Flashcards in Pathology Diabetes Deck (30)
DM is a group of conditions resulting in?
conservative or aggressive glycaemic control better?
what is the major insulin-responsive site?
Insulin receptor activation does 3 things:
1. send GLUT4 to allow glucose in
2. PI-3K: lipid, protein, glycogen synthesis/cell survival
3. MAP kinase: growth
Type 2 severe hyperglycaemic you get?
3 areas of pathology for DM/hyperglycaemia?
What kind of macrovascular effects do you get with hyperglycaemia?
atheroma in larger vessels
10x risk of CVD/stroke
What can happen at kidney macrovascularly with hyperglycaemia?
3 big regions with microvascular effects of hyperglycaemia?
delayed wound healing
Glycosalation of proteins in 2 steps:
1. initially labile (Schiff bases)
2. Stable (Advance glycation end products - AGEs)
initial presenation of diabetic nephropathy?
hyperglycaemia and immune system?
How does DM cause renal failure? 4 things:
1. diabetic glomerulosclerosis
3. papillary necrosis
4. renal infarcts
balls of collagen in the mesangium in diabetic nephropathy are called?
AGEs stand for?
Advanced glycation end products
arteriolar wall thickening in kidney called?
basement membrane in diabetic nephropathy?
thickened: though still allow protein leakage
primary cause of diabetic retinopathy?
ischaemia to retinal artery due to glycosalation
what are Kimmelstiel-Wilson nodules?
balls of collagen in the mesangium in diabetic nephropathy
Why delayed wound healing in DM2?
1. impaired perfusion
2. impaired neutrophils=infection=gangrene
3. impaired sensation=trauma
3 pathways for hyperglycaemia tissue damage?
2. Protein Kinase C
3. Intracellular Polyols
AGEs bind to what 3 things?
RAGE (receptor) on
1. Macrophages, T-cells
2. endothelial cells
3. vascular smooth muscle
what is primary source of AGEs?
diet, normally well controlled, AGEs only problem with higher levels in DM
AGEs bound to a vessel does what 4 things?
1. release cytokines
2. reactive O2
3. increase pro-coagulant
4. thicken vessel walls
Medication for AGEs?
perhaps RAGE antagonist?
What else can AGEs do besides receptor mediated effects?
Cross linking Type 1 and 4 collagen, trapping LDL > atheroma
Protein Kinase C mainly affects?
capillary beds, thickening, constriction
Peripheral nerve damage in DM just vascular problem?
3. microvascular injury
How can liver be involved in DM?
Non-alcoholic steatohepatitis (NASH) Fibrosis increases risk of insulin resistance, hyperglycaemia