1. Cellular responses to stress (Adaptations, injury and death) (2 of 5)
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

2. Most injurious stimuli are grouped into:
Oxygen deprivation
Chemical agents
Infectious agents
Immunologic reactions
Genetic factors
Nutritional imbalances
Physical agents
Aging

3. *Oxygen deprivation *Chemical agents 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

4. *Immunologic reactions...Mention 2 important general examples
*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: …….

5. Examples of genetic abnormalities

6. *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

7. *Physical agents: *Aging: -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

8. Sequence of events Cell function change: molecular
and biochemical changes

9. Example: Cardiac myocyte:
-1-2 minutes after ischemia: Non-contractile minutes: cell death -2-3 hours: by EM hours: by LM

10. Morphology of reversible injury
2 main features:
-cellular swelling…failure of Na+3/K+ pump
the first structural change
-fatty change

11. 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

12. 2 characteristics of irreversibility
Inability to correct mitochondrial function
Profound disturbances in membrane function…including lysosomal membrane
**If irreversible injury occurs death will follow

13. Necrosis…general features
Swelling
Damage of membranes
Lysosomal enzymes leakage
Digestion of the cell (moth-eaten appearance) and leakage of contents outside
Surrounding inflammation

14. 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

15. Fates of necrotic cellsor
digested by enzymes and disappear
replaced by myelin figures phagocytosed
degraded into fatty acids
may bind calcium (calcification)

16. Some terms used to describe specific patterns of tissue necrosis:
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis

17. 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

18. Coagulative necrosis

19. 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

20. Gangrenous necrosis Clinical term…when we talk about a limb
Ischemia coagulative necrosis (dry gangrene)
superimposed infection
liquifaction
(wet gangrene)…pus and smell

21. 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

22. Caseating granuloma

23. 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

24. 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:

25. Lab investigations can detect tissue-specific 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.