Cellular injury occurs when a cell is unable to maintain homeostasis in response to stress or damaging stimuli. Injury may be reversible (if mild or transient) or irreversible, leading to cell death (necrosis or apoptosis).
Hypoxia (Most Common Cause)
Hypoxia is a lack of oxygen supply that prevents the cell from producing adequate ATP via aerobic respiration. Major Mechanisms of Hypoxia:
| Mechanism | Description | Example |
|---|---|---|
| Ischemia | ↓ Blood supply (arterial obstruction or venous outflow blockage) | Atherosclerosis, thrombus, embolus |
| Cardiopulmonary failure | ↓ Oxygenation of blood | COPD, respiratory failure |
| ↓ O₂-carrying capacity | Reduced oxygen transport | Anemia, carbon monoxide poisoning |
Pathogenic Agents
Pathogens damage tissues through direct invasion, toxin release, or induction of host inflammation.
| Type of Pathogen | Mechanism of Injury |
|---|---|
| Viruses | Direct cytopathic effect or immune-mediated killing |
| Bacteria | Toxin production, inflammation |
| Fungi & Parasites | Tissue destruction, immune response |
| Prions | Abnormal protein accumulation causing neurodegeneration |
Immunologic Reactions
| Type | Description | Example |
|---|---|---|
| Hypersensitivity reactions | Exaggerated immune response against environmental antigens | Asthma, allergies |
| Autoimmune diseases | Immune attack against self-antigens | SLE, Rheumatoid arthritis |
While immune reactions protect against pathogens, overactivation or loss of self-tolerance can damage host tissues.
Genetic Abnormalities
Inherited or acquired genetic defects can disrupt normal metabolism and cause cell injury.
| Mechanism | Example |
|---|---|
| Congenital disorders | Chromosomal abnormalities (Down syndrome) |
| Lysosomal storage diseases | Tay-Sachs, Gaucher disease (protein accumulation and cell death) |
| Enzyme deficiencies | PKU, α₁-antitrypsin deficiency |
Chemical Injury
Toxic agents can directly damage cellular components or generate free radicals.
| Type of Chemical Agent | Examples / Sources | Effect |
|---|---|---|
| Drugs & poisons | Cyanide, arsenic, mercury | Inhibit enzymes, damage proteins |
| Environmental pollutants | Carbon monoxide, asbestos | Hypoxia, fibrosis |
| Occupational exposure | CCl₄ (carbon tetrachloride) | Lipid peroxidation → fatty liver |
| Lifestyle factors | Alcohol, tobacco, IV drugs | Oxidative stress, organ toxicity |
Physical Agents
| Agent | Examples | Mechanism of Injury |
|---|---|---|
| Mechanical trauma | Blunt/penetrating injuries, crush injuries | Direct tissue disruption |
| Thermal injury | Burns, frostbite | Protein denaturation, vascular damage |
| Radiation | Ionizing or UV radiation | DNA damage, free radical formation |
| Pressure changes | Barotrauma, decompression sickness | Gas bubble formation, vascular injury |
Nutritional Imbalances
Deficiency States
| Type | Example / Effect |
|---|---|
| Protein-Calorie Malnutrition | |
| • Marasmus: Calorie deficiency → | muscle wasting, cachexia |
| • Kwashiorkor: Protein deficiency → | edema, fatty liver |
| Vitamin Deficiencies | |
| • Vitamin A → | Night blindness, immune dysfunction |
| • Vitamin C → | Scurvy (defective collagen synthesis) |
| • Vitamin D → | Rickets, osteomalacia |
| • Vitamin K → | Bleeding diathesis |
| • Vitamin B12 → | Megaloblastic anemia, neuropathy |
| • Folate → | Neural tube defects, megaloblastic anemia |
| • Niacin → | Pellagra (dermatitis, diarrhea, dementia) |
Excess States
| Condition | Effect |
|---|---|
| Obesity | Atherosclerosis, Diabetes, and Hypertension |
| Hypervitaminosis | Organ toxicity (e.g., vitamin A → liver injury, teratogenic effects) |
Key Points to Remember
| Concept | Summary Tip |
|---|---|
| Hypoxia = Most common cause | Usually due to ischemia |
| Pathogens | Direct damage or toxin-mediated |
| Immunity | Can harm the host in hypersensitivity or autoimmunity |
| Chemicals | Free radicals and enzyme inhibition cause cell damage |
| Nutrition | Both deficiency and excess cause injury |
Learning Objective
By the end of this topic, the student should be able to:
- Identify the major causes of cellular injury.
- Explain how hypoxia and ischemia lead to ATP depletion and cell death.
- Correlate specific toxins, infections, and nutritional imbalances with their mechanisms of injury.
- Recognize clinical examples of each category (e.g., CO poisoning, marasmus, autoimmune disease).
