EXAM #2: PATHOLOGY OF THE ENDOCRINE PANCREAS Flashcards Preview

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Flashcards in EXAM #2: PATHOLOGY OF THE ENDOCRINE PANCREAS Deck (34):
1

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

Maturity Onset Diabetes of the Young
- Autosomal dominant glucokinase defect
- Early onset typically prior to 25 y/o

2

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

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

3

List the most common causes of death from DM.

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

4

Describe the pathogenesis of T1DM.

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*

5

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

T1DM is associated with inflammation; T2DM is NOT

6

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

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

*This is called acute insulitis

7

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

- Lymphocytic infiltration
- Affects the islet NOT the acini

8

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

Fibrosis/hyalinization

9

What does a relative lack of insulin mean in T2DM?

- Normal levels of circulating insulin
- Receptors are unable to appropriately respond to this insulin

10

Is there insulitis in T2DM?

No

11

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

Essentially, beta cells are "exhausted" due to chronic hyperglycemia

12

What is amylin?

Amyloid + insulin= amylin
- Abnormally packaged/secreted insulin
- Accumulates in beta cells

13

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

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)

14

What description is pathognomonic for T2DM and amylin?

"Cracked plate glass"

15

What is the basis for the microvascular complications of DM?

Non-enzymatic glycosylation or "glycation" of the ECM

16

What is non-enzymatic glycosylation?

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.

17

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

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

18

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

1) Retina
2) Renal glomeruli

19

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

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

20

Where does diabetic microangiopathy occur?

Small vessels

21

What is the name of diabetic microangiopathy in small vessels?

ArteriOLOsclerosis

22

What does DM microangiopathy underlie?

1) Retinopathy
2) Nephropathy
3) Neuropathy

23

What are Kimmelstiel-Wilson nodules?

Fibrosis of the nephron seen in DM nephropathy

24

What stain is best to demonstrate Kimmelstiel-Wilson nodules?

Trichrome

25

What are the three classical clinical manifestations of DM retinopathy?

1) Edema
2) Neovascularization
3) Hemorrhagic foci

26

What terms are used to describe DM macroangiopathy?

Large vessel atherosclerosis

27

Why is atherosclerosis accelerated in DM macroangiopathy?

Nonenzymatic glycosylation of lipoproteins, causing these to "stick" to arteries

28

What are the clinical manfiestations of DM macroangiopathy?

1) MI
2) CVA
3) Gangrene

29

What is the T2DM equivalent of DKA?

Nonketotic hyperosmolar coma

30

What is an insulinoma?

Beta cell tumor; the most common pancreatic neuroendocrine tumor

31

What is Whipple's triad?

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

32

What is a Gastrinoma?

Neuroendocrine tumor that consists of G-cells secreting gastrin

33

What are the clinical manifestations of a Gastrinoma?

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

34

What syndrome are Gastrinomas associated with?

MEN1