 60°)
• Iatrogenic (e.g., after gastrectomy)
• Inadequate esophageal protective factors (i.e., saliva, peristalsis)
• Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric
cardiac carcinoma
• Scleroderma
• Sliding hiatal hernia: ≥ 90% of patients with severe GERD
• Asthma

CLINICAL FEATURES
Typical symptoms
• Retrosternalburning pain (heartburn)
• Regurgitation
• Dysphagia, odynophagia
• Water brash: a symptom of excessive salivation triggered by refluxing of stomach acid

Atypical symptoms
• Pressure sensation in the chest/noncardiac chest pain
• Belching, bloating
• Dyspepsia, epigastric pain
• Nausea
• Halitosis
• Features of GERD complications, e.g., aspiration pneumonia or aspiration pneumonitis

Extraesophageal symptoms
• Chronic nonproductive cough and nighttime cough
• Hoarseness
• Bronchospasm
• Dental erosion

Aggravating factors
• Lying down shortly after meals
 • Certain foods/beverages
Red flags in GERD
• Dysphagia,
odynophagia
• Anemia and/or evidence of GI bleeding
• Unintentional weight loss
• Vomiting
DIAGNOSIS
There is no gold standard test for the diagnosis of GERD. The diagnosis is based on clinical
presentation, endoscopic evaluation, reflux assessment, and therapeutic response.
EGD
• Supportive findings (typically in the lowest third of the esophagus) [22]
o Erythema, edema, friability
o Erosions, mucosal breaks, ulcerations
o Peptic strictures and rings
o Salmon pink mucosa (suggestive of Barrett esophagus)
o Proximal migration of the gastroesophageal junction (Z line), e.g., in Barrett
esophagus or hiatal hernia

Esophageal pH monitoring
Esophageal pH monitoring can be used to objectively identify abnormal reflux of gastric content into
the esophagus; however, it is not a routine diagnostic test.
• Supportive finding: Drops in esophageal pH to 4 or less that correlate with symptoms of acid
reflux and precipitating activities.

Further diagnostic studies

Not routinely indicated, as they play a limited role in the diagnosis of GERD; useful if endoscopy is
inconclusive.
• Esophagealbarium swallow
o Consider if the main symptom is dysphagia or if there is suspicion of structural
abnormalities (e.g., esophageal rings or webs) or motility disorders
(e.g., achalasia, distal esophageal spasm)
• Esophageal manometry: Consider if achalasia or esophageal hypermotility disorders are
suspected.
TREATMENT
The initial management of GERD consists of implementing lifestyle changes and initiating acid
suppression therapy, preferably with PPIs.
Lifestyle changes
• Dietary recommendations
o Small portions
o Avoid eating at least 2–3 hours before bedtime.
 o Avoid foods and beverages that appear to trigger symptoms. [35]
• Physical recommendations
o Weight loss in patients with obesity
o Elevate the head of the bed (10–20 cm) for patients with nighttime symptoms.
• Reduce or avoid triggering substances
o Tobacco, alcohol, and/or caffeine if the patient experiences correlation with
symptoms
o Medications that may worsen symptoms (e.g., CCBs, diazepam)

Surgical therapy

− Antireflux surgery may be considered for select patients after careful evaluation.
− Fundoplication ( partial or nissen fundoplication)
4. Chronic gastritis. Main etiological agents. Clinical picture, main syndromes. Classification.
Possibilities of diagnostics. Treatment according to the form and phase of disease. Periodic health
examination.
Def : Chronic gastritis is a long-term condition in which the mucus lined layer of the stomach, also known
as the gastric mucosa, is inflamed or irritated over a longer period of time.
Etiology
Chronic gastritis is polyetiologic disease. The main causes of chronic gastritis are: 1) Infection -
Helicobacter pylori. Immunologic factors, which lead to the production of the autoantibodies to the parietal
cells. 3) Chemical factors, which lead to the injury of the gastric mucosa (alcohol, aspirin and other
NSAIDs, reflux of bile and pancreatic secretions). 4) Radiation or thermal injury.
Factors, which promote to the development of the chronic gastritis, are exogenous and endogenous.
Exogenous factors are: 1) abnormality of the order of nutrition, overeating, insufficient chewing of food,
abuse of hot and spicy food; 2) smoking and alcohol; 3) professional harm (swallowing of metallic dust or
other chemical substances); 4) prolonged intake of some medicines (aspirin and other NSAIDs,
corticosteroids).
Endogenous factors are: 1) chronic infections, 2) endocrine diseases, 3) metabolic disorders, 4)
autointoxication (renal failure).
Classification
Modified Sydney’s system, which was accepted in 1994 in Houston
• Atrophic gastritis;
• Non-atrophic gastritis;
• Special or distinctive forms of gastritis: chemical, radiative, lymphocytic, eosinophilic, isolated
granulomatous gastritis and others.
• Chronic gastritis can be diagnosed only by gastric biopsy of body or fundal mucosa.
CHRONIC ATROPHIC (AUTOIMMUNE) GASTRITIS
Clinical picture
weight loss. Tongue is smooth and shiny due to atrophy of the papillae. Bad breath (halitosis) may present.
Palpation of the abdomen may reveal epigastric pain. With severe vitamin B12 deficiency, the patient is pale
and has slightly icteric skin and eyes. The pulse is rapid, and the heart borders may be enlarged.
Auscultation usually reveals a systolic flow murmur over the apex of the heart.
Complications → Pernicious anemia; Gastric polyps; Gastric adenocarcinoma.
Diagnostics
Gastroscopy → The diagnosis of chronic gastritis can only be ascertained histologically. So histological
assessment of endoscopic biopsies is essential. Tissues sampling from gastric antrum and corpus is essential
.
Laboratory studies → Decreased serum pepsinogen I levels and the ratio of pepsinogen I to pepsinogen II
in the serum can be used to assess gastric atrophy. The finding of low pepsinogen I levels (&lt; 20 ng/mL)
has a sensitivity of approximately 96.2% and a specificity of 97% for detection of fundus atrophy.
Antiparietal and anti-intrinsic factor antibodies may be present in the serum. Low serum cobalamin
(vitamin B-12) levels (&lt;100 pg/mL).
Treatment
Once atrophic gastritis is diagnosed, treatment can be directed to correct complications of the
disease, especially in patients with autoimmune atrophic gastritis who develop pernicious anemia
(in whom vitamin B-12 replacement therapy is indicated).
CHRONIC NONATROPHIC ( H PYLORI ASSOCIATED) GASTRITIS
Helicobacter pylori (H. pylory) are gram-negative rods that have the ability to colonize and infect
the stomach. The bacteria survive within the mucous layer that covers the gastric surface epithelium
and the upper portions of the gastric foveolae. The infection usually is acquired during childhood.
Once the organism has been acquired, has passed through the mucous layer, and has become
established at the luminal surface of the stomach, an intense inflammatory response of the
underlying tissue develops. Previously this type of gastritis was known as type B gastritis.
Clinical features
Complaints → Epigastric pain, heartburn, fullness, nausea, vomiting, flatulence, malaise.
Epigastric pain usually appear after meal, lasted 1-1,5 hours and then independently disappear. In
some cases, patients may feel hungry in the morning and may have halitosis. 30-35% of patients
haven’t symptoms. Symptoms may occur with the development of complications of chronic H.
pylori gastritis.
Physical examination→ The physical examination contributes relatively little to the assessment
and management of this type gastritis. Palpation of the abdomen may reveal epigastric pain.
Investigations
Gastroscopy is helpful for analyzing the subepithelial microvascular architecture, as well as the
mucosal surface microstructure and tissue biopsy.
Methods of determining H. pylori:
• Rapid urease test from gastric biopsy tissue. Bacterial culture of gastric biopsy is usually
performed in the research setting or to assess antibiotic susceptibility in patients for whom first-
line eradication therapy fails.
• Urea breath test with nonradioactive carbon isotope ( 13 C) or with radioactive carbon isotope
( 14 C). The carbon 13 urea breath test is based on the detection of the products created when
urea is split by the organism. Patients are asked to drink urea (usually with a beverage) labeled
with a carbon isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the
labeled carbon is measured in the breath. The concentration is high only when urease is present
in the stomach. Because the human stomach does not produce urease, such a reaction is possible
only with H. pylori infection.
• H. pylori fecal antigen test. This is a novel rapid test based on monoclonal antibody
immunochromatography of stool samples. It has been reported to be very specific (98%) and
sensitive (94%). The results are positive in the initial stages of infection and can be used to
detect eradication after treatment.
• H. pylori serology. The serology test has a high (&gt;90%) specificity and sensitivity. It is
currently based on the quantitation of immunoglobulin G antibodies against H. pylori by the
means of an enzyme-linked immunosorbent assay. It is useful for detecting a newly infected
patient, but it is not a good test for follow-up of treated patients because the results do not
indicate present infection with H. pylori. The antibody titer may remain elevated for a long time
after H. pylori eradication. The number of false-positive results is age-related and increases with
age.
Complications
The non-atrophic gastritis is associated with an increased risk of the following:
- Peptic ulcers;
- Gastric mucosa-associated lymphoid tissue (MALT) lymphomas may develop in some
individuals who carry additional risk factors;
 - Gastric cancer, especially in individuals who develop extensive atrophy and intestinal
metaplasia of the gastric mucosa.
Treatment
It is now widely accepted that if H. pylori is identified as the underlying cause of gastritis, it should
be eradicated.
Triple therapies (with indicated adult dosing):
- Twice-daily proton pump inhibitors or ranitidine (lansoprazole 30mg, omeprazole 20 mg, or
ranitidine 400 mg orally twice daily);
- Clarithromycin 500 mg orally twice daily;
- Amoxicillin 1000 mg or metronidazole 500 mg orally twice daily.
Quadruple therapies (with indicated adult dosing):
- Proton pump inhibitors (lansoprazole 30 mg or omeprazole 20mg) orally twice daily;
- Tetracycline HCl 500 mg orally 4 times daily;
- Bismuth subsalicylate 120 mg orally 4 times daily;
- Metronidazole 500 mg orally 3 times daily.
CHEMICAL GASTRITIS
• Etiology → Chemical gastritis is caused by injury of the gastric mucosa by reflux of bile and
pancreatic secretions into the stomach, but it can also be caused by exogenous substances,
including NSAIDs, acetylsalicylic acid, chemotherapeutic agents, and alcohol. These chemicals
cause epithelial damage, erosions, and ulcers that are followed by regenerative hyperplasia,
histologically detectable as foveolar hyperplasia and damage to capillaries, with mucosal edema,
hemorrhage, and proliferation of smooth muscle in the lamina propria. Previously this type of
gastritis was known as type C gastritis.
• Clinical features
Complaints → are epigastric pain, which may increased after the meal, regurgitation of bile-
stained fluid, vomiting with bile, weight loss, anemia.
• Diagnostics →Gastroscopy may reveal reflux of bile to the stomach.
• Treatment → Proton pump inhibitors have demonstrated efficacy in controlled trials for the
treatment chemical gastritis. An empiric 2- 4 week trial of an oral proton pump inhibitor
(omeprazole, rabeprazole, or esomeprazole 20- 40 mg/d; lansoprazole, 30 mg/d; pantoprazole,
40 mg/d) is recommended.

5. Duodenal and gastric ulcer. Etiology. Features of pathogenesis of duodenal and gastric
ulcer. Clinical picture depending on the ulcer localization. Treatment. Periodic health
examination.
• Peptic ulcer: a defect in the gastric or duodenal mucosa with a diameter of at least 0.5 cm and a
depth that reaches the muscularis mucosae [1]
• Gastric ulcer: a peptic ulcer of the gastric mucosa, typically located along the lesser curvature
in the transitional portion between the corpus and antrum
• Duodenal ulcer: a peptic ulcer of the duodenal mucosa, usually located on the anterior or
posterior wall of the duodenal bulb
Etiology
Common causes of PUD
The two major contributing factors to the development of PUD are gastrointestinal infection with H.
pylori and nonsteroidal anti-inflammatory drug (NSAID) use. Both factors contribute to the
development of PUD and interact with other risk factors to promote ulcer formation.
• Helicobacter pylori infection
o Associated with 40–70% of duodenal ulcers and 25–50% of gastric ulcers
o The rate of H. pylori infection (and, therefore, the development of PUD) is
decreasing.
• Chronic NSAID use
o Associated with a fourfold risk of developing PUD
• Gastric acid. Gastric acid is measured at normal or decreased levels in gastric ulcers
patients. Slightly elevated levels of gastric acid are noted in basal and stimulated states in
duodenal ulcer patients. Accelerated gastric emptying also may leads to a high acid load
delivered to the first part of the duodenum, where 95% of all duodenal ulcers are located.
• Tobacco smoking. Cigarette smoking can affect gastric mucosal defense adversely.
Smoking may accelerate gastric emptying and decrease pancreatic bicarbonate production.
• Genetic factors. First-degree relatives of gastric and duodenum ulcers patients have three
times risk of development of gastric ulcers as the general population. An increased incidence
of duodenal ulcer has been documented among individuals with blood group 0 (I), those who
demonstrated elevated serum levels of pepsinogen I.
• Psychosomatic factors. Stress, anxiety, brooding (difficulty coping and difficulty expressing
emotions) are important in the initiation or perpetuation of peptic ulcer disease.
• Alcohol use. Ethanol is known to cause gastric mucosal irritation and nonspecific gastritis.
• Diet .
Pathogenesis → The normal stomach and duodenum maintain a balance between the protective
factors (mucus layer, bicarbonate secretion, protective prostaglandins, blood flow) and aggressive
factors (gastric acid and proteolytic enzyme pepsin). Peptic ulcer disease develops when aggressive
factors overcome the protective mechanism. Any process that increases gastric acidity (individuals
with increased maximal and basal acid output), decreases prostaglandin production (nonsteroidal anti-
inflammatory drugs, or interferes with the mucous layer (H. pylori infection) can cause such an
imbalance and leads to peptic ulcer disease.
Clinical features
Asymptomatic PUD
•
Up to 70% of patients with peptic ulcers do not experience symptoms.
•
Patients who take NSAIDs are more likely to have asymptomatic ulcers and present
with complications of PUD
Symptomatic PUD
• Abdominal pain
o The most common symptom of PUD
o Commonly located in the epigastrium
o Often described as “gnawing” or “burning”
o Can be related to meal intake depending on the location of the ulcer
• Other associated symptoms
o Belching
o Indigestion
 o Gastrointestinal reflux
o Nausea and/or vomiting
o Bloating/abdominal fullness

Treatment
Dietary factors
• Diet may be of some importance. Some products, which stimulate gastric acid secretion
(coffee, alcohol), should be restricted in acute cases. Ulcer patients who smoke should be urged
to decrease or stop smoking.
Acid Neutralizing / Inhibitory Drugs
• Proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, and
pantoprazole) are the most potent acid inhibitory agents available.

• H2-receptor antagonists (ranitidine, famotidine, and nizatidine) significantly inhibit basal and
stimulated acid secretion to comparable levels when used at therapeutic doses.

• Antacids are now rarely, if ever, used as the primary therapeutic agent but instead are often
used by patients for symptomatic relief of dyspepsia. The most commonly used agents are
mixtures of aluminum hydroxide and magnesium hydroxide (Maalox, Gaviscon).
Cytoprotective Agents
• Sucralfate is insoluble in water and becomes a viscous paste within the stomach and duodenum,
coats the ulcer bed and promotes healing.

• Bismuth induces ulcer healing by ulcer coating; prevention of further pepsin/HCl-induced

damage; binding of pepsin; and stimulation of prostaglandins, bicarbonate, and mucous secretion
but does not decrease gastric acid production. It is commonly used as one of the agents in an anti-
H. pylori regimen.

• Prostaglandin analogues (Misoprostol) enhance mucous bicarbonate secretion, stimulate

mucosal blood flow, and decrease mucosal cell turnover.
 Therapy of H. Pylori
H. pylori should be eradicated in patients with documented peptic ulcer disease. H. pylori therapy is
described previously (see chronic non-atrophic gastritis).
Surgery
• Indications (consider after thorough evaluation)
o Refractory symptoms or recurrence of disease despite appropriate medical
treatment
o Diseases that require the continuation of NSAIDs
o Inability to tolerate medical treatment
• Surgical procedures
o Vagotomy: surgical division of the anterior and posterior vagal trunk of the vagus
nerve (truncal vagotomy), both located along the lower esophagus. Denervation
through truncal vagotomy results in ∼ 70% reduction of acid production.
▪ To improve results, truncal vagotomy is combined with one of the
following drainage procedures:
▪ Pyloroplasty
▪ Antrectomy
▪ Subtotal gastrectomy
o Partial gastrectomy (Billroth) and reconstruction
▪ Billroth I: distal gastrectomy with end-to-end or side-to-
end gastroduodenostomy
▪ Billroth II: resection of the distal two-thirds of the stomach with a blind-
ending duodenal stump and end-to-side gastrojejunostomy
o Total gastrectomy and reconstruction: Roux-en-Y
6. Clinical picture of duodenal and gastric ulcer complications. Possibilities of early
diagnostics. Therapeutic management. Prophylaxis (seasonal and year-round) of peptic
ulcer.
Gastrointestinal bleeding
• Clinical features
o Hematemesis (coffee-grounds emesis)
o Melena
o Anemia
o Hematochezia (less common; only seen in massive bleeding)
o Orthostatic hypotension

Peptic ulcer perforation

• Clinical features
o Sudden, diffuse abdominal pain and rigidity
o Fever, tachycardia, tachypnea, hypotension
o Pneumoperitoneum
o Shoulder pain (irritation of the phrenic nerve)

Ulcer penetration and fistula formation

• Clinicalfeatures: a change in clinical symptoms that are related to the affected neighboring
organs
o Colon: Gastrocolic or duodenocolic fistulas may manifest
with copremesis and postprandial diarrhea.
o Liver, spleen, or diaphragm: Penetration may result in visceral abscesses (fever,
abdominal tenderness, and sepsis).
o Gastroduodenal artery or aorta: Vascular fistulas may result in severe hemorrhage.
o Biliary tree: Choledochoduodenal fistulas may manifest with biliary tract obstruction
(fever, jaundice, RUQ pain).
o Pancreas: increased epigastric pain and peritonitis

Gastric outlet obstruction

Clinical features :Postprandial, nonbilious vomiting

Malignant transformation
• Gastric
ulcers
o High malignant potential (progression to cancer in 5–10% of cases)
o Malignancy should be ruled out with biopsy.
• Duodenal ulcers
o Usually benign
o Routine biopsy is not required.
Diagnostics
Initial evaluation
- All pts → history , CBC, BMP , fecal occult blood test
- Pts <60 years w/o red flags for dyspepsia → Begin with noninvasive testing for H.
pylori infection (H. pylori test-and-treat strategy). ( urea breath test and h pylori stool antigen
test)
- Patients > 60 years of age, or > 45 years of age in areas with high gastric
cancer prevalence ,Patients with red flags for dyspepsia: on a case-by-case basis , Patients
unresponsive to empiric medical therapy → refer directly for EGD
-Esophagogastroduodenoscopy (EGD)
The most accurate test to confirm the diagnosis. Other clinical applications include:
• Malignancy screening: to differentiate PUD from gastric cancer
o Visualization of the lesions
oBiopsy sampling
• Invasive H. pylori testing
• Simultaneous therapeutic measures, e.g., hemostasis treatment with electrocautery for active
bleeding

-Upper gastrointestinal radiography.

Barium studies of the proximal gastrointestinal tract are still commonly used as a first test for
documenting an ulcer. These ulcers tend to project beyond the contour of the stomach, with radiating
folds extending to the ulcer margin. In contrast, malignant ulcers usually have irregular heaped-up
margins that protrude into the lumen of the stomach.
-Gastric juices analysis
may help distinguish benign from malignant gastric ulcers. Benign ulcers rarely exist in the settings
of achlorhydria, which should prompt further workup with gastric biopsy and cytology.
-Biopsy
• Gastric
ulcers
o Biopsies are recommended in most cases.
o Multiple biopsies are recommended.
▪ From the edge and base of the ulcer (essential to rule
out malignancy, which is not uncommon in gastric ulcers)
▪ Multiple biopsies from different areas of the stomach lining, including
those not surrounding the ulcer (to test for H. pylori)
• Duodenal ulcers
o Obtain biopsies from ulcers with endoscopic features that suggest malignancy.
o Duodenal ulcers are usually benign and do not require routine biopsy.

Therapeutic management (in previous Q)

Prophylaxis
Deterrence and prevention
-Primary prevention of NSAID-induced ulcers includes the following:
• Avoid unnecessary use of NSAIDs
• Use acetaminophen or nonacetylated salicylates when possible
• Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the
newer NSAIDs or COX-2 inhibitors, in high-risk patients without cardiovascular disease
-Consider prophylactic or preventive therapy for the following patients:
• Patients with NSAID-induced ulcers who require chronic, daily NSAID therapy
• Patients older than 60 years
• Patients with a history of peptic ulcer disease or a complication such as gastrointestinal
bleeding
• Patients taking concomitant steroids or anticoagulants or patients with significant comorbid
medical illnesses
-Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced
gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI according to the
following regimens:
• Misoprostol 100-200 mcg PO 4 times per day
• Omeprazole 20-40 mg PO every day
• Lansoprazole 15-30 mg PO every day
7. Chronic enterocolitis. Etiology. Pathogenesis. Clinical picture depending on the localization
and character of morphological changes. Main syndromes. Diagnosis. Treatment. Prognosis.
Periodic health examination.
Enterocolitis is an inflammation that occurs in a person’s digestive tract. The condition specifically
affects the inner linings of both the small intestine and the colon, causing several symptoms.
Etiology → Enterocolitis in adults often develops due to infections, but it may develop in infants for
reasons that are not yet clear.
Types

• Necrotizing enterocolitis (Doctors do not yet understand the cause of necrotizing enterocolitis ,
Some suggest that premature babies have an undeveloped immune system and are more prone to
bacterial attack. Excess bacteria in the intestines appear to make the problem worse.)
-Clinics : a bloated, swollen, or discolored abdomen ,bloody stools ,diarrhea ,vomiting
-The infant may also not eat correctly or want food at all. Necrotizing enterocolitis may
also produce symptoms of bacterial infection, such as: fever ,disrupted breathing
,extreme tiredness
• Antibiotic associated enterocolitis ( It is also possible for symptoms of enterocolitis to
develop after a course of antibiotics.In a healthy person’s intestines, bacteria fight for a place on
the intestinal wall, where they help break down and digest foods. When a person
takes antibiotics, most of these bacteria die.This leaves a perfect environment for more harmful
bacteria, such as Clostridium difficile (C.difficile) to cause an infection.As C. difficile bacteria
spread, they release toxins into the body. These toxins damage and inflame the inner wall of the
intestines and cause symptoms)
o Clinics cramps and bloating ,the urge to use the bathroom more frequently
,watery diarrhea ,fever ,tiredness ,a general ill feeling or malaise ,severe stomach pain

• Pseudomembranous enterocolitis (Pseudomembranous enterocolitis involves inflammation in

the lining of the bowel as well as the intestines. It typically occurs due to a bacterial infection
and after a person takes antibiotics.)
o Clinics : persistent, watery diarrhea with a particularly foul smell ,fever ,painful
cramping

• Hemorrhagic enterocolitis (Hemorrhagic enterocolitis is another type of inflammation that

occurs due to a bacterial infection. Certain strains of the Escheria coli (E. coli) bacterium infect
the intestines, producing a toxin that causes problems in the body.)
o clinics: Hemorrhagic enterocolitis typically leads to severe cramps and watery, bloody
diarrhea. Some people may also experience a fever.
Diagnostics

• Physical examination → During the exam, the doctor examines the abdomen to
check for swelling, pain, and tenderness.
 • Stool and culture test → gram stain of stool , fecal smear , stool ova and parasite
exam .
• Serological test → Different types of serologic markers including C-reactive protein,
platelet-activating factor and intestinal fatty acid binding protein are used in the
diagnosis. Complete blood count is also used to check the presence of neutropenia.
Blood culture also helps to find out any fungal infection that may cause sepsis.
• Abdominal ultrasound → gives clear insight of bowel wall i.e. its thickening or
thinning, reduced peristalsis or disturbed bowel wall perfusion. It also helps to
determine the exact status of intra-abdominal fluid. Bowel wall thickening of more
than 5mm has been reported to cause a higher mortality rate.
• Imaging techniques → CT scan allows checking for thickening in the cecum,
pericecal inflammation, and an air-filled perforation. Abdominal radiographs have
been widely used for diagnosing neutropenic enterocolitis.
Treatment
In general, patients with enterocolitis require a therapy of broad-spectrum antibiotics and
IV fluid resuscitation. Immediate medical management and introduction of antibiotic
treatment is a crucial measure to decrease morbidity and mortality in patients infected
with enterocolitis.

• In the treatment of necrotizing enterocolitis, cessation of formula feedings,

nasogastric decompression, and intravenous fluid resuscitation are commonly used.
- Nasogastric decompression- In this technique, a nasogastric tube is used to
decompress the stomach and remove gas and fluid from it. Gastric lavage basically
irrigates the stomach and helps to remove ingested toxins.
- Intravenous fluid resuscitation- It is an effective therapy in case of dehydration as a
result of enterocolitis. It compensates the loss of fluid and maintains electrolyte
balance in the body.
• In the treatment and prevention of antibiotic-associated enterocolitis use of non-
pathogenic living organisms has been reported which are capable of re-establishing
the equilibrium of the intestinal ecosystem. For example, S. boulardii has shown its
effectiveness and safety by decreasing significantly the occurrence of C. difficile colitis
and preventing the pathogenic effects of toxins.
• Antibiotics and antimicrobials are important therapies in case of Hirschsprung-
associated enterocolitis. Drugs like Ampicillin, Gentamicin and Metronidazole are
widely used.
• Surgical treatments - Despite medical management and supportive care, operative
management is needed when the symptoms are severe, which includes either
laparotomy or placement of a percutaneous peritoneal drain. In peritoneal drainage
technique a permanent peritoneal catheter is used to remove abdominal fluids and
reduce symptoms. In laparotomy, a surgical incision is done in the abdominal cavity.
Through laparoscopy the abdominal cavity can be examined closely and proper
treatment can be done.
8. Ulcerative colitis and Crohn's disease. Main causative factors. Clinical picture according to
localization and level of morphological changes. Differential diagnosis. Complications.
Treatment.
ULCERATIVE COLITIS
Ulcerative colitis is idiopathic, chronic, recurrent inflammatory disease of the colon or
rectal mucosa and submucosa.
ETIOLOGY
The exact etiology of ulcerative colitis is unknown, but the disease appears to be
multifactorial and polygenic.
Risk factors

• Genetic predisposition (e.g., HLA-B27 association)

• Ethnicity (White populations, individuals of Ashkenazi Jewish descent)
• Family history of inflammatory bowel disease
• Episodes of previous intestinal infection
• Increased fat intake (especially saturated fat and animal fat)
• Oral contraceptive use
• NSAIDs may exacerbate ulcerative colitis.

CLINICAL PICTURE
Complaints. The main complaints are diarrhea, rectal bleeding, tenesmus, passage of mucus, and
different degrees of abdominal pain, from mild discomfort to painful bowel movements or painful
abdominal cramping with bowel movements. Patients are commonly fatigued, which is often related to
the inflammation and anemia that accompany disease activity. Weight loss is also common.
Ulcerative proctitis refers to Proctosigmoiditis involves
inflammation that is limited to the rectum. In inflammation of the rectum and the sigmoid
many patients with ulcerative proctitis, mild colon (a short segment of the colon contiguous
intermittent rectal bleeding may be the only to the rectum). Symptoms of
symptom. Other patients with more severe proctosigmoiditis, like that of proctitis,
rectal inflammation may, in addition, include rectal bleeding, urgency, and
experience rectal pain, urgency (sudden tenesmus. Some patients with
feeling the need to defecate and a need to rush proctosigmoiditis also develop bloody
to the bathroom for fear of incontinence), and diarrhea and cramps.
tenesmus (ineffective, painful urge to move
one's bowels).
 Left-sided colitis involves
inflammation that starts at the rectum and Intestinal symptoms
extends up the left colon (sigmoid colon and
the descending colon). Symptoms of left- • Bloody diarrhea with mucus
sided colitis include bloody diarrhea, • Fecal urgency
abdominal cramps, weight loss, and left-sided • Abdominal pain and cramps
abdominal pain. • Tenesmus

Extraintestinal symptoms of ulcerative colitis

Fulminant colitis is a rare but severe form of
• General: fatigue, fever
pancolitis. Patients with fulminant colitis are
• Skeletal (most common extraintestinal
extremely ill with dehydration, severe
abdominal pain, protracted diarrhea with manifestation of
bleeding, and even shock. They are at risk of ulcerative colitis): osteoarthritis, ankylosing
developing toxic megacolon (marked spondylitis, sacroiliitis [10][11]
• Ocular: uveitis, episcleritis, iritis
dilatation of the colon due to severe
• Biliary: primary sclerosing cholangitis (it is
inflammation) and colon rupture
(perforation). Patients with fulminant colitis rare for patients with ulcerative colitis to
and toxic megacolon are treated in the develop PSC, but up to 90% of all patients
hospital with potent intravenous medications. with PSC will also have ulcerative colitis)
• Cutaneous
Unless they respond to treatment promptly,
o Erythema nodosum
surgical removal of the diseased colon is
o Pyoderma gangrenosum
necessary to prevent colon rupture.
o Aphthous stomatitis

Pancolitis or universal colitis refers to o Pyostomatitis vegetans

inflammation affecting the entire colon (right ▪ A very rare condition
colon, left colon, transverse colon and the that is associated with
rectum). Symptoms of pancolitis include other cutaneous diseases
bloody diarrhea, abdominal pain and cramps, and inflammatory bowel
weight loss, fatigue, fever, and night sweats. disease, particularly
Some patients with pancolitis have low-grade ulcerative colitis
inflammation and mild symptoms that ▪ Manifests with multiple
respond readily to medications. Generally, aphthae and pustules of
however, patients with pancolitis suffer more the oral mucosa
severe disease and are more difficult to treat • In children and adolescents: growth retardation
than those with more limited forms of and delayed puberty
ulcerative colitis.
DIFFERENTIAL DIAGNOSIS
• Crohn disease
• Exudative-inflammatory diarrhea
• Diverticular
disease
• Appendicitis
• Ischemic colitis
• Infectious colitis
- C. difficile colitis -Shigella dysenteriae -Salmonella enterocolitis
- Escherichia coli colitis -Campylobacter enterocolitis -Yersiniosis
- Tuberculosis -CMV colitis
• Radiation colitis
• Celiac disease
• Inflammatory diarrhea
COMPLICATIONS
• Gastrointestinal bleeding (both acute and chronic)
• Toxic megacolon
• Perforation → peritonitis
• Fulminant colitis: severe bowel inflammation that typically causes > 10 stools per day, lower
gastrointestinal bleeding, abdominal pain, and abdominal distention
• ↑ Risk of cancer
o Risk increases with duration and/or extent of disease (e.g., pancolitis).
o Colorectal carcinoma risk is not significantly increased in patients with mild
ulcerative colitis
• Colonic stricture
• Amyloidosis

TREATMENT
Goals of treatment with medication are to 1) induce remissions, 2) maintain remissions, 3) minimize
side effects of treatment, 4) improve the quality of life, and 5) minimize risk of cancer.
• Anti-inflammatory drugs → They are used to maintain remission. Sulfasalazine is useful in
treating mild-to -moderate ulcerative colitis and maintaining remission. It acts locally in the colon
to reduce the inflammatory response and systemically inhibits prostaglandin synthesis.
Mesalamine is the drug of choice for maintaining remission. It is useful for the treatment of mild-
to-moderate ulcerative colitis. It is better tolerated and has less adverse effects than sulfasalazine.
Enema and suppository forms are typically used in patients with distal colitis.
• Tumor Necrosis Factor Inhibitor→ Azathioprine (Imuran) is effective as a steroid-sparing or
steroid-reducing agent and for use in maintenance therapy. Administration is oral. Onset of
action can be delayed up to 3-6 months. Cyclosporine is effective as a means of avoiding
surgery in patients with severe ulcerative colitis refractory to intravenous corticosteroids. 6-
Mercaptopurine is effective as a steroid-reducing or steroid-sparing agent and for use in
maintaining remission. Administration is oral. Onset of action can be delayed up to 3-6 months.
• Antimicrobials→ Ciprofloxacin, Metronidazole can be used.
• Corticosteroids → Corticosteroids decrease inflammation by suppressing migration of
polymorphonuclear leukocytes and reversing increased capillary permeability. They are used
for induction of remission in moderate-to-severe active ulcerative colitis. They have no benefit
 in maintaining remission; long-term use can cause adverse effects. Methylprednisolone,
Prednisone, Hydrocortisone can be used in treatment of Ulcerative Colitis.
CROHNS DISEASE
• Crohns disease is an idiopathic , chronic , granulomatous disease that can affect any part of the GIT
from the mouth to anus.
• Unlike ulcerative colitis, CD is not limited to the colon but can manifest anywhere in
the gastrointestinal tract.
• The ileum is most often involved with ileocolitis in more than 50% of pts.
ETIOLOGY
• Cause:
exact cause remains unknown. Current theories implicate the role of genetics , microbial
, immunologic , environmental , dietary , vascular and even psychological factors as a
potential causative agents.
• Risk factors [4]
o Familial aggregation
o Genetic predisposition (e.g., mutation of the NOD2 gene, HLA-B27 association)
o Tobacco smoke
CLINICAL FEATURES
CD typically has a chronic intermittent course with episodic acute flares and periods of remission.
Clinical features differ according to the severity of CD. Patients with mild CD may be asymptomatic
while patients with fulminant CD have severe symptoms.

Constitutional symptoms
• Low-grade fever
• Weight loss
• Fatigue

Gastrointestinal symptoms [6]

CD most commonly affects the terminal ileum and colon, but involvement of any part of the GI tract (from
mouth to anus) is possible. In contrast to ulcerative colitis, rectal involvement is uncommon.
• Chronic diarrhea
• Lower gastrointestinal bleeding (uncommon)
• Abdominal pain, typically in the RLQ
• Palpable abdominal mass in the RLQ
• Features of CD complications
o Malabsorption (e.g., weight loss, anemia, failure to thrive)
o Enterocutaneous or perianal fistulas, often associated with abscess formation

Extraintestinal symptoms [8]

Extraintestinal manifestations of CD are present in 20–30% of patients with CD. [9]
• Joints →Enteropathic arthritis
▪ A seronegative spondyloarthropathy that develops in association
with inflammatory bowel disease
▪ Typically affects joints of the lower extremities but can also involve
the spine (e.g., sacroiliitis, spondylitis, inflammation of peripheral joints).
 o Nail clubbing [10]
• Eyes →Uveitis ,Iritis ,Episcleritis
• Liver/bile ducts: cholelithiasis
• Urogenital system: urolithiasis (mostly calcium oxalate stones)
• Oral mucosa → Oral aphthae ,Pyostomatitis vegetans
• Skin
o Erythema nodosum
o Acrodermatitis enteropathica
o Pyoderma gangrenosum: a neutrophilic dermatosis
▪ Associated with various conditions (e.g., IBD, rheumatoid arthritis, and trauma)
▪ Manifests with very painful, rapidly-progressive, red spots that can change
into purulent pustules or deep ulcerated lesions with central necrosis
▪ Commonly located at extensor side of the lower limbs
▪ Treated with immunosuppressants (e.g., corticosteroids, cyclosporine A)

DIFFERENTIAL DIAGNOSIS
CROHNS DISEASE UC
type of • Increased • Greatlyincreased
defecation • Typicallynonbloody, • Bloody diarrhea with mucus
watery diarrhea • Tenesmus
• May be bloody in more severe • Urgency
cases

Physical • Mostly constant pain in RLQ • Painful defecation, pain located in LLQ
examination • Palpable abdominal mass • Abdominal cramps and tenderness
• Low-grade fever • Tachycardia
• Orthostatic hypotension

Antibodies • ASCA • p-ANCA

Location • Typical • Colon and rectum (exception: backwash ileitis)

location: terminal ileum and

colon with rectal sparing
• May affect the entire GI tract

Pattern • Discontinuous (skip lesions) • Continuous

of inflammation

Surgery
Noncurative surgery may be needed Curative surgery possible (proctocolectomy)
to alleviate symptoms
Other differential diagnoses
- Acute appendicitis -Infectious gastroenteritis/colitis
- Noninfectious colitis (ischemic, after radiation therapy, after ingestion of drugs, etc.)
- Diverticulitis -Irritable bowel syndrome
- Gastrointestinal tuberculosis -Malignant intestinal transformations

COMPLICATIONS

Formation of cologastric, enterovesical, enterovaginal, and enterocutaneous fistulae.

Fistulae may manifest as feculent vomiting, recurrent urinary tract infections and
pneumaturia, feculent vaginal discharge, and feculent soiling of the skin. Development
of fistulae into the mesentery may result in intra-abdominal or retroperitoneal abscess
formation.

TREATMENT
General principles
• Tailor therapy to the severity of CD, phase of the disease (acute flare or remission), and risk of
progression of CD.
• Surgery may be required to manage complications and is an option for isolated short-segment
disease.
• Lifestyle modifications (e.g., smoking cessation) may decrease the incidence of complications.
• Regular monitoring of disease activity and screening for complications are essential aspects of
long-term management.
Pharmacotherapy
• Inductionphase
o Used to manage acute flares.
o Agents that have a rapid onset of action (e.g., corticosteroids, biologics) are used.
• Maintenance phase
o Used to maintain remission, typically in patients with moderate or severe CD and
those at high risk of progression of CD. [30]
o Biologics and immunomodulators are the principal agents of maintenance therapy.

commonly used medications

• Corticosteroids

• Primarily used to induce remission → Oral prednisolone , IV methylprednisolone.

• Biologics
o Anti-TNF-α antibodies: e.g., adalimumab, infliximab, certolizumab
▪ Increasingly used as a primary agent to induce remission. , Also used to maintain
remission and manage CD refractory to immunomodulators
 o Anti-leukocyte trafficking antibody (vedolizumab) and anti-p40 antibody (ustekinumab) :
used mainly to induce and maintain remission in moderate to severe CD
• Immunomodulators: e.g., thiopurine analogs (azathioprine, 6-mercaptopurine), methotrexate
o Primarily used to maintain remission
o Can be used as a steroid-sparing regimen to induce remission
• 5-aminosalicylic acid derivative: sulfasalazine (mesalamine is not routinely recommended)
o May be considered to induce remission of mild to moderate colonic or ileocolonic CD
o Not effective in isolated small bowel disease
9. Chronic pancreatitis. Etiology. Pathogenesis. Clinical picture. Classification. Diagnosis,
differential diagnostics. Treatment according to the form and phase of disease. Periodic
health examination.
• Chronic pancreatitis is a chronic inflammatory disease characterised by fibrosis and destruction of
exocrine pancreatic tissue.
• Diabetes mellitus occurs in advanced cases because the islets of Langerhans are involved.
ETIOLOGY
• Chronic heavy alcohol use (most common, esp. men)
• Pancreatic ductal obstruction: strictures (e.g., due to trauma, stones)
• Tobacco use
• Idiopathic pancreatitis
• Hereditary pancreatitis
Characterized by a positive family history and the absence of other risk factors
o
• Autoimmune pancreatitis
• Systemic disease
o Cystic fibrosis: ∼ 2% of cystic fibrosis patients develop chronic pancreatitis. [3]
o Severe hypertriglyceridemia (levels > 1,000 mg/dL)
o Primary hyperparathyroidism (hypercalcemia)
• Tropical pancreatitis
o Most common cause in the tropics (esp. southern India)
o Young age at onset
PATHOGENESIS
• Autodigestion and inflammation: damage to pancreatic acinar cells (e.g., alcohol), outflow
obstruction of pancreatic enzymes or premature activation
of trypsinogen to trypsin → intrapancreatic activation of digestive enzymes
(e.g., amylase and lipase) → autodigestion of pancreatic tissue → inflammatory reaction
• Fibrosis: exposure to toxins and/or inflammatory mediators (e.g., alcohol, cytokines) →
activation of pancreatic stellate cells
CLINICAL PICTURE
• Epigastric abdominal pain (main symptom)
o Pain radiates to the back, is relieved on bending forward, and is exacerbated after
eating.
o Pain is initially episodic and becomes persistent as the disease progresses.
o Often associated with nausea and vomiting
• Features of pancreatic insufficiency: late manifestation (after 90% of
the pancreatic parenchyma is destroyed)
o Steatorrhea (exocrine enzyme deficiency)
▪ Cramping abdominal pain, bloating, diarrhea
▪ Can lead to a deficiency of fat-soluble vitamins (A, D, E, and K)
o Malabsorption and weight loss
o Pancreatic diabetes (endocrine hormone deficiency)

CLASSIFICATION
TIGAR-O classification

MANCHESTER classification DIAGNOSIS

-Biochemical blood test. Elevations of
serum amylase and lipase are found only during acute
attacks of pancreatitis, usually early in the course of
the disease. In the later stages of chronic pancreatitis,
atrophy of the pancreatic parenchyma can result in
serum enzyme levels within the reference range, even
during acute attacks of pain.
-Serum bilirubin and alkaline phosphatase can
be elevated, indicating stricture of the common bile
duct due to edema, fibrosis or cancer.
-Fecal elastase →.): most common test , it Can support
a diagnosis of steatorrhea due to exocrine pancreatic
insufficiency
-72-hour quantitative fecal fat
estimation: confirmatory test for steatorrhea
o Patients consume 100 g of fat per day for 72 hours.
o Interpretation: Fecal fat > 7 g per day is diagnostic
of steatorrhea.
To check for pancreatic exocrine dysfunction,
the most sensitive and specific test is the
measurement of fecal elastase
-Abdominal x-ray.→ Pancreatic calcifications,
-Computed tomography scan. → to look for
complications of the disease and is useful in planning
surgical or endoscopic intervention.
 -Endoscopic retrograde cholangiopancreatography (ERCP) provides the most accurate visualization
of the pancreatic ductal system and has been regarded as the criterion standard for diagnosing chronic
pancreatitis.
• Ductal stones, which are visible as filling defects
• “Chain of lakes” or “string of pearls” appearance (characteristic feature)
• Irregularity and/or dilation of the main pancreatic duct

-Magnetic resonance cholangiopancreatography (MRCP) imaging provides information on the

pancreatic parenchyma and adjacent abdominal viscera
• Pancreatic ductal dilations and calcifications on plain CT (more sensitive than x-ray)
• “Chain of lakes” appearance of the main pancreatic duct

-Endoscopic ultrasonography. Recent studies suggest that endoscopic ultrasonography may be the
best test for imaging the pancreas.
DIFFERENTIAL DIAGNOSIS
- Ampullary Carcinoma -Cholangitis -Cholecystitis
- Chronic Gastritis -Community-Acquired Pneumonia (CAP)
- Crohn Disease -Intestinal Perforation -Mesenteric Artery Ischemia
- Myocardial Infarction -Pancreatic Cancer -Peptic Ulcer Disease

TREATMENT

Approach Pharmacological pain management [4]

• Provide patient education: Chronic pancreatitis is Provide pain management in a stepwise approach.
a relapsing and remitting disease. • Start with nonopioid oral
• Recommend abstinence analgesics (e.g., NSAIDs and acetaminophen if
from nicotine and alcohol for all patients. [13] not contraindicated).
• Monitor for and manage complications of chronic • Consider adjuvant analgesics. [12]
pancreatitis (e.g., pancreatic o Tricyclic
enzyme replacement therapy for exocrine antidepressants (e.g., amitriptyline)
pancreatic insufficiency). o SSRIs (e.g., fluoxetine)
• Initiate directed treatment of the o SNRIs (e.g., duloxetine)
underlying etiology of chronic pancreatitis, o Gabapentinoids (e.g., pregabalin)
e.g.: • Limit opioid analgesics.
o Management of alcohol use
disorder and nicotine addiction
o Management of hypertriglyceridemia
in adults
o Management of hyperparathyroidism

Pancreatic Enzyme Supplementation. These are used as dietary supplementation to aid digestion in
patients with pancreatic enzyme deficiency. Several preparations are available: Pancrelipase (Creon,
Pancreaze, Ultresa, Viokace, Zenpep). The aim is to provide at least 30,000 units of lipase.
Surgery. Traditional surgery for chronic pancreatitis tends to be divided into two areas - resection and
drainage procedures. New and proven transplantation options prevent the patient from becoming diabetic
following the surgical removal (resection) of their pancreas. This is achieved by transplanting back in the
patient's own insulin-producing beta cells.
10. Chronic hepatitis. Etiology. Pathogenesis. Main morphological manifestations.
Classification. Clinical picture. Main clinical syndromes. Differential diagnosis.
Treatment. Prognosis.
Chronic hepatitis is inflammation of the liver that lasts at least 6 months or longer.
ETIOLOGY
Viral Hepatitis.
▪ Viral Hepatitis B and C are the most common causes of chronic hepatitis. HBV) is a DNA virus
which is transmitted parenterally. Individuals at high risk include intravenous drug abusers,
homosexual men and those exposed to blood and blood products. The incubation period ranges from
1 to 6 months
▪ Hepatitis C (HCV) is an RNA virus that formerly accounted for 90% of post-transfusion hepatitis.
The modes of transmission (parenteral, sexual and perinatal) are similar to those of HBV. The
incubation period is 2 weeks to 6 months.
▪ Hepatitis D (Delta hepatitis, HDV) is caused by a small, defective RNA virus that is infectious only
in presence of HBV infection. It can complicate acute HBV infection, but is seen more commonly
as a superinfection in patient with chronic HBV
Autoimmune Hepatitis. Autoimmune hepatitis is now accepted as a chronic disease of unknown cause,
The trigger for autoimmune chronic hepatitis is unknown, but the damage to the liver is caused by the
individual's lymphocytes and by antibodies produced in the individual's own tissue
industrial and natural toxins (chlorinated hydrocarbons, naphthalene, benzene, arsenic, phosphorus, lead,
mercury, gold, natural mushroom poisons)

Alcoholic Hepatitis. Alcoholic hepatitis is a syndrome of progressive inflammatory liver injury

associated with long-term heavy intake of ethanol. The pathogenesis is not completely understood.
Drug-Induced Hepatitis. (AB, sulfonamides, anti-tuberculosis, psychotropic, iron preparations).Chronic
hepatitis caused by drugs is usually recognized early. Stopping the medicine before cirrhosis has
developed usually reverses the disease.
Inherited Disorders. Some inherited disorders of metabolism also can appear as chronic hepatitis.
The most frequent of these conditions is Wilson's disease - a familial disorder of copper metabolism.
Alpha-1-antitrypsin deficiency and tyrosinemia may appear as chronic hepatitis although other
features help in distinguishing these rare conditions from those caused by viruses.
PATHOMORPHOLOGY OF CH → expansion of portal tracts, inflammatory cell infiltration of portal fields,
dystrophy and necrosis of hepatocytes, moderate fibrosis while maintaining liver architectonics.

CLINICAL FEATURES
depend on the severity of the liver disease and whether or not cirrhosis has developed. It may include
pain syndrome, jaundice, dyspeptic, fever, hepatorenal syndrome of hepatocellular insufficiency,
mesenchymal-inflammatory syndrome.
Complaints. Fatigue, mild discomfort in the upper abdomen, loss of appetite and aching joints are the
common symptoms of chronic hepatitis. Fatigue is by far the most common symptom and it might be
quite disabling. Some patients may have no symptoms. Others may have signs of liver failure, jaundice,
itching of the skin, weight loss, muscle weakness, abdominal enlargement, dark urine, mild fever.
Physical examination. General inspection may reveal jaundice, petechial skin rash, palmar erythema,
spider naevi, loss of body hair, weight loss. Tongue may be bright red color (crimson), with atrophy of
the papillae. Palpation of the abdomen. Liver is enlarged, dense, painful in palpation, liver edge becomes
thicker. Spleen also may be enlarged.
CLASSIFICATION
1) by etiology : viral (viral hepatitis B, C, D, F); alcoholic; medicinal (toxic allergic); toxic; parasitic; reactive;
autoimmune (lupoid)

2) according to the clinical and morphological form :

a) chronic active hepatitis (with predominantly hepatic manifestations, with severe extrahepatic
manifestations, cholestatic) - lymphoid infiltration captures the portal tracts, destroys the border plate
and invades the hepatic lobule

b) chronic persistent hepatitis - lymphoid infiltration of the portal fields does not violate the integrity of
the border plate and does not penetrate into the hepatic lobule.

DIFF.DIAGNOSIS → autoimmune hepatitis, chronic steatohepatitis, congenital metabolic

hepatopathies and drug-induced hepatopathies.
TREATMENT

1. With a high degree of CH activity - bed rest, in other cases - sparing with limited physical
activity; rehabilitation of chronic foci of infection; table number 5 (restriction of animal fats, salts,
liquids)

2. Antiviral therapy - if a virus is detected in the replication phase: intron, alpha-interferon (for HBV -
10 million U s / c 3 times / week 4-6 months, for HCV - 3 million IU s / c 3 times /week 6-12 months,
with HD - 10 million units s / c 3 times / week 12-18 months)

3. Immunosuppressant therapy: GCS is used at a high degree of activity of the pathological process
(initial dose of prednisolone 30-40 mg/day with a gradual decrease to a maintenance dose of 10-15
mg/day after reaching the effect for 6 months and >; then the drug is gradually canceled for 2, 5 mg /
month for 4-6 weeks), with insufficient effectiveness of corticosteroids and the development of side
effects - cytostatics (azathioprine 50-100 mg / day)

4. Improving the metabolism of hepatocytes: vitamins undevit, dekamevit, duovit, vitamin B12; lipoic
acid; hepatoprotectors (Essentiale, Liv-52, Karsil)

5. Immunomodulatory therapy - to increase the activity of the T-suppressor population of lymphocytes:

levamisole (decaris) 100-150 mg / day every other day 7-10 times, then a maintenance dose of 50-100
mg / week for up to a year

6. Detoxification therapy: 200-400 ml of 5-10% glucose solution IV, 200-400 ml of 0.9% saline.

+Clinical examination: in chronic active hepatitis: every 2-3 months examination of the patient with the
determination of the main biochemical parameters in the blood (bilirubin, AST, ALT, protein fractions,
prothrombin), in chronic persistent hepatitis: examination at least 2 times a year; in the treatment of
maintenance doses of immunosuppressants - a monthly examination, general clinical and biochemical
blood tests.

PROGNOSIS → The estimated 5-year survival rates were 97% for patients with chronic persistent
hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis
with cirrhosis. The usual cause of death was liver failure and its sequelae.

11. Liver cirrhosis. Etiology. Morphological features. Main syndromes. Pathogenesis of clinical
laboratory syndromes. Differential diagnosis. Complications. Treatment.
Liver cirrhosis is a chronic polyetiological progressive liver disease characterized by a significant
decrease in the number of functioning hepatocytes, progressive fibrosis, restructuring of the normal
structure of the parenchyma, and subsequent development of liver failure and portal hypertension.
CLASSIFICATION OF LIVER CIRRHOSIS:
1) by etiology :
a) alcoholic - takes 1st place in the Republic of Belarus
b) viral - as an outcome of CVH B, C, D
c) autoimmune (lupoid)
d) medicinal (toxic)
e) primary (cholestatic) and secondary (with obstruction of extrahepatic bile ducts) biliary
f) congestive - occurs when venous congestion in the liver (former name - cardiac)
g) metabolic - genetically determined (hemochromatosis, Wilson-Konovalov's disease)
i) cryptogenic - unknown or unidentified etiology
2) according to morphological features :
a) macronodular (large-nodular) - irregularly located large nodes up to 5 cm in diameter, separated
by connective tissue strands of various widths; more often viral
b) micronodular (small-nodular) - regularly located small nodes 1-3 mm in diameter, separated by a
network of scar tissue; more often alcoholic
c) micro-macronodular (mixed)
3) According to clinical features :
a) stage of the process: initial, pronounced clinical manifestations, terminal
b) process phase: active (minimal, moderate, highly active) and inactive
c) the degree of functional disorders: mild, moderate, severe (hepatergy)
d) severity (hidden, moderate, pronounced) and type (subhepatic, intrahepatic, suprahepatic) of portal
hypertension
+e) the presence of hypersplenism: absent or pronounced
PATHOPHYSIOLOGY
• The following three mechanisms have been described for all types of liver cirrhosis: [5]
0. Degeneration and necrosis of hepatocytes
▪ Activated Kupffer cells destroy hepatocytes, activate hepatic stellate cells,
and promote inflammation.
▪ Inflammatory cytokines (e.g., TGF-β, PDGF)
→ hepatocyte apoptosis and hepatic stellate cell activation
→ excess collagen production
1. Fibrotic tissue and regenerative nodules replace the liver parenchyma
▪ Hepatocyte destruction triggers repair mechanisms → excess formation
of connective tissue (fibrosis)
▪ Excessive connective tissue in periportal zone and centrilobular
zone → regenerative nodules and fibrous septa → compression of hepatic
sinusoids and venules → ↑ portal vein hydrostatic
pressure → intrasinusoidal hypertension → ↓ functional sinusoids
2. Loss of liver function: sinusoidal capillarization → loss of fenestration
and scar tissue formation→ impaired substrate exchange → loss of
normal liver function (exocrine and metabolic)
•
Clinical and laboratory syndromes in liver cirrhosis:
• 1) mesenchymal-inflammatory syndrome - less pronounced than with chronic hepatitis; due to
inflammation of hepatocytes associated with cirrhosis
• 2) cytolytic syndrome - the numbers of hyperenzymemia are an order of magnitude lower than
with chronic hepatitis (because with cirrhosis, the synthetic function of the liver is already
sharply reduced)
• 3) dyspeptic syndrome - pain in the right hypochondrium, aggravated after eating, nausea,
vomiting, bitterness in the mouth, bloating and feeling of a full stomach after eating any food
• 4) asthenovegetative syndrome with progressive weight loss and signs of polyhypovitaminosis
with adequate nutrition
• 5) syndrome of jaundice and cholestasis - characteristic of biliary cirrhosis of the liver
(jaundice of the skin and sclera, severe itching, scratching on the skin)
• 6) portal hypertension syndrome (varicose veins of the esophagus, cardia of the stomach,
rectum, anterior abdominal wall - "jellyfish head", oliguria, ascites)
• 7) syndrome of small signs (due to hyperestrogenemia) - "spider veins" (telangiectasias) on the
skin of the upper half of the body, palmar erythema ("liver palms", "hands of beer lovers") -
bright red color of the palms in the thenar, hypothenar, phalanges fingers, varnished tongue,
carmine-red lips, gynecomastia in men, atrophy of the genital organs and a decrease in the
severity of secondary sexual characteristics
• 8) splenomegaly (due to venous stasis) and hypersplenism (increased destruction of blood cells
in the spleen with the development of pancytopenia, anemic and hemorrhagic syndromes)
• 9) hepatorenal syndrome - occurs with decompensation of cirrhosis of the liver, characterized
by azotemia and signs of renal failure (while morphological changes in the kidneys are not
detected)
• 10) toxic encephalopathy (sleep disturbance, headaches, memory loss, paresthesia, tremors,
apathy)
• 11) syndrome of hepatocellular insufficiency up to hepatic coma - develops as a result of
cirrhosis of the liver
 • On palpation, the liver is enlarged, dense ("stony"), bumpy with a sharp edge.
• Clinical triad of liver cirrhosis : signs of portal hypertension + dense "stony" liver on palpation
+ hepatic stigmas.

Complications of cirrhosis of the liver:

1) bleeding from varicose veins of the esophagus and stomach
2) hepatic encephalopathy and coma
3) erosion and ulcers of the stomach, duodenum
4) portal vein thrombosis
5) cirrhosis-cancer
6) ascites-peritonitis
7) hepatic nephropathy (hepatorenal syndrome)

DIFF.DIAGNOSE
• Primary sclerosing cholangitis • Chronic viral hepatitis (hepatitis
A, B, or C)
• Biliary obstruction
• Autoimmune hepatitis
• Budd-Chiari syndrome
• Alcoholic hepatitis
• Cystic fibrosis
• Nonalcoholic steatohepatitis
• Glycogen storage diseases (type 1, type
2, type 3, type 4, type 5, type 6, type 7) • Hemochromatosis

• Liver fluke • Alpha-1 antitrypsin deficiency

(fascioliasis, clonorchiasis, Opisthorchi
s) • Wilson disease

• Hydatid cyst • Hepatocellular carcinoma

• Schistosomiasis • Celiac disease

• Congestive heart failure (cardiohepatic • Hypothyroidism or hyperthyroidis

syndrome) m

• Malignancy (particularly metastasis to • Primary biliary cirrhosis

liver and primary liver, gastrointestinal,
• Polycystic liver disease
and biliary cancer)

• Sarcoidosis Amyloidosis (AL amyloidosis, AA

amyloidosis)

TREATMENT
General approach
 • Provide treatment for the underlying condition (e.g., treat HCV with antiviral drugs and
reduce hepatotoxic influences).
• Prevent, recognize, and treat possible complications.
• Avoidance of hepatotoxic substances (e.g., alcohol, medications such as NSAIDs)
• Routine vaccinations: pneumococcal vaccine (PPSV23), hepatitis A vaccine, hepatitis B
vaccine, influenza vaccine, tetanus vaccine
• Balanced diet with adequate calorie intake, no protein restriction

Pharmacotherapy
• Nonselective beta blockers (e.g., propranolol) to lower portal pressure and prevent variceal
bleeding
• Spironolactone and furosemide to manage ascites and edema in patients with hypoalbuminemia
• For the treatment of specific complications related to cirrhosis,

- if hepatitis viruses are detected in the replication phase - antiviral therapy (interferon as in
CVH)
- improvement of hepatocyte metabolism: vitamins Undevit, Decamevit, Duovit, vitamin
B12; lipoic acid; hepatoprotectors (Essentiale, Liv-52, Karsil)
- treatment of edematous-ascitic syndrome (lasix up to 80 mg/day, hypothiazide up to 100
mg/day, veroshpiron up to 200 mg/day); if ineffective - paracentesis
- immunosuppressive therapy: GCS is used with a high degree of activity of the pathological
process (40-60 mg / day with a gradual dose reduction, a course of up to 6 months)
- detoxification therapy: in / in 200-300 ml of 5-10% glucose solution with the addition of 10-20
ml of Essentiale or 4 ml of 0.5% solution of lipoic acid; IV gemodez 200 ml 2-3 infusions
- treatment of hepatic encephalopathy: lactulose 30 mg 3-5 times / day after meals, hepa-Merz,
urosan, ursofalk, etc.
- in the event of bleeding from varicose veins of the esophagus or stomach: strict bed rest, cold on
the epigastric region, polyglucin infusions, 5% glucose IV, vasopressin 20 IU in 100-200 ml of
5% glucose for 15-20 minutes IV in drip + sublingual nitroglycerin, general hemostatic therapy,
local hemostasis (laser therapy, endoscopic sclerotherapy), balloon tamponade

Surgical/Interventional procedures [13]

• Paracentesis: a method used to decompress abdomen due to ascites
• Transjugular intrahepatic portosystemic shunt (TIPS): a method used to lower portal
pressure and manage complications
o Indications
▪ Refractory ascites
▪ Recurring esophageal varices
▪ Bridging time until possible liver transplant
• Surgery: A liver transplant is the only curative option in patients with decompensated
cirrhosis.

12. Chronic cholecystitis. Etiological factors. Clinical picture. Diagnostic criteria. Treatment in
acute attack of disease and remission.
Chronic inflammation of the gallbladder is almost invariably associated with gallstones.
ETIOLOGY → Chronic irritation of gallbladder mucosa by cholelithiasis , Recurrent attacks of
acute cholecystitis

CLINICAL PICTURE → recurrent symptoms similar to acute cholecystitis but typically less severe
and often self-limiting

Clinical manifestations of chronic cholecystitis:

1) pain syndrome - pain is localized in the right hypochondrium, less often in the epigastric region,
almost always radiates upward - to the right shoulder blade, collarbone, shoulder, right half of the neck,
occurs or intensifies after a diet violation (eating fatty foods, eggs, cold and carbonated drinks,
hypothermia, etc.), periodic pulling or aching with acalculous XX or acute, stabbing, intense, up to
unbearable with calculous XX (hepatic colic)
Palpation - soreness in the right hypochondrium + a number of pain symptoms:
a) Kera's symptom - soreness with pressure in the projection of the gallbladder
b) Murphy's symptom - a sharp increase in pain during palpation of the gallbladder on inspiration
c) Grekov-Ortner symptom - pain when tapping along the costal arch on the right
d) Mussi-Georgievsky symptom (phrenicus symptom) - pain when pressing on the right phrenic
nerve between the legs of the right sternocleidomastoid muscle.
2) dyspeptic syndrome - belching with bitterness or a constantly bitter taste in the mouth, a feeling of
fullness in the upper abdomen, bloating, stool disorders, nausea, vomiting of bile (rare)
3) inflammatory-intoxication syndrome - an increase in temperature to subfebrile numbers (not
higher than 38 С) - occurs most often during an exacerbation of XX.
DIAGNOSTICS
• Laboratory studies: may be normal [39]
• Ultrasound abdomen or CT abdomen with IV contrast:
o Thickened gallbladder wall
o No evidence acute inflammatory changes (e.g., pericholecystic fluid);
o Cholelithiasis commonly present
• HIDA scan: delayed visualization of the gallbladder [40]
• All patients should also be evaluated for choledocholithiasis before treatment

TREATMENT of chronic cholecystitis:

1) diet - table number 5 (restriction of fatty and spicy ingredients)

2) during exacerbation - AB penetrating into the bile (erythromycin 0.25 g 4 times / day, ampicillin 0.5
g 4 times / day, oxacillin 0.5 g 4 times / day, tetracyclines 0.25 g 4 times/day)

3) antispasmodics (in some cases with analgesics): no-shpa, papaverine, platifillin, baralgin (analgesic
+ antispasmodic) 2-5 ml / m 2-3 times a day.
4) choleretic therapy to accelerate the passage of bile, improve drainage: cholekinetics (magnesium
sulfate, sorbitol, xylitol) and choleretics (dihydrocholic acid, allochol, cholenzym).

NB In calculous XX, the appointment of choleretic drugs is contraindicated, because. this can provoke
a blockage of the bile ducts with a stone and a sharp exacerbation of the process.

5) with the development of calculous cholecystitis - surgical treatment (laparoscopic cholecystectomy)

6) physiotherapy: in the subsidence phase - thermal procedures (ozocerite and mud applications)

+Dispensary observation : 2 times a year with general clinical laboratory tests and ultrasound 1 time
per year.

For acute attacks :

Empiric antibiotic therapy and laparoscopic cholecystectomy are the mainstays of
treatment. Laparoscopic cholecystectomy should be performed as soon as possible, preferably
within 72 hours of admission,
In high-risk patients with severe cholecystitis, a temporizing gallbladder drainage procedure
(e.g., percutaneous cholecystostomy, endoscopic gallbladder stenting) should be performed and
elective interval cholecystectomy scheduled after the resolution of acute symptoms.

13. Biliary dyskinesia. Etiology. Pathogenesis. Clinical picture. Differential diagnostics.

Treatment. Prophylaxis.
Biliary dyskinesia is a motility disorder that affects the gallbladder and sphincter of Oddi.
ETIOLOGY
Exact cause is not known, there are many theories such as :
 • Stress – Some evidence • Obesity • Fibromyalgia – It is
shows that stress causes common for patients
dopamine receptor Biliary dyskinesia is also with this condition to
dysfunction, which can thought to be a symptom of also have biliary
keep the gallbladder from some diseases, such as: dyskinesia. Fibromyalgia
receiving proper signals is characterised by
from the brain. • Hypothyroidism muscle spasms that can
• A problem with the • Pancreatitis also affect the muscles of
muscles of the gallbladder • Diabetes the gallbladder.
• Excessively tight muscle of • Celiac disease
the sphincter of Oddi Biliary dyskinesia is more
• Chronic inflammation common among females than
• Hormone imbalance males, and among patients aged
between 40 and 60 years old.

PATHOPHYSIOLOGY

• Biliary dyskinesia is characterized by low gallbladder ejection fraction

during cholecystokinin-stimulated cholescintigraphy
• The exact pathophysiology of biliary dyskinesia is unknown
• However, the following suggestions have been proposed as the causes of biliary dyskinesia
o The biliary pain in gallbladder dyskinesia may be the result
of gallbladder inflammation due ineffective gallbladder contraction caused
by gallbladder dysmotility following a change in bile composition.
o May be the result of visceral hypersensitivity (hypersensitivity of
the neural pathways communicating with the intestines) seen in patients
with sphincter of Oddi dysfunction or irritable bowel syndrome.
o May be the result of receptor/neurologic abnormalities (such as problems
in cholecystokinin (CCK) release, decreased sensitivity or density
of CCK receptor in the gallbladder, or increased sensitivity of CCK receptor in
the cystic duct with impaired contractility of the smooth muscle

DIFFERENTIAL DIAGNOSIS
Biliary dyskinesia should be differentiated from other disorders that caused right upper quadrant
(RUQ) pain, such as
- Abdominal disorders with pain similar to biliary pain -Peptic ulcer disease (PUD)
- Gastroesophageal reflux disease (GERD) -Irritable bowel syndrome (IBS)
- Chronic constipation -Cirrhosis
- Coronary artery disease -Costochondritis
- Musculoskeletal disorder
TREATMENT
Medical therapy

• Medical therapy mostly includes of symptomatic treatment of abdominal pain:

o Opiates (intravenous) are the drug of choice, although some studies have
suggested that opiates cause sphincter of Oddi contraction.
o Calcium channel blockers (CCB) have been reported to be ineffective.
▪ However, CCBs like nifedipine have been reported to have potential
effect in improving the pain but headache and tachycardia are
the adverse effects.

• Alternative treatments that may be effective by a cholagogue effect (increases bile discharge
from the biliary system), or a choleretic effect (increases bile secretion from the liver)
include:[4]
o Artichokes
o Celandine
o Dandelion

• Other reported effective measures in biliary dyskinesia include:[5]

o Smoking cessation
o Avoidance of fatty food
o Frequent meal consumption
o Lying on the right side after meals
o Weight loss
o Increase in physical activity
Surgery ;
• Cholecystectomy → Laparoscopic cholecystectomy is used to treat biliary dyskinesia.
• Sphincterotomy → Endoscopic biliary sphincterotomy is performed in patients with sphincter
of Oddi disorder (SOD) diagnosed by manometry.

14. Cholelithiasis (gallstone disease). Etiology. Pathogenesis. Clinical picture: acute attack of
disease and remission. Complications. Indications for surgery. Therapeutic management.
Prophylaxis.
Gallstones are abnormal, inorganic masses formed in the gallbladder and, less commonly, in the
common bile or hepatic ducts.
ETIOLOGY
Cholesterol stones
• Risk factors
o Obesity, insulin resistance, dyslipidemia
o Female sex
▪ Increased progesterone levels (during pregnancy) cause smooth
muscle relaxation, decreased gallbladder contraction, and
subsequent bile stasis with formation of gallstones.
o Multiparity or pregnancy
o Age (> 40 years of age)
o European, Native American, or Hispanic ancestry
o Family history
o Drugs: fibrates (inhibition of cholesterol 7-α hydroxylase), estrogen therapy, oral
contraceptives
o Malabsorption (e.g., Crohn disease, ileal resection, cystic fibrosis)
o Rapid weight loss
• PATHOPHYSIOLOGY: abnormal hepatic cholesterol
metabolism → ↑ cholesterol concentration in bile and ↓ bile salts and lecithin
→ hypersaturated bile → precipitation of cholesterol and calcium carbonate → cholesterol
stones or mixed stones

Black pigment stones

• Risk factors
- Chronic hemolytic anemias (e.g., sickle cell disease, hereditary spherocytosis)
- (Alcoholic) cirrhosis -Crohn disease
- Total parenteral nutrition -Advanced age
• PATHOPHYSIOLOGY: ↑ hemolysis → increase in circulating unconjugated bilirubin →
increased uptake and conjugation of bilirubin → precipitation of bilirubin polymers and stone
formation
Mixed/brown pigment stones
• Risk factors: bacterial infections and parasites (e.g., Clonorchis sinensis, Opisthorchis
species) in the biliary tract, sclerosing cholangitis [2]
• PATHOPHYSIOLOGY: infection or infestation → release of β-glucuronidase (by
injured hepatocytes and bacteria) → hydrolyzes conjugated bilirubin and lecithin in the bile →
increased unconjugated bilirubin and fatty acids → precipitation of calcium
carbonate, cholesterol, and calcium bilirubinate (dark color) in bile
COMPLICATIONS
 - Cholecystitis ( Acute cholecystitis (most common) , Chronic cholecystitis ,Porcelain
gallbladder )
- Choledocholithiasis -Acute cholangitis
- Acute biliary pancreatitis
- Complications due to gallstone impaction at the gallbladder neck or infundibulum (Mirizzi
syndrome)

INDICATIONS FOR SURGERY

• Procedure: elective laparoscopic cholecystectomy
• Symptomatic cholelithiasis
• Asymptomatic cholelithiasis with any of the following:
o Increased risk of gallbladder cancer (e.g., gallbladder polyps, porcelain
gallbladder, gallstones ≥ 3 cm) [2][17][26]
o Increased risk of developing complications (e.g., immunocompromised patients,
multiple gallstones) [17][18]
o Increased risk of becoming symptomatic (e.g., hemolytic anemia, patients
undergoing gastric bypass surgery

THERAPEUTIC MANAGENENT
Medical. Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid ,
but it may be necessary for the patient to take this medication for up to two years. Gallstones may
recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can
sometimes be relieved by endoscopic retrograde sphincterotomy following endoscopic retrograde
cholangiopancreatography. Gallstones can be broken up using a procedure called extracorporeal
shock wave lithotripsy (often simply called "lithotripsy"), which is a method of concentrating
ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed safely in
the feces. However, this form of treatment is suitable only when there is small number of gallstones.

PROPHYLAXIS
• Diet
Because cholesterol appears to play a role in the formation of gallstones, it's advisable to avoid
eating too many foods with a high saturated fat content.
• Losing weight
Being overweight, particularly being obese, increases the amount of cholesterol in your bile, which
increases your risk of developing gallstones. A more gradual weight loss plan is recommended.
• Limit alcohol consumption
• Regular exercise
 1. Diagnostic capabilities of the laboratory and instrumental methods of research in
nephrology. Assessment criteria of kidneys functional state. Main methods of
investigation and their interpretation. Kidney biopsy (indications and
contraindications).
Urinalysis
• Dipstick testing
o Screening for the presence of blood, protein, glucose, ketones, nitrates and
leucocytes and to assess pH and osmolality of urine can be achieved by dipstick
testing.

• Urine microscopy or flow cytometry, it can detect

o Erythrocytes
▪ Which are indicative of bleeding from the urogenital tract (anywhere from
kidney to tip of penis)
o Dysmorphic erythrocytes
▪ Suggest the presence of nephritis
o Red cell casts
▪ Indicative of glomerular disease
o Crystals
▪ May be observed in patients with renal stone disease.
▪ It should be noted that calcium oxalate and urate crystals can sometimes
be found in normal urine that has been left to stand, due to crystal
formation ex vivo.
o Leukocytes
▪ The presence of leucocytes and bacteria in urine is indicative of renal tract
infection.
▪ White cell casts are strongly suggestive of pyelonephritis.
o Urine pH
▪ It can provide diagnostic information in the assessment of renal tubular
acidosis
 • Urine collection over a 24-hour period can be performed to measure excretion of solutes,
such as calcium, oxalate and urate, in patients with recurrent renal stone disease.
• Proteinuria can also be measured on 24-hour collections but is usually now quantified by
protein/ creatinine ratio on spot urine samples.
• Other dynamic tests of tubular function, including concentrating ability (p. 794), ability
to excrete a water load (p. 438) and ability to excrete acid (p. 426), and calculation of
fractional calcium, phosphate or sodium excretion, are valuable in some circumstances.
Hematology
• A normochromic normocytic anemia is common in CKD and is due in part to deficiency
of erythropoietin and bone marrow suppression secondary to toxins retained in CKD.
• Other causes of anemia include iron deficiency from urinary tract bleeding, and
hemolytic anemia secondary to disorders such as hemolytic uremic syndrome (HUS) and
thrombotic thrombocytopenic purpura (TTP).
• Other abnormalities may be observed that reflect underlying disease processes, such as
neutrophilia and raised erythrocyte sedimentation rate (ESR) in vasculitis or sepsis;
lymphopenia and raised ESR in systemic lupus erythematosus (SLE); and fragmented red
cells in HUS and TTP.
Biochemistry
• Abnormalities of routine biochemistry are common in renal disease.
• Serum levels of creatinine
o May be raised, reflecting reduced GFR, although serum creatinine values can
remain within the reference range in patients with reduced muscle mass, even
when the GFR has fallen by more than 50%.
• Serum levels of urea
o are often increased in kidney disease but this analyte has limited value as a
measure of GFR since levels increase with protein intake, following
gastrointestinal hemorrhage and in catabolic states.
 o Conversely, urea levels may be reduced in patients with liver failure or anorexia
and in malnourished patients, independently of changes in renal function.
• Serum calcium
o It tends to be reduced and phosphate increased in CKD, in association with high
parathyroid hormone (PTH) levels caused by reduced production of 1,25(OH)2D
by the kidney (secondary hyperparathyroidism).
o In some patients, this may be accompanied by raised serum alkaline phosphatase
levels, which are indicative of renal osteodystrophy.
• Other biochemical abnormalities may be observed that reflect underlying disease
processes, such as raised glucose and HbA1c levels in diabetes mellitus and raised levels
of C-reactive protein (CRP) in sepsis and vasculitis.
Glomerular filtration rate
• The glomerular filtration rate (GFR) is the rate at which fluid passes into nephrons after
filtration and is a measure of renal function.
• It is proportionate to body size and the reference range is usually expressed after
correction for body surface area as 120 (plus or minus) 25 mL/ min/1.73 m2.
• The GFR may be measured directly by injecting and measuring the clearance of
compounds such as inulin or radiolabeled ethylenediaminetetraacetic acid, which are
completely filtered at the glomerulus and are not secreted or reabsorbed by the renal
tubules

• However, this is not performed routinely and is usually reserved for special
circumstances, such as the assessment of renal function in potential live kidney donors.
• Instead, GFR is usually indirectly assessed in clinical practice by measuring serum levels
of endogenously produced compounds that are excreted by the kidney.
• The most widely used is serum creatinine, which is produced by muscle at a constant
rate, is almost completely filtered at the glomerulus, and is not reabsorbed.
 • Although creatinine is secreted to a small degree by the proximal tubule, this is only
usually significant in terms of GFR estimation in severe renal impairment, where it
accounts for a larger proportion of the creatinine excreted.
• Accordingly, provided muscle mass remains constant, changes in serum creatinine
concentrations closely reflect changes in GFR, although the reference range for creatinine
is wide due to the fact that muscle mass varies widely between different individuals
• Several methods have been developed with which to estimate GFR from serum creatinine
measurements (see Box. 17.1) but the most widely used is the MDRD (Modification of
Diet in Renal Disease) equation, which is now the accepted standard for assessing
estimated GFR (eGFR).
• A potentially more accurate assessment of GFR can be obtained by collection of a 24-
hour urine sample and relating serum creatinine levels to urinary creatinine excretion
Immunology
• Antinuclear antibodies, antibodies to extractable nuclear antigens and anti-double-
stranded DNA antibodies may be detected in patients with renal disease secondary to
SLE (
• Antineutrophil cytoplasmic antibodies (ANCA) may be detected in patients with
glomerulonephritis secondary to systemic vasculitis, as may antibodies to GBM
(glomerular basement membrane) in patients with Goodpasture’s syndrome, and low
levels of complement in SLE, systemic vasculitis and HUS.
Imaging
Ultrasound
• Renal ultrasound is a valuable non-invasive technique that is indicated to assess renal size
and to investigate patients who are suspected of having obstruction of the urinary tract or
renal tumors, cysts or stones.
• It is often the only method required for renal imaging and has the advantage of showing
other abdominal, pelvic and retroperitoneal pathology.
• Ultrasound can also be used to provide images of the prostate gland and bladder, and to
estimate the completeness of emptying in patients with suspected bladder outflow
obstruction.
• Ultrasonography may show increased density of the renal cortex with loss of distinction
between cortex and medulla, which is characteristic of CKD.
• Doppler imaging can be used to study blood flow in extrarenal and larger intrarenal
vessels and can assess the resistivity index, which is the ratio of peak systolic and
diastolic velocity. This is influenced by the resistance to flow through small intrarenal
arteries and may be elevated in various diseases, including acute glomerulonephritis and
rejection of a renal transplant. High peak velocities can also occur in severe renal artery
stenosis.
Computed tomography
• Computed tomography urography (CTU) is used to evaluate cysts and mass lesions in the
kidney or filling defects within the collecting systems.
• It usually entails an initial scan without contrast medium, and subsequent scans following
injection of contrast to obtain a nephrogram image and images during the excretory
phases.
• This technique gives more information than intravenous urography (IVU) but entails a
substantially larger radiation dose.
 • Contrast enhancement is particularly useful for characterizing mass lesions within the
kidney and differentiating benign from malignant lesions
• Computed tomography without contrast (CT) gives clear definition of retroperitoneal
anatomy regardless of obesity and is superior to ultrasound in this respect. Non-contrast
CT of kidneys, ureters and bladder (CTKUB) is the method of choice for demonstrating
stones within the kidney or ureter.
Computed tomography and angiography
• This technique (CT-angiography) involves performing computed tomography, following
an intravenous injection of contrast medium, to obtain images of the renal vasculature.
• It produces high-quality images of the main renal vessels and is of value in patients who
have suffered renal trauma and those with hemorrhage from the renal tract, and in the
investigation of renal artery stenosis. Other vascular structures, such as angiomyolipoma
and aneurysms, can also be detected.
Magnetic resonance imaging
• Magnetic resonance imaging (MRI) offers excellent resolution and gives good distinction
between different tissue types
• It is very useful for local staging of prostate, bladder and penile cancers.
Magnetic resonance angiography (MRA)
• It provides an alternative to CT-angiography for imaging renal vessels but involves
administration of gadolinium-based contrast media, which may carry risks for patients
with impaired renal function
Renal arteriography
• Renal arteriography involves taking X-rays following an injection of contrast medium
directly into the renal artery.
• The main indication is to investigate renal artery stenosis or hemorrhage.
• Renal angiography can often be combined with therapeutic balloon dilatation or stenting
of the renal artery and can be used to occlude bleeding vessels and arteriovenous fistulae
by the insertion of thin platinum wires (coils).
• These curl up within the vessel and promote thrombosis, thereby securing hemostasis.
Intravenous urography
• Intravenous urography (IVU) involves taking serial plain X-rays immediately before and
after an intravenous injection of contrast medium.
• It has largely been replaced by ultrasound, CTKUB and CTU for most renal imaging
purposes but remains a useful method of viewing the renal papillae, stones and urothelial
malignancies
• The initial X-rays may show the renal outlines (if perinephric fat and bowel gas shadows
allow), as well as radio-opaque calculi and calcification within the renal tract. Early films
taken 1 minute after injection can be used to assess renal perfusion, whereas films at later
time points provide images of the collecting system, ureters and bladder.
Pyelography
• Pyelography involves direct injection of contrast medium into the collecting system from
above or below.
• It offers the best views of the collecting system and upper tract, and is sometimes used to
identify the cause of urinary tract obstruction
 • Antegrade pyelography requires the insertion of a fine needle into the pelvicalyceal
system under ultrasound or radiographic control.
• This approach is much more difficult and hazardous in a non-obstructed kidney.
• In the presence of obstruction, percutaneous nephrostomy drainage can be established,
and often stents can be passed through any obstruction.
• Retrograde pyelography can be performed by inserting catheters into the ureteric orifices
at cystoscopy
Radionuclide studies
• These are functional studies requiring the injection of gamma ray-emitting
radiopharmaceuticals that are taken up and excreted by the kidney, a process that can be
monitored by an external gamma camera.
• Dynamic radionucleotide studies are performed with mercaptoacetyltriglycine labelled
with technetium (99mTc-MAG3), which is filtered by the glomerulus and excreted into
the urine.
Renal biopsy
• Renal biopsy is used to establish the nature and extent of renal disease in order to judge
the prognosis and need for treatment
• The procedure is performed transcutaneously with ultrasound or contrast radiography
guidance to ensure accurate needle placement into a renal pole.
• Light microscopy, electron microscopy and immunohistological assessment of the
specimen may all be required’

2. Acute glomerulonephritis (etiology and pathogenesis, classification, clinical picture,

diagnostics and treatment).
• Acute glomerulonephritis (GN) comprises a specific set of renal diseases in which an
immunologic mechanism triggers inflammation and proliferation of glomerular tissue
that can result in damage to the basement membrane, mesangium, or capillary
endothelium.
• Acute nephritic syndrome is the most serious and potentially devastating form of the
various renal syndromes.
• Acute glomerulonephritis progresses to chronic glomerulonephritis in about 30% of
adults
• Acute poststreptococcal glomerulonephritis (PSGN) is the archetype of acute GN.
• GN associated with staphylococcal infection has risen, due to the increase in antibiotic-
resistant Staphylococcus aureus infections.
• Acute GN is defined as the sudden onset of hematuria, proteinuria, and red blood cell
(RBC) casts in the urine. This clinical picture is often accompanied by hypertension,
 edema, azotemia (i.e., decreased glomerular filtration rate [GFR]), and renal salt and
water retention.
• Acute GN can be due to a primary renal disease or to a systemic disease.
• One way to classify GN is according to the etiology.
• Once a kidney biopsy is done, it is possible to classify non-infectious glomerulonephritis
according to the following
o Immune complex-mediated GN
o Antineutrophil cytoplasmic antibody (ANCA)-associated GN
o Anti-glomerular basement membrane (GBM) GN
o Monoclonal immunoglobulin-mediated GN
o C3 glomerulopathy
Etiology

Pathogenesis
• Glomerular lesions in acute GN are the result of glomerular deposition or in situ
formation of immune complexes.
• On gross appearance, the kidneys may be enlarged up to 50%.
• Histopathologic changes include swelling of the glomerular tufts and infiltration with
polymorphonucleocytes.
• Immunofluorescence reveals deposition of immunoglobulins and complement
• In PSGN, there is involvement of derivatives of streptococcal proteins. A streptococcal
neuraminidase may alter host immunoglobulin G (IgG). IgG combines with host
antibodies. IgG/anti-IgG immune complexes are formed and then collect in the glomeruli
• Acute GN involves both structural changes and functional changes.
• Structurally
o cellular proliferation leads to an increase in the number of cells in the glomerular
tuft because of the proliferation of endothelial, mesangial, and epithelial cells. The
proliferation may be endocapillary (i.e., within the confines of the glomerular
capillary tufts) or extracapillary (i.e., in the Bowman space involving the
epithelial cells).
 o Leukocyte proliferation is indicated by the presence of neutrophils and monocytes
within the glomerular capillary lumen and often accompanies cellular
proliferation.
o Glomerular basement membrane thickening appears
o Hyalinization or sclerosis indicates irreversible injury. These structural changes
can be focal, diffuse or segmental, or global.
• Functional changes include
o Proteinuria, hematuria, reduction in GFR (i.e., oliguria or anuria), and active urine
sediment with RBCs and RBC casts.
o The decreased GFR and avid distal nephron salt and water retention result in
expansion of intravascular volume, edema, and, frequently, systemic
hypertension.
Clinical features
• A thorough history should be obtained, focusing on the identification of an underlying
systemic disease (if any) or recent infection.
• Symptom onset is usually abrupt. In the setting of acute postinfectious GN, a latent
period of up to 3 weeks occurs before onset of symptoms
• Identify a possible etiologic agent (e.g., streptococcal throat infection [pharyngitis], skin
infection [pyoderma]). Recent fever, sore throat, joint pains, hepatitis, travel, valve
replacement, and/or intravenous drug use may be causative factors.
• Assess the consequences of the disease process (e.g., uremic symptoms). Inquire about
loss of appetite, generalized itching, tiredness, listlessness, nausea, easy bruising,
nosebleeds, facial swelling, leg edema, and shortness of breath.
• Inquire about symptoms of acute glomerulonephritis, including the following:
o Hematuria - This is a universal finding, even if it is microscopic. Gross hematuria
is reported in 30% of pediatric patients, often manifesting as smoky-, coffee-, or
cola-colored urine.
o Oliguria
o Edema (peripheral or periorbital) - This is reported in approximately 85% of
pediatric patients; edema may be mild (involving only the face) to severe,
bordering on a nephrotic appearance.
o Headache - This may occur secondary to hypertension; confusion secondary to
malignant hypertension may be seen in as many as 5% of patients.
o Shortness of breath or dyspnea on exertion - This may occur secondary to heart
failure or pulmonary edema; it is usually uncommon.
o Possible flank pain secondary to stretching of the renal capsule
• Ask about symptoms specific to an underlying systemic disease that can precipitate acute
GN
o Triad of sinusitis, pulmonary infiltrates, and nephritis, suggesting granulomatosis
with polyangiitis (Wegener granulomatosis)
o Nausea and vomiting, abdominal pain, and purpura, observed with Henoch-
Schönlein purpura
o Arthralgias, associated with systemic lupus erythematosus (SLE)
o Hemoptysis, occurring with Goodpasture syndrome or idiopathic progressive
glomerulonephritis
 o Skin rashes, observed with hypersensitivity vasculitis or SLE; also possibly due to
the purpura that can occur in hypersensitivity vasculitis, cryoglobulinemia, and
Henoch-Schönlein purpura
• Patients often have a normal physical examination and blood pressure; most frequently,
however, patients present with a combination of edema, hypertension, and oliguria.
• The physician should look for the following signs of fluid overload:
o Periorbital and/or pedal edema
o Edema and hypertension due to fluid overload (in 75% of patients)
o Crackles (i.e., if pulmonary edema)
o Elevated jugular venous pressure
o Ascites and pleural effusion (possible)
• The physician should also look for the following:
o Rash (as with vasculitis, Henoch-Schönlein purpura, or lupus nephritis)
o Pallor
o Renal angle (i.e., costovertebral) fullness or tenderness, joint swelling, or
tenderness
o Hematuria, either macroscopic (gross) or microscopic
o Abnormal neurologic examination or altered level of consciousness (from
malignant hypertension or hypertensive encephalopathy)
o Arthritis
Diagnosis
Initial Blood Tests
• CBC: A decrease in the hematocrit may indicate a dilutional anemia. In the setting of an
infectious etiology, pleocytosis may be evident.
• Kidney function studies: BUN and creatinine levels are elevated, indicating a degree of
renal compromise. The glomerular filtration rate (GFR) may be decreased
• Electrolytes: Potassium levels may be elevated in patients with significant renal
functional impairment
• ESR: usually increased
Urinalysis and 24-Hour Urine Study
• The urine is dark. Its specific gravity is greater than 1.020. RBCs and RBC casts are
present.
• Proteinuria is observed. With the qualitative estimation of proteinuria, determination of
high-molecular-weight (HMW) protein (e.g., fractional excretion of IgG [FEIgG]) and
low-molecular-weight (LMW) protein (e.g., alpha-1-microglobulin), may help predict the
clinical outcome
• The 24-hour urine protein excretion and creatinine clearance, though not indicated in the
emergency department (ED) setting, may be helpful to document the degree of renal
dysfunction and proteinuria
Streptozyme Test
• The streptozyme tests test includes many streptococcal antigens that are sensitive for
screening but are not quantitative, such as DNAase, streptokinase, streptolysin O, and
hyaluronidase.
• Increasing ASO titers or streptozyme titers confirm recent infection. In patients with skin
infection, anti-DNAase B (ADB) titers are more sensitive than ASO titers for infection
with Streptococcus.
Blood culture
• Blood culture is indicated in patients with fever, immunosuppression, intravenous (IV)
drug use history, indwelling shunts, or catheters.
• Cultures of throat and skin lesions to rule out Streptococcus species may be obtained.
Other laboratory tests
• Levels of antibody to nephritis-associated protease (NAPR) are elevated in streptococcal
infections with GN but not in streptococcal infections without GN.
• The antinuclear antibody test is useful for patients with acute GN and symptoms of
underlying systemic illness, such as systemic lupus erythematosus and polyarteritis
nodosa.
• They include:
o Anti-DNA antibodies
o Triglyceride levels
o Hepatitis B and C serologies
o Antineutrophil cytoplasmic antibody (ANCA)
o c-ANCA (i.e., if granulomatosis with polyangiitis [Wegener granulomatosis] is
suspected).
Radiography and Computed Tomography
• Chest radiography is needed in patients with a cough, with or without hemoptysis (e.g.,
granulomatosis with polyangiitis [Wegener granulomatosis], Goodpasture syndrome,
pulmonary congestion). Abdominal radiographic imaging (i.e., computed tomography
[CT]) is needed if visceral abscesses are suspected; also look for chest abscesses.
• CT scan of the head without contrast may be necessary in any patient with malignant
hypertension or altered mental status.
Ultrasonography and Echocardiography
• Bedside renal ultrasonography may be appropriate to evaluate kidney size, as well as to
assess the echogenicity of the renal cortex, exclude obstruction, and determine the extent
of fibrosis
• Echocardiography may be performed in patients with a new cardiac murmur or a positive
blood culture to rule out endocarditis or a pericardial effusion
Treatment
• Treatment of acute poststreptococcal glomerulonephritis (PSGN) is mainly supportive,
because there is no specific therapy for renal disease.
• When acute glomerulonephritis (GN) is associated with chronic infections, the
underlying infections must be treated.
• The renal function, blood pressure, edema, serum albumin, and urine protein excretion
rate should be monitored.
Antibiotics
• Antibiotics (e.g., penicillin) are used to control local symptoms and to prevent spread of
infection to close contacts.
Other agents
• Loop diuretics may be required in patients who are edematous and hypertensive, in order
to remove excess fluid and to correct hypertension.
• Vasodilator drugs (e.g., nitroprusside, nifedipine, hydralazine, diazoxide) may be used if
severe hypertension or encephalopathy is present.
Diet and Activity
 • Sodium and fluid restriction should be advised for treatment of signs and symptoms of
fluid retention (e.g., edema, pulmonary edema). Protein restriction for patients
with azotemia should be advised if there is no evidence of malnutrition.
• Bed rest is recommended until signs of glomerular inflammation and circulatory
congestion subside.

3. Chronic glomerulonephritis: etiology and pathogenesis, classification, clinical picture

according to the type of disease, complications, treatment.

• Chronic glomerulonephritis is a term used to refer to several renal diseases (usually

affecting both kidneys).
• Many of the diseases are characterized by inflammation either of the glomeruli or small
blood vessels in the kidneys.
• What leads to irreversible and progressive glomerular and tubulointerstitial fibrosis,
ultimately leading to chronic renal failure.
Etiology
• Glomerulonephritis is considered to be an immunologically mediated disorder with
involvement of cellular immunity (T lymphocytes, macrophages/dendritic cells), humoral
immunity (antibodies, immune complexes, complement), and other inflammatory
mediators (including cytokines, chemokines and the coagulation cascade).
• The immune response can be directed against known target antigens, particularly when
glomerulonephritis complicates infections, neoplasia or drugs.
• Primary glomerulonephritis may occur in genetically susceptible individuals following an
environmental insult.
• The genetic susceptibility is usually determined by major histocompatibility complex
(HLA) genes (HLA-A1, B8, DR2, DR3).
• The environmental factors may be drugs (hydralazine), chemicals (gold, silica,
hydrocarbons) or infectious agents.
Pathogenesis
• Although the pathogenesis is not fully understood, current evidence supports that most
cases of glomerulonephritis are due to an immunologic response to a variety of different
etiologic agents.
• The immunologic response, in turn, activates a number of biological processes
(complement activation, leukocyte recruitment, and release of growth factors and
cytokines) that result in glomerular inflammation and injury.
• Humoral immune response to a variety of inciting agents results in immunoglobulin
deposition formation and complement activation within the glomeruli.
• Deposition of immune complexes on glomerular structures induces mononuclear cell
infiltration, which leads to release of chemokines.
• Neutrophils, macrophages, and T cells are drawn by chemokines into the glomerular tuft,
where they react with antigens and epitopes on or near somatic cells or their structures,
producing more cytokines and proteases that damage the mesangium, capillaries, and/or
the glomerular basal membrane.
Classification of glomerulonephritis
• Glomerulonephritis may be classified on a three-tier basis:
o Etiology
o Histological appearances
o Clinical syndromes.
Etiological classification
• Chronic glomerulonephritis can be primary when the major problem appears to start in
the glomerulus, and secondary when kidney involvement is part of a systemic disease
(lupus erythematosus, diabetes mellitus, rheumatoid arthritis, amyloidosis, ankylosing
spondylitis, multiple myeloma, vasculitis, sarcoidosis, neoplasia).
Histological classification
• Renal biopsy identifies three main histological types:
o Proliferative
o Membranous
o minimal change lesions.
• The majority of cases of primary glomerulonephritis belong to the proliferative group
(>70%) which can be further subdivided to certain histological appearances.
o Non-proliferative
▪ Minimal change disease
▪ Focal segmental glomerular sclerosis
▪ Membranous glomerulonephritis
▪ Thin basement membrane disease
o Proliferative
▪ IgA nephropathy (Berger's disease)
▪ Mesangial proliferative glomerulonephritis
▪ Membranoproliferative glomerulonephritis (type I, II, III)
▪ Rapidly progressive glomerulonephritis (idiopathic crescentic
glomerulonephritis).
Clinical classification
• Glomerulonephritis may lead to a variety of clinical syndromes including:
o asymptomatic proteinuria
o hematuria
o acute nephritic syndrome
o nephrotic syndrome
o slowly or rapidly progressive renal failure.
Clinical features
• Main clinical features of chronic glomerulonephritis are:
o Proteinuria
o Hematuria
o Hypertension
o Impairment of renal function.
Asymptomatic proteinuria or hematuria.
• Patients with glomerular disease usually have some hematuria with varying degrees of
proteinuria
• Hematuria is typically asymptomatic
• As little as 3-5 red blood cells in the spun sediment from first voided morning urine is
suspicious
• However, when red blood cell casts or dysmorphic red blood cells are found in the
sediment, glomerulonephritis is likely.
• Sustained proteinuria >1–2 g/24 h is also commonly associated with glomerular disease.
• Patients often will not know they have proteinuria unless they become edematous or
notice foamy urine on voiding
• Proteinuria in most adults with glomerular disease is nonselective, containing albumin
and a mixture of other serum proteins.
Acute nephritic syndrome
• It includes producing 1-2 g/24 h of proteinuria, hematuria with red blood cell casts,
pyuria, hypertension, fluid retention (edemas formation), and a rise in serum creatinine
associated with a reduction in glomerular filtration rate.
• Acute nephritis syndrome may be in case of rapidly progressive glomerulonephritis
(crescentic glomerulonephritis), mesangiocapillary glomerulonephritis, IgA nephropathy.
• It also may be in case of post-streptococcal glomerulonephritis, infective endocarditis,
shunt nephritis, lupus erythematosus, vasculitis, Goodpasture's syndrome.
Nephrotic syndrome
• It describes the onset of heavy proteinuria (>3.0 g/24 h), hypertension,
hypercholesterolemia, hypoalbuminemia, edema/anasarca, and microscopic hematuria.
• The glomerular filtration rate in these patients may initially be normal or, rarely, higher
than normal, but with persistent hyperfiltration and continued nephron loss, it typically
declines over months to years.
• Nephrotic syndrome may be in the case of minimal change disease, focal segmental
glomerular sclerosis, mesangial proliferative glomerulonephritis, membranoproliferative
glomerulonephritis, membranous glomerulonephritis, and in cases of diabetes mellitus,
amyloidosis, lupus erythematosus, neoplasia.
Renal failure
• Rapidly progressive glomerulonephritis or crescentic glomerulonephritis - about 90% of
patients progress to end stage renal disease within weeks or months
• Focal segmental glomerulosclerosis: - about 80% of patients progress to end stage renal
disease in 10 years; patients with the collapsing variant (malignant focal segmental
glomerulosclerosis) have a more rapid progression; this form may be idiopathic or related
to HIV infection
 • Membranous nephropathy – about 20-30% of patients with membranous nephropathy
progress to chronic renal failure and end stage renal disease in 10 years.
• Membranoproliferative glomerulonephritis: - about 40% of patients with
membranoproliferative glomerulonephritis progress to chronic renal failure and end stage
renal disease in 10 years
• IgA nephropathy – about 10% of patients with IgA nephropathy progress to chronic renal
failure and end stage renal disease in 10 years.
• Poststreptococcal glomerulonephritis - About 1-2% of patients with poststreptococcal
glomerulonephritis progress to chronic renal failure and end stage renal disease; older
children who present with crescentic glomerulonephritis are at greatest risk.
• Lupus nephritis – Overall, about 20% of patients with lupus nephritis progress to chronic
renal failure and end stage renal disease in 10 years; however, patients with certain
histologic variants (eg, class IV) may have a more rapid decline.
Investigations
• Urine analysis.
o The presence of dysmorphic red blood cells, albumin or protein, red blood cell
casts suggests glomerulonephritis.
o Waxy or broad casts are observed in all forms of chronic kidney disease,
including chronic glomerulonephritis.
o Low urine-specific gravity indicates loss of tubular concentrating ability, an early
finding in persons with chronic kidney disease.
• Urinary protein excretion
o Urinary protein excretion can be estimated by calculating the protein-to-creatinine
ratio on a spot morning urine sample.
• Estimated glomerular filtration rate.
o The estimated creatinine clearance rate is used to assess and monitor the
glomerular filtration rate.
o The 2 formulas available for calculation of the glomerular filtration rate are the
Cockcroft-Gault formula, which estimates creatinine clearance, and the
Modification of Diet in Renal Disease (MDRD) Study formula, which is used to
calculate the glomerular filtration rate directly.
• Blood test.
o Anemia
o increased ESR may present in chronic glomerulonephritis.
• Biochemical blood test
o Serum creatinine and urea levels are elevated.
o Impaired excretion of potassium, free water, and acid results in hyperkalemia,
hyponatremia, and low serum bicarbonate levels, respectively.
o Impaired vitamin D-3 production results in hypocalcemia, hyperphosphatemia,
and high levels of parathyroid hormone.
o Low serum albumin levels may be present if the patient is nephrotic.
• Renal ultrasonography
o Obtain a renal ultrasonogram to determine renal size, to assess for the presence of
both kidneys, and to exclude structural lesions that may be responsible for
azotemia.
o Small kidneys often indicate an irreversible process.
 • Kidney biopsy
o In early stages, the glomeruli may still show some histologic evidence of the
primary disease.
o In advanced stages, the glomeruli are hyalinized and obsolescent.
o The tubules are disrupted and atrophic, and marked interstitial fibrosis and arterial
and arteriolar sclerosis occur.
Treatment
• Methods of treatment of patients with chronic glomerulonephritis are determined by the
characteristics of morphological changes in the kidney, clinical presentation, and
complications of the disease.
• The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
• Diet and Activity.
o Protein-restricted diets (0.4-0.6 g/kg/day) are controversial but may be beneficial
in slowing the decline in the GFR and reducing hyperphosphatemia (serum
phosphate > 5.5 mg/dL) in patients with serum creatinine levels higher than 4
mg/dL.
o Monitor these patients for signs of malnutrition, which may contraindicate protein
restriction.
o Educate patients about how potassium-rich diets help control hyperkalemia.
o Many dietary restrictions are no longer necessary with the initiation of renal
replacement therapy. Encourage patients to increase their activity level as
tolerated.
• Pharmacological treatment.
o Treatment may involve corticosteroids, cytotoxic agents (cyclophosphamide,
chlorambucil), plasmapheresis.
o Angiotensin-converting enzyme inhibitors, diuretics, calcium channel blockers
are used to treat hypertension, edemas and proteinuria.
o Patients with hypercholesterolemia secondary to nephrotic syndrome should be
treated with lipid-lowering agents since they are at increased risk for
cardiovascular disease (these include statins, fibrates and resinous sequesters of
bile acids).
o Low molecular weight heparin and dipiridamol may be used in case of
thrombophilia.
4. Chronic kidney disease. Main causes and classification. Differential diagnosis.
Treatment. Prognosis.
• Chronic kidney disease (CKD) is defined as an abnormality of kidney structure or
function that persists for > 3 months.
• The most common causes of CKD
o Diabetic kidney disease
o Hypertension
o Vascular disease
o Glomerular disease (primary or secondary)
o Cystic kidney diseases
o Tubulointerstitial disease
o Urinary tract obstruction or dysfunction
o Recurrent kidney stone disease
o Congenital (birth) defects of the kidney or bladder
o Unrecovered acute kidney injury
• The most common causes of CKD (Causes according to AMBOSS)
o Diabetic nephropathy (38%)
o Hypertensive nephropathy (26%)
o Glomerulonephritis (16%)
o Other causes (15%, e.g., polycystic kidney disease, analgesic misuse,
amyloidosis)
o Idiopathic (5%)
Classification of CKD according to GFR and albuminuria

Differential diagnosis
 • Chronic kidney disease (CKD) can have a variety of different presentations depending on
the stage of the disease and its cause, as well as patient factors such as age.
• A detailed history and physical examination are essential.
• In addition to routine laboratory studies, the workup should include calculation of the
estimated glomerular filtration rate (GFR), measurement of albumin levels, and
acquisition of radiologic studies.
• The differential diagnosis for CKD includes the following conditions, as well as the
disorders listed in the list below:
o Systemic lupus erythematosus (SLE)
o Renal Artery Stenosis
o Urinary Tract Obstruction
o Granulomatosis with Polyangiitis (Wegener Granulomatosis)
• Other differential Diagnoses
o Acute Kidney Injury
o Alport Syndrome
o Antiglomerular Basement Membrane Disease
o Chronic Glomerulonephritis
o Diabetic Nephropathy
o Multiple Myeloma
o Nephrolithiasis
o Nephrosclerosis
Treatment
• Early diagnosis and treatment of the underlying causes are imperative in patients with
chronic kidney disease (CKD). These steps may delay, or possibly halt, progression of
the disease.
• The medical care of patients with CKD should focus on the following:
o Delaying or halting the progression of CKD
o Diagnosing and treating the pathologic manifestations of CKD
o Timely planning for long-term renal replacement therapy
Measures indicated to delay or halt the progression of chronic kidney disease (CKD) are as
follows:
• Treatment of the underlying condition if possible
• Aggressive blood pressure control
• Treatment of hyperlipidemia
• Aggressive glycemic control per the American Diabetes Association (ADA)
recommendations (target hemoglobin A1c [HbA1C] < 7%)
• Avoidance of nephrotoxins, including intravenous (IV) radiocontrast media, nonsteroidal
anti-inflammatory drugs (NSAIDs), and aminoglycosides
• Use of renin-angiotensin system (RAS) blockers in patients with diabetic kidney disease
(DKD) and proteinuria
• Use of sodium–glucose cotransporter 2 (SGLT2) inhibitors
• Use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor
blockers (ARBs) in patients with proteinuria
• Use of nonsteroidal mineralocorticoid receptor (MR) antagonists
Blood pressure control
• Aggressive blood pressure control can help to delay the decline in kidney function in
patients with CKD. The recent guidelines suggest a target blood pressure of less than
130/80 mm Hg.
• The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice
guideline for blood pressure management for adults with CKD who are not receiving
dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg
• Use ACEIs or ARBs as tolerated, with close monitoring for renal deterioration and for
hyperkalemia. With every dose change, serum creatinine levels need to be monitored
Treat these pathologic manifestations of chronic kidney disease (CKD) as follows:
• Anemia
o When the hemoglobin level is below 10 g/dL, treat with an erythropoiesis-
stimulating agent (ESA) such as epoetin alfa or darbepoetin alfa; caution should
be exercised in patients with malignancy
• Hyperphosphatemia
o Treat with dietary phosphate binders and dietary phosphate restriction
• Hypocalcemia
o Treat with calcium supplements with or without calcitriol
• Hyperparathyroidism
o Treat with calcitriol, vitamin D analogues, or calcimimetics
• Volume overload
o Treat with loop diuretics or ultrafiltration
• Metabolic acidosis
o Treat with oral alkali supplementation
• Uremic manifestations
o Treat with long-term renal replacement therapy (hemodialysis, peritoneal dialysis,
or kidney transplantation)
• Cardiovascular complications
o Treat as appropriate
• Growth failure in children
o Treat with growth hormone
Diet
• Protein restriction
• Salt restriction
• Other dietary restrictions
o The following dietary restrictions may also be indicated:
o Phosphate restriction, starting early in CKD
o Potassium restriction
o Sodium and water restriction as needed to avoid volume overload
• The KDIGO clinical practice guideline recommends that patients with CKD undertake
regular exercise, as compatible with cardiovascular health, ideally for at least 30 minutes
5 times per week.
Prognosis
• Patients with chronic kidney disease (CKD) generally experience progressive loss of
kidney function and are at risk for end-stage renal disease (ESRD).
• The rate of progression depends on age, the underlying diagnosis, the implementation and
success of secondary preventive measures, and the individual patient.
• Timely initiation of chronic renal replacement therapy is imperative to prevent the uremic
complications of CKD that can lead to significant morbidity and death.

5. Acute renal insufficiency: etiology and pathogenesis, main clinical presentations, stages
of the disease, treatment.
• Acute renal failure (also called acute kidney failure or acute kidney injury) is
characterized by a rapid decline in glomerular filtration rate (GFR) over hours to days.
• Retention of nitrogenous waste products, oliguria, electrolyte and acid-base abnormalities
are frequent clinical features of it.
Causes
• According the causes, acute renal failure divides into three major categories:
o Prerenal
o Renal
o Postrenal.
• Prerenal
o Acute renal failure is adaptive response to severe volume depletion and
hypotension.
o Prerenal acute renal failure can complicate any disease that induces low blood
pressure, hypovolemia, low cardiac output, systemic vasodilatation, or selective
intrarenal vasoconstriction (renal artery stenosis, and renal vein thrombosis).
o Prerenal acute renal failure is generally reversible when renal perfusion pressure
is restored. Renal parenchymal tissue is not damaged.
• Renal (intrinsic) acute renal failure
o It is response to cytotoxic, ischemic, or inflammatory influences to the kidney,
and diseases with structural and functional damage of renal parenchyma.
o Common causes of it are
▪ injure of kidney by exogenous toxins, recent exposure to nephrotoxic
medications (aminoglycoside antibiotics, acyclovir, anticancer drugs) or
radiocontrast agents, or endogenous toxins (calcium, myoglobin,
hemoglobin, urate, oxalate, and myeloma light chains),
▪ glomerulonephritis
▪ acute tubular necrosis
▪ acute interstitial nephritis
▪ tumor lysis syndrome, collagen vascular diseases (systemic lupus
erythematosus, scleroderma)
▪ disseminated intravascular coagulation
▪ preeclampsia
o Renal parenchymal tissue is damaged.
 • Postrenal acute renal failure
o It is due to diseases associated with urinary tract obstruction.
o This may be related to
▪ benign prostatic hyperplasia
▪ kidney stones
▪ obstructed urinary catheter
▪ bladder stone
▪ bladder or ureteral or renal malignancy.
Clinical features
• The clinical course of acute renal failure is divided into 4 stages:
o Initial
o Stage of oliguria-anuria
o Diuretic stage
o Stage of recovery.
• Initial stage
o It lasts from a few hours to 6-7 days.
o The clinical picture is characterized by symptoms of the underlying disease.
o Symptoms of prerenal acute renal failure include thirst, dizziness, orthostatic
hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor
and dry mucous membranes.
o Ask about volume loss from vomiting, diarrhea, sweating, polyuria, or
hemorrhage.
o Hypovolemia, septic shock, and major surgery are important risk factors for
prerenal acute renal failure.
o Diagnosis of renal (intrinsic) acute renal failure requires careful review of the
clinical data and records for evidence of recent exposure to nephrotoxic
medications, radiocontrast agents, or endogenous toxins.
o Fever, arthralgias, and a pruritic erythematous rash following exposure to a new
drug suggest allergic interstitial nephritis, although systemic features of
hypersensitivity are frequently absent.
o Flank pain may be a prominent symptom following occlusion of a renal artery or
vein and with other parenchymal diseases distending the renal capsule (severe
glomerulonephritis or pyelonephritis).
o Acute renal failure in association with oliguria, edema, and hypertension, with an
"active" urine sediment (nephritic syndrome), suggests acute glomerulonephritis
or vasculitis.
o Postrenal acute renal failure may present with suprapubic and flank pain due to
distention of the bladder and of the renal collecting system and capsule,
respectively.
o Colicky flank pain radiating to the groin suggests acute ureteric obstruction.
Prostatic disease is likely if there is a history of nocturia, frequency, and hesitancy
and enlargement of the prostate on rectal examination.
o Neurogenic bladder should be suspected in patients receiving anticholinergic
medications or with physical evidence of autonomic dysfunction.
 • Stage of oliguria-anuria
o It lasts 5-10 days.
o The main symptom of this period is marked reduction in daily urine output, up to
complete anuria.
o Thus there is water retention in the body which leads to general hyperhydration.
Pulmonary edema, brain edema, anasarca, ascites, hydrothorax and
hydropericardium may develop as consequence of general hyperhydration.
o The state of patients deteriorates.
o They complain of weakness, loss of appetite, headache, nausea and vomiting.
Patients may have disturbed sleep at night and somnolence during the day.
o Hypertension is rare.
o Arrhythmias occur especially with hyperkalemia. The neurologic examination
reveals encephalopathic changes with asterixis and confusion; seizures may
ensue.
o Creatinine, urea, residual nitrogen levels rapidly rise in the blood.
o There are hyperkalemia, hyperphosphatemia, hypocalcemia, and hypochloremia,
metabolic acidosis. Acute uremia develops, because of what patients can die.
• Diuretic stage.
o With a favorable outcome stage of oliguria-anuria replaces by the diuretic stage.
o Urine begins to flow, the amount of which gradually increases and reaches the
normal daily urine output, and then develops polyuria.
o Hypokalemia can be observed in the phase of polyuria.
o Hyperasotemia gradually reduced, improving state of the patient.
• Stage of recovery.
o Perhaps complete recovery, when the level of residual urea nitrogen, creatinine
becomes normal.
o Urine analysis also normalizes.
o This is the longest period (3-6-12 months), during which recovered renal function.
o With the unfavorable outcome of a full recovery is not happening.
o Diseases proceeds as chronic glomerulonephritis with the possible outcome in
chronic renal failure.
Treatment
• Diet
o The objective of nutritional management during the stage of oliguria-anuria is to
provide sufficient calories and protein to minimize catabolism.
o Dietary protein restriction of 0.6 g/kg/d helps prevent metabolic acidosis.
• Medicinal treatment.
o Maintenance of volume homeostasis and correction of biochemical abnormalities
remain the primary goals of treatment of acute failure and may include the
following measures:
▪ Correction of fluid overload with loop diuretics (furosemide)
▪ Correction of severe acidosis with bicarbonate administration, which can
be important as a bridge to dialysis
▪ Correction of hyperkalemia
▪ Correction of hematologic abnormalities (anemia, uremic platelet
dysfunction) with measures such as transfusions.
o During acute renal failure, dialysis is often used to support renal function until
renal repair/recovery occurs.
o Absolute indications for dialysis include
▪ symptoms or signs of the uremic syndrome and management of refractory
hypervolemia
▪ Hyperkalemia
▪ Acidosis
▪ Volume overload unresponsive to diuretics
▪ Uremic complications (encephalopathy, pericarditis, and seizures).
6. Chronic renal insufficiency: etiology and pathogenesis, main clinical presentations,
classification, outcomes, treatment. Treatment of chronic renal insufficiency end stage.
Extrarenal blood purification methods. Kidney transplantation.
• Chronic kidney disease (CKD) is a condition characterized by a gradual loss of kidney
function over time CKD is defined as abnormalities of kidney structure or function,
present for >3 months, with implications for health.
• Chronic kidney disease or chronic renal failure, as it was historically termed – is a term
that encompasses all degrees of decreased renal function, from damaged at risk through
mild, moderate, and severe chronic kidney failure.
(For understanding)
• A normal kidney contains approximately 1 million nephrons, each of which contributes
to the total glomerular filtration rate (GFR).
• In the face of renal injury (regardless of the etiology), the kidney has an innate ability to
maintain GFR, despite progressive destruction of nephrons, as the remaining healthy
nephrons manifest hyperfiltration and compensatory hypertrophy.
• This nephron adaptability allows for continued normal clearance of plasma solutes.
• Plasma levels of substances such as urea and creatinine start to show measurable
increases only after total GFR has decreased to 50%.
Causes of CKD
• Diabetes mellitus (diabetic kidney disease)
• Arterial hypertension
• Vascular disease
• Glomerular disease (primary or secondary)
• Cystic kidney diseases
• Tubulointerstitial disease
• Urinary tract obstruction or dysfunction
• Recurrent kidney stone disease
• Congenital (birth) defects of the kidney or bladder
• Unrecovered acute kidney injury.
• The three most common causes of CKD are diabetes mellitus, hypertension, and
glomerulonephritis. Together, these cause approximately 75% of all adult cases.
Pathogenesis
CKD can be caused by a multitude of underlying conditions; however, once about half of the
total nephrons are lost, CKD progresses similarly, regardless of etiology.
• Underlying etiology: ↓ total number of nephrons (nephron mass), which leads to:
o ↑ Glomerular permeability → ↑ filtration of proteins, which are lost in the urine
(i.e., proteinuria)
o Activation of the RAAS
o Cytokine release
o ↑ Growth factors
• These changes lead to adaptive hyperfiltration:
o GFR may actually ↑ during this time
o Occurs as a compensatory mechanism
o Leads to ↑ intraglomerular capillary pressure (i.e., glomerular hypertension)
• ↑ Intraglomerular capillary pressure and inflammatory mediators cause damage to the
remaining nephrons.
• Damage to the remaining nephrons continues the positive feedback loop, and CKD
progresses
Classification
The KDOQI (Kidney Disease: Improving Global Outcomes) classification of the stages of CKD
is as follows:
• Stage 1: Kidney damage with normal or increased GFR (90 mL/min/1.73 m2)
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2)
• Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2)
• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2);
• Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 or dialysis).
Clinical features
• The symptoms of chronic kidney disease often develop slowly and are nonspecific.
• Patients with stages 1-3 chronic kidney disease are frequently asymptomatic.
• Clinical manifestations resulting from low kidney function typically appear in stages 4-5.
• Manifestations include
o Fatigue
o Weakness
o Malaise
• Gastrointestinal complaints, such as anorexia, nausea, vomiting, a metallic taste in the
mouth, and hiccups, are common.
• Neurologic problems include irritability, difficulty in concentrating, insomnia, subtle
memory defects, restless legs, and twitching.
• Pruritus is common and difficult to treat.
• As uremia progresses, decreased libido, menstrual irregularities, chest pain from
pericarditis, and paresthesias can develop.
Physical examination
• The skin is dry, with pruritus and ecchymosis, bruises.
• Rarely seen in the current era is uremic frost, a cutaneous reflection of end stage of CKD.
• Uremic fetor, a urine-like odor on the breath, derives from the breakdown of urea to
ammonia in saliva.
• Cardiopulmonary signs may include rales, cardiomegaly, edema, and a pericardial
friction rub.
• Hypertension is common.
• Gastritis, peptic disease, and mucosal ulcerations at any level of the gastrointestinal tract
occur in uremic patients and can lead to abdominal pain, nausea, vomiting, and
gastrointestinal bleeding.
• Mental status can vary from encephalopathy with decreased concentration to confusion,
stupor, and coma.
• Myoclonus and asterixis, restless leg syndrome, are additional signs of uremic effects on
the central nervous system.
Investigations
• Estimated glomerular filtration rate is very important in diagnostics of CKD.
• Blood test
o A normocytic, normochromic anemia is observed as early as stage 3 CKD and is
almost universal by stage 4.
o The primary cause in patients with CKD is insufficient production of
erythropoietin by the diseased kidneys.
o Additional factors include iron deficiency, acute and chronic inflammation with
impaired iron utilization, shortened red cell survival in the uremic environment.
o Leukopenia and thrombocytopenia are common.
• Biochemical blood test
o Creatinine and urea level rises as kidney function worsens.
o Hypoalbuminemia, hypertriglyceridemia, hyperkalemia, low bicarbonate levels,
metabolic acidosis are common disturbance in advanced CKD.
 • Hemostasis assessment
o Patients with later stages of CKD may have a prolonged bleeding time, decreased
activity of platelet factor III, abnormal platelet aggregation and adhesiveness, and
impaired prothrombin consumption.
o Clinical manifestations include an increased tendency to bleeding and bruising,
prolonged bleeding from surgical incisions, menorrhagia, and spontaneous
gastrointestinal bleeding.
• Renal ultrasonography
o Useful to screen for hydronephrosis, which may not be observed in early
obstruction, or for involvement of the retroperitoneum with fibrosis, tumor, or
diffuse adenopathy; small, echogenic kidneys are observed in advanced renal
failure
• Retrograde pyelography
o Useful in cases with high suspicion for obstruction despite negative renal
ultrasonograms, as well as for diagnosing renal stones
• Computed tomography scanning
o Useful to better define renal masses and cysts usually noted on ultrasonograms;
also the most sensitive test for identifying renal stones
• Magnetic resonance imaging
o Useful in patients who require a CT scan but who cannot receive intravenous
contrast; reliable in the diagnosis of renal vein thrombosis
• Biopsy
o Percutaneous renal biopsy is generally indicated when renal impairment and/or
proteinuria approaching the nephrotic range are present and the diagnosis is
unclear after appropriate workup.
Treatment
• Early diagnosis and treatment of the underlying cause and/or the institution of secondary
preventive measures are imperative in patients with chronic kidney disease.
• These steps may delay, or possibly halt, progression of the disease.
• The medical care of patients with CKD should focus on the following:
o Delaying or halting the progression of CKD
o Treating the pathologic manifestations of CKD
o Timely planning for long-term renal replacement therapy.
• Other than specific treatments for certain etiologies, it is important to identify and address
risk factors for progression of CKD, to address common complications, and to consider
preventive measures needed for patients with decreased GFR . Risk factors for disease
progression
• Nonmodifiable risk factors
o Underlying genetic disease (e.g., PKD)
o African descent
o Male sex
• Modifiable risk factors:
o Proteinuria > 1 g/day is strongly associated with progression
o Hypertension
o Metabolic acidosis
o Obesity (↑ glomerular capillary pressure)
 o High-protein diet (↑ glomerular capillary pressure)
o Smoking (leads to vascular inflammation)
• Lifestyle modifications to prevent disease progression
o Smoking cessation
o Dietary changes (assisted by a nutritionist):
▪ Low-protein diet:
• Goal: approximately 0.6–0.8 g/kg/day dietary protein if GFR < 60
mL/min and non-nephrotic
• Do not restrict intake if nephrotic syndrome (> 3.5 g/day
proteinuria) is present.
▪ Low- sodium diet (< 2 g of sodium /day or 5 g/day of NaCl)
▪ Low-phosphorus diet (or take oral phosphorus binders with meals)
o Exercise
o Weight loss
• Measures indicated to delay or halt the progression of chronic kidney disease are as
follows:
o Treatment of the underlying condition if possible.
o Aggressive blood pressure control to target values per current guidelines.
o Treatment of hyperlipidemia to target levels per current guidelines.
o Aggressive glycemic control per the American Diabetes Association
recommendations (target HbA1C < 7%).
o Avoidance of nephrotoxins, including intravenous radiocontrast media,
nonsteroidal anti-inflammatory agents and aminoglycosides.
o Use of angiotensin-converting enzyme inhibitors or angiotensin- receptor blockers
in patients with proteinuria.
• Treat these pathologic manifestations of chronic kidney disease as follows:
o Anemia is treated with erythropoiesis-stimulating agents such as epoetin alfa or
darbepoetin alfa.
o Hyperphosphatemia: Treat with dietary phosphate binders and dietary phosphate
restriction.
o Hypocalcemia: Treat with calcium supplements with or without calcitriol.
o Hyperparathyroidism: Treat with calcitriol, vitamin D analogues, or
calcimimetics.
o Volume overload: Treat with loop diuretics or ultrafiltration.
o Metabolic acidosis: Treat with oral alkali supplementation.
o Uremic manifestations: Treat with long-term renal replacement therapy
(hemodialysis, peritoneal dialysis, or renal transplantation).
o Cardiovascular complications: Treat as appropriate.
o Growth failure in children: Treat with growth hormone.
• Indications for renal replacement therapy in patients with chronic kidney disease include
the following:
o Severe metabolic acidosis
o Hyperkalemia
o Pericarditis
o Encephalopathy
o Intractable volume overload
 o Failure to thrive and malnutrition
o Peripheral neuropathy
o Intractable gastrointestinal symptoms
o In asymptomatic adult patients, a glomerular filtration rate (GFR) of 5-9
mL/min/1,73 m², irrespective of the cause of the CKD or the presence of absence
of other comorbidities.
• Diet
o Protein restriction. Protein restriction early in chronic kidney disease as a means
to delay a decline in the glomerular filtration rate is controversial; however, as the
patient approaches CKD stage 5, this strategy is recommended in adults (but not
in children) to delay the onset of uremic symptoms.
• Salt restriction
o Reduction in salt intake may slow the progression of diabetic CKD, at least in part
by lowering blood pressure.
o The dietary sodium recommendation for the general population in public health
guidelines is less than 5-6 g daily.
• Other dietary restrictions
o The following dietary restrictions may also be indicated.
o Phosphate restriction starting early in CKD. Potassium restriction.
o Sodium and water restriction as needed to avoid volume overload.
• Fruits and vegetables
o It was showed that increasing the amount of alkali-inducing fruits and vegetables
in the diet may help to reduce kidney injury

Kidney transplantation (toronto)

• Provides maximum replacement of GFR
• Preferred modality of RRT in CKD, not AKI
• Best way to reverse uremic signs and symptoms
o renal transplantation has been shown to have improved long-term patient survival
and greater quality of life over dialysis
• Native kidneys usually left in situ
• 2 types: deceased donor, living donor (related or unrelated)
• Living donor transplants have been shown to have better short- and long-term outcomes
than deceased donor transplants
• Kidney transplanted into iliac fossa, transplant renal artery anastomosed to external iliac
artery of recipient
• Induction immunosuppression with IV thymoglobulin or basiliximab, followed by
maintenance oral immunosuppression with an oral immunosuppression cocktail (usually
corticosteroids, calcineurin inhibitor, anti-metabolite)
• Long-term monitoring of cyclosporine and tacrolimus levels are required
• 1 yr renal allograft survival rates ≥90%
7. Chronic pyelonephritis: etiology and pathogenesis, clinical picture, diagnostics,
treatment. Preventing exacerbations 80
Etiology
• Infections (bacteria, viral, fungi, mycoplasmas) o
o Most common is gram positive and negative conditionally pathogenic
bacteria many of which belongs to human microflora (E. coli and
enterococci)
• Predisposing factors
o Postponed acute PN
o Urological manipulations
o Retrograde pyelography
o Hypothermia
o Disorders of urodynamics
o Pregnancy
o DM
o Chronic infections in ENT, oral cavity
Pathogenesis
• Urogenic spread (ascending) – main path, prevails in chronic PN and in women
• Hematogenous spread – against background of sepsis or episodes of bacteremia,
prevails in acute PN and in men
• Predisposing factors contribute to fixation of pathogenic microorganism in
parenchyma and parenchymal hypoxia contribute to their survival
• There is reduced resistance to infections also
• Infectious pathogen lingers in venous capillaries of kidney, where distributed in
interstitial tissue, causing development of purulent inflammatory process
• First the medullary layer is affected due to less intensive blood supply and high
osmolarity which contribute to survival of L-form bacterial is nit, as well as high
content of ammonia which suppress complement component which can delay
phagocytosis and reduce bactericidal effect of antibodies
Classification

Clinical Presentation
• Subjective
o General complaints – weakness, decreased performance, appetitive,
headache o
o Pain in lumbar region, often one-sided, aching, less often intense, can
radiate to lower abdomen, genitals, thigh
o Dysuria (painful frequent urination due to concomitant cystitis, moderate
polyuria due to tubular damage)
o Discharge of cloudy urine, sometimes with an unpleasant odor, giving a
cloudy sediment when standing
o Chilling with severe exacerbation, sometimes transient rises in body
temperature up to 38.5-390 with normalization by morning
o Increased BP, headache, dizziness
• Objective
o Pallor of skin (dry, gray tint) and visible mucosa
o Pasty face (but not pronounced edema)
o Soreness when feeling or tapping lumbar region
o Tofilo symptoms – in supine, patient bends led in hip and presses thigh to
abdomen, pain in lumber increases especially after a deep breath
o Increase left boarder of heart, muffled tone, quiet systolic murmur at apex
o With progression – CRF – greater decrease in renal function during
exacerbation (fever, pyuria, increase percentage of active leucocytes) and
some recovery of renal functions (increase relative density and
improvement of biochemical) when subsiding inflammatory process
influenced by treatment
Diagnostics
• Laboratory
o Blood – anemia, leukocytosis with left shit, increased ESR
o Urine – turbid, alkaline reaction, decrease density, moderate proteinuria,
microhematuria, severe leucocyturia (>25,000), possible cylinduria,
bacteriuria (100,000)
o Nichperenko – leucocyturia over erythrocyturia
o Zimnitsky – decrease in urine density during day
o Biochemical – increase saliac acid, fibrin, serocumoid, alpha and gamma
globulins, creatinine and urea, CRP
o Prednisolone test – positive if in one portion number of WBC doubles and
active WBC
o Sterngeimer-Malbin – staining with gentian violet and safranin (“pale”
WBC with pale blue protoplasm and nucleus, enlarged, multilobular
nucleus, granularity in cytoplasm)
• Instrumental
o Plain radiography of kidney – decrease in size
o Excretory urography and retrograde pyelography – local spasms of renal
pelvis deformation, filling defects, atony, sclerosis, Hudson’s symptom
o Chromotocytoscopy – impaired renal excretory function
o Radioactive renography – violation of excretory segment
o Radioisotope kidney scanning – asymmetry in size, diffuse nature of
changes
o USG – asymmetry in size, rough contours, dilated calyx and pelvis,
↓thickness of cortex
o Biopsy
Treatment
• Mode
o In latent course with normal BP without renal function impairment – no
restriction
o In exacerbation – bed rest
• Diet
o Daily energy 2000-2500kcal
o Volume of fluid – 2-3L
o Limit salt – 4g/day
• Antibacterial therapy
o Outpatient
▪ Drugs of choice (10-21 days)
• Augmentin 625mg TDS
• Levofloxacin 250mg OD
• Lomefloxacin 400mg BD
• Norfloxacin 400mg BD
• Pefloxacin 400mg BD
• Ciprofloxacin 250mg BD
▪ Alternative (10-14 days)
• Co-trimoxazole 480mg BD
• Cefixime 400mg OD
• Ceftibuten 400mg OD
o Inpatient
▪ Drugs of choice (10-14 days)
• Augmentin 1.2g TDS IV
• Levofloxacin 500mg OD IV
• Ofloxacin 200mg BD IV
• Pefloxacin 400mg BD IV
• Ciprofloxacin 200mg BD IV
▪ Alternative (10-21 days)
• Gentamycin 80mg TDS IV/IM
• Imipenem + Celestin 500mg BD IM
• Cefotaxime 1-2g BD/TDS IV/IM
• Ceftazidime 1-2g BD/TDS IV/IM
• Ceftriaxone 1g OD IM
• Cefoperazone 2g BD/TDS IV
o Criteria for effectiveness of Abx
▪ Early (2-3 days) – reduction of fever, intoxication, improve well-being.
Normalization of kidney function, sterility of urine after 3-4 days of
treatment
▪ Late (14-20 days) – no relapses of fever, no chills within 2 weeks after end
of Abx, negative bacteriological examination of urine on 3-7th day after
Abx
 ▪ Final (1-3 months) – no repeated UTI within 12 weeks after Abx
• Physical therapy
o Electrophoresis on kidney area (furadonin, erythromycin, calcium chloride)
o UHF (in absence of urolithiasis)
o Thermal procedures on kidney (diathermy, therapeutic mud, paraffin)
• Herbal medicine
o With diuretic effect (juniper, parsley, birch leaves)
o With anti-inflammatory effect (cranberry and bearberry leaves)
o With antiseptic effect (garlic, onion, chamomile)
Prevention
• Timely elimination of foci of infection, identification of bacteriuria, appointment of
appropriate antibiotic therapy.
• Correction of hemodynamic disorders.
• Periodic examination of a previously affected kidney.
• A widespread technique of anti-relapse therapy is based on repeating courses of
combined antibacterial (10 days of each month) and herbal medicine (20 days following
the use of an antibacterial agent).
• They suggest changing the antibacterial drug every month.
8.Tubulointerstitial nephritis. Etiology, pathogenesis, clinical features, treatment.
Causes
• Drugs (Abx, sulfonamides, NSAIDs, barbiturates, captopril, cimetidine, diuretics)
• Intoxication with ethanol, ethylene glycol, mercury, lead, cadmium • Treatment with
vaccines and serums, protein preparations
• Hyperuricemia (gout, psoriasis, sarcoidosis, lymphoproliferative diseases)
• Hyperoxaluria (excess oxalates and ascorbic acid in food, hereditary oxalosis)
• Infections (TB, legionella, leptospirosis, hanta) • Idiopathic
Diagnostics
• Clinical picture
o Common signs
▪ Develops – edema, hypertension, moderate selective proteinuria (low
molecular weight), microhematuria, abacterial leucocytruia
▪ Polyuria with a reduced specific gravity
▪ Electrolyte shifts – hypokalemia and hyponatremia
o Acute
▪ Acute onset of fever, back pain, skin manifestations (hemorrhagic and
urticarial rashes)
▪ Eosinophilia and anemia
▪ Polyuria and microhematuria
o Chronic
▪ Gradual increase in water electrolyte balance
▪ Disorders of concentration function of kidneys and anemia
o Analgesic nephropathy
▪ Usually women with headache, anemia and symptoms of GI dysfunction,
renal function stabilizes with complete cessation of medication
• Blood – Eosinophilia (typical), anemia
• Urine – microhematuria predominate, abacterial leucocyturia, poorly expressed
proteinuria, polyuria with reduced specific gravity
• Protein-enzymatic studies of urine – ratio of alpha1 macroglobulin and concentration of
N-acetyl-beta-D-glycosaminidase
• Biochemical – hypokalemia and hyponatremia
• USG – reduction in length of both kidneys with uneven contours calcification of papillae
• Kidney biopsy – edema and infiltration of interstitium, changes in tubules and intact
glomeruli
Treatment
• Stop the provocation factors – kidney function usually restored and most patients recover
• Maximum exclusion of other drugs
• Antihistamines (diphenhydramine, fencarol)
• Polyuria and intoxication – IV drip 5% glucose, Ringer’s, rheopolyglucin, correction of
electrolyte
• Acute – prednisolone 20-30mg/day for several weeks and gradually reduce with
anticoagulants (heparin) and antiplatelets (courantil)
• CRF – kidney transplantation. Dialysis
9. Nephrotic syndrome: etiopathogenesis, clinical picture. Differential diagnosis.
Treatment.
Nephrotic syndrome
• Proteinuria – >3.5g/day
• Hypoalbuminemia – <30g/L
• Edema (latent to anasarca)
• Hyperlipidemia (hypercholesterolemia >5.1mmol/L, hypertriglyceremia,
hyperphospholipidemia)
Most Frequent Diseases Accompanied
• Glomerulonephritis
o Can develop in any morphological forms of GN
o In children – minimal change. In adults – membranous and focal-segmented
• Mixed connective tissue disorders and systemic vasculitis
o SLE
o Schoenlein-Henoch purpura
o Wegener’s disease
o Microscopic polyangiitis
o Nodular periarteritis
o Sjogren’s syndrome
o Serum sickness
o Erythema multiforme
o Cryoglobulinemia
• Amyloidosis of kidney
Pathogenesis
• Proteinuria
o Damage to glomerular structure (Immune inflammation in GN, amyloid
deposition in amyloidosis, glycosylation of basement membrane in DM, toxic
when exposed to drugs) Decrease in negative charge of basement
membrane and increase in interaction with negatively charged protein
molecules increase in permeability of glomerular filter
• Hypoproteinemia
o Loss of protein through urine and intestine, increase protein catabolism,
insufficient compensatory protein synthesis in liver, transduction into edematous
fluid
• Hyperlipidemia
o Increase synthesis of lipoprotein in liver due to decrease in metabolism and
accumulation of mevalonate in blood
o Decrease in their catabolism due to decrease in activity of LPL and loss of
enzymes that break down lipids (lecithin-cholesterol-acetyl transfer) in urine
o With increase synthesis of lipoproteins in response to hypoalbuminemia – change
in structure of LDL with decrease in availability for lipolytic enzyme lipiduria
(1g/day) due to hyperlipidemia and increase permeability of glomerular filter
 • Hypercoagulation
o Loss in urine and decrease synthesis of antithrombin III, decrease in activity of
anticoagulant and fibrinolytic proteinases, activation of kinin-kallikrein system,
an increase in aggregation properties of platelets
• Edema
o hypoproteinemia, renal sodium retention and systemic vascular permeability
disorder
o In hypovolemia, due to proteinuria, hypoalbuminia, hypovolemia with water
transduction in interstitial region, activation of RAA system, ADH and
catecholamine develop sodium and water retention
o In hypervolemia, sodium retention occurs, increased capillary hydrostatic pressure
and fluid movement in interstitium.
Clinical manifestations
• General weakness, rapid fatigue, malaise, headache, lack of appetite, dry mouth
• Edema, oliguria, discomfort or heaviness in lumbar region
• Patient inactive, adynamic, pale skin ]
• With severe – dry hair, hair loses its shine, fall out
• Edema pronounced in face, feet legs
o Appears on feet at the end of the day or in face in the morning, then spread to
while body, localizing depending on position of the body
o Most pronounced in areas with highest intravascular hydrostatic pressure (ankles
and feet) and lowest tissue hydrostatic pressure (genital, periorbital)
o General edema – ascites, hydropericardium, hydrothorax
• With ascites – diarrhea, bloating, nausea and vomiting
• With hydrothorax and hydropericardium – SOB
• BP can be normal or increased. Muted tone and tachycardia
Diagnostics
• Blood – Increased ESR, leukocytosis, mild hypochromic anemia
• Biochemical
o Hypoproteinemia (<50-60g/L)
o Hypoalbuminemia (<30g/L)
o Increased alpha and gamma globulins
o Hyperlipidemia (>6.5mmolL)
o Serum has a milky white appearance
o Increase creatinine, urea
o Hypocalcemia, hypokalemia
• U/E
o Massive proteinuria (>3.5g/day)
o Microhematuria, leucocyturia, cylinduria (hyaline, granular, waxy)
o Birefringent lipids
o Oliguria with high density (1030-1040)
• Coagulogram – signs of hypercoagulability
• Reberg-Tareev test – reduced GFR, tubular reabsorption increased
• USG of kidney and renal vessels, nephroscintigraphy
• Biopsy – congenital NS, child >8years at onset, steroid resistant, frequent relapse.
Treatment
• Hospitalization – newly diagnosed, relapsed, complicated
• Non-pharmacological therapy
o Mode – dosed motor activity (immobilization contributes to development of
thrombosis), physical therapy, rehabilitation of foci of infection, prevention of
constipation. With severe edematous syndrome bed rest indicated
o Diet – limit salt intake 3.5-4g/day or salt free diet rich in potassium. Moderate
restriction of proteins 0.8-1g/kg and animal fats slow progression of diabetic
nephropathy and non-diabetic kidney disease
• Medical
o Treatment of underlying diseases
o Control of glycemia in patients with diabetic nephropathy
o In primary and secondary GN – immunosuppressive therapy contributes to
remission of NS
▪ Prednisolone 1-2mg/kg/day in 2-4 doses (max in morning and last at
1600)
▪ Then prednisolone switched to every other day
▪ Pulse therapy (methylprednisolone and/or cyclophosphamide 1g for 3
days)
▪ Cyclophosphamide 2-2.5mg/kg/day IV for 8-12 weeks
▪ Chlorambucil 0.15-0.2mg/kg/day PO for 8-10 weeks
o Reduction of severity of proteinuria – ACE-I and/or ARB in diabetic nephropathy
with/without HTN
o Temporary antiproteinuric effect – NSAIDs
o Severe NS – parenteral administration of protein (albumin, plasma)
o Hypolipidemic therapy – statins
o Diuretics
▪ Thiazide – GFR 25-30ml/min (hypothiazide 25-100mg/day)
▪ Loop – furosemide 20-40 to 400-600mg/day or IV 1.2g/day)
▪ Potassium-sparing (spironolactone 100-600mg/day) + loop diuretics
▪ In edematous torpid syndrome – 100ml of 20% salt-free solution of
albumin or dextran (rheopolyglucan) with furosemide 200-240mg IV
added to diuretics
▪ Ultrafiltration of plasma with hyperhydration or no effect from diuretics –
laxative 30mg of MgSO4
o Elimination of hypercoagulation – anticoagulants
▪ Heparin 5000U QDS S/C
▪ Fraxiparin 0.3-0.6ml OD/BD S/C
▪ Dalteparin 0.2ml OD/BD S/C
▪ Enoxaparin 20-100mg OD/BD S/C
o For secondary infections – Abx
• Renal replacement therapy – GFR <30ml/min o Hemodialysis o Peritoneal dialysis o
Renal transplantation 87. Amyloidosis of the kid
10. Renal disease in diabetes, gout, systemic disease connective tissue, vasculitis. Diagnostic
capabilities. Principles of treatment.

Renal disease in diabetes

• Diabetes is the leading cause of kidney failure, accounting for 44% percent of new cases.
• Current research suggests that control of high blood pressure is a key factor in slowing
this disease.
• Strict control of blood sugar levels and reduction of dietary protein intake are also
important.
• Treatment to prevent diabetic kidney disease should begin early — before kidney damage
develops.
• Diabetes damages small blood vessels throughout the body, affecting the kidneys as well
as other organs and tissues including skin, nerves, muscles, intestines and the heart.
• Patients with diabetes can develop high blood pressure as well as rapid hardening of the
arteries, which can also lead to heart disease and eye disorders.
• High blood pressure may be the most important predictor for diabetics developing
chronic kidney disease.
• Specific high blood pressure medications such as angiotensin converting enzyme (ACE)
inhibitors and the angiotensin-2 receptor blockers (ARBs) may be the most effective in
preventing diabetic kidney disease.
• It is important for diabetics to keep their blood pressure lower than 130/80.
• Some of the signs that diabetics may be developing chronic kidney disease include
protein in the urine, high blood pressure, leg swelling or cramps, increased need to
urinate (especially at night), abnormal blood tests (glomerular filtration rate, GFR), less
need for insulin or anti-diabetic pills, nausea and vomiting, weakness, pallor and anemia,
itching and diabetic eye disease.
• Treatment for diabetic kidney disease includes controlling blood pressure and blood
sugar levels, reducing dietary protein intake, avoiding medications that may damage the
kidneys, treating urinary tract infections and exercise and weight loss

Renal disease in gout

• Uric acid moves through blood to kidneys.
• The kidneys then add that uric acid to urine, so it can be excreted.
• However, sometimes uric acid in the blood gets too high.
• This happens because: the body makes too much uric acid, and/or the kidneys can’t add
enough uric acid to urine, so it builds up in blood (the more common reason).
• That’s why having gout and high uric acid may be signs of kidney disease.
Diagnosis
• A physical exam will check for signs and symptoms related to gout.
• Medical and family history will also be reviewed.
• The levels of uric acid will be checked in the blood and urine.
• Fluid from an affected joint might also be examined for gout crystals.
• Test for gout can include the following:
o Arthrocentesis, also called synovial fluid aspiration of the joint:
 ▪ A needle is used to take fluid from a joint to see if it has uric acid crystals.
The fluid is studied under a microscope to find crystals.
▪ This method is the gold standard for diagnosing gout.
o Imaging:
▪ Ultrasound, CT scan, and magnetic resonance imaging (MRI), have also
been used for diagnosing gout.
o Uric acid level:
▪ The normal range depends on age, gender. Uric acid level should stay
below 6.0 mg/dL to prevent gout attacks.
Treatment principles
• Sudden gout flares:
o non-steroidal inflammatory drugs (NSAIDs) like ibuprofen and naproxen are pills
usually avoided in CKD.
o Colchicine is often used, but the dose is lowered for people with CKD.
o Cortisone is sometimes used in CKD, and can be given as a pill or a shot.
• Long-term treatment to lower uric acid and prevents gout flares:
o Allopurinol, febuxostat, probenecid, and lesinurad.
o Pegloticase is given through a vein for severe gout that doesn’t get better with
other drugs
• Lifestyle changes
o Avoid or limit high purine foods and drinks like organ meats, shellfish, beer, and
products with high-fructose corn syrup.
o Eating less animal protein like meat keeps the urine less acid, which may lower
the risk for gout flares and kidney stones.

Renal disease in vasculitis

• Renal vasculitis, also called ANCA glomerulonephritis, is an autoimmune disease that
causes white blood cells to attack the glomeruli
• This causes swelling and damage to the capillaries
• When the glomeruli can’t filter the blood, protein and blood leak into the urine, which
can lead to loss of kidney function or kidney failure in severe cases.
• There are two main types of renal vasculitis:
o Microscopic polyangiitis (MPA): affects small arteries and veins, and it can also
affect joints, lungs, gastrointestinal system, nerves, and skin
o Granulomatosis with polyangiitis (Wegner’s disease): causes swelling of the
blood vessels in kidneys, lungs, sinuses, and throat
Diagnoses
Biopsy
• A kidney biopsy is a tissue sample taken from the kidney through a needle and analyzed
at a lab.
• Results help doctors to diagnose the type of kidney disease, assess kidney damage, and
determine the best treatment.
Blood Tests
• Blood tests can include blood cell counts, electrolyte levels, and kidney function.
• If vasculitis is suspected, the doctor will look for anti-neutrophil cytoplasmic antibodies
(ANCA), the antibodies that cause white blood cells to attack the kidneys.
Urinalysis
• Urine samples are sent to a lab to look for red blood cells, white blood cells, infections, or
excessive protein in the urine.
• This sample can be taken from a urine collection over 24-hours, or straight from the
bladder during catheterization.
Treatments
• Medicines
o Medicines to lower immune system activity, such as steroids and
cyclophosphamide, which help reduce the swelling and damage of vasculitis.
• Total Plasma Exchange (TPE)
o Total plasma exchange, also called plasmapheresis, is a blood-cleaning therapy
that removes blood through a needle or thin, catheter (thin, flexible tube). The
plasma is separated, cleaned, and returned to body.
o TPE is used in combination with other treatment therapies for glomerular
diseases.
• Continuous Renal Replacement Therapy (CRRT)
o This therapy includes hemodialysis and other mechanical waste filtration
techniques performed slowly over long periods of time (12 to 24 hours).
 1. Etiology, pathogenesis, clinical picture, classification, diagnostics, treatment of iron-
deficiency anemia.
It is a disease caused by violation of the synthesis of hemoglobin and the production of red blood
cells, due to insufficient content of iron in the patient’s body
Pathogenesis
• There is decrease in amount of hemoglobin and RBC in the blood below the level
necessary to ensure oxygen transport function of the blood
• Under these conditions, in or der to maintain tissue respiration at a sufficient level, body
tries to increase the rate of circulation of RBC in the blood stream
• There is compensatory hyperfunction of the circulatory system in form of an increase in
shock and minute cardiac output, tachycardia, breakdown of which can lead to heart
failure
• Iron deficiency in addition to the negative impact on hematopoiesis causes degenerative
changes in almost all organs, especially pronounced and visible in tissue structures that
require intense cellular regeneration of epithelial tissues and their derivatives, endocrine
and, especially, the exocrine glands
Clinical Presentation
• Anemic syndrome
o Increased pulse, shock and minute blood volume, and hypertrophy of left
ventricle
o Ischemic, dystrophic changes in internal organs – variety of functional disorders
o Palpitation, tinnitus, SOB with moderate physical activity, muscle weakness,
dizziness, flashing dark flies in the eyes. Tendency to arterial hypotension
o Functional disorders in CNS – unmotivated weakness, reduced physical and
mental ability to work, loss of interest in earning, difficulties in volitional
concentration
o Objectively – pallor, tachycardia, functional systolic noise over all points of
auscultation
• Sideropenic syndrome
o Specific for IDA – lack of iron leads to deficiency of iron containing enzymes
(cytochrome oxidase), necessary for vital activity of absolutely all cells of the
body
o But first of all, the activity of intensively proliferating tissue structures – epithelial
integuments, hematopoietic tissue, exocrine and endocrine glands, disputed
o Atrophic changes in skins, hair, nails and mucosa. Dystrophy and functional
insufficiency of glands of internal and external secretion
o Thinning, lethargy, dry skin, fragility and hair loss
o Nail bend acquire a spoon shape (koilonychia), thin, brittle
o Smooth, shiny and crimson tongue. Burning, tingling sensation in tongue
o Angular stomatitis – ulcerations, cracks in corners of mouth
o Damage to epithelium and pharynx – choking, dysphagia for dry food, painful
spasm of upper third of esophagus – sideropenic dysphagia Plummer-Vinson
o Atrophy of secretary epithelium of stomach – decrease in secretory ability of
organ up to histamine resistant achlorhydria
o Secretory activity of salivary gland and pancreas decreases
 o Dystrophic changes in mucosa – violation of parietal digestion, absorption and
maintenance of adequate microflora in intestine
o Defeat of epithelium and sphincter of urinary system – imperative urge to urinate,
nocturnal enuresis, involuntary urination when coughing, laughing
o Perverted taste and olfactory sensation, desire to eat chalk clay lime
• Classification according to severity
o Light (Hb 110-90 g/l)
o Moderate (Hb 90-70 g/l)
o Severe (Hb <70 g/l)
• Stages
o Storage depletion – decrease serum ferritin
o Iron deficiency – decrease serum ferritin, low transferring saturation, decreased
serum iron
o IDA – along with the above, decreased hemoglobin and hematocrit
Diagnostic Criteria
• General blood test
o Hypochromic normocytes and microcytes visible in smear. In severe cases
poikilocytosis and anisocytosis
o Decrease in Hb concentration and number of RBC
o Color indicator can fall below 0.5
• Biochemical blood test
o Decease serum iron (Norm 12.5-30.4 mmol/l)
o Increased Total Iron-binding capacity (Norm 45-72 mmol/l)
o Serum ferritin decreases (Norm M-30-350ng/l, F-120-125ng/l)
o Percentage of transferrin saturation with iron decreases (Norm 15-50%)
• Sternal puncture
o Iron is deposited in hemosiderin inclusions in the plasma of macrophages –
sideroblasts (absent in IDA)
• ECG – flattening or inversion of T-wave
• Echocardiography – dilation of ventricle and atrial cavities, hypertrophy, hyperkinesis of
myocardium of ventricular walls and interventricular septum, valve prolapse
Treatment
• According to the chemical structure, drugs for IDA replacement therapy are divided into
4 groups:
o Simple, easily dissociating salts: sulfates (ferroplex), fumarates (ferro-fumarate),
gluconates (ferronal), dichloro-nicotinamides (feramide);
o Ferrocenes ( organometallic compounds) - ferroceron;
o Chelated iron compounds-ferritol, ferricite, ferkovene;
o Complex polynuclear iron hydroxide complexes - ferum-foll and ferum-lek.
• Simple salts and ferrocenes are intended for oral use only.
• Chelates and polynuclear iron hydroxide complexes can be used both orally and
parenterally-intravenously and / or intramuscularly.
• In clinical practice, preparations of simple salts - sulfate, lactate, carbonate, iron
fumarate-are most often used.
• Iron sulfate is less toxic and has increased absorbability
 o Feroplex – 50mg iron sulfate + ascorbic acid at the beginning of treatment 1-2
tabs 3-4 times/day
o Conferon – 200mg iron sulfate + succinic acid at initial stage 1cap 3-4 times/day
o Tardiferon-retard – prolonged form with 105mg iron sulfate 1-2 tabs OD before
breakfast
• 12-25% - S/E include dyspeptic disorders, constipation
• Ferroceron (300mg tab) is well absorbed in intestine and does not cause S/E, but it has
the ability to selectivey deposit in adipose tissues • Chelates iron compounds – minimal
toxicity but are rapidly eliminated from the body (IV/IM – ferbitol or ferkoven, oral –
ferricit)
• Of polynuclear iron hydroxide compounds – ferrum-foll (chewable tablet 350mg BD)
and ferrum-lek (2ml amp IM and 5ml IV – 100mg iron)
• In absence of disorders of iron absorption in intestine – treatment is oral
• Begins with small doses and gradually increased to maximal tolerable level
• In uncomplicated cases, after one week – patient condition improves
• After 8-10 days from start of treatment, reticulocytes appear in blood and after 20-30
days, Hb ↑
• After achieving stable therapeutic effect – maintenance dose
o Feroplex 1tab BD or conferon 1cap OD – 2-3 months until stabilization of normal
Hb
o The following 1-1.5 years in women within a week after each menstruation
prescribe drugs according to the above scheme of maintenance
• Parenteral administration is necessary in treatment of patients with impaired intestinal
absorption, who have undergone gastrectomy, with exacerbation of duodenal ulcer,
patient with non-specific ulcerative colitids, or if necessary, rapid saturation of body with
iron in cases of operations for uterine fibroids, hemorrhoids
o Ferrum-lek – 1st day 2ml IM, then in absence of negative reaction in following
days 2-4ml BD depending on weight
o IV drug is administered every other day 5ml direct or drip, previously diluted
200ml saline
o Chelated iron also administered by similar method
• It should be remembered that with parenteral administration of iron, serious side effects
often occur: allergic reactions to anaphylaxis, infiltrates and abscesses at sites of IM
administration.
• In case of intolerance to parenteral and oral administration of iron preparations, treatment
is carried out by intravenous transfusions of red blood cell mass
 2. Etiology, pathogenesis, clinical picture, classification, diagnostics, treatment of
vitamin B12 deficiency anemia.
• Megaloblastic anemia – a group of blood diseases, a common feature of which is the
suppression of normal hematopoiesis with the transition to the embryonic megaloblastic
type of erythropoiesis, which is due to a deficiency in the body of cyanocobalamin
(vitamin B12) and/r folic acid
Pathogenesis
• Vitamin B12 is a precursor to two coenzymes: methylcobalamin and
deoxyadeosylcobalamin
• Methylcobalamin is essential for DNA synthesis
o With its lack, folic acid conversion cycle is disrupted which ensures the transition
of uridine monophosphate to thymidine monophosphate
o Resulting disorder of the DNA structure are similar to those in folic acid
deficiency
o There is inhibition of cell division of rapidly proliferating tissues, primarily cells
of hematopoietic system
• Deoxyadenosylcobalamin is involved in metabolism of fatty acids
o With its lack, the transition of methylmalonic acid to succinic acid does not occur
o Methylmalonic acid is toxic to nervous system
o With its excess, there is degeneration of the posterolateral columns of the spinal
cord – funicular myelosis
o Folic acid deficiency does not cause such changes
Clinical Presentation
• On examination, the patient looks pale with sight greenish ictericity – ivory colour of
skin
• Elderly patients are characterized by bright, silvery gray hair
• Ictericity and pronounced jaundices is caused by unconjugated hyperbilirubinemia, which
is the result of intracoastal hemolysis of hemoglobin containing erythrocaryocytes (shunt
hemolysis)
• During exacerbation, temperature may increase from sub febrile to 38 degrees and above
• Three syndromes:
o Anemic syndrome
▪ General weakness, palpitation, SOB with little physical exertion
▪ Tinnitus, dizziness, stabbing pain in heart, pasty lower extremities
▪ Severity depends on degree and speed of development of anemia
▪ Rapid anemia often leads to cerebral ischemia with appearance of
comatose state, decompensated circulatory failure
o Syndrome of lesion of digestive organs
▪ Burning sensation in tongue, loss of taste, weak appetite, feeling of
heaviness, epigastric pain and diarrhea
▪ Gunther’s glossitis – appearance of initially bright inflammatory areas,
aphthous rashes, cracks on the tip and side surfaces of the tongue. Tongue
becomes smooth, shiny (“lacquered”), dark crimson in color
▪ Dystrophic chances in mucosa of stomach and intestine – symptoms of
atrophic gastritis, enteritis
▪ Liver is constantly moderately enlarged, painless
 ▪ Occasionally, mild splenomegaly detected
▪ In some, pronounced hepatosplenomegaly, symptoms of portal
hemodynamic disorder and other signs of cirrhosis detected
▪ Diarrhea, symptoms of malabsorption – evidence of violation of
absorption of B12
o Syndrome of neurological disorders
▪ Associated with lesion of posterolateral columns of spinal cord – funicular
myelosis
▪ In some cases, this is one of the early signs of the disease
▪ It is characterized by paresthesia, violations of vibration and deep
sensitivity
▪ Disorder of deep sensitivity appear earlier and are more pronounced in
distal parts of lower extremities
▪ In connection with disorder of deep sensitivity – ataxia develop
▪ There are motor disorders, weakness, paresis of the lower extremities,
decrease or disappearance of tendon reflexes
▪ Pathological symptoms – Babinski, Rossolimo
▪ Sometimes, ophthalmoplegia, atony of bladder retrobulbar neuritis
▪ Very rarely changes in the psych with hallucination, manic outbursts,
paranoid state, which quickly disappear with timely treatment
Diagnostic Criteria
• General blood test
o Normochromic or hyperchromic anemia, leukopenia, thrombocytopenia
o Pronounced macrovalocytosis, anisocytosis, poikilocytosis
o Irregular RBC (schizocytes) and large cells (megalocytes)
o In RBC – HB increased (hyperchromia more than 1), intracellular inclusion
visible (Joly bodies Kebot rings), diffuse polychromatophilia of cells
o Hypersegmented neutrophil
• Biochemical tests
o Increase bilirubin due to unconjugated fraction
o Increase in concentration of serum iron
o Decrease folic acid
• Immunological examination
o IgG against cytoplasmic antigens of gastric parietal cells and gastromuco proteins
• U/E – urobilin (evidence of intracerebral shunt hemolysis of erythrocaryocytes)
• Coprogram – eggs and fragments of strobila of broad tapeworm
• Sternal puncture
o Megaloblastic type erythropoiesis o Erythroid sprout prevails (ratio of
leuco/erythro becomes >1/2, in norm it is 3/1-4/1)
o Signs of abnormal leukopoiesis – unusually large granulocytes of different stags
of maturation, giant hypersegmented neutrophils
o Reduced number of megakaryocytes
o When treating sternal puncture with alizarin red, cell staining observes in B12
deficiency anemia but not in folic deficiency
• Gastric secretion – histamine resistant achlorhydria with no secretion of gastromuco
protein
 • FGDS – signs of strophic gastritis. Morphological exam of gastric biopsy reveals signs of
metaplasia. In some cases, latent stomach cancer diagnosed
• X-ray – smoothness, flattening of folds of mucosa, decrease in tone, violation of motor
function of stomach. Possible to diagnose tumor lesion of the organ
• USG – cirrhosis, portal hemodynamic disorder
• ECG – tachycardia, diffuse dystrophy of ventricular myocardium
• Echocardiography – dilation of ventricular and atrial cavities, an increase in systolic
index (with severe anemia)
Treatment
• Treatment can be started after verification of Dx by morphological analysis of sternal
myelogram
• Before a sternal myelogram, it is absolutely impossible to prescribe blindly preparation of
coenzymes of vitamin B12
• IM injection of cyanocobalamin 400-500mcg daily for 4-6 weeks
• Evidence of transition of megaloblastic hematopoiesis to normoblastic is reticulocytic
crisis (appearance of large number of young normal red blood cells in peripheral blood),
usually after 4-6 days of treatment
• Against this background, the drug continues to be administered in the same single dose,
but every other day, until the development of complete hematological remission
• Fixing treatment can be carried out with cyanocobalamin 400-500mcg IM twice a week
OR oxycobalamin 500mcg once a week for 3 months
• Criteria for remission is the normalization of composition of peripheral blood, bone
marrow hematopoiesis, and level of vitamin B12 in the blood and urine
• In the future, maintenance is carried with cyanocobalamin 400mcg twice a month or
oxycobalamin 500mcg once a month throughout patients’ life
• In severe anemia and funicular myelosis, cyanocobalamin 1000mcg daily for 5-10 days
o At the same time, it is necessary to inject coenzyme of vitamin B12 cobamin
200mcg OD IM (helps to quickly eliminated toxic effect of methylmalonic acid
on spinal cord)
o In the future, with the improvement of condition, it is administered twice weekly
until stable hematological remission is obtained
o Consolidation of remission and lifelong maintenance is carried out according to
the methods described above
• With very severe anemia and threat of anemic coma, along with the introduction of at
least 1000mmcg of cyanocobalamin and 500mcg of cobamin per day, transfusion of RBC
mass, reopoliglukin are performed
• In case of anemia resistant to treatment with Vitamin B12, when high titers of
autoantibodies to parietal cells of stomach and gastromuco protein are detected,
glucocorticoid hormones are used in medium doses (prednisone up to 40-60 mg/day PO)
• Folic acid prescribed orally in cases of proven folic deficiency at dose 5-15mg.day • With
vitamin B12 deficiency, folic acid is not included
• At the same time, such patients should be prescribed a diet that includes foods and dishes
rich in folic acid of natural origin, exclude use of drugs that have the properties of folic
acid antagonists
• Prognosis is favorable with timely diagnosis and early treatment, lifelong prevention.
 3. Classification of hemolytic anemia, main diagnostic criteria, principles of therapy.
Classification
• Hereditary
o Membranopathies – hereditary spherocytosis, elliptocytosis
o Enzymopathies – G6PD deficiency, Pyruvate kinase deficiency, Pyrimidine 5’
nucleotide deficiency
o Hemoglobinopathy Deficiency – Thalassemia Abnormality – Sickle cell
anemia
• Acquired
o Immune
▪ Auto Ab
• Warm ab
o Primary idiopathic
o Secondary – autoimmune, drugs, lymphoid malignancy
• Cold Ab
o Primary
o Secondary – infection, lymphoproliferative
▪ Allo Ab – red cell Ag induced (transfusion reaction, hemolytic disease of
NB)
o Non-immune
▪ Mechanical (prosthetic valve, microangiopathic, hemoglobinuric)
▪ Infection (intracellular organisms like malaria, toxins like C. perferengens)
▪ Chemical/physical (oxidative drugs, copper, burns, drowning)
▪ Abnormal membrane (paroxysmal nocturnal hemoglobinuria)
Diagnostic criteria/algorithm
• When hemolysis is suspected, the history should include known medical diagnoses,
medications, personal or family history of hemolytic anemia, and a complete review of
systems.
• The physical examination should focus on identifying associated conditions, such as
infections or malignancies
• The initial workup of hemolytic anemia begins with a complete blood count illustrating
normocytic (mean corpuscular volume of 80 to 100 μm3 [80 to 100 fL]) or macrocytic
(mean corpuscular volume greater than 100 μm3) anemia
• When anemia is identified, testing should include measurement of lactate dehydrogenase,
haptoglobin, reticulocyte, and unconjugated bilirubin levels, as well as urinalysis
• Lactate dehydrogenase is intracellular, and levels increase when RBCs rupture.
• Haptoglobin binds to free hemoglobin, and levels decrease in hemolysis.
• Unconjugated bilirubin levels rise as its production exceeds elimination capability.
• Hemolysis usually induces a reticulocytosis causing macrocytosis, unless significant iron
deficiency or marrow suppression is present.
• Urinalysis may be positive for hemoglobinuria in hemolytic anemia despite no visible
RBCs on microscopy.
• The constellation of reticulocytosis, increased lactate dehydrogenase levels,
increased unconjugated bilirubin levels, and decreased haptoglobin levels confirms
hemolysis.
 4. Etiology, pathogenesis, clinical picture, classification, diagnostics, treatment of
aplastic anemias.
It is a heterogenous group of diseases characterized by pancytopenia and hematopoietic
insufficiency caused by the development of bone marrow aplasia
Etiology
• Congenital – Fanconi anemia, Joseph-Daymond-Blackfen anemia, etc.
• Acquired
o Exposure to chemicals (benzene, pesticide, lead)
o Effect of drugs (chloramphenicol phenytoin, phenylbutazone, gold component,
etc.)
o Autoaggression and appearance of autoantibodies to hematopoietic cells
o Exposure to radioactive radiation o Infectious disease (HBV, HCV, infectious
mononucleosis, CMV)
o Other diseases (thymomas, lymphomas, etc.)
• Idiopathic
Pathogenesis
• Immune and/or toxic suppression of the mitotic capacity of polypotent stem cells and/or
erythropoietic progenitor cells in pure (partial) red cell aplasia.
• Immune and/or toxic suppression of the functional activity of the stem cell
microenvironment in the bone marrow.
• Genetically determined expression of apoptosis (suicide) genes in stem cells, progenitor
cells of the main hematopoietic lines.
• Reduction in the life span of red blood cells with their premature hemolysis in the bone
marrow (shunt hemolysis), caused by immune or toxic effects on the activity of certain
enzymes of the red blood cell membrane.
Role of Autoimmune Mechanism
• The peculiarity of the pathogenesis of is that the immune system's response is directed
against the antigen (s) that appear on the cytoplasmic membrane of a blood stem cell as a
result of a mutation in its genetic apparatus.
• This reaction of the immune system is similar in nature to the reactions of antitumor
immunity.
• However, this immune response on the one hand is untenable, since it does not lead to the
complete elimination of the defective cell, and on the other hand, it is excessive, since it
blocks the development of not only the defective cell, but also most normal blood stem
cells.
• These mechanisms lead to the development of cytopenic syndrome.
Major clinical signs
• Anemic syndrome
o Caused by decreased content of RBC
o General weakness, SOB, palpitations, dizziness, flashing dark flies in eyes,
inability to long-term physical and mental work
o Pronounced pallor of skin and mucosa
o Pulse is rapid and BP may be normal or low
o Percussive boundaries of thee hear are moderately expanded, tones are mutes
o Functional systolic murmur heard over all auscultation points
 o Detection of enlarged liver usually combined with other signs of congestive heart
failure
• Hemorrhagic syndrome
o Based on thrombocytopenia, caused by hypo- or aplasia of megakaryocytic germ
in bone marrow
o Tendency to bleeding with minor injury of oral mucosa, manifested by nasal
bleeding, menorrhagia, hematuria
o Bruises on skin with little physical impact or without and obvious reasons
o Small hemorrhages on mucosa of mouth, lips and conjunctiva
o At injection sites, injuries occur hematomas, often very extensive
o With severe exacerbation and severe thrombocytopenia – massive pulmonary,
gastric, intestinal, uterine bleeding, significantly exacerbating anemic syndrome
o Intracranial hemorrhage is one of the causes of sudden deaths
• Syndrome of immune disorders
o Formed when number of granulocytes are decreased
o Tendency of patients to infectious diseases
o Acute respiratory viral infection causes them to have long-term and severe
bronchitis, complicated by pneumonia
o Pustular skin lesions
o Quickly spread fungal lesion on skin, nail beds
o With severe exacerbation, ulcerative-necrotic stomatitis, angina with severe
intoxication
• Hemolytic syndrome
o Caused by occurrence in some cases of phenomenon of intracostebral hemolysis
of RBC (shunt hemolysis)
o Mild icteric, sometimes jaundice od sclera and skin, dark feces and urine
o With long course, pigmented concentration can form in gallbladder
o Spleen is not enlarged
Laboratory Diagnostics
• Normochromic (hyperchromic) anemia
• Reticulocytopenia (up to complete absence)
• Leukocytopenia due to granulocytopenia
• Thrombocytopenia
• Increased ESR (40-60mm/hr)
• Biochemical – increased unconjugated bilirubin and serum iron
• U/E – normal or hematuria, urobilin
Diagnostic Criteria
• Coprogram – positive Gregersen reaction, in which patient with severe thrombocytopenia
may indicate presence of GIT bleeding. Fresh RBC detected in hemorrhoidal bleeding.
Increased stercobilin in hemolytic form
• Sternal puncture and/or trepanobiopsy of iliac wing
o Pronounced decrease in number of cellular elements in bone marrow
o In severe cases, histological preparation looks drained
o In the field of view, single cells of a predominantly lymphoid serios
(lymphocytes, plasma cells, single erythroblasts) are visible
 o Macrophages overloaded with hemosiderin-sideroblasts, which indicates an
overflow of bone marrow depot with iron not used for erythropoiesis
• ECG – tachycardia, myocardial dystrophy (reduced QRS, isoelectric T in thoracic lead)
Treatment
• With an exacerbation, especially in cases where content of granulocytes is very low,
patient placed in sterile boxes. Patient skin treated with antiseptic solutions; oral cavity
sanitized. Hormonal drugs given to women to avoid blood loss during menstruation
• With severe anemia – RBC mass transfuses
• Decrease in platelet below 20x109/L – platelet concentrate transfusion
• For infectious complications – broad spectrum antibiotic without myelotoxic effect
• If it caused by an autoimmune process – Prednisone 80-120mg/day until signs of
remission
o Then, switch to maintenance therapy with 15-20mg/day
o If there is clinical effect, continue for 3-4 months, and if there is no effect within 4
weeks, discontinue
• In absence of positive results from glucocorticoids in mild anemia – splenectomy to
eliminate cytotoxic function of spleen
• If no effect from splenectomy – anti-lymphocytic globulin IV drops 120-160mg OD for 2
weeks
• Cyclosporin A 4mg/kg/day BD 2-3 months – hematological remission in half of patients
• Combined with parenteral anti-lymphocytic globulin, oral cyclosporin A, parenteral
colony-stimulating factor drugs (filgrastim, lenograstim, nartograstim, neupogen) and
oral methylprednisolone possible
• Main and most promising method – bone marrow transplantation o Donor compatible
with HLA system selected o Before transplantation, recipients own bone marrow is
destroyed by total irradiation of body at doses 10-11 Gy and administered large doses of
cyclophosphane 50mg/kg/day for 3 days
 5. Causes of leukemoid reactions. Complete blood count results

• The term leukemoid reaction describes an increased white blood cell count (> 50,000
cells/μL), which is a physiological response to stress or infection (as opposed to a
primary blood malignancy, such as leukemia).
• It often describes the presence of immature cells such as myeloblasts or red blood cells
with nuclei in the peripheral blood. It may be lymphoid or myeloid
• Causes of leukemoid reactions include
o Severe hemorrhage (retroperitoneal hemorrhage)
o Drugs
▪ Use of sulfa drugs
▪ Use of dapsone
▪ Use of glucocorticoids
▪ Use of G-CSF or related growth factors
▪ All-trans retinoic acid (ATRA)
o Ethylene glycol intoxication
o Infections
▪ Clostridium difficile
▪ Tuberculosis
▪ Pertussis
▪ Infectious mononucleosis (lymphocyte predominant)
▪ Visceral larva migrans (eosinophil predominant)
o Asplenia
o Diabetic ketoacidosis
o Organ necrosis
▪ Hepatic necrosis
▪ Ischemic colitis
o As a feature of trisomy 21 in infancy (incidence of ~10%)
o As a paraneoplastic phenomenon (rare)
From Russian book
• Etiology of leukemoid reactions
o Exogenous factors:
▪ Bacteria
▪ Viruses
▪ Rickettsia
▪ helminths
o endogenous factors:
▪ BAS, released during immune, allergic processes
▪ Tumor decay products
▪ erythrocyte hemolysis
Blood picture
Leukemoid reactions of the granulocytic type
• In the blood, neutrophilic leukocytosis is noted with a shift in the nuclear formula
towards myelocytes.
• Unlike chronic myelogenous leukocytosis, reactive leukocytosis is always based on a
severe process, accompanied by an increase in body temperature, the presence of foci of
inflammation, and sepsis.
• It is with the mass death of microbial bodies and the ingress of endotoxin into the blood
that the release of the granulocytic reserve of the bone marrow into the blood and the
increased production of granulocytes are associated.
• In the debut of chronic myelogenous leukemia and in sub leukemic myelosis, which can
be confused with an inflammatory blood picture, intoxication is not observed, the somatic
patient is completely preserved.
Eosinophilic blood reactions
• High blood eosinophilia requires careful investigation.
• First of all, the exclusion of drug sensitization, parasitic invasion (see Helminthiases).
• In rare cases, high eosinophilia may reflect a reaction to acute T-cell leukemia in the
aleukemic stage (when leukocytes have not yet entered the blood), cancer.
• Therefore, unmotivated high eosinophilia requires a comprehensive oncological
examination, including bone marrow puncture.
• The level of leukocytosis with high eosinophilia can reach many tens of thousands in 1
square.
• Eosinophilia is always associated with a high percentage of eosinophils in the bone
marrow.
• Occasionally, in perfectly healthy people, persistent asymptomatic eosinophilia
“constitutional eosinophilia” is observed (such a diagnosis can only be made after a
qualified special examination of the patient for parasite carriage, exclusion of other
causes indicated above, and long-term observation)
• “High eosinophilia may be accompanied by parietal fibroblastic endocarditis,
eosinophilic collagenases); both are the onset of hematosarcoma development
Leukemoid reactions of the lymphatic type
• They are most often the result of a viral infection.
• The most common reactive lymphocytosis is oligosymptomatic infectious lymphocytosis.
• From the blood picture, it is easy to mistake for chronic lymphocytic leukemia, but it
occurs almost exclusively in children, and they do not have chronic lymphocytic
leukemia.
• On examination, lymphocytosis usually lasts for several days, accompanied by mild
catarrhal symptoms.
• To differentiate the process of chronic lymphocytic leukemia, there is no need for a bone
marrow puncture, it is enough to wait a few days with a final judgment on the diagnosis.
• After splenectomy, reactive lymphocytosis may occur.
Leukemoid reactions of the monocytic type
• They are found in tuberculosis, sarcoidosis, Waldenström's macroglobulinemia, and
chronic inflammatory processes.
 6. Diagnosis and differential diagnosis of leukemoid reactions and hemoblastosis.
Principles of treatment of hemoblastosis.
Differential diagnosis of leukemia and leukemoid reaction
Criteria Leukemia Leukemoid reaction
Category Self-disease Symptoms of the underlying
disease

Causes Carcinogens, viruses, ionizing Biological factors: infectious

radiation, chemicals agents; allergic,
tumor processes; exo- and
endogenous intoxication;
injury; ionizing radiation

Development mechanism Transformation of normal Activation of normal

hematopoietic cell in hematopoiesis and
tumor entry into the vascular bed of
an excess of blood cells
or suppression of normal
hematopoiesis and inhibition
of the release of formed
elements into the vascular
bed

Manifestations – in blood An increase in the number of Presence of blast and

cells or immature forms
cytopenia. The presence of leuko-, erythro-, platelet
blasts series in proliferative forms.
leukemic cells. Absence Leuko-, erythro-,
signs of cell degeneration thrombocytopenia
(found only in chronic B- with cytopenic forms. Signs
lymphocytic leukemia). of degeneration of blood
Basophilic-eosinophilic cells. Absence of basophilic-
association, leukemic eosinophilic association,
"failure" in acute myeloid leukemic "failure" in
leukemia myeloid-type leukemoid
reactions
Manifestations – in in the bone Generalized tumor hyperplasia Focal hyperplasia of normal
brain ???? of hematopoietic tissue. Often hematopoietic cells in
large proliferative forms and their
number of blasts and immature hypoplasia
leukemic cells with cytopenic forms
Prognosis Unfavorable in most cases Favorable after treating
the primary process that
caused it
Diagnosis of leukemoid reaction
• Blood tests that, in the presence of a reaction, reveal an increased ESR and C-reactive
protein, the presence of autoantibodies. The count of leukocytes is carried out, the ratio of
their forms in percent is determined;
• Blood culture for sterility, sputum and urine examination, more aimed at accurately
identifying the pathogen. An enzyme immunosorbent test detects antibodies produced by
the body;
• X-ray examination of the chest and joints reveal darkening and infiltrates in the lungs
with their diseases (in the first case) and signs of arthritis (in the second);
• Ultrasound scanning makes it possible to determine infectious mononucleosis and other
pathologies that can lead to an increase in the number of white blood cells;
• Bone marrow histology reveals hyperplastic processes, an increase in the number of blast
cells, and a biopsy of the affected lymph node reveals abnormal collagen growth and
malignant granuloma
Diagnosis of hemoblastosis
• General, biochemical blood tests
• Biopsy of lymph nodes
• X-ray examination
• Bone marrow examination
• Cytogenetic study.
Treatment of hemoblastoses
• Bone marrow transplant
• Chemotherapy
• Surgical intervention
• Radiation therapy
• Antibiotics
• Hemostatics
• Detoxifying drugs.
 7. Acute myeloid leukemia: etiopathogenesis, clinical syndromes, diagnosis. Treatment
approaches.
Definition
• rapidly progressive malignancy characterized by failure of myeloid cells to differentiate
beyond blast stage
Pathophysiology
• etiology subdivided into:
o primary: de novo
o secondary: hematologic malignancies (e.g. myeloproliferative disorders and
MDS) or previous chemotherapeutic agents (e.g. alkylating agents)
• uncontrolled growth of blasts in marrow leads to:
o suppression of normal hematopoietic cells
o appearance of blasts in peripheral blood – risk of leukostasis
o accumulation of blasts in other sites (e.g. skin, gums)
o metabolic consequences; tumor lysis syndrome
Clinical Features
• signs and symptoms develop over a period of weeks
• manifestations of BM failure
o anemia, thrombocytopenia (associated with DIC in APL), neutropenia (and
infection/fever)
• accumulation of blast cells in marrow
o skeletal pain, bony tenderness (especially sternum)
• organ infiltration
o gingival hypertrophy (particularly myelomonocytic leukemia) – may present to
dentist first
o extramedullary involvement
o hepatosplenomegaly (also present in ALL)
o lymphadenopathy gonads (also present in ALL)
o skin: leukemia cutis or myeloid sarcoma
o eyes: hemorrhages and/or whitish plaques, Roth spots, cotton wool spots, and
vision changes (uncommon)
• leukostasis/hyperleukocytosis syndrome (medical emergency)
o large numbers of blasts interfere with circulation and lead to hypoxia and
hemorrhage – can cause diffuse pulmonary infiltrates, CNS bleeding, respiratory
distress, altered mental status, and priapism
o more commonly associated with AML than ALL
• metabolic effects (aggravated by treatment)
o tumor lysis syndrome (TLS):
▪ increased uric acid → _nephropathy, gout
▪ release of phosphate → _decreased Ca2+, decreased Mg2+
▪ release of procoagulants → _DIC (higher risk in APL)
o hyperkalemia pre-treatment from blastic proliferation and spontaneous TLS,
further hyperkalemia after treatment (from lysed cells). Note – some forms of
AML can present with hypokalemia due to secreted muramidase that causes K+
wasting from renal tubules
Investigations
• blood work
o CBC: anemia, thrombocytopenia, variable WBC (most often cytopenias + blasts)
o INR, aPTT, FDP, fibrinogen (in case of DIC)
o increased LDH, increased uric acid, increased PO43- (released by leukemic
blasts), decreased Ca2+, increased/decreased K+
o baseline renal and liver function tests
o if considering treatment: screen for HBV, HCV, HIV, CMV serology
• peripheral blood film – circulating blasts with Auer rods (azurophilic granules) are
pathognomonic for AML
• BM aspirate for definitive diagnosis
o blast count: AML >20% (normal is <5%)
o morphologic, cytochemical, and/or immunophenotypic features are used to
establish lineage and maturation
• CXR to rule out pneumonia; ECG, MUGA scan prior to chemotherapy (cardiotoxic)
Treatment
• mainstay of treatment is chemotherapy (rapidly fatal without treatment)
• patients who are not eligible for intensive chemotherapy can be treated with low-dose
cytarabine and hypomethylating agents
• all AML subtypes are treated similarly, except APL with t(15:17) translocation
o induction: chemotherapy to induce complete remission of AML
▪ several possible regimens
▪ patients with poor response to initial induction therapy – worse prognosis
▪ supportive care - management of TLS and DIC, febrile
neutropenia/infections, transfusion support (including platelet transfusions
if <10 x 10⁹/L)
o consolidation: to prevent recurrence
▪ intensive consolidation chemotherapy
▪ stem cell transplantation – allogeneic (younger patients with better
performance status and/ or adverse cytogenetics)
• supportive care
o fever: pan-cultures, CXR, and start broad-spectrum antibiotics
o platelet and RBC transfusions
o prevention and treatment of metabolic abnormalities
▪ allopurinol, rasburicase for prevention/management of hyperuricemia
o leukostasis
▪ needs immediate cytoreductive therapy (i.e. hydroxyurea)
o treatment strategy for APL
▪ APL is an emergency as DIC is often present at diagnosis
▪ ATRA added to induce differentiation (should be started ASAP if APL is
in the differential); arsenic trioxide and ATRA combination therapy for
APL is non-inferior to traditional chemotherapy
 8. Acute lymphoblastic leukemia: etiopathogenesis, clinical picture, diagnosis.
Treatment approaches.
• Acute lymphoblastic leukemia (acute lymphocytic leukemia, ALL) is a malignant
(clonal) disease of the bone marrow in which early lymphoid precursors proliferate and
replace the normal hematopoietic cells of the marrow.
• WHO subdivides ALL into two types depending on cell of origin
o B-cell: precursor B lymphoblastic leukemia
o T-cell: precursor T lymphoblastic leukemia
Etiology
• acute lymphoblastic leukemia (ALL) has a multifactorial etiology, with a two-step
process of genetic mutation and exposure to infection playing a prominent role.
• The first step occurs in utero, when fusion gene formation or hyperdiploidy generates a
covert, pre-leukemic clone.
• The second step is the postnatal acquisition of secondary genetic changes that drive
conversion to overt leukemia.
• The second step is triggered by infection. Triggering is more likely to occur in children
whose immune response is abnormally regulated because they were not exposed to
infections in the first few weeks and months of life
Pathophysiology
• The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells
(i.e., lymphoblasts) that are arrested in an early stage of development.
• This arrest is caused by an abnormal expression of genes, often as a result of
chromosomal translocations or abnormalities of chromosome number.
• These aberrant lymphoblasts proliferate, reducing the number of the normal marrow
elements that produce other blood cell lines (red blood cells, platelets, and neutrophils).
• Consequently, anemia, thrombocytopenia, and neutropenia occur, although typically to a
lesser degree than is seen in acute myeloid leukemia.
• Lymphoblasts can also infiltrate outside the marrow, particularly in the liver, spleen, and
lymph nodes, resulting in enlargement of the latter organs.
Clinical Features
• see Acute Myeloid Leukemia for full list of symptoms
• distinguish ALL from AML based on table below

• clinical symptoms usually secondary to:

o BM failure: anemia, neutropenia (50% present with fever; also, infections of
oropharynx, lungs, perianal region), and thrombocytopenia
o organ infiltration: tender bones, lymphadenopathy, hepatosplenomegaly,
meningeal signs (headache, N/V, visual symptoms; especially in ALL relapse)
Investigations
• >20% BM or peripheral blood lymphoblasts, with samples collected for flow cytometry,
cytogenetics, and molecular studies
• Ph chromosome in ~25% of adult ALL cases
• CBC: increased leukocytes >100 x 10⁹/L (occurs in 50% of patients); neutropenia,
anemia, or thrombocytopenia
• screen for tumor lysis syndrome: increased uric acid, K+, PO43-, low Ca2+, high LDH
• screen for DIC: PT, aPTT, fibrinogen
• CXR: patients with ALL may have a mediastinal mass
• CT C/A/P and testicular ultrasound to screen for extranodal disease
• lumbar puncture to assess for CNS involvement (ensure adequate platelet count and
PT/PTT and delay until blasts have cleared from peripheral blood)
• HIV, HBV, HCV serologies, CMV Ab testing
Treatment
• eliminate abnormal clonal cells
o induction chemotherapy: to induce complete remission, <5% blasts (restore
normal hematopoiesis)
o consolidation and/or intensification of chemotherapy
▪ consolidation: continuing same chemotherapy to eliminate subclinical
leukemic cells
▪ Intensification: high doses of different (non-cross-reactive) chemotherapy
drugs to eliminate cells with resistance to primary treatment
o maintenance chemotherapy: low dose intermittent chemotherapy over prolonged
period (1 yr) to prevent relapse
o prophylaxis: CNS radiation therapy or methotrexate (intrathecal or systemic)
• hematopoietic stem cell transplantation (for certain indications): potentially curative (due
to pre-transplant myeloablative chemoradiation and post-transplant graft-versus-leukemia
effect) but relapse rates and non-relapse mortality high
o if BCR-ABL positive, tyrosine kinase inhibitors started up front and given
continuously
o in relapse setting, CAR T-cell therapy, inotuzumab, or blinatumomab
 9. Etiology, pathogenesis, clinical picture, diagnostics and treatment approaches of
chronic myeloid leukemia (CML)
• Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a
myeloproliferative disorder characterized by increased proliferation of the granulocytic
cell line without the loss of their capacity to differentiate.
• The peripheral blood cell profile shows an increased number of granulocytes and their
immature precursors, including occasional blast cells.
Etiology
• CML is one of the few cancers known to be caused by a single, specific genetic mutation
• More than 90% of cases result from a cytogenetic aberration known as the Philadelphia
chromosome
Pathophysiology
• CML is an acquired abnormality that involves the hematopoietic stem cell. It is
characterized by a cytogenetic aberration consisting of a reciprocal translocation of the
Philadelphia chromosome
• This translocation relocates an oncogene called ABL
• The ABL oncogene encodes a tyrosine protein kinase
• The expression of this protein leads to the development of the CML phenotype, through
processes that are not yet fully understood
• The initiating factor of CML is still unknown, but exposure to ionizing radiation has been
implicated, as observed in the increased prevalence among survivors of the atomic
bombing of Hiroshima and Nagasaki.
• Other agents, such as benzene, are possible causes.
Clinical picture
• The clinical manifestations of chronic myelogenous leukemia (CML) are insidious.
• The disease is often discovered incidentally in the chronic phase, when an elevated white
blood cell (WBC) count is revealed by a routine blood count or when an enlarged spleen
is found on a general physical examination.
• Nonspecific symptoms of fatigue and weight loss may occur long after the onset of the
disease.
• Loss of energy and decreased exercise tolerance may occur during the chronic phase after
several months.
• Patients often have symptoms related to enlargement of the spleen, liver, or both. The
large spleen may encroach on the stomach and cause early satiety and decreased food
intake.
• Left upper quadrant abdominal pain described as "gripping" may occur from spleen
infarction.
• The enlarged spleen may also be associated with a hypermetabolic state, fever, weight
loss, and chronic fatigue. The enlarged liver may contribute to the patient's weight loss.
• Some patients with CML have low-grade fever and excessive sweating related to
hypermetabolism.
• In some patients who present in the accelerated, or acute, leukemia phase of the disease
(skipping the chronic phase), bleeding, petechiae, and ecchymoses may be the prominent
symptoms. In these situations, fever is usually associated with infections.
 • Bone pain and fever, as well as an increase in bone marrow fibrosis, are harbingers of the
blast phase.
• The blast crisis is marked by an increase in the bone marrow or peripheral blood blast
count or by the development of soft-tissue or skin leukemic infiltrates. Typical symptoms
are due to increasing anemia, thrombocytopenia, basophilia, a rapidly enlarging spleen,
and failure of the usual medications to control leukocytosis and splenomegaly.
Diagnosis
• Initial stage
o CBC: Normal/↓ RBC and Hb, Leukocytosis 15-30x109/L with a left shift to
myelocytes and promyelocytes. Basophilia, eosinophilia, moderate
thrombocytosis
o Biochem: ↑uric acid
o Sternal puncture: ↑ cells of granulocytic line with a predominance of young
forms. Blasts cells doesn’t exceed the upper limit of normal. ↑ megakaryocytes
• Expanded stage
o CBC: moderately ↓ RBC and Hb, color index ~1, Reticulocytes, single
erythrokaryocytes detected. Leukocytosis >30x109/L with a sharp shift to left to
myelocytes and myeloblasts. ↑E&B (E-B association). ↓absolute content of
lymphocytes. Thrombocytosis 600-1000x109/L
o Histochemical study of leukocytes: content of ALKP ↓↓ in neutrophils
o Biochem: ↑ uric acid, calcium. ↓ cholesterol. ↑ LDH activity. ↑ bilirubin due to
hemolysis
o Sternal puncture: rich in cells. Numbers of cells of granulocytic lines ↑↑. Blast
cells <10%. Many megakaryocytes. Number of erythrokaryocytes is moderately
reduced
o Cytogenic analysis: Ph-chromosome detected in myeloid cells of blood, BM,
spleen (absent in T-lymphocytes and macrophages)
• Terminal stage (myeloproliferative acceleration)
o CBC: ↓↓ RBC and HB with anisochromia, anisocytosis, poikilocytosis. Single
reticulocytes. Neutrophilic leukocytosis 500-1000x109/L with sharp shift to left to
blasts (15% without leukemic gap). B (20%) and ↑E. ↓PLT count. Functionally
defective megathrombocytes, fragments of megakaryocyte nuclei revealed
o Sternal puncture: Erythrocyte germ is suppressed more significant than in
expanded stage, content of myeloblastic cells, E and B ↑. Decreased
megakaryocytes
o Cytogenic analysis: Ph-chromosome in myeloid cells. Other chromosomal
abrasion – emergence of new clones of tumor cells
o Histochemical study of granulocytes and biochem are dame as in advanced stage
• Terminal stage (Blast crisis)
o CBC: deep drop in RBC and Hb with a complete absence of reticulocytes. Minor
leucocytes or leucopenia. Neutropenia. Sometimes basophilia. >30% blast cells.
Leukemic failure (mature neutrophils and blasts in smear, and no intermediate
maturing forms). Thrombocytopenia
o Sternal puncture: reduced numbers of mature granulocytes, cells of erythrocytic
and megakaryocytic lines. Number of blast cells is increases, including abnormal
ones with enlarged, deformed nuclei
 o Blasts cells in histological preparations of skin leukemoid.
• Generalized criteria for clinical and laboratory diagnosis of chronic myeloid leukemia:
o Neutrophilic leukocytosis in the peripheral blood over 20x109/ l.
o The presence of proliferating (myelocytes, promyelocytes) and maturing
(myelocytes, metamyelocytes) granulocytes in the leukocyte formula.
o Eosinophilic-basophilic association. o Myeloid hyperplasia of the bone marrow.
o Decreased activity of alkaline phosphatase of neutrophils.
o Detection of the Philadelphia chromosome in blood cells.
o Splenomegaly.
Treatment
• Cytostatic therapy begins at the advanced stage of the disease. At low and medium risk,
monotherapy with one cytostatic is used. At high risk and in the terminal stage of the
disease, polychemotherapy with several cytostatic is prescribed.
• The drug of first choice in the treatment of chronic myeloid leukemia is hydroxyurea,
which has the ability to suppress mitosis in leukemic cells. Start with 20-30 mg / kg / day
per os in one dose. The dose is adjusted weekly depending on changes in the blood
picture.
• In the absence of effect, mielosan is used at 2-4 mg per day. If the level of leukocytes in
the peripheral blood is reduced by half, the dose of the drug is also halved. When the
leukocytosis falls to 20x109/ L, myelosan is temporarily canceled. Then they switch to a
maintenance dose of 2 mg 1-2 times a week.
• In addition to myelosan, myelobromol can be used at 0.125-0.25 once a day for 3 weeks,
then maintenance treatment at 0.125-0.25 once every 5-7-10 days.
• Polychemotherapy can be carried out according to the AVAMP program, which includes
the introduction of cytosar, methotrexate, vincristine, 6-mercaptopurine, prednisolone.
There are other schemes of multicomponent therapy with cytostatics.
• The use of alpha-interferon (reaferon, intron A) is justified by its ability to stimulate
antitumor and antiviral immunity. Although the drug has no cytostatic effect, it still
contributes to leukopenia and thrombocytopenia. Alpha interferon is prescribed in the
form of subcutaneous injections of 3-4 million U / m 2 2 times a week for six months.
• Cytopheresis allows you to reduce the content of leukocytes in the peripheral blood.
Resistance to chemotherapy is a direct indication for this method. Urgent cytopheresis is
needed by patients with hyperleukocytosis and hyperthrombocytosis syndrome with
predominant damage to the brain and retina. Cytopheresis sessions are carried out from 4-
5 times/week to 4-5 times/month.
• Radiation therapy – giant splenomegaly with perisplenitis, tumor-like leukemias. 1 Gray.
• Splenectomy is used for threatening rupture of the spleen, deep thrombocytopenia, severe
hemolysis of erythrocytes.
• Bone marrow transplantation gives good results. Complete remission is achieved in 60%
of patients undergoing this procedure
 10. Etiology, pathogenesis, clinical types, diagnostics, complications, treatment of
chronic lymphocytic leukemia.
Etiology
• As in the case with most malignancies, the exact cause of CLL is uncertain
Pathophysiology
• Pathogenesis of chronic lymphocytic leukemia (CLL) is characterized by specific genetic
aberrations and alterations of cellular signaling pathways.
• In particular, a disturbed DNA damage response (DDR) and an activated B-cell receptor
signaling pathway play a major role in promoting CLL cell survival.
• External stimuli are similarly essential for CLL cell survival and lead to activation of the
PI3K/AKT and MAPK pathways.
• Activation of nuclear factor-kappa B (NFkB) influences the disturbed anti-apoptotic
balance of CLL cells.
• As these lesions define key regulatory elements of the DDR pathway, they also determine
treatment response to genotoxic therapy.
• Novel therapeutic strategies therefore try to circumvent defective DDR signaling and to
suppress the pro-survival stimuli received from the tumor microenvironment.
Clinical presentations and stages
• Initial stage
o Minimal clinical manifestations, Asymptomatic.
o In the beginning, lasts 3 years, with a progressive one for about a year
o “causeless” weakness, sweating, and increasing frequency of colds
o Lymphadenopathy (cervical, supraclavicular and less often axillary nodes),
painless, dough-elastic, not soldered to each other, moveable, no
ulceration/suppuration
• Advanced stage
o Progressive deuteriation of health
o Severe general weakness, weight loss, sub febrile fever, itching of skin, sweating
at night
o Palpitations, SOB, cough, epigastric pain
o O/E: pronounced lymphadenopathy (single / multiples, enlarged submandibular,
cervical, axillary, inguinal – size of chicken egg) can lead to thickening,
disruption of usual size of necks. Painless, mobile, elastic-dough
o Psoriasis, eczema, neurodermatitis, shingles are exacerbated. Urticaria and fungal
inf.
o T-cell CLL – leukemic infiltrates in deep layers of the skin with focal and diffuse
lesions of the papillary layers
o Splenomegaly – smooth and dense. Splenic infarctions, perisplenitis – intense
pain in Lt hypochondrium, fever and friction rub of pericardium
o Hepatomegaly maybe moderate – edge round, dense, painless palpitation or
weakly sensitive
o Enlarged mediastinal LN can compress mediastinal organs.
o Leukemic infiltrations of lungs – pleurisy (cough, SOB).
o Compression of SVC with swelling of cervical veins – puffiness of face
o Increased intra-abdominal LN – obstructive jaundice, acute pancreatitis, intestinal
obstructions. Leukemic infiltration of small intestine – diarrhea
 • Terminal stage
o Sharp, difficult to control aggravation of the patient’s condition
o Severe exhaustions, high fever, often caused by pneumonia, exacerbated TB,
generalized form of herpes infection with damage to the skin, mucosa, respiratory
track, GIT, urinary system
o Pale cyanotic, with a puffy face, icteric sclera de to anemia, cholestasis,
cardiopulmonary insufficiency due to infiltration of BM.
o Heart and lungs compressed by LN of great vessels. Infiltrative changes in liver,
compression of bile ducts
o Thrombocytopenic purpura with many multi-colored bruises of skin
o Infiltration of brain – headache, meningeal symptoms, paraplegia
o Increase in all LN, severe hepatomegaly. Giant spleen, rocky density or rapidly
enlarging LN, progressive anemia, thrombolytic purpura – CLL to
lymphosarcoma or AL
o Renal infiltrations lead to RF – death
Diagnostics
• Initial stage – Leukocytosis 10-30x109/L due to absolute lymphocytosis (60-80%) •
• Expanded stage
o CBC: ↓RBC, Hb. Color index of one. Leukocytosis 50-200x109/L due to absolute
lymphocytosis. Smear reveals Riedel cells (lymphocytes with a two-lobed kidney-
shaped nucleus), Grumprecht’s shadows (fragments of membrane and nuclei of
lymphocytes, torn during the preparation of smears). Thrombocytopenia
o Sternal puncture: 50-60% lymphoid cells in cellular composition of BM. Content
of cells of granulocytic, erythrocytic, megakaryocytic line is reduced
• Terminal stage
o CBC: same as expanded stage. Leukocytosis can transform into leucopenia.
Deeper decrease in RBC and Hb. Severe thrombocytopenia
o Sternal puncture: total lymphoid infiltration of BM. Transformation of CLL – AL,
number of blast cells increases dramatically
Treatment
• In the early stages of the disease, especially in benign CLL, drug therapy is not
performed.
• Progressive lymphadenopathy, severe splenomegaly are basis for chemotherapy with one
of the cytostatic:
o Leukeran 0.002 - 1 tablet 2 times a day with the transition to maintenance
treatment - 2 tablets (0.004) once a week.
o Cyclophosphamide 0.2 - administered intravenously at 400 mg 1 time per day,
followed by a switch to maintenance doses - 400 mg intravenously 2 times a
week.
o Prednisolone is prescribed at 10-15 mg orally daily during treatment with
cytostatic.
• In malignant, rapidly progressive forms of CLL and in the terminal stage of the disease,
the use of programs of two, three and four-component polychemotherapy is indicated.
The two-component program consists of cyclophosphamide and vincristine.
Cyclophosphamide, pafencil and prednisolone were introduced into the three-component
 CPP program. The three-component program M-2 used vincristine, cyclophosphamide,
alkane and prednisolone.
• With deep thrombocytopenia and anemia, a course of treatment is carried out with large
doses of prednisolone - 60-120 mg per day, followed by a gradual dose reduction.
• Local radiation exposure is applied to the area of the enlarged spleen and lymph node
packets at a dose of 1-1.5 Gy once, in total - 7-10 Gy.
• Cytopheresis is performed to remove excess lymphocytes from the peripheral blood. The
course of treatment is 5-8 sessions.
• Splenectomy is indicated for the formation of hemolytic anemia, deep thrombocytopenia,
ineffectiveness of glucocorticoids and radiation therapy, and frequent spleen infarctions.
• For the treatment of infectious complications of CLL, broad-spectrum antibiotics,
antifungal agents, and injections of immunoglobulin preparations are used.

11. Etiology, pathogenesis, clinical picture, diagnostics, outcome, treatment of erythema

(Polycythemia Vera).
• Polycythemia vera (PV) is a stem cell disorder characterized as a panhyperplastic,
malignant, and neoplastic marrow disorder. Its most prominent feature is an elevated
absolute red blood cell mass because of uncontrolled red blood cell production.
• This is accompanied by increased white blood cell (myeloid) and platelet
(megakaryocytic) production, which is due to an abnormal clone of the hematopoietic
stem cells with increased sensitivity to the different growth factors for maturation
Etiology
• It is caused by a malignant change in the genetic material (DNA) within a single cell of
the bone marrow (clonal disorder).
Pathophysiology
• The bone marrow of patients with polycythemia vera (PV),contains normal stem cells but
also contains abnormal clonal stem cells that interfere with or suppress normal stem cell
growth and maturation.
• Evidence indicates that the etiology of panmyelosis is unregulated neoplastic
proliferation. The origin of the stem cell transformation remains unknown.
• Progenitors of the blood cells in these patients display abnormal responses to growth
factors, suggesting the presence of a defect in a signaling pathway common to different
growth factors
• A mutation of the Janus kinase–2 gene (JAK2) is the most likely source of PV
pathogenesis, as JAK2 is directly involved in the intracellular signaling following
exposure to cytokines to which PV progenitor cells display hypersensitivity.
• Thrombosis and bleeding are frequent in persons with PV, as a result of the disruption of
hemostatic mechanisms because of (1) an increased level of red blood cells and (2) an
elevation of the platelet count
Clinical Presentation
• General weakness, redness of skin with bluish tinge (plethora)
• Pronounced hyperemia of conjunctiva (rabbit eyes), bright red tongue and soft palate
with a distinct border of transition to hard palate
• Skin of trunk and limb is pink, saphenous vein dilated
 • For any years, first symptom – skin itching, then erythromelalgia (acute burning pain in
fingertips, relived by aspirin)
• Vascular and visceral complications are rare
• Splenomegaly, but not palpable (due to increase sequestration of platelets and red blood
cells)
• Due to nosebleed or bloodletting, the patient may develop sideropenic syndrome
• 2 syndromes
o Plethoric – increase RBC, WBC, PLT in blood
o Myeloproliferative – hyperplasia of all three hematopoietic germs in BM and
extramedullary
Stages of Clinical Course
• Initial stage
o Lasts about 5 years
o Moderate erythrocytosis, small plethora, absence splenomegaly, rare vascular and
thrombotic complications. Raveled three-growth hyperplasia of bone marrow
• Advanced stage
o Without myeloid metaplasia of spleen
▪ Pronounced plethora, erythromelalgia, splenomegaly, panmyelosis
(pronounced erythromyeloid and megakaryocytic hyperplasia of bone
marrow with replacement of fat marrow with red)
▪ Thrombotic complications occur in form of heart attacks, stroke, necrosis
of fingertips
o With myeloid metaplasia of spleen
▪ Severe splenomegaly, hepatomegaly, moderate plethora, panmyelosis,
bleeding and thrombotic complications
• Terminal anemic stage
o Formation of myelofibrosis
o Aplastic anemia with pancytopenia, severe splenomegaly, hepatomegaly
o Can transform into CML, Acute leukemia
o Especially in application for treatment of radioactive phosphorus and cytostatic
Diagnosis
• Complete blood count:
o Erythrocytosis above 5.7x109/l
o Hemoglobin more than 177 g/l. Thrombocytosis.
o Neutrophilic leukocytosis with a shift to the left to single metamyelocytes and
myelocytes.
o ESR is reduced to 0.5-1 mm / hour.
• The viscosity of blood is 5-8 times higher than normal.
• Hematocrit is above 52%.
• Biochemical study: increased uric acid content, moderate increase in bilirubin levels.
• Sternal puncture: pronounced hyperplasia of all three germs of myelopoiesis -
erythrocytic, granulocytic, megakaryocytic, with the replacement of the fatty brain with
red. In the terminal stage, signs of myelofibrosis
Diagnostic Criteria
• Category A
o an increase in the mass of circulating red blood cells;
o normal oxygen saturation of arterial blood (more than 92%);
o enlargement of the spleen.
• Category B:
o leukocytosis of more than 12x109/l (in the absence of a temperature reaction,
infections);
o thrombocytosis of more than 400x109/l.;
o increased content of neutrophil alkaline phosphatase;
o increase the unsaturated vitaminB12-binding capacity of blood serum.
• The diagnosis of true polycythemia is reliable in the presence of three signs A, OR two
signs of A and one sign of B
Treatment
• Bloodletting
o In plethoric syndrome to reduce mass of circulating RBC
o 500ml removed after 1-2 days (in elderly and in presence of concomitant disease,
no more than 350ml)
o Immediately before bloodletting 400ml reopoliglykin IV and 5000U heparin
o Done until Hb decreases
o 140-150g/L, and Hct to 46-47% o Risk of vascular complication significantly
reduced, and itching reduces
• Red blood cell transpferesis
• Radioactive phorphurus-32
o To treat patient over 70 years.
o 2-3 microcuries with interval of 7 days
• Chemotherapy with active symptomatic therapy
o Pancytosis, splenomegaly visceral vascular complication
o Hydroxycarbamide 40-50mg/kg/day in 2-3 doses
o Monitor WBC
o It is combined with IF-A 3-5 mU 3-7 times a week for a long time
• Antiplatelet therapy
o To prevent thrombosis
o Acetylsalicylic acid 300-500mg/day OR dipyridamine 150-200mg/day
• Allopurinol – reduce urate diathesis 100mg TDS
• Glucocorticoids – autoimmune anemia or thrombocytopenia 80-120mg/day for 2 weeks
 12. Myeloma: pathogenesis, clinical variants, diagnostic criteria and approaches to
therapy

• Multiple myeloma is a malignant tumor of plasma cells that synthesize monoclonal

immunoglobulins or free light chains of monoclonal immunoglobulins

Pathogenesis
• Originates from a single cell belonging to B-lymphocyte systems, which has reached the
final stage of differentiation.
• All are genetic twins – evidenced by the absolute uniformity of Ig secreted by them,
which, despite their formally normal molecular structure, are called paraproteins
• Mostly they are secreted by the tumors and circulate in blood and lymph.
• Rarely, non-secreting myelomas – Ig synthesized in myeloma cells, but not released into
blood
• In accordance with class of Ig, there are G, A, D, E and Bence-Jones myelomas (only
light chains of Ig secreted)
• Rarely M and non-secreting myelomas
• Excessive concentration of proteins in blood due to Ig → increased blood viscosity,
microcirculation disorders. Ig bind to plasma clotting factors, blocking receptors on
platelet membrane →disorders of blood clotting process
• Proliferation of myeloma cells cause bone destruction – diffuse and focal osteolysis.
Spreading in BM, they displace normal sprouts of lymphocytic, granulocytic,
erythrocytic, megakaryocytic hematopoiesis → terminal stage of MM, aplastic anemia,
agranulocytosis, and thrombocytopenia. Secondary immunodeficiency. Intensive growth
and destruction of myeloma cells cause increase in Urate in blood
• Myelomatous osteolysis is accompanied by increase in content of ionized calcium
→central and peripheral neurological disorders. Excessive excretion of calcium salts by
kidney →nephropathy, interstitial nephrocalcinosis, urolithiasis →RF
• Solitary myeloma – Intra/extra osseous
• Multiple generalized myeloma – Multiple tumor, diffuse nodal, diffuse
• Depending on size of tumor mass and relation to patient’s body surface area
Clinical Variants
• Initial (asymptomatic)
o 5 -15 years, patient feels well. Proteinemia, proteinuria or Bence-Jones
proteinuria
o Electrophoresis – M-gradient or gamma globulin fraction
• Chronic (advanced)
o Not exceed beyond BM and doesn’t row into cortical layer of bone.
o Signs of hematopoietic depression absent or moderate, fever, sweating and
exhaustions are uncommon
• Terminal
o Bone destruction increases with growth of tumors into soft tissues
o Metastases in internal organs and in meninges
o General condition worse, patient lose weight, sweating, fever without foci of
infection, which doesn’t respond to Abx
o Pain in bones, weakly relieved by narcotic analgesics.
o Non-traumatic pathological fractures of flat bones, compression fractures of the
spine with secondary radicular syndrome
o Die from RF, bleeding into brain in severe thrombocytopenia
Syndromes in chronic and terminal stages
• Skeletal damage or bone-brain syndromes
o At first by non-intense, volatile, and then increasingly intense, excruciating pain
in the ribs, sternum, limbs and head
o Non-traumatic pathological bone fractures with chest deformity, compression of
lumbar and thoracic vertebrae
o Radiologically, round or irregular single effects in bones, mostly flat, at the site of
myeloma cell proliferations
o Often multiple, draining of osteolysis, giving picture of “moth-eaten cloth” or
“honeycomb”
• Syndrome of renal pathology
o Myeloma nephropathy – sever and unfavorable complication
o Excessive excretion of protein and light chain Ig
o Hyperproteinemia + proteinuria causes damage to glomeruli and tubules, activates
the formation of interstitial fibrosis in kidneys, deposits para amyloid in renal
tissue.
o Osteolysis caused by myeloma is accompanied by intensive removal of ionized
calcium from blood by kidneys, where its concentration ↑, especially in stage 3
o Tumor growth is accompanied by hyperuricemia and intensive excretion of urates
through urinary tract
o Large amount of calcium and urate condense in interstitial space of kidneys
o In end stage, kidneys are infiltrated by myeloma tumor
o All factors lead to RF and death
• High blood viscosity syndrome
o Common in pt with IgA.
o Bleeding from mucosa, retinopathy, dilated retinal veins, peripheral blood
disorders, paresthesia, Raynaud’s syndrome
o In severe cases, ulceration and gangrene of distal extremities.
 o Circulatory disorders in blood vessels of brain – coma
• Hypercalcemia syndrome
o Osteolysis, especially in terminal stage
o Nausea, vomiting, drowsiness, loss of orientations, psychotic episodes, soporotic
state and even come
o Calcium nephropathy – formation and decompensation of RF
• Syndrome of peripheral sensory neuropathy
o Violation of tactile and pain sensitivity, paresthesia – demyelination of nerve
fibers
o Possible compression of tumor infiltrated of nerve endings
o With pathological non-traumatic compression fractures of the vertebrae, radicular
disorders with pronounced pain and paraplegia
• Hemorrhagic syndrome
o Caused by high viscosity due to proteinemia (>130g/l)
o Ig from complexes with V, VII, VII CF, prothrombin, fibrinogen and are fixed on
PL → microcirculatory disorders, disorders of PLT and plasma stages of
hemostats
o In terminal period – thrombocytopenia caused by displacement of megakaryocyte
from BM
• Syndrome of depression of immune system
o Caused by displacement of normal lymphocytic and granulocytic hematopoiesis
sprouts from the bone marrow by myeloma cells →cellular and humoral
components of immunity suppressed
o Normal Ig ↓, granulocytes reduces, and circulating granulocytes have functional
defects
o They cause increased predisposition to infections, transition to more malignant
forms – ALL, lymphosarcoma
• Syndrome of impaired hematopoiesis
o Normochromic anemia. When hemorrhagic syndrome appears, become
hypochromic, IDA
o Due to intensive consumption of cyanocobalamin by tumors – B12 deficiency
anemia
• Peramelids
o Secondary from of amyloidosis with precollagen deposits
o Primarily affects organs rich in collagen-vascular adventitia, heart muscles,
tongue, dermis, tendons, and joints

Diagnostic Criteria
• Blood: Norm/Hypochromic anemia, leukopenia, thrombocytopenia, ↑ESR
• U/E: proteinuria, positive Bence-Jones protein
• Biochem: ↑proteins, urate, calcium. In terminal - ↑urea and creatinine
• Immunological: ↑monoclonal Ig of classes, light chain Ig
• Electrophoresis of blood serum proteins: high perk of M-gradient in gamma globin
• Sternal puncture: infiltration of BM with plasma cells, ↓ in normal hematopoietic cell
lines
 • Radiographically: defects in flat bones (skull, ribs, ala iliac) and vertebra in form of
single round “stamped” clearances, widespread diffuse-focal osteolysis, which gives a
picture of “moth-eaten cloth”. X-ray Dx of non-traumatic fractures

Treatment
• Stage IA and IIA – Cytostatic avoided
• Stage IIB-III – Cytostatic (Alkylating drugs – sarcolysin, cyclophosphamide, nitrosourea)
o Sarcolysin PO 10-20mg every other day (contraindi – severe
leuko/thrombocytopenia)
o Cyclophosphamide IV 100-200mg after 1-3 days (8-10 g)
• M2 treatment
o 1st day – 1.5-2mg Vincristine IV + 1mg/kg Carmustine IV OR 80-120mg
Belustine PO
o Cyclophosphamide 700-1000 mg/day IV drip o 1-7 days – Sarcolysin PO
10mg/day and prednisolone IV 1mg/kg/d
o 8th day – prednisolone reduced and discontinued on 22nd day
• Radiation therapy – large foci bone destruction, pronounced pain by fractures and not
stopped by chemo. Indicated for radicular syndrome due to compression of vertebral
bodies.
o Gamma 75-200gy (total 2500-4000gy per focus)
• Plasmapheresis to remove excess paraproteins – 3times a week, removing 1-2 L at once,
replaced by equal volume albumin, FFP
• Broad spectrum Abx to stop infection complication. To maintain anti-infective immunity,
Ig administered IM 7-10 days or every other day
• Hypercalcemia – forced diuresis, calcarine
• Prognosis is poor. Timely management – 4 years instead of 1-2 without treatment
• With prolonged treatment with cytostatic – acute leukemia
 13. Etiology, pathogenesis, classification of hemorrhagic diathesis. Treatment of
thrombocytopenic purpura.
• Bleeding diathesis refers to an increased susceptibility to bleeding or bruising. It can
occur as a result of a wide variety of underlying disorders, most of which typically affect
the clotting process.
• Clotting, or coagulation, is a normal, multistep process that creates a clot, or a clump of
semisolid blood, to prevent excessive bleeding when a blood vessel is injured.
• Clotting involves many different proteins, coagulation factors, and platelets. If one
component of the clotting system is limited, the entire process may be affected.
Etiology
• Causes can be classified into two types
o Acquired
o Congenital

• Acquired causes include

o Vascular problems
o Low platelet counts
o Vitamin K deficiency
o Increased platelet destruction
o Kidney failure
o Liver disease
o Anticoagulant therapy
o An acquired clotting factor antibody.
o Because platelets are key to coagulation, disorders that result in increased
destruction of platelets -- such as
▪ Autoimmune thrombocytopenia (ITP),
▪ Systemic lupus erythematosus
▪ Disseminated intravascular coagulation (DIC)
▪ Thrombotic thrombocytopenic purpura (TTP)
▪ Hypersplenism -- are risk factors for bleeding diathesis.
• Congenital disorders that may cause bleeding diathesis include
o Bernard-Soulier syndrome
o Glanzmann thrombasthenia
o Ehlers-Danlos syndrome
o DiGeorge syndrome.
• Some congenital causes of bleeding diathesis may also be inherited. These causes include
coagulation disorders such as
o Von Willebrand Disease
o Hemophilia.
Treatment (of hemorrhagic diathesis)
• Blood transfusion involves the transfer of plasma containing all the necessary coagulating
factors (fibrinogen, prothrombin, thromboplastin)
• Different drugs can be prescribed depending on the type of disease.
• Vitamins (K, P and C) are essential in case of obstruction to walls of blood vessels.
Treatment (ITP)
• The goal of medical care for immune thrombocytopenia (ITP) is to increase the platelet
count to a safe level, permitting patients to live normal lives while awaiting spontaneous
or treatment-induced remission.
• ITP has no cure, and relapses may occur years after seemingly successful medical or
surgical management.
• Corticosteroids (i.e., oral prednisone or high-dose dexamethasone) remain the drugs of
choice for the initial management of acute ITP
• Because corticosteroid administration may change marrow morphology, performance of a
bone marrow aspiration and biopsy should be considered to confirm the diagnosis of ITP
if the clinical presentation, patient age, or other findings are atypical for acute ITP before
the patient is treated with corticosteroids.
• Thrombopoietin receptor analogs and rituximab are second-line options for patients with
ITP lasting 3 months or more and in those who are corticosteroid dependent or have no
response to corticosteroids.
• For adults who have had ITP for longer than 12 months, splenectomy is also a second-
line option.
• Intravenous immunoglobulin (IVIG) can be the drug of second choice (after
corticosteroids) for some patients, such as when a rapid increase in platelet count is
important.
• In adults, treatment is recommended for a platelet count < 30×109/L
• The guidelines suggest either prednisone (0.5-2.0 mg/kg per day) or dexamethasone (40
mg per day for 4 days) as the type of corticosteroid for initial therapy
• In adults with ITP lasting ≥3 months who are corticosteroid-dependent or have no
response to corticosteroids, the ASH guidelines suggest either splenectomy or a TPO-RA.
• Additional precautions are required for patients with hypertension, peptic ulcers, recent
aspirin ingestion, or other risk factors for increased bleeding include
o Aspirin is contraindicated in person with ITP, because it increases the risk of
bleeding
o Platelet transfusions may be required to control clinically significant or
catastrophic bleeding but are not recommended for prophylaxis.
• In persons with acute immune thrombocytopenia (ITP), splenectomy usually results in
rapid, complete, and life-long clinical remission.
 14. Etiology, pathogenesis, clinical presentations, diagnostics, treatment of hemophilia.
• Hemophilia is a hereditary disease caused by insufficiency of blood clotting factors –
antihemophilic globulin VIII (type A) or plasma component of thromboplastin IX (type
B) and manifested by bleeding of various locations
• Mainly men get sick. The transmission of pathological gene is carried out by women
• Type A – 80% and Type B (Christmas disease) – 15-20%
Pathogenesis of Bleeding
• Genes encoding the level of factors VIII and IX are located in distal part of the long arm
of X-chromosome and are inherited by recessive type.
• Defects in these genes (duplication, shift of reading frame, inclusion of new bases,
inversion of nucleotide sequence) lead to a deficiency of clotting factors due to mutation
on the principle of “one gene-one protein”
• It is also caused by spontaneous mutation
• If disease is detected in family with no history – sporadic (1/3 of all cases)
• Hemophilia A
o Deficiency of factor VIII slowing formation of thromboplastin prothrombin
thrombin fibrinogen fibrin retraction of blood clot increased bleeding
• Hemophilia B
o Decrease in functional activity of factor IX, associated with inhibition of its
synthesis or with production of defective molecules slowdown in blood
coagulation along the internal pathway violation of formation of secondary
coagulation plug ↑ bleeding
Clinical Presentation
• Clinical picture of both types is identical
• Main clinical signs are hemorrhagic syndrome, severity of which depends on the level of
reduction of factors (Norm is 50-200%)
• Severe – 0-2%,
o Severe disease debuts in early childhood with bleeding from mucous membranes
of mouth, nose and hemorrhages in soft tissues
o Spontaneous bleeding – renal, GIT, large joints of extremities, soft tissue, CNS
o Extensive s/c and muscular hematomas, but majority is hemarthrosis with a
primary or recurrent form of damage to large joints (knees, elbows, ankles)
▪ Acute hemarthrosis – within a few hours with bleeding in intact joint, pain
and burning in extremities; amplitude of movement decreases
▪ Subacute hemarthrosis – against the background of already altered
synovial membrane after 3-4 episodes of bleeding in anamnesis and
persists despite hemostatic therapy. If it persists for several months,
hemophilic arthropathy develops •
▪ Joint pain remains at rest, limb mobility is impaired with muscle
hypotrophy
• Moderate – 2-5%,
o Bleeding first appears in preschool age (4-6 years)
o Moderate bleeding – spontaneous hemorrhage in joints, muscles, kidney or sever
hemorrhages in large joints of extremities, soft tissues, abdominal organ after
injury and operations
• Mild – 5-10%,
 o Manifested in school years by pronounced hemorrhagic syndrome after injuries
and operations (bruises, tonsillectomy, tooth extraction, appendectomy)
o Spontaneous bleeding does not occur
• Latent – over 10%
o Asymptomatic for a long time (20 years or more) and detected with trauma or
surgery (knew joint contusion, tooth extraction) with prolong bleeding in early
post-operative period
o Initial levels of factors in the blood is from 7-10 to 35%
Diagnostics
• Should be suspected in males with hemtomic type bleeding and damage to
musculoskeletal system
• Establish on the basis of comprehensive examination, including genealogical data, an
assessment of clinical manifestations and results of lab test
• Lab test
o Acute or chronic post-hemorrhagic anemia and its severity
o Increased blood clotting times
o Increase APTT at normal PT and TT
o Decrease in procoagulant activity of one of the coagulation factors; specifies the
presence or absence of level of inhibitors of deficient factor
• Joint puncture: Liquid blood in cavity
• X-ray: Hemarthrosis, erosive arthritis of knee, elbow, and other joints
• USG: s/c, i/m, subfacial, retroperitoneal hematomas, hemorrhage foci in the mesentery,
omentum, subserous tissue of thee abdominal cavity and other places
Treatment
• During the period of bleeding – bed rest.
• The basis for the treatment of hemophilia at all stages of development and progression of
these diseases is timely and sufficient dosage replacement therapy with drugs containing
VIII or IX clotting factors.
• For the treatment of severe hemorrhagic syndrome, replacement therapy is carried out
with concentrates of the deficient clotting factor VIII at an initial dose of 20-25 IU / kg
every 12 hours; the preparation of blood clotting factor IX at an initial dose of 40-50
IU/kg.
• Treatment of lesions of the musculoskeletal system
• There are 3 generations of substitution therapy drugs:
o 1st generation - cryoprecipitate and fresh frozen plasma (FFP)
o 2nd generation - concentrates of plasma coagulation factors of low and medium
purity
o 3rd generation - concentrates of plasma coagulation factors of high purity,
recombinant factors (recombinant and monoclonal purified factor VIII;
monoclonal purified factor IX).
• In acute hemarthrosis, the joint is temporarily immobilized, the blood from the joint
cavity is removed and hydrocortisone is injected. In rheumatoid syndrome, prednisolone
is prescribed at a dose of 20-40 mg / day
 15. Etiology, pathogenesis, clinical types, diagnostics, treatment of hemorrhagic
vasculitis.
Pathogenesis of Bleeding
• Stimulation of immune system by some endogenous or exogenous antigen-allergens
excess immune complex formed mainly by IgA and lesser extend IgM and IgG
immune complexes fixed in the vessels inflammation with violation of permeability of
vascular wall and subsequent hemorrhagic syndrome
• In kidney, focal mesenchymal proliferation occurs at site of deposition of immune
complexes containing IgA and complement
• Immune complexes activate the blood clotting system through C3 components DIC
with microthrombosis of small vessels
Clinical Presentation, Types, Patterns of Clinical Course
• Clinical phenomena
o Fever (first high, then sub febrile)
o Hemorrhagic purpura
o Joint syndrome o Abdominal syndrome
o Hematuric nephritis o DIC syndrome
• Clinical forms
o Skin
o Skin and joint
o Abdominal
o Renal
o Mixed
• Clinical course
o Hyperacute – development of all symptoms within few hours
o Acute – formation of clinical picture within few days
o Prolonged – skin, joint and other syndromes continue for several weeks despite
treatment
o Recurrent – proceed in waves, acute manifestation alternative with short mild
interval after which acute symptoms reappear
o Chronic persistent – constantly sees petechia of different colors on skin – red
young and greenish-yellow old
• First – pain in large joints, in abdomen without certain location, disorders of stool,
headache. Temperature is initially high, then sub febrile
• Hemorrhage maybe absent or insignificant in first day
o Skin hemorrhagic syndrome is more common – feet, shins, thighs, buttocks,
shoulder, forearms, around affected joints
o Symmetrical, accompanied by itching, paresthesia
o Pronounced on places subjected to natural trauma (inner surface of forearm,
thighs, shin, location of trouser belt, watch strap, etc.)
• Skin lesion can also be in different forms
o Small-pin point purpura, which doesn’t fade when pressed, located on an
erythematous macular background, sometime in combination with urticarial
blisters, bullae, angioedema
o Severe – diffuse erythema with ulcerative necrotic changes
o Lasts 2 days and then fade
 o In regression stage, may become purple and then brown due to degeneration of
extravascular hemoglobin
o There maybe 3-4 consecutive waves
• Joint syndrome may precede skin and abdominal manifestation, but mostly develop with
them
o Large joints affected. Hemarthrosis usually doesn’t develop
o Indistinct, volatile pain
o Less often, joint damage is persistent, with pronounced, prolonged arthralgia,
hyperemia, and edema of periarticular tissues
o There is discrepancy between severity of joint pain and absence of objective and
radiological sings of arthropathy
• Abdominal syndrome
o Hemorrhage in intestinal wall and mesentery
o Colic, nausea, vomiting, muco-bloody stool, melena
o Swollen abdomen, painful on palpitation
o Short-lived, rarely lasts 1-3 days
o In some cases, life threatening complication – obstruction, perforation with
peritonitis
• Primary acute kidney injury
o Microthrombosis in glomerular capillaries – hematuria
o Pass without traces in few days, however, in almost 2-4 weeks after onset of
disease, against background of extinction of skin, joint and abdominal symptoms,
patient again form a clinical picture of B/L kidney damage
o Acute, subacute or chronic immune complex GN
o Hematuric, nephrotic, hypertensive, mixed variant
o Severe GN with rapidly progressive renal insufficiency formed during firs year in
middle-aged and older people with recurrent course
• Relatively rare, lung lesion with pulmonary bleeding, brain hemorrhage in meninges and
acute cerebral syndrome, asphyxia due to angioedema of larynx.
Diagnostic Criteria
• Palpable purpura: slightly elevated hemorrhagic skin changes not associated with
thrombocytopenia.
• Age: age at onset of illness less than 20 years.
• Abdominal pain: diffuse abdominal pain, worse after eating, or intestinal ischemia (may
be intestinal bleeding).
• Biopsy: detection of granulocytes - histological changes manifested by granulocytic
infiltration of the walls of arterioles and venules.
• The presence of two or more of any criteria in a patient allows a diagnosis to be made
with a sensitivity of 87.1% and a specificity of 87.7%.
Diagnosis
• Cuff test – determine increased fragility of micro vessels
• Biomicroscopy of bulbar conjunctiva – sludge phenomenon, microthrombosis in
capillaries
• Blood – small and unstable leukocytosis, shift to left, anemic syndrome in massive
hemorrhage, increase ESR
• Urine – proteinuria, microhematuria, cylinduria
 • Biochem – alpha-2 and gamma globin, fibrin, fibrinogen
• Immunological – high content of immune complex, increase in IgA, in acute course IgM,
positive RF high titer of antistreptolysin-O
• Willebrand factor increases which determines degree of damage to endothelium
• Colonoscopy – spot hemorrhages
• Immunohistological examination of skin biopsy – perivascular leukocyte infiltrates near
deposits of immune complex containing IgA
• At peak – laboratory signs of DIC
Treatment
• Bed rest for at least 3 weeks
• Exclude allergenic products – cocoa, coffee, chocolate, citrus fruits, fresh berries
• Avoid prescribing antibiotic, sulfonamides and other allergenic drugs that may support
hemorrhagic vasculitis or provoke its exacerbations
• Appointment of antihistamine is of little use, not justified
• Administration of calcium, ascorbic acid, and rutin preparation
• Use of vicasol, fibrinolysis inhibitor (Epsilon-aminocaproic acid) is not indicated, since
they are usually useless or harmful
• Glucocorticoids (3-5 days) in medium doses prescribed only in a particularly severe
course with very pronounced inflammatory changes. In it necessary to “cover” such
treatment with sufficient doses of heparin, because prednisone can increase blood clotting
and block microcirculation
• Basic method of treatment – heparin 300-400 U/kg IV or every 6 hours in equal doses
under the abdominal skin
• With pronounced inflammatory syndrome diclofenac, indomethacin prescribed
• To improve microcirculation – pentoxifylline and phentolamine
• In persistent, recurrent course – therapeutic plasmapheresis
1. Diffuse toxic goiter: etiology and pathogenesis, main clinical presentations, classification,
treatment, indications for surgery.
Etiology
Genetic predisposition: 50% of patients with Graves disease have a family history of autoimmune
disorders (e.g., type 1 diabetes mellitus, Hashimoto disease, pernicious anemia, myasthenia
gravis). Also associated with HLA-DR3 and HLA-B8 alleles
Autoimmunity: B and T lymphocyte-mediated disorder
Triggers:
• Infectious agents: Yersinia enterocolitica and Borrelia burgdorferi have been shown to trigger
antigen mimicry for homologies between their protein constituents and thyroid autoantigens.
• Stress: Physical: surgery, trauma, psychological
• Pregnancy
• Environmental factors: smoke, irradiations, drugs, endocrine disruptors
Classification of goitre
Morphology:
• Growth pattern of goiter:
◦ Diffuse goiter: diffusely enlarged thyroid
▪ Graves disease
▪ Inflammation (e.g., Hashimoto thyroiditis)
▪ TSH-secreting pituitary adenoma
▪ Iodine deficiency
◦ Nodular goiter: irregular enlarged thyroid due to nodule formation
▪ Uninodular goiter (e.g., cysts, adenoma, cancer)
▪ Toxic and nontoxic multinodular goiter
• Goiter size

Thyroid function of goiter:

• Nontoxic goiter: normal TSH, fT3, and fT4 levels
E.g., Iodine deficiency
• Toxic goiter: increased thyroid hormone production
E.g., Graves disease, toxic multinodular goiter
• Hypothyroid goiter: decreased thyroid hormone production
E.g., Hashimoto's disease, congenital hypothyroid goiter

Dignity of goiter:
• Malignant goiter: e.g., thyroid carcinoma
• Benign (bland) goiter: benign thyroid enlargement
Pathogenesis
• General mechanism: B and T cell-mediated autoimmunity → production of stimulating
immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction) → ↑
thyroid function and growth → hyperthyroidism and diffuse goiter
• Thyroid-associated ophthalmopathy: activated B and T cells infiltrate retro-orbital space
targeting orbital fibroblasts → cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory
response → fibroblast proliferation and differentiation to adipocytes → production of hyaluronic
acid and GAGs and increased amount of adipocytes → ↑ in the volume of intraorbital fat and
muscle tissues → exophthalmos, lid retraction, disturbances in ocular motility (causing diplopia)
• Pretibial myxedema: dermal fibroblast stimulation and deposition of glycosaminoglycans in
connective tissue
Clinical picture
• Symptoms of hyperthyroidism
• Triad of Graves disease:
◦ Diffuse goiter
▪ Smooth, uniformly enlarged goiter
▪ Bruit may be heard at the superior poles of the lobes
◦ Ophthalmopathy
▪ Exophthalmos
▪ Ocular motility disturbances
▪ Lid retraction and conjunctival conditions
◦ Dermopathy (pretibial myxedema): non-pitting edema and firm plaques on the anterior/
lateral aspects of both legs
• β-blockers: rapid control of hyperthyroidism symptoms
• Antithyroid drugs: thionamides (e.g., methimazole, propylthiouracil)
◦ Goal: achieve euthyroid state
◦ Patients with a small goiter and mild hyperthyroidism may undergo remission on
antithyroid drugs alone (in ∼ 50% of cases).
◦ Once remission is achieved, slowly taper and stop.
• Radioactive iodine ablation:
First-line therapy in nonpregnant patients with small goiters
Second-line therapy in patients who relapse after long-term therapy with antithyroid drugs
• Surgery: near-total thyroidectomy is rarely done in Graves disease
• Complications of therapy:
Permanent hypothyroidism after radioactive iodine ablation or surgery → need for lifelong
thyroid replacement therapy
New-onset/exacerbation of Graves ophthalmopathy after radioactive iodine ablation
2. Hypothyroidism. Etiology and pathogenesis, classification, main clinical presentations,
diagnostics, treatment.
Etiology
• Primary hypothyroidism: insufficient thyroid hormone production
Hashimoto thyroiditis: The most common cause of hypothyroidism in iodine-sufficient
regions. Associated with HLA-DR3 and other autoimmune diseases (e.g., vitiligo,
pernicious anemia, type 1 diabetes mellitus, and systemic lupus erythematosus)
Postpartum thyroiditis (subacute lymphocytic thyroiditis)
De Quervain thyroiditis (subacute granulomatous thyroiditis): often subsequent to a flu-
like illness
Iatrogenic: e.g., post thyroidectomy, radioiodine therapy, antithyroid medication (e.g.,
amiodarone, lithium)
Nutritional (insufficient intake of iodine): the most common cause of hypothyroidism
worldwide, particularly in iodine-deficient regions
Riedel thyroiditis: occurs in IgG4-related systemic disease
Wolff-Chaikoff effect
Thyroid dysplasia: a disorder of embryologic development characterized by abnormal
development and/or location of thyroid tissue (e.g., lingual thyroid)
• Secondary hypothyroidism: pituitary disorders (e.g., pituitary adenoma) → TSH deficiency
• Tertiary hypothyroidism: hypothalamic disorders → TRH deficiency
Pathogenesis
The hypothalamus, anterior pituitary gland, and thyroid gland, together with their respective
hormones, comprise a self-regulatory circuit referred to as the “Hypothalamic-pituitary-thyroid
axis.”
• Primary hypothyroidism: peripheral (thyroid) disorders → T3/T4 are not produced (↓ levels) →
compensatory ↑ TSH
• Secondary hypothyroidism: pituitary disorders → ↓ TSH levels → ↓ T3/T4 levels
• Tertiary hypothyroidism: hypothalamic disorders → ↓ TRH levels → ↓ TSH levels → ↓ T3/T4
levels

Clinical features
• Symptoms related to decreased metabolic rate: fatigue, decreased physical activity, cold
intolerance, decreased sweating, hair loss (Queen Anne sign), brittle nails, and cold, dry skin,
Weight gain (despite poor appetite), Constipation, Bradycardia, Hypothyroid myopathy ,
myalgia, stiffness, cramps
• Woltman sign: a delayed relaxation of the deep tendon reflexes, which is commonly seen in
patients with hypothyroidism, but may also be associated with old age, pregnancy, and DM
• Entrapment syndromes (e.g., carpal tunnel syndrome)
• Symptoms related to generalized myxedema: Doughy skin texture, puffy appearance,
myxedematous heart disease (dilated cardiomyopathy, bradycardia, dyspnea), hoarse voice,
difficulty articulating words, pretibial and periorbital edema, myxedema coma
• Symptoms of hyperprolactinemia: Abnormal menstrual cycle (esp. secondary amenorrhea or
menorrhagia), galactorrhea, decreased libido, erectile dysfunction, delayed ejaculation, and
infertility in men
• Further symptoms: Impaired cognition (concentration, memory), somnolence, depression,
Hypertension, Goiter (in Hashimoto thyroiditis) or atrophic thyroid (in atrophic thyroiditis)
Diagnostics
Laboratory studies:
Thyroid function tests
• TSH: Best initial screening test; also used to diagnose and monitor primary hypothyroidism.
• FT4: Confirmatory test for primary hypothyroidism if TSH is elevated. Primary test in suspected
secondary or tertiary hypothyroidism and following treatment for hyperthyroidism
• Free or total T3: may be measured alongside FT4, but they are not used for the diagnosis of
hypothyroidism
Serum thyroid antibody testing: can confirm suspected autoimmune thyroid disease. Additionally,
thyroid peroxidase antibody measurements may also be considered in patients with subclinical
hypothyroidism or recurring miscarriages.
• Thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb): detectable in
the majority of patients with autoimmune hypothyroidism
• TSH receptor antibodies (TRAbs): detectable in 20% of cases of autoimmune hypothyroidism
Imaging
Imaging has no role in the primary evaluation of hypothyroidism but may be indicated if structural
abnormalities are present or suspected.
• Thyroid ultrasound: Useful for the assessment of thyroid vascularity, goiters, and thyroid
nodules. Possible findings in hypothyroidism include signs of thyroiditis.
• Nuclear medicine thyroid scan: May be indicated in the workup of thyroid nodules and goiters.
In hypothyroidism, radiotracer activity is decreased.
Treatment
• Hypothyroidism is treated with lifelong hormone substitution.
◦ Levothyroxine: synthetic form of T4
▪ First-line choice for the treatment of hypothyroidism
▪ Peripherally converted to T3 (biologically active metabolite) and rT3 (biologically
inactive metabolite)
◦ Liothyronine: synthetic form of T3
▪ Part of the treatment for myxedema coma
▪ Not recommended as monotherapy or in combination with levothyroxine for the
long-term treatment of hypothyroidism
• Reassess treatment response regularly to avoid under- and overtreatment.
Levothyroxine replacement:
• In primary hypothyroidism, levothyroxine is gradually titrated according to serial TSH
measurements targeting a normal level, for example:
◦ ↑ TSH (suggests ↓ T4 activity): typically requires a dose increase
◦ ↓ TSH (suggests ↑ T4 activity): typically requires a dose decrease
• In secondary hypothyroidism, dosage is titrated according to FT4 levels
3. Diabetes mellitus: etiology and pathogenesis, classification, clinical picture, complications
and clinical course, severity criteria, treatment.
Classification
Classification according to the WHO and American Diabetes Association (ADA)
• Type 1: formerly known as insulin-dependent (IDDM) or juvenile-onset diabetes mellitus
Autoimmune (type 1A)
LADA: Latent autoimmune diabetes in adults
Idiopathic (type 1B)
• Type 2: formerly known as non-insulin-dependent (NIDDM) or adult-onset diabetes mellitus
• Gestational diabetes
• Other types of diabetes mellitus:
MODY (maturity-onset diabetes of the young)
Multiple monogenic subtypes: MODY II, MODY III
Pancreatogenic diabetes mellitus
Endocrinopathies: Cushing disease, acromegaly
Drug-induced diabetes, e.g., due to corticosteroids (steroid diabetes)
Genetic defects affecting insulin synthesis
Infections (e.g., congenital rubella infection)
Rare immunological diseases: stiff person syndrome
Other genetic syndromes that are associated with diabetes mellitus (e.g., Down syndrome)
Etiology
Type 1 DM:
• Autoimmune destruction of pancreatic β cells in genetically susceptible individuals
• HLA association: HLA-DR3 and HLA-DR4 positive patients are at increased risk of developing
T1DM.
• Associated with other autoimmune conditions: Hashimoto thyroiditis, type A gastritis, Celiac
disease, Primary adrenal insufficiency
Type 2 DM:
• Hereditary and environmental factors
• Associated with metabolic syndrome: e.g., high waist-to-hip ratio (visceral fat accumulation)
• Risk factors for type 2 diabetes mellitus: Positive family history, Race/ethnicity (high risk factor),
Physical inactivity, History of cardiovascular disease, Polycystic ovary syndrome, Conditions
associated with insulin resistance: e.g., severe obesity and high-calorie diet, Hypertension,
Dyslipidemia, History of gestational diabetes
Pathophysiology
• Normal insulin physiology
• Secretion: Insulin is synthesized in the β cells of the islets of Langerhans. The cleavage of
proinsulin (precursor molecule of insulin) produces C-peptide (connecting peptide) and insulin,
which consists of two peptide chains (A and B chains).
• Action: Insulin is an anabolic hormone with a variety of metabolic effects on the body, primarily
contributing to the generation of energy reserves (cellular uptake and metabolism of nutrients) and
glycemic control.
Carbohydrate metabolism: insulin is the only hormone in the body that directly lowers the
blood glucose level.
Protein metabolism: insulin inhibits proteolysis, stimulates protein synthesis, and stimulates
cellular uptake of amino acids
Lipid metabolism: maintains a fat depot and has an antiketogenic effect
Electrolyte regulation: stimulates intracellular potassium accumulation
Type 1 diabetes:
• Genetic susceptibility and environmental triggers (often associated with previous viral
infection) → autoimmune response with production of autoantibodies, e.g., anti-glutamic acid
decarboxylase antibody (anti-GAD), anti-islet cell cytoplasmic antibody (anti-ICA) →
progressive destruction of β cells in the pancreatic islets → absolute insulin deficiency →
decreased glucose uptake in the tissues
Type 2 diabetes:
Mechanisms:
• Peripheral insulin resistance: Numerous genetic and environmental factors; Central obesity →
increased plasma levels of free fatty acids → impaired insulin-dependent glucose uptake into
hepatocytes, myocytes, and adipocytes.
Increased serine kinase activity in fat and skeletal muscle cells → phosphorylation of insulin
receptor substrate (IRS)-1 → decreased affinity of IRS-1 for PI3K → decreased expression of
GLUT4 channels → decreased cellular glucose uptake
• Pancreatic β cell dysfunction: accumulation of pro-amylin (islet amyloid polypeptide) in the
pancreas → decreased endogenous insulin production
• Progression: Initially, insulin resistance is compensated by increased insulin and amylin secretion.
Over the course of the disease, insulin resistance progresses, while insulin secretion capacity
declines. After a period of impaired glucose tolerance with isolated postprandial hyperglycemia,
diabetes manifests with fasting hyperglycemia.

Clinical picture
• Classic symptoms of hyperglycemia:
Polyuria, which can lead to secondary enuresis and nocturia in children
Polydipsia Polyphagia
• Nonspecific symptoms: Unexplained weight loss, visual disturbances, e.g., blurred vision, fatigue,
pruritus, poor wound healing, increased susceptibility to infections, Calf cramps
• Additionally in type 2: Benign acanthosis nigricans, Acrochordon
• Type 1 DM patients appear thin typically

Interpretation of glycemic tests

Treatment
• Main goal: blood glucose control, tailored to glycemic targets and regularly monitored
Patients with T1DM always require insulin therapy.
T2DM may be managed with noninsulin antidiabetics and/or insulin therapy.
Acute illness may require temporary changes in treatment (e.g., increased insulin demand
due to acute stress reaction).
• Comprehensive diabetes care (all patients):
◦ Continuous patient education
◦ Lifestyle modifications, including: Weight reduction, Balanced diet and nutrition
(including a high-fiber diet), Regular exercise, Smoking cessation
◦ Routine screening for and management of common comorbidities and complications
• Risk assessment and prevention:
◦ Control of blood pressure and blood lipids
◦ ASCVD risk assessment and ASCVD prevention:
▪ Patients aged 40–75 years with diabetes mellitus: Initiate moderate-intensity
statin therapy, regardless of lipid levels.
▪ Assess indications for high-intensity statins.
• Glycemic targets:
HbA1c: < 7%: suitable for most patients
Preprandial capillary glucose: 80–130 mg/dL
Peak postprandial capillary glucose: < 180 mg/dL
Anti-glycemic therapy
Type 1 diabetes mellitus
Insulin replacement therapy:
• Treatment options: Multiple daily insulin injections, Insulin pump (consider for most patients)
• Starting dose calculation: Total daily dose (TDD) of insulin is usually ∼ 0.4–1.0 units/kg per
day, divided into 50% basal and 50% prandial insulin. Consider initiating treatment with 0.5
units/kg per day.
Other treatment strategies:
• Noninsulin antidiabetics: not generally used in T1DM treatment
• Pancreas and islet transplantation: Can improve glucose control but are not standard treatments
because of the need for lifelong immunosuppressive therapy
Type 2 diabetes mellitus
• Start treatment in all patients at diagnosis:
Monotherapy with metformin is the first-line initial treatment for most patients.
If there are contraindications for metformin, choose a different noninsulin antidiabetic,
depending on patient factors.
• Consider initial or early dual therapy w/ a noninsulin antidiabetic in certain patients
• Consider the necessity for early combination therapy with insulin
• Reevaluate treatment and treatment adherence every 3–6 months.
Sequentially add noninsulin antidiabetic drugs until glucose targets are met.
If targets are still not met despite adequate treatment: Add an injectable GLP-1 receptor
agonist. Consider insulin therapy.

Non insulin anti-diabetic medications

4. Chronic adrenocortical insufficiency: etiology and pathogenesis, main clinical presentations,
complications and clinical course, treatment.
• Adrenal insufficiency is a failure of the adrenal glands to produce adequate amounts of adrenocortical
hormones. It can be primary, secondary, or tertiary
ETIOLOGY
Primary (Addison disease)
• Autoimmune adrenalitis
• Infectious adrenalitis (TB, CMV, Histoplasmosis)
• Adrenal hemorrhage
o Sepsis: especially meningococcal sepsis (endotoxic shock) → hemorrhagic necrosis (Waterhouse-
Friderichsen syndrome)
o Disseminated intravascular coagulation (DIC)
o Anticoagulation: especially heparin (heparin-induced thrombocytopenia)
o Venous thromboembolism, especially in antiphospholipid syndrome (APS)
o Adrenal tumor (most commonly pheochromocytoma) → intratumoral bleeding
o (Short-term) steroid usage
o Trauma (mostly blunt trauma, can also occur postoperatively)
o In neonates: birth trauma, difficult labor (e.g., breech delivery, forceps/vacuum delivery, prolonged
labor), maternal diabetes
• Infiltration of the adrenal glands (Tumors (adrenocortical tumors, lymphomas, metastatic carcinoma),
Amyloidosis, Hemochromatosis
• Adrenalectomy
• Impaired activity of enzymes that are responsible for cortisol synthesis (Cortisol synthesis inhibitors (e.g.,
rifampin, fluconazole, phenytoin, ketoconazole): drug-induced, 21β-hydroxylase deficiency)
• Vitamin B deficiency
Secondary – decrease ACTH production
• Sudden discontinuation of chronic glucocorticoid therapy or stress (e.g., infection, trauma, surgery) during
prolonged glucocorticoid therapy
• Hypopituitarism
Tertiary – decrease CRH production
• The most common cause is sudden discontinuation of chronic glucocorticoid therapy.
• Rarer causes include hypothalamic dysfunction (e.g., due to trauma, mass, hemorrhage, or anorexia)
PATHOGENESIS
Primary (Addison disease)
• Damage to the adrenal gland leads to the deficiency in all three hormones produced by the adrenal cortex:
androgen, cortisol, and aldosterone
• Hypoandrogenism
• Hypocortisolism leads to:
o ↑ ACTH → ↑ production of POMC (in order to increase ACTH production) → ↑ melanocyte-
stimulating hormone (MSH) → hyperpigmentation of the skin (bronze skin)
o ↑ ADH level → retention of free water → dilutional hyponatremia
o ↓ Expression of enzymes involved in gluconeogenesis → ↓ rate of gluconeogenesis → hypoglycemia
o Lack of potentiation of catecholamines action → hypotension
• Hypoaldosteronism → hypotension (hypotonic & volume contraction), hyperkalemia, metabolic acidosis
Secondary
• ↓ ACTH → hypoandrogenism and hypocortisolism
• Aldosterone synthesis is not affected (mineralocorticoid production is controlled by RAAS and
angiotensin II, not by ACTH).
Tertiary
• ↓ CRH → ↓ ACTH → hypoandrogenism and hypocortisolism
• Aldosterone synthesis is not affected.
MAIN CLINICAL FEATURES
• Hypoaldosteronism – hypotension, salt craving. Hyponatremia, Hyperkalemia, normal anion gap,
metabolic acidosis
• Hypocorticolism – weight loss, anorexia, fatigue, lethargy, depression, muscle aches, weakness, GI
complaints, sugar cravings, orthostatic hypotension. Hyperglycemia, hyponatremia
• Hypoandrogenism – loss of libido, loss of axillary and pubic hair, impaired spermatogenesis. ↓DHEA-S
• Elevated ACTH – hyperpigmentation of areas that are not normally exposed to sunlight. ↑MSH
COMPLICATIONS
• The most dangerous complication of adrenal insufficiency is an adrenal crisis
• If left untreated, adrenal crisis can result in death.
• Frequent low blood sugar levels can increase the risk of hypoglycemic shock
CLINICAL COURSE
• Cardiovascular form - the phenomena of acute circulatory failure dominate (pallor of the face with
acrocyanosis, cold extremities, severe arterial hypotension, thready pulse, anuria, loss of consciousness)
• Gastrointestinal form - similar in symptoms to an acute abdomen (abdominal pain of a spastic nature,
constant nausea, uncontrollable vomiting, sometimes with blood, diarrhea)
• Neuropsychic form - dominated by headache, meningeal symptoms, convulsions, focal symptoms,
lethargy, stupor, delirium are characteristic
TREATMENT
• Replacement therapy
o Glucocorticoids (hydrocortisone, cortisone acetate, prednisolone) – Total dose should be given in
divided doses, with highest in the morning
o Mineralocorticoids (fludricortisone)
o Androgens (as needed) (DHEA)
o Replacement of other hormones if there is concomitant hypopituitarism
• Underlying causes: Identify and treat reversible conditions in all patients.
• Prevention of adrenal crisis – stress dose steroids
5. Cushing's disease and syndrome: etiology and pathogenesis, main clinical presentations, diagnostics,
complications and clinical course, treatment.
ETIOLOGY AND PATHOGENESIS
• Exogenous (iatrogenic) Cushing syndrome
o Prolong glucocorticoid therapy → hypercortisolism → decrease ACTH → bilateral adrenal atrophy
o Most common cause of hypercortisolism
• Endogenous Cushing syndrome
o Primary hypercortisolism (ACTH-independent Cushing syndrome)
▪ Autonomous overproduction of cortisol by the adrenal gland → ACTH suppression → atrophy of
the contralateral adrenal gland
• Adrenal adenomas
• Adrenal carcinoma
• Macronodular adrenal hyperplasia
o Secondary hypercortisolism
▪ Pituitary ACTH production (Cushing disease)
• Pituitary adenomas → ACTH secretion → bilateral adrenal gland hyperplasia
▪ Ectopic ACTH production
• Paraneoplastic syndrome → ↑ ACTH secretion → bilateral adrenal gland hyperplasia
• Carcinomas include: Small cell lung cancer, Renal cell carcinoma, Pancreatic or bronchial
carcinoid tumors, Pheochromocytoma, Medullary thyroid carcinoma
MAIN CLINICAL PRESENTATIONS
• Skin
o Thin, easily bruisable skin with ecchymoses
o Stretch marks (classically purple abdominal striae)
o Hirsutism
o Acne
o If secondary hypercortisolism: often hyperpigmentation (darkening of the skin due to an overproduction
of melanin), especially in areas that are not normally exposed to the sun (e.g., palm creases, oral cavity)
o Delayed wound healing
o Flushing of the face
• Neuropsychological: lethargy, depression, sleep disturbance, psychosis
• Musculoskeletal: Osteopenia, osteoporosis, pathological fractures, avascular necrosis of the femoral head.
Muscle atrophy/weakness
• Endocrine and metabolic
o Insulin resistance; → hyperglycemia → mild polyuria in the case of severe hyperglycemia
o Dyslipidemia
o Weight gain characterized by central obesity, moon facies, and a buffalo hump
o ♂: Decreased libido
o ♀: Decreased libido, virilization, and/or irregular menstrual cycles (e.g., amenorrhea)
o Growth delay (in children)
DIAGNOSTICS
• General laboratory findings
o Hypernatremia, hypokalemia, metabolic alkalosis
o Hyperglycemia, Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia)
o Leukocytosis (predominantly neutrophilic), eosinopenia
• Screening for hypercortisolism
↑ 24-hour urine cortisol (> 3 times the normal value i.e. > 300 μg/24 h)
o
↑ Early morning serum cortisol (> 50 nmol/L) following low-dose dexamethasone suppression test
o
↑ Midnight salivary cortisol (> 4 nmol/L)
o
↑ Midnight serum cortisol (> 7.5 μg/dL)
o
• Identifying the cause
o Hormone analysis - Once glucocorticoid therapy has been ruled out, the following tests are used to
identify the cause of hypercortisolism
Low-dose High-dose CRH
ACTH
Disorder Dexamethasone Dexamethasone stimulation
level
suppression test suppression test test
↑ ACTH and
Normal ↔︎ ↓ Cortisol ↓ Cortisol
Cortisol
Primary ↔︎ ACTH and
↓ ↔︎ Cortisol ↔︎ Cortisol
hypercortisolism Cortisol
↑ ACTH and
Cushing disease ↑ ↔︎ Cortisol ↓ Cortisol
Cortisol
Ectopic ACTH ↔︎ ACTH and
↑ ↔︎ Cortisol ↔︎ Cortisol
secretion Cortisol

o Imaging to localize tumors

▪ CT/MRI of abdomen – for adrenal tumors (if primary hypercortisolism suspected)
• The adrenal cortex contralateral to the tumor shows atrophy due to reduced ACTH stimulation.
• In Cushing disease, CT and/or MRI of the abdomen shows bilateral hyperplasia of both the
zona fasciculata and zona reticularis
▪ CT/MRI of skull
• If no findings are present on neuroimaging, perform bilateral sampling of the inferior petrosal
sinus in order to measure ACTH levels
▪ Other tests – of ectopic ACTH production is suspected
• Chest X-ray and/or CT, abdominal CT, pelvic CT, Thyroid USG
COMPLICATIONS
• Cardiac decompensation, osteoporosis with multiple compression fractures of the vertebral bodies and rib
fractures, suppurative processes with the possible development of septicopyemia, severe pyelonephritis
with the development of chronic renal failure, steroid psychosis, etc.
CLINICAL COURSE
• Rapidly progressive course of the disease (rapid increase in hypercortisolism syndromes from 3-6 months)
• Torpid course (relatively slow development of hyperfunction of the adrenal cortex).
TREATMENT
• Exogenous Cushing syndrome: Consider lowering the dose of glucocorticoids. Consider the use of
alternatives to glucocorticoids (e.g., azathioprine)
• Endogenous Cushing syndrome
o Inoperable disease: (e.g., inoperable adrenal carcinomas, advanced small cell carcinoma of the lung):
drugs to suppress cortisol synthesis; (e.g., metyrapone, mitotane, ketoconazole)
o Operable disease: Surgical therapy is the treatment of choice.
▪ Adrenocortical tumor: laparoscopic or open adrenalectomy (a surgical procedure to remove one or
both adrenal glands)
▪ Pituitary adenoma: transsphenoidal resection of the pituitary adenoma
▪ ACTH-secreting ectopic tumor: resection of the ectopic foci (e.g., bronchial carcinoid)
6. Pheochromocytoma: pathogenesis of main clinical presentations, symptomatology, diagnostics,
treatment.
PATHOGENESIS OF MAIN CLINICAL PRESENTATIONS
• PCC secretes catecholamines (mainly norepinephrine, to a lesser extent adrenaline and dopamine), in rare
cases serotonin, somatostatin, corticotropin and other hormonally active substances are produced.
Adrenaline is secreted only by adrenal PCC, noradrenaline is secreted by adrenal PHC and extra-adrenal
chromaffin tissue.
• The main clinical manifestations of pheochromocytoma are due to the effect of CA (norepinephrine,
adrenaline, dopamine) on the receptors of target organs:
o Increase in the strength and frequency of heart contractions (1), vasoconstriction of the skin and
internal organs () → arterial hypertension syndrome, cardiac syndrome (shortness of breath,
palpitations, cardiac asthma phenomena)
o Influence of CA on brain receptors → neuropsychic syndrome (nervous excitability, increased fatigue,
headaches, paresthesias)
o Relaxation of the ciliary muscle (), activation of apocrine sweat glands ()
o Relaxation of the SMC of the walls of the gastrointestinal tract (2, 2), contraction of the SMC of the
sphincters (1) → gastrointestinal syndrome (abdominal pain, nausea, vomiting)
o Stimulation in the liver of gluconeogenesis and glucogenolysis (/2), lipolysis in fat cells (3), renin
release in the cells of the juxta-glomerular apparatus of the kidneys (1) → endocrine exchange
syndrome (symptomatic diabetes mellitus , decreased sexual function)
SYMPTOMS
• Episodic hypertension (or persistent hypertension in some cases)
o Triggers for paroxysmal elevations in blood pressure: foods and beverages high in tyramine; (e.g., red
wine, aged cheese), surgery, pressure on the tumor (e.g., during massage), or certain drugs (e.g., beta
blockers, MAOIs)
• Paroxysmal
o Throbbing headache
o Diaphoresis
o Heart palpitations, tachycardia
o Pallor
o Abdominal pain and nausea
o Anxiety
• Weight loss due to increased basal metabolism
• Hyperglycemia
• Signs of polycythemia, if EPO is secreted
• Other features consistent with associated familial disorders:
o MEN 2A: medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia
o MEN 2B: medullary thyroid cancer, pheochromocytoma, oral/intestinal neuromas, and marfanoid
habitus
o NF1: cutaneous neurofibromas, cafe-au-lait spots, and Lisch nodules
o VHL: renal cell carcinoma, hemangioblastoma, angiomatosis, and pheochromocytoma
DIAGNOSTICS
Laboratory tests
• Whenever possible, all medications should be put on hold one week prior to testing.
• Best initial test: plasma free metanephrines test
o Examples: homovanillic acid, vanillylmandelic acid
o High sensitivity
• Confirmatory test: metanephrines and catecholamines in 24-hour urine (high specificity)
• Clonidine suppression test (rarely used)
o Principle of the test: In healthy patients, clonidine normally significantly decreases plasma
catecholamine levels by at least 30%.
o Evaluation of results: If pheochromocytoma is present, catecholamine levels will fail to decrease upon
clonidine administration, as the tumor will continue to produce catecholamines
• Genetic testing: if MEN2A, MEN2B, NF1, or VHL is suspected
• Immunohistochemical staining: positive for chromogranin, synaptophysin, and NSE
Other diagnostic tests
• 24-hour ambulatory blood pressure monitoring
• Adrenal/abdominal CT or MRI (after positive biochemistry tests to localize tumor)
• Scintigraphy (MIBG)
• Other imagistic tests: to search for potential additional tumors in patients with pheochromocytoma and
MEN2A, MEN2B, NF1, or VHL
TREATMENT
Operable disease – Preoperative BP management and then surgery
• Preoperative blood pressure management: combined alpha-adrenergic and beta-adrenergic blockade
• First, a non-selective irreversible alpha-blocker; is given : Phenoxybenzamine blocks alpha-1 and alpha-2
adrenoceptors equally and irreversibly
• After sufficient alpha-adrenergic blockade, a beta-blocker may be started for additional blood pressure
control and control of tachyarrhythmias.
• Laparoscopic tumor resection (adrenalectomy): treatment of choice. Open surgical resection is reserved
for large or invasive tumors.
Inoperable disease
• Benign pheochromocytoma: primary therapy with phenoxybenzamine
• Malignant pheochromocytoma
o Metaiodobenzylguanidine (MIBG) therapy: Because MIBG is similar in structure to norepinephrine,
it is taken up by sympathetic nerve cells, including neuroblastoma or pheochromocytoma tumor cells,
throughout the body. When MIBG is combined with radioactive iodine, it can be used as a treatment
that delivers radiation directly to cancer cells.
o Otherwise, palliative treatment (chemotherapy, tumor embolization)
VII. Connective tissue diseases, joint diseases
1. Systemic lupus erythematosus: etiology and pathogenesis, classification, main clinical
presentations, clinical course and outcomes, treatment. Clinical pharmacology of corticosteroids.
Pulse therapy: indications, contraindications, side effects.
Def : SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread
inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and
blood vessels.
predominantly affects women of childbearing age and is the most common form of lupus.
ETIOLOGY :
The exact etiology is unknown, but several predisposing factors have been identified.
• Genetic predisposition [3]
o HLA-DR2 and HLA-DR3 are commonly present in individuals with SLE.
o Genetic deficiency of classical pathway complement proteins (C1q, C2, C4) in approx.
10% of affected individuals
• Hormonal factors: Hyperestrogenic states (e.g., due to oral
contraceptive use, postmenopausal hormonal therapy, endometriosis) are associated with an increased
risk of SLE. [4]
• Environmental factors [3][4]
o Cigarette smoking and silica exposure increase the risk of developing SLE.
o UV light and EBV infection may trigger disease flares, but there is insufficient evidence on
whether they cause SLE.
o Drugs such as procainamide or hydralazine

PATHOGENESIS :
The exact pathomechanism of SLE is not fully understood, but the following two processes are the most widely
accepted hypotheses: [5]
• Autoantibody development: deficiency of classical complement proteins (C1q, C4, C2) → failure
of macrophages to phagocytose immune complexes and apoptotic cell material (i.e., plasma and
nuclear antigens) → dysregulated, intolerant lymphocytes targeting normally hidden
intracellular antigens → autoantibody production (e.g., ANA, anti-dsDNA)
• Autoimmune reactions
o Type III hypersensitivity (most common in SLE) → antibody-antigen
complex formation in microvasculature → complement activation
and inflammation → damage to skin, kidneys, joints, small vessels
o Type II hypersensitivity → IgG and IgM antibodies directed against antigens on cells
(e.g., red blood cells) → cytopenia

CLASSIFICATION
a) by the nature of the flow :
1) acute - sudden onset of the disease, high body temperature, acute polyarthritis with sharp pain in the joints,
pronounced skin changes, severe polyserositis, kidney damage, rapid progression.
2) subacute - gradual development of the disease, normal or subfebrile body temperature, moderate articular
syndrome, minimal skin changes, long-term remissions
+3) chronic - satisfactory general condition for a long time, more often monosyndromic damage to the joints or
skin, slow progression of the process with gradual damage to other organs and systems
b) according to the degree of activity of the process :
1) active phase: high (III) degree, moderate (II) degree, minimal (I) degree
2) inactive phase (remission phase)
c) depending on the location of the lesion : damage to the skin, joints, serous membranes, heart, lungs, kidneys,
nervous system
CLINICAL PRESENTATION → SLE is a systemic disease characterized by phases of remission and
relapse. Some individuals only experience mild symptoms, while others experience severe symptoms and rapid
disease progression. SLE can affect any organ.
common
• Constitutional: fatigue, fever, weight loss
• Joints (> 90% of cases) [3]
o Arthritis and arthralgia
o Distal symmetrical polyarthritis
• Skin (85% of cases) [3][7]
o Malar rash (butterfly rash): flat or raised fixed erythema over both malar
eminences (nasolabial folds tend to be spared)
o Raynaud phenomenon
o Photosensitivity → maculopapular rash
o Discoid rash
o Oral ulcers (usually painless)
o Nonscarring alopecia (except with discoid rashes)
o Periungual telangiectasia

Less common [3]

• Hematological: petechiae, pallor, or recurrent • Vascular
infections due to cytopenias o Vasculitis
• Musculoskeletal: myalgia o Thromboembolism
• Serositis: pleuritis and pericarditis → effusions • Neurological
• Kidneys: nephritis with proteinuria o Seizures
• Heart o Psychosis
o Pericarditis, myocarditis, endocarditis o Personality changes
(Libman-Sacks endocarditis) o Lupus cerebritis
o Aortic valve lesions o Aseptic meningitis
o Coronary artery disease o Polyneuropathy
• Lungs • Eyes: keratoconjunctivitis sicca
o Pneumonitis
o Interstitial lung disease
o Pulmonary hypertension

Prognostically unfavorable signs of SLE : the onset of the disease at 14-24 years; the presence of lupus
nephritis, especially with nephrotic syndrome, at the onset of the disease; the presence of hypertension at the
onset of the disease; the presence of "evil" Raynaud's syndrome at the onset of the disease; inadequate therapy.
TREATMENT
• Patients
with SLE usually require life-long immunosuppressants.
Management is guided by disease severity and the systems or organs affected
o
• NSAIDs can provide symptomatic relief.
• Nonpharmacological measures include:
o Lifestyle changes (e.g., smoking cessation, aerobic exercise)
o Avoidance of UV light

Pharmacotherapy
• All patients: Hydroxychloroquine is the cornerstone of therapy (regardless of disease
activity).
• Mild to moderate disease (no vital organs affected): Consider the addition
of oral glucocorticoids with or without other immunosuppressive agents to achieve
remission.
• Severe or organ-threatening disease
o Induction therapy
▪ High-dose IV glucocorticoids and other immunosuppressive agents
▪ Used until symptom remission or low disease activity is achieved
o Maintenance of remission
▪ Hydroxychloroquine with or without lower dose glucocorticoids
▪ AND/OR immunosuppressants or biological agents
• Disease flares: Adjust therapy based on the severity of organ involvement.

CLINICAL PHARMACOLOGY OF CORTICOSTEROIDS

Systemic corticosteroids • Local corticosteroids (local glucocorticoids)
• Corticosteroids that are o Corticosteroids that are administered
administered orally, topically, intraarticularly,
intravenously, or as eye/ear drops, or are aerosolized and
intramuscularly inhaled (inhaled corticosteroids)
• Act systemically as they are o Act primarily at the site administered; a
distributed throughout the fraction is systemically absorbed [4]
body o Examples: beclomethasone, budesonide,
clobetasol, and fluticasone

PHARMACOKINETICS
1. Absorption and fate Readily absorbed after oral administration. Selected compounds may be
administered intravenously, intramuscularly, intra-articularly, topically, or via inhalation or intranasal
delivery. After absorption, GCS are greater than 90% bound to plasma proteins, mostly corticosteroid-
binding globulin or albumin & are metabolized by the liver microsomal oxidizing enzymes. Metabolites
are conjugated and excreted by kidney. Prednisone given in pregnancy because it minimizes steroid
effects on fetus. Its a prodrug that isn’t converted to active compound, prednisolone, in the fetal liver.
Prednisolone formed in mother is biotransformed to prednisone by placental enzymes.
Discontinuation: abrupt removal of corticosteroids causes acute adrenal insufficiency that can be fatal. This
risk, coupled with the possibility that withdrawal could exacerbate the disease, means that the dose must be
tapered slowly according to individual tolerance.
 Adverse effects:
• Skin: poor wound healing, skin atrophy, stretch marks, purpra, steroid acne, hypertrichosis, increased risk
of SCC
• Cardiovascular system: Hypertension
• Metabolism, electrolyte and endocrine system: weight gain, hyperglycaemia, hypocalcemia, Cushinglike
syndrome (redistribution of body fat, puffy face, hirsutism and increased appetite)
• GI system: ulcers, GI haemorrhage, pancreatitis
• CNS and psyche: mood disorders, cognitive disorders, psychosis
• Eyes: cataract, glaucoma
• Others: avascular bone necrosis, acute adrenal insufficiency, adrenocortical atrophy, osteoporosis,
osteopenia, corticosteroid induced myopathy, myalgia, immunosuppression, liver damage
PULSE THERAPY

pulse therapy: rapid intravenous administration of large doses of corticosteroids (at least 1000 mg of
methylprednisolone) within 30-60 minutes (at least 1000 mg of methylprednisolone) once a day for 3
days

Options for pulse therapy : classic 1000 mg for 3 days, small pulse therapy - 250-500 mg for 3
days, pulse therapy in high doses - 2000 mg for 3 days

Indications : rapidly progressive glomerulonephritis, systemic vasculitis, systemic lupus erythematosus,

acute renal allograft rejection, juvenile rheumatoid arthritis, juvenile dermatomyositis, pemphigus,
optic neuritis, multiple sclerosis and acute disseminated encephalomyelitis.

+Side effects of pulse therapy: frequent (facial flushing, transient increase in blood pressure,
transient hyperglycemia, myalgia, atralgia), rare (arrhythmias against the background of electrolyte
disturbances - furosemide cannot be used simultaneously!, intractable hiccups, anaphylactic
reactions, dissemination of infection, neurological disorders)

Contraindictaions : ( not sure if this is correct)

• Systemic infections, fungal sepsis, uncontrolled hypertension and hypersensitivity to the steroid
preparation.
• Absolutely contraindicated in pregnant, lactating patients
2. Systemic sclerosis: etiology and pathogenesis, classification, main clinical presentations,
clinical course and outcomes, treatment.
Systemic sclerosis (SSc) is a chronic disease caused by abnormal growth of connective tissue, which leads to diffuse thickening and
hardening of the skin and often the inner organs.

ETIOLOGY
Systemic sclerosis is an autoimmunologic disease, but the pathogenesis is only partially
understood. Certain factors are well known to trigger occurrence of the disease or create a
similar clinical appearance. Environmental factors include exposure to the following:
• Vibration injury (similar vascular changes)
• Silica: This may be an occupational disease in arc welders.
• Organic solvents (eg, toluene, benzene, xylene)
• Aliphatic hydrocarbons (eg, hexane, vinyl chloride, trichloroethylene)
• Epoxy resin
• Amino acid compound L-5-hydroxytryptophan
• Pesticides
• Drugs (eg, bleomycin, carbidopa, pentazocine, cocaine, penicillamine, vitamin
K): A limited form of cutaneous systemic sclerosis has been described with
paclitaxel in with the setting of breast cancer.
• Appetite suppressants (eg, phenylethylamine derivatives)
• Substances used in cosmetic procedures (eg, silicone or paraffin implants)

PATHOPHYSIOLOGY
The cause of systemic sclerosis is poorly understood. There is evidence for a genetic component and associations with
alleles at the HLA locus. Isolated cases are reported of systemic sclerosis-like disease that has been triggered by
exposure to silica dust, vinyl chloride, hypoxyresins and trichloroethylene. There is clear evidence of immunological
dysfunction; T lymphocytes infiltrate the skin and there is abnormal fibroblast activation leading to increased production
of extracellular matrix in the dermis, primarily type I collagen. This results in symmetrical thickening, tightening and
induration of the skin (sclerodactyly). Arterial and arteriolar narrowing occurs due to intimal proliferation and vessel wall
inflammation. Endothelial injury causes release of vasoconstrictors and platelet activation, resulting in further
ischaemia, which is thought to exacerbate the fibrotic process.

CLASSIFICATION

Limited cutaneous scleroderma

• Raynaud phenomenon for years, occasionally decades
• Skin involvement limited to hands, face, feet, and forearms (acral distribution)
• Dilated nailfold capillary loops, usually without capillary drop-out
• A significant (10 to 15 percent) late incidence of pulmonary hypertension, with or without skin
calcification, gastrointestinal disease, telangiectasias (CREST syndrome), or interstitial lung
disease
• Renal disease rarely occurs

Diffuse cutaneous scleroderma

 • Raynaud phenomenon followed, within one year, by puffy or hidebound skin changes
• Truncal and acral skin involvement; tendon friction rubs
• Nailfold capillary dilation and capillary drop-out
• Early and significant incidence of renal, interstitial lung, diffuse gastrointestinal,and myocardial disease

Scleroderma sine scleroderma

• Presentation with pulmonary fibrosis or renal, cardiac, or gastrointestinal disease

• No skin involvement
• Raynaud phenomenon may be present

CLINICS
Common symptoms
• Cutaneous findings
o Thickening and hardening of the skin: Skin appears smooth, shiny, and puffy.
o Sclerodactyly: fibrotic thickening and tightening of the skin of the fingers and hands
▪ Initially edema, followed by fibrosis with waxy appearance of the skin
▪ Red-blue discoloration of the fingers
▪ Limited range of motion and possibly flexure contractures and clawing of the
digits
o Multiple, painful ischemic digital ulcers with atrophy and necrotic spots
o Digital pitting: hyperkeratotic scarring, most commonly affecting the fingertips
o Lesions on the proximal nail fold
o Depigmentation of the skin with sparing of perifollicular pigmentation (salt-and-
pepper appearance)
o Face
▪ Loss of expression (mask-like facies)
▪ No wrinkles
▪ Shortened frenulum
▪ Microstomia (a disproportionately small mouth) accompanied with characteristic
perioral wrinkles
• Vascular disease→ Raynaud phenomenon , Thromboembolism
• Other → Fatigue, weakness , Joint stiffness/pain
Limited cutaneous systemic sclerosis
• Skin manifestations are usually restricted to the hands, fingers, and face.
• Disease progression is slower compared to diffuse cutaneous systemic sclerosis.
• In 90% of cases, Raynaud phenomenon precedes the onset of other symptoms.
• Extracutaneous organ involvement may occur.
• Often manifests as CREST syndrome
o C: Calcinosis cutis (small white calcium deposits on the pressure points of the extremities
such as the elbows, knees, fingertips, and, to a lesser extent, face and neck)
o R: Raynaud phenomenon
o E: Esophageal hypomotility: smooth muscle atrophy and fibrosis → esophageal
dysmotility and decreased LES pressure → dysphagia, gastroesophageal
reflux, heartburn → aspiration, Barrett esophagus, stricture
o S: Sclerodactyly
o T: Telangiectasia

TREATMENT
1. Antifibrotic therapy :
- D-penicillamine 125-500 mg orally every other day on an empty stomach (be careful if you are allergic
to penicillins!)
- enzyme preparations: lidase 64 IU subcutaneously or intramuscularly 10 injections
2. Prevention and treatment of vascular complications in violation of microcirculation :
- calcium channel blockers: amlodipine 5-20 mg/day, diltiazem 120-300 mg/day, nifedipine 10-30 mg 3
times/day orally
- sympatholytics: prazosin 1-2 mg 2-3 times / day inside
- AT II receptor antagonists : losartan 25-100 mg/day orally
- pentoxifylline (trental) 400 mg 3 times / day inside
- prostaglandins - indicated for critical ischemia in / in and / art for 6-24 hours for 2-5 days: alprostatide
0.1-0.4 mg / kg / day, iloprost 0.5-2.0 mg/kg/day
3. Anti-inflammatory therapy :
- GCS - in the edematous stage and with a pronounced active course of the process (15-20 mg / day orally
according to prednisone)
- cytostatics - with the ineffectiveness of corticosteroids: methotrexate 15 mg / week orally, cyclosporine
A 2-3 mg / kg / day orally
- NSAIDs
4. Symptomatic therapy : for esophagitis: H 2 blockers and proton pump blockers, motility regulators
(cerucal); therapy for cardiopulmonary insufficiency, etc.

OUTCOMES → 1 SSc has the highest cause-specific mortality among connective tissue diseases.
2 Progressive interstitial lung disease (ILD) is the leading cause of death in SSc.
3. Dermatomyositis: etiology and pathogenesis, classification, main clinical presentations, clinical course
and outcomes, treatment.
Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous findings that occur in
children and adults
ETIOLOGY
The cause of dermatomyositis is unknown. However, genetic, immunologic, infectious, and environmental
factors have been implicated. antibody-mediated vasculopathy, associated with malignancies (non-Hodgkin
lymphoma; lung, stomach, colorectal, or ovarian cancer are also risk factors. The average age at diagnosis is 40,
and almost twice as many women are affected as men.
PATHOGENESIS
1. Infectious agents, drugs, physical factors → toxic effects on muscle tissue and endothelium damage to
myocytes, endotheliocytes → release of autoantigens → synthesis of myositis-specific autoantibodies
2. Genetic predisposition → violation of the cellular link of immunity with a predominance of the activity of
cytotoxic T-lymphocytes over T-suppressors → immunological hyperreactivity → synthesis of myositis-
specific autoantibodies
3. Synthesis of myositis-specific auto-AT leads to the formation of circulating immune complexes, their
deposition in target organs (skin, muscles, endothelium) with the formation of immune complex inflammation.
CLASSIFICATION
a) by etiology : primary (idiopathic) and secondary (paraneoplastic)
b) downstream :
1) acute - generalized muscle damage up to complete immobility, dysphagia, erythema, damage to the heart and
other organs with a fatal outcome 2-6 months after the onset of the disease; with massive GCS therapy, a
transition to a subacute and chronic course is possible
2) subacute - a slow, gradual increase in symptoms; a detailed clinical picture is observed after 1-2 years from
the onset of the disease
3) chronic - cyclic course with moderate muscle weakness, myalgia, erythematous rash; muscle damage is often
local
c) by periods of the disease : prodromal, manifest with skin, muscle, general syndromes, dystrophic (cachectic,
terminal)
d) according to the degree of activity : I (ESR up to 20 mm/h), II (ESR 21-40 mm Hg), III (ESR > 40 mm
Hg)
A clinicopathologic classification of the idiopathic inflammatory myopathies:
- Myositis associated with another connective tissue disease.
- Juvenile myositis. Age of onset < 18 years , frequent calcifications.
- Cancer-associated myositis. -Granulomatous myositis.
- Eosinophilic myositis. -vasculitic myositis.
- orbital or ocular myositis -Focal or nodular myositis.
- Myositis ossificans. -Macrophagic myofasciitis.
CLINICS

➢ usually a gradual onset of the disease with complaints of steadily progressive weakness in the proximal
muscles of the arms and legs, less often - an acute onset with sharp pains and weakness in the muscles,
fever, skin rashes, polyarthralgia.
➢ muscle damage is the leading symptom of the disease; pronounced weakness of the proximal muscles of
the upper and lower extremities and neck muscles is characteristic: it is difficult for the patient to get out
of bed, wash, comb, dress, enter transport, in very severe cases, patients cannot raise their heads with
pillows and hold it (the head falls on the chest), cannot walk without assistance, hold even light objects
in their hands; with the involvement of the muscles of the pharynx, esophagus, larynx, speech is
disturbed, coughing fits, difficulty in swallowing food, choking appear; objectively: soreness, swelling
of the muscles, with a long course of the process - muscle atrophy
➢ Cutaneous features

• Symmetric erythematous rash on the:

o Extensor surfaces of the hand joints, elbows, and knees (Gottron sign); scaly papules may
form (Gottron papules)
o Upper eyelids (heliotrope rash); often associated with periorbital edema
o Mid-face [11]
o Upper back, posterior neck, and shoulders (shawl sign)
o Upper chest and anterior neck (V sign)
o Hips and lateral thighs (Holster sign)
• Poikiloderma may be seen in chronic disease. [12][13]
• Mechanic's hands: thickened and cracked skin on the sides of the fingers and palms (horizontal
fissures may appear darkened or dirty, hence the name)
• Periungual telangiectasias
• Calcinosis cutis (in children)
Systemic manifestations
• Interstitial lung disease
• Cardiac involvement (primarily in dermatomyositis and polymyositis), including:
o Myocarditis
o AV block
o Heart failure
• Constitutional symptoms
• Increased risk of malignancy (DM, PM, IMNM)
• Raynaud phenomenon
• Arthritis
• Gastrointestinal symptoms (e.g., abdominal pain, hematemesis, melena)

TREATMENT
All patients: Start supportive therapies (physical, occupational, and/or speech therapy, as appropriate) as soon as
possible.
1. In secondary (paraneoplastic) DM - radical surgical treatment.
2. In primary DM - pathogenetic therapy:
a) Short-acting corticosteroids: prednisolone 1-2 mg / kg / day orally, methylprednisolone; with juvenile DM,
with rapid progression of dysphagia with a risk of aspiration, the development of systemic lesions - pulse
therapy with methylprednisolone 1000 mg/day IV drip for 3 days in a row
b) cytostatics: methotrexate 7.5-25 mg/week, cyclosporine A 2.5-3.5 mg/kg/day, azathioprine 2-3 mg/kg/day,
cyclophosphamide 2 mg/kg/day (drug of choice for interstitial pulmonary fibrosis) orally
c) aminoquinoline preparations: hydroxychloroquine 200 mg/day orally
d) intravenous administration of immunoglobulins for 3-4 months
e) plasmapheresis and lymphocytopheresis in patients with severe, resistant to other methods of treatment, DM
3. Drugs that increase metabolic processes in muscle tissue (anabolic steroids, vitamin E, mildronate, etc.) -
after stopping inflammation
4. Treatment of calcification (Na-EDTA IV, colchicine 0.65 mg 2-3 times a day orally, Trilon B topically)
+5. In the inactive phase - exercise therapy, massage, FTL (paraffin, electrophoresis with hyaluronidase, etc.),
balneotherapy, spa treatment.
4. Rheumatoid arthritis: etiology and pathogenesis, classification, main clinical presentations,
diagnosis, clinical course and outcomes, treatment.
Rheumatoid arthritis (RA) – is a chronic inflammatory disease characterized by joint swelling, joint
tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. RA is an
autoimmune disease.
Felty's syndrome is a variant of RA that includes chronic polyarthritis, splenomegaly, and leukopenia.

ETIOLOGY :
• Idiopathic inflammatory autoimmune disorder of unknown etiology
• Risk factors include:
o Genetic disposition: associated with HLA-DR4 and HLA-DR1
o Environmental factors (e.g., smoking)
o Hormonal factors (premenopausal women are at the highest risk, suggesting a predisposing
role of female sex hormones)
o Infection
o Obesity
o Family history of RA

PATHOGENESIS
First is T cell activation and continuous stimulation of macrophages via IgG Fc receptors, local production of
rheumatoid factor autoantibodies in the joint. Anti-CCP antibodies react with proteins where arginine has
been replaced by citrulline. The TNF-alpha produced mainly by activated macrophages and T cells plays a
role in the development of joint inflammation. Effusion of synovial fluid into the joint space takes place
during active phases of the disease. Next the synovial villi hypertrophy, synovial cells proliferation, increased
vascularization (angiogenesis) and pannus form (granulation tissue that grows across surface of articular
cartilage from adjacent synovium). This is followed by destruction of cartilage by pannus – mediated by TNF-
alpha, interleukin-1-beta, interferon-gamma) and metalloproteases. The muscles waste around the joint,
hyperaemia develops and the joint capsule is distended. There is also destruction of unprotected bone at joint
margin and subchondral bone by pannus, later leading to marked joint damage and capsular laxity, leading to
deformity and fibrous ankylosis and eventually bony ankylosis of the joint.
CLASSIFICATION

a) according to the degree of seropositivity: seropositive and seronegative

b) according to the degree of activity: minimal, medium, high

c) according to radiography of the joints: I - periarticular osteoporosis, II - osteoporosis + slight narrowing of

the joint space, there may be single usura, III - osteoporosis + sharp narrowing of the joint space + multiple
usura, IV - osteoporosis + narrowing of the joint space + multiple usura + may be bony ankylosis

d) depending on the functional insufficiency of the joint: 0 - absent, I - limitation of professional ability to work,
II - loss of professional ability to work, III - loss of ability to self-service

CLINICS
• Polyarthralgia
o Symmetrical pain and swelling of affected joints (also at rest)
o Frequently affected joints [12]
▪ Metacarpophalangeal (MCP) joints
 ▪ Proximal interphalangeal (PIP) joints
▪ Wrist joints
▪ Knee joints
o Rarely affected: distal interphalangeal (DIP) joints, first carpometacarpal (CMC) joint, and
the axial skeleton (except for the cervical spine)
• Morning stiffness (often > 30 min) that usually improves with activity
• Joint deformities
o Rheumatoid hand is characteristic and typically manifests with one or more of the following
deformities:
▪ Deepening of the interosseous spaces of the dorsum of hand
▪ Swan neck deformity: PIP hyperextension and DIP flexion
▪ Boutonniere deformity: PIP flexion and DIP hyperextension.
▪ Hitchhiker thumb deformity (Z deformity of the thumb): hyperextension of
the interphalangeal joint with fixed flexion of the MCP joint [13]
▪ Ulnar deviation of the fingers
▪ Piano key sign: dorsal subluxation of the ulna
o Hammer toe or claw toe
o Atlantoaxial subluxation (see “Rheumatoid arthritis of the cervical spine” below)
• Physical examination: compression test (Gaenslen squeeze test)
o Painful compression of hands (or feet) at the level of the MCP joint (metatarsophalangeal
joint)
o Painful handshake is an early sign of arthritis
Extra-Articular signs and symptoms:
• Systemic: fever, weight loss, fatigue, susceptibility to infection.
• Musculoskeletal: clinical weakness and atrophy of skeletal muscle are common, tenosynovitis, bursitis
and osteoporosis manifestation. Osteoporosis secondary to rheumatoid involvement is common and may
be aggravated by glucocorticoid therapy. Glucocorticoid treatment may cause significant loss of bone
mass, especially early in the course of therapy, even when low dose are employed.
• Haematological: anaemia, thrombocytosis, eosinophilia, splenomegaly, Felty's syndrome.
• Ocular: the rheumatoid process involves the eye in less than 1% of patients. Affected individuals usually
have long standing disease and nodules. Other changes are episcleritis, scleritis, scleromalacia,
keratoconjunctivitis sicca.
• Rheumatoid vasculitis (inflammation of blood vessels), as a digital arteritis, visceral arteritis, ulcers,
pyoderma gangrenosum, mononeuritis multiplex, which can affect nearly any organ system, is seen in
patients with severe RA.
• Cardiac: pericarditis, myocarditis, endocarditis, conduction defects, coronary vasculitis, granulomatous
aortitis.
• Pulmonary: pleural effusions, fibrosing alveolitis, bronchiolitis.
• Neurological: cervical cord compression, compression neuropathies, peripheral neuropathy,
mononeuritis multiplex.
CLINICAL COURSE AND OUTCOME

a) slowly progressing - even the long-term existence of RA does not lead to severe joint disorders, damage to
the articular surfaces develops slowly, the function of the joints is preserved for a long time

b) rapidly progressive - high activity of the process with the formation of bone erosions, joint deformities or
involvement of internal organs during the first year of the disease

c) without noticeable progression - mild polyarthritis with a slight but persistent deformity of the small joints
of the hands; laboratory signs of activity are practically not expressed
IN THE OUTCOME OF RA : loss of function of the affected joints (due to deformity, ankylosis,
contractures).

DIAGNOSIS
The diagnosis of RA is clinical.
LAB :
• Nonspecific parameters Specific parameters (serological studies)
o ↑ Inflammatory markers • Anticitrullinated peptide
▪ ↑ CRP and ↑ ESR antibodies (ACPA)
▪ Other acute phase o E.g., anticyclic citrullinated pep
reactants may also be tide (anti-CCP)
elevated (e.g., ferritin). o Specificity: > 90%
o CBC: anemia of chronic • Rheumatoid factor (RF) [
disease, thrombocytosis o IgM autoantibodies against
o TFTs: to rule out an autoimmune the Fc region of IgG antibodies
thyroid disease, which is common o Present in 60–80% of patients,
in patients with RA but not specific to RA
o Serology: ↑ ANAs in 30–50% of • Serological studies may be negative
patients with RA
• Specific parameters (serological studies)

ADDITIONAL STUDIES
• Synovial fluid analysis: not routinely recommended [26]
o Findings are nonspecific [21]
▪ Cloudy, yellow appearance
▪ Sterile specimen with leukocytosis (WBC count 5000–50,000/mcL)
▪ ↑ Neutrophils, granulocytes, and ragocytes
▪ ↑ Protein level
▪ Possibly RF
IMAGING STUDIES
• X-ray: initial test
o Findings
▪ Early: soft tissue swelling, osteopenia (juxtaarticular)
▪ Late: joint space narrowing, marginal erosions of cartilage and
bone, osteopenia (generalized), subchondral cysts
• Ultrasound
o Indication: If available, perform on affected joints to detect clinical or subclinical synovitis.
o Supportive findings
▪ Early signs of inflammation: e.g., subclinical synovitis (synovial hyperemia)
▪ Synovial proliferation (pannus formation)
▪ Joint effusion: increased fluid (e.g., pus, blood, inflammatory infiltrate) within the
synovial compartment of a joint
▪ Using contrast can increase the sensitivity of detecting inflammation.
• MRI of the affected joints (with or without contrast)
o Can help detect early changes in large joints (e.g., subclinical synovitis)
 o Consider especially if cervical spine involvement is suspected

TREATMENT
1. Treatment should be permanent (all life), complex (medication + physiotherapy + sanatorium-resort +
surgical according to indications), individual, staged.
2. Drug therapy:
A. Basic therapy (slow-acting drugs):
- Arava (leflunamide) (1st most effective, used > 5 years)
- methotrexate (2nd most effective, used > 20 years)
- preparations of gold (tauredon) (3rd place in terms of effectiveness, used > 60 years)
- sulfasalazine (4th most effective, used > 50 years)
- D-penicillamine (5th most effective, used > 40 years)
- azathioprine (6th most effective, used > 30 years)
- aminoquinoline preparations (plaquenil) (7th place in terms of effectiveness, used > 40 years);
on average, the effect of basic therapy occurs after 2 months (Arava - 1 month). It is possible to combine basic
preparations (methotrexate + sulfasalazine + plaquenil, etc.), but only in case of their pathogenetic
compatibility.
B. Anti-inflammatory therapy:
1) NSAIDs: traditional, classic (indomethacin, diclofenac 75-150 mg / day in 2-3 doses, ibuprofen 1.2-3.2 g /
day in 3-4 doses, etc.) and selective COX-2 inhibitors ( less side effects: meloxicam/movalis 7.5-15 mg/day,
nimesulide/nimesil/nise 100 mg/day in 2 divided doses, celecoxib/celebrex)
- you can prescribe any drug, usually start with the classic ones, in the presence of contraindications (stomach
and duodenal ulcer, hypertension, kidney disease), selective COX-2 inhibitors are indicated (they do not start
with them because of the higher cost of these drugs)
- if there is no effect, the drug is changed (efficiency is assessed after 5-7 days of use)
- the main side effect: damage to the gastrointestinal tract in the form of dyspepsia or ulcers (stomach, 12 PC,
intestines); if ulcers are at risk, proton pump inhibitors (omeprazole) can be used
2) GCS - can be applied
a) inside in small doses: 5-7.5 mg of prednisolone
b) IV in the form of pulse therapy - only in the presence of systemic manifestations (except for amyloidosis of
the kidneys)
c) intra-articular (not > 3 times / year) - with synovitis: diprospan (betamethasone), depo-medrol
(methylprednisolone), kenalog (triamcinolone)
Each patient should be prescribed at least 2 drugs (1 from A, 1 from B), but there may be more. Only in
20% of patients it is possible to achieve remission of the disease (on some basic drug), for the second time it is
no longer effective.
Current trends in the treatment of RA - anti-TNF α -therapy : Etanercept (Immunex, Enbrel) - a soluble dimer
of the TNF α receptor coupled to IgG 1 (s.c. 2.5 mg 2 times a week), Infliximab (Remicade) - monoclonal
antibody against TNFα (in / in drip after 8 weeks); the cost of a yearly course of treatment is $ 10,000-12,000,
these drugs are highly effective, because. stop the progression of RA.
3. Physiotherapy treatment - should be aimed at reducing pain and inflammation, thermal procedures (mud,
ozocerite, paraffin) are not allowed, electro-, laser-, balneotherapy can be.
4. Sanatorium-and-spa treatment : sanatoriums
5. Surgical treatment :
a) synovectomy - causes the attenuation of the process only for 2-3 years, i.e. temporarily; currently
not used, because causes secondary arthritis
b) joint prosthetics (hip, knee and smaller)
6. Rehabilitation : changing the stereotype of motor activity for the prevention of joint deformity; orthopedic
aids that hold the joint in the correct position; physical therapy, physical therapy, sanatorium treatment.
5. Osteoarthritis: etiology and pathogenesis, classification, main clinical presentations, diagnosis,
treatment.
Osteoarthritis (OA, osteoarthrosis) also known as degenerative arthritis is a group of mechanical
abnormalities characterised by focal loss of articular hyaline cartilage with proliferation of new bone and
remodelling of joint contour. Inflammation is not a prominent feature.
ETIOLOGY
• Modifiable risk factors
o Obesity
o Excessive joint loading or overuse (mechanical stress)
• Nonmodifiable risk factors
o Age (> 55 years)
o Family history
o History of joint injury or trauma
o Anatomic factors causing asymmetrical joint stress
o Hemophilic hemarthroses and deposition diseases that stiffen cartilage
PATHOGENESIS
Due to influence of etiological factors →Decrease of cartilage resistance to usual loading due to arthritises –
inflammation, despite the noninflammatory nature of the synovial indicates that inflammatory mediators
produced by synovial tissues and cartilage well as other inflammatory mediators such as nitric oxide and
prostaglandins promote cartilage degeneration; metabolic and endocrinic disturbances; ischemia of a bone
fabric; heredity - researchers have discovered a defect in the gene coding degeneration of the type II collagen.
The presence of this abnormal gene osteoarthritis and mild epiphyseal dysplasia seen in several families.
Fast and early «ageing» of cartilage. Pathologic findings suggest that articular cartilage is the site of the
primary abnormality in osteoarthritis. There is a loss of homogeneity, and disruption and fragmentation of the
surface. Chondrocytes, which exist as isolated cells in normal cartilage,begin to proliferate and are found in
large clusters and clones, and osteophytes are formed, which are covered by irregular hyaline and
fibrocartilage. The proteoglycan content of cartilage decreases markedly as disease progresses, with
shortening of the glycosaminoglycan chains and impaired molecular aggregation. The big role in disease
development gives to changes in immune system.
All the joint tissues (cartilage, bone, synovium, capsule, ligament, muscle) depend on each other for health and
function. Insult to any one tissue impacts on the others, resulting in a common OA presentations affecting the
whole joint.
CLASSIFICATION
primary (idiopathic) or secondary to some known Secondary OA appears to result from
cause. Primary generalized OA involves the distal conditions that change the microenvironment of
and proximal interphalangeal joints (producing the chondrocyte. These include congenital joint
Heberden's and Bouchard's nodes), 1st abnormalities; genetic defects; infectious,
carpometacarpal joint, intervertebral disks and metabolic, endocrine, and neuropathic diseases;
zygapophyseal joints in the cervical and lumbar diseases that alter the normal structure and
vertebrae, 1st metatarsophalangeal joint, hip, and function of hyaline cartilage (eg, RA, gout,
knee. Subsets of primary OA include erosive, chondrocalcinosis); and trauma (including
inflammatory OA and rapidly destructive OA of fracture) to the hyaline cartilage or surrounding
shoulders and less often of hips and knees in the tissue (eg, from prolonged overuse of a joint or
elderly. Diffuse idiopathic skeletal hyperostosis is a group of joints associated with occupations such
syndrome involving large OA-like spinal osteophytes as foundry work, coal mining, and bus driving).
but little or no loss of articular cartilage.
CLINICS
Common clinical findings
• Pain during or after exertion (e.g., at the end of the day) that is relieved with rest
• Pain in both complete flexion and extension
• Crepitus on joint movement
• Joint stiffness and restricted range of motion
• Morning joint stiffness usually lasting < 30 minutes
• Possible formation of varus deformity if the knee is affected
• Joints are usually asymmetrically involved, as opposed to rheumatoid arthritis.
• Findings in late-stage disease: constant pain (including at night) and a more severely restricted range of
motion than during the early stages
Joint-specific findings
• Heberden nodes: pain and nodular thickening on the dorsal sides of the distal interphalangeal
joints, ♀ > ♂
• Bouchard nodes: pain and nodular thickening on the dorsal sides of the proximal interphalangeal
joints , ♀ > ♂
• Rhizarthrosis: osteoarthritis of the first carpometacarpal joint, between the trapezium and the
first metacarpal bone
• Hallux rigidus: osteoarthritis of the first metatarsophalangeal joint, between the first metatarsal and the
first proximal phalanx; characterized by hypertrophy of the sesamoid bones

DIAGNOSIS
Osteoarthritis is a clinical diagnosis Further investigations
Imaging • Laboratory testing: Inflammatory
First-line modality: plain radiography of markers (e.g., erythrocyte sedimentation
affected joints rate, C-reactive protein) are usually normal
in osteoarthritis.
Radiological signs of osteoarthritis [1] • Arthrocentesis: Synovial fluid
• Irregular joint space narrowing analysis usually does not show the presence
• Subchondral sclerosis: a dense area of bone of inflammation (white blood cell count<
(visible on x-ray) just below 2000 mm3). [11]
the cartilage zone of a joint that forms as a • Arthroscopy: may show a thickened capsule,
result of a compressive load on the joint synovial hypertrophy, and/or
• Osteophytes (bone spurs): spurs or ulcerated cartilage
densifications that develop on the edges of
the joint, increasing its surface area
• Subchondral cyst: a fluid-filled cyst that
develops on the surface of a joint due to
local bone necrosis induced by
the joint stress caused by osteoarthritis
DIAGNOSTIC CRITERIA

x-ray examination of the joints - stages of OA according to Kellgren and Lawrence:

0 - no radiological signs

I - racemose restructuring of the bone structure, minimal linear osteosclerosis in the subchondral regions + the
appearance of small marginal osteophytes; joint space is not changed

II - moderate osteosclerosis + small marginal osteophytes + moderate narrowing of the joint space

III - severe osteosclerosis + large marginal osteophytes + significant narrowing of the joint space

IV - a sharp compaction and deformation of the epiphyses of the bones that form the joint + coarse massive
osteophytes + the joint space is difficult to trace or absent

TREATMENT
1. Normalization of body weight with the help of diet and special complexes of physical exercises
2. Anti-inflammatory drugs (NSAIDs) courses - to reduce pain:
- with moderate intermittent pain without signs of inflammation - non-narcotic analgesics of central action
(paracetamol up to 4 g / day)
- with severe pain and signs of inflammation - NSAIDs in half the maximum doses: diclofenac 75 mg / day,
ibuprofen 1.2 g / day, etc.
- in the presence of diseases of the gastrointestinal tract, hypertension - selective inhibitors of COX-2 (movalis,
nimesulide, celebrex)
NB! Do not prescribe NSAIDs that adversely affect the synthesis of glycosaminoglycans (indomethacin)
3. Chondroprotectors: chondroitin sulfate (structum) 1000-1500 mg / day in 2-3 doses, glucosamine sulfate
(dona -200S) 1500 mg / day once, hyaluronic acid preparations (hyalgan, synvisc), unsaponifiable substances of
avacado and soy (piascledin ), diacerein (ART-50) - IL-1 blocker, alflutol, etc.
4. Surgical treatment - prosthetics of the affected joint.
5. Physiotherapy: kinesitherapy, massage, sanitary-resort treatment, for the relief of synovitis - UVR of the
affected joint in erythemal doses, UHF, magnetotherapy, hydrocortisone phonophoresis.
6. Rehabilitation: educational programs; using a cane while walking; wearing knee pads, arch supports, heel
wedges, insoles.
ITU : in primary OA, the general terms of VN for treatment in a hospital are 10-25 days.
Rehabilitation : exercise therapy using a gentle technique, gentle massage of the periarticular region and
regional muscles, sanatorium treatment (only with OA of I and II degrees without synovitis, mud resorts with
chloride, sodium, radon waters are shown)
orthopedic treatment (at the initial stage - fixation of the area of attachment of the ligaments and tendons of the
affected joint with an elastic bandage, in advanced cases - unloading orthopedic devices: sticks, crutches, joint
arthroplasty)
6. Gout: etiology and pathogenesis, classification, main clinical presentations, clinical course, diagnosis,
treatment.
Gout is an inflammatory crystal arthropathy caused by the precipitation and deposition of uric acid
crystals in synovial fluid and tissues.
ETIOLOGY
1) the reasons for the decrease in the excretion of uric acid (90%):
most common cause
• Medications (e.g., pyrazinamide, aspirin, loop diuretics, thiazides, niacin)
• Chronic renal insufficiency, lead nephropathy [5]
• Ketoacidosis (due to, e.g., starvation, diabetes mellitus) and lactic acidosis
• Postmenopause

2) the reasons for the hyperproduction of uric acid (10%):

• High cell turnover, e.g.:
• Combined decreased excretion and
o Tumor lysis syndrome
o Hemolytic anemia [6] overproduction: high alcohol consumption
o Psoriasis o Organic acids
o Myeloproliferative neoplasms
from alcohol metabolism compete
o Chemotherapy, radiation
• Enzyme defects, e.g.: [5] with uric acid to be excreted by
o Lesch-Nyhan syndrome the kidneys.
o Phosphoribosyl pyrophosphate
o Many alcoholic beverages contain a
synthetase overactivity
o von Gierke disease high level of purines.
• Diet rich in protein and
especially purine (e.g., red meat, seafood)
• Obesity
• Hypercholesterolemia, hypertriglyceridemia
• Hypertension [7]
• Sleep apnea

PATHOGENESIS

Defects in uric acid metabolism enzymes and other etiological factors → hyperproduction of uric acid and / or a
decrease in its excretion → hyperuricemia → urate deposition in tissues →

a) activation by urate crystals in the joint cavity of the Hageman factor, complement, kinins → increased
vascular permeability, influx of neutrophils releasing lysosomal enzymes, cytokines → acute gouty
inflammation

b) accumulation of urate crystals in the interstitium of the kidneys and tubules → gouty nephropathy, etc.

CLASSIFICATION (according to ICD-10):

a) idiopathic gout b) lead gout

c) drug gout d) gout due to impaired renal function

 There are primary gout (an independent disease) and secondary gout (manifestation of other diseases - myeloid
leukemia, psoriasis, chronic renal failure, taking cytostatics, etc.).

CLINICS
1. clinic of a typical acute attack of gout:
- begins suddenly at any time of the day, but more often at night or early in the morning (when the rate of
diffusion of urates into plasma decreases)
- the sharpest pains appear most often in the I metatarsophalangeal joint (even the touch of a sheet is painful)
- local symptoms of inflammation rapidly increase, reaching a maximum after a few hours: swelling, edema,
local hyperthermia; the skin over the joints is initially hyperemic, then becomes bluish-purple, shiny,
tense; characterized by significant limitation of joint mobility
- after 7-10 days there is a complete spontaneous regression of symptoms
2. manifestations of hyperuricemia (gouty status):
- subcutaneous tophi (gouty nodes) - are formed with high hyperuricemia and the duration of the disease over 5-
6 years; are yellowish nodules containing urates surrounded by connective tissue; localized most often on the
auricles, elbows, in the bursae of the elbow joints, feet, on the fingers, extensor surface of the forearm; the
content of tophi is white, during attacks it can liquefy and be released through fistulas (suppuration is not
typical, because urates have a bactericidal effect)
- urolithiasis and nephrolithiasis - urolithiasis (clinic of renal colic or associated pyelonephritis, gouty
nephropathy (gouty interstitial nephritis) with outcome in CRF
- damage to the valvular apparatus of the heart

DIAGNOSIS

Arthrocentesis and synovial fluid analysis Laboratory studies

Synovial fluid analysis is the gold standard for • Serum uric acid level [12][16]
diagnosing gout o Acute gout flare: often elevated
• Characteristic findings (hyperuricemia) ; may also be normal
o Polarized light microscopy: needle- or low
shaped monosodium urate o Intercritical stage or chronic gout
crystals that are ▪ Baseline levels are useful to
negatively birefringent [10] determine the need
▪ Crystals appear yellow for urate-lowering therapy.
when their optical axis is ▪ A normal or low level has a
oriented parallel to the very low negative likelihood
polarizer. ratio for (but does not rule
▪ Crystals appear blue when out) a diagnosis of gout.
their axis is perpendicular to • CBC and inflammatory
the polarizer. markers: WBC and ESR are typically
o Synovial fluid cell count: WBC > elevated in an acute gout attack. [19]
2000/μL with > 50% neutrophils • Urinary uric acid measurement (via 24-hour
o Gram stain: negative; useful for ruling urine collection): not routinely recommended
out septic arthritis
Imaging
Imaging is indicated if synovial fluid analysis is unsuccessful or cannot be performed, and the diagnosis remains
uncertain. It can be used to identify supportive findings of gout but cannot rule out septic arthritis.
• Ultrasound
o Signs of acute joint inflammation
o Bone erosions
o Signs of urate crystal deposition
▪ Double contour sign: a hyperechoic band of crystals covering the surface of
the hypoechoic articular cartilage, which is over the hyperechoic bone contour
▪ Tophi (pathognomonic for chronic gout)
• X-ray
o Acute gout: typically normal; useful for ruling out a fracture in patients with
posttraumatic joint inflammation
o Chronic gout
▪ Punched-out lytic bone lesions with spiky periosteal appositions (overhanging edges),
known as “rat-bite erosions”
▪ Radiopaque in surrounding soft tissue
▪ Joint space is preserved until late stages.
• Dual-energy CT : can detect crystals within deeper anatomical structures (e.g., the spine) and extra-articular
sites

Diagnostic criteria for gout:

A. Presence of characteristic monosodium urate crystals in synovial fluid and/or
B. Presence of tophi established by chemical analysis or polarizing light microscopy.
C. The presence of 6 out of 12 clinical, laboratory, radiological signs:
1) maximum intensity of inflammation on the first 7) unilateral lesion of the joints of the rear of the foot
day
8) suspicion of tophi
2) having more than one attack of arthritis
9) hyperuricemia
3) monoarthritis 10) asymmetric joint inflammation
4) joint redness 11) subcortical cysts without erosion during X-ray examination

5) pain and inflammation of the 12) the absence of microorganisms in the culture of synovial fluid
metatarsophalangeal joint of the first toe
6) symmetrical inflammation of the metatarsophalangeal joint
TREATMENT
. Diet number 6 : restriction of purines (sardines, anchovies, liver, fatty meat), fats, exclusion of alcoholic
beverages, increase in the amount of fluid you drink up to 2-3 l / day.
2. Relief of an acute gouty attack :
a) rest of the affected joint, cool compresses
b) colchicine 0.5 mg every hour until the attack stops, but not more than 6-8 mg / day (no more than 1 day)
c) NSAIDs (indomethacin, diclofenac) in high doses for 3-5 days, with a decrease in pain, the dose is reduced
d) UVI of the joints, UHF, potassium-lithium electrophoresis on the joint, dimexide applications
NB! You can not use uricostatics and uricolytics, because. fluctuations in the concentration of uric acid can
prolong the attack of gout.
3. Treatment in the interictal period :
a) uricostatics - block the formation of uric acid: allopurinol, an initial dose of 100 mg / day with a gradual
increase to 300 mg / day in 3-4 weeks
b) uricolytics - increase the excretion of uric acid: probenecid 250 mg 2 times / day for 1 week, then 500 mg 2
times / day (contraindicated in ICD, gouty nephritis)
c) drugs of combined action (uricostatic + uricolytic): allomaron 1 tab 1 time / day
d) phonophoresis with hydrocortisone, thermotherapy, balneotherapy
+4. Sanatorium-and-spa treatment is indicated only in the remission phase with preserved joint function (mud
therapy, therapeutic nutrition, alkaline mineral waters, balneotherapy - radon, hydrogen sulfide baths).
7. Psoriatic arthritis: etiology, pathogenesis, clinical picture, diagnosis, differential diagnosis,
treatment.
DEFINITION: inflammation of joints (primarily on hands, feet, spine) that may occur with psoriasis

ETIOLOGY & PATHOGENESIS

The pathogenesis of psoriatic arthritis is still not fully understood. Genetics, environmental factors, and
immune-mediated inflammation play a complex roles. Psoriasis and psoriatic arthritis are interrelated disorders,
so it is not surprising that they have commonalities in their pathogenesis.
-Genetics
-Immunologic factors
Involvement of immunological mechanisms is suggested by the inflammatory process in psoriatic skin lesions
and in the synovial fluid, which can be very similar to the inflammation seen in the synovial fluid of
RA. [39] There is an increased level of the proinflammatory cytokines including TNF-alpha, IL-1, IL-6, and IL-8
in the synovium and the synovial fluid of psoriatic arthritis patients.
-Environmental factors
Several environmental factors have been implicated in the pathogenesis of both psoriasis and psoriatic arthritis.
These mainly include bacterial and viral infections and trauma.
Pustular psoriasis is a well-described sequela of streptococcal infections.

CLINICAL FEATURES
• Psoriasis and psoriatic arthritis may occur independently or together.
• There are several types of psoriatic arthritis:
o Oligoarthritis (most common, accounting for 70% of cases): typically with asymmetric involvement
of both the distal and proximal interphalangeal joints (DIP and PIP)
o Spinal involvement (up to 40% of cases)
• Other rheumatological features [12]
o Enthesitis: inflammation of the enthesis (the connective tissue where tendons and ligaments insert
into the bone)
o Tenosynovitis
o Dactylitis: inflammation and swelling of fingers or toes (“sausage digit”)
o Arthritis mutilans: destruction of the IP joints and resorption of the phalanges with further collapse of
the soft tissue of the fingers (“telescoping fingers” or “opera glass hand”) [13]
DIAGNOSTICS
• There is no specific test for diagnosing psoriatic arthritis
• Imaging studies: joint destruction, ankylosis
o Fingers: pencil-in-cup deformity of DIP joints on x-ray
o Spine: syndesmophytes, and in particular asymmetric paravertebral ossification
Classification criteria for psoriatic arthritis (CASPAR): ≥ 3 points are required [14]
• Evidence of psoriasis (2 points)
o Current disease manifestation
o Personal or family history of the disease DIFF DIAGNOSIS
• Psoriatic nail dystrophy (1 point)
• Negative rheumatoid factor (1 point) • Gout and Pseudogout
• Dactylitis (1 point) • Osteoarthritis
• Radiologic signs (1 point) • Reactive Arthritis
TREATMENT • Rheumatoid Arthritis (RA)
- Mild disease: NSAIDs • Septic Arthritis
- Moderate to severe disease: DMARDs -Physical therapy
8. Ankylosing spondylitis: etiology, pathogenesis, classification, clinical picture, diagnostics,
differential diagnostics, treatment.
• Ankylosing spondylitis (AS), a spondyloarthropathy, is a chronic, multisystem
inflammatory disorder involving primarily the sacroiliac (SI) joints and the axial skeleton
Etiology
• The etiology of AS is unknown, but a combination of genetic and environmental factors
works in concert to produce clinical disease
Pathophysiology
• The primary pathology of the spondyloarthropathies is enthesitis with chronic
inflammation, including CD4+ and CD8+ T lymphocytes and macrophages.
• Cytokines, particularly tumor necrosis factor-α (TNF-α) and transforming growth factor-
β (TGF-β), are also important in the inflammatory process by leading to inflammation,
fibrosis, and ossification at sites of enthesitis.
• The initial presentation of AS generally relates to the SI joints; involvement of the SI
joints is required to establish the diagnosis.
• SI joint involvement is followed by involvement of the discovertebral, apophyseal,
costovertebral, and costotransverse joints and the paravertebral ligaments.
• Early lesions include subchondral granulation tissue that erodes the joint and is replaced
gradually by fibrocartilage and then ossification. This occurs in ligamentous and capsular
attachment sites to bone and is called enthesitis.
• In the spine, this initial process occurs at the junction of the vertebrae and the annulus
fibrosus of the intervertebral discs. The outer fibers of the discs eventually undergo
ossification to form syndesmophytes.
• The condition progresses to the characteristic bamboo spine appearance.
Clinical presentation
• Key components of the patient history that suggest ankylosing spondylitis (AS) include
the following
o Insidious onset of low back pain
o Onset of symptoms before age 40 years
o Presence of symptoms for more than 3 months
o Symptoms worse in the morning or with inactivity
o Improvement of symptoms with exercise
General symptoms
• Symptoms of AS include those related to inflammatory back pain, peripheral enthesitis,
arthritis, fatigue, and constitutional and organ-specific extra-articular manifestations.
• Because AS is a systemic inflammatory disease, systemic features are common. Fever
and weight loss may occur during periods of active disease.
Inflammatory back pain
• Inflammatory back pain is the most common symptom and the first manifestation
• Symptoms associated with inflammatory back pain include insidious onset occurring over
months or years, generally with at least 3 months of symptoms before presentation
• The pain often begins unilaterally and intermittently, and generally begins in the
lumbosacral region (SI joints).
Peripheral enthesitis and arthritis
• Peripheral enthesitis is the basic pathologic process, involving inflammation at the site of
insertion of ligaments and tendons on to bone.
• This often progresses from erosion and osteitis to ossification, resulting in telltale
radiological signs of periosteal new bone formation.
• The following sites are commonly involved:
o Achilles tendon insertion
o Insertion of the plantar fascia on the calcaneus or the metatarsal heads
o Base of the fifth metatarsal head
o Tibial tuberosity
o Superior and inferior poles of the patella
o Iliac crest
• Chronic involvement of the spine eventually can lead to decreases in ROM and fusion of
the vertebral bodies.
• Involvement of the cervical and upper thoracic spine can lead to fusion of the neck in a
stooped forward-flexed position (kyphosis)
Extra-articular manifestations
• Screen for extra-articular manifestations of AS by performing specific examinations (eg,
ophthalmologic, cardiac, gastrointestinal [GI]).
• Such manifestations may include the following:
o Uveitis
o Cardiovascular disease
o Pulmonary disease
o Renal disease
o Neurologic disease
o GI disease
Diagnosis
• The diagnosis of ankylosing spondylitis (AS) is generally made by combining clinical
criteria of inflammatory back pain and enthesitis or arthritis with radiologic findings.
• Two sets of sensitive and specific criteria are available for diagnosis of
spondyloarthropathy in general:
o The European Spondyloarthropathy Study Group (ESSG) criteria
o The Amor criteria
• Two other sets are used widely for diagnosis of AS
o The New York criteria
o The Rome criteria

• The New York criteria for the diagnosis of AS, which are based on clinical and
radiographic findings, include the following:
o Limitation of motion of the lumbar spine in all 3 planes
o History of pain or presence of pain at the thoracolumbar junction or in the lumbar
spine
o Limitation of chest expansion to 1 inch or less, as measured at the fourth
intercostal space
• Radiographic sacroiliac (SI) changes are graded as follows:
o Grade 0 – Normal
o Grade 1 – Suspicious
o Grade 2 – Minimal sacroiliitis
o Grade 3 – Moderate sacroiliitis
o Grade 4 – Ankylosis
Treatment
• No definite disease-modifying treatment exists for individuals with ankylosing
spondylitis (AS) although biologic agents show evidence of such activity.
• Early diagnosis is important.
• As with any chronic disease, patient education is vital to familiarize the patient with the
symptoms, course, and treatment of the disease.
• Treatment measures include pharmacologic, surgical, and physical therapy.
• No drugs have been proved to modify the course of the disease, although tumor necrosis
factor-α (TNF-α) inhibitors (TNHi) and IL-17 inhibitors (IL-17i) appear to have potential
as disease-modifying agents
• Disease progress and response to therapy can be monitored by following laboratory
values, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
level.

Painkillers and non-steroidal anti-inflammatory drugs (NSAIDs)

• Painkillers, such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs),
such as ibuprofen, are usually the first choice of treatment for ankylosing spondylitis.
Disease-modifying anti-rheumatic drugs (DMARDs)
• Drugs such as sulfasalazine and methotrexate
Biological therapies
• Biological therapies are newer treatments that can be very effective for some people with
ankylosing spondylitis and related conditions. There are a group of biological therapies
called anti-TNF drugs. The following can treat ankylosing spondylitis:
o Etanercept
o adalimumab
o certolizumab pegol
o golimumab.
o Secukinumab is a different type of biological therapy that can also treat
ankylosing spondylitis. I
Steroids
• Steroids can be used as a short-term treatment for flare-ups.
• They’re usually given as an injection into a swollen joint or as a slow-release injection
into a muscle.
• They can also treat painful tendons, for example at the heel, although they aren’t repeated
too often as they can cause tendon weakness.
Physiotherapy
9. Chlamydia-induced reactive arthritis: etiology, pathogenesis, clinical picture,
diagnostics, differential diagnostics, treatment.
• Reactive arthritis (ReA) is a non-suppurative inflammatory joint disease that develops
after a causative infection.
• Possible causative infections currently include
o Chlamydophila (Chlamydia) pneumoniae
o Mycoplasma hominis
o Escherichia coli
o Clostridium difficile
o Bacillus Calmette-Guerine (BCG)
o Helicobacter pylori
o Various intestinal parasites.
Pathogenesis
• ReA affects mainly people of working age - 20-40 years old, but can develop at any age.
• It is assumed that microorganisms and/or their antigens spread from the primary focus of
inflammation and reach the joint cavity as a result of bacteremia, with lymph flow or
through macrophage cells.
• In some cases, as a result of the interaction between the human body and the
microorganism, the antibacterial response exceeds its physiological protective role and
leads to the development of ReA.
Clinical picture
• Leading in the clinical picture of ReA is the defeat of the musculoskeletal system.
• It is characterized by a predominant lesion of the joints of the lower extremities, mainly
the knee, ankle, small joints of the feet, especially the first metatarsophalangeal joints.
• Less often, small joints of the hands, wrist and elbow joints are involved in the pathological
process.
• With the progression of the inflammatory process, multiple damage to the joints is possible
with their sequential involvement in the pathological process from the bottom up (the
"ladder" type of lesion).
• Typical are pain in the lower back, pain in the buttocks, often asymmetric, less often
radiating to the lower extremities.
• Morning stiffness in the joints and back observed in patients with ReA is usually short-
lived and mild.
• A characteristic symptom of ReA is enthesitis.
• Enthesis - places of attachment of tendons and ligaments to the bones near the joints and /
or to the synovial bags located in these anatomical regions. The most common localization
of enthesitis in ReA is the area of the heels (subcalcaneal bursitis), which is manifested by
a typical patient's complaint of pain in the heels. Less common are plantar fasciitis and
Achilles bursitis.
• Inflammatory articular syndrome leads to impaired gait in patients. Due to damage to the
joints of the tarsus and the ligamentous apparatus of the feet, a “flat” foot can form over
time.
• Urethritis, in the form of pain, burning sensation during urination, discharge from the
urethra, is one of the main clinical symptoms of ReA, and can be a manifestation of not
only urogenital, but also post-enterocolitic ReA, can precede the development of articular
syndrome for 1-3 weeks.
 • Female ReA patients are characterized by non-purulent cervicitis.
• Involvement in the inflammatory process of the mucous membrane of the eyes, manifested
by conjunctivitis, unilateral or bilateral. Signs of conjunctivitis are usually mild and
transient, with spontaneous relief within 1-4 weeks.
• Skin lesions are a rarer manifestation of ReA at present. Keratoderma is a painless focal
(in the form of papules and plaques) and confluent hyperkeratosis, with the most common
localization on the plantar part of the feet and palms. Erythema nodosum - painful red skin
lesions, with predominant localization on the shins, is rarely detected and only in patients
with ReA of yersinia etiology.
• The most common extra-articular manifestations of ReA are fever, peripheral
lymphadenopathy, weight loss, muscle wasting of the affected limb, and moderate
weakness.
Diagnostic criteria
• Peripheral arthritis:
o Asymmetric
o Oligoarthritic (affects up to 4 joints)
o Predominant damage to the joints of the legs
• Infectious manifestations:
o Diarrhea
o Urethritis
o Onset 2-4 weeks before arthritis develops
• Laboratory confirmation of infection:
o In the presence of clinical manifestations of infection - preferably
o In the absence of obvious clinical manifestations of infection, it is mandatory
• Exclusion criteria - the established cause of the development of mono- or oligoarthritic:
o Spondylarthritis
o Septic arthritis
o Crystal arthritis
o Lyme disease
o Streptococcal arthritis
Diagnosis
• Mandatory studies include:
o A general blood test
o Urine, detection of chlamydia and antibodies to them
o A study for the presence of HIV infection, gonococci
o A stool test for Salmonella, Shigella
o confirmation of the absence of antinuclear antibodies and rheumatoid factor.
• Additional tests include analysis of synovial fluid
• Signs of a reliable diagnosis of reactive arthritis are:
o Low viscosity of the synovial fluid
o Poor formation of a mucin clot
o Leukocytosis (5000-10,000/µl) with a predominance of segmented neutrophils.
• Mandatory
o X-ray examination of the affected joints
 o Characteristically: changes can be seen only with a long course of the disease; it is
possible to identify unilateral sacroiliitis, more often in carriers of the HLA-B27
antigen.
o Gross changes in bone and cartilage (ossificates) are uncharacteristic.
o Additional: echocardiography (detection of damage to the aortic valves).
Differential diagnosis
• Septic arthritis
• Viral arthritis
• Poststreptococcal arthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Psoriatic arthritis
• Lyme disease
• Tuberculous arthritis
Treatment
• The outcome of the disease is closely related to the destruction (eradication) of the
pathogen, which requires long-term use of antibacterial drugs. The goals of symptomatic
treatment are the elimination of pain and inflammation in the joints.
• Treatment is usually carried out on an outpatient basis, hospitalization is required in cases
of severe arthritis with systemic manifestations, unclear cases requiring clarification of
the diagnosis
Non-pharmacological therapy
• The motor mode is shown: rest of the affected limb during the first two weeks of the
disease, however, fixation of the joint and immobilization are not shown. Cold on the
affected joint. In the future, exercise therapy is prescribed according to an individual
plan. There is no need to follow a special diet.
Pharmacological therapy
• Antibacterial therapy is of paramount importance in case of detection of chlamydial
infection, it is carried out for a long time.
• There are mainly three groups of drugs that act on intracellular microorganisms:
o Macrolides
o Fluoroquinolones
o Tetracyclines.
• Drugs of choice:
o Doxycycline 0.3 g per day, orally in 2 doses for 30 days;
o Azithromycin 1 g per day on the first day, then 0.5 g per day orally for 30 days;
o Clarithromycin 0.5 g per day, orally in 2 doses for 30 days
o Spiramycin 9 IU per day, in 3 doses for 30 days.
• Second-line drugs (with intolerance or ineffectiveness of the above drugs):
o Ofloxacin 600 mg per day orally in 2 doses for 30 days
o Ciprofloxacin 1500 mg per day, orally in 2 doses for 30 days
o Lomefloxacin 400-800 mg per day, orally in 1-2 doses for 30 days.
o In the case of enterocolitis, the effectiveness of antibiotics has not been proven.
• NSAIDs
o Have a symptomatic effect: relieve pain and inflammation of the joints
o Diclofenac orally 2-3 mg/kg/day in 2-3 divided doses
o Naproxen PO 15–20 mg/kg/day in 2 divided doses
o Ibuprofen orally 35-40 mg/kg in 2-4 doses
o Nimesulide inside 5 mg / kg in 2-3 doses
o Meloxicam inside 0.3-0.5 mg / kg in 1 dose.
o Without exception, all NSAIDs have a negative effect on the stomach and kidneys
o Therefore, the lowest possible dose should be use
o When taking NSAIDs, it is necessary to monitor blood tests to monitor the
kidneys and liver
o It is also mandatory to use drugs to protect the stomach (omeprazole, etc.)
• Glucocorticoids
o In severe arthritis, they are used for intra-articular administration.
o A necessary condition is the exclusion of septic arthritis.
• Immunosuppressants
o Are used in severe and protracted course, the appearance of signs of
spondylarthritis, high activity of arthritis.
▪ Sulfasalazine 2-3 / g / day;
▪ Methotrexate 7.5-15 mg/week. (Not used in the modern treatment of
reactive arthritis. Not the drug of choice as it has not been shown to be
effective in studies in the group of seronegative spondylarthritis);
▪ Azathioprine 150 mg/day (Not used in modern treatment of reactive
arthritis.
▪ Not the drug of choice, as it has not been shown to be effective in studies
in the group of seronegative spondylarthritis).
10. Osteoporosis. Risk factors for osteoporosis. Classification. Clinical picture, diagnosis.
Therapy. Primary and secondary prevention of osteoporosis.
• Osteoporosis, in which low bone mass and micro-structural deterioration of bone tissue
lead to increased bone fragility
• Risk factors for osteoporotic fracture can be split between nonmodifiable and
(potentially) modifiable.
Nonmodifiable
• Personal history of fracture as an adult
• History of fracture in a first-degree relative
• White race
• Advanced age
• Female sex
• Dementia
• Poor health or fragility
Potentially modifiable
• Current cigarette smoking
• Low body weight (< 127 lb)
• Estrogen deficiency such as that caused by early menopause (age < 45 years) or bilateral
ovariectomy and prolonged premenopausal amenorrhea (>1 year)
• Low lifelong calcium intake
• Alcoholism
• Impaired eyesight despite adequate correction
• Recurrent falls
• Inadequate physical activity
• Poor health or frailty
Classification
• Two categories of osteoporosis have been identified: primary and secondary.
• Primary osteoporosis is the most common form of the disease and includes
o postmenopausal osteoporosis (type I)
o senile osteoporosis (type II).
• Secondary osteoporosis is characterized as having a clearly definable etiologic mechanism.
• Type I is associated with a loss of estrogen and androgen resulting in increased bone
turnover, with bone resorption exceeding bone formation, and a predominant loss of
trabecular bone compared with cortical bone
• Type II, which represents the gradual age-related bone loss found in both sexes caused by
systemic senescence, is induced by the loss of stem-cell precursors, with a predominant
loss of cortical bone
Clinical features
• Early symptoms:
o The patient complains of acute pain in middle or low thoracic or high lumbar
region
o Sudden movement, sitting, sneezing, cough, etc. increases pain. Rest relieves it.
 o Most common symptom of osteoporosis is back pain secondary to vertebral
compression. However, in some cases, fractures of axial skeleton may be seen
with trivial trauma.
o Round type of gibbus due to compression of thoracic vertebrae is commonly seen
o Other features of osteoporosis include
▪ Brittle hair
▪ Cervical spine compression
▪ Loss of vertebral height
▪ Skin wrinkles
▪ Wrist fractures
▪ Degenerative hip
▪ Fracture of neck of femur
▪ Fracture of long bones

Diagnosis
Radiographs
• Radiographs changes seen in the spine are:
o Loss of vertebral height due to symmetric transverse compression.
o Biconcave central compression (Codfish spine) due to the pressure of the bulging
disk into the bodies.
o Anterior wedge compression
o The bone density of the vertebra is reduced
 • Other bones
o Ground glass appearance due to generalized rarefaction.
o Singh’s index is the grading of the trabecular pattern of the neck of femur from 1-
6
o Metacarpal index, etc.
o Pathological fractures.
Densitometry
• Techniques for bone mass measurement
o Single photon absorptiometry is used to assess the amount of cortical bone
mineral in appendicular skeleton.
o Mineral status of axial skeleton is assessed by dual photon absorptiometry
(DEXA) and quantitative CT scan
o Total body neutron activation analysis to determine calcium content of the entire
body.
Transiliac bone biopsy:
• It is an important diagnostic tool in patients of more than 50 years in postmenopausal
diseases.
Blood chemistry
• Serum calcium, phosphorus and alkaline phosphatase levels are usually normal.
Treatment
• Preventing osteoporosis is lot easier than treating it.
• The treatment plan consists of general measures exercises and drug therapy.
General measures
• High protein and calcium rich diet
• Rest that is adequate
• Muscle relaxants and supports like belt, collar, etc. for symptomatic relief of pain
• Spinal orthosis when patient is erect and mobile.
Exercises
• Exercises like walking and light aerobics are beneficial
o Posture exercise: Wall arch, back bending and wall sliding postural exercises help
to improve posture and overcome hunched back
o Fall prevention is of utmost importance.
Drug Therapy in Osteoporosis
• Drugs form the mainstay of treatment of osteoporosis.
• The various combinations suggested are as confusing as the disease.
• However, an effort is made here to provide a simplistic analysis of the drugs commonly
used in osteoporosis.
Calcium and vitamin D:
• For those patients diagnosed by DEXA as osteoporosis, 1,200 mg of calcium and 700-
800 IU of vitamin D per day is recommended as the first line of therapy.
Hormone Replacement Therapy
• The role of estrogen and progestogens in preventing and treating osteoporosis has been
well documented.
• Estrogens are the most effective treatment for osteoporosis in perimenopausal and early
menopausal women.
• Estrogens dose is 0.625 mg daily or 0.3 mg if combined with calcium.
• HRT is known to reduce the rate of fractures by 75 percent in the estrogen group. Birth
control pills are also known to prevent osteoporosis.
• The role of progesterone is still not well-documented.
Biphosphonates
• These drugs inhibit the action of the osteoclast bone cells, which are responsible for
removing the bone mass by binding themselves to the inner linings of the bones.
• The dose of alendronate is 10 mg/day.
• Etidronate is another commonly used biphosphonate.
• Tiludronate, risedronate, and ibandronate are some of the newer drugs.
Calcitonin
• Salmon calcitonin has been used for treating osteoporosis.
• Calcitonin can be given in the form of injections (Dose 50-100 IU/day) or in the form of
nasal spray (dose 200 IU).
• It is used for the treatment of osteoporosis in women who are at least five years
postmenopausal and in some cases of men.
• It is known to slow down bone loss, as it is a powerful inhibitor of osteoclastic activity,
increase bone density and reduce the risk of fractures.
• It is also known to reduce the pain.
Alfacalcidol
• This is a synthetic analogue of calcitriol, an active metabolite of vitamin D.
• It changes to calcitriol in the liver. It decreases bone resorption, increases bone
mineralization and formation.
• It also reduces the rate of fractures and improves the bone quality. Recommended dose is
0.5 mcg/day.
• It is sometimes given along with calcium.
Role of Fluorides in the Treatment of Osteoporosis
• Fluorides are known to increase the bone mass.
• Lower dose of 25 mg slow release fluorides twice daily along with 400 mg of calcium
twice daily is recommended.
• The side effects are gastrointestinal upsets and increased risk of cortical bone fractures.

Common Preference of drugs for treatment of osteoporosis

• Calcium supplements in the dose of 1000-1500 mg/ day and vitamin D analogue (0.25
mg BD or vitamin D in the dose of 600–2800 IU/day).
First Preference
• Perimenopausal and early postmenopausal (first 5 years) estrogen replacement therapy
(0.625 mg/ day).
Second Preference
• For the next ten years, SERMS (e.g., Raloxofene). They are known to decrease the
estrogens dreaded side effects (like causing increased incidence of uterine or breast
cancers), while maintaining their beneficial effects (like increasing bone mineral density),
decreasing menopausal symptoms, cardioprotective activity, etc. SERMS are known to
act by selectively blocking certain estrogen receptor sites, hence their name.
Third Preference
• Alendronate (10 mg/day). This is preferred next due to its proven efficacy in decreasing
the hip fractures.
Fourth Preference
• Calcitonin 200 IU puff/day intranasal or 100 IU subcutaneously. This is found to be very
effective to reduce the pain due to crush fractures of the vertebra.
Fifth Preference
• Combination of the above drugs. However, despite of the several options, the final choice
is of the treating physician, weighing all the necessary factors.
Prevention
• Primary prevention of osteoporosis
o It starts in childhood.
o Patients require adequate calcium intake, vitamin D intake, and weight-bearing
exercise.
• Beyond this, prevention of osteoporosis has two components:
o Behavior modification
o Pharmacologic interventions.

• The National Osteoporosis Foundation specifies that the following behaviors should be
modified to reduce the risk of developing osteoporosis
o Cigarette smoking
o Physical inactivity
o Intake of alcohol, caffeine, sodium, animal protein, and calcium
• Environmental measures to prevent falls/fractures include
o Remove or anchor rugs and use nonskid mats
o Minimize clutter
o Remove loose wires
o Install handrails in bathrooms, halls, and long stairways
o Ensure hallways, stairwells, and entrances are well lighted
o Encourage patient to wear sturdy, low-heeled shoes
• Pharmacological prevention
o Patients who have disorders or take medications that can cause or accelerate bone
loss should ensure adequate intakes of calcium and vitamin D
o This include calcium supplementation and administration of raloxifene or
bisphosphonates
• Other
o Regular monitoring may be helpful. Periodic bone densitometry helps in
diagnosing osteoporosis in the early phase and aids in preventing fractures.
11. Erythema nodosum: etiology, principles of diagnosis and treatment.
Erythema nodosum (EN) is an inflammation of subcutaneous fat caused by a delayed hypersensitivity
reaction. Women in early adulthood are commonly affected.
ETIOLOGY
• Idiopathic (most common)
• Infection (e.g. streptococcal pharyngitis, histoplasmosis, coccidioidomycosis, TB, leprosy)
• Autoimmune diseases (e.g. sarcoidosis, Crohn disease, ulcerative colitis, Behcet syndrome)
• Drugs (oral contraceptives, sulfonamides, iodide)
• Pregnancy
• Malignancy

DIAGNOSIS
• Clinical diagnosis
• Imaging and laboratory tests determine the underlying condition
o CBC, ESR
o Antistreptolysin-O titer; throat or blood culture
o Chest x-ray: hilar lymphadenopathy (e.g., in sarcoidosis, tuberculosis)
o VDRL
o Inflammatory bowel disease workup
• Skin biopsy if diagnosis is uncertain

TREATMENT
• Symptomatic treatment
o Bed rest
o Leg elevation
o Heat or cool compresses
o NSAIDS (e.g., ibuprofen)
o Potassium iodide
• Treat underlying disease
• In severe or refractory cases: systemic steroids
12. Large vessels vasculitis (Takayasu's disease, Horton's disease): main clinical
manifestations, diagnosis, complications, approach hes to therapy.
TAKAYASU’S DISEASE
Definition: granulomatous inflammation of the aorta and its major branches, resulting in thickening
and stenosis of the involved blood vessels and subsequent vascular symptoms [1]
CLINICAL FEATURES
• Fever, malaise, arthralgia, night sweats
• Vascular symptoms
o Decreased bilateral brachial and radial pulses (so-called pulseless disease)
o Syncope, angina pectoris
o Bilateral carotid bruits
o Impaired vision
o Movement-induced muscular pain in one or more limbs
o Raynaud phenomenon
o Hypertension
• Skin manifestations
o Erythema nodosum
o Urticaria
DIAGNOSTICS [4]
• Laboratory findings: ↑ ESR
• Angiography (gold standard): detects vascular stenosis [5]
• Biopsy of the affected vessel
o Granulomatous thickening of the aortic arch
o Plasma cells and lymphocytes in media and adventitia
o Vascular fibrosis
• A diagnosis of Takayasu arteritis requires three or more of the following diagnostic criteria to be
fulfilled : [6]
o Age of onset: ≤ 40 years
o Claudication of upper or lower extremities while in use
o Audible bruit over the subclavian artery or abdominal aorta
o Decreased brachial artery pulse
o Blood pressure difference > 10 mm Hg between arms
o Abnormal arteriography of the aorta or large blood vessels in the extremities that is not due
to arteriosclerosis or fibromuscular dysplasia
TREATMENT
• Corticosteroids; if necessary, MTX or cyclophosphamide may be administered.
• Surgical intervention (e.g., bypass) may be required if critical stenosis of the aortic arch or its
branches occurs.
• Antihypertensive treatment

COMPLICATIONS
The overall morbidity in Takayasu arteritis depends on the severity of the lesions and their consequences.
Complications of the disease include the following:
• Stroke • Fetal injury
• Intracranial hemorrhage • Valvular heart disease
• Seizures • Retinopathy
• Graft stenosis and/or occlusion • Renovascular hypertension
• Ischemia
• Organ failure
• Complications of hypertension (eg, aortic dissection)
HORTONS DISEASE (aka giant cell arteritis)
Giant cell arteritis (GCA) is a type of autoimmune vasculitis that causes chronic inflammation of large
and medium-sized arteries, in particular the carotid arteries, its major branches, and the aorta. GCA is most
common in women over the age of 50 and of northern European descent.
CLINICS
• Constitutional symptoms
o Fever, weight loss, night sweats
o Symptoms of anemia: fatigue and malaise
o Myalgia, arthralgia (mainly of the shoulder and hip joints)
• Clinical features of arterial inflammation
o Cranial giant cell arteritis: involves the extracranial branches
of the common
carotid, internal carotid, and external carotid arteries (the temporal artery is the
most commonly affected vessel)
▪ New-onset unilateral (or bilateral) headache
▪ Can be pulse-synchronous, throbbing, dull
▪ Typically located over the temples
▪ Hardened and tender temporal artery
▪ Jaw claudication: jaw pain when chewing
▪ Vision loss: due to inflammation and occlusion of the ophthalmic artery and
its branches
▪ Scintillating scotoma
▪ Amaurosis fugax or permanent loss of vision
▪ Diplopia
o Large-vessel giant cell arteritis: less common; involves the aorta and its primary
branches
▪ Angina pectoris, acute coronary syndrome
▪ Abdominal pain
▪ Limb claudication
▪ Asymmetrical pulses, asymmetrical blood pressure
▪ Vascular bruits, aortic regurgitation murmur
▪ Features of AAA, TAA, aortic dissection
• Symptoms of polymyalgia rheumatica (if both diseases are present)

DIAGNOSIS
Demonstration of arterial inflammation on imaging and/or histopathology is required to make a diagnosis of
GCA. In patients with features of cranial GCA, the ACR classification criteria for GCA can be used to
differentiate GCA from other forms of vasculitis.
Laboratory studies
• Inflammatory markers: initial laboratory test in suspected GCA
o ↑ ESR, specifically ≥ 50 mm/h (due to Rouleaux formation of RBCs)
o ↑ CRP
• Additional laboratory tests
o CBC: normal or mild thrombocytosis, leukocytosis, or normochromic anemia
o Liver chemistries: normal or ↑ ALP, ↑ transaminases, or ↓ albumin
o Coagulation studies: normal or ↑ fibrinogen
Confirmatory diagnostic studies
[6][10][14][15]
All patients require imaging and/or a temporal artery biopsy to confirm the diagnosis.
• Temporal artery biopsy (gold standard)
• Duplex ultrasound (US)
-Supportive findings
o Edema and thickening of the vessel wall (halo sign)
o Noncompressible artery (compression sign)
o Stenosis and occlusion
TREATMENT
Glucocorticoid therapy
This is the mainstay of treatment for patients with GCA.
Initial high-dose therapy (induction therapy)
• Indication: all patients with new-onset or recurrent GCA
• Important consideration: Initiate before diagnostic workup (e.g., before TAB) if clinical suspicion
for GCA is high to minimize the risk of complications such as vision loss or stroke
• Options
o Uncomplicated disease: oral glucocorticoids, e.g., prednisolone
o Ischemic organ damage (e.g., impaired vision): Consider initial pulse therapy
with IV glucocorticoids before oral glucocorticoids.
▪ Pulse therapy with methylprednisolone
▪ Oral glucocorticoids (initially, or following pulse therapy), e.g., prednisolone
-Maintenance therapy
• Slowly taper glucocorticoids to the lowest dose needed to control symptoms.
• Administer prophylactic measures to prevent complications of glucocorticoid therapy as needed.
Adjunct therapy
• Glucocorticoid-sparing therapy
o Indications
▪ Consider in patients who relapse or are at high risk of complications
from long-term glucocorticoid therapy
▪ May be used to decrease the dose of glucocorticoids
o Options
▪ Tocilizumab (antagonizes the IL-6 receptor)
▪ Methotrexate
• Low-dose aspirin
o Not routinely recommended
o Consider in patients with preexisiting cardiovascular or cerebrovascular disease

COMPLICATIONS
• Permanent vision loss: ∼ 20–30% if giant cell arteritis is left untreated
• Cerebral ischemia (e.g., transient ischemic attack and stroke): < 2% of cases
• Aortic aneurysm and/or dissection: ∼ 12% of patients
13. Polyarteritis nodosa: etiology and pathogenesis, main clinical manifestations, course,
complications, treatment.
Etiology and Pathophysiology
• focal pan-mural necrotizing vasculitis in small and medium-sized arteries
• thrombosis, aneurysm, or dilatation at lesion site may occur
• healed lesions show proliferation of fibrous tissue and endothelial cells that may lead to
luminal occlusion
Clinical features
• Predominantly men, aged 30-60 years, characterized by acute onset with prolonged fever,
intense myalgia in calf muscle, arthralgia of large joints
• Constitutional – significant cachexia for months, lathery, fatigue
• Skin changes
o Pallor, marbling of limbs and trunk
o Reticular livedo
o Exanthema in form of erythematous, maculopapular, hemorrhagic, urticarial rash
o Small painful nodules (vascular aneurysms or granulomas) in skin or s/c tissue
along neurovascular trunks of thighs, legs, forearms
• Muscular-articular syndromes
o Intense pain in calf muscle, weakness and atrophy
o Polyarthralgia, less often – migrating non-deforming polyarthritis with
predominant lesion of one or more large joints (knee, ankle, shoulder, elbow)
• Renal syndrome
o Vascular nephropathy – proteinuria, microhematuria, cylindruria, rapid
development of chronic renal failure
o Possible kidney infarctions due to renal artery thrombosis – fever, severe ack
pain, hematuria
o Rupture of an aneurysm of the renal vessels and formation of perirenal hematoma
• Asymmetric mono- and polyneuritis
o Paresis of hands and feet, burning pain in extremities, impaired sensitivity, paresis
• Abdominal syndromes
o Severe pain in various parts of abdomen, tension of anterior abdominal wall
o Dyspeptic symptoms
o Significant bleeding of GIT, pancreatonecrosis, perforation of intestinal ulcers
with peritonitis
• CVS syndromes
o Arterial HTN
o Coronartitis with development of angina pectoris or MI
o Myocarditis, cardiosclerosis, various rhythm disturbances, blocks
• Pulmonary syndrome
o Pulmonary vasculitis or interstitial pneumonia – cough, SOB, chest pain,
hemoptysis, strengthening and deformation of pulmonary pattern, various
breathing noises and wheezing
o Pulmonary heart attacks
• Damage to testicles (orchitis, epididymitis)
Diagnosis
• Blood – moderate normochromic anemia, increased ESR, neutrophilic leukocytosis with
left shift, moderate thrombocytosis
• Biochemical – moderate hypogammaglobinemia, increased seromucoid, haptoglobin and
fibrin level
• Immunological examination – markers of viral hepatitis B, C-ANCA
• X-ray angiography, USG and NMR tomography – aneurysms, narrowing or occlusion of
medium sized arteries
• Biopsy – granulocytic and/or mononuclear infiltration f walls of arteries of muscle type
but not arterioles, venules, capillaries
Treatment
• Pulse therapy
o Methylprednisolone 1g/day for 3 days with cyclophosphane 1g on 2nd day
• Glucocorticoids
o Prednisone 1mg/kg/day – 1 month, then 2-3 months dose is gradually reduced by
2.5mg every 10 days, until half dose reached than original.
o This dose given for another 1 months, then again reduces to minimum for
maintenance
• Cyclophosphamide 2mg/kg – 1 year along with prednisolone to increase effectiveness
• IgG IV 1g/day for 3 days – can repeat up to 6 cycles (along with prednisolone and
cyclophosphamide to increase effectiveness)
• Plasmapheresis
• HBV and HCV infection – Glucocorticoids + antiviral (human leucocyte interferon,
recombinant interferon)
• Antiplatelets and LMW-heparin to prevent thrombosis
• HTN – calcium channel blockers, selective beta-blockers and diuretic
14. ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis,
eosinophilic granulomatosis with polyangiitis): main clinical manifestations, diagnosis,
complications, approaches to therapy.

• Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include

o Granulomatosis with polyangiitis (Wegener granulomatosis)
o microscopic polyangiitis
o eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
o renal-limited vasculitis.
Granulomatosis with polyangiitis
Signs and Symptoms
• systemic
o malaise, fever, weakness, weight loss
• head, eyes, ears, nose, and throat (HEENT)
o sinusitis or rhinitis, nasal crusting and bloody nasal discharge, nasoseptal
perforation, saddle nose deformity
o proptosis due to: inflammation/vasculitis involving extraocular muscles,
granulomatous retrobulbar space-occupying lesions or direct extension of masses
from the upper respiratory tract
o hearing loss due to involvement of cranial nerve (CN) VIII
• pulmonary
o cough, hemoptysis, granulomatous upper respiratory tract masses, tracheal and
bronchial stenosis
• renal
o hematuria, proteinuria, elevated creatinine, glomerulonephritis
• other
o joint, skin, eye complaints-iritis, vasculitic neuropathy
Investigations
• blood work: anemia (normal mean corpuscular volume (MCV)), increased WBC,
increased Cr, increased CRP, elevated platelet count, ANCA (PR3 > MPO)
• urinalysis: proteinuria, hematuria, RBC casts
• CXR/CT: pneumonitis, lung nodules, infiltrations, cavitary lesions
• biopsy for confirmation of disease: skin, renal (segmental necrotizing
glomerulonephritis), lung (vasculitis, necrosis)
• CRP may be used to monitor response to treatment in some patients
Treatment
• severe, life or organ-threatening disease
o induction therapy: IV glucocorticoids + either IV or oral cyclophosphamide OR
rituximab
o glucocorticoid: methylprednisolone 0.5-1.0 g/d IV x1-3 d followed by prednisone
1 mg/kg/d PO x2-4 wk and then gradual taper
o cyclophosphamide: 2 mg/kg/d (max 200 mg/d) PO for maximum of 3-6 mo OR
15 mg/kg IV (max 1200 mg) every 2 wk for 3 doses, then every 3 wk for 3-6
doses (dose adjust for older age and renal failure)
o rituximab: 375 mg/m2 x4 weekly infusions
 o maintenance therapy: initiated once remission is achieved, consider
corticosteroid-sparing agents such as rituximab for maintenance, azathioprine,
MTX, and mycophenolate are reasonable alternatives
• plasma exchange can be an adjunct treatment for patients with severe organ involvement
(renal failure, pulmonary hemorrhage) not responding to conventional induction
treatment
• non-organ-threatening disease
o prednisone 0.5-1 mg/kg/d PO and MTX 15-25 mg PO/SC weekly OR
azathioprine 2 mg/kg/d
• screening and prophylaxis
o all patients should receive screening and prophylaxis for corticosteroid-induced
osteoporosis, PUD prevention, and Pneumocystis jiroveci prophylaxis
(trimethoprim/sulfamethoxazole 160/800 mg PO 3x/wk)
Microscopic polyangiitis
Clinical features
• Constitutional manifestations of microscopic polyangiitis (MPA) include the following:
o Fever (55%)
o Malaise, fatigue, flulike syndrome
o Myalgia (48%)
o Weight loss (72%)
• Other manifestations of MPA include the following:
o Skin - Rash (50%)
o Pulmonary - Hemoptysis (11%), dyspnea, cough
o Cardiovascular – Chest pain, symptoms of heart failure
o Gastrointestinal (GI) - GI bleeding, abdominal pain
o Neurologic - Peripheral nervous system involvement manifesting as mononeuritis
multiplex (57%); CNS involvement manifesting as seizures (11%)
o Arthralgias (10-50%)
o Myalgias (40%)
o Testicular pain (2%)
o Ocular (1%) - Red eye, ocular pain, decreased visual acuity
o Symptoms of sinusitis (1%)
• The physical examination findings include fever and the manifestations of specific organ
system involvement.
• A dermato-pulmonary-renal syndrome is the feature of the disease.
Skin findings are as follows:
• Leukocytoclastic angiitis and its palpable purpura
o Leukocytoclastic purpura could be a manifestation of the systemic vasculitides or
could be a stand-alone skin disorder
• Palpable purpura (41%)
• Livedo reticularis (12%)
• Skin ulcerations
• Necrosis and gangrene
• Necrotizing nodules
• Digital ischemia (7%)
• Urticaria - Vasculitis-associated urticaria that lasts longer than 24 hours
Respiratory findings in the lower respiratory system
• Include pulmonary rales and respiratory distress.
• In the upper respiratory tract, sinusitis is less frequent than in granulomatosis with
polyangiitis (Wegener granulomatosis).
Cardiovascular findings include the following:
• Hypertension (34%)
• Signs of heart failure (17%)
• Myocardial infarction (2%)
• Pericarditis (10%)
Gastrointestinal findings include the following:
• Gastrointestinal bleeding
• Bowel ischemia and perforation
• Pancreatitis
Ocular findings (1%) include the following:
• Retinal hemorrhage
• Scleritis
• Uveitis
Renal findings comprise signs of
• uremia in advanced renal failure; 8% of patients with MPA present with renal failure and
require hemodialysis.
Musculoskeletal findings include
• synovitis
• arthritis
Neurologic findings are as follows:
• Mononeuritis multiplex - Most frequent neurologic manifestation of the disease (57%)
• CNS involvement - Includes meningeal vasculitis (11%)
Orchitis is present in 2% of male patients.
Diagnosis
• The complete blood cell count (CBC) in patients with microscopic polyangiitis (MPA)
demonstrates leukocytosis and a normocytic anemia. The erythrocyte sedimentation rate
(ESR) is elevated.
• Renal testing results are as follows:
o Elevated blood urea nitrogen (BUN) and serum creatinine levels (70%)
o Abnormal urine sediment
o Proteinuria (80%)
o Hematuria (67%)
o Leukocyturia (44%)
o Erythrocyte casts
• Antineutrophil cytoplasmic antibody (ANCA) test results are as follows:
o ANCA positive (80%)
o Perinuclear ANCA related to myeloperoxidase ANCA (60%)
o Cytoplasmic ANCA related to proteinase-3 ANCA (40%)
Imaging Studies
• Chest radiograph findings are as follows:
o Bilateral irregular, nodular, and patchy opacities
o Pulmonary cavitary lesions (less frequently than Wegener granulomatosis)
o Diffuse parenchymal infiltrates secondary to pulmonary alveolar capillaritis and
hemorrhage
Other Tests
• Other tests may be ordered according to the specific organ system involved, as follows:
o Electrocardiography (ECG) - For possible myocardial infarction, pericarditis, or
heart failure
o Gastrointestinal endoscopy - In cases of gastrointestinal bleeding
o Electromyography (EMG) - In cases of clinical evidence of neuropathy
Treatment
• Treatment of microscopic polyangiitis (MPA) is principally with corticosteroids and
other immunosuppressive agents and consists of induction and maintenance of remission.
• The treatment of relapsed MPA is the same as that of remission induction. Intravenous
immunoglobulin has been used in treatment of refractory disease.
• MPA can manifest as a mild systemic vasculitis with mild kidney insufficiency, or it can
manifest as a full-blown acute disease with rapid deterioration of kidney function and
respiratory failure due to pulmonary capillaritis.
• The choice of medication depends in part on the extent of disease, the rate of progression,
and the degree of inflammation.
Induction of Remission
• Induction of remission in MPA is customarily achieved with cyclophosphamide and
prednisone
• Cyclophosphamide is started at 1.5-2 mg/kg/d.
• The patient should be monitored for leukocytopenia and neutropenia.
• Prednisone is started at 1 mg/kg/d and is continued for 1 month. If significant
improvement is seen, the prednisone dose is decreased by 5 mg/wk
• After complete remission, the maintenance phase is started.
Maintenance of remission
• For remission maintenance, the preference is to replace cyclophosphamide, which has
high toxicity, with either methotrexate or azathioprine
• However, if the serum creatinine concentration is greater than 2 mg/dL, methotrexate is
not an option.
• At this phase, prednisone is continued and cyclophosphamide is replaced with
azathioprine at 2 mg/kg/d for 12 months.
• After a year, the dose of azathioprine is decreased to 1.5 mg/kg/d.
• If methotrexate is used for maintenance treatment, it can be started at 0.3 mg/kg once a
week, with the maximum dose of 15 mg/wk.
• This is increased by 2.5 mg/wk (maximum 20 mg/wk).
• This phase is continued for 12-24 months. Prednisone can be continued at 10 mg/d or
every other day.
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Clinical features
• Eosinophilic granulomatosis with polyangiitis (EGPA) has three phases, as follows:
o Allergic rhinitis and asthma
o Eosinophilic infiltrative disease (e.g., eosinophilic pneumonia or gastroenteritis)
o Systemic medium- and small-vessel vasculitis with granulomatous inflammation
• The vasculitic phase usually develops within 3 years after the onset of asthma, although it
may be delayed for several decades.
• The most prominent symptoms and signs are those related to pulmonary, cardiac,
dermatologic, renal, and peripheral nerve involvement.
• Mononeuritis multiplex is a major clinical finding.
• The following symptoms and signs of the disease were reported
o Constitutional symptoms - Malaise, fatigue, flulike symptoms, weight loss (70%),
fever (57%), myalgias (52%)
o Asthma symptoms - Asthma is a central feature of EGPA, occurring in 97% of
patients. They are usually treated with steroids. This, in turn, might mask other
features of the syndrome
o Paranasal sinusitis (61%) - Usually responds to oral steroids
o Allergic rhinitis
o Pulmonary symptoms (37%), including cough and hemoptysis
o Arthralgias (40%)
o Skin manifestations (49%) - Purpura - Skin nodules, urticarial rash, necrotic bulla,
digital ischemia
o Cardiac manifestations - Symptoms related to heart failure, myocarditis,
pericarditis, constrictive pericarditis, and myocardial infarction
o Gastrointestinal (GI) symptoms (31%) - Symptoms related to GI vasculitis,
eosinophilic gastritis, or colitis; these include abdominal pain (59%), diarrhea
(33%), and GI bleeding (18%).
o Peripheral neuropathy - Mononeuritis multiplex (most frequent form, occurring in
as many as 77% of patients)
• Except for fever, the physical findings in EGPA are specific to organ-system
involvement.
Skin involvement (60%) may include the following:
• Leukocytoclastic angiitis with palpable purpura
• Livedo reticularis, skin necrosis and gangrene, digital ischemia, urticaria, and
subcutaneous nodules
Upper respiratory involvement may include the following:
• Allergic rhinitis
• Paranasal sinusitis
• Nasal polyposis
Lower respiratory system physical findings are related to the following:
• Asthma (i.e., wheeze), expiratory rhonchi
• Pneumonitis
• Hemoptysis secondary to pulmonary alveolar hemorrhage (alveolar capillaritis)
Cardiovascular findings may include the following:
• Myocarditis and signs related to heart failure
• Myocardial infarction secondary to coronary vasculitis
Renal findings may include the following:
• Hypertension
• Signs of uremia and advanced renal failure
Gastrointestinal findings may include the following:
• GI bleeding
• Bowel ischemia and perforation
• Gastroenteritis
• Appendicitis
• Pancreatitis
Nervous system findings may include the following:
• Peripheral neuropathy (includes mononeuritis multiplex [77%])
• Central nervous system (includes stroke [5%])
Diagnosis
• European guidelines from the EGPA Consensus Task Force recommend the following for
the workup of eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss
syndrome)
o Serologic testing for toxocariasis and HIV
o Specific IgE and IgG for Aspergillus species
o Testing for Aspergillus spp. in sputum, bronchoalveolar lavage fluid, or both
o Tryptase and vitamin B12 levels
o Peripheral blood smear (looking for dysplastic eosinophils or blasts)
o Antineutrophil cytoplasmic antibody (ANCA) with indirect immunofluorescence
and enzyme-linked immunosorbent assay (ELISA)
o Chest computed tomography (CT) scan
o Additional investigations should be guided by patient-specific clinical findings
and an extensive search for causes of hypereosinophilia
• In patients with EGPA, the complete blood cell count (CBC) with differential typically
demonstrates eosinophilia, usually with at least 10% eosinophils (or 5000-
9000 eosinophils/µL), and anemia.
• The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are usually
elevated.
• In patients with renal involvement, blood urea nitrogen (BUN) and serum creatinine
levels are elevated.
• Urinalysis demonstrates abnormal urine sediment, proteinuria, microscopic hematuria,
and red blood cell casts.
• Antineutrophil cytoplasmic antibodies (ANCAs) are present in approximately 40% of
patients with EGPA. Most of these patients are perinuclear-ANCA (p-ANCA)–positive
(antimyeloperoxidase antibodies)
Other immunologic test results are as follows:
• Elevated serum IgE levels
• Hypergammaglobulinemia
• Positive results for rheumatoid factor at low titer
 • Elevated levels of eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-
2R), and soluble thrombomodulin (sTM), which is a marker of endothelial cell damage
Imaging studies
• They are used in the workup of patients with EGPA include chest radiography and chest
computed tomography (CT).
• Chest radiography findings are as follows
o Pulmonary opacities can be found in 26%-77% of cases of EGPA
o Localized parenchymal opacities usually are bilateral, peripheral, and patchy.
o Cavitation is rare.
o Pulmonary infiltrates may be transient;
o Pleural effusions are observed in 5%-30% of cases and can be eosinophilic.
Other Tests
The following studies are indicated for specific organ-system involvement:
• Electrocardiogram (ECG) for cardiac manifestations
• Gastrointestinal endoscopy for GI bleeding
• Electromyelography (EMG) and nerve conduction studies for peripheral neuropathies
Biopsy
• If local organ involvement exists, obtaining a biopsy of that organ is most helpful in
confirming the diagnosis. Biopsies of the following may be considered
o Skin
o Lung - Open or video-assisted thoracoscopic biopsy is preferred over
transbronchial
o Renal
o Nerve
o Muscle - Muscle biopsy has a sensitivity of about 67% in detecting systemic
vasculitis
15. Modern options of treatment for rheumatic diseases: NSAIDs, glucocorticosteroids,
cytostatic, genetic engineering biological agents.
NSAIDs
• NSAIDs interfere with prostaglandin synthesis through inhibition of the enzyme
cyclooxygenase (COX), thus reducing swelling and pain.
• However, they do not retard joint destruction and thus are not sufficient to treat RA when
used alone. Like corticosteroids,
• NSAIDs can be reduced in dose or discontinued with successful DMARD therapy.
• The several dozen NSAIDs are available can be classified into several different groups of
compounds.
• Commonly used NSAIDs include
o Ibuprofen
o Naproxen
o Ketoprofen
o Piroxicam
o Diclofenac.
Corticosteroids
• Corticosteroids are potent anti-inflammatory drugs that are commonly used in patients
with RA to bridge the time until treatment with DMARDs is effective.
• These agents are effective adjuncts to DMARD or NSAID therapy.
• Timely dose reductions and cessation are important because of the adverse effects
associated with long-term steroid use.
• Corticosteroids can be administered by oral, IV, or intra-articular routes.
DMARDs
• DMARDs can be classified into nonbiologic and biologic agents. The nonbiologic
DMARDs include the following:
o Hydroxychloroquine (HCQ)
o Azathioprine (AZA)
o SSZ
o MTX
o Leflunomide
o Cyclosporine
o Gold salts
o D-penicillamine
o Minocycline
• Biologic DMARDs: TNF inhibitors
o The TNF inhibitors that bind TNF and thus prevent its interaction with its
receptors include the following:
▪ Etanercept
▪ Infliximab
▪ Adalimumab
▪ Certolizumab
▪ Golimumab
1. Vibration disease: etiology and pathogenesis, clinical picture, diagnosis, differential diagnosis,
principles of treatment and prevention, assessment of professional suitability

- In many occupations workers are exposed to oscillatory motions (that is, vibration) of a type
not encountered by living organisms prior to the industrial revolution. Vibration of powered
hand-held tools and workpieces (that is, hand- transmitted vibration) and the vibration of
seats and floors supporting the body (that is, whole-body vibration) can cause discomfort,
interference with activities, injury, and disease.
- Vibration is 'the mechanical oscillation of a surface around its reference point'. Workplace
exposure to vibration results in local effects, mainly on the hands when the vibration is
transmitted to the upper limbs, and as general systemic effects (mainly low back pain) when
vibration is transmitted to the whole body. The clinical syndrome in the former has been
termed 'vibration white finger' or 'hand-arm vibration syndrome'.

Exposure

Occupational exposure to whole-body vibration occurs in drivers of tractors, fork-lift trucks,

mobile cranes, buses, lorries, and in helicopter pilots. The nature of the surface over which the
vehicle is driven may be as important as the characteristics of the vehicle. Hand-arm vibration
exposure occurs in factory workers involved in fettling, chipping, grinding, riveting, swaging,
and using handheld pneumatic hammers, drills, chisels, and polishing and rotary tools. It also
affects forestry, agricultural, and woodworkers using chain saws, miners drilling rock surfaces,
and construction are road workers using drills and compactors. It has been estimated that
around 3 per cent of the working population are occupationally exposed to sources of vibration.

Clinical effects

1. Whole-body vibration

"Whole-body vibration" is the mechanical vibration that, "when transmitted to the whole body,
entails risks to the health and safety of workers, in particular lower- back morbidity and trauma
of the spine"

Exposure to whole-body vibration causes physiological changes to the cardiovascular,

respiratory, and musculosketetal system. Clinical effects attributed to whole-body vibration
include headache, motion sickness, sleep and visual disturbances, and urinary and abdominal
complaints.

There are following stages of diseases:

First stage (initial manifestations):

§central or peripheral angiodystonic syndrome §vegeto-vestibular syndrome

§vegetative or vegeto-sensory polyneuropathy of lower limbs
Second stage (moderate):
§central or peripheral angiodystonic syndrome §vegetative or vegeto-sensory polyneuropathy
with:

- syndrome polyradiculoneuritis
- secondary lumbosacral radicular syndrome caused by osteochondrosis of lumbar spine
- functional disorder of nervous system (neurasthenia).

Third stage (evident manifestations):

§syndrome sensomotor polyneuropathy

§syndrome vascular encephalopathy with peripheral polyneuropathy §osteoarthrosis of spine,
large joints of limbs.

There are functional disorder of viscera (stomach, bowels, liver), visceroptosis, disordered
menstrual cycle in women.

2. Hand-arm vibration syndrome

- Until recently this was known as vibration induced white finger (VIWF), reflecting its
mode of presentation. It has been renamed to reflect the wider range of its effects.
- Though originally described in the mining, metallurgical, and engineering industries,
forestry may now be the main source of cases because of widespread use of chainsaws.
How vibration actually induces the condition is not clear, but recent studies suggest it is
probably a local effect on nerves and blood vessels.

Presentation

• This causes secondary Raynaud's phenomenon which manifests as frequent prominent

episodic pallor of the digits, usually on exposure to cold. Patients frequently describe
digital pallor in the morning, or following an outdoor activity such as fishing or
gardening, especially in cold weather. The vascular changes may be accompanied by
neurological and musculoskeletal effects which contribute to the disability experienced.
Vascular and sensorineural effects may appear and progress independently. The latent
period between initial exposure and development of symptoms is usually 5 to 10 years,
although periods as short as б months or as long as 20 years have been noted depending
on the Intensity and duration of exposure. The sequence of colour change In the affected
digits include pallor, a bluish hue due to cyanosis, and redness with spontaneous reversal
of the vascular spasm.
• With continued exposure to vibration, the vasospasm progresses proximally and to other
fingers, but the thumb is rarely affected. The vasospasm has a characteristic pattern: it is
rarely symmetrical and reflects the subject's grip on the vibrating tool--thus, an
underhand grip on a vibrating chisel affects mainly the index finger, whereas the little
finger is mainly affected with an overhand grip. After the painless vasospasm ("dead
finger"), a cyanotic phase may occur before a painful hyperaemia ("hot aches"). In some
 cases only cyanosis occurs with vasospasm. In the most severe cases the fingers are
permanently cyanosed and trophic changes of the fingertips can occur. The intermittent
neuropathy that accompanies the vasospasm becomes continuous and deteriorates with
further exposure. It affects most modalities and results in clumsiness.
• Neurological effects include paraesthesia, reduced temperature perception, loss of manual
dexterity, and pain. Severe tingling and discomfort often follow rapid warming of the
hands. Loss of proprioception causing the inability to distinguish and hold small objects
such as coins or to button up clothes contributes to physical and social disability.
Musculoskeletal effects are not as well established, but muscle weakness, exostoses and
cysts in the carpal bones, carpal tunnel syndrome, osteoarthritis, and Dupuytren's
contracture have been associated with exposure to vibration.

Management, treatment, and prevention

• Engineering controls can minimize the transmission of vibration from machinery to the
body or hands.
• The patient may be able to continue in their job following such action.
• Where the condition is severe and the source of vibration cannot be eliminated,
redeployment should be considered. In early cases redeployment may arrest or reverse
the progression of symptoms.
• In severe cases the disease can progress regardless of removal from further exposure to
vibration.
• Advice to the patient includes avoidance or reduction of further exposure to vibration, use
of appropriate gloves, keeping the body and hands warm, especially in cold weather, and
cessation of cigarette smoking.
• Vasodilatory drugs such as tolazoline, inositol, and cyclandelate, and calcium antagonists
such as verapamil and nifedipine, angiotensin-converting enzyme inhibitors,
prostaglandins, and stanazolol have been tried with varying success.
2. Pneumoconiosis: etiology and pathogenesis, main clinical presentations, treatment.

- Pneumoconiosis is a lung condition that is caused by inhaling particles of mineral dust,

usually while working in a high-risk, mineral-related industry.
- Irritating mineral dust can trigger lung inflammation. This inflammation eventually can lead
to the formation of tough, fibrous tissue deposits. This condition is called fibrosis.
- In people with severe pneumoconiosis, fibrosis can stiffen the lungs, restrict airflow and
ultimately interfere with the lung’s normal exchange of oxygen and carbon dioxide.
- This respiratory disease was first recognized in 1705 by Ramazzini who noticed sand-like
substances in the lungs of stonecutters (De Morbis Artificum Diatriba (Diseases of
Workers)).

Etiology : The following factors play a role in etiology of disease:

1. Chemical structure of particles of a dust. The high fibrogenic dust is free silicon dioxide;
the mild fibrogenic dust is talcum, cement, clay; the low fibrogenic dust is coal, asbestos.
2. Dust dispersiveness influences on the depth of its penetration in respiratory organs.

o The large particles (more than 10 microns) are quickly precipitate in the environment,
and stay in the upper airways and extrapulmonary bronchus at the inhalation.

§ The microscopic particles (0.25 -10 microns) penetrate into the lung alveolus.
§ The ultra microscopic particles (less than 0.25 microns) are suspended and play a
small role in development of diseases.

o The most aggressive dust is a dust from 1 up to 5 microns.

3. Concentration of a dust. The contents of a dust is higher in the air of a workroom,

the probability of development of disease is more. Maximum permissible
concentration (MPC) of high fibrogenic dust is 1 mg/m3, MPC of mild fibrogenic
dust is 4-6 mg/m3, MPC of low fibrogenic dust is 8-10 mg/m3.
4. Duration of work in contact to a dust. As a rule, the slowly progressive form of
disease develops after 10-15 years from a beginning of work in "dusty" working
conditions. There is a quickly progressive form of pneumoconiosis (in 3-5 years
from a beginning of work) and late pneumoconiosis (in some years after the end to
contact a dust).

In addition, various impurities of toxic substances in inhaled air, high temperature and the
individual features of worker’s organism play a role in development of pneumoconiosis.

Pathogenesis

- The inhaled dust penetrates into the lung alveolus and accumulates there. Alveolar
macrophages phagocyte the particles of a dust. Phagocytosis is accompanied by damage
phagolysosome’s membrane and death of macrophage. Lactic acid and others suboxide
 products accumulate in the intercellular space of pulmonary tissue and activate
collagenation. Pneumofibrosis develops.
- Pneumoconiosis may occur with or without fibrosis. In fibrotic forms of pneumoconiosis,
histopathologic and radiologic findings are suggestive of fibrosis. Silicosis, coal worker
pneumoconiosis, asbestosis, berylliosis, and talcosis are fibrotic forms of pneumoconiosis.
Siderosis (from iron oxide), stannosis (from tin oxide), and baritosis (from barium sulfate)
are nonfibrotic forms of pneumoconiosis.

Clinics:

- Pneumoconiosis sometimes does not cause any symptoms. When symptoms develop, they
can include:

• Dyspnea exacerbated by exertion

• Dry or severe cough, often persistent and accompanied by hoarseness of the throat
• Fatigue
• Tachypnea (rapid breathing) which is often labored
• Loss of appetite
• Chest pain
• Fever
• In advanced cases, the following may also occur: Cyanosis
• Cor pulmonale
• Respiratory insufficiency

Treatment

- Treatment options currently focus on alleviating the symptoms and preventing

complications. These include:

• Stopping further exposure to silica and other lung irritants, including tobacco smoking.
• Bronchodilators to facilitate breathing.
Cough suppressants.
Antibiotics and antitubercular agents to prevent tuberculosis and non-specific
• infections.
Chest physiotherapy to help the bronchial drainage of mucus.
Oxygen administration to avoid hypoxemia.
Lung transplantation to replace the damaged lung tissue is the most effective
• treatment, but is associated with severe risks of its own.
3. Occupational allergic diseases (bronchial asthma): features of the clinic, diagnosis, treatment and
prevention, assessment of professional suitability.
• Because it is primarily an immunological disease, occupational asthma has a number of characteristic
features that are useful clinically.
• First, it occurs only in a proportion of those exposed to the causative agent(s) presumably reflecting at least
in part a constitutional susceptibility.
• Second its onset is not immediate but because of the period required for sensitization generally several
months or more after the start of a new occupation. With the possible exception of asthma among bakers it
is unusual for occupational asthma to arise many years after the onset of a new occupation; unless of course
there has been an important change in the exposures associated with the job. Careful questioning about the
time relationship between changes in job and the onset of asthmatic symptoms can be very helpful in
distinguishing occupational asthma from work-exacerbated or irritantinduced disease.
• Third, once occupational asthma has developed then its symptoms may be provoked by very low intensity
exposures to the initiating agent. The bronchial hyperresponsiveness that universally accompanies active
occupational asthma may also mean that patients with established disease experience wheeze on exposure to
a variety of non-specific respiratory irritants both at and away from work. This can be a source of some
diagnostic confusion. In many cases the patient with occupational asthma will recount an unmistakable
history of wheeze which started after new employment (typically within 2 years) and which is worse at
work but relieved during days off. In other cases the relationship with work may be less clear. Where, for
example, the clinical response is confined to a "late phase" asthmatic reaction then symptoms, confusingly,
may be felt only after rather than at work; night waking with wheeze or cough is a useful clue.
• Those whose disease is the result of exposure to a high molecular weight agent generally (but not
exclusively) report associated symptoms typical of an immune response to an airborne protein: rhinitis,
itching and watering of the eyes and sometimes an urticarial rash.
• In most cases upper respiratory symptoms have an earlier onset than do those of asthma. Upper respiratory
and eye symptoms are less common immune responses to low molecular weight agents.
Diagnosis
- Diagnosis of occupational asthma is a process and has to be done over a period of time. First, the patient‘s
occupational and clinical history is taken and his symptoms are charted. Once this has been established, the
following diagnostic methods are used:
• Non-specific bronchial hyperreactivity
§ A non-specific bronchial hyperreactivity test involves testing with methacoline, after which
the Forced Expiratory Volume in 1 second (FEV1) of the patient is measured.
• Skin prick tests
§ Reactions, if any, occur within 10 to 15 minutes and these results can then be analyzed.
• IgE-specific tests
§ Since it can also trigger allergic reactions to specific allergens like pollen, the IgE test is
performed to evaluate whether the subject is allergic to these substances.
• Spirometric tests
§ Peak Expiratory Flow at work
§ This test uses the PEFR method. The only difference is that it measures the functioning of
the patient's airways at his place of work and not necessarily in a controlled environment.
• Specific inhalation challenge
§ Realistic method. ―The Realistic Methodǁ is a whole body sealed chamber where the
patient is exposed to articles that are present in their workplace. This method has the
advantage of being able to assess, albeit highly subjectively, ocular and nasal symptoms as
well as a reduction in FEV1.
• Closed-circuit method
§ This test requires the patient to breathe aerosols of the suspected ‗asthmagens‘ through an
oro-facial mask. These ‗asthmagens‘ are aerosolized using closed circuit chambers, and the
 quantities and concentrations administered being minute and extremely stable minimize the
risk of exaggerated responses.
Treatment
- Recovery is directly dependent on the duration and level of exposure to the causative agent. Depending on
the severity of the case, the condition of the patient can improve dramatically during the first year after
removal from exposure.
- Three basic types of procedures are used for treating the affected workers:
1) Reducing exposure This method is most effective for those affected by irritant-induced OA. Thus, by
reducing their exposure duration and level to the causative agent, the probability of suffering another
reaction is lowered. Thus, reducing exposure to known asthmagens can also be used as a preventive
measure.
2) Removal from exposure Persons affected by OA that occurred after a latency period, whether a few
months or years, must be immediately removed from exposure to the causative agent. This is their only
chance of recovery.
3) Medical and pharmacological treatment Anyone diagnosed with Asthma will have to undergo medical
treatment. This is complementary to either removing or reducing the patient‘s exposure to the causal agents.
- Two types of medication can be used:
• Relievers or bronchodilators Short-acting beta-agonists like salbutamol or terbutaline or long-acting
beta-agonists like salmeterol and formoterol or anticholinergic, etc. dilate airways which relieve the
symptoms thus reducing the severity of the reaction. Some patients also use it just before work to
avoid a drop in the FEV1.
• Preventers Anti-inflammatory agents like corticosteroids, or mast cell stabilizers can be used
depending on the severity of the case.
Prevention
- Occupationally induced disease is a rare example of asthma that can potentially be cured. It is also one that
can - theoretically at any rate - be prevented. Sufficient is known about the causes of the disease and about
how these can (at least in many cases) be rectified for disease prevention to be realistic.
- There are several approaches to primary disease prevention. Elimination of the causative agent or its
substitution by an effective but safe(r) alternative has occasionally been practised. The pre-market testing of
new agents for their sensitising potential is widely practised but it is not known how successful this has been
in avoiding the use of new agents capable of inducing asthma. The use and value of pre-employment
screening is discussed above. Most preventive programmes however employ a mix of employee education,
exposure reduction and, as a method of secondary prevention, careful surveillance of the workforce. The
results of several such programmes strongly suggest that primary disease prevention is possible given
sufficient will.
Assessment of professional suitability.
- Mild asthma – working capacity is maintained, patient should be placed in a job without exposure of
allergens.
- Moderately asthma – patient should be placed in a job without exposure of allergens, if it is necessary,
degree of disability is established.
- Severe asthma – patient is incapacitated.
4. Chronic lead intoxication: etiology and pathogenesis, main clinical presentations,
complications, treatment.

- Inorganic lead: Exposure to inorganic lead compounds occurs in mining, extrac- tion,
smelting, metal cutting, manufacture of lead pipes, lead paints, manufacture of lead batteries,
crystal glass and hot metal typesetting.
- It is absorbed as dust via the respiratory tract, and via the gastrointestinal tract with food and
drinks. Inorganic lead is not absorbed through the skin.

Pathogenesis

• In order to suffer the ill effects of a toxicant, one must be exposed to a sufficient dose,
which must in turn be absorbed into the blood. Ingestion and inhalation are both im-
portant. Approximately 10–15% of the ingested quantity is absorbed, although this can be
higher in the presence of iron deficiency, pregnancy, and fasting.
• Upon absorption, lead binds to erythrocytes, and over a period of weeks is distribut- ed
predominantly to bone, liver, kidney, marrow and brain. Over 90% of the body burden of
lead is stored in the compact bone matrix and trabecular bone from which lead may be
mobilized.
• Lead’s primary toxicity is due to its affinity for sulfhydryl groups allowing altera- tion of
protein and enzymatic function. Lead is similar to calcium in its physiochemical
properties, accounting for its osseous deposition and its effect within mitochondria where
it competitively antagonises the action of calcium. Lead causes anaemia, both by inhibit-
ing haeme synthesis and accelerating erythrocyte destruction. Renal toxicity may be re-
versible with lower exposure, as early pathological changes affect only the proximal tu-
bules.
• There is no active elimination of lead. Elimination occurs through skin desquama- tion,
nail growth, biliary secretion and glomerular filtration.

Clinical presentation

A difficulty with the presentation of lead toxicity is the nonspecific nature of symp- toms. These
symptoms range from fatigue, concentration difficulties, sleep disturbances, headache, weight
loss, nausea and myalgia.

More characteristic syndromes of lead poisoning are hematologic, neurologic, gas- trointestinal,
hepatic, cardiovascular.

Hematologic syndrome.

• Lead depress activity of enzymes, taking part in haem biosynthesis. Lead block
sulfhydric group of δ-aminolevulinic acid synthetase and δ-aminolevulinic acid dehydra-
tase, haemsynthetase. δ-aminolevulinic content in blood increase, coproporphyrin content
in urine increase.
 • Anemia from lead poisoning is associated with a reduced red cell life span and with
reticulocytosis and basophilic stippled cells in peripheral blood.
• Symptoms of this anemia include irritability, fatigue, pallor, and sallow complexion.
Bone marrow preparations show increased numbers of sideroblasts, and this is useful in
differential di- agnosis of lead poisoning from iron deficiency anemia.

Gastrointestinal syndrome

• Have been described effects of lead poisoning such as loss of appetite, metallic taste in
the mouth.
• Unique feature of lead poisoning include a blue line on the dental margins of the gums.
• Gastrointestinal sequelae of lead poisoning include also nausea often without vomiting,
and constipation (or, occasionally, diarrhea). The classic features of severe tox- icity is
abdominal cramps or intestinal colic.
• Abdominal cramps is characterized by: - sharp colicky abdominal pains
- lingering and persistent constipation - increase of arterial pressure.
• The overexcitation parasympathetic and especially sympathetic nervous system as well as
degenerative changes of ganglion underlie these disorders.
• Vegetative crisis ac- companied angiospasm and most evident spastic and atonic bowels
condition arise.

Neurologic syndrome

• Peripheral and central nervous system effects occur in severe poisoning. Peripheral
neuropathy of lead poisoning involves considerable loss of motor function but little loss
of sensory function. Extensor muscles of the hand and feet are often involved; extensor
weakness may progress to palsy, often observed as a characteristic "wrist drop" or "foot
drop".
• Encephalopathy may be either acute or chronic. Acute encephalopathy may develop
quickly to seizures, coma, and death from cardiorespiratory arrest. Chronic encephalopa-
thy usually leads to loss of motor skills and of speech, and to development of behavioral
disorders.

Nephropathy is another effect of lead poisoning. There may be a progressive and irreversible
loss of kidney function, with progressive azotemia, and occasionally hyperu- ricemia with or
without gout. Nephritis is not common, but ischemic nephritis may occur after prolonged
absorption of lead.

It distinguish following form of lead poisoning:

Initial form is characterized only by changes in the blood picture and porphyrinic exchange.
Content of hemoglobin and erythrocytes is normal. Clinical signs is absent.

In mild lead poisoning it register neural disorders: asthenic and asthenovegetative syndrome or
initial form of vegetative and sensitivepolyneuropathy.
Evident form is characterized by development of anaemic syndrome, abdominal cramps,
considerable neural disorders, sungs of toxic liver injury.

Treatment

• In all cases of suspected lead intoxication, the first step in management should be removal
of the individual from the exposure. Discontinuation of exposure is sufficient treatment or
chelation therapy should be administered depends on the blood lead concen- tration, the
severity of clinical symptoms, the biochemical and hematologic abnormalities, and the
nature of the exposure.
• Chelates are used for treatment of a poisoning of lead: ethylene diamine tetraacetate
(EDTA), D-penicillamine. Chelates connect heavy metals and assist their excretion. Be-
sides vitamins of group B, ascorbic acid, sedative and analeptic.

Prevention

The first line of defense in the elimination of occupational lead poisoning is primary
prevention – actions taken to prevent overexposure. Primary prevention is best achieved
through the use of engineering controls, personal protective equipment and good work
practices. The family physician can have the greatest impact on prevention through
worker education and instruction in proper personal hygiene techniques

Engineering control methods to prevent exposure are ventilation, mechanization and

housekeeping. Personal cleanliness, change of clothes, washing facilities and provision of
clean areas for eating and storing food will reduce uptake of lead by mouth. Periodic
med- ical examination helps detect early affection.
5. Occupational bilateral neurosensory hearing loss: pathogenesis, clinical picture, diagnosis, criteria for
determining the severity, treatment, assessment of professional suitability

Pathogenesis

• Exposure to noise results in both physiological and pathological changes. An early response to acute noise
exposure is an increase in blood pressure.
• More prolonged exposure to a sufficient intensity of noise causes a temporary shift in the threshold of
hearing (temporary threshold shift).
• Excessive noise exposure causes damage to the outer hair cells of the cochlea, with breakage and disruption
of the pattern of cilia on these cells which operate as local electromechanical amplifiers within the cochlea.
• The most important effect of exposure to noise is noise-induced hearing loss (NIHL).
• Hearing impairment is at first temporary; as exposure to noise (about 85 dB) continues, hearing impairment
becomes permanent. NIHL usually takes many years (7-10 years) to develop.
• The most hazardous is high intensity, high frequency, continuous noise. Personal susceptibility has a
definite effect.

Clinical picture

• Clinical presentation noise induced hearing loss develops insidiously.

• A gradual loss of clarity in perceived speech occurs, which is often attributed to inattention or to others not
speaking clearly because when the sufferer looks at speakers he or she can understand them.
• Difficulty in understanding others in a crowd is, in the same way, presumed to be due to competition with
background noise (perceptual rivalry).
• Eventually, the sufferer realises that others do not have this problem.
• A high pitched tinnitus, initially intermittent, becomes continuous in up to 20% of cases and can be a
presenting symptom.
• The other feature (usually revealed on direct questioning) is loudness recruitment: at a certain volume
perceived sound suddenly becomes more intense

Diagnosis
- Audiometry reveals early hearing impairment at frequencies of 3000-6000 Hz before hearing of normal
speech is affected. Hence, the importance of measurement of hearing on pre-placement and periodic hearing
examinations.
- A programme of screening audiometry should be introduced where daily personal exposure to noise (a time-
weighted measure) is of the order of 85 to 90 dB(A), and in conformity with relevant national legislation
and guidance.
- The technical requirements for industrial hearing conservation audiometry are specified in ISO 6189.
- Measures are normally taken to void temporary threshold shifts at the time of testing, with examinations
repeated every 2 to 3 years.
- Audiometric characteristics of noise induced hearing loss:
* Bilateral notch in hearing threshold at 3, 4, or 6 kHz with recovery at 8 kHz
* Progressive deepening and widening of notch with increasing exposure to noise
- Where abnormalities are detected, it is important to establish the history of occupational and leisure noise
exposure, the use of hearing protection, exposure to ototoxic drugs and chemicals, and relevant past diseases
and injuries, and tinnitus.
- Otoscopic examination, bone conduction audiometry, tympanometry to determine middle ear function, and
evoked response audiometry may have a role in clinical assessment.
- Referral for a specialist opinion is relevant where pathology other than noise-induced hearing loss is
suspected (such as the rare acoustic neuroma) and where it is thought that a hearing aid or tinnitus masker
may be of help to the individual.
Criteria for severity

Treatment

• Prevention is better than cure.

• Treatment include medicamental and non-drug means. Following drugs are used:
- Drugs, improving of cerebral circulation (cavinton, vinpocetine, cinnarizine);
- Drugs, improving of cellular metabolism (pyracetam, vitamins B, emoxipin);
- Drugs, improving of nerve conduction (proserin);
- Sedative drugs (bromine, valerian).
1. Tuberculosis causative agent, transmission of disease.
Mycobacterium Tuberculosis- An Acid-Fast Bacilli
Natural reservoirs of MBT are – human, domestic and wild animals, birds.
MBT are slender, curved rods that are resistant (fast) to acids, alkalis, and dehydration. The cell
wall contains complex waxes and glycolipids.
MBT can multiply within macrophages, and also extra-cellular.

source of infection. The basic source of MBT is the tuberculous patient

Ways of transmission
1) air-born; - cough droplets, sneezing and conversation
2) alimentary (digestive);
3) contact;
4) intrauterine tuberculosis infection.
Stages.
1. Spreading of infection (contamination).
2. Beginning of infection, proliferation and dissemination in an infected host.
3. Formation of immune reaction in the host.
4. Formation of caseous necrosis, and proliferation of bacteria.
5. Secondary spreading of infection (ability to infect).

2. Milliary and disseminated pulmonary tuberculosis, clinical picture and differential

diagnostics.
Clinical Feature
• primary infection usually asymptomatic, although progressive primary disease may occur,
especially in children and immunosuppressed patients
• secondary infection reactivation usually produces constitutional symptoms (fatigue,
anorexia, night sweats, weight loss) and site-dependent symptoms
1. pulmonary TB
■ chronic productive cough ± hemoptysis, fever, night sweats, weight loss, chest pain,
anorexia
■ CXR consolidation or cavitation, lymphadenopathy, predominantly upper lung findings
but variable ■ non-resolving pneumonia despite standard antimicrobial therapy
2. miliary TB
■ widely disseminated spread especially to lungs, abdominal organs, marrow, CNS
■ CXR: multiple small 2-4 mm millet seed-like lesions throughout lung
3. extra-pulmonary TB
■ can occur in any organ - lymphadenitis, pleurisy, pericarditis, hepatitis, peritonitis,
meningitis, osteomyelitis (vertebral = Pott’s disease), adrenal (causing Addison disease), renal,
ovarian

Disseminated lung tuberculosis : To this form miliary, sub acute disseminated and chronically
proceeded disseminated lung tuberculosis is referred.
Miliary Tuberculosis:
• M.tuberculosis overrun draining Lymph Nodes and enter the Circulation.
• Organisms are ‘seeded’ back into the lung—>Forming Many lesions
• Miliary lesions Coalesce & Erode the lung parenchyma—>Pleural Effusion/Haemoptysis/
Empyema.
 • common acute intoxication and functional disturbances : loss of appetite, weakness,
temperature up to 39-40°C, dyspnoea, dry cough sometimes with expectoration of small
amount of sputum, acrocyanosis of the lips.

Milliary lung tuberculosis: On the chest x-ray multiple, fine (1-2 mm) of the same type focuses, rich
and in regular intervals distributed in all lung fields. The focuses are precisely outlined, do not
merge. Their intensity is average. Picture of lung vessels is not seen because of a big number of
focuses.
• High-resolution CT scan obtained with lung windowing demonstrates numerous fine, discrete
nodules bilaterally in a random distribution.
• Focuses can completely dissolve or calcify at reverse development of tubercular process. The
quantity of calcified focuses is less, than in the period of dissemination, because of partial
dissolving of focuses.
• Dissemination of focuses is settled down symmetrically, as a rule, in all lung fields, on a
background of pneumosclerosis and is kept on for all life.
• Disintegration of lung tissue appears as thin-walled cavities, at progression of process, owing to
trophic changes in lungs.
• Usually cavities are multiple, oval, identical in a form and in sizes. Therefore they are named
"stamped". Sometimes they are located by a chain, quite often are symmetric in both lungs. They
are named as system cavities in such cases.

• Subacute disseminated tuberculosis on chest x-ray is characterised by representing larger and

merged focuses; lymphangitis in the form of peribronchial "couplings" along with multiple fine
focuses in both lung fields Cavities are the same, as at miliary tuberculosis, thin-walled,
"stamped".
complains - non-severe cough with sputum expectoration, and rise in temperature.
The signs - are diverse, hemoptysis
The disease can proceed under the symptoms of influenza and focal pneumonia.

• chronic disseminated tuberculosis on chest x-ray is characterised by presence of the focuses of

various size and intensity, places of formed conglomerates, and also net like fibrosis of the upper
lobes. The roots and the vessels of the upper lobes are displaced up.
• The process is bilateral, but frequently asymmetrical - one lung can be struck more than another.
Cavities are thin-walled, but usually deformed.
• Exudative pleuritis is observed quite often at disseminated tuberculosis.
• weakness, adynamia, fever (subfebrile temperature), cough with sputum, dyspnoea, increasing
with physical load. The disturbance of nervous system cerebral cortex disturbance psychic
liability, irritability, reduction of work capacity, loss of sleep, neurotic reactions.
• The disturbances of endocrine system: hyper- or hypothyroidism. the dispersed dry rales, fine
moist rales, pleural friction rubs hemoptysis and lung hemorrhage, symptoms of obstructive
bronchitis with bronchospasm.
• The signs of lung-heart insufficiency – cyanosis, tachycardia, dyspnoea, hypostatic phenomena
in lungs, liver, kidneys and edema of lower extremities.
• blood – neutrophil nuclear shift to the left, lymphopenia, monocytosis, elevation of ESR. МВТ +

Differential diagnosis: pneumonia of non-tuberculosis genesis, hemosiderosis, mycosis, sarcoidosis,

pneumoconiosis, carcinomatosis, histiocytosis, fibrosating alveolitis,
FROM STUD
Milliary tuberculosis (MT) is a form of disseminated TB (acute disseminated TB).
Pathomorphology: multiple prosovid 1-2 mm diameter yellowish-gray foci along the course of
capillaries in both lungs.
Milliary TB Clinic:
- acute onset with increasing symptoms of intoxication, hectic fever
- shortness of breath, dry cough, percustoonously over the entire surface of the lungs, auscultatively
weakened vesicular breathing, a small number of small bubble or dry wheezing
- delicate roseolous rash on the skin (toxic-allergic thrombovasculitis)
Clinical forms of MT:
a) typhoid form - pronounced symptoms of intoxication with deep CNS disorders
b) pulmonary form - asphyxic type of breath, dry supersadnozzle cough (due to the rash of foci on
the bronchi mucosa), acrocyanosis, increasing tachycardia
MT diagnostics:
1. Mantoux test: negative anergy
2. Bacteriological study: bacterial excretion is not characteristic or little (due to the lack of
destruction foci)
3. X-ray diagnostics: total focal dissemination; focal shadows not > 2 mm, rounded, low intensity,
with fuzzy contours, often arranged in the form of a chain along the course of vessels
Differential diagnosis: pneumonia of non-tuberculosis genesis, hemosiderosis, mycosis, sarcoidosis,
pneumoconiosis, carcinomatosis, histiocytosis, fibrosating alveolitis

Disseminate TB (DTB) is a post-primary TB resulting from multiple damage to organs and tissues
by tuberculosis foci due to their hematogenic, lymphohematogenic or lymphogenic dispersion:
1) generalized
2) with predominant lung damage
3) with a predominant defeat of other organs.

Pathogenesis: complication of the course of primary TB (early generalization) or reactivation of

inflammation in residual changes in postpartic TB (more often intrathoracic L.) in
immunodeficiency, non-specific sensitization of the body, additional exogenous superinfection (late
generalization) -->
1) bacteremia, hypersensitization of tissues to MBT and their toxins --> hematogenesemia -->
symmetrical lesion of both lungs OR
2) lymphostasis, retrograde lymph current from intrathoracic l.u. --> lymphogenic dissemination -->
asymmetric lung damage more often on one side in the root zone

Pathomorphology:
a) acute disseminated TB (milliary) - see question 102, occurs in severe immunodeficiency.
b) subacute disseminated TB - foci of medium and large sizes (5-10 mm) more often located
subpleurally in the upper and middle parts of the lung, merging with the formation of foci of
destruction, occurs in case of moderate immunodeficiency in bacteremia
c) chronic disseminated TB - floor-by-floor appearance of fresh foci in previously intact areas of
the lung, starting with the apex and posterior segments; dissemination is polymorphic, exudation
prevails in fresh foci, the old ones are replaced by fibrous tissue, contain calcium salts, are not
prone to merging; stamped (pointer) caverns are characterized - symmetrical cavities decay in the
upper lobes with thin walls and free lumen; occurs in case of moderate deficiency in
lymphohematogenic dissemination
Clinical manifestations of DTB:
(a) Miliary TB - see question 102.
b) subacute - develops gradually: first astheno-vegetative syndrome, shortness of breath, periodic
productive cough, then - signs of complications (side pain in pleurisy, voice hoarseness in laryngeal
tuberculosis), etc.; physically symmetrical dulling of the pulmonary sound, unstable dry wheezing
in the interscapular space
c) chronic - occurs with phases of exacerbation, when the general condition worsens, dry cough,
remission is expressed; dyspnea gradually progress due to pneumofibrose, neurotic reactions,
endocrine disorders; physically, trapping of the supra- and subclavian spaces, dulling of pulmonary
sound over the foci of lesion, signs of emphysema of the lower parts, dry, and with aggravation of
the process, wet wheezing over the foci of lesion.

Diagnostics of DTB.
1. Mantoux test: normalgic outside exacerbation, hypo- or anergic in case of exacerbation.
2. Bacteriological study: bacterial excretion is not characteristic or little (due to the lack of
destruction foci)
3. X-ray diagnostics: focal dissemination syndrome
a) subacute DTB: subtotal (more in the upper and middle sections) large (5-10 mm) dissemination
in the form of different foci of medium and low intensity with fuzzy contours; some foci merge and
form focal dimming with areas of enlightenment (due to destruction)
b) chronic TB: subtotal or total relatively symmetrical polymorphic multi-intensity equal
dissemination; sometimes decay cavities in the form of annular enlightenments with clear internal
and external boundaries (stamped caverns); s-m "splumping willow": lung root shadows are
symmetrically tightened upwards; "drop heart"; volumetric lung changes, interstitial fibrosis

Outcomes of disseminated tuberculosis: death; transformation in fibroce-cavernous; diffuse fibrosis;

resorption; multiple fibrous foci; cavern; tuberculosis

Differential diagnosis: pneumonia of non-tuberculosis genesis, hemosiderosis, mycosis, sarcoidosis,

pneumoconiosis, carcinomatosis, histiocytosis, fibrosating alveolitis,
3. Infiltrative pulmonary tuberculosis, clinical picture and differential diagnostics.
• On chest x-ray most often infiltrative focuses are defined in the upper lung lobes of various size:
from 1,5 cm in a diameter up to defeat of the whole segment of lobe.
• Intensity of focuses is various. Frequently they are bordered by an indistinct, dim contour, having
wrong form, not homogeneous structure.
• According to localisation of extent of process infiltrative-pneumonic lung tuberculosis is divided
into the following forms:
- limited and oval with near lung root localization,
- cloudy infiltrations,
- periscissuritis, and
- lobitis.
• The contours of infiltration are precise at tubercular damage of a segment or lobe. Focuses of
various sizes, architectural distortion of the lung tissue, and inflammation "path" to a root are
defined in contiguous areas of lungs.
• Infiltrative-pneumonic lung tuberculosis is complicated by disintegrations with formation of a
cavity. The cavity is found out as enlightenment in infiltration, having oval or irregular form, with
precise internal contour.
• In most cases, infiltrative TB begins acutely with high temperature and can proceed as lobar
pneumonia or influenza.
• hemoptysis or bleeding
• pains in the chest
• dry cough or cough with poor sputum expectoration
• The signs of tubercular intoxication : poor appetite, sweating, disturbances of sleep, raised
excitement and tachycardia

From stud
Clinical picture:
a) broncholobular and rounded infiltrates - a weak clinic in the form of asthenovegetative
syndrome, often detected accidentally during fluorography; the affected half of the chest lags
behind in the act of breathing, there may be pleurisy with respiratory muscle tension, tension and
soreness of the shoulder muscles (Voroby
b) cloud-shaped infiltration and perississuritis - clinically acute onset, pronounced intoxication,
slight productive cough, sometimes hemoptysis; dulling of the pulmonary sound, increased voice
trembling, vesiculobronchial breathing, small vesicle (above the affected area) and medium-
c) lobitol - pronounced intoxication, cough, a large amount of sputum; intoxication periodically
increases and decreases (due to the appearance of new bronchogenic dropout foci)
Places of the most frequent localization of infiltrates - alarm zones (over- and subclavian spaces,
adscapular, interscapular, armpit areas)

Differential diagnosis: lung cancer, non-specific pneumonia, eosinophilic lung infiltrate,

pneumomycosis, lung infarction
4. Fibro-cavernous pulmonary tuberculosis, clinical picture and differential diagnostics.
• On chest x-ray the picture of fibrosis of shrinking of a lung, old fibrous cavity (one or several),
pleual depositions are defined.
• At fibrous cavernous lung tuberculosis the cavity settles down among rough lung fibrosis, its
walls are deformed, are dense, are thick more often.
• Quite often at the bottom of the cavities the small level of a liquid is defined.
• At an aggravation and progressing of the process, the sites of infiltration are visible around a
cavity.
• Sometimes fibrous cavity comes to light only at tomography, as on chest x-ray the shadow of a
cavity can be closed by layering shadows of the focuses, fibrosis and pleural stratifications.
• The picture of fibrosis and shrinking of lungs are found out in the upper lobes, with a
predominant defeat of one of them.
• Mediastinum and trachea are shifted to the site of biggest defeat. T
• he upper lobes are reduced in volume, their transparency is sharply lowered because of
hypoventilation.
• Architecture of the lung tissue is sharply distorted because of rough fibrosis.
• The transparency of lungs is often increased owing to inflation.
• Usually in both lungs groups of focuses of various intensity are visible.
• The roots, as a rule, are displaced up. The large vessels are defined as direct, equal regular — a
so-called symptom « of the tense string ».
• Anamnesis of patients with fibrous-cavernous TB is characterized by complaints of long standing
diseases, its wavy course.
• Intervals between outburst and clinical favorable condition can be very long or very short.
Sometimes patients subjectively do not feel symptoms of the disease.
• Clinical signs of fibrous-cavernous tuberculosis are multiform. They depend on tubercular
process itself and on development of complications
- There are temperature rises in periods of acute worsening.
- Temperature can be high when a secondary infection joins the disease. The inflammation of
bronchi is accompanied by long «hoarse» cough with hardly discharged viscous mucous-purulent
sputum.
- Haemoptysis.
- Lung haemorrhage.

From stud
- astheno-vegetative syndrome, in case of exacerbation of the process - hectic fever, night sweats
- shortness of breath, cough with a small amount of sputum (50-100 ml), sometimes with an
admixture of blood
- displacement of mediastinum organs towards defeat
- on the side of the defeat: trapping of intercostal spaces, superpodclavian pits, dulling of
pulmonary sound, weakened breathing, wet multi-caliber (depending on the diameter of draining
bronchi) wheezing in the cavern area, with pronounced fibrous compaction - bronchial breathin

Differential diagnosis: bronchiectatic disease, chronic abscess, decaying lung cancer, air cysts,
suppurated cysts
lung abscess, cystic pulmonary hypoplasia (polycystic lung, congenital bronchiectatic cysts, cystic
lung, developmental adenomatous defect, bronchiectatic disease, cavernal type of lung cancer,
bronchogenic cysts, and emphysemous bullas.
5. Pulmonary tuberculoma, clinical picture and differential diagnostics.
• The source of LT formation is infiltrative-pneumonic and focal forms of pulmonary TB.
cavernous pulmonary TB by means of filling the cavity with caseous masses.
• The lung tuberculoma has the distinctive original clinical and anatomical display of secondary
form of the pulmonary tuberculosis. It is characterized by the development of the dense caseous
focus (some time several focuses) in lungs, of rounded forms, sharply outlined from surrounding
tissue by fibrotic capsule.
• three clinical variants of tuberculoma course:
!1) progressing, described by occurrence of disintegration at some stage of illness, perifocal
inflammation around tuberculoma, bronchogenic dissemination in surrounding lung tissue.
!2) stable – absence of tuberculoma X-ray changes or rare aggravations without signs of
tuberculoma progressing;
!3) regressing tuberculoma is characterized by its slow reduction in size, with subsequent
formation of focus or group of foci, induration field or combination of these changes
• Clinical pattern. As tuberculoma itself is a parameter of high body resistance, patients with this
form of pulmonary tuberculosis frequently are revealed accidentally, at fluorography
examinations, preventive examinations, and in presence of other diseases. Practically, patients
have no complaints.
• At physical examination of a patient, there are no pathological signs in lungs. Crackles are heard
only at massive flare-up with extensive infiltrative changes in lung tissue around tuberculoma.
• Blood -without peculiarities. Sometimes moderate elevation of ESR and moderate leukocytosis
are observed at acute stages. MBT is not found in sputum at stable course of tuberculoma.
Discharge of bacilli exists in tuberculoma at presence of disintegration if there is connection with
drainage of bronchus. Tuberculin tests -positive reaction, often hyperergic.
6. Pulmonary hemoptysis and pulmonary hemorrhage. Diagnostics and approaches to
treatment.
The treatment of lung hemorrhages consists of:
1. patient is assigned to rest and be in half-sitting position;
2. reduction of blood pressure in bronchial artery or pulmonary artery;
3. increase coagulation property of blood.
Reduction of blood pressure in bronchial arteries could be achieved by:
1. intravenous injection of Sodium Nitroprusside;
2. intravenous injection of аrphonade (quick action ganglio blockers).
Systolic blood pressure should not be lower than 90 mm Hg.
Pressure in system of pulmonary artery could be reduced:
1. by applying venous tourniquet on extremities for not more than 40 min.
2. by intravenous injection of eophylline (theophylline).
For amplification of blood coagulation intravenous introduction:
1. 10% solution of sodium chloride or Calcium gluconate;
2. intravenous 1% solution of protamine sulfate;
3. intravenous fibrinolis inhibitor – 5% solution of aminocapronic acid.
At profuse bleedings there can be a necessity of partial replacement of the lost blood.
It is necessary to assign additional methods during lung hemorrhages for prevention of aspiration
pneumonia and worsening of the condition:
1. antibiotics of a wide spectrum;
2. anti-tuberculosis drugs.
Performing artificial pneumothorax or pneumoperitoneum help to stop hemorrhage as soon as
possible in tuberculous patients. Artificial pneumothorax is necessary to apply in patients, for whom
bleeding arises in fresh cavities, without expressed fibrosis. If a source of bleeding is fresh and
destructive processes located in the lower lobes, then it is recommended to impose
pneumoperitoneum.
Treatment with the above mentioned medical measures allow stopping hemorrhages in up 80-90%
of the patients. Surgical intervention is indicated during inefficiency of these methods, and life
threatening condition.
The operations on lung hemorrhages can be done during:
1. extreme cases – at moment of blood loss;
2. urgent need – after arrest of bleeding;
3. scheduled or planned – after stopping of hemorrhage, fulfilled special investigation and
full preoperational preparations.
Emergency surgical methods
To stop hemorrhage it is necessary to organize immediate surgical help, perform resection of a part
or the entire lung. Depending on the form, prevalence of tubercular process, and functional data
segmental resections, lobotomy or pulmonectomy can be performed. Blood transfusion is obligatory
during preparation of the patients for surgery in case of massive bleeding.

Occlusion of a bleeding vessel is the most effective method to stop hemoptysis.

During occlusion of bronchial artery, it is possible to catheterize immediately after bronchial
arteriography and refinement to topical diagnostics of bleeding. For this purpose through catheter
enter slices of Teflon velour, silicon balls, fibrin sponge, clots of own blood, and in a case of a very
wide vessel – a special metal spiral with a loop from Teflon strings. It is possible to use other
materials, which promote thrombosis and to stop bleeding from bronchial arteries.
7. Spontaneous pneumothorax: diagnosis, treatment.
The reason for spontaneous pneumothorax can be perforation of sub pleural localized focus,
cavernous, and emphysematous bullas.
The size of a gas cavity depends on presence of pleural adhesions, which considerably complicates
the ability of lungs for compression; therefore, limited closed spontaneous pneumothorax is formed.
If the pleural adhesions are not present, the formation of large gas cavity is possible with
subsequent squeeze of the lung. Thus, the quick stoppage of one lung function can result in the
stopping of respiratory function and then give rise to lung-heart insufficiency.
The first hours are most dangerous after spontaneous pneumothorax to the patient.
If the perforation is not closed, it causes open spontaneous pneumothorax.
At formation of pleural – pulmonic fissure, valvular (gated) pneumothorax is formed.
Limited closed spontaneous pneumothorax can proceed asymptomatically if the gaseous balbe is
small and hemodynamic disturbance is not observed.
The perforation is quickly closed, the gas is absorbed, and spontaneous pneumothorax disappears
without leaving any trace.

Clinical signs.
pain in the side of spontaneous pneumothorax, especially during cough and physical stress,
dyspnoea occurs.
Large and fast lung shrinking cause collaptoid state: weakness, pallor, cold sweat, frequent and
thread pulse.
On auscultation of the patient above the area of spontaneous pneumothorax, there is decrease in
breathing.
On X-ray, gas bubble is found in the pleural cavity.

Open and valvular spontaneous pneumothorax is complicated sometimes with exudative

pleurisy resulting in prolonged duration of illness and severe than in closed pneumothorax.

Closed limited pneumothorax without damage of heart-lung function is preserved without

intrapleural interventions. Gradually gas is absorbed, and the lung expands.
8. Laboratory diagnostics of tuberculosis (bacterioscopic, bacteriological, molecular genetic).
The laboratory MBT identification consists of the following methods:
1) sputum collection and processing;
2) microscopic identification of MBT in secretions or tissues;
3) culture techniques;
4) drug susceptibility testing;
5) serological testing;
The latest scientific research is directed to following c seroantigens and techniques:
– аntigen of 38 Kilodaltons;
– аntigen 5;
– аntigen A60;
– аntigen of 88 Kilodaltons;
– мultiantigen аnalysis
• Proteins connected with immune reaction IgG, IgA, IgM, СЗ, С4 – complement components.
• Proteins, reactants of a sharp phase of an inflammation: C-reactive protein, alpha1 – acidic
glycoprotein, alpha1 – antitrypsin.
• Transport proteins: albumin, haptoglobin, alpha2 – macroglobulin, ceruloplasmin.
• Proteins entering in the host, mainly, in process of nutrition: transferrin, ferritin, pre-
albumin.
6) performance of new molecular biological methods of MBT identification, including
polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP)
• The simplest and fastest method of revealing acid-fast bacilli (AFB) used for over 100 years:
sputum microscopy. AFB –mycobacterium that remain stained even after they washed in an acid
solution and could be detected under a microscope in a stained smear.
• Isolation of MBT from clinical samples by culture still is main method tuberculosis diagnosis.
▪ CXR
◆ classic triad: apical-posterior infiltrates, lung volume loss, cavitation
◆ atypical features: hilar/mediastinal lymphadenopathy, non-cavitary infiltrates
◆ signs of complications: endobronchial spread, pleural effusion, pneumothorax
◆ ghon complex: a parenchymal granuloma, indicating a previous tuberculosis infection,
and an involved hilar lymph node on the same side

9. Main approaches and methods of treatment of patients suffering from tuberculosis.

Treatment of Active Infection
• pulmonary TB: INH (isoniazid)+ rifampin+ pyrazinamide+ ethambutol x2mo (initiation
phase),
• then INH+ rifampin x 4 mo in fully susceptible TB (continuation phase), total 6 mo. Extend
continuation phase to 7 mo if >65, pregnant or risk of hepatotoxicity
• extra pulmonary TB: same regimen as pulmonary TB but increase to12mo in bone/joint,
CNS, and miliary/disseminated TB + corticosteroids for meningitis, pericarditis
• empiric treatment of suspected MDR(multi drug resistant) or XDR(extensively drug-
resistant) TB requires referral to a specialist
■ MDR=resistance to INH and rifampin ± others
■ XDR = resistance to INH + rifampin + fluoroquinolone + ≥1 of injectable, second-line
agents
• ■ suspect MDR TB if previous treatment, exposure to known MDR index case, or
immigration from a high-risk area
10. Infection control in tuberculosis facilities.
• In anti-tuberculosis establishments the personnel communicate with the tuberculous patients,
including those who are secreting bacteria. These contacts take place in out-patient reception of
the patients, at service in clinics and in the apartments, where the transmission of the infection is
possible through dust, contact, drops and alimentary ways.
• Incidence of tuberculosis among medical staff of anti-tuberculosis establishments is 8- 10 times
higher, than in all population.
• In every anti-tuberculosis establishment, there are rules with the purpose to minimize the danger
of infection by tuberculosis and to create the most favorable working conditions for the personnel.
These rules should be strictly observed.
Individual means of protection of respiratory organs
The general regulations. Individual means of respiratory organ protection (respirators, gauze
bandages) serve for medical workers as "last boundary of defense" against concomitant MBT
distribution.
• Respirator’s use is limited in places of high risk, namely:
1) in boxes of the tuberculous patients or MDR-TB;
2) at stimulation of sputum expectoration or other procedures causing cough; 3) at bronсhoscopy;
4) at section halls;
5) at spirometry;
6) during emergency surgery on the potentially infectious tuberculous patients.
• Surgical masks. Between a surgery mask and respirator there are important differences. Surgical
masks for example (made of cloth or of paper):
1. really provide prevention of distribution of microorganisms from their source (for example,
tuberculous patient) to other persons by retention of large particles separated near nose and
mouth;
2. do not provide protection of the user (for example, medical worker, patient, member of
family) from inhalation of the infectious agent in air droplets.

• Means of disinfection. Now there is a wide spectrum of disinfectants. However at application it is

necessary to check their activity to disinfect contaminated MBT material.

1. Chloride of lime – white powder containing 28,0-35,0 % of active chlorine.

2. Chloramin B and XB – powder of cream color, contents of active chlorine 27,0-28,0 %.
For preparation of 5 % chloramin disinfectant solutions 500 g. of chloramin powder dissolve in 10,0
liters of water.

Disinfection of objects of personal and public use

• Spittoons. Plates and dishes with remains of food. The remains of food. Wash basin, urinals,
lavatory pans, taps. Subjects of patient’s care: bedpans, urinals, tips for clysters.
Methods of disinfection.
1. Boiling in soda solution.
2. Immersing in a pan with a cover containing chloramin solution.
3. Autoclaving.
4. To cover with chloride of lime.
• Service rooms (wall, floor, doors, furniture) in wards, in procedure units, in places of common
usage.
Methods of disinfection.
1. Wiping with tatters moistened in the activated solutions of chloramin.
2. Washing with hot soap-soda solution.
3. Immersing in a vessel with a cover containing solution of chloramin.
4. To cover with chloride of lime.

• Linen (bed, from dining rooms, underwear, furniture cases, gauze masks, respirators,
handkerchiefs, personal linen and bed cloths).
Methods of disinfection.
1. Boiling in soda solution.
2. Ironing by a hot iron.
3. Disinfection in gas-chamber.

• Soft furniture. Fine objects of use, toy (metal, rubber, wooden, plastic). Books, notes, paper etc.
Methods of disinfection.
1. Immerse in disinfection solutions and disinfect according to regimes.
2. The objects of little value are burnt, and valuable ones are disinfected in gas chamber.
3. Cleaned by a brush moistened in one of disinfectant solutions.

In anti-tuberculosis hospitals at reception of the patients, and then regularly sanitary – educational
work with the patients should be carried out. With the purposes of protection of the personnel from
infection, special attention should be paid to the rules of behavior, obligatory for the patients.
When discharged, the patient must receive explanations about the rules of his behavior at his place
of living and in public places, warning him about the spread of tuberculosis infection to the
surrounding.
1. Differential diagnosis for pulmonary infiltration syndrome.
2. Differential diagnosis for chest pain.

Pulmonary causes
Gastrointestinal causes
3. Differential diagnostics in pulmonary edema.
4. Differential diagnosis in swallowing disturbances (dysphagia).

Description of dysphagia Possible associated findings and

conditions
Oropharyngeal • Difficulty initiating swallowing, which • Reduced cough reflex
dysphagia can lead to repeat swallow attempts • Drooling
• Predominantly experienced in the throat • Nasal regurgitation
or neck • Voice changes (nasal speech, wet
• May be associated with coughing or a voice)
choking sensation early in the • Recurrent pneumonia (aspiration
swallowing process. pneumonia)
• Malnutrition and/or anorexia
• Neurological symptoms (e.g.,
dysarthria)

Esophageal • Symptoms occur seconds after • Halitosis

dysphagia swallowing • Bolus impaction
• Predominantly experienced retrosternally
• May be associated with coughing late in
the swallowing process
Motility-related • Dysphagia predominantly with liquids • Esophageal hypermotility disorders:
dysphagia (or liquids and solid food) episodic central chest pain.
• May be aggravated by cold foods • Esophageal hypomotility disorders
• Intermittent symptoms or progression of • Regurgitation of undigested food
symptoms over a long duration (months (achalasia)
to years) • Systemic features of underlying
disease (e.g., scleroderma)

Structural • Dysphagia predominantly with solid food • Depends on the underlying cause;
dysphagia (or initially to solids that progressed to examples include:
liquids)
• May be aggravated by large food boli - Symptoms of GERD in reflux
and dense food esophagitis
- Red flags for dysphagia in
esophageal cancer
- Fever in infectious causes (e.g., deep
neck infection, infectious
esophagitis)

CAUSES

Motility-related dysphagia Structural dysphagia

Oropharyngeal • Mucosal disorders
dysphagia • Neurological disorders
o Stroke o Local infection (e.g., epiglottitis, acute
tonsillitis)
o Neurodegenerative diseases
 o Corrosive injury (e.g., thermal or
o Parkinson disease chemical burn)
o Brain tumor o Zenker diverticulum
o Mucositis (e.g., caused by radiation
o Traumatic brain injury therapy or chemotherapy)
o Cerebral palsy o Oropharyngeal cancer
o Head and neck dissection
o Guillain-Barré syndrome
o Other (e.g., iatrogenic nerve • Extramural disorders

damage, post-polio syndrome) o Deep neck infection

• Muscular disorders o Cricopharyngeal muscle spasm
o Osteophytes
o Myasthenia gravis o Thyroglossal duct cyst
o Progressive muscular dystrophies
o Paraneoplastic syndrome
o Sarcoidosis
o Mixed connective tissue
disorders (e.g., systemic
sclerosis, CREST
syndrome, Sjogren syndrome)
o Inflammatory
myopathies (e.g., polymyositis, de
rmatomyositis, inclusion body
myositis)

Esophageal • Intraluminal disorders: impacted foreign

dysphagia • Achalasia
object or food bolus
• GERD • Mucosal disorders (intrinsic narrowing)
• Esophageal hypermotility disorders o Esophagitis (e.g., infectious esophagitis,
• Mixed connective tissue diseases eosinophilic esophagitis, corrosive
esophagitis, or secondary to GERD,
chemotherapy, or radiotherapy)
o Esophageal webs (e.g., in Plummer-Vinson
syndrome)
o Esophageal rings (e.g., Schatzki ring)
o Esophageal cancer
o Esophageal diverticulum
o Autoimmune conditions (e.g., CREST
syndrome, Crohn disease, Behcet disease,
pemphigus syndromes)
• Extrinsic compression

o Thyromegaly, substernal thyroid

o Hilar lymphadenopathy,
o Neoplasia (e.g., mediastinal tumor, thyroid
tumor)
o Cardiac dysphagia: a group of cardiovascular
anomalies that cause dysphagia due to
compression of the esophagus

§ Includes vascular ring anomalies (e.g.,

double aortic arch), dysphagia lusoria
(abnormal right subvlavian artery),
severe atherosclerosis, and aneurysms
§ Dysphagia megalatriensis: compression
of the esophagus by a giant left atrium,
most commonly caused by mitral
stenosis due to rheumatic heart disease
and a left atrial myxoma

o Hiatal hernia
5. Differential diagnosis in gastrointestinal bleeding.

MAIN CAUSES

UPPER GI BLEEDING LOWER GI BLEEDING

Erosive or • Peptic ulcer disease (∼ 30% of cases) • Diverticulosis (∼ 30% of cases)
inflammatory • Esophagitis • Inflammatory bowel
• Erosive gastritis and/or duodenitis disease (IBD), i.e., ulcerative
colitis and Crohn disease
• Invasive or inflammatory
diarrhea (bacterial gastroenteritis,
due to e.g., Shigella, EHEC)

Vascular • Esophageal varices or gastric varices • Hemorrhoids

• Gastric antral vascular ectasia: a dilation • Ischemia (e.g., ischemic
of small blood vessels in the antrum of colitis, mesenteric ischemia)
the stomach • Arteriovenous malformation
• Dieulafoy lesion: minor mucosal trauma to an • Rectal varices
abnormal submucosal artery (usually located in • Angiodysplasia
the proximal stomach) leads to major
bleeding (acute upper GI bleeding)
o It can be hard to visualize a Dieulafoy
lesion on endoscopy because it is missing
an ulcer base.
o Treatment includes
endoscopic hemostasis (injection therapy,
hemoclips, etc.) or excision of the
susceptible mucosa
• Angiodysplasia

Tumors • Esophageal cancer and/or gastric carcinoma • Colorectal cancer and/or anal
cancer
• Colonic polyps
Traumatic • Hiatal hernias • Lower abdominal trauma
or iatrogenic • Mallory-Weiss syndrome • Anorectal trauma (e.g., anorectal
• Boerhaave syndrome avulsion, impalement injuries)
• Following open or endoscopic surgery (e.g., • Following open or
anastomotic bleeding following a gastric endoscopic surgery (e.g.,
bypass) anastomotic bleeding following a
gastric bypass)

Other causes • Portal hypertensive gastropathy • Anal fissures

• Coagulopathies
FEATURES OF OVERT GI BLEEDING

DESCRIPTION CAUSES
Hematemesis Vomiting blood, which may be red Most commonly due to bleeding in
or coffee-ground in appearance the upper GI
tract (e.g., esophagus, stomach)

Melena Black, tarry stool with a strong Most commonly due to bleeding in
offensive odor the upper GI tract

Can also occur in bleeding from

the small bowel or the right colon

Hematoschezia The passage of bright red (fresh) Most commonly due to bleeding in
blood through the anus (with or the lower GI tract (e.g., in
without stool) the distal colon)

Colonic bleeding: maroon, jelly- Rapid passage of blood from the

like traces of blood in stools upper GI tract may also result
in hematochezia.
Rectal bleeding: streaks of fresh
blood on stools
6. Differential diagnosis in pulmonary and gastric bleeding.
Pulmonary bleeding

Disease
Pulmonary
• Infection (most common cause)
o Acute viral or bacterial
o Tuberculosis
o Aspergillosis
• Neoplasm, e.g., bronchogenic carcinoma (second most common cause)
• Bronchiectasis
• Cystic fibrosis
• Lupus pneumonitis due to systemic lupus erythematosus

Cardiac
• Congestive heart failure
• Mitral stenosis
• Pulmonary hypertension
Vascular
• Pulmonary embolism
• Vasculitis
o Granulomatosis with polyangiitis
o Goodpasture syndrome
o Behcet disease
• Vascular malformation (e.g., pulmonary artery aneurysm, arteriovenous malformations)
• Pulmonary vascular fistula
• Tracheoinnominate artery fistula
• Pulmonary artery rupture
• Hereditary hemorrhagic telangiectasia
Hematologic
• Coagulopathy
• Anticoagulant use
• Thrombocytopenia
Trauma
• Lung contusion
• Airway trauma
• Foreign body
Iatrogenic
• Injury to structures during:
o Lung biopsy
 o Right heart catheterization
o Pulmonary artery catheterization
o Airway stenting
Other
• Thoracic endometriosis (catamenial hemoptysis)
• Idiopathic pulmonary hemosiderosis
• Cryptogenic: no identified cause on CT or bronchoscopy (50% of cases in high-income
countries)
7. Differential diagnosis in jaundices.
PREHEPATIC CAUSES

MECHANISM CAUSES
Hemolysis
• G6PD deficiency
• RBC structural defects: e.g., sickle cell
anemia, hereditary spherocytosis
• Autoimmune hemolytic anemia
• Hemolytic transfusion reaction
Ineffective erythropoiesis
• Thalassemia
• Pernicious anemia
• Sideroblastic anemia
Increased bilirubin production
• Massive blood tranfusions
• Superficial and internal hematoma resorption
Medication side effect (e.g., impaired hepatic uptake
of bilirubin) • Rifampin
• Probenecid
• Ribavirin
• Protease inhibitors: e.g., atazanavir, indinavir

INTRAHEPATIC JAUNDICE

MECHANISM TYPE OF CONDITIONS

HYPERBILIRUBINEMA
Impaired bilirubin conj Unconjugated
• Gilbert syndrome
ugation hyperbilirubinemia
• Crigler-Najjar syndrome

Hepatocellular injury Mixed unconjugated

and conjugated • Viral hepatitis: e.g., hepatitis A–
hyperbilirubinemia E, EBV, CMV, yellow fever
• Liver disease e.g., alcoholic hepatitis, nonalcoholic
steatohepatitis, cirrhosis, congestive
hepatopathy, Wilson disease, autoimmune hepatitis
• Drug toxicity:
e.g., acetaminophen, estrogens, macrolides, arsenic

Impaired hepatic Conjugated

excretion of bilirubin hyperbilirubinemia • Dubin-Johnson syndrome
• Rotor syndrome
Intrahepatic cholestasis
• Intrahepatic biliary tract disorders: e.g., primary
biliary cholangitis, primary sclerosing
cholangitis , vanishing bile duct syndrome,
postoperative cholestasis
• Infiltrative disease:
e.g., tuberculosis, sarcoidosis, amyloidosis, lympho
ma
• Progressive familial intrahepatic cholestasis
• Intrahepatic cholestasis of pregnancy
• Total parenteral nutrition
• Nonhepatobiliary sepsis
• Infectious diseases: e.g., malaria, icteric
leptospirosis

POST HEPATIC JAUNDICE

MECHANISM CONDITIONS
Malignancy • Cholangiocarcinoma
• Pancreatic cancer
• Liver cancer
• Gallbladder cancer
• Ampullary cancer
• Liver metastases

Gallbladder and gallstone disease • Cholelithiasis

• Choledocholithiasis
• Cholangitis
• Postoperative bile leaks or biliary strictures
• Mirizzi syndrome

Inflammatory processes • Primary sclerosing cholangitis

• Pancreatitis (acute and chronic)

Infection • AIDS cholangiopathy

• Liver flukes
• Ascariasis
8. Differential diagnostics in ascites.
• The etiology can be determined using the serum-ascites albumin gradient (SAAG) based on Starling's law.
• SAAG = (albumin levels in serum) - (albumin levels in ascitic fluid)
ETIOLOGY PATHOPHYSIOLOGY
High SAAG ascites
• Portal hypertension • All result in ↑ pressure in portal
≥ 1.1 g/dL (obsolete
term: transudate) o Presinusoidal vein → ↑ hydrostatic pressure in
§ Splenic or portal vein thrombosis the hepatic vessels → pushing
§ Schistosomiasis of fluid out from
o Sinusoidal the intravascular space to
§ Hepatic (common) the peritoneal cavity
§ Cirrhosis
§ Alcohol-related liver disease
§ Liver metastases
o Postsinusoidal
§ Cardiac
§ Right heart failure
§ Constrictive pericarditis
§ Budd-Chiari syndrome

• Hypoalbuminemia
o Nephrotic syndrome
o Severe malnutrition
o Protein-losing enteropathy

Low SAAG ascites

< 1.1 g/dL (obsolete • Malignancy • All result in ↓
term: exudate) intravascular osmotic
gradient → secondary influx of
water from
the intravascular space to
the peritoneal cavity

• Infections (e.g., tuberculosis)

• Pancreatitis
9. Differential diagnostics in renal colic
10. Differential diagnosis for joint disorders.
 11. Differential diagnostics in broncho-obstructive syndrome.

Bronchiectasis:

• Chronic productive cough (lasting months to years) with copious mucopurulent sputum ;
• Auscultation
o Crackles and rhonchi
o Wheezing (due to obstruction from secretions, airway collapsibility, or a concomitant condition)
o Bronchophony
• Rhinosinusitis
• Dyspnea
• Hemoptysis: usually mild or self-limiting, but severe hemorrhage that requires embolization may occur
• Nonspecific symptoms (i.e., fatigue, weight loss, pallor due to anemia)
• Clubbing of nails (uncommon)
12. Differential diagnostics in sudden suffocation.
13. Differential diagnosis for fever of unknown origin in the clinic of internal diseases.

Category Common causes Less common causes

Infection
(11–55%) • Tuberculosis • Infrequent
• Brucellosis o Typhoid fever
• Q fever o Toxoplasmosis
• Subacute bacterial o Cat scratch disease
endocarditis o Extrapulmonary tuberculosis
• Complicated UTI o Viral infection (e.g., EBV, CMV, HIV)
• Abscess • Rare
o Leptospirosis
o Periapical dental abscess
o Chronic sinusitis
o Mastoiditis
o Vertebral osteomyelitis
o Tick-borne diseases
o Chronic prostatitis
o Recurrent cholangitis
o Whipple disease
o Parasitic infections (e.g., malaria, visceral
leishmaniasis)
o Fungal infections
(e.g., histoplasmosis, coccidioidomycosis)
Inflammatory or rheumatic
conditions • Adult-onset Still disease • Infrequent
(12–34%) • Temporal arteritis o SLE
o Systemic vasculitis: e.g, polyarteritis
nodosa
• Rare
o Takayasu arteritis
o Kikuchi disease
o Behcet disease
o Gout or pseudogout
o Felty syndrome
 Malignancy
(7–35%) • Hodgkin lymphoma • Castleman disease
• Non-Hodgkin lymphoma • Atrial myxoma
• Leukemia • Colonic adenocarcinoma
• Renal cell carcinoma • Multiple myeloma
• Melanoma
Miscellaneous
(2–20%) • Drug fever • Infrequent
• Cirrhosis o Subacute thyroiditis
• Postmyocardial infarction o Inflammatory bowel disease
syndrome o Sarcoidosis
• Stroke • Rare
o Pulmonary embolism
o Familial periodic fever syndromes:
e.g., familial Mediterranean fever
o Cyclic neutropenia
o Factitious fever

Healthcare-associated FUO
In addition to the common causes of fever, consider the following in this group of patients:
• Drug fever
• Intravascular catheter-related infection
• Venous thromboembolism (DVT, pulmonary embolism)
• Clostridioides difficile colitis
• Inflammatory response to major surgery
• Occult abscess
• Transfusion reactions
• Sinusitis
• Candidemia (if critically ill)

Immunodeficiency-associated FUO
In addition to the common causes of fever, consider the following in this group of patients:
• Opportunistic infections (e.g., candidiasis, aspergillosis, CMV infection)
• Drug fever (more common in neutropenic patients)
• Malignancy
• In people living with HIV, also consider HIV-associated conditions (e.g., Pneumocystis pneumonia, MAC
infection, Kaposi sarcoma) and immune reconstitution inflammatory syndrome.
12. Differential diagnosis in the syndrome of elevated ESR.

Conditions that may be associated with a highly elevated ESR (>100 mm/hr) include the following:
• Hypersensitivity vasculitis
• Giant cell arteritis
• Waldenström macroglobulinemia
• Polymyalgia rheumatica
• Metastatic cancer
• Chronic infection
• Hyperfibrogenemia
1. Pathogenesis and clinical picture of acute radiation sickness due to external radiation
exposure.
Pathogenesiss
Radiation usually affects the dividing cells of the body. These include sperms, blood cells and the
cells lining the digestive system. Children and elderly are more susceptible to radiation injury. At
lower doses, the bone marrow is usually affected. At higher doses, the digestive system is also
involved. Very high dose exposure could be fatal with the patient, besides suffering from the above
features, also suffers from very low blood pressure, seizures, confusion and death
The severity of signs and symptoms of radiation sickness depends on how much radiation patient
have absorbed. How much patient absorb depends on the strength of the radiated energy and the
distance between patient and the source of radiation. • Signs and symptoms also are affected by
the type of exposure — such as total or partial body and whether contamination is internal or
external — and how sensitive to radiation the affected tissue is. • For instance, the gastrointestinal
system and bone marrow are highly sensitive to radiation.
Initial signs and symptoms
• The initial signs and symptoms of treatable radiation sickness are usually nausea and vomiting.
The amount of time between exposure and when these symptoms develop is an indicator of how
much radiation a person has absorbed. • After the first round of signs and symptoms, a person
with radiation sickness may have a brief period with no apparent illness, followed by the onset of
new, more serious symptoms

Signs and symptoms

• Classically acute radiation syndrome is divided into three main presentations: hematopoietic,
gastrointestinal and neurological/vas cular. These symptoms may or may not be preceded by a
prodrome • These presentations presume whole-body exposure and many of them are markers
which are not valid if the entire body has not been exposed. Each syndrome requires that the
tissue showing the syndrome itself be exposed. The hematopoietic syndrome requires exposure
of the areas of bone marrow actively forming blood elements (i.e., the pelvis and sternum in
adults). The neurovascular symptoms require exposure of the brain. The gastrointestinal
syndrome is not seen if the stomach and intestines are not exposed to radiation.
Hematopoietic
• This syndrome is marked by a drop in the number of blood cells, called aplastic anemia. This
may result in infections due to low white blood cells, bleeding due to low platelets, and anemia
due to low red blood cells. [1] These changes can be detected by blood tests after receiving a
wholebody acute dose as low as 0.25 Gy, though they might never be felt by the patient if the
dose is below 1 Gy. Conventional trauma and burns resulting from a bomb blast are complicated
by the poor wound healing caused by hematopoietic syndrome, increasing mortality.
Gastrointestinal
• This syndrome often follows absorbed doses of 6–30 (10-20) Gy (600– 3000 rad).[1] Nausea,
vomiting, loss of appetite, and abdominal pain are usually seen within two hours. Vomiting in
this time-frame is a marker for whole body exposures that are in the fatal range above 4 Gy.
Without exotic treatment such as bone marrow transplant, death with this dose is common.[1]
The death is generally more due to infection than gastrointestinal dysfunction.
Neurovascular
• This syndrome typically occurs at absorbed doses greater than 30 Gy (3000 rad), though it may
occur at 10 Gy (1000 rad). It presents with neurological symptoms such as dizziness, headache,
or decreased level of consciousness, occurring within minutes to a few hours, and with an
absence of vomiting. It is invariably fatal.
The four stages of ARS are:
• Prodromal stage (N-V-D stage)– The classic symptoms for this stage are nausea, vomiting and
diarrhea that occur from minutes to days following exposure. The symptoms may last
(episodically) for minutes up to several days.
• Latent stage – In this stage the patient looks and feels generally healthy for a few hours or even
up to a few weeks.
• Manifest illness stage – In this stage the symptoms depend on the specific syndrome (see
Appendix) and last from hours up to several months.
• Recovery or death – Most patients who do not recover will die within several months of
exposure. The recovery process lasts from several weeks up to two years.

2. Features of radiation sickness caused by the ingress of radioactive substances into the
body.
3. General principles of treatment of acute radiation sickness

The treatment goals for radiation sickness are to prevent further radioactive contamination; treat
life-threatening injuries, such as from burns and trauma; reduce symptoms; and manage pain.
• Decontamination
Decontamination is the removal of as much external radioactive particles as possible. Removing
clothing and shoes eliminates about 90 percent of external contamination. Gently washing with
water and soap removes additional radiation particles from the skin. • Decontamination prevents
further distribution of radioactive materials and lowers the risk of internal contamination from
inhalation, ingestion or open wounds.
Treatment for damaged bone marrow
• A protein called granulocyte colony-stimulating factor, which promotes the growth of white
blood cells, may counter the effect of radiation sickness on bone marrow. Treatment with this
proteinbased medication, which includes filgrastim (Neupogen) and pegfilgrastim (Neulasta),
may increase white blood cell production and help prevent subsequent infections. • If you have
severe damage to bone marrow, you may also receive transfusions of red blood cells or blood
platelets.
Treatment for internal contamination
Some treatments may reduce damage to internal organs caused by radioactive particles. Medical
personnel would use these treatments only if you've been exposed to a specific type of radiation.
These treatments include the following:
• Potassium iodide. This is a nonradioactive form of iodine. Because iodine is essential for
proper thyroid function, the thyroid becomes a "destination" for iodine in the body. If you have
internal contamination with radioactive iodine (radioiodine), your thyroid will absorb radioiodine
just as it would other forms of iodine. Treatment with potassium iodide may fill "vacancies" in
the thyroid and prevent absorption of radioiodine. The radioiodine is eventually cleared from the
body in urine. Potassium iodide isn't a cure-all and is most effective if taken within a day of
exposure.
• Prussian blue. This type of dye binds to particles of radioactive elements known as cesium and
thallium. The radioactive particles are then excreted in feces. This treatment speeds up the
elimination of the radioactive particles and reduces the amount of radiation cells may absorb.
• Diethylenetriamine pentaacetic acid (DTPA). This substance binds to metals. DTPA binds
to particles of the radioactive elements plutonium, americium and curium. The radioactive
particles pass out of the body in urine, thereby reducing the amount of radiation absorbed.
Supportive treatment
• If you have radiation sickness, you may receive additional medications or interventions to treat:
• Bacterial infections
• Headache
• Fever
• Diarrhea
• Nausea and vomiting
• Dehydration
• Burns
End-of-life care
• A person who has absorbed large doses of radiation (6 Gy or greater) has little chance of
recovery. Depending on the severity of illness, death can occur within two days or two weeks.
People with a lethal radiation dose will receive medications to control pain, nausea, vomiting and
diarrhea. They may also benefit from psychological or pastoral care.
4. Chronic radiation sickness: symptomatology, diagnosis, treatment.
CRS is a general disease of the body that develops as a result of prolonged exposure to ionizing
radiation in relatively small doses, but exceeding the dose limit established for persons who are
constantly in contact with sources of ionizing radiation.
Etiology : safety violations when working with x-ray machines, in radiological laboratories,
enterprises for the enrichment of natural radioactive ores, flaw detectors. start of irradiation.
Pathogenesis is based on tissue damage, the death of poorly differentiated mitotically active cells
(i.e., the death of not a cell, but its offspring)
Clinic
Variants of the course: - CRS, caused mainly by external gamma radiation with a uniform
distribution in the body - CRS, due to selective. or local irradiation (mainly respiratory syst-
bronchitis, radiation pneumonitis, pneumofibrosis, pneumosclerosis, bronchogenic lung cancer)
Flow periods
1) the period of formation is a polysyndromic course, depending on the severity. from 1 to 6
months, the severity is determined by the following. Syndromes: - bone marrow - s-m disturbed
neurovascular regulation - asthenic s-m-s-m of organic lesions of the nervous system
2) the recovery period with a mild form - ending with recovery within 1-2 months
3) the period of long-term consequences and outcomes. character for cf. and severity of degrees
According to the severity of the clinic:
1 step stage complaints of headache, fatigue, increased irritability, sleep disturbance, ↓appetite,
dyspepsia, ↓body weight, ↓sexual desire, vegetative-vascular disorders (acrocyanosis,
hyperhidrosis, hand and eyelid tremor, diffuse dermographism), pulse lability, skin changes
(dryness, thinning, peeling, pigmentation, hair loss, cracks)
In the blood - leukopenia, rel. Lymphocytosis, hyperpigmentation of nuclei, toxic granularity of
neutrophils . at different times, not stopped by drugs. All symptoms are brighter, disrupted the
menstrual cycle, thermoregulation, bleeding of the mucous membranes. Dystrophic changes in
the myocardium. ↓albumin content in the blood) Erythrocytes↓up to 3*10 12 /l, anisocytosis,
poikilocytosis, platelets↓up to 100*10 9 /l, leukocyte↓up to 2., bone marrow suppression,
perversion of poetry. 3 step.also only stronger, bleeding of mucous membranes and subcutaneous
hemorrhage, hair loss. muscle tone and static, arising. Opto-vestibular symptoms and nystagmus.
CCC dystrophic changes in the myocardium and vascular structures.
+In the blood, a hypoplastic state of the bone marrow, a perversion of erythropoiesis according
to the megaloblastic type + associated infections. complications (pneumonia, sepsis).

Diagnosis of chronic radiation sickness

1. Professional history
2. Act of radiation-hygienic examination
3. Calculation of the total exposure dose for the entire period of work with sources of
ionizing radiation
4. Evaluation of the severity of clinical and hematological signs

Treatment of mild chronic radiation sickness

  Active motor mode;
 Vitamin therapy, herbal adaptogens;
 sedatives;
 Physiotherapy (sequentially sedative and tonic procedures [hydrotherapy]);
 Spa treatment.

Treatment of moderate and severe chronic radiation sickness

 Hospitalization (bed rest options);

 High-calorie, fortified mechanically and chemically sparing diet;
 Stimulation of hematopoiesis (B 12 , pentoxyl, sodium nucleinate);
 Antihemorrhagic therapy (ascorbic acid, dicynone, calcium preparations, infusions of
blood products);
 Anabolic therapy (retabolil, potassium orotate);
 Antibacterial therapy (including antifungal);
 Symptomatic therapy;
 Physiotherapy and therapeutic exercises.

5. Combined radiation injuries: structure, diagnostics.

Combined radiation injury (CRI) is a type of injury that occurs when the body is exposed to
ionizing radiation and damaging factors of non-radiation etiology simultaneously or sequentially,
leading to the failure of the victim, disruption of his ability to work and combat ability, or the
appearance of pronounced changes in clinical and laboratory parameters. CRPs are characterized
by the mutual influence on the body of all factors involved in the formation of the general
pathological process and influencing its course and outcome, and differ in their course and
outcomes from isolated lesions by the same factors.

Depending on the number and combination of etiological factors, CRP are divided into:

 two-factor (radiation-mechanical, radiation-thermal, radiation-chemical, radiation-

biological);
 three-factor (radiation-mechano-thermal, radiation-mechano-chemical, radiation-
mechano-biological, radiation-thermo-chemical, radiation-thermo-biological, radiation-
chemical-biological);
 four-factor (radiation-mechano-thermo-chemical, radiation-mechano-thermo-biological,
radiation-mechano-chemical-myco-biological, radiation-thermo-chemical-biological);
 five-factor (radiation-mechano-thermo-chemical-biological).

ICR can be the result of a nuclear explosion, be the result of man-made disasters and terrorist
attacks on nuclear power facilities. In the case of the use, along with nuclear, biological and (or)
chemical weapons, radiation-biological and radiation-chemical CRPs or their combinations may
occur.

The most typical are CRPs that occur during the simultaneous action of the damaging factors of
a nuclear explosion, as a result of which combinations of acute radiation injuries with burns and
(or) mechanical injuries can occur. When medium-caliber nuclear weapons (20-50 kt) are used,
up to 60-70% of all sanitary losses fall to the share of the PKK. When nuclear weapons of small
and ultra-small calibers are used, "pure" y-neutron damage predominantly occurs. However, the
remaining part of the irradiated in the ranks may subsequently (after hours and days) be hit by
other types of weapons. This can also happen during combat operations on the trail of a
radioactive cloud, where conditions are also created for a combination of prolonged exposure
with gunshot wounds and burns from fires or fire mixtures (napalm, pyrogels, etc.). Besides,

In other words, the occurrence of CRP is possible not only as a result of the simultaneous action
of the damaging factors of a nuclear explosion, but also in cases where the action of ionizing
radiation precedes non-radiation effects or non-radiation injuries occur before radiation
ones. The “irradiation + injury” variant is characterized by a more severe course compared to
simultaneous lesions or the “injury + exposure” sequence. It should be remembered that in the
case of non-simultaneous exposure to damaging factors, only those lesions will be combined, in
which the time between the action of radiation and non-radiation damaging factors does not
exceed the duration of the course of the first lesion, otherwise these will be successive lesions
independent of each other.

The most characteristic feature of CRP is the presence of signs of two or more pathologies in the
victim. Since early (symptoms of the primary reaction to radiation) or late (signs of the outbreak
of ARS) clinical manifestations of radiation pathology are combined in the same affected person
with local and general symptoms of burns, wounds, fractures, etc., a peculiar motley clinical
picture of radiation and traumatic or burn symptoms (syndromes).

The second characteristic feature of CRP is the predominance of one, the most severe and most
pronounced at a particular moment, the pathological process caused by the action of one of the
etiological factors of CRP, the so-called "leading component". The leading component in the
clinical sense determines the greatest danger to the life and health of the victims, and in the
organizational sense it requires the most urgent assistance at this particular moment. As the
pathological process develops, the type and value of the leading component may change.

Finally, the third characteristic feature of CRP is the mutual influence (mutual aggravation) of its
non-radiation and radiation components, which manifests itself in the form of a more severe
course of the pathological process than is characteristic of each component separately. As a
result, the lethality rate for CRP is significantly higher than for each of its constituent injuries,
and exceeds their combined effect.

It should be noted that even an isolated effect of one of the CRP components, which caused
acute radiation sickness, extensive or deep burns, severe mechanical injury, often leads to
death. This is due to the lack of evolutionarily developed mechanisms that can lead to recovery
from severe burns or mechanical damage, as a result of which the developing compensatory-
adaptive processes are characterized by instability and deliberate inefficiency. The combination
of several damaging factors leads to the emergence of a qualitatively new condition,
characterized not just by the summation of damage, but by the development of a syndrome of
mutual burdening.

The syndrome of mutual burdening is an increase (or aggravation) of the pathological process
when exposed to two or more etiological factors of CRP or a complex of symptoms indicating a
more severe course of each component of CRP than would be expected with an isolated course
of the same lesions. The reason for its development is that the adaptation processes in burn and
traumatic disease require a high functional activity of organs and systems that are largely
affected by radiation. On the other hand, the recovery of the body from radiation injury is
significantly hampered due to additional infection, toxemia, and other manifestations of a
traumatic or burn disease.

The main pathogenetic mechanism for the development of the syndrome of mutual burdening is
the limitation or loss of the body's ability to resist infection, as well as various toxic substrates of
histogenic and bacterial origin due to radiation suppression of immunity. An important role in
the pathogenesis of this syndrome is also played by generalized metabolic disorders, leading to a
disruption in the energy supply of cells and insufficiency of a number of organs and systems
(adrenal, thyroid, renal, hepatic).

It should be remembered that the syndrome of mutual burdening develops only when the
components of the CRP are combined at least of moderate severity. The sequence of various
damaging effects is also essential, if they did not occur simultaneously. So, if non-radiation
damage occurred during the height of ARS, the syndrome of mutual burdening is characterized
by maximum severity. When a mechanical injury or burn is applied during the recovery period
from ARS, in most cases, the syndrome of mutual aggravation does not occur. If a mild
mechanical injury precedes radiation injury, a milder course of ARS is often noted. This
phenomenon is explained by the fact that a previously inflicted mild injury causes the activation
of non-specific adaptive mechanisms and, as a result,

In the case of the development of the syndrome of mutual burdening, the clinical course of each
of the components of the CRP is more severe. Compared to “pure” radiation injuries, the clinical
course of CRP is distinguished by the absence of a latent period (it is “filled” with the clinical
picture of non-radiation components), the peak period begins earlier and is more difficult, in case
of recovery, the recovery period lasts longer. The radiation dose at which a favorable outcome
can be expected is reduced by 1.5–2 times. On the other hand, traumatic and burn diseases in
CRP are characterized by a more severe clinical course, an increase in wound necrosis zones, a
slowdown in reparative processes, the regular development of wound infection and its frequent
generalization.
  more frequent occurrence and more severe course of burn and (or) traumatic shock,
complications of the post-shock period;
 earlier development and more severe course of the main syndromes of the peak period of
ARS - pancytopenic, infectious, hemorrhagic;
 an increase in the frequency of infectious complications, an increased tendency to
generalize infection, the development of sepsis;
 slow down the process of regeneration of damaged organs and tissues.

Despite the diversity of the clinical picture of CRP, due to the presence of manifestations of
several pathological processes at once, in it, as a rule, at any given moment it is possible to single
out the leading component that mainly determines the clinical picture of the lesion and the
severity of the victim's condition. Over time, the leading component changes and, as a result, the
manifestations of the clinical picture of CRP change. However, despite the fact that its external
manifestations are dynamically changing, this process from the beginning to the end develops
according to a single mechanism, which makes it possible to distinguish four periods in the
clinical picture of CRP.

1. The acute period, or the period of primary reactions to radiation and non-radiation injuries,
develops in the first hours and days after exposure to the etiological factors of CRP. This period
is mainly represented by clinical manifestations of non-radiation components of CRP: the
victims develop traumatic or burn shock with severe pain, massive blood loss, acute respiratory
failure, focal and cerebral neurological disorders. Signs of a primary reaction to radiation
(nausea, vomiting, etc.) are usually masked by more pronounced symptoms of non-radiation
components. More typical for non-radiation than for radiation injuries, and early hematological
changes: neutrophilic leukocytosis, anemia (with massive blood loss), hemoconcentration (with
extensive burns or prolonged compression syndrome). An important diagnostic sign of CRP is
the absolute lymphopenia that occurs against the background of leukocytosis, while with “clean”
burns and injuries, only relative lymphopenia is observed.

2. Dominance period of non-ray components corresponds to the early post-shock period

of traumatic disease or the period of acute burn toxemia of burn disease. However, due to
the development of the syndrome of mutual burdening, the victims develop more often
and more severely the complications characteristic of these periods (adult respiratory
distress syndrome, fat embolism, acute renal failure, disseminated intravascular
coagulation syndrome) and more pronounced posthemorrhagic anemia. In the case of a
sufficient duration of the latent period of ARS (with ARS of mild or moderate severity)
and a non-severe course of non-radiation injuries or burns during the second period of
CRP, even complete healing of wounds is possible. At the same time, by the end of this
period, the victims usually develop hematological changes characteristic of radiation
injuries: leukocytosis is replaced by leukopenia, and lymphopenia increases. It is during
this period that the most serious pathogenetic mechanisms of the syndrome of mutual
burdening are formed.
3. Dominance period of the ray component characterized by a predominance of
symptoms typical of the peak period of ARS. During this period, the syndrome of mutual
burdening is maximally manifested: both the signs of radiation pancytopenic syndrome,
infectious complications and bleeding, and the severity of non-radiation components of
CRP are aggravated. Against the background of a slowdown in wound regeneration, a
wound infection develops, the likelihood of toxic-septic complications and secondary
bleeding increases, there is an increased vulnerability of tissues during operations and
manipulations, demarcation of necrotic areas of burned skin is suppressed, and multiple
organ failure progresses. Accumulating already in the second period of CRP, in the
period of predominance of the radiation component, these changes significantly increase
the risk of death.
 4. The recovery period is characterized by a gradual activation of regenerative processes,
restoration of immunity, the appearance of positive dynamics in the healing of wounds,
fractures, and burns. At the same time, many consequences of non-radiation injuries
(trophic ulcers, osteomyelitis, false joints, contractures, cicatricial deformities, etc.) can
persist for a long time, since they occur in conditions of functionally defective hemo- and
immunopoiesis, which in turn adversely affects on the effectiveness of the treatment of
victims and increases the duration of their disability.

Diagnosis of CRP consists in establishing the nature and localization, assessing the severity of
mechanical and burn injuries, identifying and establishing the severity of radiation exposure. In
this case, data from the anamnesis, an objective examination and laboratory tests are used.

In the acute period, the main problem in the diagnosis of CRP is the indication and determination
of the dose parameters of the radiation component. Indication of radiation injury is carried out on
the basis of anamnesis data (the presence of the victim in the zone of action of the damaging
factors of a nuclear explosion or radiation catastrophe), physical and biological dosimetry data,
in particular, the time of onset and severity of symptoms of the primary reaction, especially
vomiting. Indicative data on the frequency and timing of the occurrence of clinical
manifestations of an emetic reaction in the case of CRP are presented in Table. 74. The diagnosis
of CRP is specified by hematological indicators of exposure (lymphopenia, leukopenia), if
possible, karyological and cytological studies should be carried out.

Table 74

Expected frequency and characteristics of radiation-induced emetic reaction in combined

radiation injuries (according to Britun A. I. et al., 1992)

Irradiation Characterization of the emetic reaction

doses
during
CRP, Gy
0.8-1.2 Single vomiting in 10% of those affected. Occurs within
the first day
1.2-1.7 Single or repeated vomiting in 25% of those
affected. Occurs in 12-24 hours
1.7-2.2 Repeated vomiting in 50% of those affected. Occurs after
6-12 hours
2.2-3.3 Frequent repeated vomiting in 70-90% of those
affected. Occurs after 4-6 hours
3.3-4.5 Indomitable vomiting in 100% of those affected. Occurs
after 2-3 hours
Over 4.5 Indomitable vomiting in 100% of the injured. Occurs after
0.5-1 h. Hemodynamic disorders (collapse) may occur

In addition, an important sign of CRP is the discrepancy between the clinical symptoms and the
general severity of the condition and the nature and severity of non-radiation injuries. As an
example, in Table. 75 shows the dependence of the severity of CRP on the area of thermal burns
and the severity of acute radiation sickness.

Table 75
Predicted severity of combined radiation-thermal injury depending on the severity of acute
radiation sickness and the area of deep thermal burn (according to Selidovkin G.D., Gusev I.A.,
2001)

Severity of Deep thermal burn area, % of body surface area

ARS
I Less than 10 10-20 20-30 Over 30
II—IV Less than 1 1-5 More than 10
Severity of I II III IV
CRP (light) (medium) (heavy) (extremely
heavy)

Measures of medical protection in CRP include the complex use of anti-radiation protection
and methods of providing assistance in case of non-radiation injury.

At the advanced stages of evacuation in the provision of first aid and first aid, the presence or
absence of radiation damage does not significantly affect the usual scope of activities. In addition
to the usual list, antiemetics are injected inside, and if there is a threat of incorporation of
radioactive substances, a respirator is put on.

At the stage of first medical aid, intra-point sorting provides for the allocation of three groups of
victims:

 lightly affected: not needing or needing minimal assistance at this stage;

 in need of first aid with subsequent evacuation to the stage of qualified or specialized
care;
 affected in an extremely serious condition, for whom only symptomatic therapy is
indicated.

To the usual volume of first aid measures, determined by the nature and severity of non-radiation
injuries, partial sanitization, change of dressings contaminated with radioactive substances, relief
of manifestations of the primary reaction are added.

The basic principles of triage in the provision of qualified and specialized medical care are the
same. Only at these stages does it become possible to perform an exhaustive medical triage for
all groups of patients with CRP. It should be remembered that victims with mild CRP do not
need specialized treatment, and victims with extremely severe lesions are referred for
symptomatic care.

The key point in the treatment of CRP is the use of the latent period of acute radiation sickness
for surgical interventions, which is due to the impossibility of long-term open management of
wounds and the need to achieve their healing before the onset of the peak period of ARS.

+In the first period of CRP (primary reaction to radiation and non-radiation injuries), the main
efforts should be aimed at eliminating the consequences of non-radiation injuries and preventing
their complications. To this end, measures are being taken to restore external respiration, stop
bleeding, anesthetize, immobilize, prevent wound infection, etc., and if there are signs of a
primary reaction to radiation, they must be stopped with antiemetics. In the second period (the
predominance of non-radiation components), the primary surgical treatment of wounds and open
fractures, the treatment of burns, as well as all the activities of qualified and specialized surgical
care, the implementation of which cannot be delayed until the end of the ARS peak period, are
carried out. In the third period of the CRP (the predominance of the radiation component),
medical measures are taken to combat pancytopenic, infectious and hemorrhagic
syndromes. Surgical interventions are performed only for health reasons (external and internal
bleeding, perforation of hollow organs, etc.). In the fourth period (recovery), pathogenetic and
symptomatic therapy of residual effects of radiation injury and treatment of the consequences of
non-radiation injuries are carried out.

6. Diseases of internal organs in gunshot and mine-explosive injuries: classification,

characteristics of syndromes and organopathological changes, clinical picture, diagnosis,
treatment
A gunshot wound (GSW), also known as ballistic trauma, is a form of physical trauma sustained
from the discharge of arms or munitions. The most common forms of ballistic trauma stem from
firearms used in armed conflicts, civilian sporting, recreational pursuits and criminal activity.
Damage is dependent on the firearm, bullet, velocity, entry point, and trajectory.
Signs and symptoms
Gunshot wounds can be particularly devastating compared to other penetrating injuries because
the trajectory and fragmentation of bullets can be unpredictable after entry.  Additionally,
gunshot wounds typically involve a large degree of nearby tissue disruption and destruction due
to the physical effects of the projectile correlated with the bullet velocity classification
Classification  Gunshot wounds are classified according to the speed of the projectile:
Low-velocity: < 1,100 ft/s (340 m/s)
Medium-velocity: 1,100 ft/s (340 m/s) to 2,000 ft/s (610 m/s)
High-velocity: > 2,000 ft/s (610 m/s)

Physics
 The degree of tissue disruption caused by a projectile is related to the cavitation the projectile
creates as it passes through tissue.  A bullet with sufficient energy will have a cavitation effect
in addition to the penetrating track injury.  As the bullet passes through the tissue, initially
crushing then lacerating, the space left forms a cavity; this is called the permanent cavity.
Blast injury
A blast injury is a complex type of physical trauma resulting from direct or indirect exposure to
an explosion. [1] Blast injuries occur with the detonation of high-order explosives as well as the
deflagration of low order explosives. These injuries are compounded when the explosion occurs
in a confined space.
Classification Blast injuries are divided into four classes:
 primary,
 secondary,
 tertiary,
 quaternary.
Primary injuries
Primary injuries are caused by blast overpressure waves, or shock waves. These are especially
likely when a person is close to an exploding munition, such as a land mine.  Injury from blast
overpressure is a pressure and time dependent function. By increasing the pressure or its
duration, the severity of injury will also increase
Secondary injuries
Secondary injuries are caused by fragmentation and other objects propelled by the explosion. 
These injuries may affect any part of the body and sometimes result in penetrating trauma with
visible bleeding.  At times the propelled object may become embedded in the body, obstructing
the loss of blood to the outside.  However, there may be extensive blood loss within the body
cavities.
Tertiary injuries
Displacement of air by the explosion creates a blast wind that can throw victims against solid
objects.  Injuries resulting from this type of traumatic impact are referred to as tertiary blast
injuries. Tertiary injuries may present as some combination of blunt and penetrating trauma,
including bone fractures and coup contre-coup injuries
Quaternary injuries
Quaternary injuries, or other miscellaneous named injuries, are all other injuries not included in
the first three classes.  These include flash burns, crush injuries, and respiratory injuries.
DIAGNOSIS and TREATMENT

7. Early and late diseases due to blast injury. Treatment.

Prehospital Care
EMS personnel should attempt to determine and report any information regarding the nature and
size of the explosion; the time of occurrence; the proximity of the victim to the epicenter of the
blast; victim displacement by the blast wind if any; the presence of secondary fires, smoke, dust,
or chemical or radioactive contamination; and history of entrapment in collapsed structures.
EMS personnel are responsible for activating appropriate disaster and/or hazardous material
responses as early as possible.
Analysis of blast incidents indicates that "upside-down" triage is common; less injured patients
typically arrive at the hospital, via ambulance or private vehicle, before the most severely injured
victims.
Screening for radioactive contamination with a hand-held Geiger counter is a prudent precaution
for any explosion that may involve radioactive material, including any explosion that may have
been deliberately set. If radioactive material is detected, decontamination of personnel and
equipment as well as notification of the receiving hospital is required. The Radiation Emergency
Action Center and Training Site (REAC/TS) provides advice and assistance; their 24-hour
emergency telephone number is +1 (865) 576-1005 (Ask for REAC/TS).
Significant extremity trauma and associated death from exsanguination is a major cause of
preventable death. EMS personnel should rapidly identify patients with life-threatening external
hemorrhage and control bleeding. Early use of tourniquets may be life-saving, especially in the
setting of multiple seriously injured casualties.
High-flow oxygen should be administered to all patients with respiratory distress, abnormal
findings on auscultation, and evidence of significant thoracic trauma.
EMS personnel should avoid administration of large quantities of intravenous fluid in patients
with a high suspicion of ongoing internal hemorrhage. Judicious fluid boluses may be required if
patients exhibit signs and symptoms of inadequate perfusion, such as deteriorating mental status,
in this setting. Experiences on the battlefield suggest that Hextend is the preferred resuscitation
fluid for the prehospital setting.
EMS personnel should initiate measures to reduce heat loss and prevent hypothermia in the
trauma patient, since this condition is associated with increased mortality.
In cases of life-threatening extremity trauma secondary to blast injuries, early use of tourniquets
may prove lifesaving. In a study comparing combat application tourniquet (CAT) to the newer
emergency and military tourniquet (EMT) pneumatic tourniquet, the CAT tourniquet proved
ineffective in controlling arterial blood flow when applied at mid-thigh level while EMT was
successful in a significantly larger number of patients. [27]
The FDA has approved an expandable, multi-sponge, temporary wound dressing (XSTAT) to
control bleeding from certain types of wounds received in battle. The dressing, which can be
used for up to 4 hours, consists of 3 syringe-style applicators with 92 compressed cellulose
sponges that have an absorbent coating. These sponges expand and swell to fill the wound
cavity, creating a temporary physical barrier to blood flow. Each tablet-shaped sponge measures
9.8 mm in diameter and 4-5 mm in height and can absorb 3 ml of blood or body fluid.

Emergency Department Care

Examine the lungs, abdomen, and TMs of all patients exposed to a significant explosion.
Penetrating wounds (secondary blast injury), blunt trauma (tertiary/secondary blast injury), and
burns receive standard treatment. Shrapnel wounds (secondary blast injury) are treated as low-
velocity gunshot wounds.
Hemodynamically unstable patients with significant trauma may benefit from early use of
packed red blood cells (PRBC) and fresh frozen plasma (FFP) in a 1:1 ratio, as well as platelets.
Battlefield experience suggests a benefit to the early use of fresh whole blood if available.
Additionally, cryoprecipitate and recombinant factor VIIa should be considered in the severe
trauma patient, especially in the setting of massive transfusion requirements. One review of 3
mass casualty incidents following explosive events in Iraq suggested that this resuscitation
strategy resulted in the transfusion of an average 3.5 units of PRBC and 3.8 units of plasma, as
well as a mortality of 8%. [29]
The prevention of hypoxia and hypotension are critical in patients with traumatic brain injury to
prevent significant increases in mortality. [22] Because pulmonary contusion tends to evolve
over several hours, a period of observation and repeat radiography may be necessary if indicated.
Definitive airway management and ventilatory support may be required. If abdominal pain
persists or vomiting develops, consider admitting the patient for observation. Intestinal
hematoma may be difficult to detect in the ED.
White phosphorus (WP) burns require unique management. Initial management of WP-
contaminated burns consists of copious lavage of the area, removing identifiable particles (which
should be placed in water to prevent further combustion), and covering the area with saline-
soaked gauze to prevent further combustion. Use of a Wood lamp in a darkened resuscitation
suite or operating room may help identify WP particles in the wound.
Definitive treatment consists of a rinse using 1% copper sulfate (CuSO4) solution and removing
the WP particles. Copper sulfate combines with phosphorous particles to create a blue-black
cupric phosphide coating. This impedes further WP combustion and makes particles easier to
find. Rinse the contaminated burn with copper sulfate solution, remove WP particles, and then
use copious saline lavage to rinse off the copper sulfate. Never apply copper sulfate as a
dressing. Excess copper sulfate absorption can cause intravascular hemolysis and renal failure.

WP injury can lead to hypokalemia and hyperphosphatemia, with ECG changes, cardiac
arrhythmias, and potentially death. Place the patient on a cardiac monitor and closely track
serum calcium levels. IV calcium may be required. Moistened face masks and good ventilation
help protect patients and medical personnel from the pulmonary effects of phosphorous
pentoxide gas. Naturally, avoid the use of flammable anesthetic agents and excessive oxygen
around WP.

A high rate of ICU admission and ventilator requirement should be anticipated. In a review of 3
mass casualty incidents, approximately 50% of surgical patients with injuries resulting from
blasts required each of these. [29] Limited data prevent establishing the optimal duration of
observation.

Consider the following guidelines:

Persons who are exposed to open-space explosions and who have no apparent significant injury
and normal vital signs and unremarkable lung and abdominal examinations generally can be
discharged after 4 hours of observation. Return instructions should include shortness of breath,
abdominal pain, vomiting, or other symptoms.
Persons exposed to significant closed-space explosions or in-water explosions and those who
incur tympanic membrane (TM) rupture are at higher risk of delayed complications. All these
patients should have achest radiography, and selected patients should have imaging of other
organs. Even if no injury is identified, these patients should receive more intensive observation
over a longer period. Motivated, reliable, and completely asymptomatic patients may be sent
home after 4 hours of observation.
Admit to the hospital all patients with significant burns, suspected air embolism, radiation or WP
contamination, abnormal vital signs, abnormal lung examination findings, clinical or
radiographic evidence of pulmonary contusion or pneumothorax, abdominal pain, vomiting,
evidence of renal contusion/hypoxia, or penetrating injuries to the thorax, abdomen, neck, or
cranial cavity.
For patients thought to have arterial gas embolism (AGE) or cerebral AGE, note the following
recommendations:

Positive pressure ventilation (PPV) and positive end expiratory pressures (PEEP) should be
avoided whenever possible in the setting of pulmonary blast injury due to the risk of pulmonary
alveolar rupture and subsequent formation of air emboli. However, mechanical ventilation often
cannot be avoided. Due to the nonhomogeneous pulmonary compliance that characterizes the
blast lung, localized overinflation of the more compliant lung segments occurs when high
ventilatory pressures are used. Whenever possible, reduce the tidal volume to limit peak
inspiratory pressure (PIP) and minimize ventilator-induced lung barotrauma injury. If necessary,
consider permissive hypercapnia ventilation: reduce the tidal volume to maintain PIP less than
35-40 cm H 2O; make no attempts to control PaCO 2 levels until the arterial pH falls below 7.20.
When respiratory acidosis becomes too severe, increase the respiratory rate until the arterial pH
rises above 7.25.
Patients thought to have AGE require recompression treatment. Place patients on 100% oxygen
by tight-fitting face mask and, if possible, place them in the left lateral recumbent position to
minimize the risk of travel of the air embolism out of the heart. Trendelenburg (head down)
position is no longer recommended. If the side of the lung responsible for the AGE can be
identified, unilateral lung ventilation may prevent further introduction of air into the vascular
system during positive pressure ventilation.
In the setting of acute mental status, cerebral AGE should be considered as well as other causes
of symptoms (eg, traumatic CNS injury).
Hyperbaric oxygen (HBO) treatment is the definitive procedure for AGE and cerebral AGE.
Transfer of the patient to a facility with HBO therapy may be required.
Research suggests that aspirin is helpful in AGE. Aspirin may reduce inflammation-mediated
injury in pulmonary barotrauma as well. However, it may be unwise to give an antiplatelet agent
to a patient with acute trauma

Medical Care
As symptoms of pulmonary contusion and intestinal hematoma may take 12-48 hours to develop,
instruct all discharged patients to return for reevaluation if they develop breathing problems,
increasing abdominal pain, or vomiting.

Outpatient treatments for blast-related lacerations, burns, contusions, fractures, and other injuries
are the same as for these injuries from other causes.
Tympanic membrane (TM) rupture by itself does not require specific treatment or
hospitalization. Patients should be instructed not to put anything in the affected ear and should be
referred to an ENT specialist for follow-up care. Remember that neomycin (a component of otic
solutions and suspensions) is ototoxic and theoretically contraindicated in cases of TM
perforation.

Most cases of TM perforation heal spontaneously; however, complications such as ossicle

disruption, cholesteatoma formation, and development of perilymphatic fistulae are possible.
About one third of patients with TM perforation have permanent hearing loss.

Exposure to blasts may induce vestibular disorders that progress over time. Referral to a
neurologist and ENT should be considered for follow-up care. [30] Physical therapy referral
may be required for vestibular rehabilitation. [31]

Exposure to blasts may result in mild traumatic brain injury (mTBI) and predispose to
posttraumatic stress disorder (PTSD). [32] Patients with residual symptoms should be referred
to neurologists and mental health specialists as required. Although insufficient data exist to make
a definitive recommendation, hyperbaric oxygen (HBO) may be of some benefit in the treatment
of blast-related postconcussive symptoms. [33]

8.Crush syndrome: etiology, pathogenesis, clinical picture, diagnosis, treatment.

Prolonged crush syndrome (SDS) is a symptom complex that reflects general and local
pathological changes in the body resulting from prolonged (4-8 hours) compression or crushing
of the soft tissues of the extremities, which are based on ischemic muscle necrosis, intoxication
with necrosis products with the development of hepatic kidney failure.
SDR was identified as a nosological unit in 1941 by Bywaters EG to denote pathological
changes in the body during prolonged tissue compression.
The following terms are also used in the literature: long-term compression syndrome (SDS),
Crush syndrome, traumatic toxicosis, release syndrome, hemoglobinuric nephritis, Bywaters
syndrome.
Etiology and pathogenesis
In the development of pathological changes in SDR, the main role in the period
compressions are played by traumatic tissue ischemia and angiospasm due to pain; in the post-
compression period - resorption of toxic metabolites, zndotoksikoz, multiple organ failure.
To date, the most complete classification of SDRs is the classification proposed by E.A. Nechaev
et al.
CLASSIFICATION.
TYPE OF COMPRESSION: crushing, direct compression, compression compression.
LOCALIZATION: upper, limbs, lower limbs, one limb, etc. COMBINATION OF DAMAGES
OF SOFT TISSUES WITH DAMAGE: 1. Internal organs. 2. Bones and joints.3. Main vessels,
nerve trunks.
COMPLICATIONS: limb ischemia, from internal organs and systems, purulent-septic.
GRAVITY DEGREES: light, medium, heavy.
COMPRESSION PERIODS: early, intermediate, late.
COMBINATIONS: with other types of injury (burns, frostbite, exposure, etc.).
Depending on the nature of compression, the following types of lesions are distinguished,
according to their severity: positional compression; prolonged pressure; prolonged crushing;
The positional compression syndrome develops as a result of compression of the limb by the
mass of one's own body during a coma or as a result of a long stay of the victim in a tight
enclosed space (for example, in rubble).
Direct and prolonged compression of body segments by various objects leads to
to the development of the syndrome of prolonged compression (prolonged crushing).
The most common complications of SDR include acute limb ischemia, multiple organ (primarily
renal and hepatic) insufficiency, as well as purulent-septic complications, the most severe of
which is anaerobic infection.
Clinical symptoms
In the early period (from the first hours to 3 days after the removal of compression),
hemodynamic disturbances characteristic of traumatic shock come to the fore in the clinical
picture.
There is a sharp or gradual increase in edema of the affected organs, the formation of conflicts
and foci of skin necrosis in places of greatest compression.
As a rule, the pulsation of the main arteries is preserved, the distal parts of the limb are warm.
As the edema increases, the skin becomes pale, cyanotic or marble, cold to the touch, the
sensitivity of the limb decreases, the pulsation of the arteries distal to the affected area weakens.
In the interim period (up to 18-21 days after the injury), impaired renal function comes to the
fore, up to acute renal failure, with characteristic clinical manifestations.
Water-electrolyte and protein disorders, anemia, intoxication and multiple organ failure progress.
The most formidable complication in the interim period is the development of anaerobic
infection.
Tissue damage manifests itself in the form of cellulitis, fasciitis and myositis.
In the late period, local changes and purulent complications come first: necrosis and
sequestration of dead muscles with the formation of extensive phlegmon of the limbs, atrophy
and scarring of significant muscle masses, traumatic neuritis and joint contractures.
Diagnostics.
The diagnosis of SDR is established on the basis of anamnesis, a sharp increase in edema of the
affected segments and the addition of a clinical picture of kidney damage.
Physical examination does not always allow us to judge with sufficient certainty the degree of
changes in the deep layers of tissues.
To clarify the indications for surgery and the possibility of saving the limb, a number of
diagnostic tests have been proposed: dopplerography, duplex scanning of arteries and veins,
rheovasography, radioisotope scintigraphy, thermography, capillary photometry, ultrasound
scanning of soft tissues, computed tomography, histological examination, electromyography,
skeletal muscle impedance, serum myoglobin blood, K + in serum, medium molecules,
tryptophan in serum protein filtrate.
However, the use of most of these methods in the early postoperative period of the disease is
difficult, especially in conditions of mass influx of victims. At the same time, their reliability is
not always sufficient due to the mosaic nature of tissue damage.

Treatment is conservative.
In practice, in the first days after the elimination of compression, it is extremely difficult to
determine the nature and extent of local changes.
Treatment of SDR begins after the elimination of compression, since massive resorption of tissue
decay products begins immediately after the restoration of blood flow.
The imposition of a tourniquet on the limb is indicated only for arterial bleeding, complete
destruction of the limb and its gangrene.
To prevent the development of postischemic edema, instead of applying a tourniquet, it is
advisable to perform elastic bandaging of the limb immediately after the compression is
removed.
The basis for further treatment of SDR in the early stages is intensive anti-shock and
detoxification therapy, prevention and control of renal failure, anemia and hypoproteinemia.
Treatment is operative.
With the ineffectiveness of the therapy, the increase in edema of the limb, in the presence or
threat of development of renal failure, there is a need for decompressive surgical intervention.
If there are no such indications, then it is not advisable to operate closed injuries until the
patient's condition stabilizes and necrosis is demarcated.
The presence of extensive foci of muscle destruction in itself cannot serve as an indication for
immediate surgical treatment in the early and intermediate periods of the disease.
Several methods of fasciotomy have been proposed, the main purpose of which is to decompress
deep layers of soft tissues and improve blood circulation in the affected segment.
The operation of choice for a complicated course of SDR is open fasciotomy, supplemented, if
necessary, with necrectomy.
The imposition of primary sutures on post-traumatic and postoperative wounds in SDR leads to
the development of a severe purulent infection, the spread of the lesion far beyond the primary
injury, a sharp deterioration in the general condition and an increase in acute renal failure.
Open wound management allows for dynamic monitoring of the wound process and timely re-
surgery.
Surgical tactics in the treatment of patients with SDR complicated by purulent infection should
be based on the principles of the method of active surgical treatment of purulent wounds.
The results of treatment of patients with SDR depend, first of all, on the organization of medical
care and the coherence of the actions of physicians at all stages of treatment. This is especially
important when providing assistance to victims of mass disasters.
The nature of damage in SDR contributes to the formation of atrophic changes, joint
contractures, and neurotrophic disorders in the long-term period

9. Burn disease: classification, characteristics of common syndromes, clinical picture,

treatment.
Etiology of Burns
Thermal burns may result from any external heat source (flame, hot liquids, hot solid objects, or,
occasionally, steam).
Radiation burns most commonly result from prolonged exposure to solar ultraviolet radiation
(sunburn) but may result from prolonged or intense exposure to other sources of ultraviolet
radiation (eg, tanning beds) or from exposure to sources of x-ray or other nonsolar radiation (see
Radiation Exposure and Contamination).
Chemical burns may result from strong acids, strong alkalis (eg, lye, cement), phenols, cresols,
mustard gas, phosphorus, and certain petroleum products (eg, gasoline, paint thinner). Skin and
deeper tissue necrosis caused by these agents may progress over several hours.
Electrical burns result from heat generation and electroporation of cell membranes associated
with massive currents of electrons. High voltage (> 1000 volts) electrical burns often cause
extensive deep tissue damage to electrically conductive tissues, such as muscles, nerves, and
blood vessels, despite minimal apparent cutaneous injury.
Pathophysiology of Burns
Heat from burns causes protein denaturation and thus coagulative necrosis. Around the
coagulated tissue, platelets aggregate, vessels constrict, and marginally perfused tissue (known
as the zone of stasis) can extend around the injury. In the zone of stasis, tissue is hyperemic and
inflamed.

Damage to the normal epidermal barrier allows

 Bacterial invasion
 External fluid loss
 Impaired thermoregulation
Damaged tissues often become edematous, further enhancing intravascular volume loss. Heat
loss can be significant because thermoregulation of the damaged dermis is absent, particularly in
wounds that are exposed.

Burn depth
First-degree (also sometimes called superficial) burns are limited to the epidermis.

Partial-thickness (also called 2nd-degree) burns involve part of the dermis and can be
superficial or deep.

Superficial partial-thickness burns involve the papillary (more superficial) dermis. These burns
heal within 1 to 2 weeks, and scarring is usually minimal. Healing occurs from epidermal cells
lining sweat gland ducts and hair follicles; these cells grow to the surface, then migrate across
the surface to meet cells from neighboring glands and follicles.

Deep partial-thickness burns involve the deeper dermis and take ≥ 2 weeks to heal. Healing
occurs only from hair follicles, and scarring is common and may be severe.

Full-thickness (3rd-degree) burns extend through the entire dermis and into the underlying fat.
Healing occurs only from the periphery; these burns, unless small, require excision and skin
grafting.

Complications of Burns
Burns cause both systemic and local complications. The major factors contributing to systemic
complications are breakdown of skin integrity and fluid loss. Local complications include
eschars and contractures and scarring.

Systemic burn complications

The greater the percentage of total body surface area (TBSA) involved, the greater the risk of
developing systemic complications. Risk factors for severe systemic complications and mortality
include all of the following:

 Second- and third-degree burns of ≥ 40% of TBSA

 Age > 60 years or < 2 years
 Presence of simultaneous major trauma or smoke inhalation
The most common systemic complications are hypovolemia and infection.

Hypovolemia, causing hypoperfusion of burned tissue and sometimes shock, can result from
fluid losses due to burns that are deep or that involve large parts of the body surface; whole-body
edema from escape of intravascular volume into the interstitium and cells also develops. Also,
insensible fluid losses can be significant. Hypoperfusion of burned tissue also may result from
direct damage to blood vessels or from vasoconstriction secondary to hypovolemia.

Infection, even in small burns, is a common cause of sepsis and mortality, as well as local
complications. Impaired host defenses and devitalized tissue enhance bacterial invasion and
growth. The most common pathogens are streptococci and staphylococci during the first few
days and gram-negative bacteria after 5 to 7 days; however, flora are almost always mixed.

Metabolic abnormalities may include hypoalbuminemia that is partly due to hemodilution

(secondary to replacement fluids) and partly due to protein loss into the extravascular space
through damaged capillaries. Dilutional electrolyte deficiencies can develop; they include
hypomagnesemia, hypophosphatemia, and hypokalemia. Metabolic acidosis may result from
shock. Rhabdomyolysis or hemolysis can result from deep thermal or electrical burns of muscle
or from muscle ischemia due to constricting eschars. Rhabdomyolysis causing myoglobinuria or
hemolysis causing hemoglobinuria can lead to acute tubular necrosis and acute kidney injury.

Hypothermia may result from large volumes of cool IV fluids and extensive exposure of body
surfaces to a cool emergency department environment, particularly in patients with extensive
burns.

Ileus is common after extensive burns.

Local burn complications

Eschar is stiff, dead tissue caused by deep burns. A circumferential eschar, which completely
encircles a limb (or sometimes the neck or torso), is potentially constricting. A constricting
eschar limits tissue expansion in response to edema; instead, tissue pressure increases, eventually
causing local ischemia. The ischemia threatens viability of limbs and digits distal to the eschar,
and an eschar around the neck or thorax can compromise ventilation.

Scarring and contractures result from healing of deep burns. Depending on the extent of the scar,
contracture deformities can appear at the joints. If the burn is located near joints (particularly in
the hands), in the feet, or in the perineum, function can be severely impaired. Infection can
increase scarring. Keloids form in some patients with burns, especially in patients with darker
skin.

Symptoms and Signs of Burns

Wound symptoms and signs depend on burn depth:

First-degree burns: These burns are red, blanch markedly and widely with light pressure, and
are painful and tender. Vesicles or bullae do not develop.
Superficial partial-thickness burns: These burns blanch with pressure and are painful and
tender. Vesicles or bullae develop within 24 hours. The bases of vesicles and bullae are pink and
subsequently develop a fibrinous exudate.
Deep partial-thickness burns: These burns may be white, red, or mottled red and white. They
do not blanch and are less painful and tender than more superficial burns. A pinprick is often
interpreted as pressure rather than sharp. Vesicles or bullae may develop; these burns are usually
dry.
Full-thickness burns: These burns may be white and pliable, black and charred, brown and
leathery, or bright red because of fixed hemoglobin in the subdermal region. Pale full-thickness
burns may simulate normal skin except the skin does not blanch to pressure. Full-thickness burns
are usually anesthetic or hypoesthetic. Hairs can be pulled easily from their follicles. Vesicles
and bullae usually do not develop. Sometimes features that differentiate full thickness from deep
partial thickness burns take 24 to 48 hours to develop.

Diagnosis of Burns
Clinical assessment of burn extent and depth
Laboratory testing and chest x-ray in admitted patients
Location and depth of burned areas are recorded on a burn diagram. Burns with an appearance
compatible with both deep partial-thickness and full-thickness are presumed to be full-thickness.

The percentage of TBSA involved is calculated; only partial-thickness and full-thickness burns
are included in this calculation (1). For adults, the percentage TBSA for parts of the body is
estimated by the rule of nines (Professional.Fig. # (A) Rule of nines (for adults) and (B) Lund-
Browder chart (for children) for estimating extent of burns); for smaller scattered burns,
estimates can be based on the size of the patient’s entire opened hand (not the palm only), which
is about 1% of TBSA. The hand size method is particularly helpful in calculating the burn
surface area of a partially burned area. For example, if an arm (which would represent 9% if
totally involved) is not completely burned, the patient's hand size can used as a template to
estimate the extent of scattered uninvolved (or involved) areas. The uninvolved area can be
subtracted from the 9% area of the arm to more accurately calculate the burned surface area of
the arm. Children have proportionally larger heads and smaller lower extremities, so the
percentage TBSA is more accurately estimated using the Lund-Browder chart (Professional.Fig.
# (A) Rule of nines (for adults) and (B) Lund-Browder chart (for children) for estimating extent
of burns).

Burn infection is suggested by wound exudate, impaired wound healing, or systemic evidence of
infection (eg, feeding intolerance, decrease in platelet count, increase in serum glucose level).
Fever and white blood cell count elevation are common in burn patients without infection and
therefore are unreliable signs of developing sepsis. If the diagnosis is unclear, infection can be
confirmed by biopsy; cultures from the wound surface or exudate are unreliable. Many centers
test patients on admission for colonization with methicillin resistant staphylococcus aureus
(MRSA).
Treatment of Burns
IV fluids for burns > 10% TBSA
Wound cleaning, dressing, and serial assessment
Supportive measures
Transfer or referral of selected patients to burn centers
Surgery and physical therapy for deep partial-thickness and full-thickness burns
Initial treatment
Treatment begins in the prehospital setting. The first priorities are the same as for any injured
patient: ABC (airway, breathing, and circulation). An airway is provided, ventilation is
supported, and possible associated smoke inhalation is treated with 100% oxygen. Ongoing
burning is extinguished, and smoldering and hot material is removed. All clothing is removed.
Chemicals, except powders, are flushed with water; powders should be brushed off before
wetting. Burns caused by acids, alkalis, or organic compounds (eg, phenols, cresols,
petrochemicals) are flushed with copious amounts of water continuing for at least 20 min after
nothing of the original solution seems to remain.

Intravenous fluids
IV fluids are given to patients in shock or with burns > 10% TBSA. A 14- to 16-gauge venous
cannula is placed in 1 or 2 peripheral veins through unburned skin if possible. Venous cutdown,
which has a high risk of infection, is avoided.

Initial fluid volume is guided by treatment of clinically evident shock (1). If shock is absent,
fluid administration aims to replace the predicted deficit and supply maintenance fluids. The
Parkland formula (4 mL/kg) × % TBSA burned (second-degree and third-degree burns) is used
to estimate fluid volume needs in the first 24 hours after the burn (not after presentation to the
hospital) and determines the rate of IV fluid administration. Half the calculated amount is given
over the first 8 hours; the remainder is given over the next 16 hours. Fluid is given as lactated
Ringer's solution because large amounts of normal saline could result in hyperchloremic
acidosis.
For example, in a 100-kg man with a 50% TBSA burn, fluid volume by the Parkland formula
would be

equation
Half of the volume, 10 L, is given in the first 8 hours after injury as a constant infusion, and the
remaining 10 L is given over the following 16 hours. In practice, this formula is only a starting
point, and infusion rates are adjusted based on clinical response. Urine output, typically
measured with an indwelling catheter, is the usual indicator of clinical response; the goal is to
maintain output between 30 and 50 mL/hour in adults and between 0.5 and 1.0 mL/kg/hour in
children. When giving typical large volumes of fluid, it is also important to avoid fluid overload
and consequent heart failure and compartment syndrome. Clinical parameters, including urine
output and signs of shock or heart failure, are recorded at least hourly on a flow chart.

Some clinicians give colloid, usually albumin, after 12 hours to patients who have larger burns,
are very young or very old, or have heart disease and require large fluid volumes.

If urine output is inadequate despite administration of a large volume of crystalloid, consultation

with a burn center is necessary because these patients are at increased risk of resuscitation
complications including compartment syndromes of the abdomen and extremities. Patients with
inadequate urine output despite administration of a large volume of crystalloid may respond to
an infusion of colloid or other measures. In meta-analyses, administration of albumin was shown
to decrease total fluid volumes by about half at 72 hours post-injury. Other studies have shown
an association between decreased total fluid resuscitation volumes and lower patient mortality. A
large multicenter prospective trial comparing crystalloid and colloid is underway (2, 3).

For patients with rhabdomyolysis, fluid administration is the mainstay of treatment, and the goal
should be to maintain urine output of at least 0.5 and 1.0 mL/kg/hour. Although some authorities
have recommended alkalinizing the urine by giving IV fluids containing sodium bicarbonate to
treat rhabdomyolysis, there is little evidence of improved patient outcomes, and alkalinization is
no longer recommended.

Initial wound care

After adequate analgesia, the wound is cleaned with soap and water, and all loose debris is
removed. Water should be room temperature or warmer to avoid inducing hypothermia.
Ruptured blisters, except for small ones on palms, fingers, and soles, are debrided. Unruptured
blisters can sometimes be left intact but should be treated by application of a topical
antimicrobial. In patients who are to be transferred to a burn center, clean dry dressings can be
applied (burn creams may interfere with burn wound assessment at the receiving facility), and
patients are kept warm and relatively comfortable with IV opioids.

After the wound is cleaned and is assessed by the final treatment provider, burns can be treated
topically. For shallow partial-thickness burns, topical treatment alone is usually adequate. All
deep partial-thickness burns and full-thickness burns should ultimately be treated with excision
and grafting, but in the interim, topical treatments are appropriate.
Topical treatment may be with

Antimicrobial salves (eg, 1% silver sulfadiazine, mafenide acetate)

Commercial dressings incorporating silver (eg, sustained-release nanocrystalline silver
dressings)
Biosynthetic wound dressings (also called artificial skin products)
Silver dressings should be considered only in partial-thickness burns with significant wound
moisture because activation of silver requires wound moisture. Silver sulfadiazine may induce
transient leukopenia. Some (but not all) silver-impregnated dressings must be kept moist but can
be changed as infrequently as every 7 days (to minimize pain associated with repeated wound
care).

Topical salves must be changed daily. Artificial skin products and silver impregnated dressings
are not changed routinely but can result in underlying purulence necessitating removal,
particularly when wounds are deep. Burned extremities should be elevated. Compression
dressings such as elastic wraps should be used to reduce edema and improve wound healing.

A tetanus toxoid booster (0.5 mL subcutaneously or IM) is given to patients with all but minor
burns who have been previously fully vaccinated and who have not received a booster within the
past 5 years. Patients whose booster was more remote or who had not received a full vaccine
series are given tetanus immune globulin 250 units IM and concomitant active vaccination (see
Prevention).

Escharotomy (incision of the eschar) of constricting eschars may be necessary to allow adequate
expansion of the thorax or perfusion of an extremity. However, constricting eschars rarely
threaten extremity viability during the first few hours, so if transfer to a burn center can occur
within that time, escharotomy can typically be deferred until then. If timely transfer is not
possible, escharotomy should be done with the input of a consulting burn center.

Supportive measures
Hypothermia is treated, and pain is relieved. Opioids (eg, morphine) should always be given IV,
and large doses may be needed for adequate pain control. Treatment of electrolyte deficits may
require supplemental calcium (Ca), magnesium (Mg), potassium (K), or phosphate (PO4).

Nutritional support is indicated for patients with burns > 20% TBSA or preexisting
undernutrition. Support with a feeding tube begins as soon as possible if oral nutrition is not
feasible or adequate. Parenteral support is rarely necessary.

Hospitalization and referral

After initial treatment and stabilization, the need for hospitalization is assessed. Consultation
with a burn center, is strongly suggested for
Physical and occupational therapy
Physical and occupational therapy are begun at admission to help minimize scarring and
contractures, particularly for body surfaces with high skin tension and frequent movement (eg,
face, hands), and to optimize function. Active and passive range-of-motion exercises become
easier as the initial edema subsides (enhanced by appropriate elevation and compression); they
are done once or twice daily. After grafting, exercises are often suspended for 3 days, then
resumed, but at some centers are initiated within 24 hours of grafting. Extremities affected by
deep partial-thickness burns or full-thickness burns are splinted in functional positions as soon as
possible and kept splinted continuously (except during exercise) until the graft has been placed,
healing has occurred, or both.

Outpatient burn treatment

Outpatient treatment includes keeping burns clean and, to the extent possible, keeping the
affected body part elevated and, for extremities, compressed (eg, by elastic wraps over
dressings). Dressings should be changed daily for burns treated with topical salves. The salve is
applied and then covered with a dry nonadherent gauze dressing and compression wraps. Silver
dressings should be changed every 7 to 10 days, depending on the specific product
recommendation. Dressing change simply involves removing the older dressing and replacing it
with a new one. Biosynthetic wound dressings should not be changed in the absence of
purulence. Biosynthetic dressings should simply be covered with dry gauze, which is changed
daily. (See also How To Debride and Dress a Burn.)
Outpatient follow-up visits are scheduled as needed depending on burn severity (eg, for very
minor burns, initial visit within 24 hours, then subsequent visits every 7 to 10 days). Visits
include debridement if indicated, reassessment of burn depth, and evaluation of the need for
physical therapy and grafting. Patients should return earlier if they note signs of infection, such
as increasing redness extending from the wound edges, increasing purulence and pain, or a
change in the appearance of the wound with development of black or red spots. Should these
signs occur, medical evaluation should ensue urgently. Outpatient treatment is acceptable for
minor burn-wound cellulitis in healthy patients aged 2 to 60 years; hospitalization is indicated
for other infections.
10. Electromagnetic radiation of the microwave range: mechanism of action, classification,
clinical picture, diagnosis, treatment

Microwave - radiation - a type of non-ionizing radiation, characterized by a frequency of

electromagnetic oscillations from 3 × 10 8 to 3 × 10 11 Hz and a wavelength from 1 meter to 1
millimeter.

Classification of microwave waves

Type of microwave waves Wavelength Oscillation frequency, Hz

meter (1 – 10) m 3 10 7 – 3 10 8

decimeter (10 – 100) cm 3 10 8 – 3 10 9

centimeter (1 – 10) cm 3 10 9 – 3 10 10

millimeter (1 – 10) mm 3 10 10 – 3 10 11

An electromagnetic field (EMF) is formed around any source of electromagnetic radiation,

which consists of alternating electric and magnetic fields.

Biological effect of microwave electromagnetic radiation on the human body.

Unlike ionizing radiation, which directly creates electric charges, EMPs do not have an ionizing
ability and act only on already existing free charges or dipoles. There are a number of
hypotheses, most of which are based on the provisions set out in the biophysics course. It is
known from the theory of the electromagnetic field that if a charge moving under the influence
of a magnetic field is simultaneously affected by an electric field directed along the movement of
the charge, then a significant acceleration of charged particles is achieved. It can be imagined
that similar processes occur in a living system when an electromagnetic field is applied to an
organism.

The second position is that when an electromagnetic field is applied to the human body, the
conductivity and dielectric constant of tissues change, which increases the amount of absorbed
energy, especially in tissues with a high water content.

At present, it is customary to distinguish between the so-called thermal effect (heating of

irradiated tissues) with an energy flux exceeding 10–15 mW/cm 2 and athermal effect with an
irradiation intensity below the threshold of thermal effect (PES value >10 mW/cm 2 ).

The thermal effect is caused by an increase in the kinetic energy of biomolecules, which is
introduced by an external electromagnetic field. Molecular dipoles, especially water dipoles,
change the speed and direction of their movement, receive a certain acceleration, due to inertia,
some of the molecular dipoles do not have time to orient themselves in the direction of the
rapidly changing field, which causes the moving dipoles to collide with each other and,
ultimately, leads to an increase in temperature.

When absorbing EMR in the microwave range, in addition to integral heating, due to the
chemical heterogeneity and structural features of tissues, loci of more intense energy absorption
("hot spots") appear in them. If they are located in or near vital regulatory centers, irreversible
changes are possible.
The resulting heat can lead to heating, overheating, and even burns to certain parts of the
body. Naturally, tissues with a high water content heat up more and this process is carried out
faster, blood circulation for the time being reduces the temperature of tissues, especially those
where it is carried out intensively. In the same place where blood circulation is slowed down or
the exchange occurs with the help of diffusion, heating occurs quickly, metabolic processes in
the tissues are significantly accelerated.

Obviously, such a change in metabolic processes, especially in those organs and tissues where
the usual optimal metabolic process occurs at low temperatures, can lead to pronounced
pathological changes. The following scale of sensitivity to EMR of the microwave range has
been established : lens , vitreous body , liver , intestines , testicles .

The pathogenesis of radio wave disease.

In the general pathogenesis of microwave EMR lesions, there are three stages (according to E.V.
Gembitsky):

1 - functional (functional-morphological) changes in cells, primarily in the cells of the central

nervous system, developing as a result of direct exposure to EMR;

2 - change in the reflex-humoral regulation of the functions of internal organs and metabolism;

3 - predominantly indirect, secondary change in the functions (organic changes are also possible)
of the internal organs.

Stages of formation of microwave EMR lesions.

Adaptive reactions of the body under the

influence of microwave electromagnetic
fields are conventionally divided
into specific and non-specific . Adaptive
specific reactions are aimed at combating
overheating. This is vasodilation,
tachycardia, tachypnea, increased sweating,
etc.

Nonspecific adaptive reactions are associated with a reflex response of the central nervous
system and endocrine glands. At the beginning of exposure to a microwave field or under the
influence of its low intensities, stimulation of the reflex activity of the central nervous system,
endocrine glands and metabolism occurs, and with further exposure - their
inhibition. Pathological reactions are manifested in the form of foci of hemorrhage, cataracts,
degenerative changes in the testes, stomach ulcers, neuroses, neurocirculatory asthenia,
hyperthermia, etc.

Classification of lesions by microwave electromagnetic radiation.

I. The period of formation of radio wave disease .

1. Acute lesions:
a) I degree (mild);

b) II degree (moderate);

c) III degree (severe).

2. Chronic lesions:

a) initial (initial) manifestations;

b) I degree (mild);

c) II degree (moderate);

d) III degree (severe).

II. Recovery period.

III. Consequences and outcomes of EMR lesions in the microwave range.

Clinic of acute and chronic lesions by microwave electromagnetic radiation.

Acute lesions are relatively rare, most often in emergency situations when exposure to
microwaves of high thermal intensity occurs. Therefore, the first clinical manifestations are
symptoms of overheating of the body and damage to the nervous system, especially when the
head area is irradiated. There are 3 degrees of severity of acute EMR lesions : I (mild), II
(medium) and III (severe).

With lesions of I (mild) severity , thermoregulation disorders accompanied by thermal fatigue,

asthenic reactions, headache, autonomic disorders with short-term fainting, severe bradycardia or
tachycardia come to the fore. The blood reaction is limited to a slight leukocytosis.

For lesions II (medium) severity more pronounced violations of thermoregulation are

characteristic, leading to changes in sweating, oxidative processes and shifts in water and
electrolyte balance. Clinically, this is manifested by hyperthermia (general body temperature
rises to 39 - 40 °), CNS function disorders in the form of motor excitation, retarded
consciousness, sometimes hallucinations and delusional states. There is a tendency to instability
of blood pressure, possible heart rhythm disturbances (paroxysmal tachycardia, frequent
polytopic extrasystoles, impaired atrioventricular conduction), nosebleeds, burns of open parts of
the body (erythematous dermatitis) may occur. Some time after the lesion, a cataract is
detected. In the study of peripheral blood, in addition to pronounced leukocytosis, signs of blood
clotting and hypercoagulation are revealed.

With a lesion of the III (severe) degree , a rapid development of the process is noted with a
predominance of cerebral phenomena, manifested by confusion and loss of consciousness and
the occurrence of hypothalamic disorders with angiospastic manifestations (diencephalic
crisis). Affected people note fever throughout the body, the state of health quickly deteriorates, a
sharp headache appears, sometimes dizziness and decreased visual acuity, nausea, and less often
vomiting. The expressed arterial hypertension is defined. The treatment of such lesions always
requires a whole range of urgent intensive care measures.

Those who have undergone an acute lesion may subsequently experience instability in blood
pressure, phenomena of prolonged asthenia and desynchronosis (mood instability, sharply
reduced performance, muscle weakness, tremor of the limbs, insomnia or drowsiness, sleep
perversion, aching pain in the arms and legs). In case of damage by millimeter and centimeter
waves, burns of open parts of the body and damage to the eyes (cataract, the development of the
so-called "dry desquamative" conjunctivitis) are possible.

Chronic EMR lesions are much more common than acute ones and occur as a result of
prolonged repeated exposure to doses exceeding the maximum permissible levels. Chronic
lesions of EMR in the microwave range do not have clearly defined (specific) signs and can
manifest themselves as functional disorders, primarily of the nervous, cardiovascular and
endocrine systems as a result of changes in the reflex-humoral regulation of internal organs and
metabolism. In the advanced stages of the disease, organic changes in the internal organs are also
possible. In some cases, local changes are added, mainly of the skin and its appendages, of the
organ of vision (damage to the lens of the eye, the occurrence of chronic conjunctivitis).

In chronic exposure to electromagnetic radiation, there are initial (initial) manifestations

and lesions of three degrees of severity : I (mild), II (medium) and III (severe). For the initial
manifestations of the lesion, the basis of the clinical picture is asthenic (asthenoneurotic)
syndrome; with mild lesions, asthenovegetative (vegetative) syndrome debuts, and with lesions
of moderate severity, angioedema and diencephalic syndrome (hypothalamic) occur. In severe
lesions, they are accompanied by symptoms indicating a violation of other organs and systems.

The first signs of asthenic (asthenoneurotic) syndrome appear, as a rule, after 2–3 years of
constant (continuous) work under exposure to EMR in the microwave range. Patients complain
of frequent headaches of a dull nature that occur towards the end of the working day, general
weakness, fatigue, irritability, a feeling of weakness, drowsiness during the day and insomnia at
night (desynchronosis), memory loss, inability to concentrate and engage in creative mental
work, sexual disorders gradually occur. various types, there are transient paresthesias, pain in the
distal extremities. In general, signs of the predominance of inhibitory processes in the central
nervous system are objectively revealed, occasionally - vegetative disorders.

There may be an increase in the excitability thresholds of the olfactory and visual analyzers and
the threshold of sensitivity in the distal extremities, an increase in neuromuscular excitability, an
increase in the time of sensorimotor reactions, a deterioration in light and dark adaptation, the
stability of clear vision, and distinctive eye sensitivity. Temporary suspension from work under
the influence of EMR generators in the microwave range and adequate treatment at this stage of
the disease lead, as a rule, to the complete disappearance of the above disorders.

Persistent asthenovegetative syndrome most often occurs in individuals exposed to relatively

high intensities (up to several mW/cm 2 ). Vegetative disorders are manifested by hyperhidrosis,
a decrease in tactile sensitivity and temperature of the skin of the hands, pallor of the skin,
cyanosis of the distal extremities, muscle hypotension, persistent red diffuse dermographism,
changes in galvanic skin reflexes, weakening of the skin-vascular and cardiovascular reflexes,
and a sluggish vascular reaction. on intradermal administration of histamine, asymmetry of
vascular tone, changes in position reflexes - ortho- and clinostatic.

Vegetative dysfunctions most noticeably affect the reactions of the cardiovascular system. The
predominance of the vagus nerve tone, the combination of arterial hypotension with a tendency
to bradycardia, pronounced vagotonic reactions during the Ashner test are characteristic. On the
ECG, sinus arrhythmia and bradycardia, atrial and ventricular extrasystoles, a moderately
pronounced violation of atrioventricular conduction are recorded. Vegetative disorders create
certain conditions for the formation of dystrophic changes in the myocardium, which are initially
compensated and are detected only after exercise and during pharmacological tests. In some
cases, signs of myocardial dystrophy progress (an increase in the size of the heart, a deaf I tone, a
pendulum rhythm are detected).
For a lesion of moderate severity, the presence of a diencephalic syndrome is
characteristic.With a further increase in vascular-vegetative disorders, angiospastic reactions
appear and become predominant, blood pressure rises, a spasm of the fundus vessels and skin
capillaries is detected. Changes in the myocardium become more permanent and pronounced,
there are signs of coronary circulation disorders with compressive pains in the region of the
heart. If the phenomena of hypotension and bradycardia can be characterized as neurocirculatory
dystonia of the hypotonic type, then the presence of angiospastic reactions with pain in the heart,
increased blood pressure can be defined as a manifestation of diencephalic disorders that
periodically reach the level of vascular crises. The latter appear suddenly or after a short
prodromal period and are manifested by a sharp onset of headache, sometimes with fainting or
short-term disturbance of consciousness. Soon, pains in the region of the heart of a compressive
nature join, accompanied by severe weakness, sweating, and a feeling of fear. During an attack,
pallor of the skin, chills, blood pressure rises to very significant numbers (180/110 - 210/130 mm
Hg. Art.). With frequently recurring crises, there may be a sharp drop in blood pressure with the
onset of collapse.

In patients with periodically manifested diencephalic syndrome, electroencephalography data

indicate diffuse changes in the bioelectrical activity of the brain with symptoms of irritation of
the limbic-reticular complex. According to the majority of researchers, as the length of service in
the conditions of exposure to EMR of the microwave range increases, peripheral vascular
resistance increases, there is a tendency to increase blood pressure, especially diastolic, and the
systolic and minute volume of the heart decreases.

Against this background, neurocirculatory dystonia of the hypertensive type subsequently

transforms into arterial hypertension, coronary heart disease of a high functional class
develops. All of these conditions can develop many years after the cessation of work with EMP
generators.

With moderate severity of chronic lesions, against the background of the listed
syndromes, endocrine disorders often appear: activation of the thyroid function with an
increase in its mass (sometimes with a clinic of thyrotoxicosis I-II degree), sexual dysfunction
(impotence, menstrual irregularities). This is facilitated by the occurrence of chronic gastritis,
usually atrophic with intestinal dysplasia of the gastric mucosa; gradually there are signs of
damage to other organs and systems. Trophic disorders are possible - brittle nails, hair loss,
weight loss.

Both with mild and moderate severity of chronic lesions, blood counts are unstable. More often,
moderate leukocytosis is noted with a tendency to neutropenia and lymphocytosis, sometimes
structural changes in neutrophils (pathological granularity, vacuolization of the cytoplasm,
fragmentation and hypersegmentation of the nuclei), reticulocytosis, a decrease in the acid
resistance of erythrocytes, and slight spherocytosis are often found. With severe forms of
damage, there may be a tendency to leukopenia with lymphopenia and monocytosis,
thrombocytopenia, signs of delayed maturation of granulocytes and erythroid cells in the bone
marrow. Some biochemical indicators can be changed - a slight decrease in cholinesterase
activity, a violation of the release of catecholamines, hypoproteinemia, an increase in the level of
histamine, a slight decrease in glucose tolerance.

With various options for exposure to EMR in the microwave range with a wavelength of 1 mm
to 10 cm, clouding of the lens (cataract) develops. It can occur both after a single intense
irradiation, and with chronic exposure to EMR of non-thermal intensity, especially when the
radiation directly hits the eyes (it often occurs in technicians who are directly involved in the
repair and adjustment of the equipment of microwave EMR generators). Pulse radiation has the
greatest damaging effect.
With severe severitythe picture of disturbances of the electromagnetic nature
progresses. Complaints of patients are aggravated, there are phenomena of obsessive fears and
viscosity of thinking. Organic lesions of the brain are often diagnosed, manifested by
dysfunction of the cranial nerves, symptoms of oral automatism, increased tendon reflexes, and
parasthesias. Hemodynamic disturbances become pronounced in the form of often recurrent and
difficult to stop diencephalic crises. The condition is aggravated by the addition of coronary
heart disease, duodenal ulcer. An imbalance in the endocrine system is revealed (sexual function
is inhibited, thyroid function is disturbed). Indicators of cellular and humoral immunity decrease,
autoimmune processes increase.

Diagnosis of acute and chronic lesions by microwave field

Diagnosis of acute lesions of microwave EMR, as a rule, does not present great difficulties.

Diagnosis examples:

- acute damage to the EMR of the microwave range of moderate severity. Acute overheating of
the body of a moderate degree (hyperthermic form). Acute psychomotor agitation. An attack of
paroxysmal tachycardia (gastric form). Nose bleed;

– chronic damage of EMR of the microwave range of the II degree of severity. Neurocirculatory
dystonia of hypertonic type (protracted course). Chronic gastritis with a decrease in acid-forming
function, atrophic;

– chronic damage of EMR of the microwave range of the II degree of severity. Protracted
astheno-vegetative syndrome. Dry desquamative conjunctivitis, fading exacerbation.

Prevention of acute and chronic lesions by microwave electromagnetic radiation.

Prevention of the adverse effects of EMR on persons working with microwave sources is a set of
technical, sanitary and hygienic and medical measures defined in the Republic of Belarus by
Sanitary Rules and Regulations 2.2.4 / 2.1.8.9-36-2002 "Electromagnetic radiation of the radio
frequency range (EMR RF)"

A set of measures for the prevention of microwave radiation damage

Preventive measures include:

1. Placement of PJIC, radio engineering systems (RTS) at safe distances from barracks,
service and residential buildings, establishment of a sanitary protection zone and a
restricted zone. The intensity of EMIPJIC, RTS in the territory of populated areas located
in the near zone of the radiation diagram should not exceed 10 μW / cm 2 and in the
 territory of populated areas located in the far zone of the radiation diagram - 100 μW /
cm 2 .
2. Shielding of all elements capable of emitting electromagnetic radiation, shielding of
workplaces, grounding of screens.
3. Special metallized clothing and goggles for PES above 1.0 mW/cm 2 .
4. When working inside shielded rooms, the walls, floor and ceiling of these rooms must be
shielded with radio-absorbing materials.

Methods of protection are determined individually in each specific case (during certification of
workplaces).

Sanitary and hygienic preventive measures include:

1. Monitoring the level of exposure in the workplace and the surrounding area. The
data of periodic measurements are entered in the sanitary passport of the facility
and are used in the certification of workplaces, monitoring of working conditions
and the health of workers, in the development of safety and/or prevention
measures.
2. Sanitary education, training of personnel serving microwave generators in safety
rules.
3. Establishment of benefits (additional leave and reduction of working hours).

4 Regulation of the time of contact with the EMR source and reduction of the duration of work
in the irradiation zone if it is impossible to reduce the EMR PES to the maximum permissible
levels.

Currently, in the Republic of Belarus, the permissible levels of continuous exposure to

microwaves for those working with radiating equipment are calculated in accordance with the
adopted document “Sanitary rules and regulations 2.2.4 / 2.1.8.9-36-2002 “Electromagnetic
radiation of the radio frequency range (EMR RF)”.

The maximum allowable value of energy exposure (EE PD ) per shift should not exceed 200 (μW
/ cm 2 ) x h. Next, the maximum allowable energy flux density ( PEF pdu ) is calculated using the
formula:

Principles of treatment of lesions by microwave electromagnetic radiation .

So far, there is no pathogenetically substantiated scheme for the treatment of lesions with a
microwave field. Treatment is carried out symptomatically in compliance with the principle of
individualization.

The volume of medical care for acute lesions of microwave electromagnetic fields

First aid

1. Remove the victim from the zone of action of the damaging factor.

2. Lay on your back with legs raised.

3. Carry out external cooling (place in a cool place; apply a cold compress on the head, wipe the
body with a wet towel; wipe the skin of the forehead, temporal areas with 70% alcohol (vodka),
ammonia; while maintaining consciousness, drink cold water.
4. In case of violation of breathing, activity of the cardiovascular system, carry out
cardiopulmonary resuscitation.

First aid

1. Continue external cooling.

2. In case of respiratory failure - restore airway patency, oxygen therapy.

3. In case of symptoms of cardiovascular insufficiency, administer cordiamine (1 ml

subcutaneously), caffeine-sodium benzoate (1 ml of a 2% solution intramuscularly).

4. In case of psychomotor agitation and fear reaction, give 1-2 tablets of phenazepam or
diazepam orally.

First aid

1. Supplement local cooling with the following measures:

- apply ice packs to the groin areas, along the torso;

– wrap with wet sheets for a short time;

- apply a cold compress to the head, apply electric fans (one on each side of the body),

Intravenous administration of chilled solutions: 100 ml of 40% glucose solution with 10 units of
insulin, 100-200 ml of 0.9% NaCl solution.

A solution of chlorpromazine 2.5% - 1 - 2 ml intramuscularly.

Prednisolone 60 - 120 mg intravenously.

In pain syndrome, a solution of analgin 50% 2-4 ml is administered intravenously per 10 ml of

0.9% sodium chloride solution.

With the development of convulsive syndrome: 0.5% solution of diazepam 2 - 4 ml

intravenously.

Monitoring the state of the cardiovascular and respiratory systems, correcting their function if
necessary.

When assisting patients with hyperthermia, it is necessary to avoid the appointment of

anticholinergic drugs. Also limit the use of non-steroidal anti-inflammatory drugs.

Qualified help

In the qualified help affected only II and III degrees of severity need . Measures aimed at
stopping the syndrome of overheating of the body, arterial hypertension, and pain are continuing.

With the development of acute respiratory failure, artificial lung ventilation and oxygen therapy
are performed. The syndrome of acute cardiovascular insufficiency, including those with
arrhythmia, is eliminated with the help of inotropic drugs, antiarrhythmic drugs, and infusion
therapy.
In the syndrome of CNS damage, depending on the degree and type of disorders, sedatives,
neuroleptics, tranquilizers, hypnotics, drugs that affect the tone of the CNS vessels, nootropic
drugs can be used. Noteworthy is the use of sodium oxybutyrate, which has a sedative effect and
reduces the sensitivity of the brain to hypoxia.

In the event of nosebleeds, tamponade with a hemostatic sponge is performed, intravenous

administration of epsilon-aminocaproic acid, ascorbic acid, dicynone. It is necessary to apply
cold to the nose area.

In case of acute visual impairment (blurred vision, double vision, sudden decrease in vision),
anticonvulsants and antispasmodics are indicated - 2.4% solution of eufillin 10 - 20 ml
intravenously, papaverine solution 2% - 2 ml, dibazole 1% - 1 ml intramuscularly.

Specialized assistance

As part of the provision of specialized care, it is necessary to continue a set of therapeutic

measures aimed at the final and complete relief of life-threatening conditions (hyperthermia,
respiratory failure, cardiovascular insufficiency), early diagnosis of complications and
consequences of microwave field lesions, specialized treatment in full with full rehabilitation of
the injured. In the general complex of measures, dietary nutrition, vitamin therapy, the use of
adaptogens, physiotherapeutic, psychotherapeutic treatment are of great importance.

The treatment of chronic forms of damage by the microwave field is non-specific and requires
an integrated approach . It consists of a diet, regimen, exercise therapy, psychotherapy, and, if
necessary, physio and pharmacotherapy. Methods of psychotherapy are of great importance.
 XII. Infectious diseases
1. Differential diagnostics of fever of unknown origin. Algorithm of the patient’s examination. The
diagnostic measures to establishing the infectious and non-infectious etiology of fever.
• A temperature of > 38.3°C (> 100.9°F) of at least 3 weeks’ duration that remains undiagnosed following
three outpatient visits or 3 days of hospitalization.
CLASSIFICATION
• Classic FUO:
o Fever for > 3 weeks with no identified cause after 3 days of hospital evaluation or ≥ 3 outpatient
visits
o Common Etiologies – infection, malignancy, collagen vascular disease
• Health care–associated FUO:
o Fever in hospitalized patients receiving acute care and with no infection present or incubating at
admission if the diagnosis remains uncertain after 3 days of appropriate evaluation
o Common Etiologies – C. difficile enterocolitis, drug-induced PE, septic thrombophlebitis, sinusitis
• Immune-deficient (neutropenic) FUO:
o Fever in patients with neutropenia (≤500/mm3) and other immunodeficiency if the diagnosis remains
uncertain after 3 days of appropriate evaluation, including negative cultures after 48 hours
o Common Etiologies – Opportunistic bacterial infections, aspergillosis, candidiasis, herpes virus
• HIV-related FUO:
o Fever for > 4 weeks in outpatients with confirmed HIV infection or > 3 days in inpatients with
confirmed HIV infection if the diagnosis remains uncertain after appropriate evaluation
o Common Etiologies – CMV, M. avium-intracellulare complex, Pneumocystis carinii pneumonia,
drug-induced, Kaposi’s sarcoma, lymphoma
DIFFERENTIAL DIAGNOSIS / ETIOLOGIES
• Infections (~30%)
o TB – extra-pulmonary (most common), miliary, pulmonary (if pre-existing disease)
o Abscess – subphrenic, liver, splenic, pancreatic, perinephric, diverticular, pelvis, psoas
o Osteomyelitis
o Bacterial endocarditis (negative culture)
o Uncommon – viral (CMV, EBV), bacterial (brucellosis, bartonellosis), fungal (histoplasmosis,
cryptococcosis), parasitic (toxoplasmosis, leishmaniasis, amoebiasis, malaria)
• Malignancies (~20%)
o Most commonly lymphomas (especially non-Hodgkin’s) and leukemias, also MM, myelodysplastic
syndrome
o Solid tumors – RCC (most common), also breast, liver (hepatoma), colon, pancreas, or liver
metastases
• Collagen vascular diseases (~30%)
o SLE, RA, RF, vasculitis (temporal arteritis, PAN), JRA, Still’s disease
• Misc (~20%)
o Drug induced (Anti-microbial (sulfonamides, penicillin, nitrofurantoin, antimalarials), Anti-
hypertensives (hydralazine, methyldopa), Anti-epileptic (barbiturate, phenytoin), Anti-arrhythmic
(quinine, procainamide), Anti-inflammatory (NSAIDs), Anti-thrombotic (ASA), Anti-histamines
o Factitious fever
o Sarcoidosis, granulomatous hepatitis, IBD
o Hereditary periodic fever syndromes (such as familial Mediterranean fever)
o Venous thromboembolic disease: PE, DVT
o Endocrine – thyroiditis, thyroid storm, adrenal insufficiency, pheochromocytoma
• Idiopathic in 10-15% despite detailed workup
EVALUATION
• The initial approach to the patient presenting with fever should include a comprehensive history,
physical examination, and appropriate laboratory testing.
• As the underlying process develops, the history and physical assessment should be repeated.
• The first step should be to confirm a history of fever and document the fever pattern.
• Classic fever patterns such as intermittent, relapsing sustained, and temperature-pulse disparity may
prove to be useful but rarely are diagnostic
• In taking a history from a patient with FUO, particular attention should be given to recent travel,
exposure to pets and other animals, the work environment, and recent contact with persons exhibiting
similar symptoms. In patients returning from areas where tuberculosis and malaria are common, the
index of suspicion for these diseases should be elevated. In patients who have had contact with pets or
other animals, diseases common to animal handlers must be suspected.
• The family history should be carefully scrutinized for hereditary causes of fever, such as familial
Mediterranean fever. The medical history also must be examined for conditions such as lymphoma,
rheumatic fever, or a previous abdominal disorder (e.g., inflammatory bowel disease), the reactivation of
which might account for the fever. Finally, drug-induced fever must be considered in patients who are
taking medications
• Diagnostic clues often are not readily apparent on physical examination; repeated examination may be
essential. Careful attention to the skin, mucous membranes, and lymphatic system, as well as abdominal
palpation for masses or organomegaly, is important. The physician's choice of imaging should be guided
by findings from a thorough history and physical examination (e.g., a cardiac murmur in the presence of
negative blood cultures should be investigated with a transthoracic echocardiogram or, if needed,
transesophageal echocardiogram). Also, Duke's clinical criteria include two major and six minor criteria
that help determine the likelihood of endocarditis. A cost-effective individualized approach is essential
to the evaluation of these patients, and without a thoughtful and focused investigation, inappropriate tests
might be performed.
• The preliminary evaluation helps in the formulation of a differential diagnosis and guides further studies
that are more invasive or expensive. These preliminary investigations should include a complete blood
count, liver function test, erythrocyte sedimentation rate, urinalysis, and basic cultures. Simple clues
found during initial testing often will guide the clinician toward one of the major subgroups of FUO. The
decision to obtain further diagnostic studies should be based on abnormalities found in the initial
laboratory work-up and not represent a haphazard use of costly or invasive modalities.
• Skin testing for tuberculosis with purified protein derivative (PPD) is an inexpensive screening tool that
should be used in all patients with FUO who do not have a known positive PPD reaction. However, a
positive PPD reaction alone does not prove the presence of active tuberculosis. A chest radiograph also
should be obtained in all patients to screen for possible infection, collagen vascular disease, or
malignancy. If this initial assessment does not disclose the source of fever, more specific investigatory
techniques, such as serology, sonography, computed tomography (CT), magnetic resonance imaging
(MRI), and nuclear medicine scanning should be conducted, based on clinical suspicion.
• Abdominal sonography, pelvic sonography, or CT scanning should be performed early in the diagnostic
process to rule out such common causes of FUO as intra-abdominal abscess or malignancy, depending
on the primary evaluation. This testing, including directed biopsies, has greatly reduced the need for
more invasive operative studies.
• MRI should be reserved for clarifying conditions found through the use of other techniques or when the
diagnosis remains obscure. The use of radionucleotide scanning, such as gallium 67, technetium Tc 99m,
or indium-labeled leukocytes, is warranted for detecting inflammatory conditions and neoplastic lesions
that often are underdiagnosed by CT scans; however, these tests tend not to detect collagen vascular
disease and other miscellaneous conditions
• Endoscopic procedures may be helpful in the diagnosis of disorders such as inflammatory bowel disease
and sarcoidosis. The newest diagnostic technique in the evaluation of the patient with FUO is positron
emission tomography (PET). This modality appears to have a very high negative predictive value in
ruling out inflammatory causes of fever. However, because of its limited availability it is too early to
determine if PET scans will prove to be a useful diagnostic tool in the evaluation of these patients.
• More invasive testing, such as lumbar puncture or biopsy of bone marrow, liver, or lymph nodes, should
be performed only when clinical suspicion shows that these tests are indicated or when the source of the
fever remains unidentified after extensive evaluation. When the definitive diagnosis remains elusive and
the complexity of the case increases, an infectious disease, rheumatology, or oncology consultation may
be helpful.
2. Differential diagnosis of infectious diseases occurring with CNS lesions. Syndromes of defeat of the
membranes of the brain and the substance of the brain and spinal cord. Clinical manifestations.
Complications. Diagnostic algorithm. Interpretation of the liquorogram. Principles of antimicrobial
and pathogenetic therapy.
DIFFERENTIAL DIAGNOSIS OF INFECTIOUS DISEASES OCCURRING WITH CNS LESIONS
Serous Serous Purulent
Subarachnoid
Normal Meningism Viral Bacterial Bacterial
Hemorrhage
Meningitis Meningitis Meningitis
Colorless or Colorless or
Colour Colorless Colorless Colorless Bloody
Yellow Greenish
Transparent
Yellow
Transparency Transparent Transparent or Opalescent Cloudy
sediments
Opalescent
Pressure
50-250 N/↑ N/↑ ↑ ↑ ↑
(mmH2O)
RBC (x106/L) 0-4 N N N N ↑
10-2000 50-5000 1000-5000
WBC (x106/L) 0-4 N N/↑
Lymph Lymph PMN
>50-60% of
Glucose N N/↑ ↓ ↓ N
blood level
Protein <0.45 g/L N N/↑ ↑ ↑ ↑

SYNDROMES OF DEFEAT OF THE MEMBRANES OF THE BRAIN AND THE SUBSTANCE OF

THE BRAIN AND SPINAL CORD.
Meningeal syndrome
• Meningeal syndrome or meningeal irritation syndrome occurs with hemorrhage in the subarachnoid space,
with meningitis of various etiologies, with cerebral edema.
• Components of the syndrome:
o headache; nausea, vomiting; pain on percussion of the skull; general hyperesthesia to light, sound,
tactile stimuli; meningeal symptoms.
• Signs of irritation of the meninges is the tonic tension of some groups of skeletal muscles:
o head extensor muscles; flexor muscles of the hip and knee joints.
• With a pronounced meningeal syndrome, a peculiar posture occurs: the patient lies on his side, his head is
thrown back, the hips are pressed to the stomach, the legs are pressed to the hips (bent at the hip and knee
joints, the muscles that extensor the spine are tense) - opisthotonus.
• Examine the following meningeal symptoms :
o A symptom of neck stiffness - when you try to passively bend your head, resistance arises due to tension
in the posterior group of the cervical muscles, the chin does not reach the sternum by several fingers.
o Kernig's symptom - in a patient lying on his back, leg is bent at hip and knee joints at a right angle,
when you try to straighten leg in knee joint, there is resistance from muscles, flexors of the lower leg.
o Lower Brudzinski's syndrome occurs when examining Kernig's symptom (flexion of opposite leg).
o Upper Brudzinski's syndrome - occurs during study of stiff neck, characterized by flexion of legs
o Middle Brudzinsky syndrome - occurs with pressure on the area of the pubic joint, is characterized by
flexion of the legs in the hip and knee joints.
o Bekhterev's symptom - increase in headache, appear painful grimace when tapping on zygomatic arch.
o With Lessage's suspension symptom , it is observed in children when lifting by the armpits (there is a
reflex bending of the legs and bringing them to the stomach)
• If the symptoms of irritation of the meninges are detected without changes in the cerebrospinal fluid, they
speak of meningism (possible with various diseases, often observed in children).
 Hypertensive syndrome
• Hypertensive syndrome is a symptom complex caused by a stable or progressive increase in ICP.
• Intracranial pressure (ICP) is understood as the total value, in the formation of which the following are
involved: cerebrospinal fluid, intracellular and extracellular fluids, arterial and venous systems of the
brain. It is conventionally accepted that ICP corresponds to the hydrostatic pressure of the CSF.
• Long term hypertensive syndrome leads to hydrocephalus
• Characterized by the occurrence of cerebral symptoms :
o Headache often worsens at night or in the morning, which is due to a violation of the venous and liquor
outflow, characterized by an increase in headache when coughing, straining. Headache can be
paroxysmal and constant.
o Vomiting occurs at height of headache, is not associated with food intake, leads to decrease in headache.
o Dizziness is non-systemic, disappears after dehydration.
o Characterized by paresis or insufficiency of the abducens nerves, which occurs as a result of
compression of the roots of these nerves in intracranial hypertension.
o Meningism or false meningeal symptoms.
o Mental disorders: apathetic-abulic syndrome, indifference, decreased motor activity, psychomotor
agitation.
o Epileptic syndrome is characterized by the occurrence of generalized paroxysms.
o Occlusive syndrome: occurs when the CSF outflow pathways from the cranial cavity are blocked (at
the level of the ventricles, interventricular openings, cerebellar-cerebral cistern).
• Neurological symptoms.
o Focal neurological symptoms are different when blocks occur at different levels:
▪ at the level of the Sylvian aqueduct , compression of the upper sections of the brain stem and
quadrigemina occurs, which is characterized by the occurrence of paresis of the vertical gaze,
miosis, mydriasis, paresis of the oculomotor nerves, vertical nystagmus, and hearing loss.
▪ at the level of the openings of Magendie and Luschka , compression of the medulla oblongata and
cerebellum occurs, which is characterized by dizziness, nystagmus, vomiting, bradycardia, impaired
coordination of movements, "floating" gaze, ataxia.
▪ with blockade at the level of the lower parts of the IV ventricle : bulbar syndrome, bilateral
pathological foot signs, paresis, cerebellar disorders.
▪ In acute occlusion that occurs when the tumor is localized on the pedicle, Bruns syndrome occurs,
which can be provoked by a sharp turn of the head and torso. Clinical manifestations: severe
headache, repeated vomiting, bradycardia, psychomotor agitation alternating with lethargy,
respiratory failure, hyperhidrosis, pallor or flushing of the face, dizziness, stem tonic convulsions.
Dislocation syndrome
• With an increase in ICP, especially if it is due to a volumetric process, the difference in pressure between
the different spaces of the skull, separated by processes of the dura mater, and also between the posterior
cranial fossa and the subarachnoid space of the spinal cord increases. This leads to displacement of entire
regions of the brain, and spaces with more pressure are sent to spaces with less pressure through holes that
form formations of the dura mater (falciform processes, cerebellar tenon) or bony structures (foramen
magnum). This process is called wedging , and in this case, an infringement of substance of brain occurs.
• Distinguish :
o tentorial herniation , in which there is a displacement of the medial part of the temporal lobe into the
notch of the cerebellum and compression of the midbrain.
o cerebellar herniation , accompanied by displacement of the cerebellar tonsils into the foramen magnum
and compression of the medulla oblongata.
• Wedging of the brain leads to dangerous and often fatal complications. Due to the compression of arteries
and veins, hemorrhages and foci of ischemia occur in the brain stem. The outflow of cerebrospinal fluid
is even more disturbed, the dislocation phenomena are intensified. Therefore, it is very important to
recognize these complications in a timely manner.
• Symptoms of wedging of the brain into the tentorial foramen.
o Increasing headache, increasing disorders of consciousness, symptoms of damage to the quadrigemina
(restricted gaze up, uneven pupils, weakening their reaction to light, vertical nystagmus, tonic
convulsions, respiratory failure). With lateral displacement, one of the initial manifestations of
infringement in the tentorial foramen is paresis of the oculomotor nerve (of the same name or opposite),
which often occurs with tumors of the temporal lobes.
• Symptoms of wedging of the brain into the foramen magnum.
o Observed with volumetric processes of the posterior cranial fossa. Characterized by: a sharp headache,
stiff neck, forced head position, swallowing disorders, respiratory failure, bradycardia, disorders of
consciousness.
• The following diagnostic methods are used: computed tomography, magnetic resonance imaging.
• If signs of herniation are recognized at an early stage, urgent measures are taken: ventricular drainage,
removal of a hematoma, tumor. In the later stages of herniation, the damage to the brain stem becomes
irreversible
ALGORITHM OF DIAGNOSTICS
• Signs of intoxication reveled, general cerebral symptoms, meningeal syndromes → NO → encephalitic
syndromes signs → YES → inflammatory changes of CSF → YES → Encephalitis
• Signs of intoxication reveled, general cerebral symptoms, meningeal syndromes → YES → encephalitic
syndromes signs → YES → inflammatory changes of CSF → YES → Meningoencephalitis
• Signs of intoxication reveled, general cerebral symptoms, meningeal syndromes → YES → inflammatory
changed of CSF → YES → meningitis
• Signs of intoxication, general cerebral symptoms, meningeal syndromes → YES → inflammatory changes
in CSF → NO → Meningism
TREATMENT
• Bacterial:
o Antibiotic therapy, depending on the sensitivity of the pathogen, is carried out intramuscularly and / or
intravenously before the rehabilitation of the cerebrospinal fluid (the average duration after
normalization of temperature is 10-14 days). The criterion for the rehabilitation of cerebrospinal fluid
is cytosis of less than 100 cells (mainly lymphocytic).
o Fight against cerebral edema (corticosteroids)
o Detoxification (hemodesis).
o Maintenance of the introductory electrolyte balance.
o Maintenance of blood pressure, treatment of systemic disorders (shock, DIC syndrome,
thromboembolism, etc.)
o Antiepileptic therapy according to indications.
o Isolation of a patient with meningococcal meningitis for 24 hours after the start of a/ b therapy and
chemoprophylaxis of persons in contact.
• Viral:
o Etiotropic
▪ Polyvalent immunoglobulin and hyperimmunoglobulin preparations
▪ Virosostatic drugs (acyclovir for herpes infection)
o Analgesics, antiemetics.
o Detoxification
o Bed rest
3. Clinical and laboratory diagnosis of influenza. Features of highly endemic strains. Etiotropic and
pathogenetic therapy. Preventive measures in the treatment of patients at home and in the clinic.
CLINICAL FEATURES
• The clinical presentation of influenza infection is asymptomatic or mild in 75% of cases
• Influenza presents with very characteristic features, hence the term “flu-like symptoms”
• IP = few hours to several days
• Sudden onset of high fever, chills, headache, arthralgia, myalgia, fatigue, and malaise
• Patients often develop acute bronchitis with a cough that is usually dry but may produce small amounts
of clear or blood-tinged sputum
• Hypotension and bradycardia are common (especially among women and older patients)
• After 2-3 days, acute symptoms rapidly subside, although fever may last up to 5 days
• Cough, weakness, sweating, and fatigue may persist for several days or occasionally for weeks
DIAGNOSIS
• RT-PCR – preferred diagnostic tool for the detection of influenza virus in both outpatient and
hospitalized patients
• Rapid antigen test – should only be used if more sensitive diagnostics (e.g. RT-PCR) are not available
o Used for early diagnosis
o Detection of various influenza A/B antigens via nasal or pharyngeal swabs
o High specificity, limited sensitivity
• Blood tests – Normal or slightly elevated inflammatory markers, Relative lymphocytosis
• Serology (e.g. complement fixation) – used to diagnose an infection after it has resolved; should not be
used for primary diagnosis
FEATURES OF HIGHLY ENDEMIC STRAINS
• Antigenic Shift
o Two subtypes of viruses (e.g. human and swine influenza) infect the same cell and exchange genetic
segments (reassortment) to create new subtypes (e.g. H3N1 → H2N1)
o Occurs particular when human pathogenic and animal pathogenic influenza viruses exchange
genetic information
o Causes pandemics (limited to a specific time period)
• Antigenic Drift
o Minor changes in antigenic structure (hemagglutinin and/or neuraminidase) via random point
mutation
o Does not alter the subtype (e.g. H5N1 or “avian flu”)
o Cause epidemics (limited to a specific population or region)
TREATMENT
• Supportive
o Rehydration
o Antipyretics and analgesia to decrease fever
o Antitussives (e.g. dextromethorphan) to relieve dry cough
• Antiviral
o Indications
▪ Patients with severe disease or patient at risk of developing complications
▪ Sometimes considered if there is a high suscipicion of early disease (e.g. prodromal symptoms
and recent exposure)
o Administration – should be initiates as soon as possible (within the first 48 hours)
 o Drugs used – Neuraminidase inhibitors (Oseltamivir, Zanamavir, and Peramavir), Endonuclease
inhibitor (Baloxavir)
o Neuraminidase inhibitors interfere with release of influenza virus from infected cells and thus halt
spread of infection.
o The endonuclease inhibitor baloxavir interferes with viral replication by blocking viral RNA
transcription. It is active against influenza A and B and may be an important new treatment option
should resistance to neuraminidase inhibitors develop.
o Zanamivir is given by an inhaler, 2 puffs (10 mg) 2 times a day; it can be used in adults and
children ≥7 years. Zanamivir sometimes causes bronchospasm and should not be given to patients
with reactive airway disease; some people cannot use the inhalation device.
o Oseltamivir 75 mg orally 2 times a day is given to patients >12 years; lower doses may be used in
children as young as 1year. Oseltamivir may cause occasional nausea and vomiting. In children,
oseltamivir may decrease the incidence of otitis media; however, no other data clearly show that
treatment of influenza prevents complications.
o Peramivir is given IV as a single dose and can be used in patients > 2 years who cannot tolerate
oral or inhaled drugs. Studies of its use for influenza B are limited.
o Baloxavir is given as a single 40 mg dose orally to patients ≥ 12 years and 40 to 80 kg or a single
80 mg dose for patients>80 kg. It can be used in patients ≥ 12 years with uncomplicated influenza
who have been symptomatic for ≤ 48 hours and who are otherwise healthy and not at high-risk
PREVENTION
• Influenza Vaccine
o Annual flu shots for all persons aged 6 months and older ever fly season; as soon as vaccine become
available
o Particularly important in health care professionals and individuals with an increased risk of
influenza-related complications
o Egg allergy is no longer considered a contraindication
o Vaccines consist of viral strains that most likely appear during the flu season
o It can either be
▪ Inactivated vaccine (more common)
▪ Live attenuated – intranasally administered
• The influenza mutant is temperature-sensitive and therefore replicated in the nose
but not in the lungs
o Trivalent or Quadrivalent
▪ The trivalent vaccine protects against 2 influenza A viruses and 1 influenza B virus
▪ Quadrivalent vaccine protects against 2 influenza A and 2 influenza B virus
• Hygiene
o Hand hygiene
▪ Wash with soap and water before and after each patient contact
▪ Alternatively, use an alcohol-based hand rub
o Avoid contact with infected individuals and stay home when sick
o Adhere to standard precaution
▪ Surface cleaning with alcohol- or aldehyde-based agents
▪ Face masks
▪ Gloves and gown for contact with potentially infectious materials
• Chemoprophylaxis
o Antiviral medications may be considered in patients with exposure to an infected person under
certain circumstances (e.g. high risk of complications, contraindications for the vaccine, and
influenza outbreaks in nursing homes)
4. Differential diagnosis of acute intestinal infections. Infectious diarrhea: etiological, epidemiological,
pathogenetic, clinical and laboratory aspects. Differential diagnostic with acute surgical pathology
(acute appendicitis, acute pancreatitis, acute cholecystitis, mesotrombosis, peritonitis). Algorithm for
examining patients with diarrhea syndrome. Assessment of the severity of exsiccosis. Rehydration
therapy, principles of etiotropic therapy.
ETIOLOGY
Pathogen Acute watery diarrhea Dysentery Persistent diarrhea
BACTERIAL
V. cholera and other vibrios + - -
ETEC + - -
EPEC + - +
EAEC + - +
EIEC + + -
EHEC + + -
Shigella spp + + +
Salmonella spp + + +
Campylobacter spp + + +
Yersinia spp + + +
Clostridium difficile + + +
M. TB - + +
VIRAL
Rotavirus + - -
Calcivirus + - -
Enteric adenovirus + - -
Astrovirus + - -
CMV + + +
PROTOZOAL
G. intestinalis + - +
Cryptosporidium parvum + - +
E. histolytica + + +
Balantidium coli + + +
HELMINTHIC
Strongyloides stercoralis - - +
Schistosoma spp - + +

EPIDEMIOLOGY
• Diarrhea is a leading cause of illness and death among children in developing countries, where an
estimated 1.5 million episodes and 0.5 million deaths occur each year in under-fives
• The infectious agents are usually transmitted by fecal-oral route, which include ingestion of fecally
contaminated water or food, person-to-person transmission, and direct contact with infected feces
• Most episodes occur during the first 2 years of life, highest incidence in 6-11 months
• Distinct seasonal patterns occur in many geographical areas. In temperate climates, bacterial diarrhea
tend to occur more frequently during the warm season, whereas viral diarrhea, particularly disease
caused by rotavirus, peak during the winter. In tropical areas, rotavirus diarrhea tends to occur
throughout the year, increasing in frequency during drier, cool months, whereas bacterial diarrhea tend
to peak during warmer, rainy seasons
• Two enteric pathogens Vibrio cholerae O1 and Shigella dysenteriae type 1 causes major epidemics
• Since 1961, cholera caused by the El Tor biotype of V. cholerae 01 has spread to countries in Asia, the
Eastern Mediterranean, and Africa, and to some areas in Europe and North America. During the same
period, S. dysenteriae type 1 has been responsible for large epidemics of severe dysentery in Central
America, and more recently in Central Africa and Southern Asia
PATHOGENESIS
Viruses
• Viruses, such as rotavirus, replicate within the villous epithelium of the small bowel, causing patchy
epithelial cell destruction and villous shortening.
• The loss of normally absorptive villous cells and their temporary replacement by immature, secretory,
crypt-like cells causes the intestine to secrete water and electrolytes.
• Villous damage may also be associated with the loss of disaccharidase enzymes, leading to reduced
absorption of dietary disaccharides, especially lactose.
• Recovery occurs when the villi regenerate and the villous epithelium matures.
Bacteria
• Mucosaladhesion. Bacteria that multiply within the small intestine must first adhere to the mucosa to
avoid being swept away. Adhesion is through superficial hair-like antigens, termed pili or fimbriae, that
bind to receptors on the intestinal surface; this occurs, for example, with enterotoxigenic E. col; and V:
cholerae O1. In some instances, mucosal adherence is associated with changes in the gut epithelium that
may reduce its absorptive capacity or cause fluid secretion (e.g. in infection with entero~athogenic or
enteroaggregative E. coli).
• Toxins that cause secretion. Enterotoxigenic E. coli, V: cholerae O1 and some other bacteria produce
toxins that alter epithelial cell function. These toxins reduce the absorption of sodium by the villi and
may increase the secretion of chloride in the crypts, causing secretion of water and electrolytes.
Recovery occurs when the affected cells are replaced by healthy ones after 2-4 days.
• Mucosal invasion. Shigella, C. jejuni, enteroi nvasive E. coli and Salmonella can cause bloody
diarrhoea by invading and destroying mucosal epithelial cells. This occurs mostly in the colon and the
distal part of the ileum. Invasion may be followed by the formation of microabscesses and superficial
ulcers; hence the presence of red and white blood cells, or visible blood, in the stool. Toxins produced by
these organisms cause tissue damage and possibly also mucosal secretion of water and electrolytes.
Protozoa
• Mucosal adhesion. G. larnblia and Cryptosporidiurn adhere to the small bowel epithelium and cause
shortening of the villi, which may be how they cause diarrhoea.
• Mucosal invasion. E. histolytica causes diarrhoea by invading epithelia1 cells in the colon (or ileum)
and causing microabscesses and ulcers. This only happens, however, when the infecting strain of E
histolytica is virulent. In about 90% of human infections the strains are nonvirulent; in such cases there
is no mucosal invasion and no symptoms occur, although amoebic cysts and trophozoites may be present
in the faeces.
CLINICAL
• Diarrhea
o Diarrhea is present if one of the following criteria is fulfilled:
▪ Frequent defecation: ≥ 3 times per day
▪ Altered stool consistency: increased water content
▪ Increase in stool quantity: more than 200–250 g per day
o Acute diarrhea: lasting ≤ 14 days. Persistent: lasting > 14 days. Chronic: lasting > 30 days
• Further possible symptoms
o Fever, Abdominal pain and cramping, Blood in stool
o Nausea and vomiting
o Signs of dehydration (e.g., low BP, dry mucosa, decreased urine output) in severe cases
o Chronic cases: malnutrition and, in children, failure to thrive
• Disease courses can range from mild to severe with need of hospitalization.
 Pathogen IP Fever Bloody stool Abd pain N/V Duration
BACTERIAL
B. cereus – Type A (emetic) 1-6 h - - - + <12h
B. cereus – Type B (diarrheal) 8-16h - - - - <24h
Campylobacter jejuni 2-10d + + + +/- <1wk
C. difficile Unclear +/- +/- +/- - Variable
C. perfringens 8-12h +/- - +/- - <24h
EIEC 1-3d + +/- + - 7-10d
ETEC 1-3d - - + - 3d
EHEC 3-8d - + + +/- 5-10d
S. typhi, S. paratyphi 10-14d + +/- + +/- <5-7d
Non-typhoidal salmonella 12-72h + +/- + + 3-7d
S. dysenteriae 1-4d + +/- + + <1wk
S. aureus 2-4h - - + + 1-2d
V. cholerae 1-3d - - - - 3-7d
Yersinia 5d + +/- + +/- <3wk
VIRAL
Norovirus 24h - - + + 24h
Rotavirus 2-4d +/- - - +/- 3-8d
PARASITIC
Cryptosporidum 7d +/- - - + 1-20d
E. hystolytica 2-4wk +/- + - + Variable
G. lamblia 1-4wk - - + + Variable

DIAGNOSTIC
• Laboratory tests are usually not required in acute cases and are instead reserved for the diagnosis of
severe or chronic disease.
• CBC: may show anemia or leukocytosis
• Stool samples: leukocytes, ova, and/or parasites
• Stool culture
o Stool cultures are not generally recommended, as the tests are expensive and have low sensitivity.
o Indications: suspected invasive bacterial enteritis, severe illness, or fever (> 38.5°), required
hospitalization, and/or stool tests positive for leukocytes/occult blood/lactoferrin
• C. difficile toxin assay
• Stool osmotic gap: an equation used to identify if watery diarrhea has an osmotic or secretory etiology
o Equation: 290 - [2x (stool sodium + stool potassium)]
o A low stool osmotic gap (< 50 mOsm/Kg) is suggestive of secretory diarrhea
o A high gap (> 100 mOsm/Kg) is suggestive of osmotic diarrhea
• Serodiagnosis
• Abdominal imaging – plain imaging / transabdominal USG
• Endoscopy
• Histology
DIFFERENTIAL DIAGNOSIS BETWEEN ACUTE SURGICAL PATHOLOGIES

ALGORITHM OF EXAMINING PATIENTS

ASSESSMENT OF SEVERITY OF DEHYDRATION

Characteristic 0 1 2
General Thirsty, restless, lethargic, but irritable Drowsy, limp, cool or sweaty;
Normal
appearance when touched +/- comatose
Eye Normal Slightly sunken Very sunken
Mucous
Moist Sticky Dry
membrane
Tears Tears Decreased Absent
0 points = No dehydration
1-4 points = Mild-to-moderate dehydration
5-8 points = Severe dehydration

Sensorium Eyes Thirst Skin Pinch Decision

Abnormal sleep or Drinks poorly or Goes back very
Sunken ≥2 sign = severe
lethargic not at all slowly (>2sec)
Goes back slowly
Restless, irritable Sunken Drinks eagerly ≥2 sign = some
(<2sec)
Drinks normally,
Well, alert Normal Goes back quickly None = no
not thirsty
TREATMENT (Rehydration therapy, Etiotropic therapy)
Rehydration therapy
• No Dehydration – Give ORS after each loose stool
o <2 year – 50-100ml
o 2-9 year – 100-200ml
o ≥10 year – as much as patient wants
• Mild-to-Moderate Dehydration – Give ORS
o 75ml/kg in first 4 hours. Then assess, and if patient still shows signs of dehydration, repeat
o If not, use ORS to replace ongoing diarrheal losses using the above plan
o Patients do not need IV fluids, but need close monitoring during the first 4 hours
• Severe Dehydration – IV Ringer’s lactate or, if not available, normal saline and ORS
o < 1 year
▪ 0-60 mins – 30ml/kg
▪ 1-6h – 70ml/kg
▪ 6-24h – 100ml/kg
o ≥ 1 year
▪ 0-30 mins – 30ml/kg
▪ 30min-3h – 70ml/kg
o Switch from intravenous hydration to oral rehydration solution once hydration is improved and the
patient can drink. This will conserve IV fluids and reduce the risk of phlebitis and other
complications.
o You can use nasogastric tubes to administer oral rehydration solution if the patient is alert but unable
to drink sufficient quantities independently.
Etiotropic Therapy
• Antibiotic therapy for infectious diarrhoea is controversial. Those with mild symptoms and those who
are clearly improving probably do not need antibiotic treatment.
• However, there are certain infectious diarrhoeas in which treatment is recommended: dysenteric
shigellosis, cholera, pseudomembranous enterocolitis, that due to parasites, and sexually transmitted
diseases.
• There are several diseases in which the indications are less clear but treatment is usually recommended:
infection with the non-cholera vibrios, prolonged or protracted infection with yersinia, early in the
course of campylobacteriosis, aeromonas and plesiomonas infections, and outbreaks of enteropathogenic
E coli diarrhoea in nurseries.
• Patients should be treated if they are debilitated, particularly with malignancy, immunosuppressed, have
an abnormal cardiovascular system, have valvular, vascular, or orthopaedic prostheses, have haemolytic
anaemia (especially if salmonellosis is involved), or are extremely young or old.
• Treatment is also advised for those with prolonged symptoms and those who relapse.
 Pathogen Efficacy of Rx Drug of choice Alternative choice
BACTERIA
V. cholerae Proven Doxycycline, 300-mg single Azithromycin, 1-g single
dose dose
Tetracycline, 500 mg QDS
for 3 days
TMP/SMX DS, 160/800
mg BD for 3 days
ETEC Proven Ciprofloxacin 500mg BD 3 TMP/SMX DS, 160/800
mg BD for 3 days
Azithromycin 500mg OD 3
days
EPEC/EIEC Possible Ciprofloxacin, 500mg BD 3 TMP/SMX DS, 160/800
days mg BD for 3 days
EHEC Controversial - -
Shigella spp Proven in dysenteric Ciprofloxacin, 500 mg BD Azithromycin, 500 mg BD
shigellosis for 3 days, or 2-g single dose for 3 days
TMP/SMX DS, 160/800
mg BD for 5 days
Ceftriaxone, 2- to 4-g
single dose
Salmonella Doubtful efficacy in Ciprofloxacin 500 mg BD 5-
enterocolitis. Proven 7 days.
efficacy in severe TMP/SMX DS, 160/800mg
salmonellosis (dysentery, BD 5-7 days
fever) Azithromycin 500mg OD 5-
7 days
Campylobacter Possible efficacy in Azithromycin, 500 mg OD Erythromycin, 500 mg
spp campylobacter enteritis. for 3 to 5 days QDS for 3 to 5 days
Proven efficacy in Ciprofloxacin, 500 mg BD
campylobacter, for 5 to7 days
dysentery/sepsis
Yersinia spp Doubtful efficacy in Ciprofloxacin 500 mg BD Tetracycline 250 mg QDS
Yersinia enteritis. Proven 7–10 days 7–10 days
efficacy in Yersinia
septicaemia
C. difficile Proven Metronidazole 500 mg TDS Vancomycin 125 mg QDS
10 days 10 days.
PROTOZOA
E. histolytica Proven Metronidazole 750 mg TDS Tinidazole, 2 g per day for
5-10 days plus 3 days, plus paromomycin,
paromomycin, 25 to 35 mg 25 to 35 mg per kg per day
per kg per day in 3 divided in 3 divided doses for 5 to
doses for 5 to 10 days 10 days
Balantidium Proven Metronidazole 400 mg TDS Tetracycline 500 mg QDS
coli 10 days 10 days
G. intestinalis Proven Metronidazole, 250 to 750 Tinidazole, 2-g single dose
mg TDS for 7 to 10 days
5. Clinical, epidemiological and laboratory criteria for the diagnosis of viral hepatitis A, B, C, D and
E. Antiviral therapy of chronic hepatitis B and C.
EPIDEMIOLOGY

• Most common cause of acute viral hepatitis

• 5-14 year old mostly
• Mostly in Central and South America, Africa, India and Middle East
A • WOT: Fecal oral – water/food (shellfish in contaminated water) and contact in household (within
family), Swimming, Sexual (MSM), Contact with jaundice patient
• Previous disease forms life-long immunity
• Risk groups: children in day care centers, tourists, soldiers, prisoners, health workers
• Source – patient with acute and chronic hepatitis B and chronic “carriers” of HBsAg
B • WOT: Parenteral (injection of drugs users, blood transfusion, insufficiently cleaned instruments).
Close and sexual contact (toothbrush, razor blade, swing needles). Perinatal
• WOT: Parenteral. Vertical and Sexual (rare)
C
• Silent killer due to its asymptomatic form
• Source – infected person with active viral replication of HDV
D
• WOT – parenteral and sexual
• Main principle is similar to HAV mostly
• Lifelong immunity is missing
• Develops at any age, mostly adolescent and those aged 30-40 years, mostly women, especially
pregnant women
E
• Widespread in tropical and subtropical climates
• Source: Human / Animals (pig)
• From uncooked meat
• WOT – Fecal-oral

CLINICS

•Prodromal phase
o IP = 2 weeks to 1 month (7-45 days)
o GE syndrome – nausea, vomiting, loss of appetite, diarrhea/constipation
o Intoxication – Weakness (Specific), Febrile (“catarrh”, 38-39oC, 3-4/7 days)
o Catarrhal syndrome
• Preicteric (1 week)
o Fever, malaise, fatigue – influenza like / intoxication / Catarrhal syndrome
o Nausea, emesis, diarrhea – GE syndrome
A o Arthralgia
o Until jaundice appear (1 week prior to appearance of dark urine)

•Icteric (2-3 weeks)

o General condition becomes better (no virus – cleared through immunity)
o Jaundice and pale colored stool,
o Itching due to cholestasis (bile acid)
o Hepatocyte injury (increase ALT/AST)
o hepatosplenomegaly
• Prodromal phase
o IP = 1.5-6 months (9-12 months)
o During prodromal phase, its same as HAV
B o Arthralgia prodrome – mono/polyarthritis
o Asthenovegetattive and dyspeptic syndromes
o Fever in beginning is less common
o Vague abdominal pain (sometimes RUQ), nausea, vomiting, anorexia, diarrhea
 CHRONIC
• Most patients asymptomatic but may develop hepatic cirrhosis signs or symptoms
o Fatigue, weakness, anorexia,
o Gynecomastia, palmar erythema, renal insufficiency,
o Thrombocytopenia, anemia, coagulopathy
• Extra hepatic HBV manifestations
o Polyarteritis nodosa
▪ Small-vessel vasculitis characterized by neuropathy, dermatological ulcers, fevers, HTN
and abdominal pain
o Glomerulonephritis
▪ Most commonly membranous GN – hematuria and proteinuria
• Physical Examination
o Ophthalmologic exam – jaundice
o Neurological exam (asterixis and other signs of encephalopathy)
o Abdominal exam – hepatosplenomegaly
•
• Prodromal phase
o IP = 6-12 weeks (2 months)
o Acute phase not diagnosed in most patients
o Nausea, vomiting, pain in RUQ, dark urine
CHRONIC
• Patient becomes chronic with slow interval development of hepatic cirrhosis and/or HCC
• Chronic infection is infection more than 6 months
• Most common manifestation is FATIGUE, but can have cirrhosis findings:
o Anorexia, GI bleeding
C o Altered mental status (hepatic encephalopathy or asterixis)
o Jaundice, palmar erythema and/or spider angiomas
o Ascites and splenomegaly
o Testicular atrophy or gynecomastia
o Dupuytren’s contractures
• Can develop DM due to insulin resistance
• Extra-hepatic manifestations
o Autoimmune: cryoglobulinemia II or III and/or vasculitis, membranoproliferative GN, Lichen
planus, Sicca syndrome, porphyria cutanea tarda
o Lymphoproliferative: Non-Hodgkin B-cell lymphoma
• Co-infection
o In healthy person simultaneously with HBV and HDV
o Clinical picture indistinguishable from Hep-B. Self-limiting. Favorable prognosis. 2 phases
▪ 2 wave elevation of ALT and AST in 2-4-week interval (thymol test value also increases
which is not typical for Hep-B)
▪ 2nd phase maybe with fever and worsening of clinical syndromes
o Fulminant form is possible, but is less frequent
• Superinfection
o Layering HDV with chronic HBV or asymptomatic HBsAg carriage
D o Extremely unfavorable. More severe and even fulminant
o Most severe in patients with chronic active Hep-B – fulminant form develops or becomes
undulating in character with rapid progression in the liver
o When transaminase constantly elevated, AST predominant over ALT (de Ritis coefficient
become higher than 1.0). Splenomegaly
o Chronic hepatitis clinics changes to active cirrhosis clinic
o In asymptomatic HBsAg carriers – Hep-D results in recovery
o Previously healthy carrier state of HBV due to viral superinfection D – activation of process
with development of rapidly progressing chronic hepatitis with cirrhosis
o HDV inhibits replication of virus B, so HBsAg disappears in 2-10% patients
 • Begins after IP of 14-70 days as an active viral syndrome with mild fever, marked loss of appeitis,
aversion to food, upper abdominal discomfort, N/V
• Within a few days haundice can appear with resolution of non-specific symptoms and persists for
E
1-6 weeks and then gradually resolves.
• In children, mostly occurs without any symptoms or as a mild illness without jaundice.
• In adults, may have a prolonged cholestatic phase with significant itching

LABORATORY

• Anti-HAV IgM
o Positive anti-HAV IgM indicates acute hepatitis A infection. This will resolve spontaneously.
A
No further serological testing is required.
• Anti-HAV IgG (indicates past infection/vaccination)
• HBsAg – indicates HBV infection
• Anti-HBs – indicates immunity to HBV due to past infection or immunization
• Anti-Hbc – IgM (acute/recent infection). IgG (past or chronic infection)
• HBeAg – indicates active viral replication therefore high transmissibility and poorer prognosis
• Anti-HBe – indicates low transmissibility
B o Active infection → HBsAg, HBeAg and Anti-HBc IgM
o Window → Anti-HBe, Anti-HBc IgM
o Chronic (high infectivity) → HBsAg, HBeAg, Anti-HBc IgG
o Chronic (low infectivity) → HBsAg, Anti-HBe, Anti-HBc IgG
o Recovery → Anti-HBs, Anti-HBe, Anti-HBc IgG
o Immunised → Anti-HBs
• Anti-HCV
o A positive anti-HCV indicates exposure to the hepatitis C virus but does not distinguish current
C
from previous infection. This requires referral to a specialist
• HCV-RNA
• Anti-HDV IgM, HDV RNA and HBsAg
D • Superinfection – Absent anti-HBc IgM and HBeAg. Present anti-HBc IgG and anti-HBe
• Co-infection – Present anti-HBc IgM and HBeAg
• Anti-HEV IgM (indicates acute infection)
E
• Anti-HEV IgG (indicates past infection)
ANTIVIRAL THERAPY
Chronic Hepatitis B
• Viral load ≥ 2000 → Antiviral
• If less or if negative HBsAg / IgM HbcAg → no need for treatment
• Pegylated IF alpfa-2a and 2b
o S/C 180mcg weekly for 48 weeks
• Antiviral
o Tenofovir – 300mg PO OD
o Entecavir – 0.5mg PO OD
• GCS – bilirubin < 60 – oral, >60 IV in the morning

Chronic Hepatitis C
• Genotype 1
o Weekly PEF-IFN
o Daily Ribavirin (1g) and Sofosbuvir (400mg) for 12 weeks
o Ledipasvir/sofosbuvir for 12 weeks
o PEG-IFN, Ribavirin and Boceprevir
• Genotype 2
o Sofosbuvir (400mg) + Ribavirin for 12 weeks
• Genotype 3
o Sofosbuvir + Ribavirin for 24 weeks
• Genotype 4
o IFN regimen as genotype 1
o Sofosbuvir + Daclatasvir (60mg) (+Ribavirin if cirrhosis)
• Genotype 5 and 6
o Weekly PEG-IFN
o Daily Ribavirin + Sofosbuvir for 12 weeks
6. HIV infection. Epidemiological situation in the world and the Republic of Belarus. Ways of
infection. Risk groups. Classification of HIV Infection (WHO Classification). Diagnostic of HIV
Infection. Principles of antiretroviral therapy. Clinical examination, prevention of opportunistic
infections.
EPIDEMIOLOGY
• 28.2 million people were accessing antiretroviral therapy as of 30 June 2021.
• 37.7 million people globally were living with HIV in 2020.
o 36.0 mil adults. 1.7 million children (0–14 years). 53% of all living with HIV were women and girls
• 1.5 million people became newly infected with HIV in 2020.
• 680 000 people died from AIDS-related illnesses in 2020.
• 79.3 million people have become infected with HIV since the start of the epidemic.
• 36.3 million people have died from AIDS-related illnesses since the start of the epidemic.
• 84% of all people living with HIV knew their HIV status in 2020.
• As of 30 June 2021, 28.2 million people were accessing antiretroviral therapy, up from 7.8 million in
2010. In 2020, 73% of all people living with HIV were accessing treatment.
• New HIV infections have been reduced by 52% since the peak in 1997.
• Sub-Saharan Africa is home to two thirds (67%) of people living with HIV.
• Belarus
o 1st case – 1987 was transmitted due to intravenous drug use
o Nowadays 80% cases are due to sexual transmission (mostly heterosexual) while 15% is due to IV
drug use and 5% due to MSM
o As of January 1, 2022, 32,026 cases of HIV infection were registered. In December 2021, 158 new
cases of HIV infection were detected
o Grodno region – 1300 cases (mostly in Lida and Grodno), leading cause is IV drug use and sexual
transmission
o Most number of cases is seen in Gomel region which is 10 times more than Grodno region and
mainly due to IV drug use
WAYS OF INFECTION
• Sexual
• Perinatal (intrapartum, peripartum, BF)
• Blood transfusion
• IDU / sharing needles
• Occupation (Needlestick injury, mucocutaneous exposure)
• The greatest epidemiological danger is posed by blood, semen and vaginal secretions, which have a
sufficient proportion of the infection for infection.
RISK GROUPS
• homosexuals, prostitutes
• IV drug addicts
• persons who often change sexual partners
• patients with hemophilia and other blood recipients
• heterosexual partners
• children of parents of one of the risk groups
• medical workers and police officers.
WHO CLASSIFICATION
Stage • Asymptomatic
1 • Persistent generalized lymphadenopathy
Stage • Moderate unexplained weight loss(<10% of presumed or measured body weight)
2 • Recurrent respiratory tract infections sinusitis, tonsillitis, otitis media and pharyngitis)
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulceration
• Papular pruritic eruptions
• Seborrheic dermatitis
• Fungal nail infections
Stage • Unexplained severe weight loss (>10% of presumed or measured body weight)
3 • Unexplained chronic diarrhea for longer than one month
• Unexplained persistent fever (above 37.6°C intermittent or constant, for longer than one
month)
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Pulmonary tuberculosis (current)
• Severe bacterial infections (such as pneumonia, empyema, pyomyositis, bone or joint
infection, meningitis or bacteremia)
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Unexplained anemia (<8 g/dl), neutropenia (<0.5 × 109 per liter)
• or chronic thrombocytopenia (<50 × 109 per liter)
Stage • HIV wasting syndrome
4 • Pneumocystis pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s
duration or visceral at any site)
• Esophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary tuberculosis
• Kaposi’s sarcoma
• Cytomegalovirus infection (retinitis or infection of other organs)
• Central nervous system toxoplasmosis
• HIV encephalopathy
• Extrapulmonary cryptococcosis including meningitis
• Disseminated non-tuberculous mycobacterial infection
• Progressive multifocal leukoencephalopathy
• Chronic cryptosporidiosis (with diarrhea)
• Chronic isosporiasis
• Disseminated mycosis (coccidiomycosis or histoplasmosis)
• Recurrent non-typhoidal Salmonella bacteremia
• Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated tumors
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or symptomatic HIV-associated cardiomyopathy
DIAGNOSTIC

• The methods of viral detection are used to diagnose HIV-infection when serological tests can be false-
negative → its used in babies and in healthcare workers who comes in contact with fluids of HIV patient
o HIV1 DNA PCR → detects proviral DNA in peripheral CD4 cells
o HIV RNA PCR →detects viral genome in plasma
o HIV RNA (VL) →diagnosis of acute infection (before seroconversion) and monitoring ART
PRINCIPLES OF ANTIRETROVIRAL THERAPY
• There are five classes of antiretroviral agent:
1) nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs);
▪ Retrovir, Divir, Stavir, Epivir, Ziagen, Tenofavir, Emtricitabine.
2) non-nucleoside reverse transcriptase inhibitors (NNRTIs);
▪ Delaverdin, Nevirapine, Ephavirenz
3) protease inhibitors (PIs);
▪ Invirase, Indinavir, Nelphinavir, Norvir, Kalerta, Fortavaza, Azatanovir, Fosamprenavir,
Darunovir, Tipranovir.
4) entry inhibitors:
▪ co-receptor antagonists - Malavroc
▪ fusion inhibitors - Enphuvirtide
5) integrase inhibitors (IIs).
▪ Raltegravir
• ART must be started for all patients with CD4 < 350 cells/mcL or with symptomatic diseases or AIDS
(stage 3 or 4 by WHO or category B or C by CDC).
• Usually prescribed HAART regimen contains 2NRTI+NNRTI or 2NRTI+PI. For example, according
WHO recommendation the regimen of the first choice is tenofovir (TDF)+emtricitabine
(FTC)+efavirenz (EFV).
• But any HAART regimen should be individualized to result the best therapeutic response, tolerability
and adherence, it could be possible only in the case of minimal toxicity and drug interaction.
• The treatment success or failure are determined using virologic, immunologic and clinical criteria.
• The virologic success is defined as VL decline below the level of detection (depending on assay, usually
< 50 copies/mL) and the retention of this result.
• Regardless of VL at the ART start VL must reduce by 1 log10 in 4 weeks and be undetectable in six
months at the latest.
• Immunologic success is evaluated by the CD4 count dynamics.
• Usually cells count grows 50–100 cells/mcL/year, but speed depends on many factors
OPPORTUNISTIC INFECTIONS (Clinical Exam, Prevention)
Indication for
Pathogen Clinical Exam Treatment
prophylaxis
P. jirovecii History of fever, progressive dyspnea, non- CD4+ HD IV TMP-SMX +
productive cough and hypoxemia on the exam <200/mm3, prior tapered-dose steroids
are characteristic. Chest x-ray shows diffuse, P. jirovecii (TMP-SMX 480 mg
bilateral, symmetrical interstitial infiltrates infection 1–2 tab q24h, or 960
with a ground glass pattern Discontinue mg 3 times weekly
when CD4+ until CD4 > 200
>200/mm3 for c/mcL at least 3
more than 3 months)
months
M. avium In the lung, nodules and cavitary lesions are CD4+ <50- Weekly azithromycin
complex common. Other manifestations include 100/mm3
pericarditis, soft tissue abscesses, skin lesions, Discontinue
lymph node enlargement, central nervous when CD4+
system lesions, and bone infection >100/mm3 for
more than 6
months
T. gondii •Focal encephalitis - headache, confusion, CD4+ DS TMP-SMX
moto weakness, fever <100/mm3 + (10 - TMP-SMX 480
•Non-focal - non-focal headache, psychological positive IgG mg 1–2 tab q24h. 20 –
symptoms serology ½ dose)
•Seizures, stupor, coma and death
M. fatigue, weakness, weight loss, and fever. PPD>5mm or INH for 9 months
tuberculosis Pulmonary tuberculosis features chronic cough high risk (+pyridoxine) or
and spitting of blood. Meningitis and urinary rifampin for 4 months
tract involvement may occur. Disseminated
bloodstream infections lead to lesions in many
organs (miliary tuberculosis)
Candida Oropharyngeal infections present as painless, Multiple Esophagitis –
creamy, white, plaque-like lesions in the oral recurrences fluconazole
cavity. These lesions scrape off easily. Angular Oral – fluconazole or
cheilosis is another feature. Esophageal nystatin swish and
candidiasis can present with retrosternal swallow
burning pain, odynophagia. Endoscopic testing
reveals white plaques as seen in the oral cavity.
HSV oropharyngeal disease, keratoconjunctivitis, Multiple Daily suppressive
genital herpes, eczema herpeticum, recurrence acyclovir,
encephalitis, and neonatal herpes. HSV famciclovir, or
proctitis, with deep, extensive, nonhealing valacyclovir
ulcers, generally seen in male patients in sexual
relations with male HIV patients
S. All pts PCV13 followed by
pneumoniae PSV23 in 2 months.
Give q5 years if
CD4+ >200/mm3
Influenza All pts Influenza vaccine
annually
7. Sepsis, septic shock. Etiological structure of sepsis in the clinic of infectious diseases. Classification.
Diagnostic criteria. Multiple organ failure. Principles of etiological verification and antibacterial
therapy of sepsis.
• Sepsis: a severe, life-threatening condition that results from a dysregulation of the patient's response to
an infection, causing tissue and organ damage and subsequent organ dysfunction. Diagnostic criteria
(SIRS criteria + suspected or confirmed underlying infection)
• Septic shock: a sepsis syndrome accompanied by circulatory and metabolic abnormalities that can
significantly increase mortality. Diagnostic criteria:
o Persistent hypotension: Vasopressors are required to maintain MAP ≥ 65 mm Hg.
o Persistent lactic acidosis: lactate > 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation
• Multiple organ dysfunction syndrome (MODS)
o Progressive and potentially reversible failure in the physiologic function of several organs and/or
systems
o The more organs that are affected, the greater the mortality risk
ETIOLOGY
• Common sources of sepsis:
o Respiratory: pneumonia (most common cause of sepsis)
o Abdominal infections (e.g., intraabdominal abscess)
o Genitourinary: pyelonephritis
o Skin and soft tissue infections
o Implanted devices (e.g., central venous catheter, port-a-cath, urinary catheter, endotracheal tube)
• Pathogens
o Bacterial: gram-positive bacteria (most common in the US); gram-negative bacteria
o Fungal, viral, or parasitic infection (rare)
• Common risk factors
o Age: < 1 year or > 75 years
o Primary comorbidities (diabetes mellitus, cirrhosis, community acquired pneumonia, bacteremia,
alcoholism)
o Immunosuppression (neutropenia, corticosteroid treatment)
o Intensive care or prolonged admission (nosocomial infections)
o Recent antibiotic or corticosteroid treatment
o Invasive medical devices (e.g., endotracheal tubes, intravenous lines, urinary catheters)

• Gram ⊕ shock (eg, staphylococci and streptococci) 2° to fluid loss caused by exotoxins.
• Gram ⊝ shock (eg, E coli, Klebsiella, Proteus, and Pseudomonas) 2° tovasodilation caused by
endotoxins (lipopolysaccharide).
• Neonates: GBS, E coli, Listeria monocytogenes, H influenzae.
• Children: H influenzae, pneumococcus, meningococcus.
• Adults: Gram ⊕ cocci, aerobic gram ⊝ bacilli, anaerobes (dependent on the presumed site of infection).
• IV drug users/indwelling lines: S aureus, coagulase ⊝ Staphylococcus species.
• Asplenic patients: Pneumococcus, H influenzae, meningococcus (encapsulated organisms).
CLASSIFICATION
• On clinical picture
o Systemic Inflammatory Response Syndrome (SIRS)
▪ Core body temperature >38°C or <36°C
▪ HR ≥90 bpm
▪ Respirations ≥20/min (or PaCO2 <32 mmHg)
▪ WBC ≥12,000/μl or≤4000/μl or >10% immature forms
o Sepsis
▪ At least two SIRS criteria caused by known or suspected infection
o Severe sepsis
▪ Sepsis with acute organ dysfunction
o Septic shock
▪ Sepsis with persistent or refractory hypotension or tissue hypoperfusion despite adequate fluid
resuscitation
▪ Sepsis + Vasopressin needed + Lactate ≥2
o Multi-Organ Dysfunction Syndrome (MODS)
▪ The presence of organ dysfunction in an acutely ill patient such that homeostasis cannot be
maintained without intervention
• On origin
o Community acquired
o Nosocomial
• On pathogen
o Bacterial
▪ MRSA (most common) / Bacteria resistant to Abx
▪ Nosocomial pathology
▪ Streptococcus / Klebsiella / Listeria / Enterococci / Clostridium / Pseudomonas aeruginosa /
Acinetobacter baumannii
o Viral - Herpes (1,2, CMV)
o Fungal - Candida
o Parasitic - Protozoa (toxoplasma gondii)
o Helminthic
• On location
o Urosepsis, Intrabdominal, odontogenic, pulmonary, cryptogenic, etc..
• On Focus
o Primary
▪ Percutaneous (surgical/gynecological – abortion)
▪ Dental (uveitis)
▪ Chronic tonsillitis
o Secondary
▪ Endogenous (by blood)

SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE (SOFA)

• Used in critical care settings as a tool to identify organ failure and predict mortality
• The score should be calculated after 24 hours of ICU admission and then every 48 hours.
• Should not be used to diagnose sepsis
QUICK SOFA (qSOFA)
• Is done when you think about possible sepsis. It uses three criteria, assigning one point for each
o Hypotension (SBP <100mmHg)
o Tachypnea (≥22 breaths/min)
o Altered mentation (GCS<15)
• ≥ 2 points means possible sepsis (high risk) and to confirm the diagnosis have to do SOFA
• A “positive" qSOFA Score (≥2) suggests high risk of poor outcome in patients with suspected infection.
These patients should be more thoroughly assessed for evidence of organ dysfunction.
• A positive qSOFA Score by itself should not trigger sepsis-directed interventions like initiation of broad-
spectrum antibiotics; rather, it should prompt clinicians to further investigate for presence of organ
dysfunction or to increase frequency of monitoring.
• The Sepsis-3 task force recommends that a positive qSOFA Score should prompt the calculation of a
SOFA score to confirm the diagnosis of sepsis. This remains controversial, as qSOFA has been shown to
be more predictive than SOFA outside of the ICU setting.
• Even if the qSOFA Score is initially "negative" (<2), it can be repeated if there is a change in the
patient’s clinical status
PRINCIPLES OF ETIOLOGICAL VERIFICATION
Microbiology
• In addition to blood cultures, consider additional cultures guided by clinical judgment
o Urinalysis and urine culture
o Sputum culture
o Consider also: CSF, wound secretion, tissue/fluid Diagnostic procedures as indicated to obtain
samples for cultures (e.g., lumbar puncture, thoracentesis, paracentesis, arthrocentesis)
• Pan cultures are discouraged unless the source of infection is unclear.
• When possible, obtain the additional samples before starting antibiotic treatment, but DO NOT DELAY
ANTIBIOTICS if samples are not rapidly available
Imaging
• Direct decisions based on clinical suspicion. Examples of commonly performed imaging include:
o Chest x-ray: if pneumonia is suspected and/or to determine if ARDS is present as a complication
o Abdominal x-ray: if a perforation or obstruction is suspected (pneumoperitoneum, air-fluid levels)
o Ultrasound
▪ Abdominal ultrasound: initial abdomen assessment in most cases
▪ Soft tissue: initial assessment of cellulitis and, in most cases, soft tissue abscess
o CT scan: for a more detailed assessment of thoracic and abdominal/pelvic pathology
o Echocardiography: to identify valve vegetations

ANTIBACTERIAL THERAPY FOR SEPSIS

• General recommendations
o Broad-spectrum antibiotics are part of the hour-1 bundle and should be started early (ideally as soon
as possible after blood cultures have been drawn).
o Choice of empiric antimicrobial therapy should be guided by:
▪ Source of infection
▪ Local prevalence of common and resistant pathogens
▪ Prior infections, immune status, and patient comorbidities
▪ Presence of implanted devices (e.g., urinary catheter, central lines)
o Therapy should be narrowed once the pathogen is identified.
o Control the source of infection as early as possible.
• Antibiotic therapy for sepsis
o There is no consensus regarding empiric antibiotic regimens for patients with sepsis and septic
shock, especially when the source of infection is unclear. The regimens mentioned here are examples
commonly mentioned in the literature.
o Unknown risk Factors
▪ Vancomycin
▪ PLUS one of the following
• Broad-spectrum carbapenem – Meropenem / Doripenem
• Extended-range penicillin/ B lactamase inhibitor – Piperacillin/tazobactam or
Ticarcillin/clavunate
• Third-generation (or higher) cephalosporin – Cefotaxime/Ceftriaxone/Ceftazidime/Cefipime
o At risk for specific pathogens
▪ MRSA – Vancomycin
▪ Resistant gram-negative organisms (e.g. Pseudomonas)
• At least one of the following – Carbapenem, Piperacillin/tazobactam or Cefepime
• Consider the addition of one of the following – Polymyxin B, Colistin or Aminoglycoside
▪ Anaerobes – consider adding Metronidazole
o Evident source of infection
▪ Start antibiotics effective against common pathogens of the source
▪ Some common infections responsible for sepsis include – pneumonia, PN, iintraabdominal
infections
8. Tropical malaria. Clinic, diagnostics, treatment and prevention. Complications of tropical malaria,
treatment.
• Plasmodium Falciparum
CLINIC
• More severe
• Relapsing / permanent fever – less correct temperature curve
• Less distinctly separated stages of attack
• General intoxication: headache, insomnia, nausea, vomiting, muscle and joint pain
• Relapse occur within a short period of time with great tenacity, but milder
• Malignant forms:
o Cerebral, with massive septic parasitemia and severe involvement of CVS, algid form with
predominantly vascular insufficiency, bilious fever, where signs of liver involvement on first place, as
well as swelling, renal form, hemorrhagic form
DIAGNOSTICS
• Blood:
o Anemia, thrombocytopenia, increased LDH, Uremia, reticulocyte, leucopenia, neutropenia with left
shit, lymphocytosis, monocytosis, (Monocytosis, eosinophilia and increased ESR in severe form)
• Thick and thin blood smear – check for erythrocytic parasite
o Giemsa staining, light microscopy
o Difficult to detect in first day of disease, but large amount is in 2-3 days
o Thick is done to confirm, thin is done to check for species
o Should be done in every 6 hours for 2-3 days
o Plasmodium disappears in blood after 3-4 days of treatment
• Rapid dipstick test
o Malarial Ag target
o Detect plasmodium LDH
• PCR

TREATMENT
• If not severe
o Chloroquine sensitive
▪ Chloroquine phosphate
• 1st: 1000mg of salt (600mg base) PO
• 2nd-4th: 500mg of salt (300mg base) PO at 6, 24 and 48 hours
▪ Hydroxychloroquine
• 1st: 800mg salt (620mg base) PO
• 2nd-4th: 400mg of salt (310mg base) PO at 6, 24 and 48 hours
o Chloroquine resistant
▪ Artemether-lumefantrine (1tab is 20mg artemether and 120mg lumefantrine) – 4 tabs PO/day.
• 3 -day course – Day 1 initial and second dose 8 hours apart, Day 2-3 BD
▪ Atovaquone-proguanil (tab 250mg atovaquone and 100mg proguanil) – 4 tabs PO OD 3 days
▪ Quinine sulfate + Doxycycline or Tetracycline or Clindamycin
• 650mg salt (542mg base) PO TDS 3 days Quinine sulfate
• Doxycycline: 100mg PO BD 7 days
• Tetracycline: 250mg PO QID 7 days
• Clindamycin: 20mg/kg/day PO TDS 7 days
▪ Mefloquine
• 1st: 750mg salt (648 base) PO
• 2nd: 500mg salt (456 base) PO at 6-12 hours after 1st
 o After completing the course (anti-relapse therapy)
▪ Primaquine phosphate 30mg base PO OD 14 days
▪ Tafenoquine 300mg PO 1 dose
• If severe
o IV artesunate 2.4mg/kg – 3 doses in 0, 12 and 24 hours
o If its not available, follow oral treatment as 3day malaria and discontinue when its available
o Monitor condition and if parasite density <1% give oral regimen.
o If >1% continue artesunate 6 more days until density goes below 1%
o If can’t tolerate oral meds, try NG tube administration or continue the IV artesunate

PREVENTION
• Fight against mosquito
o Eliminate its breeding sites
o Destruction of larvae and pupae in reservoirs
o Winged mosquito extermination
• Personal chemoprophylaxis
o In endemic population especially in hyperendemic foci
▪ Chloroquine 250mg twice a week
▪ Amodiaquine 400mg once a week
▪ Bigumal 300mg twice a week
▪ Chloridin 25mg weekly
o In non-immune to malaria visitors to hyperendemic foci
▪ 4-aminoquinolines 250mg twice a week
▪ 3 weeks before travel and continue whole trip and lasts 3-4 week after

COMPLICATIONS
• Allergic vasculitis
o Malarial purpura nephritis
o Necrosis in internal organs
o Malignant cerebral malaria: First excitement → stupefaction → coma
• True coma
o True coma only in tropical malaria: 3 periods
▪ Somnolence (stupefaction, sleepiness)
▪ Sopor, hibernation (consciousness returns at times, lies still)
▪ Full coma
o Patient is in full prostration: pale face, earthy, sunken eyes tightly closed
o Cause is large amount of blockage of brain capillaries with thrombi with subsequent organic changes
in it due to circulatory disorders and nutrition
o Dies in 3-5 days in absence of treatment
• Malarial Algid (Tropical malaria)
o Patient conscious. State of severe collapse, indifferent,
o Facial features are sharp, skin pale, cold to touch covered with sticky sweat
o Body temperature lowered, thread pulse, tendon reflex reduced, diarrhea
o Prognosis difficult, often active Rx and CV drugs cannot bring pt. out of collapse
• Hemoglobinuric fever (Tropical malaria)
o After taking quinine or other antimalarial drugs
o Acute hemolysis of RBC, hemoglobin saturation and excretion of Hb in urine
o Cause is autohemoglutination and hemolysis due to autoantibodies
o In urine when standing a copious sediment is grayish brown, occupying 1/3rd or half of total and
composed Hb and hyaline cylinders, particulate detritus, renal epithelium, RBC, WBC amount is not
big, supernatant is clear, red-brown or nearly black
o Methemoglobin band in spectral analysis of urine
o Profuse GI bleeding, retinal hemorrhage, anuria, fever and death in 3-5 days of RF
TREATMENT OF COMPLICATIONS
• At the development of malarial coma an initial dose of Quinine is 20 mg/kg in 10 ml/kg of 0.9% sodium
chloride/drip for 4 hours, 8 hours after the initial dose is changed to maintenance – 10 mg/kg/in for 4
hours, then repeated every 8 hours until the patient is able to take Quinine inside. When comatose and
algid form of tropical malaria and vivax form of three-day m., antimalarial drugs are administered
parenterally. With the improvement, the second dose can be given per os. In severe cases, the first dose of
Chloroquine is administered intravenously in isotonic glucose solution.
• Besides urgent antimalarial drugs in the treatment of malignant cerebral forms of tropical malaria,
emergency pathogenetic therapy is important. It is aimed at eliminating the increased permeability of the
vessel walls, the regulation of water-salt balance, elimination of edema of the brain, reducing hypoxia.
Steroid hormones are administered intravenously at the rate of 30 mg of prednisolone or 50 mg of
hydrocortisone in 250 ml of 5% glucose or dextrose solution, together with 10.5 ml of 5% solution of
Chloroquine, every 8 hours. Treatment is continued until a stable improvement of the patient
9. Dengue fever. Ebola Fever. Etiology. Epidemiology. Clinic, classification, diagnostics, treatment
and prevention.
DENGUE FEVER
ETIOLOGY
• Dengue virus (serotype: DENV 1-4)
• RNA virus of the genus Flavivirus
• Transmission
o Vector-borne; mosquito most commonly from the species Aedes aegypti
o Because of the approximately 7-day viremia in humans, bloodborne transmission is possible through
exposure to infected blood, organs, or other tissues (such as bone marrow).
o In addition, perinatal dengue transmission occurs when the mother is infected near the time of birth,
in which infection occurs via microtransfusions when the placenta is detached or through mucosal
contact with mother’s blood during birth.
EPIDEMIOLOGY
• Dengue is endemic throughout the tropics and subtropics and is a leading cause of febrile illness among
travelers returning from Latin America, the Caribbean, and Southeast Asia
CLINIC AND CLASSIFICATION
• Dengue fever without warning signs
o IP = 4-0 days after mosquito bite
o Duration of febrile phase = 2-7 days
o High fever (40oC) + 2 of the following symptoms during the febrile phase indicate dengue
▪ Severe headache
▪ Retro-orbital pain
▪ Severe arthralgia and myalgia (often referred to as “break-bone fever”)
▪ Maculopapular measles-like exanthem (typically 2-5 days after fever onset)
▪ Generalized lymphadenopathy
o Positive capillary fragility test
o Children are usually asymptomatic
• Dengue fever with warning signs
o Critical phase = increased risk of clinical deteriorations that occurs 3-7 days after symptoms onset
(coincides with fever abatement)
o Population at risk = individuals with a history of previous dengue infections, infants <1 years of age,
patients with severe comorbidities
o Abdominal pain, persistent vomiting, lethargy or restlessness, hepatomegaly (>2cm)
o Signs of fluid accumulation (pleural effusions +/- ascites)
o Hemorrhagic manifestations – petechia, epistaxis, gingival bleeding
• Severe dengue (formally called Dengue Hemorrhagic Fever or DHF)
o Typically occurs due to an Ab dependent reaction in patient who are reinfected with a different
serotype (occurs in 1-2% of cases)
o Generally develops as the initial fever subsides (~1 week after onset)
o Temperature change: ranges from hypothermia to a second spike in fever
o Severe hemorrhagic manifestations (e.g., petechiae, ecchymoses, purpura, hematemesis, melena) due
to thrombocytopenia (< 100,000/mm3)
o Severe organ involvement: Hepatomegaly, liver failure, Changes in mental status (e.g., confusion)
o Severely increased vascular permeability: Pleural effusion, respiratory distress, Ascites, abdominal
pain, Severe ↑ or ↓ Hct
o Positive capillary fragility test
• Dengue Shock Syndrome (DSS)
o Develops due to further deterioration of severe dengue
o Presence of both symptoms of severe dengue and circulatory collapse and shock due to plasma
leakage
DIAGNOSTICS
• Laboratory tests: Leukopenia, Neutropenia, Thrombocytopenia, ↑ AST, Hct significantly increased or
decreased in DHF (due to plasma leakage)
• Confirmation of diagnosis
o Acute phase (≤ 7 days after symptom onset)
▪ Serologic tests: MAC-ELISA to detect IgM
▪ Molecular Tests (NAAT) to detect viral RNA
▪ NS1 antigen test: detection of the Dengue NS1 antigen (Dengue non-structural protein 1) via
ELISA
• Allows early detection of the viral antigen in the serum
• A positive test confirms the diagnosis (without identifying the dengue serotype)
• A negative test does not rule out dengue infection; IgM testing should be performed
• Not recommended after day 7 of symptomatic infection (low sensitivity)
▪ Tissue tests (IHC)
o Convalescent phase (i.e., > 7 days after symptom onset)
▪ Serologic tests (IgM, IgG), Molecular Tests (NAAT), Tissue tests (IHC)
TREATMENT
• Symptomatic treatment
o Fluid administration to avoid dehydration
o Acetaminophen (avoid aspirin and other NSAIDs due to their anticoagulant properties)
• Dengue with warning signs and severe dengue
o Blood transfusions in case of significant internal bleeding (e.g., epistaxis, gastrointestinal bleeding,
or menorrhagia)
o Urgent resuscitation with IV fluids
PREVENTION
• Avoid exposure, use of mosquito repellent
• A tetravalent attenuated live vaccine (CYD-TDV)
o Recombinant yellow virus in which genetic material coding for the Dengue virus envelope and
premembrane proteins has been inserted
o Has been approved for use in children between 9–16 years of age who live in endemic areas and
have a laboratory confirmed prior dengue virus infection
 EBOLA FEVER
ETIOLOGY
• Etiology: Mononegavirales → Filoviridae → Ebolavirus
• Features of virus: elongated, negative sense RNA
• Zoonotic with bats being the most likely reservoir
• WOT – Direct contact (broken skin/mucosa) with sick patients’ body fluid (saliva, urine, feces, vomit,
semen), contaminated object and infected animal

CLASSIFICATION AND EPIDEMIOLOGY

• Ebola virus (Zaire ebolavirus):
o First isolated in 1976 during an outbreak in northern Zaire (now known as the Democratic Republic
of the Congo [DRC]). Seems to be the most virulent of the six species and has the highest case
fatality rate out of all species. It is responsible for the largest outbreak that started in West Africa in
2014, as well as smaller outbreaks in the DRC from 2017-2021.
• Sudan ebolavirus:
o First isolated in 1976 during an outbreak in southern Sudan. Causes an identical syndrome to Zaire
ebolavirus; however, the case fatality rate is lower
• Tai Forest ebolavirus (formerly known as Cote d'Ivoire ebolavirus):
o Only one case has been documented in 1994 in a Swiss researcher who performed an autopsy on a
dead chimpanzee in Tai National Park in Cote d’Ivoire. She recovered from the febrile phase of the
illness with no hemorrhagic complications.
• Bundibugyo ebolavirus:
o Discovered in 2007 during a single outbreak in the Bundibugyo district of western Uganda. The
isolated virus was identified as a distinct species, distantly related to Tai Forest ebolavirus.
• Reston ebolavirus:
o First isolated in Reston, Virginia, US in 1989 where it was found in Cynomolgus monkeys imported
from Philippines. Several workers exposed to infected animals were found to have positive serology,
but no clinical symptoms. Since then, the virus has also been isolated from swine in the Philippines.
• Bombali ebolavirus:
o First discovered in Sierra Leone in 2018 in the organs of the Angolan free-tailed bat (Mops
condylurus) and the little free-tailed bat (Chaerephon pumilus). It has also been identified in bats in
Kenya and Guinea. It is unknown whether this virus is pathogenic in humans.
CLINIC
• IP = 5-10 days (2-21 days)
• Abrupt onset of Fever (>38.6oC), myalgia and headache
• Nausea, vomiting, diarrhea, chest pain, cough, pharyngitis
• Photophobia, lymphadenopathy, conjunctival injection, jaundice and pancreatitis
• CNS → somnolence, delirium and coma
• Bleeding → petechia, hemorrhage, ecchymoses around needle puncture sites, mucosal hemorrhage
• Maculopapular rash in 7-10 days (1-21 days) after onset
• In 2nd week → defervesces and improves markedly or dies in shock with organ failure, accompanied by
DIC, anuria and liver failure
• Convalescence maybe protracted accompanied by arthralgia, orchitis, recurrent hepatitis, transverse
myelitis or uveitis
DIAGNOSTICS
• Clinical – epidemic and clinical (acute febrile illness, hemorrhagic signs)
• CBC: Lymphopenia, neutrophilia, thrombocytopenia and abnormal PLT aggregation.
• Increase AST > ALT
• ELISA and RT-PCR (sero conversion in about 8-12 days)
• Skin biopsy (viral Ag)
• Isolated from serum or anterior chamber fluid in orchitis or uveitis
TREATMENT
• Isolation
• Supportive (control blood volume and electrolyte balance, manage complications)
• Human IF and convalescent plasma have been used
• Recombinant inhibitor of TF VII complex in severe cases
PREVENTION
• Sterilize injection equipment, protect from body fluids and skin contact during preparing dead, barrier
nursing precaution
• Adenovirus-vectored Ebola glycoprotein gene undergoing trials
10. Yellow fever. Etiology. Epidemiology. Clinic, classification, diagnostics, treatment and prevention.
ETIOLOGY
• Pathogen: yellow fever virus
o Genus: flavivirus, type of arbovirus
o Genetics: single-stranded, positive-sense, linear RNA virus
o Appearance: enveloped, icosahedral
• Transmission
o Vectors: mosquitoes; (primarily Aedes aegypti)
o Main reservoir: primates (human and non-human)
o Different transmission cycles (depending on local circumstances and geography)
▪ Sylvatic (jungle) – transmission between nonhuman primates and mosquitos in forest canopy.
Transmitted via mosquito from monkeys to humans when occupational or recreational activities
encroach into jungle
▪ Intermediate (savannah) – in Africa, transmission from tree hole-breeding Aedes spp to humans in
jungle boarder areas. Maybe transmitted from monkeys to humans or from humans to humans via
these mosquitos
▪ Urban – transmission between humans and peridomestic mosquitoes, primarily Ae. Aegypti
EPIDEMIOLOGY
• Sub-Saharan Africa and Tropical South America – Endemic and intermittently epidemic
• Most due to sylvatic or intermediate transmission, but urban occurs periodically in Africa and sporadically
in America
• In Africa with persistent circulation, natural immunity accumulates with age; infants and children are at
high risk
• In South America most frequently occurs in unimmunized
CLINIC AND CLASSIFICATION
• Incubation time: 3–6 days
• The majority of infected individuals remain asymptomatic.
• In symptomatic patients: classic progression in three stages
o Period of infection (3–4 days)
▪ Sudden onset of high fever (up to 41°C, or 105°F)
▪ Headaches, chills, Nausea, vomiting
o Period of remission (up to 2 days)
▪ Easing of symptoms and decline in fever
o Period of intoxication (only in ∼ 15% of symptomatic patients)
▪ Hemorrhage (epistaxis, mucosal bleeding, melena, hematuria, black vomiting)
▪ Multiorgan dysfunction (e.g., acute kidney and liver failure)
▪ Abdominal pain, severe jaundice
DIAGNOSTICS
• Laboratory tests:
o ↑ ALT/AST, Leukopenia
o In period of intoxication: Thrombocytopenia, ↑ PTT, Signs of organ failure
• Virus detection: PCR, ELISA
• Liver biopsy
o Used for definitive diagnosis (e.g., postmortem)
o Must not be done while the patient has an active yellow fever infection
o May show Councilman bodies (eosinophilic apoptotic globules)
TREATMENT
• There are no specific medications to treat YF virus infections; treatment is directed at symptomatic relief
or life-saving interventions.
• Rest, fluids, and use of analgesics and antipyretics may relieve symptoms of aching and fever.
• Care should be taken to avoid medications such as aspirin or nonsteroidal anti-inflammatory drugs, which
may increase the risk for bleeding.
PREVENTION
• YF can be prevented by a relatively safe, effective vaccine.
• All YF vaccines currently manufactured are live attenuated viral vaccines.
• YF vaccine is recommended for people aged ≥9 months who are traveling to or living in areas with risk
for YF virus transmission in South America and Africa.
• For all eligible people, a single 0.5-mL injection of reconstituted vaccine should be administered
subcutaneously
11. Visceral and cutaneous leishmaniasis: etiology, epidemiology, clinical presentation, diagnostics,
treatment, prevention.
ETIOLOGY
• Pathogen: Leishmania donovani (protozoan)
o Cutaneous leishmaniasis
▪ Americas: L. mexicana, L. braziliensis, L. guyanensis, L. panamensis (L. braziliensis, L.
guyanensis, L. panamensis can also cause mucosal leishmaniasis)
▪ Asia/Africa: L. major, L. tropica. L. aethiopica
o Visceral leishmaniasis: L. donovani, L. infantum
• Transmission
o Vector: phlebotomine sandflies
o Reservoir: mammals (especially dogs, humans, and rodents)
EPIDEMIOLOGY
• Distribution: endemic in the Mediterranean region, Africa, India, southwest and central Asia, South and
Central America
• Incidence (worldwide):
o Visceral: 50,000– 90,000 infections/year
o Cutaneous: 600,000–1,000,000 infections/year
CLINIC - CUTANEOUS
• Localized cutaneous leishmaniasis
o Incubation period: weeks to months
o Manifestation: solitary or multiple reddish macules/papules around the sandfly bite that quickly
increase in size and develop central ulceration
• Mucosal leishmaniasis
o Some Leishmania subtypes (e.g., L. braziliensis, L. guyanensis, L. panamensis) cause mucosal
leishmaniasis, which can develop months to years after cutaneous leishmaniasis that was not treated
properly
o Manifestation: commonly affects the nasopharynx (mucosal bleeding, nasal blockage)
CLINIC – VISCERAL
• Incubation period: 2–6 months
• Many patients are asymptomatic.
• Kala-azar (Hindi for “black fever,” in reference to the darkening of the skin it can cause)
• Usually insidious progression
• Flu-like symptoms, spiking fevers
• Weight loss
• Lymphadenopathy
• Hepatosplenomegaly
• Ascites and edema
• Pancytopenia
• Possible darkened or gray skin color (especially on the palms and soles)
• Immunosuppression may lead to secondary bacterial infections in advanced disease
DIAGNOSTICS – CUTANEOUS
• Detection of the pathogen in skin biopsy
o Microscopy: macrophages that contain amastigotes, the intracellular, nonmotile form of Leishmania
(appear as ovoid inclusions)
o PCR
o Culture (Novy-Nicolle-McNeal medium)
DIAGNOSTICS – VISCERAL
• Laboratory tests: Hemolytic anemia, Neutropenia, eosinopenia, thrombocytopenia
• Detection of pathogen
o Microscopy of tissue biopsy (e.g., bone marrow) with visualization of macrophages with amastigotes
o PCR
TREATMENT - CUTANEOUS
• The objective of treatment is to manage clinical symptoms.
• Uncomplicated disease (no immunosuppression, small lesions, no mucosal involvement)
o No systemic treatment
o Local treatment (cryotherapy, thermotherapy, or topical paromomycin) for skin lesions that do not heal
spontaneously.
• Complicated disease (mucosal involvement, numerous lesions, immunosuppression) – treat as visceral
TREATMENT - VISCERAL
• Amphotericin B is the preferred monotherapy in Europe, North America, and South America.
• Other drugs that may be used include: Sodium stibogluconate, Miltefosine, Paromomycin
PREVENTION
• Early diagnosis and effective prompt treatment reduces the prevalence of the disease and prevents
disabilities and death. It helps to reduce transmission and to monitor the spread and burden of disease.
• Vector control helps to reduce or interrupt transmission of disease by decreasing the number of sandflies.
Control methods include insecticide spray, use of insecticide–treated nets, environmental management and
personal protection.
• Control of animal reservoir hosts is complex and should be tailored to the local situation
12. Cholera: etiology, epidemiology, pathogenesis, clinic. diagnostics, treatment and prevention.
ETIOLOGY
• Vibrio cholerae
• Family is Vibrionaceae, and shares common characteristics with Enterobacteriaceae
• Curved gram-negative bacilli
• Ag structure: H (Flagellar) and O (Somatic) – O1 and Non O1
• Out of 206 serogroups, O1 and O139 are associated with clinical cholera
• 2 biotypes of O1
o Classic – responsible for first 6 pandemics, cause an approx. equal number of symptomatic and
asymptomatic cases
o El tor – causes more asymptomatic infection 20-100:1
EPIDEMIOLOGY
• Endemic, Epidemic (Ukraine and Africa) and Pandemic disease
• 2 main reservoirs – Humans and Water
• Transmission – Fecal-oral via contaminated water*/food. Can also be contact way
• Children are mostly infected
PATHOGENESIS
• Enters through oral route and are partially killed in stomach due to acid, and the other part goes into small
intestine → alkaline medium promotes growth of pathogen → forms endotoxin, enterotoxin and
permeability factor
• Exotoxin choleragen (main) → activate adenylatecylase → increases cAMP → block absorption of
Na+/Cl- in lumen → promotes secretion of water and electrolytes into lumen
• In severe form, hypovolemic shock develops with tissue hypoxia, metabolic acidosis and respiratory
alkalosis, renal, liver and myocardium insufficiency, dehydration
CLINIC
• IP=1-2 days
• Begins with sudden onset of painless watery diarrhea (rice water) that may quickly become voluminous
and often followed by vomiting (like stool – rice water)
• Fever absent (or low grade)
• Nowadays mostly asymptomatic and mild to moderate form will not be clinically distinguishable from
other causes of gastroenteritis
• Cholera gravis – Severe watery diarrhea, vomiting and dehydration
• If untreated → isotonic dehydration → acute tubular necrosis and renal failure
• In severe → vascular collapse, shock (vomiting and diarrhea stops as pressure drops and secretion
decreases) and death
• Consciousness well up to death
DIAGNOSTICS
• WHO
o In an area where disease not epidemic – patient age ≥5 years develop severe dehydration or dies from
acute watery diarrhea
o In an area where cholera is epidemic – patient age ≥5 years develops acute watery diarrhea, with or
without vomiting
• Direct microscopy of stool with gram staining, culture, and serotype and biotype identification
• PCR
• Leukocytosis with stab shift, Hct 65-70%
• Electrolytes concentration decreased, decompensated metabolic acidosis and respiratory alkalosis
observed
TREATMENT
• WHO
1. Assess for dehydration.
2. Rehydrate the patient and monitor frequently, then reassess hydration status.
3. Maintain hydration; replace ongoing fluid losses until diarrhea stops.
4. Administer an oral antibiotic to the patient with severe dehydration.
5. Feed the patient
• Main goal is to restore fluid losses by rehydration
o Rehydration:
▪ Restore to normal in < 4hours
▪ IV inf in severely dehydrated patients 50-100 ml/kg/hr
▪ Lactate Ringer solution preferred over isotonic NaCl because saline doesn’t correct metabolic
acidosis
▪ After rehydration, all signs of dehydration abated and patient should be able to pass urine at
rate 0.5 ml/kg/hr or more
o Maintenance:
▪ Maintain normal hydration status by replacing ongoing losses
▪ PO 50-100 ml/hr
• Abx
o Ciprofloxacin 500mg OD/BD (Nowadays use 1g one dose)
o Tetracycline 500mg QID
o Doxycycline 100mg BD
o Azithromycin 1g one dose
o Ampicillin 500mg QID
• Hypovolemic shock
o IV access
o O2
o Inotrope (NE, Dopamine) – increase heart contractility
o Rehydration therapy

PREVENTION
• Safe food and water precautions and frequent handwashing are critical in preventing cholera.
Chemoprophylaxis is not indicated.
• CVD 103-HgR, a single-dose oral cholera vaccine (Vaxchora, Emergent BioSolutions), is licensed and
available in the United States. The vaccine was previously marketed under the names Orochol and Mutacol
in other countries. Vaxchora was approved in June 2016 for use in adults ≥18 years of age.
13. African trypanosomiasis (Gambian and Rhodesian). Etiology, epidemiology, clinic, diagnostics,
treatment and prevention.
ETIOLOGY
• Pathogen: Trypanosoma brucei
o T. brucei is a hemoflagellate protozoan
o Two subspecies: Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense
o A rare but new form of T. evansi that causes sleeping sickness has been identified in India.
• Route of infection: vector transmission by the bite of the tsetse fly (the bite is usually painful and
remembered by the patient)
EPIDEMIOLOGY
• Distribution: sub-Saharan Africa
CLINIC
• Stage I (hemolymphatic phase)
o Intermittent fever: caused by antigenic variation
o Painless lymph node enlargement
o Winterbottom sign: painless cervical lymphadenopathy in the posterior triangle of the neck
o Trypanosomal chancre (local primary lesion)
▪ A red, painful, indurated, nodular swelling; 2–5 cm in size that develops at the bite site within 2
weeks of the bite
▪ Resolves spontaneously within 1–2 weeks
▪ The nodule may ulcerate and form a painful chancre
o Erythematous, annular (targetoid), or maculopapular rash that may or may not be pruritic
o Malaise, headache, arthralgia
o Symptoms of anemia
o Facial edema, Possible hepatosplenomegaly
o Occasionally, arrhythmias, hypotension, and symptoms of myocarditis
• Stage II (neurologic phase)
o Headache, Weight loss
o Behavioral changes: confusion, apathy, psychosis
o Daytime somnolence, which may be associated with night-time insomnia
o Ataxia
o Kerandel sign: delayed hyperesthesia
o Cachexia
o Coma
o Death
DIAGNOSTICS
• General findings: anemia, granulocytopenia, ↑ ESR, ↑ IgM levels
• Confirmatory tests
o Local primary lesion: direct visualization of trypomastigotes using a Giemsa stain in chancre fluid
o Stage I: direct visualization of trypomastigotes in thin and thick peripheral blood smears or lymph
node aspirates using a Giemsa stain
o Stage II: lumbar puncture and CSF examination
▪ Trypomastigotes may be directly visualized.
▪ Lymphocytic pleocytosis
▪ ↑ IgM and protein levels
▪ Morula cells of Mott
TREATMENT
• Early in-patient treatment is very important.
• The drug of choice for trypanosomiasis is dependent on the stage of the disease and the subspecies of T.
brucei (see the table below).
• Follow-up: CSF examination should be repeated every 6 months for 2 years.
PREVENTION
• Instructions for people traveling to or working in endemic regions
o Use preventive measures in the daytime (tsetse flies bite during the day)
o Wear long-sleeved protective clothing with neutral colors
o Use insect repellants
o Avoid tsetse fly habitats (e.g., thickets, bushes)
o Inspect vehicles before entering
• Public health measures in endemic regions
o Vector control methods such as insecticide spraying and fly traps
o Population screening programs and early treatment of infections to decrease number of human hosts
West African Sleeping Sickness East African Sleeping Sickness
(Gambian trypanosomiasis) (Rhodesian trypanosomiasis)
Pathogen T. brucei gambiense T. brucei rhodesiense
Vector Tsetse fly (Glossina palpalis) Tsetse fly (Glossina morsitans)
Region Central and West Africa Eastern and SE Africa
1o Reservoir Humans Cattle, antelope
o Acute disease with poor demarcation
o Chronic, slowly progressive disease between stages
o Trypanosomal chancre is less common o Trypanosomal chancre is more
o Low parasitemia common
Clinical
o Lower risk of myocarditis o High parasitemia
course
o Trypanids are less common o Higher risk of myocarditis
o Prominent lymphadenopathy o Trypanids are more common
o Late CNS manifestations o Mild lymphadenopathy
o Early CNS manifestations
Treatment
• Stage o First line – Pentamidine, Fexinidazole
o Suramin
I o Second line – Suramin
o First line – Eflornithine + Nifurtimox.
• Stage
Fexinidazole o Melarsoprol
II
o Second line – Melarsoprol
14. Brucellosis: etiology, epidemiology, clinic, diagnostics, treatment and prevention.
ETIOLOGY
• Pathogen: Brucella spp. are facultative intracellular, gram-negative, aerobic, coccobacilli.
o Brucella melitensis: mainly affects sheep, goats, and camels → Malta fever
o Brucella abortus: mainly affects cattle, but also bison, deer, and elk → Bang disease
o Rare causes of disease in humans
▪ Brucella suis: mainly affects (feral and domestic) pigs and reindeer, but also cattle and bison
o Brucella canis: affects dogs
• Transmission: zoonotic
o Contaminated food, esp. raw meat, unpasteurized dairy products
o Contact with infected animals
o Inhalation of contaminated aerosol
• Risk factors: occupational or recreational exposure to infected animals and animal products (e.g., farmers,
veterinarians, hunters, slaughterhouse workers, laboratory personnel)
EPIDEMIOLOGY
Type Source of infection Distribution
B. abortus Cattle Japan, Canada, N. Europe, Israel, Australia, NZ
B. suis Pigs, hares, deer S. America, A. Asia, USA, Australia
B. melitensis Goats, sheep, camels Mediterranean, Asia, Latin America, Africa, S. Europe
B. canis Dogs N and S America, Japan, C. Europe
B. ovis Sheep -

CLINIC
• Incubation period: 1–3 weeks
• General
o Flu-like symptoms
o Night sweats
o High, potentially undulant fever
o Painful lymphadenopathy
• Localized infection
o Arthralgias, low back pain → osteoarticular infection (e.g., osteomyelitis, spondylitis)
o Epididymal and testicular tenderness, flank pain → genitourinary infection (e.g., epididymo-orchitis,
pyelonephritis)
o Murmurs, friction rubs, tachycardia → cardiac infection (e.g., endocarditis, myocarditis)
DIAGNOSTICS
• Laboratory studies: may show anemia, neutropenia, mild elevation of liver enzymes
• Serology
o Rose Bengal test: a rapid agglutination assay used for the serological diagnosis of brucellosis
o ELISA
• Confirmatory test
o Blood culture (may be false negative)
o Lymph node or bone marrow biopsy specimen and culture
▪ Histopathology: noncaseating granulomas
▪ Culture medium for isolation: charcoal yeast extract agar (cysteine and iron buffered)
TREATMENT
• >8 years
o Combination therapy to decrease the incidence of relapse:
▪ Oral doxycycline (2–4 mg/kg per day, maximum 200 mg/day, in 2 divided doses) or oral
tetracycline (30–40 mg/kg per day, maximum 2 g/day, in 4 divided doses) -and-
▪ Rifampin (15–20 mg/kg per day, maximum 600–900 mg/day, in 1 or 2 divided doses).
▪ Recommended for a minimum of 6 weeks.
o Combination therapy with trimethoprim-sulfamethoxazole (TMP-SMZ) can be used if tetracyclines
are contraindicated.
• <8 years
o Oral TMP-SMZ (trimethoprim, 10 mg/kg per day, maximum 480 mg/day; and sulfamethoxazole, 50
mg/kg per day, maximum 2.4 g/day) divided in 2 doses for 4 to 6 weeks.
o Combination therapy: consider adding rifampin. Consult physician for dosing or if rifampin is
contraindicated. Tetracyclines (such as doxycycline) should be avoided in children less than 8 years
of age.
• Complicated cases
o Streptomycin or gentamicin for the first 14 days of therapy in addition to a tetracycline for 6 weeks
(or TMP-SMZ if tetracyclines are contraindicated).
o Rifampin can be used in combination with this regimen to decrease the rate of relapse.
o For life-threatening complications, such as meningitis or endocarditis, duration of therapy often is
extended for 4 to 6 months.
o Case-fatality rate is < 1%.
o Surgical intervention should be considered in patients with complications such as deep tissue
abscesses.
PREVENTION
• The best way to prevent brucellosis infection is to be sure you do not consume:
o undercooked meat
o unpasteurized dairy products, including: milk cheese ice cream
• People who handle animal tissues (such as hunters and animal herdsman) should protect themselves by
using:
o rubber gloves
o goggles
o gowns or aprons
15. Typhoid fever: etiology, epidemiology, clinical presentation, diagnostics, treatment and prevention.
ETIOLOGY
• Salmonella typhi and Salmonella paratyphi (serotypes A, B, and C)
o Gram -ve rod, encapsulated
o Faculatative intracellular, motile, non-spore forming
o Facultative aerobe, can ferment glucose but NOT lactose
EPIDEMIOLOGY
• Host: Humans
• Way of transmission:
o Food/water (mostly) contaminated by fecal matter of ill or asymptomatic carriers
o Sexual in MSM
o In Healthcare workers after exposure to patients / handling specimen
• Most prevalent in South-central and SE Asia
• Medium in rest of Asia, Africa, Latin America and Oceania (excluding Australia and NZ)
• Low in rest of the world
• Most common in urban areas and in young children and adolescence
• Risk Factors
o Contaminated ice/water
o Flood
o Food purchased from street vendors
o Raw fruits and vegetables grown in field fertilized with sewage
o Ill household contact
o Lack of hand hygiene and toilet access
o Evidence of prior H. pylori infection
• 1:4 → paratyphoid : typhoid
CLINIC
• IP = 7-14 days
• 1st Week
o Mounting fever with relative bradycardia, malaise, headache and cough (dry)
o Epistaxis and abdominal pain
o Constipation
• 2nd Week
o Continuous high fever (40oC) and bradycardia (sphygmothermic dissociation, with dicrotic pulse wave
o Delirium, mostly calm, but sometime agitate. “nervous fever”. Apathy
o Rose spots on lower chest and abdomen (resolve in 2-5 days)
o Diarrhea (6-8/day, green with smell like pea soup)
o Hepatosplenomegaly, abdominal distention
• 3rd Week
o Continuous fever, delirium (typhoid state), drowsiness, gross abdominal distension, diarrhea
o Complications start to occur
o Intestinal perforation
o Encephalitis
o Neuropsychiatric complication (“muttering delirium”) with imaginary object
o By the end, fever starts to subside (defervesce)
• 4th Week
o Recovery stage, fever and delirium begin to recede which can last up to 2 or more months
DIAGNOSTICS
• So, test is specific other than positive culture (blood, BM, other sterile sites, rose spots, stool or intestinal
secretions)
o Sensitivity of blood culture is 90% at first and decrease to 50% by third week
o Bone marrow culture is highly sensitive 90% even with Abx treatment
o Intestinal secretion can be positive despite negative BM culture
o Stool although negative in 60% cases in 1st week, becomes positive in 3rd week
• CBC: lymphocytosis (mostly in children <10 years), leucopoenia and neutropenia
• Stool: increase leukocytes
• Biochem
o Increased creatinine and urea
o Decreased electrolytes
o Decreased AST, ALT and bilirubin
• WIDAL (≥ 1:200)
o Negative in first week
o Strongly positive in 2nd week with antiO and antiH antibodies
o Raising high titer of “O” Ab Acute
o Raising high titer “H” Ab identify type
TREATMENT
• First-line treatment: fluoroquinolones (e.g., ciprofloxacin 500mg BD PO 5-7 days OR 400mg BD IV)
• Azithromycin (1g/d PO 5 days), if resistance to fluoroquinolones is suspected (e.g., in patients with
infection acquired from certain regions, such as South Asia)
• Third-generation cephalosporins (e.g., ceftriaxone 1-2g/d IV 7-14 days) are preferred for severe infection.
• Antibiotics prolong the duration of fecal excretion of bacteria.
PREVENTION
• Food and water safety
• Vaccination
o Indication: The WHO recommends typhoid fever vaccination to those traveling to high-risk areas (East
and Southeast Asia, South and Central America, Africa).
o Administration: A parenteral, inactivated vaccine and an oral, live vaccine are available for active
immunization, and both provide similar levels of protection.
▪ Inactivated vaccine: one intramuscular injection containing Vi polysaccharide (part of S. typhi
capsule), ideally administered at least 10 days before traveling
▪ Live-attenuated vaccine: oral ingestion of capsules containing live attenuated S. typhi; ideally
administered at least 10 days before traveling
16. Schistosomiasis: etiology, epidemiology, clinical presentation, diagnostics, treatment and prevention
of intestinal, urinary and Japanese schistosomiasis.
ETIOLOGY
• Pathogen: schistosomes (parasitic trematodes or flukes of the genus Schistosoma)
o Schistosoma mansoni: Africa, South America, and the Carribean
o Schistosoma haematobium: Africa and the Middle East
o Schistosoma japonicum: China and Southeast Asia
• Lifecycle
o Infected humans (definitive host) excrete schistosome eggs in urine or feces.
o Eggs hatch in water and release miracidia
o Miracidia infect specific freshwater snails (intermediate hosts) where they develop into cercaria, which
are released back into the water.
o When humans come in contact with contaminated water (e.g., while swimming), cercaria can penetrate
the skin and enter the circulation.
o Maturation into adult schistosomes and migration to the veins of the target organs
o Females lay eggs, leading to capillary closure and chronic inflammation in the affected organs.
o Penetration of eggs in lumen of the intestine or bladder (depending on the species).
EPIDEMIOLOGY
• Mainly rural areas with freshwater sources and poor sanitation
CLINIC – Clinical features depend on the stage, schistosome type, and infected organs.
• Local reaction (swimmer's itch or cercarial dermatitis): pruritic maculopapular rash at the point of
entry of cercaria into human skin
• Acute schistosomiasis syndrome (Katayama fever)
o Serum sickness-like disease: immune complex formation of antigens released from eggs and/or adult
worms with host antibodies
o Incubation period: 3–8 weeks
o Clinical features: fever, fatigue, cough, myalgia, angioedema
o Patients usually spontaneously recover after 2–10 weeks.
• Chronic schistosomiasis: Deposition of eggs leads to chronic inflammation and granuloma formation.
Subtypes
• Genitourinary (S. haematobium)
o Hematuria, dysuria
o Complications (especially with chronic infection)
▪ Squamous cell carcinoma of the bladder (may cause painless hematuria)
▪ Infertility (particularly in women )
▪ Bladder neck obstruction and hydronephrosis
• Hepatosplenic (S. mansoni, S. japonicum, S. haematobium (less common))
o Children and adolescents: hepatosplenomegaly
o Adults with chronic infection: periportal fibrosis and portal hypertension
o Complications: pulmonary schistosomiasis, neuroschistosomiasis
• Intestinal (S. mansoni, S. japonicum, S. haematobium (less common))
o Diarrhea, abdominal pain, intestinal bleeding, bowel strictures
• Pulmonary (S. mansoni, S. japonicum, S. haematobium)
o Pulmonary HTN and cor pulmonale
• Neuro (S. mansoni, S. japonicum, S. haematobium)
o Headache, transverse myelitis, sensory and motor deficits, epilepsy
DIAGNOSTICS
• Laboratory tests: eosinophilia
• Pathogen detection
o Serology
o Definitive diagnosis (gold standard): direct visualization of schistosome eggs via stool or urine
microscopy. Egg morphology is indicative of Schistosoma subtype:
▪ Schistosoma mansoni: Eggs have a prominent lateral spine.
▪ Schistosoma haematobium: Eggs have a prominent terminal spine.
▪ Schistosoma japonicum: Eggs have a miniscule lateral spine.
• Further tests
o Imaging may be required to rule out specific organ involvement.
o Detection of antigens in urine/stool sometimes used to measure treatment efficacy
TREATMENT
• Acute schistosomiasis syndrome
o Corticosteroids
o Praziquantel should only be administered after symptoms of acute illness have resolved.
• Chronic schistosomiasis: praziquantel
• Swimmers itch: symptomatic with cool compresses, baking soda, or antipruritic lotions. Topical
corticosteroids can also be used.
PREVENTION
• Avoid swimming in freshwater or wear protective clothing if contact is unavoidable.
• Boil water prior to drinking.
• Drinking water or water used for bathing should not come into contact with sewage systems, feces, or
urine.
17. Drankunculosis: etiology, epidemiology, clinic, diagnostics, treatment and prevention.
ETIOLOGY
• Causal Agents
o Dracunculiasis (Guinea worm disease) is caused by the nematode (roundworm) Dracunculus
medinensis.
• Life Cycle
o Humans become infected by drinking water containing infected microcrustaceans (copepods).
o Larvae are released, penetrate bowel wall, and mature in abdominal cavity into adult worms in ~1 year.
o After mating, the male dies, and the gravid female migrates through subcutaneous tissues, usually to
the distal lower extremities.
o The cephalic end of the worm produces an indurated papule that vesiculates and eventually ulcerates.
o On contact with water (eg, when a person attempts to relieve the severe discomfort by immersing the
affected limb), a loop of the worm’s uterus prolapses through the skin and discharges motile larvae.
o Worms that do not reach the skin die and disintegrate or become calcified.
o Larvae are ingested by copepods.
o In most endemic areas, transmission is seasonal and each infectious episode lasts about 1 year.
EPIDEMIOLOGY
• An ongoing eradication campaign has dramatically reduced the incidence of dracunculiasis, which is now
restricted to rural, isolated areas in a narrow belt of African countries.
CLINIC
• Dracunculiasis is typically asymptomatic for the first year.
• Symptoms develop when the worm erupts through the skin.
• Local symptoms include intense itching and a burning pain at the site of the skin lesion.
• Urticaria, erythema, dyspnea, vomiting, pruritus are thought to reflect allergic reactions to worm antigens.
• If worm broken during expulsion/extraction, severe inflammatory reaction ensues, causing disabling pain.
• Symptoms subside and the ulcer heals once the adult worm is expelled.
• In about 50% of cases, secondary bacterial infections occur along the track of the emerging worm.
• The chronic stage of infection is associated with inflammation and pain in the joints and other signs of
arthritis. Sequelae include fibrous ankylosis of joints and contraction of tendons
DIAGNOSTICS
• Clinical evaluation
• Diagnosis of dracunculiasis is obvious once white, filamentous adult worm appears at the cutaneous ulcer.
• Calcified worms can be localized with x-ray examination; they have been found in Egyptian mummies.
TREATMENT
• Manual removal
• Treatment of dracunculiasis consists of slow removal of the adult worm (which may be up to 80 cm long)
over days to weeks by rolling it on a stick. Surgical removal under local anesthesia is an option but is
seldom available in endemic areas.
• There are no effective anthelmintic drugs for this disease; beneficial effect of metronidazole (250 mg
orally TDS for 10 days) has been ascribed to the drug’s anti-inflammatory and antibacterial properties.
PREVENTION
• Filtering drinking water through a piece of fine-mesh cloth, chlorination, or boiling effectively protects
against dracunculiasis. Infected people should be instructed not to enter drinking water sources to avoid
contaminating them
18. Strongyloidosis: etiology, epidemiology, clinical picture, diagnostics, treatment and prevention.
ETIOLOGY
• Strongyloides stercoralis (threadworm)
• Threadworms are nematodes
• Mode of transmission: percutaneous penetration of larvae (primarily via the feet)
Life cycle
• The Strongyloides eggs hatch in the human intestine and release larvae→ Larvae are excreted with the
feces and contaminate the soil→ Larvae penetrate the intact skin of the definitive host upon contact with
contaminated soil → Larvae migrate to the lungs via the bloodstream → Larvae migrate to the pharynx
via the alveoli and bronchial system → Larvae are swallowed, causing autoinfection → Larvae mature
into adult, egg-producing worms in the intestine → Eggs develop into infectious larvae and are excreted
in feces.
• Hyperinfection: Some larvae may penetrate the intestinal wall and enter the bloodstream (rare).
• Incubation period: 1–4 weeks
EPIDEMIOLOGY
• Strongyloidiasis is distributed mainly in countries of the tropical and subtropical zone. Sporadic cases are
possible in countries with a temperate climate. Helminthiasis occurs in Moldova, Central Asia, Russia (in
the southern and some central regions), in Ukraine, in the Transcaucasian countries.
CLINIC
• Cutaneous phase
o Swelling, erythema, maculopapular rash
o Serpiginous lesions or urticarial tracts (larva currens is pathognomonic)
o Pruritus
• Pulmonary phase: dry cough and wheezing, hemoptysis, rarely pneumonia (Loeffler syndrome)
• Intestinal phase: inflammation (e.g., duodenitis)
o Abdominal pain
o Diarrhea
o Anorexia, nausea, vomiting
DIAGNOSTICS
• Initial test: CBC may show eosinophilia.
• Confirmatory test: consecutive stool examination for mobile rhabditiform larvae
TREATMENT
• Albendazole 0.4 g per day, 3 days
• Thiabendazole (mintezol) 25 mg/kg per day, 2 days
• Ivermectin 200 mcg/kg/days, 2 days
PREVENTION
• Identification and treatment of patients.
• Compliance with the rules of personal hygiene, careful processing of vegetables and fruits, prevention of
environmental pollution with feces, disposal of sewage (boiling water in a ratio of 1: 2, or a 3% solution
of carbation in a ratio of 1: 1, or falling asleep with bleach (200 g per serving of feces) on 1 hour).
• Wearing shoes and avoiding contact between bare body parts and soil in endemic areas.
• Sanitary and educational work.
19. Echinococcosis: etiology, epidemiology, clinic, diagnostics, treatment and prevention.
ETIOLOGY
• Pathogens: Echinococcus tapeworms
o Echinococcus granulosus causes Cystic echinococcosis (CE)
o Echinococcus multilocularis causes Alveolar echinococcosis (AE)
• Transmission
o Hand-to-mouth
o From the fur of definitive hosts (e.g., petting a dog or cat)
o Contaminated dirt (e.g., dog feces)
o Fecal-contaminated food or water (e.g., wild berries, mushrooms)
• Definitive hosts: foxes, dogs, and cats
• Intermediate hosts: hoofed animals; (e.g., sheep, goats, camels, horses, cattle, and pigs)
• Humans are accidental hosts (e.g., sheep farmers)
EPIDEMIOLOGY
• With echinococcosis, the natural focus of E. granulosus is livestock pastures, E. multilocularis is common
in the arctic and subarctic zones
CLINIC
Feature Cystic Alveolar
Incubation Up to 50 years 5-10 years
Onset Usually asymptomatic Typically non-specific symptoms
Hepatic cyst
Single hepatic cyst (hydatid cyst) • Hepatomegaly → RUQ pain
• Symptoms depend on the location and • Malaise, weight loss, nausea, vomiting
size of the cyst Cyst that invades and destroys the liver and
Hepatic • Cyst rupture may cause anaphylactic surrounding tissue
reaction • Portal hypertension
Hepatomegaly → RUQ pain • Budd-Chiari syndrome
Malaise, nausea, vomiting • Liver cirrhosis
• May resemble hepatocellular carcinoma
• Primary involvement of other organs is
• Lung involvement in 25% of cases →
Extra- very rare (< 1% of cases)
chest pain, cough, dyspnea, hemoptysis
hepatic • Metastasis to other organs (especially
• Involvement of other organs is rare
lungs, brain, spleen) in ∼ 13% of cases
DIAGNOSTICS
• Suspected echinococcosis is generally confirmed via ELISA and ultrasonography.
• Laboratory tests: (nonspecific; low diagnostic value): mild eosinophilia, leukopenia or
thrombocytopenia, liver function abnormalities
• Serology: positive ELISA (false negatives are common)
• Imaging
o Ultrasonography
▪ Cystic echinococcosis: unilocular, anechoic, smooth, well-defined hepatic cyst with or without
daughter cysts
• Possibly daughter cysts and hyperdense internal septa
• Eggshell calcifications within the wall of a hydatid cyst may be visible
▪ Alveolar echinococcosis: lesions with irregular, poorly defined margins, central necrosis, and
irregular calcifications within the cyst and cyst wall
o CT scan: indicated for further evaluation of cysts
▪ Alveolar echinococcosis usually not well-defined, but shows infiltration of the liver and
surrounding tissue
▪ Best test for evaluating extrahepatic cysts
TREATMENT
• Cystic echinococcosis
o Observation: inactive cyst with heterogeneous hypoechoic/hyperechoic contents, or solid, calcified
wall
o Medical therapy: may be considered as the sole treatment for cysts < 5 cm
▪ Drug of choice: albendazole
▪ Alternative drugs: mebendazole, praziquantel
o Ultrasonography/CT-guided percutaneous drainage
▪ Commonly conducted using the PAIR (puncture, aspiration, injection , reaspiration) procedure
▪ Should only be done in combination with medical therapy (albendazole)
▪ Indications: > 5 cm and/or septations
o Surgery
▪ Goal: resect the whole cyst to prevent spillage of its content
▪ Indications: > 10 cm, complicated cysts
• Alveolar echinococcosis
o Curative resection followed by at least 2 years of treatment with albendazole to prevent a potential
relapse
o Palliative care if surgery is not possible or unsuccessful: see “Medical therapy” above
PREVENTION
• Identification and treatment of patients, preventive deworming of dogs (2 times a year).
• Disinfection of dog faeces (boiling in water for 10-15 minutes or pouring 10% bleach solution for 3 hours).
• Constant monitoring of the epidemiological situation, veterinary control.
• Compliance with the rules of personal hygiene.
• Exclusion of eating organs affected by echinococcus and dead animals by dogs.
• Culling and destruction of infested carcasses of domestic animals.
• Destruction of stray dogs.
• Construction of typical slaughterhouses and enterprises for the processing of confiscated meat and
carcasses of dead animals.
• Sanitary and educational work.
20. Cysticercosis: etiology, epidemiology, clinic, diagnostics, treatment and prevention.
ETIOLOGY
• A tissue infection with tapeworm larvae.
• Symptoms depend on the infected organ (e.g., muscles, brain, skin).
• Taenia solium (pork tapeworm)
• Fecal-oral: eggs are ingested from contaminated water or vegetables
• Eggs hatch in the human intestine → Develop into adult worms → Produce proglottids which can detach
from the tapeworm and are passed in the feces
EPIDEMIOLOGY
• Human cysticercosis is found worldwide, especially in areas where pig cysticercosis is common.
• Cysticercosis are most often found in rural areas of developing countries with poor sanitation, where pigs
roam freely and eat human feces.
• Cysticercosis are rare among persons who live in countries where pigs are not raised and in countries
where pigs do not have contact with human feces.
CLINIC
• Symptoms caused by cysticerci accumulation in subcutaneous tissue, muscles, brain, spinal cord, and eyes
o Palpable subcutaneous cysts
o Myalgia
o Neurocysticercosis (cysticerci-containing cysts in the CNS): increased intracranial pressure,
neurological deficits, seizures
o Ocular cysticercosis: eye pain, loss of visual acuity or vision in one eye
DIAGNOSTICS
• Initial test: CBC may show eosinophilia
• Cerebral MRI/CT showing multiple, small (< 1 cm) cystic lesions with a membranous wall and an
invaginated scolex (“dot sign”)
• CT/MRI may also show
o Cysts with an invaginated scolex during earlier stages
o Calcified cyst remnants in later stages
• Lumbar puncture: ↑ protein, ↓ glucose, mononuclear pleocytosis
• Confirmatory test: serum enzyme-linked immunotransfer blot (EITB) assay
TREATMENT
• Praziquantel
• For neurocysticercosis: albendazole PLUS corticosteroids
PREVENTION
• Avoid raw pork and inspect for cysticerci
• Adequately freeze and cook meat to destroy viable cysticerci
• Dispose of human feces properly
• Hand washing before meal preparation
21. Amebiasis: etiology, epidemiology, clinic, classification, diagnostics, treatment, prevention.
ETIOLOGY
• Pathogen: Entamoeba histolytica, a protozoan
• Transmission
o Fecal-oral
▪ Amebic cysts are excreted in stool and can contaminate drinking water or food
▪ Transmission may also occur through sexual contact.
o Infection typically occurs following travel to endemic regions such as the tropics and subtropics
EPIDEMIOLOGY
• Occurence: E. histolytica is very common in tropical and subtropical regions; (e.g., Mexico; , Southeast
Asia, India) and affects more than 50 million people worldwide. Amebic infection is relatively rare in the
US.
• Men and especially immunocompromised individuals have a higher risk of developing liver abscesses
CLINIC
• Intestinal amebiasis (Amebic dysentery)
o IP = 1-4 weeks
o Loose stools with mucus and bright red blood (raspberry jelly)
o Painful defecation, tenesmus, abdominal pain, cramps, weight loss, and anorexia
o Fever in 10–30% of cases and possible systemic symptoms (e.g., fatigue)
o High risk of recurrence, e.g., through self-inoculation (hand to mouth)
o A chronic form is also possible, which is clinically similar to inflammatory bowel disease
• Extraintestinal amebiasis
o IP = few weeks to several years
o Mostly acute onset of symptoms; subacute courses are rare
o In 95% of cases: amebic liver abscess, usually a solitary abscess in the right lobe
▪ Fever in 85–90% of cases (compared to amebic dysentery)
▪ RUQ pain or pressure sensation
▪ Chest pain, pleuralgia
▪ Diarrhea precedes only a third of all cases of amebic liver abscesses
o In 5% of cases: abscesses in other organs (e.g., especially the lungs; in rare cases, the brain), with
accompanying organ-specific symptoms
CLASSIFICATION
• Asymptomatic
• Intestinal
o Amebic colitis
o Ameboma
o Toxic megacolon
o Peritonitis
o Cutaneous amebiasis
• Extraintestinal
o Amebic liver abscess
o Splenic abscess
o Brain abscess
o Empyema
o Pericarditis
DIAGNOSTICS
• Intestinal amebiasis
o Stool analysis
▪ Microscopic identification of cysts or trophozoites in fresh stool
• Trophozoites often contain ingested erythrocytes
• Cysts contain up to four nuclei
▪ The following tests confirm the microscopic findings (important since E. histolytica and Entamoeba
dispar are morphologically identical ):
• EIA or coproantigen ELISA
• Molecular methods: e.g., PCR
▪ Stool microscopy is not sensitive; , especially in later phases, so at least three stool samples should
be examined before reporting a negative result.
o Colonoscopy with biopsy: flask-shaped ulcers
• Extraintestinal amebiasis
o Serological antibody detection
o Aspiration of abscesses: shows brown fluid/pus (exudate resembles anchovy paste)
o In amebic hepatic abscess
▪ Liver function tests: ALP, AST, ALT, bilirubin slightly elevated
▪ Imaging: shows a solitary lesion, typically in the right lobe of the liver
• Ultrasound: hypoechoic
• CT/MRI
o Well-defined, rounded lesions with contrast-enhancing wall
o Can be unilocular or septate
TREATMENT
• Medical therapy
o Asymptomatic intestinal amebiasis
▪ No treatment in endemic areas
▪ In nonendemic areas
• Luminal agents such as paromomycin, diloxanide, or iodoquinol
• Goal: To prevent the development of invasive disease and the shedding of cysts.
o Symptomatic intestinal amebiasis and invasive extraintestinal amebiasis
▪ Initial treatment with a nitroimidazole derivative such as metronidazole or tinidazole to eradicate
invasive trophozoites
▪ Followed by a luminal agent (e.g., paromomycin, diloxanide, or iodoquinol) to eradicate intestinal
cysts and prevent relapse
• Invasive procedures
• Aspiration: ultrasound or CT-guided puncture of complicated liver abscesses at risk for perforation
o Indications: Localized in the left lobe, Pyogenic abscess, Multiple abscesses, Failure to respond to
pharmacotherapy
• Surgical drainage: should generally be avoided, but may be indicated for inaccessible abscesses or
ruptured abscesses in combination with peritonitis
PREVENTION
• Unpeeled fruits or vegetables should not be consumed if there is a potential risk of contamination by
Entamoeba histolytica cysts (e.g., endemic region with low hygiene standards).
• Even chlorinated water can contain high concentrations of amebae; therefore, water should be boiled
before use
22. Vukhirerioz: etiology, epidemiology, clinic, classification, diagnostics, treatment, prevention.
ETIOLOGY AND CLASSIFICATION
• Wuchereria bancrofti: a nematode; responsible for most cases of lymphatic filariasis worldwide
• Brugia malayi and Brugia timori: found in Asia
• Mode of transmission: female mosquito bite (Aedes, Mansonia, Anopheles, and Culex)
• Incubation period: 9–12 months
• Life cycle: Mosquito introduces filarial larvae into host via bite wound → Larvae mature into adult worms
that reside in the lymphatic system → Adult worms produce microfilariae (the blood circulating stage of
filariasis-causing roundworms) → microfilariae move throughout vascular and lymphatic system →
microfilariae are consumed by a female mosquito during a blood meal → microfilariae mature into larvae,
thus completing the cycle
EPIDEMIOLOGY
• Wuhereriosis is common in tropical and subtropical countries.
• A large population infestation has been registered in Equatorial Africa, Indochina (found in India, China,
Japan), in the countries of Central and South America, on the islands of the Pacific and Indian Oceans, in
the coastal zone of Australia
CLINIC
• Fever
• Painful lymphadenopathy (due to worms invading lymph nodes, causing inflammation); and retrograde
lymphangitis → lymphedema with disfiguration of the lower extremities (elephantiasis)
• Hydrocele
DIAGNOSTICS
• Blood smear obtained at night (and staining with Giemsa or hematoxylin and eosin): detection of
microfilariae
• Serology: elevated levels of antifilarial IgG4
TREATMENT
• Diethylcarbamazine (DEC): drug of choice (1st day 0.05 g orally after meals, 2nd day 0.05 g, 3rd day 0.1
g, days 4–21 2 mg/kg; course 21 days
• Ivermectin: used in areas where onchocerciasis is prevalent, as DEC can worsen onchocercal eye disease
• Elevation of the affected extremity, exercise, and wearing therapeutic shoes: recommended for those with
lymphedema
• Surgery for hydrocele
PREVENTION
• Identification, isolation and treatment of patients.
• Protection of the population from mosquito attacks (use of repellents, protective clothing, curtains,
screening of windows, doors, treatment of premises with effective insecticides).
• Destruction of mosquito breeding sites (treatment with insecticides), sanitary improvement of cities and
towns, equipment of water supply and sewerage systems on their territory.
• Sanitary and educational work.
23. American trypanosomiasis. Etiology, epidemiology, clinic, diagnosis, treatment and prevention.
ETIOLOGY
• Pathogen: Trypanosoma cruzi
• Route of infections
o Vector transmission
▪ Is realized by numerous triatomine species of the Reduviidae family (also called kissing bug
because it typically bites around the mouth or eyes)
▪ T. cruzi is shed in the feces of the reduviid bug; feces is then rubbed into the bite site while
scratching.
o Contaminated food and drinks
o Transplacental transmission from the mother to the fetus
o Blood transfusion, solid organ transplantation
EPIDEMIOLOGY
• Endemic in Central and South America
CLINIC
• Incubation period: 1–2 weeks
• Acute phase (acute American trypanosomiasis): lasts ∼ 8–12 weeks
o Fever, malaise, loss of appetite
o Cutaneous manifestations
▪ Chagoma: inflammatory edema at the bite site (usually in the face)
▪ Romana sign: unilateral painless edema of the eyelids and periocular tissue
o Generalized lymphadenopathy and hepatosplenomegaly
o Rarely (∼ 1% of cases): myocarditis, meningoencephalitis
• Indeterminate phase
o Patient enters an asymptomatic latent phase.
o Patients in the indeterminate phase are serologically positive but do not develop signs and symptoms
associated with the chronic phase.
• Chronic phase (chronic American trypanosomiasis): develops after ∼ 10–20 years
o Chagas cardiomyopathy
▪ Conduction disorders: right bundle branch block (RBBB)
▪ Biventricular dilative cardiomyopathy → heart failure
▪ Atrophy of the apex, which may lead to ventricular aneurysm
▪ Mural thrombi → stroke
o Gastrointestinal tract
▪ Damage to the submucosal and myenteric plexus → inability to relax lower esophageal sphincter
and impaired gut motility → progressive dilation of the esophagus and colon
• Megaesophagus and achalasia: dysphagia, weight loss, regurgitation
• Megacolon: abdominal pain, chronic constipation
DIAGNOSTICS
• Confirmatory tests
o Acute phase
▪ Best initial test: direct visualization of T. cruzi trypomastigotes in thin and thick peripheral blood
smears using a Giemsa stain
▪ PCR to detect T. cruzi DNA
o Indeterminate and chronic phase: serological assays to detect IgG antibodies against T. cruzi
• Additional tests
o Regular ECG monitoring
▪ Patients with symptoms or ECG signs of Chagas cardiomyopathy
o Patient with symptoms of GI involvement: barium radiography, endoscopy, and manometry
TREATMENT
• Treatment against Chagas disease is most effective when initiated early (in the acute phase).
• First-line: benznidazole [5mg/kg/d PO BD 2 months] (generates free radicals that cause DNA damage in
the parasite)
• Second-line: nifurtimox [8-10mg/kg/d PO QID 4 months]
PREVENTION
• Instructions for people traveling to or working in endemic regions
o Use insect repellents and insecticide-treated bed nets.
o Avoid sleeping in poorly constructed houses with thatched roofs and cracked walls.
• Public health measures
o Screening of blood donors
o Screening of neonates born to infected mothers
o Vector control methods such as insecticide spraying and reduviid-proof housing
o Food hygiene
1. Methods of medical rehabilitation, indications and contraindications for medical
rehabilitation.

Methods of medical rehabilitation:

• Psychological R
• Physical R
• Therapeutic R
• Reconstructive surgery
• Clinical nutrition
• Occupation therapy
• Use of medical techniques.
• Kinesiotherapy, reflexology, massage, herbal medicine,
According to the degree of invalidism, there are two varieties of R:
1. Course rehabilitation: Short term rehabilitation carries out for limited, not permanent
trauma. Course period is from several weeks up to 1,5 years to get maximum results in
functional, home and professional sphere.
2. Continuous rehabilitation: For chronic patients, it is long-term, sometimes permanent
process of medical rehabilitation.
• Individualism takes place when IPR (individual program of rehabilitation) will be
accomplished. It is based on the specifics of organism functions disturbance in present
disease, clinical course feature in present patient and his reaction on different forms of
rehabilitation programs.
General contraindications for medical rehabilitation:
• resistant to drug correction hypertension
• ischemic heart diseases with frequent rest angina pectoris attacks
• myocardial infarction with heart insufficiency or angina pectoris attacks
• active phase of rheumatism
• circulatory insufficiency II – III degree
• cardiopulmonary insufficiency II – III degree
• active pulmonary tuberculosis
• frequent epileptic seizures
• marked psychic disorders
• high body temperature, fever
• acute inflammatory diseases
• venereal diseases
• malignant neoplasms
• ununited fractures
• unreduced joint dislocations
• not healed (nonepithelizated) burns
• unstable osteosynthesis.
General indications for medical rehabilitation:
Use indications from different systems rehab indications
2. Principles of medical rehabilitation. The difference between medical rehabilitation
and treatment.
• Early start of rehabilitation.
• Individual rehabilitation program.
• Complexity in building an individual rehabilitation program, taking
• into account all the characteristics of the patient.
• Collegiality in building an individual rehabilitation program
• Continuity and duration of rehabilitation.
• Continuity between stages.
• Availability of rehabilitation for everyone who needs it.
The difference between medical rehabilitation and treatment.
Talk about how medical treatment consists of pharmacological medication while rehab
consists of different methods used to improve quality of life and restore function of patient.

3. Criteria of life activity, the concept of a functional class. Evaluation of the

effectiveness of medical rehabilitation.
• Functional class is defined according to patient’s life activities potential limitation.
Criteria of life activity:
1. Movement.
2. Orientation.
3. Self-care.
4. Learning capability.
5. Communication.
6. Working potential.
Gitkina’s criteria of life activities:
- FC0 - normal parametric indications.
- FC1 - minimal degree (0-25%).
- FC2 - medium degree (26-50%)
- FC3 - sub-maximum (51-75%)
- FC4 - maximum (>75%).
Effectiveness evaluations of medical rehabilitation
1. By clinical criteria:
• visual evaluation (gait, behavior, state of skin and musculoskeletal system);
• clinical indices (Ps, AP, joint movements, muscular contraction or rigidity presents);
• functional systems indices;
• instrumental and apparatus indices;
• evaluation of adaptive capacity to perform work and home skills.
2. By scales, tests, questionnaires.
3. By economical criteria.
4. By social criteria:
• indices of temporary disability;
• indices of disability
• indices of working capacity potential.
4. Massage as a means of rehabilitation of patients in the clinic of internal diseases,
classification, indications and contraindications.
Massage (French word, means “to rub”) is a complex of science- based methods of
mechanical dosed actions which a massage therapist performs on the surface of human body
with his hands, or with the help of apparatus or water current.
Massage Classification:
The following types of massage can be distinguished:
I - According to the purpose:
1. Therapeutic massage (used in treatment of most diseases).
2. Hygienic massage (used for health strengthening, improvement of the functional state of
organism, prevention of complications).
3. Sports massage:
a - preliminary (used by sportsmen as a preparation for trainings or competitions);
b - compensative (used after trainings or competitions);
c - training (used in addition to trainings).
4. Cosmetic massage (face massage).
a - hygienic (for hygienic purposes and prophylaxis of skin aging);
b - therapeutic (used in treatment of diseases of maxillofacial region).
5. Gynaecological massage - therapeutic bimanual massage (used in gynaecology).
II- According to methods:
- classical (based on effecting tissue in a layerwise way, with the use of four basic classic
methods);
- reflexosegmental (based on affecting reflexogenic zones, and zones of hypersensitization);
- nerve-point massage (effects biologically active points).
Other types: periosteal, connective-tissue, intestinal, oriental, Swedish, Finnish. These types
of massage are used rarely in Belarus.
III - According to technique:
1. Manual.
2. Instrumental (brush, cupping glass, massager).
3. Apparatus.
4. Hydromassage.
Massage mechanism is based on complex interdependent reflectory, neurohumoral and local
processes, caused by dosed mechanical effect.
Mechanical stimulations, caused by special massage methods, excite mechanoreceptors
which are intended for transforming energy of mechanical stimulation into a neural one
(initial link in the chain of neuro- reflexive reactions). Receptor stimulation in the form of
centripetal (afferent) impulses is carried through sensory pathways to CNS (spinal cord,
cerebellum, functional formations of the brain stem and cerebral cortex), where it
transforms into a general complex reaction and causes different functional changes in
organism.
With massaging actions the heat is formed in tissues, so massage stimulates thermal receptor
system. Aroused stimulation is transmitted into the regulating vasomotor centre, located in
the medulla oblongata, and then moving to sympathetic and parasympathetic nerves causes
reflectory changes in vessel lumen.
Massage enhances the synthesis of histamine and acetylcholine in skin, which dilate
arterioles, mobilize body defences, stimulate muscular activity, accelerate transmission of
stimuli from neuron to neuron and to myocyte (neurohumoral massage action).
Besides its neuroreflexive and neurohumoral action, massage has a mechanical effect on
muscular capillaries, which may contract at the expense of Rouget cells located in their
walls. However, capillary lumen is also affected by chemical stimulants: hormones
(adrenaline, noradrenalin), lactic acid, ATP.
In different illnesses massage helps organism to get rid off catabolic products, normalizes
gaseous, mineral and protein metabolism, also stimulates protective-adaptive mechanisms
and factors of specific and non- specific immunity (N.A. Belaya, 1983).
It is believed that the most physiological massage is massage performed by a qualified
specialist. Duration and intensity of the procedure depend on a character and phase of
pathological process, clinical presentation, and localization of massaging area, age and
complications. Accordingly, massage has indications and contraindications.
• General indications for massage therapy in acute illnesses: satisfactory patient’s
condition, termination of illness acute phase, periods of early and late convalescence,
absence of complications and relapse signs, consent of a patient for a procedure.
• General indications for massage therapy in chronic illnesses: end of acute phase,
satisfactory patient’s status, absence of febrile temperature and decompensation signs of
the main and concomitant disease.
Indications: In every particular case, indications are determined by the character of the
clinical course, the predominant involvement of one or another system, organ, area and etc.
According to this, in cases of:
- cardiovascular system involvement indications for massage therapy are the
following: ischemic heart disease, myocardial infarction, cardio sclerosis, hypertension,
arterial hypotension, myocardial dystrophy, valvular defects, venous and arterial diseases.
- Massage indications in respiratory system diseases: chronic non- specific lungs
diseases, chronic pneumonia, bronchitis, emphysema, pneumosclerosis, and bronchial
asthma.
- Massage therapy in gastrointestinal tract pathology along with chronic diseases of
that system in remission:if there are syndromes stating the involvement of certain
digestive organs: esophagitis, gastritis, duodenitis, enteritis, colitis and their combination
(gastroenterocolitis), cholecystitis, cholangitis, hepatitis, pancreatitis, stomach and
duodenum ulcerous disease, Crohn’s disease, nonspecific ulcerative colitis, allergic and
autoimmune diseases, and other pathological conditions. The mentioned syndromes often
develop in alimentary toxic infections, acute and chronic enteric infections, acute and
chronic viral hepatitis, cholangitis, amebiasis, and other diseases.
- Disorders of CNS, mainly of traumatic origin, can be often found in general hospitals.
- Massage therapy is indicated in traumas, consequences of stroke, cerebral atherosclerosis,
infantile cerebral paralysis, neurologic manifestations of osteochondrosis, consequences
of poliomyelitis and others.
- Indications for massage therapy in locomotor apparatus disorders: soft tissue
bruises, sprain of ligaments and tendons, fractures and their consequences. Massage is
used in cases of Bechterew’s disease, osteoarthritis deformans, scoliosis, platypodia.
• General Contraindications: acute phase of disease, febrile temperature, hypotonic
(collaptoid) state, dizziness, strong asthenia, haemorrhages, thrombosis, severe heart
rhythm disturbance, circulatory deficiency of III degree, blood diseases, suppurative
processes of any localization, strong physical and mental fatigue, benign and malignant
tumours, poor general condition, Quincke's edema and other acute manifestations of
allergy.
• Contraindications to massage in cardiovascular diseases: acute myocardial ischemia of
a sudden character, hypertonic or hypotonic crisis, arterial thrombosis of the lower limbs
in decompensation phase, aneurism of vessels, aorta, heart, acute inflammation,
thrombosis, acute varix dilatation with trophic disorders, vessels and lymph nodes
inflammation, pulmonary-cardiac insufficiency of III degree.
• Contraindications to massage in respiratory system abnormalities: acute febrile
conditions, sever phase of exudative pleuritis, multiple bronchoectasis in acute phase
(with disintegration), pulmonary-cardiac insufficiency of III degree, and active form of
tuberculosis, neoplasms, acute trauma and burn of respiratory organs.
• In infectious diseases contraindications: haemoptysis, acute bronchospasm, croup of II-
III degree, uncontrollable cough with sputum excretion, artificial pulmonary ventilation,
inflammatory processes on the chest’s skin (pyoderma, bedsores) and others.
• Contraindications to massage in gastrointestinal diseases: abdominal palpatory
tenderness, nausea, vomiting and signs of inflammatory process exacerbation; tendency to
haemorrhages: peritoneum and intestine tuberculosis, swelling of abdominal organs.
• Therapeutic massage is not used in the following cases: acute (subacute) hepatic and renal
insufficiency, toxic hepatic encephalopathy, DIC syndrome, strong diarrheal (colitis)
syndrome, ascites and skin disease of abdominal and contiguous areas.
• Contraindications to massage in diseases of central and peripheral nervous system:
acute pains of different localization, including causalgia, acute radiculoneuritis, acute
radicular syndrome based on osteochondrosis or another genesis, encephalitis, myelitis
with trophic disorders in acute phase, swellings of different localization, diencephalic
crisis, vasomotor abnormalities related to endocrine system disturbance, neurosis with
affective burst, impulsive obsession, attacks, also sexual neurosis, impotency based on
irritable weakness, strong physical or mental fatigue. Massage is not applied in the cases
of symptoms of intoxication (temperature), exacerbation of the process (meningeal, focal,
pathologic signs occur), impossibility to make a diagnosis, complications related to the
main disease, and others.
• The presence of the rash of any origin, haemorrhagic eczemas, bruises, staphylococcal
and streptococcal dermatitis, bedsores, wounds, aseptic dressings are contraindications to
massage therapy in various diseases. Massage is not applied in the cases of tuberculosis,
skin tumours, eczemas, fungus disease of the nails and pilar parts of the body and some
other diseases.
The types of therapeutic massage. As it was mentioned before, classical, reflexosegmental
and nerve-point massages are mainly used in clinical practice.
Classic Massage
The basic methods of classic massage are effleurage, rubbing, petrissage, and vibration.
• Effleurage. According to this method, the massaging hand slides along the skin surface,
pressing it without making folds. Several types of effleurage can be distinguished, such as
area-based (superficial and deep), covering (continuous, discontinuous), tongs-, rake-,
comb-like effleurage, and crosslike effleurage technique. These methods precede
massage, and also can be performed in the period between other basic methods, or finish
the procedure. In the result effleurage accelerates lymph and blood stream, improves
sweat glands activity, and causes hemostimulation (V.N. Moshkov, 1954). Action of this
method is directed towards surface layers of skin (epidermis, dermis).
• Rubbing. It is the movement of the hand along body surface with deep pressing that
moves skin and forms skin folds in front of the massaging hand. Rubbing is performed
with fingers, by ulnar side or base part of the palm in a straight or helical manner. Besides,
auxiliary methods are used: tongs- and comb-like rubbing, sawing, hatching, and slicing.
Rubbing method precedes petrissage and acts on all skin layers, including subcutaneous
fat and fasciae.
• Petrissage. It is intended for acting on muscles. The principle of this method is that the
muscle is seized with hands, slightly raised, pulled off, then squeezed and kind of pushed
to release. Two types of petrissage can be distinguished: longitudinal and cross petrissage.
The auxiliary methods include fulling, rolling, moving, grasping, pressing, pulling.
• Vibration. It is the most deeply acting method, which has a strong reflexive effect. There
are two types of vibration: continuous and discontinuous. Continuous vibration consists in
messaging series of continuous vibrational movements to the body. In the course of
continuous vibration, masseur’s hands while pressing tissues do not lose contact with the
massaging area, and create vibrational movements with the frequency 100-300/min.
Auxiliary methods of continuous vibration: stable and instable vibration, shaking,
joggling, and slight pushing. Methods of discontinuous vibration: puncturing, tapotement,
slight slapping, cutting, whipping. They provoke vasodilatation, hyperaemia, decrease of
nerve endings sensitivity, increase of oxygen and nutrients inflow and some other positive
effects.
The general requirement for massage therapy is to reach average physiological condition by
finding optimal position of the body or certain area, in which muscles are relaxed, as much
as possible.
It is important to remember that different skin areas have different degree of tactile
sensitivity. The minimal sensitivity to pressure is found in the back area along the middle
line of the spinal column, conditionally taken as 1. The sensitivity of the middle line of the
abdomen - 1,06, the middle line of the chest - 1,39, flexor surface of shoulders - 3,01, back
surface of foot - 3,38, wrist joint - 3,80, forehead - 7,54.
Reflexosegmental massage
Functional interconnections between internal organs and segments of spinal innervation can
be the reason for administration of reflexosegmental massage. The present type of massage
is based on using features of segmental structure of the body: receptor stimulation of certain
zones (Zaharyin- Head) affects corresponding organs and systems, innervated by the same
segments of the spinal cord.
Collar and lumbar massages, offered by A.E. Scherbak and his colleagues, are the most
often used techniques of reflexosegmental massage. Collar massage is used in treatment of
arterial hypertension, migraine, sleep disorders, trophic disorders of the upper limbs.
Lumbar massage is used in treatment of vascular diseases of the lower limbs, also for
stimulation of sex glands function.
All methods of classic massage and its variants are used in reflexosegmental massage
therapy, with consideration of phase, activity, localization of pathological process and
patient’s condition.
Nerve-point massage
This type of massage is a variety of chzen-dzu therapy (traditional medicine of China).
Nerve-point massage affects biologically active points (BAP) by using methods of pressing,
rubbing and stable continuous vibration unless the feeling of swelling, heaviness, numbness,
aches and pricking occurs.
The types of nerve-point massage:
1. Strong (inhibitory variant) - analgetic and relaxing action (duration of the action on BAP -
5 min.).
2. Mild (inhibitory variant) - relaxing action (duration of acting on BAP - 2-3 min.).
3. Weak (excitative variant) - stimulatory and tonic action(duration of acting on BAP - 1-1,5
min.).
Massage points can be corporeal and auricular.
Massage therapy must be performed by a qualified specialist only. Before starting the
procedure, he should do a number of exercises to prepare his hands:
1. Stand on toes, extend arms at shoulder level, raise them (inspiration), stand on feet, arms
down (expiration).
2. Bend arms in elbow joints, hands to shoulders, circular movements of shoulders joints.
3. Raising arms clench fingers at the same time and then unclench.
4. Relax hands, raising arms up, down, then extend, and shake them. 5. Lock palms in front
of the chest, strongly pressing fingertips move
hands to the right and left side.
6. Lock hands strongly, pressing fingertips, move hands to the sides without moving fingers.
7. Extend arms forward, perform circular movements.
8. Hands in front of the chest, bend and unbend fingers in interphalangeal and MCP joints.
9. Lock fingers closely and move palms to the sides in radio-carpal joint.
10. Clench fingers and move them in radio-carpal joints in a circular manner.
The knowledge of basis of general, reflexosegmental, nerve-point massage, adequate
administration, combination with other methods of rehabilitation therapy, proper conducting
of massage procedure (according to methodology) increase considerably effectiveness of
therapy and rehabilitation, allow to decrease percentage of disability cases in different
pathologic conditions.
5. Classification of means of kinesitherapy, their description. Contraindications for the
appointment of physical therapy.
• KT is a method of non-medicinal supportive therapy, which is extremely important in the
period of convalescence and remission. It can be considered as a method of prophylactic
therapy, because physical exercises increase the resistance of organism to unfavourable
factors.
• The basic means of KT include physical exercises, natural factors of environment and
massage. Physical exercises, as the main mean of KT, should be classified according to
the method of their application, the character of muscle contraction, the principle of
exercise intensity, the anatomical principle.
Classification of the means of kinesitherapy.
1. Gymnastic exercises:
a) isotonic (dynamic) - with muscle contraction the movement in a joint occurs - isotonic
lengthening and shortening;
b) isometric (static) - when a muscle works isometrically it shortens its muscular length and
slightly lengthens its non-contractile components, and as the result no movement occurs in
any of the joints;
c) active and passive;
d) specific - have selective effect on certain muscles and internal organs physiologically
connected with them;
e) developmental;
f) reflexive - based on unconditioned motor reactions;
g) corrective;
h) exercises for muscle relaxation, stretching, coordination, strength, balance;
i) respiratory exercises:
• static (pectoral, diaphragmatic and complete type) - performed only at the expense of the
main respiratory musculature being contracted
• dynamic (symmetric and asymmetric) - performed with participation of the auxiliary
respiratory musculature
• drainage exercises - for improving of sputum discharge;
respiratory exercises - to prevent formation of adhesions in the pleural cavity and exercises
to reduce bronchial spasms.
2. Sports: a) walking; b) running; c) climbing and crawling; d) swimming; e) skiing; f)
cycling and others.
3. Games: passive, of little activity, active, sports.
Absolute contraindications to KT are important to be aware of:
1. Critical status of a patient, requiring resuscitation measures and intensive care
conducting. 2. Acute phase of illness. 3. Febrile temperature (above 38° C).
4. Decompensation or increasing insufficiency of any system of the organism.
5. Haemorrhage. 6. Thrombosis.
7. Strong spontaneous pains.
8. Suppurative diseases before lancing (carbuncle, furuncle, phlegmon, abscess).
9. There is no contact with patients due to mental impairments and unconscious state.
As a rule, the mentioned contraindications have a temporary character. KT is indicated when
positive dynamics of illness is observed.
6. Reflexotherapy, methods of influence in reflexotherapy, acupuncture point, its
properties, search methods.
Methods of influence in reflexotherapy
• The philosophical framework for the practice of acupuncture is grounded in Traditional
Chinese medicine (TCM). In TCM theory, the human body is an energetic system in
which energy (QI) flows along defined pathways (meridians) throughout the body. When
the body is in harmony and balance the flow is smooth. An imbalance disrupts the flow of
QI and manifests as pain, dysfunction, injury, disease and/or disorders. Reflexotherapy is
a therapy to restore the flow of Qi to promote health and balance.
• According to modern science the needles used in acupuncture causes local irritation which
activates energy or suppresses it in the energy channels. In other forms of reflexotherapy
like using bees and leeches the mechanism is different. This is because leeches secrete
peptides and proteins such as hirudin that work to prevent blood clots. Magnetic therapy is
used together with light in reflexotherapy.
Acupuncture points
• Acupuncture points are strictly defined by location, smallest in size and special in
properties, areas of the skin surface of the body, used for various influences in order to
normalize the functional state of individual organs or body systems.
• In all people, most of the points have the same anatomical localization. The irritation of
which is the basis of the reflexotherapy method, its feature, in contrast to other methods of
exposure. All acupuncture points have a strictly defined anatomical location and
functional purpose, regardless of whether their location is determined by traditional canals
(meridians) or by anatomical regions and lines.
• Acupuncture points are a skin projection of nerve and other elements embedded in the
underlying tissues at a depth of several centimeters to several millimeters.
By location they are divided into:
- cutaneous-nervous,
- muscular-tendon-nervous,
- neurovascular.
According to the direction of action and innervation connections, acupuncture points
can be conditionally divided into:
1) points of general action, the irritation of which has a reflex effect on the functional state
of the central nervous system and the whole organism;
2) segmental points located in the area of skin metameres corresponding to the zone of
innervation of certain segments of the spinal cord, which are influenced by a segmental-
reflex effect on the organs innervated with these segments;
3) spinal points located along the vertebral and paravertebral lines, respectively, at the exit
site of the nerve roots and autonomic fibers;
4) regional points located in the zone of projection on the skin of certain organs - the
Zakharyin-Ged zone;
5) local points intended mainly for affecting the underlying tissues (muscles, blood vessels,
ligaments, joints).
There are good reasons to consider acupuncture points as zones of maximum reception or as
limited areas of maximum concentration of receptors embedded in the skin and underlying
tissues.
Dung (1984) classifies the location of acupuncture points as follows:
1)along large nerve trunks;
2) in the places of maximum approach of the nerve trunks to the surface of the body;
3)in the area of intersection of the deep fascia by the cutaneous nerves:
4) in the places where nerves exit from the bony holes (especially on the skull);
5) in the area of neuromuscular connections;
6)over the neurovascular bundles;
7) over the muscle nerves;
8) above the bifurcation points of large nerve trunks;
9) over the sensitive points of the tendons and ligaments;
10) along the seams of the skull.
Properties of acupuncture points:
• low threshold of sensitivity, high local temperature, increased skin respiration, low
electrical resistance when investigating with direct or alternating current (20-250kOhm),
large electrical capacity (0.1-1.0 uF), high electrical potential (up to 350 mV).

Search methods
• There are various ways to find them on the human body.
• The main reference point in determining the localization of acupuncture points is
anatomical and topographic data.
• When describing the topography of points, they most often focus on the body area, nearby
anatomical formations, skin folds, tubercles, borders of hairy areas, nails, muscles,
intermuscular spaces, tendons, ligaments, joints, cartilaginous and bone formations,
arterial trunks, etc.
• The generally accepted anatomical lines are widely used: anterior and posterior median,
midclavicular (nipple), anterior, middle and posterior axillary, scapular, paravertebral, etc.
• In some areas (for example, on the anterior abdominal wall, scalp, etc.) anatomical
landmarks are either poorly expressed or insufficient to accurately describe the location of
the acupuncture point. In these cases, the method of measuring proportional segments
(proportional tsuni) is used. The method of proportional (or, more precisely, individually
proportional) tsun is the division of a certain distance between pronounced anatomical
landmarks into a known number of equal parts, but different for different areas of the
body.
• Acupuncture points are also determined by palpation. In the area corresponding to the
localization of the desired point, palpation is performed with the tip of a bent finger with
light pressure. This reveals: points with maximum pain sensitivity; points with reduced
tissue turgor; points with tissue tension; points with some compaction of tissues.
• Electro-acupuncture diagnostics method -based on low resistance and increased electrical
conductivity in the area of points.
• Energy channels (meridians) are imaginary lines that connect acupuncture points located
on the body with the same properties. Ancient Chinese medicine studied 14 main
channels: the lung canal, the colon canal, the stomach canal, the spleen-pancreas canal,
the heart canal, the small intestine canal, the bladder canal, the kidney canal, the
pericardial canal (sexual canal), the triple warmer canal, the biliary canal bladder, liver
canal, posterior canal - median and anterior canal - median.
7. Ergotherapy, as a method of medical rehabilitation. Principles, indications.
• Ergotherpy is a method aimed at restoring, maintaining and developing individual skills
necessary for daily activities, work, leisure and recreation for people who, due to illness or
injury, have lost the ability to take care of themselves, work and do their usual activities. It
is based on the understanding that, using movements as a physiological stimulant, labor
activity contributes to an increase in the amplitude of movements, a decrease in muscle
rigidity, an increase in muscle strength and plasticity, which ultimately leads to the
restoration of impaired motor functions.
Principles, types, methods of occupational therapy.
• Ergotherapy is needed in cases where the patient experiences problems with self-care,
work and rest, but if the environment is fully adapted to his needs, then he will not need
the intervention of an ergotherapist even when he still has dysfunction.
• Program is usually carried out in a natural environment for a person - at home, at work,
etc., since the performance of any task depends on the motivation of the patient and the
environment in which it occurs.
• The ergotherapist can adapt the items the patient uses (cutlery, clothing, computer, etc.),
the environment (install handrails, pick furniture, rearrange items in the room, remove
thresholds, widen doorways, etc.) or pick up necessary special equipment (wheelchair,
walkers, devices for grasping objects and fastening buttons, etc.).
• The following general principles of ergotherapy can be distinguished:
1. Has no contraindications. There are practically no age restrictions for labor treatment.
2. Should be carried out in combination with other methods of treatment, both
pharmacological and non-pharmacological.
3. Should be included in the treatment process as early as possible, which will provide the
possibility of a more favorable course and outcome of the disease.
4. It should be carried out constantly throughout the disease, since any break, even
insignificant in terms of time characteristics, can lead to a deterioration in the patient's
functional capabilities.
5. Must be physiologically sound and psychologically comfortable. This means that the
dosage of the load should be determined by the general condition of the patient, including
psychological, the degree of disease activity and functional disorders, the expected period of
rehabilitation treatment.
6. Should be of an individual nature, which is determined by the characteristics of the
physical and psycho-emotional development, the clinical picture of the disease, as well as
the working and living conditions of the patient. It is necessary to inform the patient about
the goals and methods of treatment, together with him to establish the goal (restoration of
lost functions, disability, etc.) of the measures taken.
There are three main forms of occupational therapy in rehabilitation:
a) general strengthening (tonic), aimed at increasing the vitality of the patient. Creates the
psychological prerequisites necessary for the restoration of working capacity;
b) restorative (functional), based on the prevention of motor disorders or the restoration of
temporarily reduced functions of the motor apparatus through the development of a lost
function or the launch of compensatory mechanisms. For this, light labor loads are used that
provide the maximum amplitude of movement (winding threads, making toys, etc.)
c) professional (production), which contributes to the restoration of production skills
impaired as a result of the disease. In this type of occupational therapy, the patient's
professional capabilities are assessed; in case of lost professional ability to work or its
partial persistent decrease, the patient is prepared for learning a new profession.
• Of greatest importance for the practice of rehabilitation treatment has a recovery TT.
When it is performed, the muscles of the hand are strengthened and finely coordinated
movements are restored, the ability to grasp and hold various objects with fingers, as well
as endurance with the possibility of long-term static and dynamic work (general and
local).
• General strengthening TT affects the patient's body, in particular, the activity of the
neuromuscular apparatus and internal organs. The strengthening effect of TT on the
patient's body, aimed at maintaining overall performance, is achieved in various ways:
a) during the period of bed rest, labor operations are selected for patients without the
expenditure of great physical effort, but requiring a certain attention, mobilization of the
will;
b) walking patients who are in the hospital are first offered to perform simple work in the
ward (restoration of everyday skills), then in the department (neurological, traumatological,
etc.).
Goals, tasks of ergotherapy
• To restore lost motor skills functions and also re-adapt a person to normal life, help him to
achieve maximum autonomy and independence in everyday life.
• Ergotherapy includes knowledge in several specialties - psychology, pedagogy, sociology,
biomechanics and physical therapy. With help of ergo therapy improves not only motor,
but also cognitive and emotional possibilities.
• The main task of treatment with the use of labor is to give a person the joy of creativity.
So, to restore the ability of the hand to compress and decompress, frequent repetition of
these movements is required. Such an exercise can be performed in the aquatic
environment (squeezing and unclenching a rubber sponge), but the patient quickly
develops physical and psychological fatigue.
• But if he is offered to work with plasticine (clay), to which he can give various shapes
(figures), he will not feel tired, as he will focus on the manufacture of a particular object.
At the end of such a lesson, the patient sees the result of labor and is satisfied with it, and
in addition, notes an improvement in hand function.
• The second task is to save the residual function. Due to a disease or damage to the
nervous system, the patient is excluded from everyday life. He is set up for a normal
active life, but his physical abilities are sharply limited. At first, the patient needs all the
strength to overcome the disease or its consequences, after a while he regains his strength
and wants to become more active, participate in labor processes.
• The third task is labor training for later life. With the help of appropriate work, which is
carried out at first only for a short time and later for longer and longer periods, this goal
can be achieved. Realizing the importance of work as a healing factor, it is necessary to
constantly look for new opportunities to apply the method of occupational therapy in all
medical institutions.
8. Medico-technical means of rehabilitation.
9. Functional stress tests. Classification of stress tests. Indications for exercise testing.
Functional research methods this is specific methods use to assess functional status of
human organism.
Functional test: an exercise uses to assess the human tolerance and changes in function of
different organs and systems following this exercise.
Criteria of physical exercises:
• Test must not be harmful.
• Test must be proper, i.e. to evoke the proper and constant changes in human body.
• Must be reliable and adequate to those in the daily life.
• Must be standard and easy to realize.
• Must be objective, i.e. the same result for the same group of people.
• Must be informative and test scores must concise the sportive results.
Indications for the functional tests:
1. To assess the readiness to physical exercise, therapeutic exercise or sport.
2. To assess the different organs, e.g. CNS, CVS, RS of healthy and ill individuals.
3. To assess the effectiveness of exercise programs for different purposes, e.g.
rehabilitation and fitness.
4. To expertise professional validity.

• Contra indications for the functional tests:

1. Grave common condition of patient.
2. In severe phase of disease.
3. High temperature.
4. Haemorrhage.
5. Circulatory dysfunction.
6. Not stable or rapid progression of angina pectoris.
7. Hypertensive crises.
8. Aneurism of blood vessels.
9. Aortic stenosis.
10. Acute heart rhythm disturbance (tachycardia more than 100-110
beats per minute; group, frequent or polytopic extrasystoles; ciliary arrhythmia at alias).
11. Acute thrombophlebitis.
12. Acute respiratory insufficiency.
13. Bronchial asthma exacerbated by physical exercises.
14. Acute psycho-mental disorders.
15. If the test cannot be done when the patient has musculoskeletal or neuromuscular
disorders.
10.Acupuncture in internal diseases, possible complications and their prophylaxis.
Reflexotherapy contraindications.
Possible complications of acupuncture and their prevention:
If the rules for using this method are not followed, some complications are possible: a pronounced
autonomic reaction, needle, retention, hematoma, residual, sensation, etc.
• Pronounced vegetative reaction: In most cases, the autonomic reaction occurs due to too rough
manipulation of the needle
• Haematoma: The appearance of a hematoma is the result of vascular damage. In these cases, in
the first hours, local application of cold is indicated, and subsequently, for quick resorption, a
light massage and a warm compress.
• Residual sensation: Severe irritation can cause an unpleasant breaking sensation at the puncture
site after removing the needle. In these cases, a light massage is recommended.
• Stuck needle: In rare cases, due to the unusual reaction of the surrounding tissue, the needle gets
stuck, it becomes impossible to manipulate it or remove it. The patient is asked to relax and a
circular massage is performed within the radius of the needle insertion; usually you can then
remove the needle by turning it gently. If the blockage persists, then it is necessary to inject with
another needle in the immediate vicinity of the blocked one and wait a few minutes.
• Curvature and fracture of the needles: mainly due to the poor quality of the needles or the
incorrect technique of their insertion. In these cases, withdraw the needle slowly in the direction
of the tilt side of the needle handle, but under no circumstances rotate the needle! In the event of a
needle fracture, the fragment is removed with tweezers by the visible end or by surgery.
Absolute contraindications:
• Diseases of the blood (leukemia and hemophilia).
• Mental disorders: Since acupuncture can be accompanied by mild pain and stress, it can provoke
an inappropriate response and arousal in the patient.
• The state of alcoholic and drug intoxication: In such a situation, the patient behaves
inappropriately and cannot follow the doctor's instructions.
• Feverish states.
• Diseases accompanied by an increase in temperature disrupt the functioning of the central
nervous system > the mechanisms that provide therapeutic effect of acupuncture are disrupted
• Infectious diseases (AIDS, open form of tuberculosis, hepatitis, venereal diseases, purulent
inflammation) in this case, acupuncture can promote the spread of the pathogen throughout the
body. There is evidence that the use of reflexology can provoke an inadequate immune response
and cause autoimmune diseases.
• Acute surgical pathology (acute appendicitis, entrapment of an inguinal hernia, rupture of a cyst,
perforated ulcer). In such cases, patients need emergency surgery.
• Pathological pregnancy: can cause the uterus to contract and stimulate premature labor.

Relative contraindications:
• age up to 1 year. Young children have very thin skin, so inserting needles increases the risk of
damage to internal organs
• tumors: Acupuncture improves blood circulation and therefore can promote tumor growth and
metastasis;
• age over 70, exhaustion, uncomplicated pregnancy, poliomyelitis, violation of cerebral circulation
(stroke), multiple sclerosis, progressive muscular dystrophy, a state of strong and physical fatigue
or emotional stress, Local contraindications (exposure to points in the affected area is not
recommended) for children under 7 years of age, exposure to points located on the face and front
of the head is not recommended;
11. Methods of physiotherapy, indications and contraindications for their application.
PT common contraindications:

1) malignant neoplasms;
2) systemic blood disorders;
3) marked cachexia;
4) circulatory decompensation;
5) haemorrhage or suspicion on it; 6) sever psychosis;
7) fever;
8) active tuberculosis;
9) individual intolerance of PT.

Methods PT classification:

1) Group - permanent electric current of low voltage (galvanization, drug electrophoresis).

2) Group - impulsive current of low voltage (electrosleep, diadynamic (currents) therapy,

amplipulse therapy, interference therapy, fluctuorization, electrodiagnosis,
electrostimulation).

3)Group - electrical current of high voltage (diathermia, ultratonotherapy, local

d'arsonvalization).

4) Group - electric, magnet and electromagnetic fields of different characteristics

(franklinization, magnetic therapy, thermal induction, ultra high frequency therapy,
microwave therapy).

5) Group - electromagnetic oscillation of optical diapason (infrared therapy, phototherapy,

ultraviolet and laser therapy).

6) Group - mechanical oscillation of medium (massage, ultrasound therapy, drug

phonophoresis, vibration therapy).

7) Group – modified or special air medium (inhalation therapy, or aerosol therapy, electro-
aerosol therapy, barotherapy, aeroionotherapy, climate therapy).

8) Group - sweet water, natural mineral waters and their artificial analogues.

9) Group - heat (heat therapy) and cold (cryotherapy, hypothermia). In the capacity of
thermal mediums used therapeutic muds (peloids, paraffin, ozokerite, naphthalanum, sand,
clay, ice and others).
12.Means and methods of medical rehabilitation used for patients with cardiovascular
diseases.

• It must be remembered that kinesiotherapy for patients with pathology of the vascular
cardiovascular system in the decompensation phase is contraindicated! To assess the functional
state of regional hemodynamics, it is necessary to conduct this test: flexion and extension of the
legs in the ankle joints in full amplitude from the supine position with slightly bent legs in the hip
and knee joints until fatigue or slight soreness in the legs, while determining the number of
exercises performed (Pirogov L. A., 1986).
• When conducting special training, the amount of physical activity should be 75% of the number
of exercises when performing a functional test. Special exercises include: flexion and extension
of the toes, flexion and extension in the ankle joints, circular movements in the ankle joints,
flexion and extension in the knee and hip joints, abduction and rotation of the lower extremities in
the hip joints, exercises and positions for the lower extremities for relaxation muscles, walking.
• Along with special training, general exercises are necessarily included in the therapeutic
gymnastics procedure: breathing, isotonic gymnastic exercises for the upper limbs, as well as the
muscles of the neck and torso.
• Features of medical rehabilitation of patients with vascular pathology:
1. the degree of functional hemodynamic disorders should be strictly taken into account;
2. individual dosage of physical activity during a special training without transfusion therapy should
be 75% of the load that causes local muscle fatigue
3. when conducting transfusion therapy, it is advisable to carry out therapeutic exercises and dosed
walking in certain periods: between 1-3 hours after intravenous administration of drugs
4. when using drugs that reduce pain, the individual dosage during a special training should
correspond to the value of the tolerant load determined using functional test before drug
administration
5. intervals between series of special physical exercises should be 4-8 minutes. After surgery on the
vessels, it is important not to lose sight of the prevention of broncho-pulmonary complications. In
the early days, it is necessary to perform static, dynamic and drainage breathing exercises every
hour, as well as massage movements of the back and lateral sections of the chest.
• Another important task in the postoperative period is the prevention of thromboembolic
complications, which is implemented by performing active movements of small muscle groups.
On the 3-4th day after the operation, the amplitude of movements increases, medium and large
muscle groups are included in the work. From the 5-6th day, the period of medium loads begins,
from a lying position and sitting in bed, it is necessary to move to a sitting position on a chair.
• Then - the 7-10th day - a period of moderate exercise, it is allowed to get up, walk, perform
breathing and gymnastic exercises in a standing position. The period of increased loads is
associated with preparation for discharge. Great attention should be paid to walking along the
corridor and stairs. As a rule, there are no contraindications to therapeutic exercises and dosed
walking in this period, deep bends, squats and jumps are excluded.
• It should be noted that the method of therapeutic exercises in the postoperative period is selected
depending on the timing and nature of the surgical intervention, the state of the peripheral
circulation and the function of the cardiovascular system as a whole. The correct selection of the
amount of physical activity at the stage of rehabilitation contributes to an increase in motor
function, a reduction in the duration of treatment, prevention and treatment of postoperative
complications.
• Views on medical rehabilitation for myocardial infarction have changed over the past decades:
from prolonged strict bed rest to a relatively rapid activation of patients with an uncomplicated
course of the disease.
• Patients on the 3-4th day begin to walk around the ward, and on the 8-10th day they are
discharged home, where the outpatient treatment continues.
• Taking into account the peculiarities of the disease and the real danger of severe complications up
to death at any time from the onset of myocardial infarction, methods for assessing the patient's
response to physical activity are of particular importance.
• With an adequate response of a patient who has had a myocardial infarction to physical activity,
there should not be any unpleasant sensations (maybe mild fatigue that passes within a few
minutes), increased heart rate should not exceed 20-50% of the original, respiratory rate - no
more than 10 per 1 min; it is also possible to decrease the pulse (in the early stages of
rehabilitation) by no more than 10 per 1 min. The rise in systolic blood pressure should not
exceed 20-40 mm Hg. Art., diastolic - 10 mm Hg. Art.;
• The stationary phase of medical rehabilitation is conditionally divided into four stages of motor
activity:
• The first stage corresponds to the period of the patient's stay on bed rest, the second stage
corresponds to the loads of the ward regime, the third stage includes the period from the first exit
to the corridor to the first walk along the street, the fourth stage provides for a further exit to the
street, adaptation to increasing loads and preparation for discharge from the hospital .
• Massage for myocardial infarction is prescribed in the absence of contraindications to stimulate
extracardiac circulation, prevent vascular thrombosis, improve metabolism and eliminate
congestion. In the first days, a light massage of the lower legs is performed with the patient lying
on his back with his legs slightly bent at the knees. The following techniques are used: superficial
and deep embracing stroking, spiral rubbing, light longitudinal continuous and transverse
kneading; the pace of execution is slow.
13. Exercise tests used in cardiology.

Martine-Kushelevskij test:
• This test for mass prophylactic consult of students, pupils, sportsmen of mass classes, also in
clinics of internal diseases, but the amount of squatting decrease in accordance to the ability of
each patient.
• The tested people sit to left side of the doctor.
• Tonometer cuff fix on the left shoulder. AP - registered 3 times and the minimal systolic and
diastolic readings should be considered. Ps - registered in 10 sec. spaces of time, if two will be the
same (Ps - 12, 12 in 10 sec.) indicate rhythmic pulse, if not i.e. (12, 13,) not rhythmic pulse. Then
the tested man do 20 deep squatting in 30 sec. In every squatting he must put his hands in front of
him. After exercise, he sits on chair. Ps count in first 10 sec. of first restoration minute with
stopwatch, than AP in 40 second and again Ps - in last 10 sec. Repeat this in the 2nd and 3rd
minute also. Register pulse character (rhythm, fullness), auscultation pattern (tones and
murmurs). The example of these data in form of table.
• In accordance to character of
change types of Ps and AP
after the exercise, 5 types CVS
reactions noticed:
1) normotonic, 2) asthenic or
hypotonic, 3) hypertonic, 4)
dystonic, 5) stepwise reactions.
1)Normotonic reaction.
Character of this reaction is
increasing Ps frequency, increasing systolic pressure; diastolic pressure not change or decrease.
Pulse pressure increase. When Martine-Kushelevskij test done, systolic AP rise at the average to
18 mm Hg, diastolic - not change or decrease to 5 mm Hg. Restoration period last 1 to 3
minutes. Outlook character of tiredness is slight face hyperaemia. This reaction considered
physiological, because of maximum AP considered indirect character heart beats force,
minimum AP - general peripheral vessels tone, pulse AP - volume beats, middle AP- general
work of vessels contour, (middle AP = AP minimum + pulse AP/ 2). In this case, maximum
effectiveness of heart work obtained by combining incensement of heart frequency (heart rate)
and pulse AP (for account of decreasing AP minimum and increasing AP maximum), and
therefore in the case of relatively stable middle AP. Well known, the increment of heart rate
proportional depend on physical exercise potential, increasing in beats volume has exponential
dependency. And frequently the increment of heart rate dominates over the increment of AP,
and increasing of minimum circulatory volume takes place at the expense of heart rate
increasing.
2) Hypotonic (asthenic) reaction: Main properties are: considerable increasing of heart rate,
moderate increasing of systolic pressure, not change or moderate increasing in diastolic
pressure, pulse pressure not changed or even decreased. Exercise results in increasing of blood
circulation depending mostly on increasing of heartbeats and not in beats volume, which is
extremely not rational for heart. Period of restitution prolonged (heart rate up to 5-7 min., AP up
to 2-4 min.). Sings of tiredness include pale skin colour, lips cyanosis, breathlessness and cold
sweat. Found in patients with cardio-vascular diseases. Some authors (V.I. Dubrovskij, 1999;
G.M. Zagorodny and others, 2000) consider this type of reaction as hypotonic, but our
experience indicate that in some cases when systolic and diastolic AP parallel decreasing after
 exercise without change in pulse pressure. Heart rate increases considerably and restitution time
prolonged. Such reaction can be considered as a typical hypotonic reaction.
3) Hypertonic reaction: It Characterised by sharp and significant increasing of systolic pressure
up to 180-190 mmHg synchronously with diastolic pressure increasing to 90 mm Hg or more
and considerably increasing of Ps frequency. Restitution period prolonged up to 3-7 min., and
outward signs of tiredness characterised by breathlessness, hyperhydrosis, and expressed face
hyperaemia. G.M. Zagorodny and others, (2000) recognised hypertonic reaction types with
increasing diastolic AP, without increasing diastolic AP and stepwise. These types of hypertonic
reactions possible with stepwise exercises among qualified sportsmen.
4) Dystonic reactions: This type characterized by considerable increasing systolic pressure more
than 180 mmHg simultaneously decreasing of diastolic pressure, sometimes it’s not determine
(the mistakes limit of Korotkov auscultatory method allows fixation of zero division mmHg). In
this case speaks about «endless tone» phenomenon. Heart rate increasing sharp, restitution time
prolonged up to 4-5 min. Main mechanism of this phenomenon is discrepancy of cardiac output
and peripheral vessels tone.
During to stepwise increasing veloergometric test, moderated to “deny” an exercise, in healthy
swimmers 12-14 years old (males and females) we detect an «endless tone» phenomenon appears in
75-80% and consider it as a normal variant. At this moment at the peak of physical exercise, heart
rate reaches 200-210 beats/min. Combination of this phenomenon with nervous system and cardiac
pathology, especially in adults (sportsmen), considered as unfavourable.
5) Stepwise reaction type: Systolic pressure increases stepwise after the 2nd and 3rd restitutions
minutes, when systolic pressure more than that in 1st min. Restitutions period dragged on till 7 min.
Such reaction reflects inadequate circulatory system regulatory action and assessed ass
unfavourable.
Also Martine-Kushelevskij test assess by index quality of reaction (IQR) of cardiovascular system
response to exercise. For this Kushelevskij and Zislin formula have used:

Where: Pa1 - pulse pressure before exercise, Pa2 - pulse pressure after
exercise, P1 - pulse before exercise in 1st min., P2 - pulse after exercise in 1st
min., positive IQR = 0,5–1.

Three steps test of speed and exercise tolerance (prof. S.P. Letunov):
• Test includes three exercise components, use for sportsmen high qualifications. The 1st is 20
squatting in 30 sec. - warm-up, 2nd run in place during 15 sec. with maximum intensity - exercise
for speed, 3rd run in place duration 3 min., 180 steps /min. - exercise for tolerance. Ps and AP
fixed before and in restitutions period by Martine-Kushelevskij test principle, consider the
restitution time after 20 squatting is 3 min., after 15 sec. run - 4 min., after 3 min. run - 5 min.
General test assessment will be given, after analysis CVS type of reaction each of exercise
component.
14. Medical rehabilitation of patients with diseases of the joints.
Joint diseases (arthritis) are a large group of diseases of inflammatory and non-inflammatory
origin. Joint diseases are quite common and cause not only a limitation of the patient's ability to
work, but often lead to disability of still able-bodied people. The main manifestations of diseases:
pain in the joints, crunching during movement, swelling of the joint, deformity of varying degrees,
limitation of movement in the form of temporary stiffness, pain contractures to complete immobility
in ankylosis. When the joints are affected, tendon sheaths, ligaments, nearby muscles, and nerves
are often involved in the process. Their involvement in the pathological process gives a clinical
picture of tendovaginitis (swelling along the tendon sheath, pain on movement). Bursitis -
inflammation of the mucous bags, swelling due to the accumulation of serous exudate in the
bag. Neuritis in arthritis is associated with pressure on the nerve of connective tissue formations
and deposited salts. With neuritis, pain, impaired movement and muscle atrophy in the innervated
area are observed.
All diseases of the joints are classified according to the nomenclature adopted by the Antirheumatic
Committee: the first group - arthritis of infectious origin (rheumatic polyarthritis, tuberculosis,
tonsillogenic, gonorrheal, etc.); the second group - arthritis of non-infectious origin (gouty arthritis,
menopausal arthritis); the third group - traumatic arthritis (with open and closed injuries of the
joints) and the fourth group - rare forms of joint damage (for example, psoriatic arthritis, etc.). In
the course of the process, arthritis is divided into 3 periods: acute, subacute, chronic . The
dynamics of the process in the joint is determined by three stages according to A.I. Nesterov.
I stage . The patient's performance was preserved. Pain is noted in the places of attachment of the
tendons, in the area of the articular capsules and along the muscles. The joints are externally
unchanged or slightly deformed. There are no radiological changes.
II stage . The patient's ability to work is lost. Severe pain in the joint, deformity, significant
limitation of movement, contractures, bursitis. The x-ray shows limited osteoporosis.
Stage I II . Complete loss of ability to work. Deformation of varying degrees, arthrosis, muscle
atrophy. Movement in the joint is severely limited. On the radiograph, osteoporosis, fibrous or bone
ankylosis.
Treatment of diseases of the joints is carried out accordingly, taking into account the period. In the
acute period of the disease, the treatment of arthritis is based on the principles of maintaining rest
for the diseased joint. Treatment is carried out with position, heat and ultraviolet radiation are
applied to reduce pain in the affected joints. In the subacute stage, in order to preserve the
functions of diseased joints, complex physical rehabilitation is indicated: treatment with position,
therapeutic massage, therapeutic exercises in combination with physiotherapy procedures (UV,
thermal procedures, hydrogen sulfide baths). In chronic In the process, complex physical
rehabilitation includes therapeutic massage, therapeutic gymnastics, balneotherapy (hydrogen
sulfide, radon baths), mud therapy in combination with sanatorium conditions.
The whole system of physical rehabilitation is divided into 3 stages: in a hospital; in a sanatorium or
clinic; at home with the advice of specialists in physical rehabilitation. In the process of physical
rehabilitation are
the following tasks:
- impact on the affected joints in order to develop their mobility and prevent further dysfunction;
- strengthening the muscular system and increasing its performance;
— improvement of blood circulation in the joints, the fight against atrophy in the muscles;
- counteracting the negative effects of bed rest (stimulation of the functions of blood circulation,
respiration, increased metabolism);
- reduction of pain sensations by adapting the affected joints to dosed physical activity;
- rehabilitation of physical performance.
Stage I of physical rehabilitation in a hospital refers to the beginning of the subacute period of the
disease (pronounced exudative phenomena - swelling, pain contractures, limitation of movements,
deformity of varying degrees, muscle atrophy). In the first period, passive exercises are used for
diseased joints. They should not be accompanied by pain and a pronounced protective reaction in
the form of reflex muscle tension. Passive movements should be preceded by a therapeutic massage
to relax the muscles. The dosage of passive exercises is 4-6 times, followed by a rest pause to relax
the muscles. In addition to passive exercises, active ones are used for healthy limbs. The duration of
therapeutic exercises is 25-30 minutes.
To obtain a better therapeutic effect, it is recommended to give tasks to patients to independently
perform exercises with a diseased limb with the help of a healthy one (autopassive exercises)
several times a day (8-10 times).
In the second period of physical rehabilitation at this stage, with a decrease in exudative
phenomena, the patient can make the first active movements in diseased joints in the most
comfortable initial positions. Active and passive exercises are used, as well as passive exercises
with the help of a healthy limb to increase the range of motion, exercises with shells (ladder for
developing movements in the joints of the fingers, sticks, maces, dumbbells - 0.5 kg), simulators
and a gymnastic wall are used. Rocking exercises are used to develop the radio-metacarpal, elbow,
shoulder, knee and hip joints.
Therapeutic exercises are carried out at a slow or medium pace. Repetition of exercises - 12-14
times, duration of classes - 35-40 minutes. Before performing the exercises, a therapeutic massage
is performed, physiotherapeutic procedures are applied (UV, paraffin applications,
ozocerite). Patients conduct independent exercises to perform exercises.
Stage II of physical rehabilitation in a sanatorium or clinic is prescribed when there are no
inflammatory phenomena in the affected joints, but there are still some restrictions on
movements. Special exercises are aimed at stretching the ligamentous apparatus of the affected
joints and strengthening the muscles, especially the extensors. Therapeutic exercises are carried out
in the initial standing position, active exercises are used for sick and healthy joints. In therapeutic
exercises, exercises are widely used on simulators, on the gymnastic wall (mixed and pure hangs,
etc.), with stuffed balls, dumbbells. The pace is slow and medium, the dosage is 12-14 times, the
duration of classes is 40-45 minutes. A therapeutic massage is applied before therapeutic
gymnastics.
The complex of physical rehabilitation at this stage includes mud therapy (Staraya Russa) or
balneotherapy (Matsesta and others). These procedures are used before therapeutic exercises. Self-
execution of physical exercises by patients is mandatory to ensure the best therapeutic effect.
Stage III physical rehabilitation refers to the period of convalescence, has a preventive value and is
carried out in a clinic or at home. The main task of the stage is to maintain and preserve the
achieved movements in the joints. Without systematic training, movements in the affected joints
may gradually deteriorate. Patients are engaged in a developed set of exercises depending on the
affected joints. It is recommended to perform a set of exercises twice a day: in the morning after
sleep and in the evening, no later than 2 hours before bedtime. Dosage - 8-10 times, the pace is
average. For young and middle-aged people, skiing, short-term rowing, swimming (water
temperature 28-29 ° C), tennis, volleyball can be recommended. Elderly people with ischemic heart
disease, angina pectoris, stage II B hypertension, only walking is allowed. All of the above forms of
exercise therapy are used under the supervision of a doctor, exercise therapy methodologist and the
attending physician of the clinic.
The effectiveness of treatment is determined by the range of motion in the joints of the limbs using
a goniometer.
15. Means and methods of medical rehabilitation used in pulmonology.
• Pulmonary Rehabilitation (RP) is an evidence-based. interdisciplinary and comprehensive
intervention for patients with chronic lung disease who have impaired function resulting in
disability.
• When organizing pulmonary rehabilitation, it is recommended, along with the clinical diagnosis,
to use the concept of rehabilitation diagnosis, which is a complex characteristic of the patient's
medical, psychological, and social problems, describing all health domains in the categories of the
International Classification of Functioning, Disabilities and Health
Contraindications to the inclusion of a patient in a respiratory rehabilitation program are:
• angina pectoris
• recent myocardial infarction
• severe pulmonary hypertension
• chronic heart failure
• decompensation of diabetes mellitus
• inability to exercise due to orthopedic or other reasons
• mental illness
• dementia
• severe hypoxemia (uncorrected by oxygen therapy)
• lack of motivation.

Routine (steps) for pulmonary patients can be as follows:

• The first stage is inpatient (intensive care unit, intensive care unit, pulmonary unit, surgical /
thoracic unit).
• The second stage is a rehabilitation department or a center for patients with somatic pathology
(pulmonological profile), a day hospital of the polyclinic.
• The third stage: a polyclinic for outpatient rehabilitation, a program of "home" pulmonary
rehabilitation under the patronage, spa treatment, remote online or off-line rehabilitation.
• Pulmonary rehabilitation includes remedial gymnastics (special complexes of respiratory and
general exercise therapy aimed at maximum adaptation of the patient to the usual way of life),
dosed walking, terrenkur, hydrokinesitherapy, exercise on simulators (cyclic and strength), spatial
gymnastics, skiing, game sports, physiotherapy (inhalation, various methods of postural drainage,
magnetotherapy, laser therapy, balneotherapy, aromatherapy, acupuncture, special methods -
apparatus respiratory training, ozone therapy), massage, the use of oxygen therapy (if necessary),
smoking cessation programs

Means, forms, methods of exercise therapy for organ diseases:

• Breathing exercises are divided into the following:
1. Dynamic breathing exercises are combined with movements of the arms, shoulder girdle, trunk
(increase in the volume of the ventilated surface)
2. Static breathing exercises are carried out with the participation of the diaphragm, intercostal
muscles, abdominal muscles and are not combined with the movements of the limbs and trunk.
E. a) exercises that change the type of breathing: chest breathing, abdominal breathing, full
breathing
F. b) exercises with dosed resistance
3. General breathing exercises
4. Special breathing exercises
5. Drainage breathing exercises are called exercises that promote the outflow of secretions from
bronchial tubes into the trachea, followed by the production of sputum during coughing.
• Distinguish between drainage body positions and drainage exercises.
• Drainage positions of the body - postural drainage. The method consists in taking a specially set
individual position of the body, aimed at the outflow of exudate along the respiratory tract
according to the gutter principle.
• Drainage exercises - exercises that improve the outflow of sputum (static and dynamic), i.e. active
drainage. Exercises for different groups are performed using frequent changes of starting positions
and postural drainage techniques.

Sound gymnastics:
• special breathing exercises, consisting in pronouncing consonant sounds in a certain way -
buzzing, whistling and hissing, growling and their combinations.
• The mechanism of the therapeutic effect: the vibration of the vocal cords is transmitted to the
smooth muscles of the bronchi, lungs, chest, relaxing the spasmodic bronchi and bronchioles.
• The purpose of the classes is to develop the correct ratio of inhalation and exhalation, i.e.
normalize this ratio as 1: 2, at which the most complete gas exchange occurs in the alveoli.
• In bronchial asthma, buzzing, growling, hissing sounds are pronounced loudly, energetically,
exciting. In chronic obstructive pulmonary disease with severe respiratory failure - gently, quietly,
you can whisper, soothing.

Method of volitional elimination of deep breathing by K.P. Buteyko:

• The technique was developed by the Novosibirsk physician K.P. Buteyko in 1960 and is aimed at
volitional correction of incorrect (deep) breathing with a gradual complete rejection of it, since
deep breathing causes a lack of carbon dioxide in the blood, a change in the acid-base state
towards alkalosis and tissue hypoxia (with a lack of carbon dioxide in the body, oxygen firmly
binds to hemoglobin and does not enter cells and tissues).
• The objectives of the method: to normalize the ratio of inhalation and exhalation, to reduce the
speed and depth of inhalation, to develop a compensatory pause after a long calm exhalation, to
normalize the carbon dioxide content in the blood. to reduce the number of asthma attacks, to
prevent their occurrence.
Paradoxical breathing exercises by AN. Strelnikova:
• This breathing exercise was developed by AN. Strelnikova in 1940-1950. to restore the voice and
expand its range in professional singers, then it was accidentally discovered that this technique
helps to relieve an attack of suffocation.
• Gymnastics is called "paradoxical", since inhalation and exhalation are performed simultaneously
with the movements of the arms, trunk and legs, which impede this phase of breathing.
• When the chest is compressed, inhalation is made, when the chest expands, exhale. The inhalation
should be short, sharp, noisy, active, forced by the diaphragm; exhalation occurs passively,
spontaneously. Inhalation is carried out only through the nose, exhalation independently, passively
(so that it cannot be heard), preferably through the mouth, you should not delay the exhalation.
Healing walking:
• For patients with a high tolerance to physical activity, walking is alternated with dosed jogging at
a slow pace without acceleration and jerking. Such running should not cause shortness of breath
and cardialgia. The pulse rate is not higher than 80% of the threshold individual submaximal load.
Terrenkur:
• Alternating walking on flat terrain and ascents from 3 to 15 °. The load is determined by the pulse
rate, which should be 50-60% submaximal for a given age or be individual for a given patient.
The pace of walking should be slow (60-80 steps per minute) or medium (80-100 steps per
minute).
Anti-inflammatory methods:
• Ultraviolet irradiation (UV) of the chest area in erythemal increasing doses, the use of ultra-high
frequency (UHF) currents with high penetrating ability. High-frequency electromagnetic fields
(inductothermy), affect the area of projection of the roots of the lungs, with a sluggish protracted
course of the process, the phenomena of hypocorticism, it is possible to influence the area of
projection of the adrenal glands in order to stimulate their secretory activity. Decimeter wave
therapy (DWT) has a sparing effect on hemodynamics. In patients with concomitant diseases of
the cardiovascular system, weakened and elderly patients, as anti-inflammatory therapy, it is most
advisable to use a low-frequency alternating (LFA) and rotating pulsed magnetic fields (RIMP),
which have a hypotensive, sedative, decongestant, anticoagulant effect. With a sluggish
inflammatory process, it is preferable to use drug electrophoresis; the choice of a medicinal
substance is determined by its pharmacological properties and the characteristics of the clinical
course of the disease. A distinct regression of inflammation is provided by low-frequency
ultrasound therapy. Heat and mud therapy (paraffin, ozokerite, therapeutic mud peloids), has a
resorbing, antispasmodic effect, increases mucociliary clearance.
2. Mucolvtic methods
• The use of inhalation of various mucolytic drugs: lazolvan, acetylcysteine, fluimucil, mucosolvin
and others, which help thin sputum and improve its evacuation from the respiratory tract. The
course of treatment is 5-7 inhalations.
• When bronchospasm is attached, bronchodilator methods are used - in order to increase bronchial
patency, nebulizer inhalations of various bronchodilators (anticholinergics, adrenomimetics,
sympathomimetics, calcium antagonists, etc.) are used.
• Speleotherapy - the therapeutic effect of the microclimate of salt mines and karst caves, in
addition to the low content of allergens and pollutants in the air, is due to its high ionization and
the presence of highly dispersed aerosols in it (especially in the case of salt caves, sodium
chloride), as well as constant moderate temperature, humidity and stable pressure.
• Flutter therapy - in the rehabilitation of patients with COPD, "breathing with positive expiratory
pressure", or "PEP-therapy" (from the English "PEP" - Positive Expiratory Pressure) is
successfully used.

3. Improving the drainage function and ventilation of the bronchopulmonary system:

• Diadynamic currents (DDC) or Bernard currents activate the vasomotor and respiratory centers,
which is accompanied by relaxation of bronchial smooth muscles and stimulation of mucociliary
clearance. Sinusoidal modulated currents (SMC) or amplipulse therapy freely penetrate deep into
tissues, have a direct effect on nerve receptors, including tusogenic (cough) receptors located in
large bronchi, in the tracheal bifurcation region, as well as on striated and smooth ones, including
respiratory muscles, which leads to an increase in sputum evacuation and a decrease in bronchial
obstruction. High frequency ultrasound (880 kHz) to eliminate bronchospastic reactions.
Electrosleep during attacks of respiratory dyspnea in persons with psychoneurotic reactions.

4. Immunostimulating methods:
• Supravenous laser blood irradiation (SLBI) on the projection of the cubital vein. Extremely high-
frequency therapy (EHF) on the area of the lower third of the sternum, paravertebrally in the area
of C6-D4, on acupuncture points.
5. Antihypoxic methods:
• Due to the fact that respiratory failure is the main cause of death in patients with COPD, in
international documents, a pathogenetically substantiated method for correcting hypoxemia
provides for oxygen therapy - short-term and long-term.
Normobaric hypoxic therapy (interval hypoxic training): Achievement of a positive effect of
hypoxic exposure is associated with an increase in the body's nonspecific resistance to a wide range
of adverse environmental factors.

6. The use of massage in patients with respiratory diseases:

• Massage for diseases of the respiratory system is prescribed when the acute manifestations of the
disease subside, the body temperature drops to subfebrile, the symptoms of intoxication disappear
and the general condition of the patient is normalized. Massage is indicated for diseases such as
resolving pneumonia, bronchial asthma, COPD.
• Mainly used are classical manual massage, acupressure, segmental-reflex. vibration using various
vibrating massagers, cupping massage.
• Massage area: chest, back and back of the neck, lower limbs.

7. The use of Reflexology in patients with respiratory diseases:

Reflexology is a method of treatment based on physical impact on acupuncture points (AP). The
following types of reflexotherapy are most often used in
clinical practice: classical acupuncture, laser puncture, magnetopuncture, moxibustion, su-jok,
electropuncture (impact on AP with impulse currents of low strength and low frequency), extra
high-frequency puncture.

8. Psychotherapy:
Psychotherapy methods can significantly improve the condition of patients with chronic respiratory
diseases, especially with COPD and bronchial asthma.
• reduction of clinical manifestations of the disease;
• improving the quality of life;
• increasing physical and emotional participation in daily life.

9. Nutritional therapy:
Pulmonary cachexia is one of the systemic manifestations of COPD. Under the influence of
inflammatory mediators and products of oxidative stress, pronounced dystrophic changes in
myocytes and damage to skeletal muscles occur. Loss of muscle mass, including respiratory
muscles, aggravates respiratory failure, impairs the ability of patients to adequately participate in
training programs, which can reduce and limit the effectiveness of medical rehabilitation.
10. Phytotherapy:
Taking into account the etiopathogenetic features of inflammatory diseases of the respiratory
system, medicinal plants of several pharmacotherapeutic groups are mainly used.
16. Exercise testing used in pulmonology.
Shtange test:
• The tested man/woman in sitting position after 3-5 min. rest do deep inspiration and deep
expiration then stop breathing after deep but not maximum inspiration with close mouth
and hold one's nose. Stopwatch used; normal breath-holding is 40-50 sec., well trained
sportsmen up to 5 min., children 6 years old: from 15 sec. (for girls) to 20 sec. (for boys);
children 10 years old: from 20 sec. (for girls) to 35 sec. (for boys).
• Genshi test (or respiration stop in expiration phase):
• The same as in Shtange test but breath hold in expiration phase. Not trained people: 25-30
sec., sportsmen: 30-90 sec.

Rosental test:
• This test assesses the functional capacity of respiratory muscles. Using spirometer 5 times
with 10-15 sec. interval, fix Lungs Vital Capacity (LVC). Normally same readings fixed,
when LVC gradually increase (good), when decrease (not satisfied).

Serkin combined test:

• The first phase: determine time of breath-holding in inspiration phase in the sitting
position
• second phase: determine time of breath-holding in inspiration phase straight after 20
squatting in 30 sec
• third phase: after 1 min. repeat the first phase.

Skibinskaja index:
• Takes measure of lung vital capacity (LVC) (ml), breath-holding (T) (sec.) and Ps (per
min). Assessment of cardio-respiratory system formula:

• Index assessment: less than 5 – very bad, 5-10 – poor, 10-30 – satisfactory, 30-60 – good,
more than 60 – excellent. Trained sportsmen have index more than 80.
17. Basic principles and methods of using electrotherapy. Indications and
contraindications.
Direct current:
Galvanization and drug electrophoresis
Galvanization – therapeutic procedure that uses direct continuous current of low voltage
(30-80 V) and also of low strength (up to 50 mA), connected to the patient via contact
electrodes. Graphically it is a type of direct line.
Method:
• Current is connected to the patient via two electrodes.
• Electrodes – this is electro conductive plate of milled lead (aluminium, noble metals) or
carbonaceous cloth and rather greater gasket from hydrophilic material (gauze, flannel,
thick flannelette) for protect skin under electrolysis products. If the surface is uneven
galvanization conducts through the water (glass or porcelain basins can be used).
• Electrode can be situated longitudinal, transversely and obliquely- transversal.
• Classification according to pathological areas:
- local influence: when the pathological area is between the electrodes;
- general influence: galvanization of the whole body (four-chamber bath, by Vermel);
- segment-reflex influence: electrodes are located in the reflexogenic zones of the skin
(which is specified to this pathology, e.g. tender Zahar’in-Head's zones, BAP).
Dose depends on current force and its duration.
Indications:
• injuries, infections, toxicities, PNS (radiculitis, neuritis, neuropathy, neuralgia,
neuromyositis);
• diseases of CNS (blood vessels, infections, trauma) and their complications: migraine,
brain transient ischemia and encephalitis complications);
• gastrointestinal diseases (gastritis, colitis, cholecystitis);
• CVS, cardiac ischemic diseases, hypertension;
• chronic inflammatory diseases including;
• obstetrics and gynaecological diseases;
• in surgery: chronic osteomyelitis, fractures;
• in ophthalmology: glaucoma, retina degeneration and infections;
• in stomatology: neural and infectious diseases.
Drug electrophoresis:
This is special electro-pharmacological method, which use permanent electrical current to
introduce drugs to organism.
The drugs introduced to organism follow the route of current i.e. places of low resistance:
• ducts of skin glands;
• intracellular spaces;
• at 8-10% intra skin via membranes.
Advantage of drug electrophoresis:
1. Local high drug concentration can be achieved, i.e. there is no need to saturate the whole
organism.
2. No side effects.
3. Supports the prolongation of drug action.
4. The ion form of drugs is more effective than the molecular one (Mg2SO4).
5. Painless.
6. Has a complex and integral action.
Impulse electrotherapy:
In comparison with direct current impulse therapy has the advantage:
• Less probability of adaptation because the possibilities and action parameters and the
diapason of changes are vast enough to be adapted.
• Can reach deep tissues.
• Used for the best realization specific component this indicates or illustrates its amplitude
value.
• Tolerated better by pts., especially by patients with CVD.
• Impulse effects are different by their physical characteristics (impulse duration, pause,
frequency and depth of modulations).
• A big advantage is its huge physical impulse therapeutic potential, this can be explained by
the fact that all bio systems act in impulse regimen, i.e. the reaction to impulsive therapy is
physiological.
DDC (Bernar’s current) method – is a method of impulse therapy, by which patients get a
low frequency half-sinusoidal form of impulse current, of 50-100 Hz, during the period of
0,01 sec. they can be mobilized and their frequency is changeable.
Mechanism is the same as for the galvanic current. And therapeutic effects from these
currents are results of galvanic currents.
Amplipulse therapy:
Alternating current - SMC. Amplipulse therapy: a method of electrotherapy which uses
alternating sinusoidal modality current (SMC) of low voltage and low frequency 10-150 Hz.
Therapeutic effects:
- Stimulation (cell depolarization and repolarisation).
- Pain relief.
- Spasmolytic.
Electrosleep:
• A method of neurotropic therapy, the basic idea is to affect the CNS with permanent
impulse current (right angle form) of low frequency (1- 160 Hz) and low voltage (up to 10
mA). Impulse currents 0,2-0,5 mc (corresponding to the chronaxia of the brain) are used.
Impulse current with such parameters stimulate physiological sleep when it acts by eye-
occipital method. Mechanism based on the reflex & direct action of current on the brain.
There are two phases of therapeutic effects of electrosleep:
• Inhibition: sleepy situation; Ps decrease, respiration, AP and electro activities of
braindecreasing.
• Stimulation: or reactivated directly when the stimulating agent stops its action, i.e.
patient is in a good mood, active and able to work.
• Indications: neuroses, NCD, starting phase of cerebral vessels atherosclerosis; - injuries of
skull and brain complications, chorea, encephalitis complications, AP increase and
decreasing of AP I- II, ischemic heart diseases I-II, bronchial asthma, diseases of GIT,
eczema, gestosis of second half of pregnancy.
• Contraindications: eye/ face/skin diseases, hysterical conditions, epilepsy, presents of
metal things in skull area, current intolerance, general contraindications to PT
18.Basic principles and methods of application of magnetotherapy. Indications and
contraindications.

• Electromagnetic therapy or Electromagnetic field therapy refers to therapy involving the

use of magnets or electromagnets.
• Types include:
- Bioelectromagnetics, the study of how electromagnetic fields interact with and influence
biological processes.
- Electrotherapy, the use of electrical or electromagnetic energy in medicine;
- Electromagnetic therapy (alternative medicine), evidence of efficacy is lacking.
- Pulsed Electromagnetic Field Therapy, or PEMF, the use of weak electromagnetic fields
to initiate osteogenesis.
• Low frequency electromagnetic therapy has been proposed by practitioners for a variety
of purposes, including cell growth promotion, pain reduction, improved blood circulation,
bone repair, increased wound healing, sedative effects, enhanced sleep, and arthritic relief.
• Pulsed electromagnetic field therapy (PEMF) is a medical treatment that purportedly helps
to heal bone tissue reported in a recent NASA study.
• This method usually employs electromagnetic radiation of different frequencies - ranging
from static magnetic fields, through extremely low frequencies (ELF) to higher radio
frequencies (RF) administered in pulses.
• Delayed and no-union fractures: It was demonstrated that a pulsed magnetic field applied
across the site of a bone fracture can accelerate the healing process. The mechanism of
osteogenesis is not clear; however, the use of PEMF therapy as an adjuvant therapy for
delayed- and non-union fractures was supported by empirical evidence collected through
clinical studies.
• While PEMF therapy may offer some benefit in the treatment of fractures, the evidence is
inconclusive and is insufficient to inform current clinical practice.
• Post op pain and edema: There are few clinical trials that have found PEMF therapy to be
an effective treatment for tissue trauma, particularly in the early stages of inflammation.

EHF therapy
• EHF therapy is a biophysical theory studying mechanisms of action on the living
organism of electromagnetic radiation (EMR) of millimeter range (1– 10 mm) high
frequency (30–300 GHz) of low intensity, and medical practice using effects of the above
mentioned action at treatment of different ailments.
• Electromagnetic waves of millimeter range are of low penetrative capacity in biological
tissue (0,2 - 0,8 mm), they are practically fully absorbed by surface layers of the skin
(water molecules, hydrated albumens, molecules of collagen, cells of connective tissue),
without any thermal action. Thus, EHF waves don’t act directly on internal organs of the
patient.
19.Basic principles and methods of application of light therapy. Indications and
contraindications.
Phototherapy - is therapeutic usage of electromagnetic oscillation of optic diapason,
including infra-red, visible and ultra-violet rays.
Infra-red rays: The spectre of electromagnetic oscillation with wavelength from about
800nm to 1 mm. In phototherapy the waves used are from 760nm – to 2 µm, which obtained
from artificial sources of light. These rays absorbed to the depth of 1 cm. The longest infra-
red reaches to 2-3 cm deeper.
The infra-red radiation has relatively low kinetic energy, so, when this energy absorbed
causes the increasing of oscillatory and rotational movements of atoms and molecules:
• Brownian motion.
• Electrolytic dissociation.
• Ions movements.
• Accelerate electrons speed in their orbits.
• The result is temperature generation.
All worm objects are sources of infra-red rays, human body is not
exclusion; on the contrary it’s a potential source of these radiation and also good
absorptive of it. Temperature generation leads to rise of temperature of illuminated
cutaneous covering on 1-2°C and provoke local vessels reactions.
• The heat energy considerably accelerates tissues metabolic processes. Activation of
microcirculatory bed and vascular permeability increasing enable to evacuate the cell
autolysis products. Some fluid evaporates with sweat enhancing the dehydration of
inflammatory focus so IR radiation use is effective in last phase of inflammatory process.
Therapeutics effects: anti-inflammatory, metabolic, local analgesic, vasoactive.
• Indications: bad healing ulcers and wounds, chronic and subacute nonsuppurative
inflammatory diseases of internal organs, burns and frostbites, diseases of peripheral
nervous system with the pain syndrome (neuralgia, myositis), complications of
musculoskeletal system injuries.
• Contra-indications: acute purulent inflammatory diseases, brain circulation
insufficiency, vegetative dysfunction, sympathalgia, propensity to haemorrhage, active
tuberculosis.
Chromotherapy: is the therapeutic usage of seen rays (400-760 nm).
Seen rays have a signal or stimulated character and via sight organ they determine the
human daily biorhythm.
Colours selectively effect the excitability of higher cortical and subcortical nervous centres,
therefore they modulate the human psycho- emotional status:
• red and orange rays - stimulate cortical and subcortical centres
• blue and violet - inhibit those centres;
• green and yellow - balance stimulation and inhibition processes in brain cortex;
• white light - balance the human vital activity and his efficiency. Now known, the sky blue
and blue radiation photobiologically destructs hematoporphyrin, and, as the blue spectrum
not penetrates deep, it is used to cure the jaundice of the newborn. So, as a result of action
of these rays, bilirubin catabolic products will be formed, they are water soluble and they
have excreted with urine and bile.
• Therapeutic effects: psycho-emotional, metabolic, photo destructive
• Indications: tiredness, neuroses, sleep disturbance, trophic ulcers, bad healing wounds,
jaundice of the newborn.
• Apparatus:Minin's lamp, Solux - with light filters.

Ultra-violet radiation
• UVR-used when patient needed to be radiated with ultra-violet lights
• UVL- Radiation with UVL stimulates photo-chemical and photo-biological reactions in
the skin: destruction of protein molecules (photolysis), synthesis of more complex
biological molecules (photo-biosynthesis) or synthesis of molecules with more
complicated photo biophysical, chemical characters (photo isomerisation).
Therapeutic effects: anti-inflammatory, desensitizing, anaesthetic, trophic (metabolism
time), bactericidal, immunostimulating (UVR of blood), Support function of CVS, RS and
CNS.
• Devices:
1. Integral - radiate all spectrum of UVR.
2. Selective - radiate LUV or SUV.
a) Arc mercury quartz tubular torch – AMТ; for group, individual,
general and local irradiation.
b) Arc bactericidal lamp – AB; for local irradiation or irradiation of
mucous membranes.
Methods: 1. General. 2. Local. 3. UVR of blood.

20.Complex application of therapeutic physical factors. Classification of therapeutic

physical factors, general contraindications to their appointment.
Classification of physical factors:
• Electric current with various characteristics (electrotherapy);
• Electromagnetic fields (magnetic therapy);
• Electromagnetic radiation in the optical range -the light (phototherapy);
• Temperature (heat therapy, cryotherapy);
• Water (hydrotherapy);
• Modified air (aerotherapy);
• The mechanical vibrations of the medium (ultrasound therapy).

Contraindications:
1) malignant neoplasms;
2) systemic blood disorders;
3) marked cachexia;
4) circulatory decompensation;
5) haemorrhage or suspicion on it; 6) sever psychosis;
7) fever;
8) active tuberculosis;
9) individual intolerance of PT.
 1. Anaphylaxis, principles of diagnosis, emergency care, prevention
Anaphylaxis is an acute, potentially life-threatening, type 1 hypersensitivity reaction,involving the
sudden IgE-mediated release of histamine mediators from mast cells and basophils in response to a
trigger (e.g., food, insect stings, medication). Anaphylactoid reactions (a subtype of pseudoallergy) are
IgE-independent reactions that result from direct mast-cell activation (e.g., in response to opioids); the
clinical presentation and management are the same as for anaphylaxis.
Diagnostic criteria for anaphylaxis
If any of the following criteria are fulfilled, anaphylaxis is likely. The onset of symptoms must be acute
(minutes to hours).
1) Known allergen exposure with hypotension (SBP < 90 mm Hg or ≥ 30% decrease from the
baseline)
2) Acute illness with skin and/or mucosal symptoms (e.g., hives, swollen lips, tongue, and/or uvula)
AND ≥ 1 of the following:
Cardiovascular: SBP < 90 mm Hg or ≥ 30% decrease from baseline and/or altered mental status,
syncope, ischemic chest pain, incontinence, or anuria
Respiratory: dyspnea, hypoxia, stridor, hoarseness, wheezing, cough
3) Suspected allergen exposure AND ≥ 2 of the following:
 Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea
 Cardiovascular: systolic BP < 90 mm Hg or ≥ 30% decrease from baseline, and/or altered
mental status,syncope, ischemic chest pain, incontinence, anuria
 Respiratory: dyspnea, hypoxia, stridor, hoarseness, wheezing, cough
 Skin/mucosal: hives, angioedema, pruritus, flushing
Management
Stabilize the patient (ABCDE approach).
 Airway assessment and management (see “Airway management and ventilation in anaphylaxis”)
 Rapid sequence intubation (RSI) for airway compromise
 Oxygen: Provide FiO of 100% (e.g., high-flow O by nonrebreather mask).
 Aggressive IV fluid resuscitation if hypotension present (large-bore IV access; administer 1–2 L
0.9% saline IV bolus)
 Position the patient supine.:
Remove inciting allergen
Administer epinephrine IM 1:1,000 (1 mg/mL) into the anterolateral thigh
 Repeat every 5–15 minutes as needed
 IM epinephrine injections always require a more concentrated solution (1:1,000)
 Epinephrine autoinjector may be used.
Once stabilized, consider adjunctive therapy with antihistamines; , corticosteroids (e.g., methylprednisolone)
Continuous reassessment and subsequent management
PREVENTION
Pre-treatment for in-hospital triggers
Consider corticosteroid and/or antihistamine pre-treatment if known triggers are crucial to clinical care
and difficult to avoid: e.g., radiocontrast material (most common), chemotherapeutic agents, blood
products, antivenom.
 2. Urticaria, etiopathogenesis, principles of treatment and prevention.
Definition
Urticaria (from Latin irtica - nettle) is a group of diseases, the main clinical symptom of which is transient
itchy rashes ranging in size from a few millimeters to several centimeters.
Pathogenesis.
Urticaria can proceed by immune (I-IV types of reactions) and non-immune mechanisms (Table 2).
Table 2. Etiological classification of urticaria
Etiology Mechanism
idiopathic Unknown.
autoimmune IgG autoantibodies to mast cell IgE receptors
or to IgE receptors associated with mast cells.
Physical stimuli Direct release of mediators by mast cells
mi.
The action of drugs Decreased kinin metabolism, increased levels
leukotrienes.
infectious agent Complement activation by immune complexes.
allergic reactive type.
IgE-unbound degra- Unrelated to receptor activation.
nullification of mast
cells
Inflammation of small vessels with the participation of
Vasculitis immunoglobulin
lins.
DIAGNOSIS
Clinical picture
The clinical picture of urticaria is characterized by:
1. Rashes in the form of blisters, accompanied by skin itching at the site of formation of skin elements.
2. Rashes are usually characterized by complete resolution within 24 hours and the possibility of occurrence
on any area of the skin.
3. With physical urticaria, complaints about the occurrence of rashes and itching after contact with heat, cold,
solar radiation, vibrating objects, rubbing the skin against some things.
4. Some patients describe ARVI, stress, medication, climate change as provoking factors.
5. Positive effect when using H1-blockers of histamine.
6. The presence of contact with the allergen.
7. Burdened allergic history of the patient or relatives.
8. In the anamnesis, the patient may have undergone surgical interventions, parasitic invasions, autoimmune
and infectious diseases, pregnancy, stress oncopathology, etc.
9. After the disappearance of the rash at the site of the blister , no changes remain.
10. For rashes, the presence of cyclical relapses is characteristic (for example, connection with the menstrual
cycle).
11. In 50% of cases, urticaria is combined with angioedema.
Urticaria can be an independent disease (primary) or a symptom of other diseases (secondary).
Acute urticaria can last from several hours to several days and weeks, most often acute urticaria is allergic in
nature. In contrast, chronic urticaria (occurs for months, and in some cases - years) and rarely has an allergic
nature.
Features of the clinical picture for various types of urticaria:
Allergic urticaria.
1. More often acute or episodic.
2. The most common allergens are food, drugs, insect venom, latex.
3. Concomitant allergic diseases and aggravated allergic history.
4. Positive results of an allergological examination.
5. Efficiency of elimination measures.
Autoimmune urticaria.
1. The course of the type of chronic idiopathic urticaria.
2. Frequent presence of autoimmune thyroiditis.
3. Severe general symptoms (weakness, gastrointestinal dysfunction).
4. Presence of histamine-releasing anti -Fcε-RI antibodies and anti-IgE antibodies.
5. Positive test with autoserum.
Cold urticaria.
1. Occurrence upon contact with cold.
2. Positive cold test.
3. It can be acquired ( against the background of the underlying disease, for example: viral hepatitis,
lymphoproliferative disease, etc.) or congenital.
Solar urticaria.
1. Occurs under the action of ultraviolet radiation on open areas of the body after exposure to the sun, there
may be a fixed light urticaria
2. The disease can be primary (idiopathic luminous urticaria) and secondary, when luminal urticaria is
associated with the action of drugs (tetracyclines) or with the underlying disease (systemic lupus
erythematosus, thyroiditis, gastrointestinal dysfunction).
Dermographic urticaria.
1. The appearance of blisters with mechanical irritation of the skin.
2. Itching precedes the appearance of rashes.
3. The phenomenon of dermographism is reproduced by intense dashed skin irritation with a blunt object
(spatula).
Vibratory urticaria/angioedema.
1. It is characterized by the appearance of a rash and edema in places exposed to vibration.
2. Rash and swelling appear 4-6 hours after exposure to vibration, persist up to 24 hours.
5
Special forms of urticaria: Aquagenic urticaria
1. A rash with severe itching occurs immediately after contact with water of any temperature.
2. Characterized by the appearance of small blisters surrounded by erythematous spots.
Cholinergic urticaria
1. It occurs more often in young people.
2. Characterized by the appearance of pale pink blisters 1-5 mm in diameter, often surrounded by erythema,
rashes are generalized.
3. A provocative factor is physical exercise, stress, sweating, hot showers.
4. May be accompanied by systemic manifestations (hot flashes, weakness, palpitations, abdominal pain,
shortness of breath.
5. Reproduced by subcutaneous injection of acetylcholine.
Anaphylaxis/urticaria due to physical exertion
1. It is characterized by the appearance of skin itching, rashes, angioedema during or immediately after physical
activity.
2. May be accompanied by systemic manifestations, including bronchospasm, laryngeal edema, vascular
collapse.
3. The provoking factor may be the use of certain foods (alcohol, apples, shrimp, tomatoes, nuts, celery) before
physical activity.
Diagnosis of urticaria.
Urticaria is usually diagnosed visually
Table 3. Specific diagnostic tests for suspected physical urticaria.
Form of urticaria Test
Dermographic Stroke irritation of the skin of the forearm.
Cholinergic Physical exercise: walking up to 30 minutes, diving
in a hot bath (40-45 C) for 10-20 minutes or local
methacholine test.
Limited warmly- Heated cylinder with hot water (50-55 C) for 5 min.
wai
Cold 1. Application of an ice cube on the forearm area on
10-15min.
Physical exercise for 15 minutes in the cold (4
2. C).
3. Stay in a cold room (4 C) without clothes in
within 10-20 min.
from Walking for 20 minutes with a load of 6-7 kg
Slow yes- suspended
leniya on the shoulder.
Vibrating Attach a working laboratory to the forearm
vibrator for 4 min.
Aquagenic Apply a water compress at 35C for 30 minutes.
Irradiation of the skin with light of different
Sunny wavelengths.
Chronic urticaria.
The prognosis of the course of the disease is often unclear. In half of the patients, remission occurs within 6
months. from the onset of the disease, 40% - within 8 years, less than 2% will suffer from chronic urticaria for
more than 25 years.
Diagnosis example.
Acute allergic urticaria of moderate severity.
Treatment
1. Elimination therapy.
2. Exclude NSAIDs, ACE inhibitors and angiotensin-II blockers.
3. Treatment of infectious and chronic inflammatory processes.
4. Eliminate the impact of provoking physical factors.
5. Local use of coolants (0.5-1% menthol) in patients with mild urticaria.
6. MGCS is used for delayed pressure urticaria.
7. Drug treatment (Table 4, Table 5).
Table 4. Algorithm for the treatment of chronic urticaria in adults.
Patient education
and one. Standard doses of non-sedating H1 blockers
removing triggers 2. Increasing the dose of H1-blockers (maximum 4
times))
3. Add a second non-sedating H1 blocker
Trigger
identification 4. Consider prescribing a sedative
gerov, treatment of
basic H1 blocker at night
disease 5. Add or replace second line drugs
an example of antileukotriene drugs.
6. Add or replace with other second drugs
lines such as ciclosporin or low-dose
corticosteroids
Treatment for most patients with chronic urticaria is characterized by regular therapy for 3-6 months.
Features of the treatment of various types of urticaria:
1. Delayed urticaria from pressure: the use of GCS 20-40 mg / day, sometimes MGCS. The expediency of
using the remaining groups has not been clearly established.
2. Cholinergic urticaria: additional anticholinergics (bellantaminal), special physical education classes.
3. Cold urticaria: additional membrane stabilizers (ketotifen), short courses of oral prednisolone, cold
desensitization.
4. Solar urticaria: optional PUVA therapy, use of high protection sunscreen, hydroxychloroquine.
5. Chronic urticaria: the appointment of treatment is indicated for a long time. For most patients , 3-6 months,
and sometimes up to 12 months. with a gradual withdrawal for several weeks
Table 5. Rarely used drugs for urticaria.

Prevention of recurrence of urticaria of various types:

1. Allergic urticaria: general principles for the prevention of allergic diseases.
2. Urticaria associated with overheating: wear light clothing, refuse to visit the bath, sauna, do not drink very
hot drinks, avoid excessive physical activity.
3. Pressure urticaria: avoiding tight clothing, etc.
4. Cold urticaria: wear warm clothes, do not eat cold foods, etc.
5. Solar urticaria: avoid direct sunlight, use sunscreen.
6. Vibration urticaria: limiting exposure to triggers.
7. Anaphylaxis/Exercise-induced urticaria: Avoid contact with suspected allergens several hours before
exercise, or avoid contact after exposure.
3. Angioedema, etiopathogenesis, diagnosis and treatment.

Angioedema is a self-limited, localized swelling of the dermis, subcutaneous tissues, and/or submucosal
tissues caused by fluid leakage into the interstitial tissue. It is mediated by vasoactive substances and can be
classified as histamine-mediated (often secondary to allergic reactions and NSAIDs), bradykinin-mediated
(due to ACE inhibitor use or enzyme deficiencies), or unknown (idiopathic)
DIAGNOSIS
Initial evaluation
 The diagnosis is mainly based on history and clinical findings.
 Flexible fiberoptic laryngoscopy should be performed if there is no clear obstruction but clinical
suspicion of angioedema is high.
Further evaluation: indicated for follow-up or if the etiology is unclear [1][2]
Laboratory studies
 Serum mast cell tryptase: increased in histamine-mediated angioedema
 Evaluation of C1-INH deficiency in bradykinin-mediated angioedema
Imaging: not routinely recommended
 Neck x-ray or CT: may be used to rule out conditions that mimic angioedema, e.g., retropharyngeal
abscess
 Ultrasound or abdominal CT: may show bowel wall thickening

APPROACH
Emergency management
 Treat anaphylaxis, if present.
 Airway management
 Stop any potential triggers.
Once the patient has been stabilized, identify and treat the cause of angioedema
 Histamine-mediated angioedema treatment
 Bradykinin-mediated angioedema treatment

Emergency management
Evaluate for anaphylaxis: See anaphylaxis diagnostic criteria.
If there is concern for anaphylaxis:
 Give IM epinephrine
  Start aggressive supportive care (e.g., IV fluids, supplemental oxygen): See treatment of anaphylaxis
for the full algorithm.
Airway management
If airway compromise is present:
 See airway management and ventilation in anaphylaxis.
 Call anesthesia/otolaryngology for help.
 Prepare for difficult airway with rescue devices and set up for surgical airway.
 Awake fiberoptic intubation is preferred; RSI with paralytics should be avoided if
possible.
 A supraglottic airway (e.g., laryngeal mask) is not appropriate.
 Only attempt unassisted intubation if the risk of death is imminent and there is no expert available.
Stop any potential triggers: Remove potential exposures or offending medications (e.g., ACE inhibitors).
If airway compromise is suspected (stridor, wheezing, diminished air movement) or the patient is in shock,
administer IM epinephrine immediately, start oxygen and IV fluids, and consider intubation to protect the
airway. Once acute therapy has been initiated, the type and cause of angioedema should be determined.

Intubation is very risky in patients with angioedema and should only be performed by an expert. If there is
no time for help, then preparation for the procedure must also include rescue devices and surgical airway
equipment.

Case-based specific treatment

 ABCs intact and no airway compromise: Proceed with histamine-mediated angioedema treatment.
 Poor response to repeated IM epinephrine administration: Consider bradykinin-mediated angioedema
treatment.
Treatment of histamine-mediated angioedema and treatment of idiopathic angioedema
Standard therapy
 IV antihistamines: e.g., diphenhydramine
 IV glucocorticoids: e.g., methylprednisolone
 Positive response: Continue standard treatment.
 Poor response: Consider bradykinin-mediated angioedema treatment.
Idiopathic angioedema typically responds well to standard anaphylaxis treatment
If the initial response to standard therapy is followed by progression to anaphylaxis : see treatment of
anaphylaxis and acute management checklist for anaphylaxis.
Treatment of bradykinin-mediated angioedema and treatment of hereditary angioedema
 Administer one of the following targeted therapies:
o Purified C1-INH concentrate (protein replacement)
 Plasma-derived [1]
 Recombinant
o Kallikrein inhibitor: ecallantide
o Bradykinin-B2 receptor antagonist: icatibant
 Second-line or suspected ACE inhibitoR-induced etiology: fresh frozen plasma (FFP)
 Angioedema associated with tPA: requires special treatment algorithm; See “Complications of
thrombolysis.”
3. Primary immunodeficiency. Principles of diagnosis and treatment.
Diagnosis of Immunodeficiency Disorders
 Blood tests
 Skin tests
 A biopsy
 Sometimes genetic testing
Doctors must first suspect that an immunodeficiency exists. Then they do tests to identify the specific
immune system abnormality.

Doctors suspect immunodeficiency when one or more of the following occur:

 A person has many recurrent infections (typically sinusitis, bronchitis, middle ear infections, or
pneumonia).
 Infections are severe or unusual.
 A severe infection is caused by an organism that normally does not cause severe infection (such as
Pneumocystis, fungi, or cytomegalovirus).
 Recurring infections do not respond to treatment.
 Family members also have frequent and severe recurring infections.
Physical examination
Results of a physical examination may suggest immunodeficiency and sometimes the type of
immunodeficiency disorder. For example, doctors suspect certain types of immunodeficiency disorders
when the following are found:

The spleen is enlarged.

There are problems with the lymph nodes and tonsils.
In some types of immunodeficiency disorders, the lymph nodes are extremely small. In some other types,
lymph nodes and tonsils are swollen and tender.

History
To help identify the type of immunodeficiency disorder, doctors ask at what age the person began to have
recurring or unusual infections or other characteristic symptoms. Different types of immunodeficiency
disorders are more likely depending on the age at which infections starts, as in the following:

Younger than 6 months: Usually an abnormality in T cells

Age 6 to 12 months: Possibly a problem with both B cells and T cells or with B cells
Older than 12 months: Usually an abnormality in B cells and antibody production
The type of infection may also help doctors identify the type of immunodeficiency disorder. For example,
knowing which organ (ear, lungs, brain, or bladder) is affected, what the infecting organism is (bacteria,
fungus, or virus), and what the organism's species is can help.

Doctors ask the person about risk factors, such as diabetes, use of certain drugs, exposure to toxic
substances, and the possibility of having close relatives with immunodeficiency disorders (family history).
The person may also be asked about past and current sexual activity, use of intravenous drugs, and previous
blood transfusions to determine whether HIV infection could be the cause.

Tests
Laboratory tests are needed to confirm the diagnosis of immunodeficiency and to identify the type of
immunodeficiency disorder.

 Blood tests, including a complete blood count (CBC), are done. CBC can detect abnormalities in
blood cells that are characteristic of specific immunodeficiency disorders. A blood sample is taken
and analyzed to determine the total number of white blood cells and the percentages of each main
type of white blood cell. The white blood cells are examined under a microscope for abnormalities.
Doctors also determine immunoglobulin levels and the levels of certain specific antibodies produced
after the person is given vaccines. If any results are abnormal, additional tests are usually done.
  Skin tests may be done if the immunodeficiency is thought to be due to a T-cell abnormality. The
skin test resembles the tuberculin skin test, which is used to screen for tuberculosis. Small amounts
of proteins from common infectious organisms such as yeast are injected under the skin. If a reaction
(redness, warmth, and swelling) occurs within 48 hours, the T cells are functioning normally. No
reaction could suggest a T-cell abnormality. To confirm a T-cell abnormality, doctors do additional
blood tests to determine the number of T cells and to evaluate T-cell function.

 A biopsy may be done to help doctors identify which specific immunodeficiency disorder is causing
the symptoms. For the biopsy, doctors take a sample of tissue from the lymph nodes and/or bone
marrow. The sample is tested to determine whether certain immune cells are present.

 Genetic testing may be done if doctors suspect a problem with the immune system. The gene
mutation or mutations that cause many immunodeficiency disorders have been identified. Thus,
genetic testing can sometimes help identify the specific immunodeficiency disorder.

Screening
Genetic testing, usually blood tests, may also be done in people whose families are known to carry a gene
for a hereditary immunodeficiency disorder. These people may wish to be tested to learn whether they carry
the gene for the disorder and what their chances of having an affected child are. Talking with a genetic
counselor before testing is helpful.

Several immunodeficiency disorders, such as X-linked agammaglobulinemia, Wiskott-Aldrich syndrome,

severe combined immunodeficiency, and chronic granulomatous disease, can be detected in a fetus by
testing a sample of the fluid around the fetus (amniotic fluid) or the fetus’s blood (prenatal testing). Such
testing may be recommended for people with a family history of an immunodeficiency disorder when the
mutation has been identified in the family.

Some experts recommend screening all newborns with a blood test that determines whether they have
abnormal T cells or too few T cells—called the T-cell receptor excision circle (TREC) test. This test can
identify some cellular immune deficiencies, such as severe combined immunodeficiency. Identifying infants
with severe combined immunodeficiency early can help prevent their death at a young age. TREC testing of
all newborns is now required in many U.S. states.

Prevention of Immunodeficiency Disorders

Some of the disorders that can cause secondary immunodeficiency can be prevented and/or treated, thus
helping prevent immunodeficiency from developing. The following are examples:

HIV infection: Measures to prevent HIV infection such as following safe sex guidelines and not sharing
needles to inject drugs can reduce the spread of this infection. Also, antiretroviral drugs can usually treat
HIV infection effectively.
Cancer: Successful treatment usually restores the function of the immune system unless people need to
continue taking immunosuppressants.
Diabetes: Good control of blood sugar levels can help white blood cells function better and thus prevent
infections.
Treatment of Immunodeficiency Disorders
 General measures and certain vaccines to prevent infections
 Antibiotics and antivirals when needed
 Sometimes immune globulin
 Sometimes stem cell transplantation
Treatment of immunodeficiency disorders usually involves preventing infections, treating infections when
they occur, and replacing parts of the immune system that are missing when possible.

With appropriate treatment, many people with an immunodeficiency disorder have a normal life span.
However, some require intensive and frequent treatments throughout life. Others, such as those with severe
combined immunodeficiency, die during infancy unless they are given a stem cell transplant.

Preventing infections
 Strategies for preventing and treating infections depend on the type of immunodeficiency disorder.
For example, people who have an immunodeficiency disorder due to a deficiency of antibodies are at
risk of bacterial infections. The following can help reduce the risk:

 Being treated periodically with immune globulin (antibodies obtained from the blood of people with
a normal immune system) given intravenously or under the skin
 Practicing good personal hygiene (including conscientious dental care)
 Not eating undercooked food
 Not drinking water that may be contaminated
 Avoiding contact with people who have infections
 Vaccines are given if the specific immunodeficiency disorder does not affect antibody production.
Vaccines are given to stimulate the body to produce antibodies that recognize and attack specific
bacteria or viruses. If the person's immune system cannot make antibodies, giving a vaccine does not
result in the production of antibodies and can even result in illness. For example, if a disorder does
not affect production of antibodies, people with that disorder are given the influenza vaccine once a
year. Doctors may also give this vaccine to the person's immediate family members and to people
who have close contact with the person.

 Generally, vaccines that contain live but weakened organisms (viruses or bacteria) are not given to
people who have a B- or T-cell abnormality because these vaccines may cause an infection in such
people. These vaccines include rotavirus vaccines, measles-mumps-rubella vaccine, chickenpox
(varicella) vaccine, one type of varicella-zoster (shingles) vaccine, bacille Calmette-Guérin (BCG)
vaccine, influenza vaccine given as a nasal spray, and oral poliovirus vaccine. The oral poliovirus
vaccine is no longer used in the United States but is used in some other parts of the world.

Treating infections
 Antibiotics are given as soon as a fever or another sign of an infection develops and often before
surgical and dental procedures, which may introduce bacteria into the bloodstream. If a disorder
 (such as severe combined immunodeficiency) increases the risk of developing serious infections or
particular infections, people may be given antibiotics long-term to prevent these infections.

 Antiviral drugs are given at the first sign of infection if people have an immunodeficiency disorder
that increases the risk of viral infections (such as immunodeficiency due to a T-cell abnormality).
These drugs include oseltamivir or zanamivir for influenza and acyclovir for herpes or chickenpox.

 Replacing missing parts of the immune system

 Immune globulin can effectively replace missing antibodies (immunoglobulins) in people with an
immunodeficiency that affects antibody production by B cells. Immune globulin may be injected into
a vein (intravenously) once a month or under the skin (subcutaneously) once a week or once a
month. Subcutaneous immune globulin can be given at home, often by the person with the disorder.

 Stem cell transplantation can correct some immunodeficiency disorders, particularly severe
combined immunodeficiency. Stem cells may be obtained from bone marrow or blood (including
umbilical cord blood). Stem cell transplantation, which is available at some major medical centers, is
usually reserved for severe disorders.

 Transplantation of thymus tissue is sometimes helpful.

 Gene therapy, along with transplantation, is an intervention with the potential to cure genetic disease.
In gene therapy, a normal gene is inserted into someone's cells to correct a genetic abnormality
causing a disorder. Gene therapy has been used successfully in various primary immunodeficiency
disorders such as severe combined immunodeficiency, chronic granulomatous disease, adenosine
deaminase deficiency, and others. Although there are various limitations and obstacles with the
procedure, gene therapy provides promise for potential cures in the future.
5. Physiological immunodeficiencies (early childhood, pregnancy, old age). Clinical and laboratory
features, prevention of infectious diseases.
6. Side effects of drugs: etiology, pathogenesis, classification, clinical manifestations, course, treatment

Adverse reactions (AR), or adverse drug reactions , are harmful reactions that occur as a result of an
intervention associated with the use of a medicinal product, making it dangerous to continue taking it and
requiring prophylaxis or specific treatment, or a change in dosing regimen, or drug withdrawal. Unlike side
effects, toxic effects develop as a result of exceeding the dose of drugs and do not occur at usual therapeutic
doses.
Classification of side effects of drugs:
A. By predictability:
1. Predictable - due to the pharmacological action of drugs (80% of all PR), dose-dependent, have a certain
clinical picture (arterial hypotension when taking beta-blockers, etc.)
2. Unpredictable - not associated with the pharmacological action of drugs, not dose-dependent, develop
much less frequently than predicted, are caused by disorders of the immune system and exposure to external
environmental factors and do not have certain clinical manifestations.
B. By the nature of occurrence : direct and indirect.
B. According to the localization of manifestations : local and systemic.
G. Downstream:
1. Acute forms that develop within the first 60 minutes after taking the drug (anaphylactic shock, severe
bronchospasm, acute hemolytic anemia, vomiting).
2. Subacute forms developing 1-24 hours after taking the drug (serum sickness, allergic vasculitis, diarrhea)
3. Latent forms that occur 2 days or more after taking the drug (skin rashes, delayed dyskinesia of the
gastrointestinal tract, organotoxicity)
D. According to the severity of the clinical course:
1. Mild degree (skin itching, urticaria, taste perversion), in which there is no need to cancel the drug; side
effects disappear with a decrease in its dose or short-term use of antihistamines
2. Moderate severity (eczematous dermatitis, toxic-allergic myocarditis, fever, hypokalemia) - therapy needs
to be adjusted, drug withdrawal and specific treatment (for example, GCS 20-40 mg / day for 4-5 days in a
hospital)
3. Severe - conditions that pose a threat to life or prolong the patient's stay in the hospital (anaphylactic
shock, exfoliative dermatitis) - drug withdrawal and drug therapy for complications are necessary
E. Clinical classification:
1. General reactions (anaphylactic shock, angioedema, hemorrhagic syndrome)
2. Damage to the skin and mucous membranes (Laella's syndrome)
3. Damage to the respiratory system (bronchial asthma, allergic pleurisy and pneumonia, pulmonary edema)
4. Heart damage (conduction disorders, toxic myocarditis)
G. Etiopathogenetic classification:
1. Toxic effects:
a) an absolute increase in the concentration of drugs in the blood (with their overdose)
b) a relative increase in the concentration of drugs in the blood:
- due to genetically determined changes in the pharmacokinetics or pharmacodynamics of drugs
- due to non-genetically determined changes in pharmacokinetics (in case of impaired functions of the liver,
kidneys, thyroid gland) and pharmacodynamics (with changes in the sensitivity of -adrenergic receptors
associated with long-term use of inhaled -adrenergic agonists)
+c) long-term effects without a significant change in the concentration of drugs (teratogenic and
carcinogenic effects
2. Effects due to the pharmacological properties of drugs:
a) direct adverse pharmacodynamic effects (ulcerogenic effect of NSAIDs and glucocorticoids, orthostatic
reactions to ganglioblockers)
b) indirect adverse pharmacodynamic effects:
- superinfection and dysbacteriosis (for example, when using AB)
- bacteriolysis (Jarisch-Herksheimer reaction) when prescribing AB
- withdrawal syndrome (for example, the development of severe hypertensive crises with abrupt withdrawal
of clonidine)
- drug addiction.
3. True allergic reactions:
a) mediator or reagin type
b) cytotoxic type
c) immunocomplex type
d) delayed hypersensitivity
4. Pseudo-allergic reactions (for example, exacerbation of asthma due to the release of histamine during
the use of cholinomimetic agents)
5. Idiosyncrasy - a genetically determined, perverted reaction to the first administration of drugs.
6. Psychogenic effects (eg headache, sweating).
7. Iatrogenic effects (for example, with polypharmacy, improper administration of drugs).
Clinical picture of PR : in 70-80% of cases they manifest themselves in the form of allergic reactions (see
questions 154, 185), in other cases, PR is determined by the pharmacodynamic and pharmacokinetic
characteristics of drugs.
Diagnosis of side effects of drugs:
1. Establishing the fact that the patient is taking drugs (including over-the-counter drugs, phytopreparations)
2. Establishing a relationship between a side effect and the use of drugs according to the following
indicators:
- the time of taking the drug and the occurrence of adverse reactions
- compliance of the type of adverse reaction with the pharmacological action of the drug
- the frequency of occurrence of this side effect in the population, incl. and from the intended drug
- the concentration of the suspected drug in the blood plasma
- reaction to provocative tests with a suspected drug (first drug withdrawal, then its re-appointment)
- reaction to skin tests (informative for immediate-type reactions to polypeptides, such as antilymphocyte
globulin, insulin, streptokinase, less informative when using low molecular weight substances, such as
penicillins); a positive result indicates the presence of specific IgE, a negative result indicates either their
absence or the nonspecificity of the test reagent
- the results of the contact test.
- results of a skin biopsy in a skin rash of unknown etiology
3. Conducting diagnostic tests.
- general laboratory tests for organ-specific lesions (for example, serum transaminase activity in liver
damage)
- biochemical and immunological markers of activation of immunobiological pathways: determination of the
concentration of the total hemolytic component and antinuclear antibodies in drug-induced lupus, histamine
metabolites in the urine during anaphylaxis, tryptase concentration (marker of mast cell activation),
leukocyte transformation test, etc.
Treatment: with the development of drug AR, the drug that caused them should be discontinued or its dose
reduced, as well as desensitization and symptomatic therapy should be carried out.
In order to reduce the risk of developing PR, when prescribing drugs, the following should be taken
into account:
- affiliation of drugs to the pharmacological group (determines all possible pharmacological effects)
- age and anthropometric characteristics of the patient
- functional state of organs and systems of the body that affect the pharmacodynamics and pharmacokinetics
of drugs
- Presence of comorbidities
+- lifestyle (during intense physical activity, the rate of drug excretion is increased), the nature of nutrition
(in vegetarians, the rate of drug biotransformation is reduced), bad habits (smoking accelerates the
metabolism of some drugs)