1. Amos Rodger MWAKIGONJA, MD, MMed, PhD, FCPath ECSA Senior Lecturer
CELL INJURY
Amos Rodger MWAKIGONJA,
MD, MMed, PhD, FCPath ECSA
Senior Lecturer

2. Lecture objectives Define cell injury
Explain causes and classification
Recognize the morphology of cell injury and distinguish between reversible & irreversible injury

3. outline: Definition Classification Causes Morphology Mechanisms
Responses to cell injury/ cellular adaptations

4. definition
Cell injury refers to a sequence of events in a cell which follow when either
Excessive physiologic stress or
Pathologic stimuli
It may be due to a variety of stresses a cell encounters in its
Internal
External environment
surpass the limits of adaptive response or when adaptation to such stimuli is not possible.

5. classification Cell injury can be reversible or
Irreversible if the stimulus
persists or if it is
Severe enough from the outset.

6. causes Exogenous causes (external environment) e.g.
Physical agents
Endogenous causes (internal environment) e.g. metabolic factors, etc.
Congenital or Acquired

7. list of the causes Physical agents: Mechanical trauma
Temperature extremes
Sudden changes in atmospheric pressure
Radiation
Electric shock

8. Chemical agents and drugs:
Innumerable chemicals inflict cell injury e.g. glucose, salt, oxygen, poisons like arsenic, cyanide, mercury, etc., pollutants, insecticides, herbicides, carbon monoxide, asbestos, alcohol, narcotics and therapeutic drugs.
Infectious agents:
Microbes
parasites

9. Immunologic reactions:
Double edged sword
Defensive functions primarily but can be
Injurious e.g. anaphylaxis and autoimmunity.
Genetic derangements: germline or somatic
Gross malformations e.g. Downs syndrome
Subtle alterations at DNA level e.g. SCA
Nutritional imbalances:
Deficiencies e.g. PEM, avitaminosis
Excesses e.g. hyperlipidemia (atherosclerosis), hypervitaminosis

10. morphology Morphology of reversible injury: Light microscopy:
Cellular swelling due to inability to maintain homeostasis
Fatty change in cells involved in and dependent on fat metabolism e.g. hepatocytes and myocardial cells;
Intra-cytoplasmic lipid vacuoles
Appearing in hypoxic and toxic injury

11. Vacuolar degeneration Ultrastructural changes-
Hydropic change
Vacuolar degeneration
Ultrastructural changes-
Plasma membrane alterations-blebbing, blunting, microvilli distortion, myelin figures, loosening of intercellular attachments
Mitochondrial changes
Dilation of endoplasmic reticulum
Nuclear alterations
Gross: organ pallor, turgor and increased weight

12. Morphology of irreversible cell injury (Necrosis): Light microscopy:
Membrane rupture
Dispersal of organelles
Breakdown of lysosomes
Nuclear changes-
Karyolysis (DNA breakdown)
Pyknosis (nuclear shrinkage)
Karyorrhexis (nuclear fragmentation)
Gross tissue changes: coagulative (denaturation), liquifactive (enzymatic digestion), caseous and fat necrosis.

13. Mechanisms (Pathogenesis) of cell injury
Depends on:
1. Type, duration & severity of stress
2. Type, status & adaptability of target cell
3. Underlying intracellular phenomena-reversal mechanisms
4. Morphologic consequences

14. Pathogenesis (continued)
For some injurious agents the biochemical platforms of attack is well defined, viz:
Glycolysis
Citric acid cycle and
Oxidative phosphorylation in mitochondrial inner membranes.

15. Common biochemical pathways of cell injury:
ATP depletion-ATP is produced by
Oxidative phosphorylation and
Glycolysis
Oxygen & oxygen-derived free radicals (reactive oxygen species)
Loss of calcium homeostasis (intracellular calcium accumulation)
defects in selective membrane permiability-xteristic of all forms of cell injury.

16. Responses to cell injury
Lysosomal catabolism-residual bodies, lipofuscin pigment granules,
Induction (hypertrophy of smooth endoplasmic reticulum)
Mitochondrial alterations-number, size, shape e.g. in cell hypertrophy and atrophy.

17. IRREVERSIBLE CELL INJURY
This results in cell death and there are two types:
Necrosis
Infarction
Apoptosis

18. IRREVERSIBLE CELL INJURY
Types of necrosis
Liquifactive
Coagulative
Caseous
Traumatic fat necrosis, etc.

19. Patterns of Necrosis In Tissues or Organs
As a result of cell death the tissues or organs display certain macroscopic changes:
Coagulative necrosis: the outline of the dead cells are maintained and the tissue is somewhat firm. Example: myocardial infarction 
Liquifactive necrosis: the dead cells undergo disintegration and affected tissue is liquified. Example: cerebral infarction.

20. Patterns of Necrosis In Tissues or Organs
Caseous necrosis: a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions.
Fat necrosis: enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes.
Gangrenous necrosis: Necrosis (secondary to ischemia) usually with superimposed infection. Example: necrosis of distal limbs, usually foot and toes in diabetes.