1. Cell injury-1

2.  Cells are constantly exposed to a variety of stresses.  At first cells try to adapt themselves to overcome this stressful condition, but When stress is too severe or for prolonged duration, injury results.  Injury of the cell may be; 1. Reversible: 1. Reversible: if the affected cells recover from the injury. 2. irreversible: 2. irreversible: injury: cell may die 2

3. * Causes of cellular injury:  Physical agents: Hypoxia, mechanical trauma, burns, radiations, electric shock  Chemical agents: poisons (toxins), insecticides, alcohol, tobacco.  Infectious agents: viruses, bacteria, fungi, parasites.  Immunologic reactions: anaphylaxis, autoimmune disease.  Genetic derangements: abnormal proteins (hemoglobinopathies), abnormal or absent enzymes (storage disorders). 3

4. - The cellular response to injurious stimuli depends on : 1. Type, duration and severity of injurious agent. 2. The type, status, adaptability of the injured cell. 4

5. Adaptation 5

6. a. Hyperplasia: b. Hypertrophy: a. Hyperplasia: increase in cell number e.g. compensatory hyperplasia of the kidney after nephrectomy. b. Hypertrophy: increase in cell size. Hypertrophy of the left ventricle due to aortic stenosis of systemic hypertension.

7. c. Atrophy: d. Metaplasia: c. Atrophy: decrease in cell number and/ or size e.g. atrophy of the female breast after menopause. d. Metaplasia: change of type of cell to another type of the same category (epithelial to epithelial or connective tissue to connective tissue e.g. squamous metaplasia of urinary bladder epithelium in case of bilharziasis. 7

8. Reversible cell injury 8

9. * Mechanisms of reversible cell injury: 1. Cell membrane damage: leading to Loss of structural integrity and Loss of function. 2. Mitochondrial damage: leading to decreased energy production (decrease ATP). 3. Ribosomal detachment: leading to decreased protein synthesis. 4. Production of oxygen derived free radicals. 9

10. Hypoxic cell injury

11. - The most common cause of cell injury. * Definition: inadequate oxygenation of tissue. * Causes: 1.Ischemia: decreased arterial blood flow to tissues. – Most common cause of hypoxia. – Ex: Atherosclerosis (lesion in intima = atheroma) in coronary arteries. 2.Hypoxemia: decrease in the amount of oxygen dissolved in plasma. Seen in: Atelectasis, pulmonary embolus and interstitial fibrosis of lung. 3.Hemoglobin related abnormalities – Anemia – Carbon monoxide poisoning (CO has high affinity for hemoglobin). 11

12. * Consequences of tissue hypoxia: Decreased synthesis of ATP by oxidative phosphorylation causing ATP depletion. This leads to; 1.Impaired Na + /K + -ATPase pump: – Diffusion of Na + and water into cells  cellular swelling. 2. Shifting to anaerobic glycolysis: leads to; Accumulation of lactic acid. Decrease in intracellular pH  denaturation of proteins  decreased activity of many enzymes  clumping of nuclear chromatin. 12

13. 3. Ribosomal detachment: Leads to decreased protein synthesis. - ↓protein synthesis leads to ↓ synthesis of apolipoproteins (lipid carriers in blood)  accumulation of lipid in the cell (fatty change). 13

14. Ischemia ↓ oxidative phosphorylation  Na pump Influx of Na, H 2 O & Ca 2+ Efflux of K Cell Swelling  Glycolysis  Lactic acid  pH Ribosomal Detachment  Protein Synthesis Nuclear chromatin clumping ↓↓ ATP 14

15. * Morphology of reversible cell Injury: 1.Cell Swelling: 1.The first manifestation of cell injury. 2.Occurs when cells fail to maintain ionic and fluid homeostasis. 3.Manifests as small clear vacuoles inside the cytoplasm. 4.Also known as hydropic change. 2.Fatty change: 1.Manifested by appearance of lipid vacuoles in the cytoplasm. 2.Seen in kidney, heart and liver. 15

16. Endoplasmic reticulum Mitochondria Nucleus Lysosome Normal cell 16

17. Normal cell Reversible injury Injury (hypoxia) Recovery Cell swelling, Swelling of ER and mitochondria Chromatin clumping 17

18. Cell swelling - Light Microscopy Normal epithelium Cellular Swelling = hydropic change 18

19. Myocardium: cell swelling= hydropic change 19

20. Normal liver histology Hepatocytes showing fatty change 20

21. Good luck