Cellular responses to stress (Adaptations, injury and death) (2 of 5)
Most injurious stimuli are grouped into: Oxygen deprivation Chemical agents Infectious agents Immunologic reactions Genetic factors Nutritional imbalances Physical agents Aging
*Oxygen deprivation What is the most common cause? Ischemia is different from hypoxia Examples of hypoxia not due to ischemia: -Anemia -CO poisoning *Chemical agents Many agents and many effects (damage to membranes, proteins or changes in gradients) Even oxygen, glucose, salts, or even water
*Infectious agents *Immunologic reactions...mention 2 important general examples *Genetic factors: -Direct phenotypical abnormalities or -Increased susceptibility to injurious factors 2 persons are phenotypically normal (= no disease) but one is susceptible to have disease while the other is not and this is called:.
Examples of genetic abnormalities
*Nutritional imbalances nutrients: -Protein-calorie deficiencies chiefly among underprivileged populations -Vitamin deficiencies or abnormalities such as: -obesity -self-induced starvation, called:.. -diets rich in animal fat
*Physical agents: -Trauma -Radiation -Electric shock -Extremes of temperature -Sudden changes in atmospheric pressure - etc *Aging: = cellular senescence -problems in replication and repair more susceptibility to cell damage and death of the cell or the organism
Sequence of events Cell function change: molecular and biochemical changes
Example: Cardiac myocyte: -1-2 minutes after ischemia: Non-contractile -20-30 minutes: cell death -2-3 hours: by EM -6-12 hours: by LM
Morphology of reversible injury 2 main features: -cellular swelling failure of Na+3/K+ pump the first structural change -fatty change
Morphology of reversible injury, by organelles Plasma membrane changes: -blebbing -distortion of microvilli -loosening of intercellular attachments Mitochondrial changes: -swelling -amorphous densities rich in phospholipids ER: -swelling -detachment of ribosomes -dissociation of polysomes -pinched-off segments vacuolar (hydropic degeneration) Nucleus: clumping of chromatin Cytoplasm: -Fatty change (lipid vacuoles) esp. cells participating in fat metabolism (myocardial cells, hepatocytes etc.) -myelin figures (phospholipid masses from damaged membranes) -eosinophila
2 characteristics of irreversibility Inability to correct mitochondrial function Profound disturbances in membrane function including lysosomal membrane **If irreversible injury occurs death will follow
Necrosis general features Swelling Damage of membranes Lysosomal enzymes leakage Digestion of the cell (moth-eaten appearance) and leakage of contents outside Surrounding inflammation
Necrosis Cytoplasm: - eosinophilia mention the causes for this - glassy (homogenous) appearance due to loss of glycogen - myelin figures are more prominent Membranes: more damage than injury esp. damage of lysosomes Mitochondria: more damage than injury large amorphous densities Nucleus: -Karyolysis: fading of basophilia due to DNase -pyknosis: shrinkage with increased basophilia -karyorrhexis: fragmentation 1-2 days: disappears
Fates of necrotic cells Necrotic cell or digested by enzymes and disappear replaced by myelin figures phagocytosed degraded into fatty acids may bind calcium (calcification)
Some terms used to describe specific patterns of tissue necrosis: Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis
Coagulative necrosis Architecture is preserved because enzymes of proteolysis are also denatured by the injury Eosinophilic anucleate cells ghosts of cells Surrounded by inflammation will be phagocytosed Infarcts of all solid organs except ------- Infarct = ischemic necrosis
Coagulative necrosis
Liquefactive necrosis Infections inflammatory cells, their enzymes and bacterial products liquefy the tissue Ischemic necrosis of brain In acute inflammation: pus creamy yellow in color
Gangrenous necrosis Clinical term when we talk about a limb Ischemia coagulative necrosis (dry gangrene) superimposed infection liquifaction (wet gangrene) pus and smell
Caseous necrosis Most often in tuberculosis (TB) Cheesy appearance On LM: -granular pink material of lysed cells -no cellular outlines -often surrounded by epithelioid histiocytes = caseating granuloma
Caseating granuloma
Fat necrosis = necrosis of adipose tissue *Typical example: pancreatitis (pancreatic cells die due to inflammation and lipases are released from them digesting peritoneal fat (TGs FAs) Fatty acids may bind calcium chalky white material (saponification) *On LM: shadows of fat cells with basophilic material (calcium) and surrounding inflammation
Fibrinoid necrosis Usually in vasculitis usually autoimmune antigen-antibody complexes in the vessel wall + leaked fibrin from the vessels Detected by LM, not grossly bright pink material in the vessel wall:
Lab investigations can detect tissuespecific necrosis (increased serum levels of cell products) Heart creatine kinase (CK-MB) and troponin I Bile ducts alkaline phosphatase (ALK) Hepatocytes transaminases (ALT and AST) etc.