Pathology Diabetes

Question 1

DM is a group of conditions resulting in?

Answer 1

chronic hyperglycaemia

Question 2

conservative or aggressive glycaemic control better?

Answer 2

aggressive

Question 3

what is the major insulin-responsive site?

Answer 3

muscle

Question 4

Insulin receptor activation does 3 things:

Answer 4

1. send GLUT4 to allow glucose in
2. PI-3K: lipid, protein, glycogen synthesis/cell survival
3. MAP kinase: growth

Question 5

Type 2 severe hyperglycaemic you get?

Answer 5

hyperosmolar coma

Question 6

3 areas of pathology for DM/hyperglycaemia?

Answer 6

Macrovascular
Microvascular
Cellular/extravascular

Question 7

What kind of macrovascular effects do you get with hyperglycaemia?

Answer 7

atheroma in larger vessels

10x risk of CVD/stroke

Question 8

What can happen at kidney macrovascularly with hyperglycaemia?

Answer 8

atheroemboli

Question 9

3 big regions with microvascular effects of hyperglycaemia?

Answer 9

kidney
retina
delayed wound healing

Question 10

Glycosalation of proteins in 2 steps:

Answer 10

1. initially labile (Schiff bases)

2. Stable (Advance glycation end products - AGEs)

Question 11

initial presenation of diabetic nephropathy?

Answer 11

proteinuria

Question 12

hyperglycaemia and immune system?

Answer 12

impaired neutrophils

Question 13

How does DM cause renal failure? 4 things:

Answer 13

1. diabetic glomerulosclerosis
2. infection
3. papillary necrosis
4. renal infarcts

Question 14

balls of collagen in the mesangium in diabetic nephropathy are called?

Answer 14

Kimmelstiel-Wilson nodules

Question 15

AGEs stand for?

Answer 15

Advanced glycation end products

Question 16

arteriolar wall thickening in kidney called?

Answer 16

hyaline arteriolosclerosis

Question 17

basement membrane in diabetic nephropathy?

Answer 17

thickened: though still allow protein leakage

Question 18

primary cause of diabetic retinopathy?

Answer 18

ischaemia to retinal artery due to glycosalation

Question 19

what are Kimmelstiel-Wilson nodules?

Answer 19

balls of collagen in the mesangium in diabetic nephropathy

Question 20

Why delayed wound healing in DM2?

Answer 20

1. impaired perfusion
2. impaired neutrophils=infection=gangrene
3. impaired sensation=trauma

Question 21

3 pathways for hyperglycaemia tissue damage?

Answer 21

1. AGEs
2. Protein Kinase C
3. Intracellular Polyols

Question 22

AGEs bind to what 3 things?

Answer 22

RAGE (receptor) on

1. Macrophages, T-cells
2. endothelial cells
3. vascular smooth muscle

Question 23

what is primary source of AGEs?

Answer 23

diet, normally well controlled, AGEs only problem with higher levels in DM

Question 24

AGEs bound to a vessel does what 4 things?

Answer 24

1. release cytokines
2. reactive O2
3. increase pro-coagulant
4. thicken vessel walls

Question 25

Medication for AGEs?

Answer 25

perhaps RAGE antagonist?

Question 26

What else can AGEs do besides receptor mediated effects?

Answer 26

Cross linking Type 1 and 4 collagen, trapping LDL > atheroma

Question 27

Protein Kinase C mainly affects?

Answer 27

capillary beds, thickening, constriction

Question 28

Peripheral nerve damage in DM just vascular problem?

Answer 28

Combo of:

1. AGEs
2. Polyols
3. microvascular injury

Question 29

How can liver be involved in DM?

Answer 29

Non-alcoholic steatohepatitis (NASH) Fibrosis increases risk of insulin resistance, hyperglycaemia

Question 30

Common cause of DM death?

Answer 30

Macrovascular (MI, stroke, renal failure)