SLIIT Pathology (NS2012) Higher National Diploma in Nursing Cell Injury, Cell Death and Cellular Adaptations -I PDF

Pathology (NS2012) Higher National Diploma in Nursing Cell Injury, Cell Death and Cellular Adaptations -I Dr Gihani Jayaweera Senior Lecturer Department of Basic Sciences, Faculty of Allied Health Science, KD...

Pathology (NS2012) Higher National Diploma in Nursing Cell Injury, Cell Death and Cellular Adaptations -I Dr Gihani Jayaweera Senior Lecturer Department of Basic Sciences, Faculty of Allied Health Science, KDU  Intended learner outcomes At the end of the lecture, student should be able to Explain the overview of cell injury, cellular adaptations and cell death. Outline the causes of cell injury, cellular adaptations and cell death. Outline the morphological changes of cell injury, cellular adaptations and cell death. Causes for Cell injury Interfere with aerobic respiration Oxygen Deprivation Caused by loss of blood supply or inadequate oxygenation of blood Oxygen in high pressure, Sugar, Salt Chemical agents Poisons, CO, Drugs, Asbestos Infectious agents Virus, Bacteria, Protozoa, Fungi,Parasites  Immunologic Autoimmune reactions Allergic reactions reactions Enzyme deficiencies Accumulations of damaged DNA Genetic defects Misfolded proteins e.g Sickle cell anemia, Thalassemia Nutritional Deficiencies-Vitamin Deficiency Overnutrition- imbalances Physical Trauma, Thermal injuries, irradiation, High agents pressure, Electric shock Alterations in cellular Aging capacity to replicate and repair. The outcomes of cellular reaction depend on: Type of cell In hypoxia Neurons will die in 3-5 minutes Cardiac muscle 30min – 2hours Skeletal muscle/ skin much longer time Duration Severity  Important Targets of Cell Injury Mitochondria – ATP depletion or decreased synthesis. Cell membranes - plasma membranes, mitochondrial, lysosomal and other organelle membranes. Protein synthesis. Cytoskeleton. Genetic apparatus. Morphological changes in Reversible cell injury Cellular swelling and vacuole formation (Hydropic changes) Intracellular accumulation of water due to loss of fluid and ionic homeostasis. Fatty changes- Lipid vacuoles Hydropic Changes Gross examination: The affected organ is enlarged, pale and soft. Microscopic examination: Cells are enlarged with a clear or pale vacuoles in the cytoplasm Fatty Changes in Liver The lipid accumulates in the hepatocytes as vacuoles. These vacuoles have a clear appearance The most common cause of fatty change is alcoholism. Diabetes mellitus, obesity, and severe gastrointestinal malabsorption are additional causes. Ultrasound changes in reversible injury Changes in Plasma Membrane: blebbing, blunting and distortion of microvilli Changes in Mitochondria: swelling of mitochondria Changes in ER: dilatation of ER, detachment of ribosomes. Nuclear alterations: clumping of chromatin.  Irreversible cell Injury-CELL DEATH Death of cells occur in two ways Necrosis Enzymatic digestion of dead cellular material. Membrane integrity is disrupted and cellular material leak out. Apoptosis Vital process that helps eliminate unwanted cells Tightly regulated programmed series of events.  Necrosis Major pathway of cell death Always associated with pathologic process. Enzymes leak out from the lysosomes due to membrane damage. Digest the cellular components. Plasma membrane get disrupted and enzymes leak out. Elicits inflammation in adjacent tissue.  Morphological features of Necrosis Nuclear changes: Karyolysis (Fading of the chromatin). pyknosis (Nuclear Shrinkage and increased basophilia, DNA condensed). Karyorrhexis (Pyknotic nucleus undergo fragmentation).  Morphological features of necrosis Cytoplasmic Changes: Increased eosinophilia-due to binding of eosin to denatured protein. Glassy homogenous appearance-loss of glycogen Vacuolation -loss of cellular organelles Myelin figures-dead cells are replaced by phospholipid masses. Calcification. Damages plasma and organelles membranes. Necrotic kidney tubules Cellular fragmentation Loss and fading of nuclei-- karyolysis Burst membranes Loss of tissue architecture  Morphological patterns of Necrosis Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis  Coagulative Necrosis Cells are dead but the basic tissue architecture is preserved. Denaturation of proteins destruct the enzymes and block the proteolysis of the dead cells. Finally necrotic cells are removed by phagocytosis. Eg: Infarction( Necrosis due to ischemia) of solid organs except brain. Coagulative Necrosis- Kidney infarction Renal cortex has undergone anoxic injury. Gross examination: Wedge shaped pale area of necrosis Coagulative necrosis- Myocardial infarction Gross examination: A pale whitish infarct is surrounded by zone of hyperemia. Liquefactive Necrosis Occurs in bacterial or fungal infections Microbes stimulate the accumulation of inflammatory cells. Enzymes in the leucocytes digest the dead cells. Complete digestion of dead cells result in transformation of necrotic tissues into viscous liquid mass. Gross tissue architecture lost due to degradation of connective tissue E.g. Infarctions central nervous system. Brain infarction Gross examination: Dissolution of the tissue. Gangrenous Necrosis Applied to infarctions in limbs e.g. Lower limb. Coagulative necrosis of limb: Dry Gangrene Gross appearance- bluish black discoloration. Liquefactive necrosis: Wet Gangrene. Dry gangrene Caseous Necrosis Gross appearance- Friable, Yellow-White(Cheese like) Cell architecture is completely destructed and cellular outlines are not clear. E.g. Tuberculosis infection Caseous necrosis of lung Fat necrosis Focal area of fat destruction. Occurs due to release of pancreatic lipases to pancreas and peritoneal cavity. Lyses the fat cell membranes and fat. Released fatty acids combine with calcium- Gives chalky appearance. E.g. Acute Pancreatitis. Fat necrosis in pancreatitis Fibrinoid necrosis Occurs in immune reactions associated with blood vessels. Deposition of Ag-Ab complexes on the walls of the arteries with fibrin that has leked out of vessels. E.g. Immune mediated diseases- Polyarteritis nodosa  Apoptosis Apoptosis is a pathway of cell death. Tightly regulated suicide program Fragments of apoptotic cells(Apoptotic bodies) are break off and undergo phagocytosis. Membrane integrity remains intact. Dead cells are rapidly removed by phagocytosis before they leak out. Does not elicit inflammation in adjacent tissues. Causes for apoptosis Physiologic conditions: Eliminates unwanted cells and maintains steady number of cell populations in tissue. E.g. Programmed cell death during embryogenesis Involution of Hormone- dependent tissue- breakdown of cells during Menstural cycle, breast tissue after weaning. Cell loss in proliferating cell populations Eg: Bone marrow, T cells  :Pathological conditions: To eliminate genetically altered cells and injured cells. E.g. DNA damage Accumulation of misfolded proteins. Cell death in certain infections Pathological atrophy in parenchymal organs after duct obstructions Eg; kidneys, Pancreas and parotid gland. Morphological features of Apoptosis Cytoplasm become more eosinophilic. Nuclear chromatin condensation and aggregation followed by karyorrhexis. Cells get shrunk and fragmented into apoptotic bodies.  Necrosis Vs Apoptosis Feature Necrosis Apoptosis Cell size Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis → karyorrhexis → karyolysis Fragmentation into fragments Plasma membrane Disrupted Intact; altered structure, especially orientation of lipids Cellular contents Enzymatic digestion; may leak out of Intact; may be released in apoptotic cell bodies Adjacent inflammation Frequent No Physiologic or pathologic role Pathologic Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage