Pathology of Diabetes Flashcards
What is the pathophysiology of impaired wound healing?
Microvascular damage causes impaired perfusion and immune response is impaired (poor neutrophils)
Neuropathy and macrovascular disease contributes
What non receptor mediated effects do AGEs have?
Cross-linking of collagen matrix
Alteration of collagen IV in endothelial basement membrane
Capture of LDLs > accelerated atheroma?
Generally, what is the overall effect of activation of protein kinase C in DM?
Pro-inflammation
Pro-coagulation
What are the three pathological molecular effects seen in DM?
AGEs
Activation of protein kinase C
Intracellular hyperglycaemia and abnormal Polyol pathways
The effects of chronic hyperglycaemia can split into what?
- Macrovascular
- Microvascular
- Cellular
What is the major macrovascular effect of in DM?
Accelerated and more severe atheroma formation
What are the 4 factors that lead to diabetic nephropathy?
Dabetic glomerulosclerosis/arteriolosclerosis
Infection - due to impaired neutrophils
Papillary necrosis
Accelerated atherosclerosis in larger arteries
What is the acute consequence of hyperglycaemia in T2DM?
Hyperosmolar coma
How does nephropathy usually present?
Proteinuria
Which liver disease is associated with T2DM?
NASH - non-alcoholic steatohepatitis
What do you seen microscopically in diabetic nephropathy?
Spherical nodules arrising in mesangium - eventually become collagen - Called Kimmelstiel-Wilson nodules
Hyaline arteriolosclerosis
Thickening of glomerular BM
What are the microvascular consequences of DM?
Retinopathy
Nephropathy
Impaired healing
Why are AGEs a problem in diabetes when they are produced normally in non-diabetes?
There are more than normal
The labile form changes into a stable form that activates receptors
Why is atheroma more severe and rapid in diabetics?
Increased production of atherogenic lipoprotein factors by the liver
Suppression of lipid uptake in peripheral tissues
Abnormal endothelial function with pro-coagulation results
Associated risk factors like dyslipidaemia and hypertension
What is the pathophysiology of diabetic retinopathy?
Ischaemia of retina due to small vessel damage
Vascular proliferation in response
What are some downstream effects of AGEs binding to their receptors?
Release of pro-inflammatory cytokines and growth factors
Generation of ROS
Pro-coagulative activity of vascular endothelials
Proliferation and matrix production of vascular smooth muscle cells
What are advanced glycosylation end products (AGEs)?
The end produce of glycosylation of amine groups on intra and extracellular proteins
Why do you get damage to nerves in DM?
AGE related damage to axons and schwanna cells
Polyols related damage
Impairment of microvascular leading to neuronal ischaemia
