Cell Injury Pathophysiology PDF

## II. HYPOXIA - Low oxygen delivery to tissue; important cause of cellular injury - Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation. - Decreased oxygen impairs oxidative phosphorylation, resulting in decreased ATP production. - Lack of...

## II. HYPOXIA - Low oxygen delivery to tissue; important cause of cellular injury - Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation. - Decreased oxygen impairs oxidative phosphorylation, resulting in decreased ATP production. - Lack of ATP (essential energy source) leads to cellular injury. - Causes of hypoxia include ischemia, hypoxemia, and decreased O₂-carrying capacity of blood. - Ischemia is decreased blood flow through an organ. Arises with: - Decreased arterial perfusion (e.g., atherosclerosis) - Decreased venous drainage (e.g., Budd-Chiari syndrome) - Shock-generalized hypotension resulting in poor tissue perfusion - Hypoxemia is a low partial pressure of oxygen in the blood (Pao₂ < 60 mm Hg, Sao₂ < 90%). Arises with: - High altitude-Decreased barometric pressure results in decreased PAO2. - Hypoventilation-Increased PACO₂ results in decreased PAO2. - Diffusion defect-PAO₂ not able to push as much O₂ into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis) - V/Q mismatch-Blood bypasses oxygenated lung (circulation problem, e.g., right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, e.g., atelectasis). - Decreased O₂-carrying capacity arises with hemoglobin (Hb) loss or dysfunction. - Examples include: - Anemia (decrease in RBC mass)-Pao₂ normal; Sao₂ normal - Carbon monoxide poisoning - Treatment is intravenous methylene blue, which helps reduce Fe³⁺ back to Fe²⁺ state. ## III. REVERSIBLE AND IRREVERSIBLE CELLULAR INJURY - Hypoxia impairs oxidative phosphorylation resulting in decreased ATP. - Low ATP disrupts key cellular functions including: - Na⁺-K⁺ pump, resulting in sodium and water buildup in the cell - Ca²⁺ pump, resulting in Ca²⁺ buildup in the cytosol of the cell - Aerobic glycolysis, resulting in a switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA. - The initial phase of injury is reversible. The hallmark of reversible injury is cellular swelling. - Cytosol swelling results in loss of microvilli and membrane blebbing. - Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis. - Eventually, the damage becomes irreversible. The hallmark of irreversible injury is membrane damage. - Plasma membrane damage results in: - Cytosolic enzymes leaking into the serum (e.g., cardiac troponin) - Additional calcium entering into the cell - Mitochondrial membrane damage results in: - Loss of the electron transport chain (inner mitochondrial membrane) - Cytochrome c leaking into cytosol (activates apoptosis) - Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn, are activated by the high intracellular calcium. - The end result of irreversible injury is cell death. The image describes two images: - The first image is of a human eye under a microscope. - The second image shows cellular necrosis of the kidney under a microscope. The description of the first image is: Fig. 1.3 Keratomalacia. (Courtesy of motherchildnutrition.org). The description of the second image is: Fig. 1.5 Coagulative necrosis of kidney. A, Gross appearance. B, Microscopic appearance. C, Normal kidney histology for comparison. (A, Courtesy of Aliya Husain, MD)