Endocrine Pancreas Pathology

Question 1

4 cell types of the islets of langerhans and their phormone products

Answer 1

Beta cells — insulin

Alpha cells — glucagon

Delta cells — somatostatin

PP cells — pancreatic polypeptide

Question 2

Hormone product of D1 cells of the pancreas

Answer 2

Vasoactive intestinal polypeptide (VIP)

Question 3

______ is the transporter responsible for glucose uptake into beta cells. Glucose metabolism generates ATP which inhibits the membrane K+ channel, allowing ____ influx, which results in insulin release

Answer 3

GLUT-2; Ca++

Question 4

During processing, proinsulin is cleaved to form insulin and ____, which a marker of endogenous insulin

Answer 4

C peptide

Question 5

Oral glucose stimulates the release of ______ which stimulate insulin release and inhibit glucagon release resulting in lower blood glucose

Answer 5

Incretins

Question 6

What are examples of incretins?

Answer 6

Glucagon-like peptide-1 (GLP-1)

Glucose-dependent insulin-releasing polypeptide (GIP)

Question 7

Incretins are inactivated by _______

Answer 7

Dipeptidyl peptidase-4 (DPP-4)

Question 8

Difference in age of onset between T1D and T2D

Answer 8

T1D: usually childhood and adolescence

T2D: usually adult, increasing incidence in childhood and adolescence

Question 9

Difference in autoantibodies between T1D and T2D

Answer 9

T1D: presence of circulating islet autoantibodies (anti-insulin, anti-GAD, anti-ICA512) [major linkage to MHC class II genes — specifically HLA gene cluster on Chr6p21]

T2D: no islet antibodies [no HLA linkage]

Question 10

Difference in pathogenesis between T1D and T2D

Answer 10

T1D: dysfunction in T cell selection and regulation, leading to breakdown in self-tolerance to islet autoantigens

T2D: insulin resistance in peripheral tissues, failure of compensation by beta cells; multiple obesity-associated factors

Question 11

What is insulitis, and which type of DM is it associated with?

Answer 11

Insulitis = inflammatory infiltrate of T cells and macrophages — associated with T1D

[T2D is NOT associated with insulitis, but may show amyloid deposition in islets]

Question 12

What disease resembles T2DM clinically, but happens in youth — presenting with increased blood insulin but NO autoantibodies and is nonketotic?

Answer 12

Maturity-onset diabetes of the young (MODY)

Question 13

Maturity-onset diabetes of the young (MODY) is most often caused by mutations resulting in loss of function of _______

Answer 13

Glucokinase

Question 14

Risks to mom vs. risks to fetus with gestational diabetes

Answer 14

Mom: cesarean section (usually due to large size of fetus)

Fetus: neonatal hypoglycemia may lead to seizures and subsequent brain damage; macrosomia, congenital malformations, stillbirth

Question 15

What are the 2 opportunities for gestational diabetes screening?

Answer 15

Screen at first prenatal visit for pre-existing DM — measure fasting plasma glucose (FPG), HgbA1c, or random plasma glucose

Screen at 24-28 weeks gestation with oral glucose tolerance test (OGTT) — glucose levels measured while fasting, 1 hour post-oral glucose, and 2 hours post-oral glucose

Question 16

Classic triad of T1DM

Answer 16

Polyphagia
Polyuria
Polydipsia

Severe = diabetic ketoacidosis

[T2DM usually identified on screening — fatigue, vision changes, etc.]

Question 17

Signs/symptoms of T1DM

Answer 17

Increased thirst and frequent urination

Extreme hunger

Weight loss

Fatigue

Irritability or behavior changes

Fruity-smelling breath

Question 18

How is T1DM distinguished from T2DM based on lab results?

Answer 18

Autoantibodies — present in T1DM only

HLA typing — HLADR/DQ on Chr6

[note that autoantibodies are more reliably detected in caucasian children with T1DM than AA and hispanic children]

Question 19

Clinical triad of DKA

Answer 19

Hyperglycemia (usually of T1DM)

Ketonemia

Metabolic acidosis

[presenting signs/symptoms include dehydration, polydipsia, polyuria/ketonuria, N/V, tachycardia, and Kussmaul respirations]

Question 20

Pathogenesis of DKA

Answer 20

Body can’t use flucose, so it accumulates in the blood

Glucagon is released, promoting gluconeogenesis

Kidenys dump glucose and ketones, osmotic diuresis occurs

Shock, dehydration, more epinephrine

Insulin deficiency promotes FFA release generating ketones

Question 21

DKA treatment

Answer 21

Insulin
Hydration
Potassium

[hypokalemia will rapidly occur when you give insulin, so you must also give K+]

Question 22

What is hyperglycemic hyperosmotic syndrome (HHS)?

Answer 22

Acute hyperglycemic crisis in T2DM

Culmination of prolonged insulin deficiency —> increased gluconeogenesis and decreased glucose uptake in peripheral tissues

Question 23

Presenting signs/symptoms of hyperglycemic hyperosmotic syndrome (HHS) — note which sign makes it different from DKA!

Answer 23

Glucose >600 mg/dL

Severe dehydration

Hyperosmolality (>350 mOsm/L) leading to obtundation, coma

Impaired renal function

[NO KETONES! — distinguishes it from DKA]

Question 24

What lab provides a measure of long-term diabetic control?

Answer 24

Hemoglobin A1c

Question 25

Major complications of diabetes

Answer 25

Eye: retinopathy, cataracts, glaucoma

Kidney: nephropathy

PNS: peripheral neuropathy

Brain: increased risk of stroke and cerebrovascular disease

Heart: coronary heart disease, 2x risk of MI (note it may present differently in diabetics)

Extremities: peripheral vascular disease + neuropathy —> gangrene

Question 26

Most common cause of death in diabetics

Answer 26

Myocardial infarction

Question 27

Leading cause of end-stage renal disease in the US

Answer 27

Diabetic nephropathy

Question 28

How is diabetic nephropathy tested for, and what are the 3 primary pathologic lesions

Answer 28

Albumin:Cr ratio in urine (gold standard)

3 primary pathologic lesions:
Glomerular sclerosis
Renal vascular lesions
Pyelonephritis

Question 29

What is Kimmelstiel-Wilson disease?

Answer 29

Nodular glomerulosclerosis associated with diabetic nephropathy

Question 30

Clinical features of diabetic retinopathy

Answer 30

Hemorrhages

Abnormal growth of blood vessels

Cotton wool spots

Hard exudates

Question 31

Pathogenesis of diabetic retinopathy

Answer 31

Neovascularization —> hypoxia leads to VEGF overexpression, hemorrhage, blindness

Question 32

Unifying features of pancreatic neuroendocrine tumors

Answer 32

Gross appearance — solid, tan-yellow

Predilection for the pancreatic neck and tail

Histology — well-differentiated

EM — secretory granules

Question 33

Amyloid is a common histologic finding among just one type of pancreatic neuroendocrine tumors — which one?

Answer 33

Insulinoma

Question 34

Insulinomas are small tumors that can produce episodes of symptomatic hypoglycemia (<50mg/dL). What lab finding is used to dx insulinoma?

Answer 34

Elevated C peptide levels

Question 35

Triad associated with gastrinoma (Zollinger Ellison syndrome)

Answer 35

Islet cell tumor

Gastric acid hypersecretion

Peptic ulceration

[diagnostic clue is when ulcers do not respond to conventional therapy]

Question 36

Triad associated with somatostatinoma

Answer 36

Diabetes

Cholelithiasis

Steatorrhea

[somatostatin functions as a paracrine regulator, so manifestations are typically inhibitory — reduced insulin, reduced gallbladder motility, reduced exocrine pancreatic secretions]

Question 37

What pancreatic neuroendocrine tumor presents with mild diabetes and a characteristic rash affecting the groin and lower extremities known as necrolytic migratory erythema?

Answer 37

Glucagonoma

Question 38

4 D’s of glucagonomas

Answer 38

Diabetes
Dermatitis
Depression
DVTs

Question 39

What pancreatic neuroendocrine tumor might be mistaken for a carcinoid tumor, due to the tendency to induce flushing and diarrhea?

Answer 39

VIPoma

Question 40

WDHA syndrome associated with VIPomas (triad)

Answer 40

Watery diarrhea

Hypokalemia

Achlorhydria