E: Pathology Of Diabetes Mellitus

Front 1

What are some microvascular complications of DM?

Macrovascular?

non-vascular?

Back 1

- nephropathy (renal failure), retinopathy (blindness), neuropathy (motor, sensory, autonomic)

CVA, MI, PVD

^risk of infections (UTI), dyslipidemia, cataracts, glaucoma

Front 2

What cells don't req insulin for glucose uptake? Does this make them more or less likely to be affected by DM complications?

Back 2

all but adipose and muscle.

more.

Front 3

What is the basic mechanism for DM pathogenesis?

Back 3

^^G --> ^^glycolysis --> overloads cell's G metabolic pathways --> dysregulation of mitochondrial e transport chain --> ^^Free radicals and \\their depletion = oxidative stress

Front 4

What are the 4 pathways that are more prominent in DM b/c of ^^G? Why are they so prominent?

Back 4

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.

Front 5

Describe the negative effects of upreg of the following pathways
- polyol
- hexosamine
- PKC
- AGE
+ reversible?

Back 5

- 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

Front 6

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?

Back 6

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

Front 7

What kinds of changes can DM effect in the kidney?

Back 7

glomeruli:
- thickening of mesangium
- thickening of GBM
- K/W nodules (nodular glomerulosclerosis)
- proteinuria

microvascular:
- microangiopathy --> arteiosclerosis --> ischemia

tubulointerstitium
- ^infection risk
- pyelonephritis
- papillary necrosis

Front 8

What changes are characteristic of diabetic retinopathy?

Back 8

- thickened capillary basement membrane
- loss of pericytes (regen. vessel cells)
- aneurysms (vessel wall weakened)
- exudates (^ wall permeability)
- stenosis --> ischemia
- neovascularization (^VEGF)

Front 9

What are the basic pathogenic steps in the development of diabetic macroangiopathy?
- How is this different from microangiopathy?

Back 9

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.

Front 10

Does atherosclerosis have an accelerated development in DM?

Back 10

yes.

Front 11

Can MI be silent in DM? Why?

Back 11

Yes, because the neuropathy can make it so that no pain is felt.