15.9 Endocrine Pancreas

Question 1

DKA:

-Tx (3)

Answer 1

1. fluids (because of osmotic diuresis of glucose)
2. insulin
3. replace electrolytes (esp K)
   - replace K because giving insulin will reverse the hyperkalemia and put serum K inside cells, leading to hypokalemia. Also, even though DKA pt had hyperkalemia, total K was being lost in the osmotic diuresis.

Question 1

T2DM

-What is the mechanism by which obesity contributes to this?

Answer 1

-Obesity leads to decreased numbers of insulin receptors

Question 1

Diabetic nephropathy:

-stages of renal damage (3)

Answer 1

1. microalbuminuria–initial preferential involvement of efferent arterioles of glomeruli leads to glomerular hyperfiltration
2. nephrotic syndrome–hyperfiltration leads to this. characterized by Kimmelstein-Wilson nodules in glomerulus
3. Chronic renal failure–afferent arterioles damaged later, leading to Diffuse sclerosis of glomerulus

Question 2

Pt presents with hypoglycemia and you measure high insulin levels.

-Think what? and how to differentiate

Answer 2

1. insulinoma (high C peptide)
2. exogenous insulin (low C peptide)

Question 3

Insulin effect on skeletal, adipose tissue

-mech

Answer 3

• increase GLUT4 transporter on surface of cells to allow glucose intake
• increased glucose uptake leads to increased glycogen synthesis, protein synthesis, and lipogenesis

Question 4

Diabetes long term complications

-divided into 2 categories of mechanism

Answer 4

1. NEG–non enzymatic glycosylation of vascular basement membranes
   - atherosclerosis, hyaline arteriolosclerosis, HbA1C
2. Osmotic damage
   - diabetic neuropathy, retinopathy, cataracts

Question 5

Diabetes: Non-enzymatic glycosylation

-effects (3)

Answer 5

NEG of vascular basement membranes:

1. med/large vessels: atherosclerosis
   - peripheral vascular disease
2. small vessels: hyaline arteriolosclerosis
   - diabetic nephropathy
3. glycated hemoglobin: Hb A1C

Question 5

Pancreatic endocrine tumors:

-assoc with what syndrome

Answer 5

MEN 1

PPP:

pituitary, pancreatic, parathyroid

Question 6

Somatostatinoma

-clinical presentation (2) and why?

Answer 6

1. achlorhydria (inhibition of gastrin)
2. steatorrhea (inhibition of CCK)

Question 7

Pancreatic endocrine neoplasms:

-name 4

Answer 7

1. insulinoma
2. gastrinoma (ZE syndrome)
3. somatostatinoma
4. VIPoma

Question 8

Histology of pancreas islet of Langerhans

-describe

Answer 8

beta cells: insulin

alpha cells: glucagon

delta: somatostatin

beta cells in center of islet, alpha surround them, and exocrine acini surround the islet

Question 9

T2DM

• what % of diabetics
• what % of US population
• arises classically what population
• genetic predisposition?

Answer 9

• 90% of diabetics
• 5-10% of US population
• middle aged, obeses
• Yes, strong genetic predisposition

Question 9

T2DM

• risk for what acute crisis
• mech

Answer 9

Hyperosmolar non-ketotic coma

• high glucose (>500) leads to life-threatening diuresis with hypotension and coma
• Ketones are absent because small amount of insulin counteracts glucagon’s effect of lipolysis

Question 11

Pt presents with T2DM

-would you expect to see high or low insulin levels?

Answer 11

• High, if early in disease
• Low, if late in disease–beta cell exhaustion causes insulin deficiency. (Give insulin)

Question 12

T1DM

• etiology
• what type of hypersensitivity reaction?
• assoc with what HLA’s

Answer 12

• autoimmune destruction of beta cells by T lymphocytes
• type 4 HSR
• HLA DR3 and DR4

Question 13

Diabetes: long-term osmotic damage

• mech
• effects: (3)

Answer 13

• glucose free enters certain cells, where Aldose reductase converts glucose to sorbitol, resulting in osmotic damage
  1. Schwann cells (myelinate peripheral nerves)–peripheral neuropathy
  2. Pericytes of retinal blood vessels–retinopathy
  3. Lens–cataracts

Question 15

-fasting glucose: normal, prediabetic, diabetic

Answer 15

normal 70-99

prediabetic 100-125

diabetic >125

Question 16

DKA:

What type of acidosis?

what happens to serum K and why? (2 mechs)

Answer 16

• anion gap (ketones) met acidosis
• hyperkalemia because:
  1. K is a buffering mechanism for acidosis–intracellular K leaves cells, allowing H+ to enter cells
  2. Insulin induces K to enter cells (this protects you from hyperkalemia after a meal). T1DM has no insulin.

Question 18

DKA

-in treatment, why give pt K+ even though pt has hyperkalemia?

Answer 18

• Prevent hypokalemia
• When you give pt insulin, the insulin will push K inside cells, reversing the hyperkalemia to hypokalemia. Also, total K is low since K was excreted in the osmotic diuresis.

Question 19

T1DM

-what may be present in the blood years before clinical disease develops?

Answer 19

-Ab against insulin are often present in T1DM, and may be present years before clinical symptoms

Question 20

Diabetes: what glucose levels:

• random glucose
• fasting glucose
• glucose tolerance test

Answer 20

random >200

fasting >125

glucose tolerance test: >200, 2 hours after glucose loading

Question 21

VIPoma

-clinical presentation

Answer 21

“WDHA”

1. watery diarrhea
2. hypokalemia
3. achlorhydria–VIP inhibits gastric acid secretion

VIP relaxes intestinal smooth m, with NO

Ach and Substance P contract it

Question 22

Names of ketones in DKA

Answer 22

1. beta-hydroxybutyric acid
2. acetoacetic acid

Question 24

T1DM

• risk of what deady acute complication?
• when does it occur
• mech

Answer 24

• DKA–diabetic ketoacidosis
• often arises with stress (eg infection)–Epi stimulates glucagon secretion, increasing lipolysis (and gluconeogenesis, glycogenolysis), leading to increased free fatty acids. FFA are converted by liver into ketones to supply energy to brain.
• Ketones are acidic

Question 25

Insulinoma - clinical presentation - Tx - dx

Answer 25

- presents as episodic hypoglycemia (mental status changes) - Tx with glucose - Dx with low glucose levels, high insulin, and high C-peptide