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."

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

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.

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.

Cell Injury and Necrosis

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

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

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

Infectious Agents Parasites Fungi Bacteria Rickettsiae Viruses Causes of Cell Injury

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

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

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

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

Na + K+K+ Ca 2+ Mechanisms of Cell Injury Depletion of ATP

Mitochondrial Damage Mechanisms of Cell Injury Causes Hypoxia, Toxins Cytosolic Ca 2+ Oxidative stress Lipid breakdown product

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

Mechanisms of Cell Injury Mitochondrial Damage

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

Morphology of Cell Injury and Necrosis Cell Injury – Reversible – Irreversible Cell Death – Necrosis – Apoptosis

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

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)

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

Morphologic pattern of Necrotic Cell mass Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis

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

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

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

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

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

A tuberculous lung with a large area of caseous necrosis

fat necrosis Foci of fat necrosis with saponification in the mesentery

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

Coagulative Describe Patterns of Necrosis in Tissues or Organs As 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

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

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

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