NURSING 2LA2 Chapter Notes -Gangrene, Lipid Peroxidation, Cranial Nerves
9 Feb 2014
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Pharmacologic agents that target these pathophysiological pathways are being evaluated: polyol pathway, formation of advanced glycation end products, problems with tissue oxygenation, oxidative stress, protein kinase c, increased hexosamine pathway activity. The polyol pathway is an alternative metabolic pathway for tissue not requiring insulin for glucose transport. These include the kidney, red blood cells, blood vessels, eye lens, and nerves. Aldose reductase normally converts toxic aldehydes to inactive alcohols, however, in the presence of hyperglycemia, glucose is shunted to this pathway and aldose reductase converts glucose to sorbitol. In the process, a co-factor called nicotinamide adenine dinucleotide phosphate (nadph) is consumed. Nadph is normally an essential co-factor for regenerating glutathione which is a critical intracellular antioxidant. This increases the susceptibility of the cell to intracellular oxidative stress. Sorbitol is then slowly converted to fructose by sorbitol dehydrogenase. The accumulation of sorbitol and fructose causes increases in intracellular osmotic pressure which attracts water and leads to cell injury.
