Important mechanisms of cell injury
1. Damage to DNA, proteins. lipid membranes, and circulating lipids (LDL) can be caused by oxygen-derived free radicals, including superoxide anion, hydroxyl radical (OH‘), and hydrogen peroxi .
ATP depletion, because of the cell’s dependence on ATP, several important changes (damage to Na+/K+ pumps, to mitochondria, etc.) disrupt the production of AT P, which is then rapidly depleted by other cellular processes.
iii. Increased cell membrane permeability, several defects can lead to movement of fluids into the cell, including formation of the membrane attack complex via complement, breakdown of Na+/K+ gradients (i.e., causing sodium to enter or potassium to leave the cell), etc.
iv. Influx of calcium can cause problems because calcium is a second messenger, which can activate a wide spectrum of enzymes. These enzymes include proteases (protein breakdown), ATPases (contributes to ATP depletion), phospholipases (cell membrane injury), and endonucleases (DNA damage).
v. Mitochondrial dysfunction causes decreased oxidative phosphorylation and ATP production, formation of mitochondrial permeability transition (MPT) channels, and release of cytochrome c (a trigger for apoptosis).
The loss of membrane integrity (cell ‘ death) allows intracellular enzymes to leak out, which can then be measured in the blood. Detection of these proteins in the circulation serves as a clinical marker of cell death and organ injury. Clinically important examples:
Myocardial injury: troponin (most specific), CPK-MB, lactate dehydmgenase (LDH)
Hepatitis : transaminase
Pancreatitis: amylases and lipase
Biliary tract obstructian: alkaline phosphatase
‘ If the cells in the interdigital Space fail to
undergo apoptosis, the fetus will be born with webbed hands and [or webbed feet, a condition known as syndactyly. Another‘ example is the hormone-dependent apoptosis prior to menstruation; this occurs as the body withdraws from estrogen and LH surges, signaling the endometrial cells to undergo apoptosis.