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11 Cards in this Set
- Front
- Back
What are some microvascular complications of DM?
Macrovascular? non-vascular? |
- nephropathy (renal failure), retinopathy (blindness), neuropathy (motor, sensory, autonomic)
CVA, MI, PVD ^risk of infections (UTI), dyslipidemia, cataracts, glaucoma |
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What cells don't req insulin for glucose uptake? Does this make them more or less likely to be affected by DM complications?
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all but adipose and muscle.
more. |
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What is the basic mechanism for DM pathogenesis?
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^^G --> ^^glycolysis --> overloads cell's G metabolic pathways --> dysregulation of mitochondrial e transport chain --> ^^Free radicals and \\their depletion = oxidative stress
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What are the 4 pathways that are more prominent in DM b/c of ^^G? Why are they so prominent?
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polyol pathway
hexosamine pathway protein kinase C pathway AGE pathway ^ROS i/DM inhibits a glycolytic enzyme creating a rate-limiting step --> backup of the glycolysis chain --> these pathways get used more. |
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Describe the negative effects of upreg of the following pathways
- polyol - hexosamine - PKC - AGE + reversible? |
- depletes glutathione --> ^ROS
- ^ECM \fibrolysis, \NO --> vasc occlusion from collagen laydown, decreased lysis, and vasoconstriction --> vascular stenosis & other vascular changes) - ^PKC, affects many different genes. stuff like ^endothelin --> \NO, etc. This promotes vasconstriction, vascular permeability, vascular occlusion, and proinflammatory gene expression. - intracellular oxidation of G --> makes a species that can b/ to proteins and change their function. these bound proteins = AGE (advanced glycosylation end-products) + initially reversible, eventually irreversible |
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What is the pathology of DM microangiopathy?
- what is this stuff made up of? - where in the body are these changes especially prevalent? - in what other condition are these changes also seen? |
diffuse hyaline thickening of microvascular arterioles and capillaries.
- ^ basement membrane, ^ ECM (morphed into AGE), leaked plasma proteins changed into AGE - retina, peripheral nerves, kidney. - benign HTN |
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What kinds of changes can DM effect in the kidney?
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glomeruli:
- thickening of mesangium - thickening of GBM - K/W nodules (nodular glomerulosclerosis) - proteinuria microvascular: - microangiopathy --> arteiosclerosis --> ischemia tubulointerstitium - ^infection risk - pyelonephritis - papillary necrosis |
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What changes are characteristic of diabetic retinopathy?
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- thickened capillary basement membrane
- loss of pericytes (regen. vessel cells) - aneurysms (vessel wall weakened) - exudates (^ wall permeability) - stenosis --> ischemia - neovascularization (^VEGF) |
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What are the basic pathogenic steps in the development of diabetic macroangiopathy?
- How is this different from microangiopathy? |
basically the same, except for the inciting CAUSE of the oxidative stress.
- insulin resistant adipocytes release FFA which are readily taken up by macrovascular endothelial cells (but not microvascular endothelium.) Mitochondrial oxidation of FFA leads to ↑↑ROS. |
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Does atherosclerosis have an accelerated development in DM?
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yes.
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Can MI be silent in DM? Why?
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Yes, because the neuropathy can make it so that no pain is felt.
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