Notes on Cell Injury

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• Inadequate oxygenation.

• Decreased ATP synthesis.

Causes of hypoxia:

• Ischemia.

• Hypoxemia: decreased PaO2 due to respiratory acidosis, defective ventilation, diffusion, perfusion.

• Hemoglobin-related abnormalities: anemia, methemoglobinemia, CO poisoning, left-shifted OBC, defective oxidative phosphorylation.

Tissues susceptible to hypoxia:

• Water-shed areas between two blood supplies (Eg. area between ACA and MCA)

• Subendocardial tissue.

• Renal cortex and medulla.

Consequence of hypoxic cell injury:

• Decreased ATP production.

• Anaerobic glycolysis is used to generate ATP.

• Decreased protein synthesis.

• Irreversible cell changes.

Free radicals:

• Damage nucleic acid and membrane molecules.

Neutralized by:

• Superoxide dismutase (neutralizes superoxide free radicles).

• Glutathione peroxidase (neutralizes peroxide).

• Catalase (neutralizes peroxide free radicles).

• Vitamin antioxidants (block free radical formation).

Examples of free radical injury:

Acetaminophen radicals:

• Diffuse hepatitis.

• Renal papillary necrosis.

CCl4 radicals:

• Liver cell necrosis with fatty change.

Ischemia/reperfusion injury:

• Damage by oxygen radical and Ca2+.

RDS treatment in newborn:

• Blindness / retinopathy.

Iron-overload disorders:

• Hemochromatosis and hemosiderosis.

• Damaged parenchymal liver cells.

Acetaminophen radicals:

• Acetaminophen radicals (that cause fulminant hepatitis) treated with N-acetylcysteine.

Consequences of cellular injury:


• Cytochrome c release causes apoptosis.


• Fluctuating levels of cytochrome P-450 enzymes; disturbed SER activity and drug detoxification.


• Mannose-6-phosphate direct proteins to lysosomes.

I-Cell disease:

• Proteins lack M6P marker; sent to wrong destination.

Gaucher's disease:

• Deficiency of lysosomal enzymes.

Chediak-Higashi syndrome:

• No fusion between lysosomes and phagocytic vacuoles.


• Mitotic spindle: lack of assembly.

• IF: hyperactive ubiquitin binding produces Mallory bodies; IF degradation.

• Rigor mortis.

Intracellular accumulations:

Fatty Liver Change:

• Accumulation of cystolic triglyceride.

• Increased G3-P; increased fatty acid synthesis and mobilization.

• Decreased fatty acid beta-oxidation; decreased synthesis of apolipoprotein B-100; decreased LDL.


• Ferritin.

• Hemosiderin.


• Dystrophic; necrotic tissue calcification; eg., pancreatitis.

• Metastatic; normal tissue calcification; eg., nephrocalcinosis.

Cell Changes:


• Decrease in size of tissue or organ.


• Increase in size.


• Increase in the number of cells.


• Replacement of one cell type by another.


• Disordered cell growth.

Cell Necrosis:

Coagulation necrosis:

• Accumulation of heavy metals and lactate; exposure to ionizing radiation; infarction.

Liquefactive necrosis:

• CNS infarction; abscess in bacterial infection.

Caseous necrosis:

• TB, fungi.

Enzymatic fat necrosis:

• Fat tissue like female breast following trauma; pancreatitis.

Fibrinoid necrosis:

• Muscular arteries, arterioles, venules and glomerular capillaries.


• TP53: repairs damaged DNA; aborts apoptosis. If irreparable, activates the BAX gene.

• BAX: apoptosis gene.

• BCL2: activates anti-apoptosis products.

Appearance of dying cells:

• Detachment, eosinophilic-staining, anucleated, and no infiltrate around the cell.

Enzyme Markers:


• Alcoholic liver necrosis.


• Viral liver necrosis.


• AMI.

Amylase and lipase:

• Pancreatitis.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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