1-Cell Injury: Mechanisms of Damage

1-Cell Injury: Mechanisms of Damage

• Ischemia is a common cause of clinically significant cell damage, primarily due to hypoxia (lack of oxygen).
• Arterial occlusion is the most frequent cause of ischemia.
• Hypoxia initially affects mitochondria.
• The Na-K pump malfunctions, leading to increased sodium, water, and calcium entry into cells and potassium loss.
• Cellular swelling is the initial morphological change observed in hypoxic cells.
• The first organelle affected during hypoxia is the mitochondria.
• Aerobic respiration is first affected in hypoxic cells.
• Anaerobic glycolysis increases to produce energy, but this increases lactate levels and lowers the pH.
• Protein synthesis decreases and intracellular lipid accumulates.
• The Na-K pump dysfunction, coupled with increased intracellular sodium, leads to cellular swelling and efflux of potassium.
• Microvilli (small finger-like projections) disappear.

Acute Cellular Swelling

• Cellular swelling is the first detectable morphological change in cell injury due to hypoxia.
• The affected cell's mitochondria are the first organelle to be impacted.
• Aerobic respiration is the first system disrupted in hypoxic cells.

Cellular Swelling and Lubrication

• Cellular swelling and lubrication are the first morphological signs during light microscopic examination.

Further Mechanisms of Cell Injury

• The Na-K pump's failure leads to increased sodium, water, and calcium influx into the cell and potassium efflux.
• Cell and endoplasmic reticulum swell.
• Anaerobic glycolysis increases to provide energy.
• Glycogen decreases, while lactate and lactic acid increase (lowering internal pH).
• Chromatin aggregates and become more coarse.
• Protein synthesis slows.
• Intracellular lipid begins to accumulate.

Calcium Imbalance and Apoptosis

• Calcium pump impairment (due to ATP depletion) results in calcium increase inside the cell.
• Elevated intracellular calcium activates enzymes (ATPases, phospholipases, proteases, endonucleases), leading to membrane damage, cytoskeletal damage, and nuclear chromatin damage.
• Calcium disrupts mitochondrial function, increasing cytochrome C release.
• Cytochrome C triggers caspase activation, initiating apoptosis (programmed cell death).

Substances Affected in Hypoxic Cells

• Decreased Substances: Potassium, protein, glycogen, and ATP.
• Increased Substances: ADP, inorganic phosphates, sodium, chloride, calcium, purine nucleosides, lactic acid, and water.

This quiz explores the mechanisms involved in cell injury, focusing on ischemia and hypoxia. Key processes such as mitochondrial dysfunction, changes in the Na-K pump, and the implications of anaerobic glycolysis are examined. Understand how these factors contribute to cellular swelling and other morphological changes in hypoxic cells.