pancreas path

Question 1

Type 1 DM vs Type 2 DM

Answer 1

• Type 1
  
  • Beta-cell destruction in the islet cells, leads to ABSOLUTE INSULIN DEFICIENCY
  • immune mediated
  • idiopathic
• Type 2
  
  • INSULIN RESISTANCE with RELATIVE insulin deficiency

Question 2

MODY (not to important)

Answer 2

Maturity-Onset Diabetes of the Young (MODY)

• Primary defect in Beta-function due to genetic function
  
  • no loss or change in beta-cell numbers
  • NO INSULIN RESISTANCE and NO ANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE
• early onset usually < 25 years old
• no obesity

Question 3

Diagnosis criteria for diabetes

Answer 3

1. HbA1c > 6.5%
2. Fasting plasma glucose > 126mg/dL
3. 2-h plasma glucose > 200mg/dl during an ORAL GLUCOSE TOLERANCE TEST (OGTT)
4. Random (casual) glucose > 200mg/dL WITH classic symptoms of hyperglycemia or hyperglycemic crisis

**blood glucose values are normal (70-120 mg/dL)**

Question 4

Most commonc auses of death in order of frequency**

Answer 4

DOESN”T MATTER WHICH TYPE OF DIABETES THE PTS HAS

1. MI (DM MI) (LEADING CAUSE)
2. Renal failure
3. cerebrovascular disease
4. hypertensive heart disease
5. infections

Question 5

Morphologic changes in Type 1 DM

Answer 5

• Acute Insulitis –> infiltrate of neutrophils
  
  • early in disease you see inflammation, degranulation of Beta-Cells, and death of beta-cells
• following inital acute inflammation –> reduce in number and size of islets (loss of beta cells
  
  • later islets will become hyalinized

Question 6

Pathogenesis of Type 2 DM

Answer 6

• RELATIVE LACK OF INSULIN
  
  • normal levels of insulin are circulating but cells are not appropriately responding to the insulin (INSULIN RESIStANCE)
• Genetic predisposition (mutliple)
  
  • PRIMARY Beta-cell defect
  • Deranged insulin secretion
• environoment –> obesity
  
  • Peripehral tissue insulin resitance
    
    • inadewuate glucose utilization

BOTH LEAD TO HYPGLYCEMIA –> BETA-CELL EXHAUSTION

Question 7

Type 2: progression

Answer 7

• Early:
  
  • normal insulin secretion and plasma levels
  • loss of pulsatile, oscillating patterns of secretion
  • NO insulinitis
• Later
  
  • mild/moderate insulin deficiency, may be due to beta cell damage (beta cells may be exhausted due to chronic hyperglycemia-glucose toxicity)
• AMYLIN
  
  • insulin, abnormally packaged and secreted, tends to accumulate outside beta cells and resembles amyloid

Question 8

Amylin

Answer 8

• lots of pink structure in the islet (looks pink)

Question 9

describe the underlying cause of complications of DM

Answer 9

Non-enzymatic glycosylation of extracellular matrix is the MOST common underlying cause in the pathogenesis of complications of DM

Question 10

describe pathogenic effects of advanced glycation end-products (AGEs)

Answer 10

• Potentially pathogenic effects of AGEs
  
  • plasma proteins can bind to glycated basement membranes
  • can induce cross-linking in type IV collagen in basement membranes
  • can trap LDL particles in artery walls
  • Can bind to receptors on numerous cell types, inducing:
    
    • release of cytokins and growth factors from macrophages
    • increase endothelial permeability
    • increase procoagulant acitivty
    • increase extracellular matrix production by vascular smooth muscle cells as well as increase proliferation