8. Pathology of Diabetes

Question 1

diabetic complications are a result of what?

Answer 1

anatomic consequences of altered glycemic control

Question 2

7 major pathologies associated with diabetes?

Answer 2

-Brain: stroke
-Eye: retinopathy
-Heart: atherosclerosis
-Extremities: ischemia
-Bone: osteomyelitis
-Kidneys: glomerulus, arteriosclerosis, pyelonephrosis
Nervous system: pain, sensation loss

Question 3

describe the risk of stroke due to diabetes

Answer 3

due to microvascular occlusion.

Question 4

describe the risk of heart damage due to diabetes

Answer 4

accelerated atherosclerosis. both endothelial injury and inflammatory agents. may cause hypoperfusion.

Question 5

what are the 4 damaging processes that result from diabetic microangiopathy?

Answer 5

• Diffuse basement thickening
• endothelial injury and proliferation
• increased protein leakage
• thrombosis

Question 6

What is the process that leads to diffuse basement thickening?

Answer 6

non-enzymatic glycosylation.

Question 7

what process leads to endothelial injury and proliferation?

Answer 7

increased glucose in cells, metabolized to sorbitol. cells that do not have sorbitol dehydrogenase get accumulation of sorbitol. now cell is hyperosmolar –> fluid flows in, cell swells, capillaries become leaky, endo cells eventually die or proliferate or both.

Question 8

what processes lead to increased protein leakage from microvessels?

Answer 8

both basement thickening and endothelial injury

Question 9

what processes lead to thrombosis?

Answer 9

endothelial damage is part of Virchow’s triad -> hypercoag state

Question 10

ultimately, diabetic microangiopathy leads to what?

Answer 10

tissue ischemia

Question 11

diabetic microangiopathy has what features on histo?

Answer 11

endothelial cell swelling, nuclei sticking out into lumen. thickened/duplicated basement membrane (looks like tree rings on EM). glycosylation of endothelial cells -> pink rind around endo cell.
degeneration, fragmentation of pericytes.

Question 12

what are the 4 main clinical complications of diabetic microangiopathy?

Answer 12

peripheral/skin
retinopathy
nephropathy
neuropathy

Question 13

what process leads to ischemic injury of nerves?

Answer 13

diabetic microangiopathy (pale, thickened basement membrane etc) -> nerve ischemia.

Question 14

what is the mechanism that leads to injury of schwann cells?

Answer 14

sorbitol accumulation in schwann cells, because they don’t have sorbitol dehydrogenase

Question 15

diabetic retinopathy can ultimately lead to what?

Answer 15

loss of night vision, loss of vision

Question 16

what processes occur to microvasculature of the retina?

Answer 16

• microaneurysms
• vascular proliferation
• vascular occlusion
• vascular thickening

Question 17

what are cotton wool spots?

Answer 17

fluffy white patches on retina. caused by damage to neurons (due to vascular ischemia and reduced nerve axonal transport). cytoplasmic material accumulates in neurons, escapes nerve cell and forms C-W spots on retina.

Question 18

what does the retina do?

Answer 18

absorbs light (allows night vision) and notices movement in periphery. most of actual vision is in macula

Question 19

what are the characteristics of diabetic glomerulopathy?

Answer 19

kimmelstiel-wilson lesions along with increased mesangium/thickened basement membranes.

Question 20

what do K-W lesions look like on histo?

Answer 20

focal nodules within glomerulus, dark pink and nodular.

Question 21

how does diabetic glomerulopathy affect kidney function?

Answer 21

impair renal glomerular filtration and lead to renal failure

Question 22

what is diabetic nephropathy?

Answer 22

diabetic glomerulopaty has progressed to the entire kidney

Question 23

what results from diabetic peripheral microvasculopathy?

Answer 23

Chronic ischemic ulcers (usually in feet). These are further complicated by increased risk of infection resulting in osteomyelitis and by the atherosclerosis of large vessels resulting in gangrenous necrosis.

Question 24

big 3 complications of atherosclerosis (med/large vessels)?

Answer 24

stroke, MCI, gangrenous necrosis

Question 25

what might a section of coronary artery look like on histo?

Answer 25

plaque within intima, thrombus in lumen

Question 26

what are two locations where opportunistic infections may occur in diabetics?

Answer 26

``` nasal sinus (fungus: mucormycosis) bladder (candida) ```

Question 27

why are diabetics more susceptible to infections?

Answer 27

altered immune function, immunosuppression. due to ischemia, lowered 02 in tissue makes it more susceptible??

Question 28

what type of pyelonephritis is more common in diabetics?

Answer 28

necrotizing papillitis

Question 29

what does necrotizing papillitis look like on gross? histo?

Answer 29

gross: triangular area of pale yellow kidney, representing area of infection. involves the area of the renal papilla. histo: renal tubules and parenchyma filled with PMNs and necrotic debris

Question 30

what do the islets look like in T1DM, both early and later in the disease? (histo)

Answer 30

early: autoimmune attack of islet cells, late: islet atrophy due to collapse/loss of beta cells, no immune cells.

Question 31

what do the islets look like in T2DM, early, mid- and later in the disease? (histo)

Answer 31

early: no change, no inflammation midway: beta cell depletion/atrophy, but still present late: amylin accumulation leading to amyloid deposits in islet.

Question 32

what is the distribution of beta, alpha, and delta cells in an islet?

Answer 32

beta are in middle. alpha are around the periphery (make glucagon), delta cells scattered at margin btwn beta and alpha.

Question 33

what do delta cells secrete?

Answer 33

somatostatin

Question 34

what is the 'honeymoon period' in T1DM patients?

Answer 34

beta cells attempt to regenerate, and secrete unpredictable amounts of insulin. may lead to unpredictable hypoglycemia during initiation of insulin treatment because effect is additive with exogenous insulin

Question 35

describe the overall pathway from hyperglycemia to cell damage

Answer 35

hyperglycemia -> pathways (aldose reductase pathway, advanced glycosylation endpoint pathway, ROS pathway, PCK pathway) -> reactive metabolits, changed gene expression and protein function -> cell damage (micro, macro, decr immune function)