Preface

Chapter One Introduction to Pathology Section A What is pathology?

Definition of Disease Disease may be defined as an abnormal alteration of structure or function in any part of the body.

Classification of Diseases: Developmental – genetic, congenital. Inflammatory – Trauma, infections, immune, etc. Neoplastic – tumors, cancers Degenerative – ageing.

Pathology Study of what is abnormal or wrong or disease…! “ Scientific Study of Disease” Normal  Abnormal  Treat

Study of Disease: Epidemiology Etiology - Causes Pathogenesis - Evolution Morphology - Structural Changes Clinical Significance – Functional Changes Clinical manifestation Complications Prevention Pathology

Pathology focuses on 4 aspects of disease ETIOLOGY: Cause of disease. PATHOGENESIS: Mechanisms of development of disease. MORPHOLOGY: The structural alterations induced in cell and tissues. FUNCTIONAL CONSEQUENCES: Functional consequences of the morphologic changes, as observed clinically. Knowledge of etiology remains the backbone: Disease diagnoses Understanding the nature of diseases Treatment of diseases.

Etiology: Environmental agents: Physical Chemical Nutritional Infections Immunological Psychological Genetic Factors: Age Genes Multifactorial:

One etiologic agent—one disease. Several etiologic agents—one disease. One etiologic agent—several diseases.

Diseases are “caused” due to internal or external factors. Multifactorial: No more “one cause to one disease” Genetic factors affect acquired diseases and environment has profound effect on genetic diseases.

Pathogenesis: “Sequence of events in the response of cells & tissues to a stimulus/pathogen” starting from the initial stimulus to the ultimate expression of disease.” Gross and microscopic Structure, Function, Chemistry & molecular mechanisms.

Pathogenesis The sequence events in the response of the cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease.

Pathogenesis Immunologic, cytogenetic and molecular analyses of tissues and cells are increasingly becoming guides to render diagnoses, to assess prognosis, and to suggest therapy.

W hile much still needs to be uncovered to link abnormal genes and the expression of disease, gone are the time when the mechanisms of most diseases were unknown? or obscure? or mysterious?

Morphologic change Characteristic of the disease Diagnostic of the etiologic proceess Functional derangements Clinical significance MORPHOLOGY Morphology remains at the heart of diagnostic pathology.

Morphology: Structural and associated functional changes in cells, tissues and organs that are characteristic of the disease or condition.

Clinical Significance: Functional derangements and its clinical manifestations resulting from the morphologic changes. Signs and symptoms, course and prognosis of disease depend on the morphology.

Pathology Summary: Etiology : Carcinogenesis. DNA Damage, Mutation. Pathogenesis : Uncontrolled cell division, tumor. Morphology : Enlarged lymphnodes, liver, spleen, microscopically – lymphoma cells. Clinical Features : Fever, Wt loss, tumor-Ln, Liver, Spleen.

Section B What do pathologists do?

Human Pathology Experimental Pathology Scope of Pathology

Human Pathology Autopsy Biopsy Cytology

Autopsy The internal examination of the body after death performed scientifically for medical or legal purposes.

Roles: to clarify the nature of many diseases. to determine the cause of death and to collect evidence to gather accurate statistics about disease incidence

Biopsy to establish a precise diagnosis by the removal and examination of tissue from the living body.

Tissue sections are embedded with paraffin.

stony hard lump or mass on palpation

Diagnosis: Carcinoma of the breast The invasive duct carcinoma usually has an abundant fibrous stroma, so it is also refered to as scirrhous carcinoma. Dense collagenous background

3 ） Cytology Single cells or clumps of cells exfoliated from their surrounding tissues. Sputum, urine and abdominal fluid

Pap smear of CIN-III Large hyperchromatic nuclei, nuclear pleomorphism .There are some interspersed neutrophils with lobated nuclei and much smaller size.

Diagnosis What is “Diagnosis”? The formal name(s) used to describe a patient’s disease The process of identifying a disease based on the patient’s symptoms, the doctor’s findings, and the results of investigations and laboratory tests What do you need to make a diagnosis? A system of classification that supplies the necessary names, definitions, and criteria The means to ascertain the defining characteristics of a disease in the individual patient

Clinical Details: 34 year , male Neck swelling, 2-3 months, Fever, weight loss, no other lymphadenopathy Lymphnode biopsy done

Lymphnode Biopsy Diffuse tumour Capsule

Lymphnode Biopsy Large cells Mitotic figures

Histiocytic/Tcell NHL Diffuse pattern – no follicles. Large cells with moderate cytoplasm Plenty of mitotic figures, Nuclei are vesicular prominent nucleoli Features suggest T-cell NHL – malignant lymphoma. Needs further marker studies for typing & management. cancer Chemotherapy.

Experimental Pathology In vitro: Tissue culture Organ culture Cell culture In vivo: Experimental animals Nude mice

Cell and tissue culture : cellular environment can be modified and the responses to it monitored.

Animal experiments ： to observe the effect of manipulations on the animal model of disease .

Section C How do pathologists do?

RESEARCH METHODS Macroscopic observation Microscopic observation (HE) EM Immunohistochemistry Hybridization Cell Cultures, Medical Microbiology Molecular Pathology PCR Flow cytometry

Gross Investigation Size Shape Color Weight Morphologic features

Congestive Splenomegaly: the volume of the spleen is increased and swollen, red-brown. Irregular tan-white fibrous plaques can be seen over the purple surface.

Histopathological and Cytopathological Investigation The microscopic examination of tissue and cell samples with LM on H.E. sections or smears. Frozen sections sometimes for a very urgent diagnosis and histochemistry.

3.Electron Microscopic Investigation study disorders at an organelle level and subcellular details. transmission and scanning EM

4.Histochemical and Immunohistochemical Investigation Histochemistry is the study of the chemistry of tissues after treated with specific reagents, so that the chemical features of individual cells can be visualised.

A masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen. Chronic glomerulonephritis:

Immunohistochemistry Ag-Ab complexes The bound Ab is then visualized, using another Ab and a dye complex such as diaminobenzidine.

Section D about the subject of Pathology, How to learn pathology?

Pathology “ Is the foundation of medical science and practice. Without pathology, the practice of medicine would be reduced to myths and folklore”

Pathology The Status of Pathology in Medicine a bridging discipline the clinical practice of medicine basic science

Learning Pathology: General Pathology Common changes in all tissues. E.g.. Inflammation, cancer, ageing. Systemic Pathology Specific changes in organs. E.g.. Goiter, pneumonia, breast cancer.

General pathology is concerned with the basic reactions of cells and tissues to abnormal stimuli that underlie all diseases. Systemic pathology examines the specific responses of specialized organs and tissues to more or less well defined stimuli.

Subdivisions of Pathology: Histopathology Cytopathology Haematology Microbiology Immunology Chemical Pathology Genetics Toxicology Forensic Pathology Histopathologist Cytologist Haematologist Microbiologist Biochemist Geneticist Toxicologist Forensic Pathologist Molecular Biologist

Chinese proverb I hear, I forget; I see, I remember; I do, I understand.

Past and Present….! In the past, .. people mistook magic for medicine…! Now people mistake medicine for magic….!

Preface

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Preface

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