Hypoxia: Causes and Effects

Study Notes

Low oxygen delivery to tissues, a major cause of cellular damage
Oxygen acts as the final electron acceptor in oxidative phosphorylation, a process that generates ATP
Decreased oxygen impairs oxidative phosphorylation, resulting in reduced ATP production
Lack of ATP, the essential energy source, leads to cellular injury
Causes of Hypoxia:
- Ischemia: Reduced blood flow to an organ due to:
  - Decreased arterial perfusion (e.g., atherosclerosis)
  - Impaired venous drainage (e.g., Budd-Chiari syndrome)
  - Shock: Generalized hypotension, leading to inadequate tissue perfusion
- Hypoxemia: Low partial pressure of oxygen in the blood (PaO₂ < 60 mmHg, SaO₂ < 90%)
  - High Altitude: Decreased barometric pressure leads to reduced PaO₂
  - Hypoventilation: Increased PaCO₂ results in decreased PaO₂
  - Diffusion Defect: Thickened diffusion barrier (e.g., interstitial pulmonary fibrosis) hinders oxygen transfer into the blood
  - V/Q Mismatch: Blood bypasses oxygenated lungs (circulation problem, e.g., right-to-left shunt) or oxygenated air cannot reach blood (ventilation problem, e.g., atelectasis)
- Decreased Oxygen-Carrying Capacity:
  - Anemia: Reduced red blood cell mass, leading to normal PaO₂ and SaO₂
  - Carbon Monoxide Poisoning: CO binds to hemoglobin, hindering oxygen transport
Treatment for certain types of hypoxia may involve intravenous methylene blue, which helps reduce Fe³⁺ to Fe²⁺, promoting oxygen transport

Hypoxia disrupts oxidative phosphorylation, causing a decrease in ATP production
Low ATP levels impact critical cellular functions:
- Na⁺-K⁺ Pump: Reduced activity leads to sodium and water accumulation within the cell
- Ca²⁺ Pump: Impaired function results in calcium buildup in the cytoplasm
- Aerobic Glycolysis: Switch to anaerobic glycolysis occurs, leading to lactic acid buildup, lowering pH, and damaging proteins and DNA
The initial phase of cellular injury is reversible
The hallmark of reversible injury is cellular swelling
- Cytosol swelling leads to loss of microvilli and membrane blebbing
- Rough endoplasmic reticulum (RER) swelling causes ribosome dissociation, decreasing protein synthesis
Irreversible injury occurs when the damage progresses beyond repair
The hallmark of irreversible injury is membrane damage