01-06 PATH of Diabetes

Question 1

AGEs/RAGEs stand for?

Answer 1

(Receptor of) Advanced Gylcosylation Endproduct

Question 2

What are the 3 major complications of uncontrolled DM?

Answer 2

1. microangiopathy - see w/ fundoscopy
—CVAs
—retinopathy
—nephrosclerosis, etc 
2. accel. athero
—MI
—PVD → gangrene → amputation
3. opportun. infx - 2° to ‪↓‬ imm fxn
—osteomyelitis

Also neuropathy, both peripheral and autonomic

Question 3

Microangiopathy
—characterized by?
—occurs where?
—end result?

Answer 3

CHARACTERIZED BY

1. Diffuse BM thickening
2. endothel. injury & prolif
3. ↑ protein leakage
4. thrombosis

OCCURS
—in capillaries throughout the body
—main clinical complications: skin (periph microangio), retinopathy, nephropathy, and neuropathy

END RESUT
—tissue ischemia

Question 4

Diabetic neuropathy

Answer 4

2° to both angiopathy and direct nerve and Schwann cell injury

Question 5

What do you see here?

[IMAGE q5]

Answer 5

This is diabetic retinopathy
—microaneurysms
—vascular proliferation
—vasc occlusion
—thickening of vasc

Question 6

What do you see here?

[IMAGE q6]

Answer 6

—Kimmelstiel-Wilson (KW) nodular glomerulosclerosis as seen w/ PAS stain
—reflects microvasc injury to glomeruli 2° to DM

Question 7

Pathophys of diabetic ulcer?

Answer 7

2° to microvasculopathy and further complicated by:
—↑ r/o infx → osteomyelitis
—atherosclerosis (macrovasculopathy) of larger vessels → gangrenous necrosis

Question 8

Consequences of immune suppression?

Answer 8

—imm sys suppressed by variety of mechs
—opportunistic infections result: both fungal (mucormycosis of nasopharynx, Candidia cystitis) and bacterial
—pyelonephritis also more common in DM

Question 9

What is this organ? What’s happening here?

[IMAGE q9]

Answer 9

This is kidney

—pyelonephritis

Question 10

Course of Islet ∆s in DM1?

Answer 10

1. Early - Ilitis which is an autoimmune attack on the pancreatic β cells → cell death → inflamm
2. Late - Islet atrophy: no β cells left
   —check this w/ an IHC for insulin: see none

Question 11

Course of Islet ∆s in DM2?

Answer 11

1. Early - no ∆s
2. Mid-course - β cell malfxn (meanwhile insulin resistance is happening in periph)
3. Later - β cell depletion/atrophy (but NOT complete, still some left)
4. Amylin* accumulation → amyloid deposits in islets

Question 12

Amylin

Answer 12

cosecreted w/ insulin from β-cells in ~100:1 ratio
—plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.

Question 13

What is this? What’s going on here?

[IMAGE q13]

Answer 13

Pancreatic islet
—amyloid deposition from accumulation of amylin in DM2
—RE-CALL: glassy pink? think amyoid
—Stain w/ Congo red to verify

Question 14

What is this? What’s going on here?

[IMAGE q14]

Answer 14

—pancreatic islet cells

—lymphocytic infiltration only around β-cells due to auto-immunity in DM1

Question 15

What is this? What’s going on here?

[IMAGE q15]

Answer 15

—this is a normal, healthy pancreatic islet