Adaptations injury and death 2 of 5 Ali Al Khader MD Faculty of Medicine AlBalqa Applied University Most injurious stimuli are grouped into Oxygen deprivation Chemical agents ID: 650083
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Cellular responses to stress (Adaptations, injury and death)(2 of 5)
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied UniversitySlide2
Most injurious stimuli are grouped into:Oxygen deprivationChemical agentsInfectious agentsImmunologic reactionsGenetic factorsNutritional imbalancesPhysical agentsAgingSlide3
*Oxygen deprivation What is the most common cause?Ischemia is different from hypoxiaExamples of hypoxia not due to ischemia: -Anemia -CO poisoning*Chemical agentsMany agents and many effects (damage to membranes, proteins or changes in gradients)Even oxygen, glucose, salts, or even waterSlide4
*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: …….
Slide5
Examples of genetic abnormalitiesSlide6
*Nutritional imbalances nutrients: -Protein-calorie deficiencies…chiefly among under- privileged populations -Vitamin deficiencies or abnormalities such as: -obesity -self-induced starvation, called: …….. -diets rich in animal fat Slide7
*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 Slide8
Sequence of eventsCell function change: molecular and biochemical changesSlide9
Example: Cardiac myocyte:-1-2 minutes after ischemia: Non-contractile-20-30 minutes: cell death-2-3 hours: by EM-6-12 hours: by LMSlide10
Morphology of reversible injury2 main features: -cellular swelling…failure of Na+3/K+ pump the first structural change-fatty changeSlide11
Morphology of reversible injury, by organellesPlasma membrane changes: -blebbing -distortion of microvilli -loosening of intercellular attachmentsMitochondrial changes: -swelling -amorphous densities rich in phospholipidsER: -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)
-eosinophilaSlide12
2 characteristics of irreversibilityInability to correct mitochondrial functionProfound disturbances in membrane function…including lysosomal membrane**If irreversible injury occurs death will followSlide13
Necrosis…general featuresSwellingDamage of membranesLysosomal enzymes leakageDigestion of the cell (moth-eaten appearance) and leakage of contents outsideSurrounding inflammationSlide14
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 lysosomesMitochondria: more damage than injury…large amorphous densitiesNucleus: -Karyolysis: fading of basophilia due to DNase -pyknosis: shrinkage with increased basophilia
-karyorrhexis: fragmentation
…1-2 days: disappearsSlide15
Fates of necrotic cellsNecrotic cell or digested by enzymes and disappear replaced by myelin figures phagocytosed degraded into fatty acids
may bind calcium (calcification)Slide16
Some terms used to describe specific patterns of tissue necrosis:Coagulative necrosisLiquefactive necrosisGangrenous necrosisCaseous necrosisFat necrosisFibrinoid necrosisSlide17
Coagulative necrosisArchitecture is preserved because enzymes of proteolysis are also denatured by the injuryEosinophilic anucleate cells…ghosts of cellsSurrounded by inflammation…will be phagocytosedInfarcts of all solid organs except -------Infarct = ischemic necrosisSlide18
Coagulative necrosisSlide19
Liquefactive necrosisInfections…inflammatory cells, their enzymes and bacterial products “liquefy” the tissueIschemic necrosis of brainIn acute inflammation: pus…creamy yellow in colorSlide20
Gangrenous necrosisClinical term…when we talk about a limbIschemia coagulative necrosis (dry gangrene) superimposed infection liquifaction (wet gangrene)…pus and smell Slide21
Caseous necrosisMost often in tuberculosis (TB)Cheesy appearanceOn LM: -granular pink material of lysed cells -no cellular outlines -often surrounded by epithelioid histiocytes… = caseating granulomaSlide22
Caseating granulomaSlide23
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 inflammationSlide24
Fibrinoid necrosisUsually in vasculitis usually autoimmune antigen-antibody complexes in the vessel wall + leaked fibrin from the vesselsDetected by LM, not grossly…bright pink material in the vessel wall:Slide25
Lab investigations can detect tissue-specific necrosis (increased serum levels of cell products)Heart…creatine kinase (CK-MB) and troponin IBile ducts…alkaline phosphatase (ALK)Hepatocytes…transaminases (ALT and AST)…etc.