What is Pathology?

1. What is Pathology? “Scientific study of disease" or the alterations that occur when abnormal influences (bacteria, viruses, etc.) affect cells, tissues, or body systems. More specifically, pathology may be defined as the "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents or adverse influences."

2. Pathology Deals with… • The causes of disease (etiology) • Mechanisms of disease (pathogenesis) • Structural alterations of cells and tissues • Functional alteration and consequences of disease

3. Function of Pathology Pathology serves as a "bridge" or "link" between the preclinical subjects (anatomy, physiology, etc.) and the courses in clinical medicine. Actually, pathology provides a logical means of relating the knowledge of normal structure and function (anatomy and physiology) to abnormal structure and function as encountered in a diseased animal.

4. General Pathology It explores and explains the development of basic pathologic mechanisms: Introduction to pathology Inflammation, repair and regeneration, Cell injury, degenerations and infiltrations Haemodynamic (circulatory) disorders. Granulomatous inflammations. Growth disorders and neoplasia.

5. Cell Injury and Necrosis

6. Causes of Cell Injury • Oxygen Deprivation • Physical Agents • Chemical Agents and Drugs • Infectious Agents • Immunologic Reactions • Genetic Derangements • Nutritional Imbalances

7. Causes of Cell Injury Oxygen Deprivation • Hypoxia – deficiency of oxygen • Ischemia – loss of blood supply(arterial flow or reduced venous drainage)

8. Causes of Cell Injury Physical Agents • Mechanical trauma • Extremes of temperature – burns, deep cold • Radiation • Electric shock

9. Causes of Cell Injury Chemical Agents and Drugs • Hypertonic concentration of salt – deranging electrolyte homeostasis • Poisons–arsenic, cyanide, or mercuric salts • Insecticides and Herbicides • Air pollutant – carbon monoxide • Occupational hazard – asbestos • Alcohol and Narcotic drugs

10. Causes of Cell Injury Infectious Agents • Parasites • Fungi • Bacteria • Rickettsiae • Viruses

11. Causes of Cell Injury Immunologic Reactions • Anaphylactic reaction to foreign protein or drug • Reactions to endogenous self-antigens – autoimmune diseases

12. Causes of Cell Injury Genetics Derangements • Congenital malformation – Down syndrome • Decreased life of red blood cell – Thalassemia, Sickle cell anemia • Inborn errors of metabolism

13. Causes of Cell Injury Nutritional Imbalances • Protein-calorie deficiencies • Vitamin deficiencies • Anorexia nervosa • Excesses of lipids – Obesity, Atherosclerosis • Metabolic diseases– Diabetes

14. Mechanisms of Cell Injury • Depletion of ATP • Mitochondrial Damage • Influx of Intracellular Calcium and Loss of Calcium Homeostasis • Accumulation of Oxygen-Derived free radical (Oxidative stress) • Defects in Membrane Permeability

15. Na+ K+ Ca2+ Mechanisms of Cell Injury Depletion of ATP

16. Mechanisms of Cell Injury Mitochondrial Damage Causes Hypoxia, Toxins Cytosolic Ca2+ Oxidative stress Lipid breakdown product

17. Mechanisms of Cell Injury Mitochondrial Damage • Mitochondrial permeability transition of inner membrane (formation of high-conductance channel) • Leakage of Cytochrome c into cytosol Mitochondrial Oxidative Phosphorylation ATP production

18. Mechanisms of Cell Injury Mitochondrial Damage

19. Mechanisms of Cell Injury Influx of Intracellular Calcium and Loss of Calcium Homeostasis

20. Mechanisms of Cell Injury

21. Morphology of Cell Injury and Necrosis • Cell Injury – Reversible – Irreversible • Cell Death – Necrosis – Apoptosis

22. Morphology of Cell Injury Reversible Injury • Plasma membrane alteration • Mitochondrial Changes • Dilation of Endoplasmic reticulum • Nuclear Alteration Cellular swelling Fatty change

24. Morphology of Necrotic Cells • Increased Eosinophilia - loss of RNA (basophilia) - denatured cytoplasmic protein • Nuclear Changes - Pyknosis - Karyorrhexis - Karyolysis • Myelin figure – large, whorled phospholipid mass (phospholipid precipitate)

25. HISTOLOGIC FEATURES OF COAGULATIVE NECROSIS Karyorrhexis Normal cell Reversible cell injury with cytoplasmic & organelle swelling, blebbing & ribosome detachment Irreversible cell injury with rupture of membrane & organelles, & nuclear pyknosis Karyolysis

26. Morphologic pattern of Necrotic Cell mass • Coagulative necrosis • Liquefactive necrosis • Caseous necrosis • Fat necrosis

27. Morphologic pattern of Necrotic Cell mass • Coagulative Necrosis :intracellular acidosis – protein denatured – proteolysis inhibited

28. Ischemic necrosis of the myocardium A, Normal myocardium. B, Myocardium with coagulation necrosis

29. Morphologic pattern of Necrotic Cell mass • Liquefactive Necrosis :focal bacterial (or fungal) infections – accumulation of inflammatory cells :hypoxic death of cells within CNS

30. Coagulative and liquefactive necrosis A, Kidney infarct exhibiting coagulative necrosis B, A focus of liquefactive necrosis in the kidney

31. Morphologic Pattern of Necrotic Cell Mass • Caseous necrosis :gross appearance :microscopic – granulomatous inflammation

32. A tuberculous lung with a large area of caseous necrosis

33. Foci of fat necrosis with saponification in the mesentery

34. Explain the difference(s) between reversible and irreversible cell injury. REVERSIBLE IRREVERSIBLE Loss of ATP  Irreversible mitochondrial damage Phospholipid breakdown Massive peroxidation due todue to PLPase activation  uncontrolled chain reaction Depolymerization of actin  Cleavage of CSK proteins by proteases  Increase in ROS  Uncontrolled ROS; inflammation Release of calcium from Uncontrolled calcium influx storage site   Altered metabolism  Loss of amino acids

35. Describe Patterns of Necrosis in Tissues or OrgansAs a result of cell death the tissues or organs display certain macroscopic changes:1. Coagulative necrosis outline of the dead cells is maintained and the tissue is somewhat firm. Example: myocardial infarction 

38. 3. Caseous necrosis form of coagulative necrosis (cheese- like) Example: tuberculosis lesions

39. 4. Fat necrosis enzymatic digestion of fat example: necrosis of fat by pancreatic enzymes.

40. 5. Gangrenous necrosis Necrosis (secondary to ischemia) usually with superimposed infection example: necrosis of distal limbs, usually foot and toes in diabetes