Lecture 1 - Principles of General Pathology PDF

Arab Republic of Egypt Ministry of Higher Education Egyptian Chinese University College of Physical Therapy Dr. Ahmed Fawzi Elshaieb Professor of Pathology  What is pathology? Pathology is the study of disease by scientific met...

Arab Republic of Egypt Ministry of Higher Education Egyptian Chinese University College of Physical Therapy Dr. Ahmed Fawzi Elshaieb Professor of Pathology  What is pathology? Pathology is the study of disease by scientific methods. It is the study of how the organs and tissues of healthy body change to those of sick person. So, the study of pathology provides an understanding of the disease processes. Clinical Pathology Bridging Subject Foundation  Medical Knowledge: what should we know about a disease? Definition Epidemiology – Where & When.. Etiology – What is the cause? Pathogenesis - Evolution of dis. Morphology - Structural Changes Clinical Significance – relate.. Prognosis Management Prevention  Scope of Pathology Clinical Pathology Experimental Pathology Molecular Pathology Forensic Pathology Chemical / Microbiology Immunopathology Genetics & Disease.  Subdivisions of Pathology: Histopathology Cytopathology Hematology Microbiology Immunology Chemical Pathology Genetic Pathology Toxicology Forensic Pathology  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.  What is general pathology? The various types of lesions that may occur are grouped into categories sharing common features for purposes of study. The common categories of lesions are those associated with degeneration and death of cells, circulatory disorders, inflammation and repair, disturbances in growth and development of cancer. These are the topics of general pathology.  The objective of general pathology is to learn the basic lesions and pathogenetic mechanisms associated with disease presence.  What is the lesions Lesion: it is the abnormal structural changes in the living body which caused by an irritant.  What is pathologist? The pathologist may be a person with a doctorate (PhD) in pathology who has been trained to perform and interpretation of laboratory procedures. The objective of the pathologist is to find, name and interpret the lesions in the tissues examined and attempts to made a diagnosis. Why does a clinician need pathology? The main role of a medical doctor is to diagnose, treat, prevent and control disease. The key to these functions is diagnosis The key to diagnosis is the ability to recognize lesions in the live or dead person, to understand their pathogenesis and, through these, to make rational conclusions and recommendations for treatment, control and prevention.  Etiology This means the causes of the disease. The etiology includes : Predisposing factors: Factors which help the development of the disease. Exciting factor: Is the direct cause of the disease.  Etiology: What is the cause? Environmental agents: – Physical – Chemical – Nutritional – Infections Multifactorial: Diabetes, – Immunological Hypertension Cancer – Psychological Genetic Factors: – Age – Genes  Disease Disease Disease Disease Disease One agent  One disease - Malaria Several agents  One disease - Diabetes One agent  Several diseases - Smoking  Pathogenesis The mechanism by which the causative agent produces the pathological changes in the tissues  Pathological picture Includes : a) Gross picture ( macroscpic picture ): these are the changes in the tissues and organs detected on naked- eye examination. b) Microscopical picture ( histopathology): these are the changes in the tissues detected on microscopic examination. c) Electron microscopic, immunohistochemical, cytogenetic and molecular studies of diseased tissues and organs.  Prognosis is the expect outcome of disease. A prognosis can not be accurately provided without an understanding of pathogenesis and an ability to mentally visualize the disease process. The patient’s concern is prognosis; the doctor’s concern is diagnosis and prognosis. Both diagnosis and prognosis require comprehension and recognition of lesions and their pathogenesis. Pathology is truly the cornerstone of medicine.  Fate The end result of the disease condition either cure or death of the patient.  Complications Are additional pathological changes which may occur during or after the termination of the usual course of the disease  Cell injury and Cell death Refers to any biochemical or structural alteration that impairs the ability of a cell to function normally, or it may be of such severity and duration that it becomes irreversible.  reversible cell injury (cell swelling) Cell injury Irreversible cell injury (cell death) I- Programmed cell death (Apoptosis) II- Accidental cell death (Necrosis)  Cell injury is a reversible changes Cell death: is defined as that point when cell injury become irreversible or has passed the “point of no return”.  Causes of cell injury and cell death 1- Oxygen Deprivation. Hypoxia, or oxygen deficiency, 2- Deprivation of essential nutrients (water, foodstuff) 2- Chemical agents. 3- Infectious agents, 4- Immunologic reactions, 5- Genetic disorders (congenital malformation). 6- Physical agents (trauma, extreme temperature and radiation). 7- Free radicals. 8- Aging.  Hypoxic cell injury Acute cellular swelling Swelling of the cells is one of the earliest recognizable microscopic changes following cellular injury. If severe it is visible by light microscopy and is known as hydropic or vacuolar degeneration.  Acute cellular swelling Causes and mechanism: Toxins and hypoxia damage the mitochondria. Damaged mitochondria disturbed ionic concentration in the cells. The cells leave its potassium and accumulate sodium. Accumulation of sodium is followed by entry of water. The cells become markedly swollen.  Cell injury induced by chemicals Exogenous chemicals induce cell injury and death by one of two methods: 1. Binding directly to critical structural or reactive chemicals of cellular organelles and thereby damaging cell membranes or the ability of cell to generate the ATP and energy that are required for maintenance of normal homeostasis function. 2. By being chemically transformed to more reactive metabolites that are capable of generating free radicals which subsequently cause permanent membrane damage and cell death  Cell injury induced by free radicals Free radicals are chemical species with a single unpaired electron in an outer orbital. Free radicals are chemically unstable and therefore readily react with other molecules, resulting in chemical damage. The three most important are: 1) Superoxide (O2) 2) Hydrogen peroxide (H2O2) 3) Hydroxyl ions (OH) 1) Superoxide (O2) generated by autooxidative and oxidase reactions in the mitochondria and cytoplasm respectively, and neutralized by the enzyme superoxide dismutase. 2) Hydrogen peroxide (H2O2) generated by dismutation of O2 by superoxide dismutase and by catalase reactions occuring in peroxisomes. 3) Hydroxyl ions (OH) resulting from hydrolysis of water by ionizing radiation and interaction of hydrogen peroxide with certain metals, especially iron and copper. Three basic mechanisms by which free radicals can damage cells: 1.Lipid peroxidation of membranes: results in membrane damage. 2.DNA fragmentation: results in apoptosis and carcinogenesis. 3.Protein cross-linking: results in membrane damage.  Irreversible cell injury (cell death) is defined as that point when cell injury become irreversible or has passed the “point of no return”. Cell death occurs in two biochemically and morphologically distinct ways “accidental cell death” and “apoptosis”. Finally, the term necrosis refers to the characteristic light microscopic changes resulting from enzymatic degradation of the nucleus and cytoplasm that define cell death. Irreversible cell injury (cell death) I- Programmed cell death (Apoptosis) II- Accidental cell death (Necrosis)  II- APOPTOSIS Regulated mechanism of cell death that serves to eliminate unwanted damaged cells, with the least possible host reaction. This term has been used for a mechanism of cell death affecting single cells scattered in a population of healthy cells. In many organs cells are shed as they come to the end of their life span. This programmed obsolescence involves cell death by the process of apoptosis. * Its designation „apoptosis“- it is a word from Greek language, which originally refers to falling of leaves from trees in the autumn  Significance of apoptosis Significance of Physiological apoptosis: Significance of Pathological apoptosis: Is involved in normal tissue turnover. Apoptosis may be involved in response to pathologic stimuli, In hormone-induced atrophy - Such as viral infection. (endometrium in menstrual cycle). - Tumor regression induced by chemotherapy. In developing tissues, programmed cell destruction in embryogenesis.  Criterion Accidental cell death Apoptosis cells affected Numerous Single or small clusters causes Physical, chemical, Protease nutritional, viable nature Pathologic Pathologic or physiologic Cellular membrane Damaged (damaged Intact( intact sodium sodium potassium pump) potassium pump) Cell size Swollen Shrunk Apoptotic bodies Absent present Pyknosis , karyorrhexis and present absent karyolysis inflammation Present Absent disposal By inflammation By phagocytosis