Chapter OneChapter OneIntroduction to PathologyIntroduction to Pathology

Chapter OneChapter OneIntroduction to PathologyIntroduction to Pathology

What is pathology?

Definition of Disease Definition of Disease

• Disease may be defined as an Disease may be defined as an abnormal alteration of structure abnormal alteration of structure or function in any part of the or function in any part of the body.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 diseasePathology focuses on 4 aspects of disease

• ETIOLOGY:ETIOLOGY: Cause of disease. Cause of disease.• PATHOGENESIS:PATHOGENESIS: Mechanisms of development of disease.Mechanisms of development of disease.• MORPHOLOGY:MORPHOLOGY: The structural alterations induced in cell The structural alterations induced in cell

and tissues.and tissues.• FUNCTIONAL CONSEQUENCES:FUNCTIONAL CONSEQUENCES: Functional consequences of the morphologic changes, as Functional consequences of the morphologic changes, as

observed clinically.observed clinically.

Knowledge of etiology remains the backbone:Knowledge of etiology remains the backbone:

Disease diagnosesDisease diagnoses

Understanding the nature of diseasesUnderstanding the nature of diseases

Treatment of diseases.Treatment of diseases.

Etiology:• Environmental agents:

– Physical– Chemical– Nutritional– Infections– Immunological– Psychological

• Genetic Factors:– Age– Genes

Multifactorial:Multifactorial:

One etiologic agent—one disease.One etiologic agent—one disease.

Several etiologic agents—one disease.Several etiologic agents—one disease.

One etiologic agent—several diseases.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.

PathogenesisPathogenesis

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.

PathogenesisPathogenesis

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

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

• Morphologic changeMorphologic change Characteristic of the diseaseCharacteristic of the disease

Diagnostic of the etiologic proceessDiagnostic of the etiologic proceess

• Functional derangementsFunctional derangements

• Clinical significanceClinical significance

MORPHOLOGYMORPHOLOGY

Morphology remains at the heart of Morphology remains at the heart of diagnostic pathology.diagnostic pathology.

Morphology:

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

Renal Infarction

Normal glomerulusNormal glomerulus

Membranous GNMembranous GN

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.

What do pathologists do?

1.Human Pathology

2.Experimental

Pathology

Scope of Pathology

1.Human Pathology

1)Autopsy

2)Biopsy

3)Cytology

1) Autopsy• The internal examination of the body after death

performed scientifically for medical or legal purposes.

• Roles:

a) to clarify the nature of many diseases.

b) to determine the cause of death and to collect evidence

c) to gather accurate statistics about disease incidence

2) 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

Sputum smears of cytology

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

Sample Case:

Clinical Details:

• 34 year , male

• Neck swelling, 2-3 months,

• Fever, weight loss,

• no other lymphadenopathy

• Lymphnode biopsy done

Right neck mass

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.

2. Experimental Pathology

In vitro:In vitro: Tissue cultureTissue culture Organ cultureOrgan culture Cell cultureCell culture In vivo:In vivo: Experimental animalsExperimental animals Nude miceNude 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.

Nude miceNude mice

How do pathologists do?

RESEARCH METHODSRESEARCH METHODS

• Macroscopic observationMacroscopic observation• Microscopic observation (HE)Microscopic observation (HE)• EMEM• ImmunohistochemistryImmunohistochemistry• HybridizationHybridization• Cell Cultures, Medical MicrobiologyCell Cultures, Medical Microbiology• Molecular PathologyMolecular Pathology PCR Flow cytometry

1. Gross Investigation

1) Size

2) Shape

3) Color

4) Weight

5) 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.

Renal Infarction

2. 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.

Renal Infarction

Liver cirrohsis

Liver carcinoma

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.

Normal glomerulusNormal glomerulus

Membranous GNMembranous GN

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

Chronic glomerulonephritis:glomerulonephritis:

• Immunohistochemistry• Ag-Ab complexes• The bound Ab is then visualized,

using another Ab and a dye complex such as diaminobenzidine.

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 General pathology is concerned with the basic reactions of cells and tissues to basic reactions of cells and tissues to abnormal stimuli that underlie all diseases.abnormal stimuli that underlie all diseases.

• Systemic pathology examines the specific Systemic pathology examines the specific responses of specialized organs andresponses of specialized organs and tissues to more or less well defined stimuli.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 proverbChinese proverbI hear, I forget;I hear, I forget;

I see, I remember;I see, I remember;

I do, I understand. I do, I understand.

Past and Present….!

•In the past, .. people mistook magic for medicine…!

•Now people mistake medicine for magic….!