Nephrology - ARCHER USMLE STEP 3

Nephrology & Urology Archer Online USMLE Reviews www.ccsworkshop.com All rights reserved Archer Slides are intended for use with Archer USMLE step 3 video lectures. Hence, most slides are very brief summaries of the concepts which will be addressed in a detailed way with focus on High-yield concepts in the Video lectures. These slides are only SAMPLES

Renal Failure Acute Vs. Chronic Acute : Pre-Renal, Renal, Post –renal, Glomerular, tubular, intersititial Indicators : BUN/CREA, FeNA, Urine Spgravity, serum Sodium, serum osmolality, urine output. Chronic – stages  elective hemodialysis Stage V, Emergent hemodialysis indications Acute tubular necrosis : toxic, pigment induced, Ischemic Evaluating renal function : urinalysis - ? Protein, ?rbc , ? Wbc, ? Casts , ? Crystals, ? Bacteria, ? Nitrite, ? Cytology , ? Leucoesterase, - Creatinine clearance, Renal ultrasound, Renal biopsy

RENAL BIOPSY Indications: Nephrotic syndrome Glomerular disease Unexplained renal failure Contraindications: single kidney, bleeding, severe hypertension. obesity and uncooperative patient

DEFINITION OF ARF P Cr > 0.5mg/dL if baseline < 3.0mg/dL P Cr > 1.0 mg/dL if baseline > 3.0 mg/dL Urine Output : TOTAL ANURIA 0 cc ANURIA < 100 cc OLIGURIA 100-400 cc NON OLIGURIA 400-1000cc POLYURIA > 1000cc

CAUSES OF NONOLIGURIC PRE RENAL ARF Diuretics Osmotic diuresis Hypercalcemia Protein malnourished Post obstructive diuresis Diabetes Insipidus

NSAID ARF Form of pre renal Occurs in states where RBF decreased and thus prostaglandin dependent Nonselective and selective NSAID’s inhibit compensatory afferent arteriolar vasodilation Volume contraction, CHF, cirrhosis, CKD, vascular disease and elderly – increases risk. COX-2 inhibitors have similar effect Allergic interstitial nephritis can also occur

ACE INHIBITOR ARF Rapidly reversible ARF Increase S Cr > 0.5Mg/dL if < 2.0 mg/dL or increase S Cr > 1.0 mg/dL if > 2.0 mg/dL Bilateral renal artery stenosis, unilateral stenosis in solitary kidney, small vessel disease and decreased RBF: CHF, cirrhosis, decreased ECF Inhibition of A-II efferent arteriole vasoconstriction leads to decrease P GC and GFR Age, diuretics, diabetes, NSAID’s, cyclosporine and CKD are risk factors ARB’s pose similar risk

POST RENAL ARF Caused by anatomic obstruction of urine flow Accounts for 5-10% of ARF Patients are often asymptomatic and thus should always be considered Ultrasound useful, but can have 10-20% false negatives Patients are often oligo-anuric, but any pattern of urine output may occur Intraureteric obstruction, Extraureteric obstruction, Urethral obstruction

INTRARENAL ARF Renal parenchymal diseases Glomerular Vascular Tubular Interstitial Acute tubular necrosis – most common

Glomerular syndromes – Nephrotic Vs Nephritic Syndromes NEPHROTIC SYNDROME Urinary albumin > 3.0 – 3.5 gm/24 hours Hypoalbimunemia Edema Hyperlipidemia Lipiduria FSGN ( HIV), MGN( SLE, hepb, Cancer – solid tumors ), Minimal ( children), MPGN ( HepC) FSGN – Rx High dose steroids, cyclosporine MGN – Methylprednisolone pulse, cyclosporin Others : DM, Malignancy, vasulitis, amyloidosis Nephritic Syndrome Hematuria/ RBC Casts Oliguria Hypertension Decreased GFR Proteinuria +/-  Focal glomerulonephritis IgA nephropathy Focal SLE ( Type III )  Diffuse glomerulonephritis Post infectious Diffuse SLE ( Type IV )  IgA nephropathy : most common presentation asymptomatic microhematuria with mild proteinuria

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Characterized by > 50% decrease in GFR over days to weeks Characterized pathologically by crescent formation and clinically by progression to ESRD in untreated patients within weeks Related to the degree of crescent formation Present with active urine sediment, hypertension and oliguric ARF Nephrologic emergency Classification of RPGN: Type 1: Anti GBM Type 2: Immune complex Type 3: Pauci-immune ( p-ANCA ) Early evaluation and biopsy

Proteinuria - Microalbuminuria Normal: 150 mg/day Albumin 30 mg Plasma proteins 60 mg Tubular protein 60 mg Dipstick test detects (-) charge Does not detect light chains Function of urine concentration Total Protein : creatinine ratio estimates 24 hour urine collection Microalbuminuria  Albumin excretion rate > 15 ugm/min = 30 mg/day Predictor of early diabetic nephropathy and CVD Urine albumin: urine creatinine < 0.03 Positive in exercise, fever, stress, CHF Repeat urinalysis in 3-6 months if u think its transient proteinuria ACE Inhibitor *****

ATN Ischemic (50%) Toxic: EXOGENOUS TOXIN ATN : -Antibiotics, Radiocontrast, Non steroidals, Anesthetics, Chemotherapeutics, Heavy metals/ solvents ENDOGENOUS TOXIN ATN : Pigment Nephropathy  Myoglobin, Hemoglobin Crystal Nephropathy  Uric acid , Calcium, Oxalate

RADIOCONTRAST ATN Risk factors: CRF especially diabetic, CHF, elderly and multiple myeloma ATN begins abruptly and S Cr peaks in 3-5 days Usually reversible, but some have prolonged renal damage Usually nonoliguric, but oliguria can be seen and FE Na decreased Prevention : Consider non contrast study if high risk D/C NSAID’s, ACE inhibitors. ARB’s etc Ensure optimal volume status and RBF 0.9% saline @ 1cc/kg/hr for 6 hours prior D 5 W + 3 amps NaHCO3 @ 3.5 cc/kg/hr for 1 hour and then 1 cc/kg/hour for 6 hours after N-acetylcysteine 600mg bid pre and day of study Minimize amount of contrast and consider iso-osmolar agent - nonionic and/or isosmolar contrast are less nephrotoxic

ATHEROEMBOLIC ARF Results from cholesterol emboli to small renal arteries and arterioles Livedo reticularis – A clue!!! Aortic surgery, trauma, angiography, fibrinolytic therapy or spontaneously Eosinophilia, eosinophiluria, leukocytosis and complement activation Retinal, peripheral and abdominal vessels

MYOGLOBINURIC ARF Rhabdomyolysis: trauma,alcohol, cocaine, seizures, hypokalemia, hypophosphatemia ECF volume depletion Heme (+) urine without RBC’s, hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia Decreased FE Na ECF volume repletion, ?mannitol, and ?alkaline diuresis Hypercalcemia during recovery

ACUTE INTERSTITIAL NEPHRITIS Fever, rash, eosinophila, eosinophiluria and active urine sediment Occurs 10-15 days after exposure to usually new medication NSAID induced associated with nephrotic syndrome ? Renal biopsy Rx: Stop the agent and ?steroids

CRYSTAL INDUCED ARF Uric acid Calcium oxalate Methotrexate Sulfonamides Acyclovir Indinavir

DIAGNOSTIC MANAGEMENT ARF History / Chart review Physical exam Urinalysis Urine indices Radiologic studies Miscellaneous studies

NON DIALYTIC MANAGEMENT ARF Preventive measures Fluid balance Acid base balance Electrolyte balance Nutritional balance Drug management Management of uremia

INDICATIONS FOR Emergency DIALYSIS REFRACTORY Hyperkalemia Acidemia Hypoxemia/ volume overload Uremia - manifestations ? Prophylactic when BUN > 60-100 mg/dL

Chronic Tubulo-Interstitial Diseases Chronic issues : Toxins: Analgesics, Heavy metals, Chinese herbs, Lithium, Cyclosporine, Radiation, Cisplatin Hematologic diseases: Myeloma Immunologic: Sjogren’s syndrome, Transplant rejection Infection: Bacterial pyelonephritis, Tuberculosis, Sarcoid Anatomic: Obstruction, Reflux Metabolic disorders: Gout, Oxalosis, Hypercalcemia, Hypokalemia, Cystinosis Hereditary: ADPKD, MCD Vascular : Nephrosclerosis, Ischemic nephropathy, Atheroembolic disease Acute cases : check urine eosinophil count, peripheral eosinophilia

Oxalate Nephropathy Precipitation of calcium oxalate can cause interstitial and intratubular crystals leading to inflammation and fibrosis Primary hyperoxaluria leads to ESRD Ethylene glycol, methoxyflurane, excessive intake ascorbic acid Increase intestinal absorption: Ileal bypass, short bowel syndrome and Crohn’s disease

Chronic Urate Nephropathy Related to deposition of sodium urate in the medullary interstitium Secondary inflammation and interstitial fibrosis and CRF Hypertension, bland urinalysis and hyperuricenia Associated with tophaceous gout or an increase in uric acid out of proportion to degree of CRF

Analgesic Nephropathy NSAID induced interstitial nephritis ( associated with nephrotic syndrome  proteinuria) NSAID induced vasomotor renal insufficiency

Hepatorenal Syndrome The diagnosis of HRS iS of exclusion and depends mainly on serum creatinine level, as no specific tests establish the diagnosis of HRS. Serum creatinine level is a poor marker of renal function in patients with cirrhosis. But no other reliable noninvasive markers exist for monitoring renal function in these patients. Diagnosis of HRS depends on the presence of a reduced GFR in the absence of other causes of renal failure in patients with chronic liver disease. Major criteria ( All major criteria are required to diagnose HRS .) Low GFR, indicated by a serum creatinine level higher than 1.5 mg/dL or 24-hour creatinine clearance lower than 40 mL/min Absence of shock, ongoing bacterial infection and fluid losses, and current treatment with nephrotoxic medications No sustained improvement in renal function (decrease in serum creatinine to <1.5 mg/dL or increase in creatinine clearance to >40 mL/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L of plasma expander Proteinuria less than 500 mg/d and no ultrasonographic evidence of obstructive uropathy or intrinsic parenchymal disease Additional criteria (Additional criteria are not necessary for the diagnosis but provide supportive evidence.) Urine volume less than 500 mL/d Urine sodium level less than 10 mEq/L Urine osmolality greater than plasma osmolality , Urine red blood cell count of less than 50 per high-power field & Serum sodium concentration greater than 130 mEq/L Urinary indices are not considered major criteria because a subset of patients with HRS may have high urine sodium levels and low urine osmolality (similar to acute tubular necrosis [ATN]), while other patients with cirrhosis and ATN may have low urine sodium levels and high urine osmolality.

Case Studies ) A 25 y/o male comes to your office with complaints of dark red colored urine and pain in the legs that started this morning. He has been working out at the local gym excessively for the past three days. He does consume alcohol on weekends but reports having involved in a binge drinking episode that included 10 beers yesterday. On physical examination, he weighs 70kg and he has some tenderness in his calf muscles which he attributes to the excessive squats he performed yesterday. Urine dipstick reveals large blood. If this patient develops acute renal failure , the most likely mechanism would be: A) Interstitial nephritis due to pigment B) Glomerulonephritis C) Acute Tubular necrosis due to pigment deposition D) Acute Tubular Necrosis due to Ischemia E) Alcohol related direct toxic injury 1b) Lab studies revealed normal electrolytes and normal creatinine but a CPK of 50,000. His Urine output has been at 70 ml/hr for the past 6 hours. Your first step in the management to prevent development of patient's Acute Renal Faliure : A) Intravenos Fluids B) Furosemide C) Calcium Gluconate D) No treatment because serum creatinine is normal D) Sodium Bicarbonate

Case Study A 7-year-old boy is brought to the emergency department by his mother because of "tea-colored urine" for the last several days. He has also had some nausea and vomiting, and his eyes appear swollen when he wakes up in the morning. The eye swelling tends to resolve over the course of the day. He is generally very healthy and there is no family history of any chronic diseases. His temperature is 36.7 C (98.0 F), blood pressure is 130/90 mm Hg, pulse is 96/min, and respiratory rate is 16/min. Physical examination is unremarkable. A urinalysis shows red cell casts. At this time the most appropriate study to confirm your diagnosis is A. antinuclear antibody B. antistreptolysin O antibody C. renal biopsy D. renal ultrasound E. urine culture

Case studies contd… 1c) The above patient has been adequately treated but his repeat CPK after 2 days is still elevated at 48,000. He complains of increasing pain in his left leg and some tingling and pricking sensations. On examination his left leg was mildly swollen and there was pain on passive stretching of the leg muscles. Dorsalis pedis and posterior tibial pulses are intact. The most likely diagnosis at this time: A) Deep Vein Thrombosis B) Cellulitis C) Compartment Syndrome D) Edema due to renal failure E) Congestive Heart Failure 1d) The immediate course of treatment in this condition would be : A) Anticoagulation with Heparin B) Antibiotics C) Emergency Fasciotomy D) Loop diuretics E) Elevation of the leg

Case Study 2 Q1) A 12 y/o boy is brought to you by his mother for skin rash and complaints of intermittent abdominal pain, joint pains for past 2 days. He did have an upper respiratory infection about 2 days ago. On physical exam, his vitals are normal. Abdomen is benign with out any tenderness or rigidity. However, you notice patchy purple discolorations on his extremities and the back. Lab studies are obtained that revealed WBC: 6.6 , HGB: 15.3 , MCV: 88 , Platelets: 290,000 ( normal 180k to 400k) BUN: 11 , Creatinine : 0.6 ( normal) , Anti streptolysin O titer : negative Streptozyme : negative ,Urine dipstick : normal without any blood Urinalysis : normal/ no rbcs/ no protein The mother is very anxious and asks about the long term prognosis of her son. Your response : A) Reassure the mother that boys disorder is self limiting and does not require any follow up B) Tell her the boy needs to be admitted and treated vigorously to prevent renal failure C) Tell her that renal failure develops 100% of such cases and hence needs very cautious follow up D) Tell her that 50% of such cases progress to end stage renal disease. E) Tell her that the boy requires follow up monthly urinalysis for at least 3 months in order to make sure there is no heamaturia/ renal dysfunction. If the boy presented with Renal failure in the above case, the most likely underlying pathology would be : A) IgA mediated vasculitis B) Post streptococcal glomerulonephritis C) Anti GBM disease D) Acute tubular necrosis E) Interstitial Nephritis.

ADPKD Autosomal Dominant Polycystic Kidney Disease Clinical features Associations Prognosis Screening for Berry Aneurysms: MRA of head – recommended screening test to detect berry aneurysms Screen only if family history of subarachnoid hemorrhage ( Family hx of a ruptured berry aneurysm) not just a family history of berry aneurysm. Patients with with high risk jobs (pilots/ bus-drivers) - an event during such a job is a risk to other’s safety as well. Patients with symptoms suggestive of a berry aneurysm ( severe headache, focal neurological deficits)

Q A 46 y/o woman who is a school bus driver by occupation presents to your office for regular follow up. She has a history of ADPKD. Her blood pressure is well controlled at 120/70 on enalapril. She has no other problems. She denies any headache. There is no family history of intracranial or subarachnoid hemorrhage. However, she is concerned that her head might explode because her sister who also has ADPKD was recently diagnosed of having a berry aneurysm. She wants to be screened for berry aneurysm as soon as possible. Her physical examination is benign and does not reveal any focal neurological deficits. Which of the following suggests the necessity for screening in her case? A. Family history of berry aneurysm B. Polycystic kidneys C. School bus driving D. Cysts in the liver E. No screening necessary in her case Copy right: Archer

Ans. C High risk jobs ( pilot, bus driver etc) is one of the indications to screen for berry aneurysm in asymptomatic ADPKD patients. Family hx of berry aneurysm alone does not warrant screening for berry aneurysm in asymptomatic ADPKD patients. Asymptomatic ADPKD patients must be screened if there is a family history of “ Ruptured” berry aneurysm ( history of SAH in the family etc) E. is not the answer because this patient is a school bus driver by occupation and needs to be screened

CASE STUDY A 76 YO DEBILITATED MALE, In extended care facility , develops every 6 months mild fever, frequency of micturation with urinary incontinence. USUALLY E.COLI count is >100,000. What is the appropriate treatment? A. CYSTOSCOPY and IVP B. Continuous low dose antibiotics C. Catheterize and irrigate the Bladder daily D. Treat only the acute episode of infection E. No need of treatment as this is colonization

Symptomatic complicated UTI should be treated. Number of UTI are less than 2 in 6 mos- no need for continuous Abx. His Symptoms are associated with UTI and are not persistent. So just treat the acute episode REMEMBER THE INDICATIONS FOR TREATING “ASYMPTOMATIC “ BACTERIURIA.

Recurrent UTIs DEFINED AS 2 OR MORE EPISODES IN PAST 6 MONTHS OR 3 OR MORE EPISODES IN PAST ONE YEAR. Use Bactrim DS post sexual activity for women with hx of recurrent UTIs related to sexual activity. Use daily bactrim for people withj no relation to sex activity.

OTHER ISSUES Evaluating painless hematuria elderly Painful hematuria Treating asymptomatic bacteriuria Pyelonephritis – pyonephric abscess When to admit and when to order imaging studies in pyelonephritis?

Hematuria Painless ( Asymptomatic) Hematuria Painful Hematuria Gross Hematuria Microscopic Hematuria

Hematuria “ Not every red urine needs to be a Hematuria” A reddish discoloration of urine can occur with out a positive dipstick or urine microscopy . Causes of “Red” urine but negative dipstick test Ingestion of red pigmented foods ( eg: beets, berries, rhubarbs, paprika) Drugs like Rifampin or Phenazopyridine derivatives ( remember these drugs only cause reddish urine but NOT a positive dipstick) Diseases such as “ Porphyria” Causes of a Positive Dipstick but no true Hematuria : Here Dipstick stains positive for blood but no RBCs in the urine: Myoglobinuria ( Rhabdomyolysis, vigorous exercise) Hemoglobinuria ( Intravascular hemolysis)

Hematuria Screening test for hematuria is urine dipstick. Dipstick : Dipstick is highly sensitive but not specific. False negatives are very rare but false positives are common. Dipstick detects “blood" but it does not say whether this "blood" is an RBC or a Pigment. Pigments such as myoglobin ( as in rhabdomyolysis) or Hemoglobin ( as in hemoglobinuria, Black water fever) can stain as "Blood" on dipstick but there are no RBCs on urine microscopy. So, a dipstick positivity should be confirmed always with “urine microscopy” before calling it a hematuria.

Hematuria “ Painful” vs. “Painless” Hematuria The distinction is important so that you can consider the relevant differential diagnosis and choose appropriate investigations. Painful hematuria is often associated with urolithiasis ( renal calculi) or inflammation/ infection of the bladder ( Cystitis). Painless or Asymptomatic hematuria is often seen with tumors of the urinary tract, bladder cancer, glomerulonephritis and benign prostatic hypertrophy. A hematuria accompanied by a classic flank pain should raise a suspicion of renal calculus and the next investigation in such a scenario should be a Non-Contrast CT scan. Approach to painless hematuria depends on the risk profile of the patient ( i.e; risk of having a renal/ urological disease)

Gross Hematuria Grossly Reddish or Tea colored urine, dipstick positive for blood and urine microscopy shows RBCs. Any patient with gross hematuria should always be referred for urological evaluation unless this is secondary to an infection . If a woman has gross hematuria but the urine dipstick also reveals leucoesterase or nitrite or if the woman has symptoms of UTI ( dysuria etc) or if the cultures are growing bacteria, this can be treated as UTI ( cystitis) with antibiotics with out referring for further evaluation. A repeat urinalysis should be obtained after resolution of the infection. Even in this setting of infection, if there are risk factors for urological malignancy the patient should still be referred for further evaluation ( since hematuria from cancer can also be intermittent). Runner's hematuria or March hematuria is another benign condition that presents as gross hematuria after a severe physical activity. In such cases, patients may be observed for resolution. However, if the hematuria is persistent or if the patient has any risk factors for having a urological malignancy, must be referred to a urologist

Microscopic Hematuria Microscopic hematuria is defined as three or more red blood cells per high-power field on microscopic evaluation of urinary sediment from two of three properly collected urinalysis specimens. ( >3rbc/hpf on 2 or more occassions). Always confirm on repeat testing. Repeat urinalyses to establish whether significant hematuria is present must be done within 3 to 6 months of the initial test. Look for glomerular origin of hematuria – If urinalysis reveals Red cell casts/ dysmorphic RBCs or Renal function is compromised/ new onset HTN, combined with mild proteinuria  consider glomerulonephritis or renal parenchymal disease  in such cases, next step is referral to a nephrologist and renal biopsy.

Microscopic Hematuria Rule out benign causes first. Some benign causes of Microhematuria : A) Exercise B) Sexual activity C) Menstruation D) UTI If UTI is present ( symptoms and dipstick for leucoesterase are clues that point towards infection) - treat it with antibiotics and repeat urinalysis after the infection has cleared. E) Benign Prostatic Hypertrophy F) Prostatitis Recurrent painless Hematuria  consider IgA nephropathy Other clues 1. Consider strongly CA.Bladder in the elderly and in smokers 2. R/O benign causes like BPH ( Ask for symptoms of BPH) 3. R/O Prostate Ca in the elderly and in those with family history DO NOT NEGLECT POSSIBILITY OF BLADDER CA IN Patients WITH HEMATURIA

Microscopic Hematuria Symptomatic Microhematuria : If the microhematuria is associated with classic flank pain  next step is Non Contrast CT scan to rule out renal calculus. In pregnant women  do ultrasound to avoid radiation. Asymptomatic MicroHematuria : Patients without the classic flank pain of urolithiasis should be evaluated extensively. Once benign causes such as infection and the kidney ( glomerular) origin are ruled out, further approach should be defined based on the patient's risk profile. For patients with low risk of urological disease, a less extensive work-up may be appropriate ( First do upper tract imaging and if this is negative, add urine cytology+cystoscopy). If the patient is a high risk of having a urological malignancy, extensive work-up is needed ( see the risk factors below) --> Upper tract imaging + cystoscopy+ urine cytology all are needed. Urine cytology should be obtained in all patients with asymptomatic hematuria since it is an easy and non invasive step. Sensitivity of urine cytology is only 48% but remember that if it is positive it is highly specific for urological cancer ( 94% specificity)

Painless Hematuria Risk Factors for Significant Disease in Patients with Microscopic Hematuria : Smoking history Occupational exposure to chemicals or dyes (benzenes or aromatic amines) History of gross hematuria Age >40 years History of urologic disorder or disease History of irritative voiding symptoms History of urinary tract infection Analgesic abuse History of pelvic irradiation Previous use of Cyclophosphamide ( increases the risk of bladder cancer where as ongoing use often causes hemorrhagic cystitis as a adverse effect) These high-risk patients require aggressive work up with CT Urogram + Cystoscopy + Urine Cytology!

What Imaging Studies? What imaging studies should be done as initial step in evaluating Asymptomatic Hematuria? For both high risk and low risk patients, upper tract imaging must be performed as an initial step. For upper tract imaging, CT urography ( i.e; non-contrast CT followed by contrast CT imaging from kidney to bladder) is best recommended initial test now to evaluate asymptomatic hematuria. CT urography is less affected by overlying bowel gas and is more sensitive for detecting small tumors and calculi than the IVP. IVP used to be the best preferred test for upper tract imaging in hematuria evaluation but now CT urogram is becoming the preferred method. IVP and ultrasound are good to image the urinary tract but they do not completely assess the renal parenchyma. If you order an IVP, you may eventually need to order a CT urogram again to image the parenchyma better - so, in order to avoid ordering multiple studies, CT urogram is recommended as the best initial test.

Upper tract imaging – preferred modality is Helical CT or CT Urogram ( If you do not find CT Urogram in the choices or if you want to reduce radiation exposure such as in pregnant women, you can choose IVP+renal ultrasound for upper tract imaging  remember IVP is more invasive and we are not using now. So, where available, CT urogram is first choice for imaging the upper tract. But if IVP is used it must be combined with renal ultrasound because IVP only images the tract but does not look at the kidney itself). In patients with high risk of bladder ca, Helical CT followed by urine cytology and cystoscopy must all be performed. In patients with low risk for bladder ca, you may choose step-wise approach. First step then is upper tract imaging. Then urine cytology or cystoscopy.

Bladder Ca Most common histology is Transitional Cell ca Routine screening in all patients for bladder ca with either urinalysis or cytology is not recommended Screening for bladder cancer in high risk individuals ( those exposed to dyes/ leather, smokers) is controversial  no clear recommendations. High risk History : Smoking history, Occupational exposure to dyes, rubber, or leather, previous exposure to Cyclophosphamide

Bladder Ca Do not routinely screen but however, if you find Hematuria ( even microscopic) on routine urinalysis that was done for another purpose  do not neglect this finding. ABNORMAL LAB always need to be addressed  pursue further w/u for this hematuria ( BPH, Ca.Bladder, ca.prostate, cystitis, r/o glomerulonephritis) Remember Micro-HEMATURIA is the most common manifestation of bladder cancer.

Clinical Symps/ Signs Hematuria Urinary frequency or dysuria Flank or suprapubic pain Constitutional symptoms, such as weight loss Weight loss Adenopathy Palpable suprapubic mass Organomegaly BLADDER CA CAN BE TOTALLY ASYMPTOMATIC

IMPORTANT Refer all patients ( especially those at high risk) presenting with unexplained hematuria for cystoscopy, even if their hematuria is intermittent , and regardless of the findings on history and physical exam.

Bladder Ca - Diagnosis Freshly voided urine sample for cytology Imaging of the urinary tract Cystoscopy and exam under anesthesia with biopsies Additional diagnostic evaluations, based on findings from the cystoscopy and pathologic evaluation of the tumor, to assess the upper urinary tract or to look for metastatic disease  lfts, ivp, cxr, ct scan of abd/pelvis, bone scan.

Bladder Ca - Rx Surgical resection for non invasive bladder ca. Radical Cystectomy – Rx of choice for muscle-invasive bladder ca. Adjuvant Intravesical therapy with BCG/ mitomycin-c for  Cis, T1 tumors, tumor > 5cm size. Adjuvant chemotherapy on case-by case basis  gemcitabine+cisplatin or methotrexate Local side effects of BCG include: Cystitis (90% of patients) , Hematuria (30%) , Contracted bladder , Ureteral obstruction, Inflammation (prostatitis, epididymitis, epididymoorchitis) Systemic side effects of BCG, which should resolve in 48 hours, include: Flu-like symptoms , Arthralgias , Rash

Bladder Ca Post – radical cystectomy requires urinary diversion External diversions include conduits, usually composed of a section of bowel (ileum or colon). Internal conduits include those that require a stoma to empty the reservoir (Kock pouch and Indiana pouch) and orthotopic replacements (e.g., Le Bag, Mainz pouch,

Complications – Urinary diversion Watch for the following after urinary diversion: Bleeding , Infection , Hernias , Necrosis , Reflux, Incontinence , Obstruction of conduit, upper tract, or intestines and Recurrent cancer Monitor for bacteremia, treat patients with Proteus or Pseudomonas sp., and observe patients with other organisms if they are asymptomatic. Monitor closely: Vitamin B12 levels , Acid/base status , Electrolyte levels and Bone mineralization

Painful Hematuria UTI/ Cystitis/ Pyelonephritis Renal Calculi IMAGING CHOICES: Computed tomography ( NON CONTRAST) is the best imaging modality for the evaluation of urinary stones, renal and perirenal infections, and associated complications Ultrasound : Excellent for detection and characterization of renal cysts (Limitations in detection of small solid lesions (<3 cm))  Also, used for stones eval in pregnancy.

Prostate Disorders Benign Prostate Hypertrophy Prostatitis – Acute & Chronic Carcinoma of Prostate Chemoprophylaxis of Prostate cancer Utility of PSA ( see Oncology)

Hypernatremia Defined as serum sodium > 145 meq/L Hospital acquired in >80% of patients Requires defect in renal concentrating ability and defect in thirst mechanism Normal patients do not become hypernatremic Hypernatremia occurs in very young and very old with a defect in thirst Isovolemic, Hypovolemic & Hypervolemic

Isovolemic Hypernatremia : Usually hemodynaically stable unless serum sodium > 170 meq/L Causes: Hypodipsia Increases insensible losses Nephrogenic diabetes insipidus – congenital, acquired  CRF, Hypokalemia, Hypercalcemia, Sickle cell disease Amyloidosis, Obstruction, Alcohol, Lithium, Demeclocycline, Glyburide, Amphotericin Essential hypernatremia Central Diabetes Insipidus : Granulomas, Histiocytosis, Infections, CVA, Postpartum necrosis, Pregnancy, Head traumaPost hypophysectomy, Suprasellar masses, Intrasellar masses

Polyuria ? Water or solute diuresis Water diuresis i.e. diabetes insipidus vs polydipsia ( U osm < 150 mOsm ) Solute diuresis i.e. electrolyte vs non electrolyte ( U osm 300 - 400 mOsm ) Diagnostics: Urinalysis, urine osmolality, and urine electrolytes

Hypovolemic Hypernatremia Causes Renal causes Loop diuretics Osmotic diuresis Gastrointestinal causes Vomiting / nasogastric drainage Diarrhea / cathartics Water loss into cells Exercise / seizures Cuteaneous causes Burns / excessive sweating

Hypervolemic Hypernatremia Causes : Hypertonic sodium solutions Hypertonic feedings Ingestion of sea water Hypertonic dialysis Primary aldosteronism Cushing’s syndrome

Signs and Symptoms Hypernatremia Depend on rate, degree and duration Depressed sensorium Irritability Focal neurologic deficits / seizures Muscle spasms Nausea/vomiting Thirst / fever Volume depletion / hyperglycemia

Therapy of Hypernatremia Hemodynamic or osmolal problem? Acute or chronic problem? Prior losses and present losses? Rate of correction? Acute: 1-1.5 meq/L/hour reduction Chronic: 0.5 meq/L/hour reduction or 50% within first 24hours -  WHICH FLUID ? Isovolemic water: PO or intravenous Water deficit = 0.6 (BW Kg ) x (P na /140 -1) Hypovolemic – unstable pt???? Correct volume problem i.e. normal saline Correct osmolal problem Hypervolemic Salt removal with loop diuretics and free water

Hypercalcemia Etiology Clinical features : bones, moans, stones, groans Investigations: Ca, Phos, EKG, PTH, Urinary calcium excretion ( R/o familial hypocalciuric hypercalcemia) Management: Criteria for surgery in primary hyperparathyroidism Sestamibi scan only if surgery is planned/indicated Hypercalcemic crisis management – ivf + lasix after volume repletion only Indications for corticosteroids : are useful for treating hypercalcemia caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease  Indicated for hypercalcemia with parathyroid carcinoma. Do not lower Calcium too much  Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany;

Criteria for Surgery – Primary hyperparathyroidism Serum total calcium level >12 mg per dL (3 mmol per L) at any time Hyperparathyroid crisis (discrete episode of life-threatening hypercalcemia ) Marked hypercalciuria (urinary calcium excretion more than 400 mg per day) Nephrolithiasis Impaired renal function Osteitis fibrosa cystica Reduced cortical bone density (measure with dual x-ray absorptiometry or similar technique) Bone mass more than two standard deviations below age-matched controls (Z score less than 2) Classic neuromuscular symptoms Proximal muscle weakness and atrophy, hyperreflexia , and gait disturbance Age younger than 50

Hypercalcemia – Breast Cancer Management: Principal Rx : Bisphosphonates for moderate to severe hypercalcemia ( Aridia, Zolendronic acid) ( and also prevent osteoporosis) ( esply pts on Aromatase inhibitors are even prone to osteoporosis)  Manage hypercalcemic crises as in all other cases ( IV Fluids and only after complete hydration, then furosemide)

Hyponatremia Classify – Hypotonic, Isotonic and Hypertonic Classify – hypovolemic or euvolemic Hypovolemic Hyponatremia – Diarrhea, Vomiting, early excess diuresis Euvolemic Hyponatremia  SIADH Isotonic Hyponatremia  Pseudohyponatremia ( Hyperglycemia, Hypertriglyceridemia, does not occur with uremia) Rx  Correct volume and then osmolal problem Volume problem  Isotonic saline always !!!!!!!!!! Asymptomatic  fluid restriction CNS symptoms  3% Saline

Hyperkalemia Several causes : Medication interaction is a common one ( ACEI+Spironolactone+beta blocker, HEPARIN), renal failure, Addisons disease, Rhabdomyolysis, Metabolic acidosis, Hyperglycemic states. Effects : arrhythmias, Can lead to tall tented t-waves on EKG

Ekg- Hyperkalemia The following changes may be seen in hyperkalaemia small or absent P waves atrial fibrillation wide QRS shortened or absent ST segment wide, tall and tented T waves ventricular fibrillation

58 year old man on haemodialysis presents with profound weakness after a weekend fishing trip.

The man’s K was 9.6 Next Step  IV CALCIUM CHLORIDE ( CALCIUM GLUCONATE AN ALTERNATIVE)

30 y/o woman evaluated in the emergency department for a 2-day history of muscle weakness. An electrocardiogram taken in the emergency department is shown. Which of the following is the best immediate treatment option? ( A ) Hemodialysis ( B ) 50% glucose, 50 mL, intravenously ( C ) Calcium gluconate, 10 mL ( D ) Sodium polystyrene sulfonate (Kayexalate), 50 g, in sorbitol, rectally ( E ) Peritoneal dialysis

Hyperkalemia - Treatment MNEMONIC – CBIGKDrop Check the EKG  If EKG changes, calcium gluconate IV B – BICARBONATE/ Beta agonists I – INSULIN G – DEXTROSE K – KAYEXALATE If total body potassium is an issue D – Hemodialysis for refractory Hyperkalemia

HYPOKALEMIA - EKG The following changes may be seen in hypokalaemia. small or absent T waves prominent U waves first or second degree AV block slight depression of the ST segment

Acid Base Disorders Formulas, Case studies and Management

Acid Base Disorders Metabolic Alkalosis Respiratory Alkalosis Metabolic Acidosis Respiratory Acidosis Mixed Disorders

Acid Base Disorders Common clinical problems Associated with life threatening conditions Often misdiagnosed Demands an understanding of physiology and pathophysiology pH is a major determinant of enzymatic reactions – Acedemia denatures the enzymes, decreases threshold for ventricular fibrillation and increases respiratory drive. Alkalemia suppresses respiratory drive, can cause myocardial ischemia, coronary vasospasm etc

Acid Base Disorders - CARBONIC ACID - BICARBONATE SYSTEM : H + HCO 3 ↔ H 2 CO 3 ↔ H 2 O + CO 2 HENDERSON-HASSELBACH EQUATION : pH = pK a + log HCO 3 / H2CO 3 PLASMA ACIDITY : determined by : Balance between concentration of plasma bicarbonate and pCO2 Measured as pH or H ion concentration

Acid Base Disorders 1. Factors affecting plasma Bicarbonate : Rate of H ion input Rate of H ion excretion via kidneys Rate of H ion or bicarbonate loss via GI tract Availability of non bicarbonate buffers Volume of distribution of bicarbonate 2. Factors affecting pCO2 Rate of CO2 excretion via alveolar ventilation Rate of CO2 production

ACIDEMIA-ALKALEMIA Refers to plasma acidity Acidemia: pH < 7.36 Alkalemia: pH > 7.44 Metabolic Disorder: - Acid-base disorder caused by primary change in plasma bicarbonate - Plasma bicarbonate = 24-28 meq/L Respiratory Disorder - Acid-base disorder caused by primary change in pCO2 pCO2 = 36 - 44 mmHg Compensatory Mechanisms : Appropriate proportional physiologic responses which tend to restore pH toward, but not to normal Terms “over” and “under” compensation should be avoided – INSTEAD USE “ MIXED “ DISORDER!!!

Metabolic Acidosis Calculate Anion Gap : Na - (Cl + HCO 3 ) - Normal 3 - 10 meq/L Given entirely by Unmeasured anions are related to (-) charge on albumin  One gram albumin = 2.5 meq/L anion i.e. Albumin of 4 gm/L, baseline anion gap would be 10 meq/L which is Normal. Correct Gap for Albumin!!!  If albumin is 2gm%, the baseline anion gap should be 5 in which case 10 should be assumed as increased Anion gap. Delta Gap : Delta AG / Delta HCO3: 1:1 = Anion gap acidosis >1 = Anion gap acidosis plus metabolic alkalosis < 1 = Increased Anion gap acidosis plus normal anion gap acidosis Classify Metabolic Acidosis – Increased Gap - Normal Anion gap - Mixed : Gap + non gap

Calculate Compensation Compensation Metabolic Acidosis Occurs in 12-24 hours and limit PCO2 10 mmHg : Expected pCO2 = 1.5x HCO3 + 8 +/- 2 pCO2 = last 2 digits pH pCO2 = HCO3 + 15 If measured Pco2 is less than expected pco2 as calculated by this equation – suspect a primary respiratory alkalosis. If it is more than expected suspect primary respiratory acidosis. This is how you diagnose mixed disorders!!!

Example 65 y/o man with CAD  and then cardiogenic shock. Ph 7.26. PCo2 40 HCO3- 10 Na+ 136 Cl- 110 Albumin 2.0 What's the Anion Gap? Corrected Anion Gap ? {gap + 2.5(measured albumin)} Delta Anion Gap? Delta Hco3-? ( 24 – bicarb) Delta Gap? Adequately Compensated or mixed ? Name the disorder ?

Normal Anion-Gap Metabolic Acidosis Gastrointestinal Loss of Bicarbonate Diarrhea Urinary diversion Small bowel, pancreatic, or bile drainage ( fistulas, surgical drains ) Cholestiramine Renal Loss of Bicarbonate ( or Bicarbonate equivalent ) Renal tubular acidosis Recovery phase of Ketoacidosis Renal Insufficiency Acidifying Substances- HCl, NH4Cl, Arginine HCl, Lysine HCl, Sulfur To differentiate calculate Urinary Anion Gap = Urine (Na + k) – (cl-). Normal is from +10 to -10. If UAG > +10  Renal loss. If UAG < -10 or more negative  GI Causes ( neGUTive)

Increased Anion Gap Acidosis Ketoacidosis - diabetic, alcoholic, starvation Lactic acidosis Uremia Toxins - Ethylene glycol, methanol, salicylate, paraldehyde Osmolar Gap = Measured Osmolarity – Calculated Osmolarity Calculated Serum osm = 2(Na) + Glucose/18 +BUN/2.8 ( + ethylalcohol/4.5)

Plasma Level v. Osmolality Ethanol ÷ 4.6 Methanol ÷ 3.2 Ethylene glycol ÷ 6.2 Isopropanol ÷ 6.1 For example, a blood ethanol level of 100mg/dL would increase plasma osmolality 100/4.6 or 22 mOsm/L

Case Study Sam is a 35 y/o alcoholic who is brought to the ER in a comatose state. Sam’s wife tells you that she had an argument in the evening about 5 hrs ago over Sam’s alcohol habits. Sam apparently got mad over the discussion, drove his car and returned an hour ago in a very intoxicated state. Wife called the EMS and rushed him to the ER. On examination Sam is disoriented and hallucinating , Pulse 120 Tm 99, RR 26 BP 126/76. The rest of the physical exam is normal except for stuporos state and alcohol smell. Lab studies revealed Na 130 k 3.4 cl- 95 Hco3 16, Glucose 90 Creatinine 1.6 BUN 45. Blood Ethylalcohol level was 180. Serum osmolarity was 360mg%. ABGs revealed 7.28, Pco2 28, Po2 76 Sao2 93. The next best step in management ? A) Endotracheal intubation in view of severe acidosis B) Hemodialysis because this is an acute renal failure causing acidosis C) Fomepizole because of suspicion of ethylene glycol intoxication D) Supportive treatment for now because this is an ethylalcohol induced lactic acidosis E) Bicarbonate drip to reverse the acidosis because this is renal tubular acidosis

Ethylene Glycol Poisoning Envelope shaped crystals Treatment : Consider Antidote ( Fomepizole or Ethanol ) if Level > 20mg% or if you suspect ethylene glycol intake with 2 or more – a) arterial ph < 7.3, Hco3 <20, osmolar gap>10, calcium oxalate crystals in urine. Antidote blocks Alcohol dehydrogenase and prevents the Glycolic acid formation. In case of methanol, toxic meatbolite is formic acid Ethylene glycol found in antifreeze and de-icer Toxicity results at doses >1.0 ml/kg Ethylene glycol causes CNS depression , converts to Glycolic Acid (metabolite) effects  Metabolic Acidosis & Renal Failure Oxalic acid (metabolite) effects  Calcium oxalate crystal deposition C/F: Confusion, Ataxia, Slurred speech ,Hallucination, Tetany Seizure s ( Hypocalcemia ) Hypertension Tachycardia

Increased Osmolal Gap Ethanol Methanol Ethylene Glycol Formaldehyde Paraldehyde Lactic Acidosis ESRD Ketoacidosis Mannitol Isopropyl alcohol Hyperlipidemia Hyperproteinemia Diethyl ether

Isopropanol Ingestion Present with CNS depression, hypotension, arrhytmias and gastritis Acetest reaction positive Increased osmolal gap No metabolic acidosis Anion gap normal

Renal Tubular Acidosis Type 1 ( distal) Type 2 (proximal) Type 4 (hyporeninemic hypoaldosteronism)

Type I RTA (Distal) Causes: autoimmune diseases, hyperglobinemia states and hereditary Present with normal anion gap acidosis, urine pH >5.5, hypokalemia, hypercalciuria, nephrocalcinosis and stones Treatment: alkali i.e. K citrate

Type II RTA (Proximal) Isolated defect or associated with generalized proximal dysfunction i.e. Fanconi syndrome Failure to reclaim filtered bicarbonate Increase FE HCO3 Urine pH > 5.5, but may be < 5.5 once HCO 3 < 16 meq/L Causes: Multiple myeloma Acetozolamide Ifosfamide Lead, cadmium, copper

Type 4 RTA Hypoaldosteronism or aldosterone resistance Causes: diabetes mellitus, HIV and tubulo- interstitial disease Present with hyperkalemia, normal anion gap acidosis and normal urine pH

Metabolic Alkalosis Calculate compensation PCO2= ( 0.7 x HCO3 ) + 21 . If measured Pco2 is more than this then there is concomitant respiratory acidosis. If less than this then concomitant respiratory akalosis. Delta Gap to r/o mixed disorder – metabolic acidosis + metabolic alkalosis if delta gap >1

Causes of Metabolic Alkalosis Saline responsive : ECF depleted ( contraction alkalosis ), Urine chloride < 10 meq/L, do not go by urine sodium in assessing volume status  Gastrointestinal Loss eg : Surreptious vomiting, NG tube suctions,Villous adenoma, Chloride diarrhea, Diuretics (late),Post hypercapnea Saline resistant : Saline Resistant Metabolic Alkalosis , Increased mineralocorticoid effect,Urine Cl > 20 meq/L  Hypertensive causes:Primary aldosteronismCushing’s syndrome, 11 or 17 hydroxylase deficiency, Licorice / carbenoxolone, Liddle’s syndrome, Steroids  Normotensive causes: Bartter’s syndrome ( thiazide), Gitelman’s syndrome ( like loop diuretic), Diuretics (present), Severe potassium depletion, Severe magnesium depletion

Metabolic Alkalosis - Treatment Saline responsive Normal saline to volume replete KCl Saline resistant Inhibit or remove excess mineralocorticoid effect Miscellaneous Acetazolamide, HCl, NH4Cl Hemodialysis

Case Study A 26 year old woman presents to the ER with generalized weakness associated with perioral numbness. She is moderately built and looks slightly depressed. On physical exam, she has mild pallor. She denies use of any medications. BP 120/88 mmHg and physical exam is normal. Lab data: Cr 1.2mg/dL, BUN 15mg/dLNa 136 , K 2.8 , Cl 88 , HCO3 38. Urine Na 45 meq/L, Urine K 35 meq/L, Urine Cl 8 meq/L, Urine specific gravity 1.010, Urine pH 7 The most likely diagnosis is : Laxative Abuse Surreptious vomiting Licorice abuse Malabsorption Syndrome Hyporeninemic Hypoaldosteronism Treatment : IV normal saline Spronolactone Amiloride Psychiatry consult Reassurance because this is self limiting

Nephrology - ARCHER USMLE STEP 3

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Nephrology - ARCHER USMLE STEP 3