EXAM #2: PATHOLOGY OF THE ENDOCRINE PANCREAS Flashcards
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
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
List the most common causes of death from DM.
1) MI
2) Renal failure
3) CVA
4) HTN
5) Infection
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
Histologically, what is the main difference between T1DM and T2DM?
T1DM is associated with inflammation; T2DM is NOT
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
In the late stage of T1DM, what do you see histologically?
- Lymphocytic infiltration
- Affects the islet NOT the acini
In the end stage of T1DM, what do you see histologically?
Fibrosis/hyalinization
What does a relative lack of insulin mean in T2DM?
- Normal levels of circulating insulin
- Receptors are unable to appropriately respond to this insulin
Is there insulitis in T2DM?
No
In the later stage of T2DM, why is there mild/moderate insulin deficiency?
Essentially, beta cells are “exhausted” due to chronic hyperglycemia
What is amylin?
Amyloid + insulin= amylin
- Abnormally packaged/secreted insulin
- Accumulates in beta cells
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)
What description is pathognomonic for T2DM and amylin?
“Cracked plate glass”
What is the basis for the microvascular complications of DM?
Non-enzymatic glycosylation or “glycation” of the ECM
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.
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
Where is the thickening of the basement membrane caused by AGEs most common?
1) Retina
2) Renal glomeruli
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
Where does diabetic microangiopathy occur?
Small vessels
What is the name of diabetic microangiopathy in small vessels?
ArteriOLOsclerosis
What does DM microangiopathy underlie?
1) Retinopathy
2) Nephropathy
3) Neuropathy
What are Kimmelstiel-Wilson nodules?
Fibrosis of the nephron seen in DM nephropathy
What stain is best to demonstrate Kimmelstiel-Wilson nodules?
Trichrome
What are the three classical clinical manifestations of DM retinopathy?
1) Edema
2) Neovascularization
3) Hemorrhagic foci
What terms are used to describe DM macroangiopathy?
Large vessel atherosclerosis
Why is atherosclerosis accelerated in DM macroangiopathy?
Nonenzymatic glycosylation of lipoproteins, causing these to “stick” to arteries
What are the clinical manfiestations of DM macroangiopathy?
1) MI
2) CVA
3) Gangrene
What is the T2DM equivalent of DKA?
Nonketotic hyperosmolar coma
What is an insulinoma?
Beta cell tumor; the most common pancreatic neuroendocrine tumor
What is Whipple’s triad?
1) Hypoglycemia less than 45 mg/dL
2) Symptomatic
3) Induced by fasting/exercise; relieved by glucose administration
What is a Gastrinoma?
Neuroendocrine tumor that consists of G-cells secreting gastrin
What are the clinical manifestations of a Gastrinoma?
1) Multiple peptic ulcers
2) Multiple locations
3) Elevated gastric acid secretion
What syndrome are Gastrinomas associated with?
MEN1
