EXAM #2: PATHOLOGY OF THE ENDOCRINE PANCREAS

Question 1

What is MODY? What causes MODY and when does it typically present?

Answer 1

Maturity Onset Diabetes of the Young

• Autosomal dominant glucokinase defect
• Early onset typically prior to 25 y/o

Question 2

What is unique about MODY compared to other forms of DM?

Answer 2

1) No insulin resistance
2) No GAD65 antibodies
3) No loss of beta cell numbers

Question 3

List the most common causes of death from DM.

Answer 3

1) MI
2) Renal failure
3) CVA
4) HTN
5) Infection

Question 4

Describe the pathogenesis of T1DM.

Answer 4

Genetic predisposition + environmental insult= immune response against normal beta cells

• Genetic predisposition= HLA loci
• Environmental= viral infection/ molecular mimicry

Note that this is a Type IV hypersensitivity reaction

Question 5

Histologically, what is the main difference between T1DM and T2DM?

Answer 5

T1DM is associated with inflammation; T2DM is NOT

Question 6

In the early stage of T1DM, what do you see histologically?

Answer 6

• Infiltration of neutrophils i.e. acute inflammation
• Affects the islet NOT the acini

*This is called acute insulitis

Question 7

In the late stage of T1DM, what do you see histologically?

Answer 7

• Lymphocytic infiltration

- Affects the islet NOT the acini

Question 8

In the end stage of T1DM, what do you see histologically?

Answer 8

Fibrosis/hyalinization

Question 9

What does a relative lack of insulin mean in T2DM?

Answer 9

• Normal levels of circulating insulin

- Receptors are unable to appropriately respond to this insulin

Question 10

Is there insulitis in T2DM?

Answer 10

No

Question 11

In the later stage of T2DM, why is there mild/moderate insulin deficiency?

Answer 11

Essentially, beta cells are “exhausted” due to chronic hyperglycemia

Question 12

What is amylin?

Answer 12

Amyloid + insulin= amylin

• Abnormally packaged/secreted insulin
• Accumulates in beta cells

Question 13

Describe the pathogenesis of T2DM. What are the important differences from T1DM?

Answer 13

Genetic predisposition + environmental factors= DM

• Genetic predisposition is NOT associated with HLA
• Environmental factor= OBESITY causing peripheral tissue insulin resistance (b/c obesity decreases the number of insulin receptors)

Question 14

What description is pathognomonic for T2DM and amylin?

Answer 14

“Cracked plate glass”

Question 15

What is the basis for the microvascular complications of DM?

Answer 15

Non-enzymatic glycosylation or “glycation” of the ECM

Question 16

What is non-enzymatic glycosylation?

Answer 16

1) Formation of a schiff base intermediate
2) This gets transferred to form a stable fructose derivative + protein

E.g. Hemoglobin, albumin, basement membrane…etc.

Question 17

What are AGEs? How are these implicated in the pathogenesis of DM?

Answer 17

Advanced Glycation End-products

• Allow plasma proteins that bind glycated basement membrane
• Can induce cross-linking
• Can trap LDL particles

*This makes the BM thick but leaky

Question 18

Where is the thickening of the basement membrane caused by AGEs most common?

Answer 18

1) Retina

2) Renal glomeruli

Question 19

Aside from interactions with the basement membrane, what else can AGEs induce?

Answer 19

1) Release of cytokines/ growth factors from macrophages
2) Increased endothelial permeability
3) Endothelial procoagulant activity
4) ECM production by vascular smooth muscle cells/ proliferation

Question 20

Where does diabetic microangiopathy occur?

Answer 20

Small vessels

Question 21

What is the name of diabetic microangiopathy in small vessels?

Answer 21

ArteriOLOsclerosis

Question 22

What does DM microangiopathy underlie?

Answer 22

1) Retinopathy
2) Nephropathy
3) Neuropathy

Question 23

What are Kimmelstiel-Wilson nodules?

Answer 23

Fibrosis of the nephron seen in DM nephropathy

Question 24

What stain is best to demonstrate Kimmelstiel-Wilson nodules?

Answer 24

Trichrome

Question 25

What are the three classical clinical manifestations of DM retinopathy?

Answer 25

1) Edema
2) Neovascularization
3) Hemorrhagic foci

Question 26

What terms are used to describe DM macroangiopathy?

Answer 26

Large vessel atherosclerosis

Question 27

Why is atherosclerosis accelerated in DM macroangiopathy?

Answer 27

Nonenzymatic glycosylation of lipoproteins, causing these to “stick” to arteries

Question 28

What are the clinical manfiestations of DM macroangiopathy?

Answer 28

1) MI
2) CVA
3) Gangrene

Question 29

What is the T2DM equivalent of DKA?

Answer 29

Nonketotic hyperosmolar coma

Question 30

What is an insulinoma?

Answer 30

Beta cell tumor; the most common pancreatic neuroendocrine tumor

Question 31

What is Whipple’s triad?

Answer 31

1) Hypoglycemia less than 45 mg/dL
2) Symptomatic
3) Induced by fasting/exercise; relieved by glucose administration

Question 32

What is a Gastrinoma?

Answer 32

Neuroendocrine tumor that consists of G-cells secreting gastrin

Question 33

What are the clinical manifestations of a Gastrinoma?

Answer 33

1) Multiple peptic ulcers
2) Multiple locations
3) Elevated gastric acid secretion

Question 34

What syndrome are Gastrinomas associated with?

Answer 34

MEN1