I NTRODUCTION TO P ATHOLOGY Dr. Temur Ahsan Khan PATH 303General Pathology4(3-2)

INTRODUCTION TO PATHOLOGY

Dr. Temur Ahsan Khan

PATH 303 General Pathology 4(3-2)

PATHOLOGY Pathos (suffering or disease) logos (science) Pathology is the study of structural and functional

changes of body in disease, including changes in cell, tissues, organs and body fluids.

Pathology forms a bridge between basic studies of Anatomy, Physiology, biochemistry and clinical subjects of Medicine and Surgery

DISEASE French word “Des” (away) “aise” (ease)

it is a condition in which the individual suffers from discomfort i.e. not at harmony with its environment.

PATHOGNOMONIC LESION

It is the abnormal structural or functional change in the body as a result of disease and may be detected by gross (necropsy), microscopic (histopathology) or biochemical methods (clinical pathology).

LesionLesion

An alternation that indicates without doubt the cause of a particular disease e.g. finding of Negri bodies in rabies etc

PATHOGENESIS It is a progressive development of a disease

process from its initiation to conclusion in recovery or death.

Disease is a dynamic process which progresses from molecular or bio-chemical alternations to structural (ultrastructural, microscopic and gross lesions) and to functional changes which are seen as signs and symptoms of disease.

Pathological changes

Functional

Structural

Moderate

Time

DIAGNOSIS It is the identification of disease through the clinical examination and application of various laboratory tests.

A pathological diagnoses should include lesions, etiology (cause) pathogenesis and clinical consequences.

PrognosisPrognosis • It is the estimation of the clinician or pathologist

regarding the expected outcome of disease like favorable, guarded or grave ete

EtiologyEtiology It is a study of the causes of disease. An etiologic agent induces cell and tissue injury

leading to clinical manifestations of disease There are numerous causes of disease which are

divided into

1. Exogenous (Environmental or extrinsic factors) 2. Intrinsic Internal defects

BIOLOGICAL AGENTS (INFECTIOUS AGENTS, PATHOGENS, MICROORGANISMS) These are diverse group of biological agents,

ranging from a few nm to a few meters in size. The disease producing biological agents mostly have a parasitic mode of life and include prions, viruses, chlamydia, rickettsia, mycoplasma, bacteria, fungi, protozoa and metazoa.

CHARACTERISTICS OF MICROBIOLOGICAL AGENTS Biological associations and relationships. Commensals: coexistence without injury

or benefit Symbiotic: Mutually beneficial

coexistence.Example: microflora and fauna in the

rumen and colon of herbivores and E.coli in the gut of humans producing vit.K.

Parasitic/Predators: causing morbidity and mortality in the host (man and animals)

PORTAL OF ENTRY IN THE BODY: Lungs and mucociliary mechanisms Mouth and GIT. Gastric acidity Intact membranes Size of inoculum-MID 50 and MLD 50

HOST DEFENSE MECHANISMS. Humoral- innate natural immunity, acquired

immunity, antibody formation. Cellular defense- Phagocytosis by neutrophils

and monocytes.

SURVIVAL OF MICROORGANISMS IN THE BODY: Spreading factor- Hyaluronidase Evasion of phagocytosis- capsule formation Sequestration-coagulase,collagenase,

organotropism

INTRACELLULAR LOCALIZATION Facultative- Mycobacterium, Brucella,

Histoplasma, Nocardia, Toxoplasma, Theileria Obligate- Rickettsia, Viruses, Plasmodium.

HOW MICROORGANISMS CAUSE DISEASE

Host factors- age, nutrition, immune status, intercurrent disease, opportunistic infection, predisposing factors

GENERAL MECHANISM OF DISEASE PRODUCTION: Dysfunction and death of host cells Release of endotoxins and exotoxins Induction of immune and inflammatory

responses causing injury and disease.

MECHANISMS OF VIRAL INJURY: Host cell receptors Type- specific transcription factors Crossing physical barriers Immune cell-mediated killing Alteration of apoptosis pathway

MECHANISMS OF VIRAL INJURY: CONT….. Induction of cell proliferation and

transformation Inhibition of host cell DNA,RNA or protein

synthesis Damage to plasma membrane Damage to cells involved in antimicrobial

defense

MECHANISMS OF BACTERIAL INJURY:Depends upon their ability to

(a) Adhere to host cells(b) Invade the cells and tissues(c) To deliver toxins that damage the cells and

toxins Bacterial adherence to host cellsMechanisms- Adhesins, fibrils and fimbrae

VIRULENCE OF INTRACELLULAR BACTERIA: Facultative intracellular bacteria Subversion of host immune response Inhibition of synthesis of host cell proteins

ELABORATION OF BACTERIAL ENDOTOXINS: Septic shock Disseminated intravascular coagulation cytokines

BACTERIAL ENDOTOXINS Bacterial enzymes Inhibition of protein synthesis Cellular necrosis Neurotoxins- Cl.Botulinum and Cl.Tatani,

paralysis, respiratory failure

WHAT IS PATHOLOGY? Study of derangement of molecules, cells,

tissues, and function in the living organisms in response to injurious agents and deprivations

COMMON TERMS USED IN PATHOLOGY Lesions (Gross, microscopic, chemical, molecular,

immunologic) Etiology Pathogenesis Symptoms Postmortem examination/autopsy/necropsy Biopsy Morbid changes Postmortem changes

HISTORY The first concept of disease The demoniac

concept of disease- witch doctor (17 thousand years old-Paintings in the caves of Pyrenees mountains)

Theological concept of disease 4000 B.C. (embalming)- disease due to divine displeasure- Priest

Humoral concept of disease- Greece-Hippocrates (460-377 B.C.)-Blood-warm and moist (air)Phlegm- cold and moist (water)Yellow bile- warm and dry (fire)Black bile- cold and dry (earth)

DEVELOPMENT OF ANATOMY, PHYSIOLOGY, AND PATHOLOGY Aristotle (384-322 B.C.) - modern anatomy

and physiology

Claudius Galen (131-206 A.D.)- Father of anatomy

FIRST TEXTBOOK ON VETERINARY MEDICINE Renatus Vegetius (450-500 A.D.) “Book of the

Veterinary Art” – father of veterinary medicine

CENTURY OF ANATOMYAntanio Benivieni (1440-1502)- postmortem examination- father of Pathological anatomy

Leonardo da Vinci (1452-1519)- Artist- Anatomy of horse

Andreas Vesaleus (1514-1564)- Belgian- At the age of 24 became Professor of anatomy at Padua, in Italy

DISCOVERY OF BLOOD CIRCULATION William Harvey (1578-1657)- Englishman-

airtree Marcello Malpighi (1628-1694)- Italian-

capillaries and erythrocytes, and microscopic description of kidney, lungs, and spleen

INVENTION OF MICROSCOPE Antony van Leeuwenhoek (1632-1723)-

Dutch draper- made 200 microscopes

FIRST TEXT BOOK OF PATHOLOGYJean Fernet (1497-1558)-Frenchman

Giovanni Battista Morgagni (1682-1771)-modern Pathology- Seats and causes of disease in 5 volumes- correlation of lesions with the symptoms

FATHER OF HISTOLOGY Marei-Farancois Xavier Bichat (1771-1802)-

Frenchman – body composed of 21 tissues

FATHER OF IMMUNOLOGY Edward Jenner (1749-1823)- Englishman-

discovered vaccination Material from cowpox lesions could be used

to protect small pox in humans

ESTABLISHMENT OF FIRST VETERINARY SCHOOL Jacques Labessie De Solleysel (1617-1680) – Complete book on veterinary medicine

Claude Bourgelat (1712-1779) – lawyer – book on equine medicineJanuary 1, 1762 in Lyon, France

FIRST EXPERIMENTAL PATHOLOGISTJohn Hunter (1728-1793) – Scotch- Blood, inflammation, gunshot wounds, monograph “Venereal Disease”- SyphilisTreponema pallidum

Julius Cohnheim (1839-1884) – German - Inflammation

CELLULAR PATHOLOGYJohannes Mueller (1801-1858)- German- used microscope to study tissues

Rudolph Virchow (1821-1902)- Book “Cellular Pathology” . Father of Cellular Pathology or Father of Modern Pathology.Most of the terms used in pathology are coined by him

GERM THEORY OF DISEASE Louis Pasteur (1822-1895) – France – germ

theory of disease Robert Koch (1843-1910)-

DISCOVERY OF PHAGOCYTOSIS Elie Metchnikoff (1845-1916) - Russian

DISCOVERY OF LYSOSOMES Christian de Duve (1955) in Belgium-

fractional centrifugation Novikoff Confirmed presence of lysosomes by EM.

DISCOVERY OF PRIONSProteinaceous infective particle (Prion)

Lack nucleic acid(RNA, DNA)No inflammatory or immune reponse

Resistant to UV light & disinfectants

Cause tranmissible spongiform encephalopathies (TSE’s)