Pathology of Diabetes

Question 1

What is the pathophysiology of impaired wound healing?

Answer 1

Microvascular damage causes impaired perfusion and immune response is impaired (poor neutrophils)

Neuropathy and macrovascular disease contributes

Question 1

What non receptor mediated effects do AGEs have?

Answer 1

Cross-linking of collagen matrix

Alteration of collagen IV in endothelial basement membrane

Capture of LDLs > accelerated atheroma?

Question 1

Generally, what is the overall effect of activation of protein kinase C in DM?

Answer 1

Pro-inflammation

Pro-coagulation

Question 2

What are the three pathological molecular effects seen in DM?

Answer 2

AGEs

Activation of protein kinase C

Intracellular hyperglycaemia and abnormal Polyol pathways

Question 4

The effects of chronic hyperglycaemia can split into what?

Answer 4

1. Macrovascular
2. Microvascular
3. Cellular

Question 5

What is the major macrovascular effect of in DM?

Answer 5

Accelerated and more severe atheroma formation

Question 5

What are the 4 factors that lead to diabetic nephropathy?

Answer 5

Dabetic glomerulosclerosis/arteriolosclerosis

Infection - due to impaired neutrophils

Papillary necrosis

Accelerated atherosclerosis in larger arteries

Question 8

What is the acute consequence of hyperglycaemia in T2DM?

Answer 8

Hyperosmolar coma

Question 9

How does nephropathy usually present?

Answer 9

Proteinuria

Question 9

Which liver disease is associated with T2DM?

Answer 9

NASH - non-alcoholic steatohepatitis

Question 10

What do you seen microscopically in diabetic nephropathy?

Answer 10

Spherical nodules arrising in mesangium - eventually become collagen - Called Kimmelstiel-Wilson nodules

Hyaline arteriolosclerosis

Thickening of glomerular BM

Question 11

What are the microvascular consequences of DM?

Answer 11

Retinopathy

Nephropathy

Impaired healing

Question 12

Why are AGEs a problem in diabetes when they are produced normally in non-diabetes?

Answer 12

There are more than normal

The labile form changes into a stable form that activates receptors

Question 13

Why is atheroma more severe and rapid in diabetics?

Answer 13

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

Question 15

What is the pathophysiology of diabetic retinopathy?

Answer 15

Ischaemia of retina due to small vessel damage

Vascular proliferation in response

Question 16

What are some downstream effects of AGEs binding to their receptors?

Answer 16

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

Question 17

What are advanced glycosylation end products (AGEs)?

Answer 17

The end produce of glycosylation of amine groups on intra and extracellular proteins

Question 18

Why do you get damage to nerves in DM?

Answer 18

AGE related damage to axons and schwanna cells

Polyols related damage

Impairment of microvascular leading to neuronal ischaemia