Pathology of the Endocrine Pancreas

Question 1

What is a defining features of all types of diabetes mellitus?

Answer 1

Hyperglycemia

Question 2

What other major disease is diabetes mellitus associated with?

Answer 2

• Renal Failure
• Heart Disease
• Stroke

Question 3

What are the requirements for a Dx of diabetes from a random glucose test?

Answer 3

Classical signs of diabetes mellitus - polyuria, polydypsia, unexplained weight loss with a random glucose level greater than 200 mg/dL

Question 4

What are the requirements for a Dx of diabetes from a fasting glucose test?

Answer 4

Fasting glucose greater than or equal to 126 mg/dL

Question 5

What level of HbA1C is Dx for DM?

Answer 5

HbA1C greater than or equal to 6.5

Question 6

DM Type I

Answer 6

Autoimmune and is due to pancreatic beta cell destruction that leads to insulin deficiency

Question 7

What is the pathogenesis of DM Type I?

Answer 7

– Failure of self‐tolerance in T‐cells
– Activated T‐cells cause ‐cell injury
• CD8 CTLs directly injure  cells
• TH1 cell injury via cytokines

Question 8

What can trigger DM Type I onset?

Answer 8

Stressing factors such as illness can turn someone on the verge to having full DM.

Question 9

What will be seen in the islets for a patient with DM Type I?

Answer 9

Lymphocytes

Question 10

DM Type II

Answer 10

Peripheral Insulin RESISTANCE - the beta cells are initially in tact and crank up insulin production due to the decreased peripheral response, but over time, the increased production wears the beta cells out.

Question 11

What is the function of adiponectin?

Answer 11

Adiponectin sensitizes tissues to insulin

Question 12

What are the function of adipokines?

Answer 12

Adipokines cause insulin resistance

Question 13

How do FFAs affect insulin?

Answer 13

They increase insulin resistance

Question 14

What will be seen in the islets in DM Type II?

Answer 14

Amyloid deposition of the protein amylin

Question 15

Nonketotic Hyperosmolar Coma

Answer 15

Seen rarely with extreme hyperglycemia (greater than 600) more often in nursing home patients

Question 16

What is the age of patients in Type I VS II DM?

Answer 16

Type I - young children or adolescents

Type II - adults

Question 17

What happens to DM Type I patients in the absence of insulin therapy?

Answer 17

Diabetic Ketoacidosis

Question 18

Nonenzymatic Glycosylation (AKA Glycation)

Answer 18

Glucose covalently attaches to multiple proteins nonenzymatically like cellular basement membrane proteins in the ocular lens

Question 19

Over time labile products of glycaion undergo complex chemical rearrangements to form _________________.

Answer 19

Advanced Glycosylation End-Products (AGEs)

Question 20

What happens due to non enzymatic glycosylation to the vasculature?

Answer 20

• Deposition of extracellular matrix
• Increase vascular stiffness
• Increase vascular permeability

Question 21

What are the effects of hyperglycemia on PKC?

Answer 21

Intracellular hyperglycemia results in activation of Protein Kinase C which causes:
• Production of VEGF
• Decreased expression of endothelial nitric oxide
synthase
• Production of profibrinogenic factors(TGF‐beta)

Question 22

What is the effect of increased intracellular glucose?

Answer 22

Excess glucose metabolized by aldose reductase to sortibol via NADPH co‐factor which depletes NADPH, an antioxidant and can also mediate cell damage via sorbitol.

Question 23

Diabetic Retinopathy

Answer 23

Microvascular changes lead to increased production of VEGF and retinal angiogenesis with retinopathy caused by new vessel formation on disc, retina, and elsewhere

Question 24

Insulinoma

Answer 24

Arise in beta cells and most are benign and solitary

Question 25

What is Whipple’s triad for insulinomas?

Answer 25

• Hypoglycemia (less than 50)
• CNS symptoms
• Symptoms resolve with feeding or glucose

Question 26

What are the lab findings for insulinoma?

Answer 26

• Hypoglycemia
• High circulating levels of insulin
• High insulin:glucose ratio

Question 27

Gastrinoma

Answer 27

Gastrin producing cells found in pancreas, duodenum, and in peripancreatic tissue

Question 28

Zollinger‐Ellison Syndrome

Answer 28

Hypergastrinemia causes gastric acid secretion and peptic ulceration often in unusual places like the jejunum

Question 29

Alpha‐cell tumors presenting with diabetes, a skin rash, often middle aged and older women, anemia, high glucagon levels.

Answer 29

Glucagonoma

Question 30

Diabetes and malabsorption associated with d‐cell tumors, very hard to localize pre-op.

Answer 30

Somatostatinoma

Question 31

Severe secretory diarrhea‐‐‐can be associated with neural crest tumors

Answer 31

VIPoma