Endocrine pancreas pathology

Question 1

What do alpha cells secrete?
Beta cells?
Delta cells?
PP cell? 
D1 cell?

Answer 1

1. glucagon
2. insulin
3. somatostatin
4. pancreatic polypeptide
5. VIP

Question 2

What is the marker of endogenous insulin?

Answer 2

C peptide

Question 3

What is glucose homeostasis regulated by?

Answer 3

1. Hepatic release of glucose
2. Tissue utilization of glucose
3. Hormonal control of glucose by insulin and glucagon (amongst others)

Question 4

Steps of insulin release

Answer 4

1. GLUT-2 (glucose transporter) takes glucose into beta cells
2. Glucose metabolism generates ATP
3. ATP inhibits the membrane K+ channel
4. Depolarization results in Ca2+ influx
5. Ca2+ influx results in insulin release

Question 5

Oral glucose stimulates release of what?

Answer 5

Incretins:
•Glucagon-like peptide-1 (GLP-1)
•Glucose-dependent insulin-releasing polypeptide (GIP)

Question 6

MOA of incretins

Answer 6

1. stimulate insulin release
2. inhibit glucagon release

resulting in lower blood glucose

Question 7

What are incretins inactivated by?

Answer 7

dipeptidyl peptidase-4 (DPP-4)

Question 8

Describe diabetes mellitus

Answer 8

Impairment of normal glucose homeostasis resulting in hyperglycemia
◦ Defective insulin secretion
◦ Defective insulin effect

Question 9

What is T1DM

Answer 9

Autoimmune disease due to failure of T-lymphocyte self tolerance

Question 10

How many islet cells must be destroyed to give overt T1DM symptoms?

Answer 10

> 90%

Question 11

What must be present for T2DM to manifest?

Answer 11

Beta cell dysfunction

Question 12

Describe MODY: Maturity-onset diabetes of the young

Answer 12

Resembles T2DM clinically, but happens in youth!

Increased blood insulin
NO autoantibodies
Nonketotic

Question 13

What is MODY most often caused by

Answer 13

Mutations resulting in loss of function of glucokinase

Question 14

Risks to fetus of gestational diabetes

Answer 14

◦ Neonatal hypoglycemia –> seizures –> brain damage
◦ Macrosomia
◦ Congenital malformations
◦ Stillbirth

Question 15

Classic triad of T1DM

Answer 15

◦ Polyphagia
◦ Polyuria
◦ Polydipsia

◦ Severe: Diabetic ketoacidosis

Question 16

When is T2DM usually identified

Answer 16

On screening

-fatigue, vision changes

Question 17

4 T’s of T1DM

Answer 17

toilet
thirsty
tired
thinner

Question 18

HLA associated with T1DM

Answer 18

HLA DR/DQ on chr. 6

Question 19

Triad of DKA

Answer 19

◦ Hyperglycemia
◦ Ketonemia
◦ Metabolic acidosis

Question 20

What ketones accumulate and should be tested for in DKA

Answer 20

Acetoacetic acid

Beta-hydroxybutyrate

Question 21

What is Hyperglycemic hyperosmotic syndrome (HHS)

Answer 21

Acute hyperglycemic crisis in T2DM

Culmination of prolonged insulin deficiency
◦ Increased gluconeogenesis
◦ Decreased glucose uptake in peripheral tissues

Question 22

What are presenting signs/symptoms of HHS

Answer 22

◦ Glucose >600 mg/dL
◦ Severe dehydration
◦ Hyperosmolality (>350 mOsm/L) –> obtundation, coma
◦ Impaired renal function

NO KETONES

Question 23

What is a measure of long term diabetic control

Answer 23

Hgb A1c

Question 24

What is target A1c

Answer 24

6.5-7 or lower

Question 25

What is the most common cause of death in diabetics

Answer 25

Myocardial infarction

Question 26

Chronic hyperglycemia increases risk of

Answer 26

• Stroke • Myocardial infarction (2x) • Lower extremity gangrene (100x)

Question 27

What is the gold standard for urine albumin testing? To diagnose what

Answer 27

Urine Albumin:creatinine ratio (UACR) Diabetic nephropathy

Question 28

What are the 3 primary pathologic lesions of diabetic nephropathy

Answer 28

1. Glomerular sclerosis 2. Renal vascular lesions 3. Pyelonephritis

Question 29

pathogenesis of diabetic retinopathy

Answer 29

Neovascularization ◦ Hypoxia leads to VEGF overexpression ◦ Hemorrhage ◦ Blindness

Question 30

Unifying features of pancreatic neuroendocrine tumors

Answer 30

Gross appearance – solid, tan-yellow Predilection for the pancreatic neck and tail Histology – well-differentiated neuroendocrine tumors EM – secretory granules

Question 31

What is an insulinoma What is a common histiologic finding? What can make the diagnosis?

Answer 31

1. Small tumors (<2 cm) can produce episodes of symptomatic hypoglycemia ◦ (<50mg/dL) 2. Amyloid 3. C peptide

Question 32

What is the triad for a gastrinoma (zollinger ellison syndrome)

Answer 32

◦ Islet cell tumor ◦ Gastric acid hypersecretion ◦ Peptic ulceration

Question 33

Typical manifestations of a somatostatinoma

Answer 33

Somatostatin functions as a paracrine regulator, so manifestations are typically inhibitory ◦ Reduced insulin ◦ Reduced gallbladder motility ◦ Reduced exocrine pancreatic secretions

Question 34

What are the 4 D's of a glucagonoma

Answer 34

Diabetes Dermatitis Depression DVT's

Question 35

What is the characteristic rash of a glucagonoma? Location?

Answer 35

NECROLYTIC MIGRATORY ERYTHEMA Groin, lower extremities

Question 36

How do VIPomas present?

Answer 36

WDHA syndrome ◦ Watery diarrhea ◦ Hypokalemia ◦ Achlorhydria 20% of pts will have flushing as well

Question 37

What does VIP do

Answer 37

Vasoactive intestinal Peptide: Secreted by D1 cells | ◦ Intestinal fluid secretion