Ex 4 - Pathology of the endocrine Pancreas

Question 1

What cells make of the Islets of Langerhans? What do each of these cells secrete?

Answer 1

1. Alpha –> glucagon
2. Beta –> Insulin, islet amyloid polypeptide (IAPP)
   * *most prominent cells
3. Delta –> somatostatin

Question 2

What stimulates release of insulin? How is it secreted?

Answer 2

Hyperglycemia

Exocytosis

*requires appropriate ECF conc of Ca++

Question 3

What effects does insulin have on carbohydrate metabolism?

Answer 3

• Facilitates uptake of glucose by mm, adipose, etc.
• Stimulates storage of glycogen in liver
• Dec blood glucose

Question 4

What effects does insulin have on lipid metabolism?

Answer 4

• Stimulates synthesis of fatty acids in liver
• inhibits breakdown of fat
• Storage/accumulation of fat

Question 5

Overall function of insulin

Answer 5

Functions are anabolic

–> energy is used to build up larger molecules and store substrates

–> blood glucose levels decreased

Question 6

Overall function of glucagon

Answer 6

Functions are catabolic

–> releases energy from larger molecules and as they are broken down

–> blood glucose levels increased

Question 7

Type 1 vs Type 2 DM

Answer 7

Type 1: autoimmune Abs attack the beta cells –> dec insulin production

Type 2: abnormal insulin resistance +/- abnormal insulin secretion
(not an autoimmune disorder, but rather a chronic condition)

Question 8

Hypofunction of islet cells (DM) - Primary

Answer 8

• Developmental
• aplasia/hypoplasia –> keeshonds, chows, goldens
• Destructive
• DEGENERATIVE, atrophy, INFLAMMATORY, neoplasia

Question 9

Hypofunction of islet cells (DM)- Secondary

Answer 9

Insulin antagonists

Question 10

Hypofunction of islet cells (DM) - Insulin Resistance

Answer 10

Decreased effectiveness of insulin (resistance)

• anti-insulin Abs
• inactive insulin complexes
• dec sensitivity of target tissues

Question 11

Islet cell degeneration - dogs

Answer 11

dogs = islet destruction

• more like a Type 1 diabetes
• chronic relapsing pancreatitis occurs more freq. than acute pancreatic necrosis

Question 12

Islet cell degeneration - cats

Answer 12

Cats = loss of number and function of beta cells

• amyloidosis
• exhaustion secondary to peripheral insulin resistance (glucose toxicity)
• -> obesity –> decreased number/function of insulin receptors on target tissues
• *More like a Type 2 diabetes

Question 13

How can obesity lead to insulin resistance?

Answer 13

Obesity –> increased FFA production and release of adipokines
(highly immunogenic molecules)

Infiltration by inflammatory MO –> chronic inflammation –> down regulation of insulin receptors or inhibition of insulin triggered signaling pathways = insulin resistance

Question 14

Clinical Signs of DM

Answer 14

• PU/PD/Polyphagia
• Wgt loss
• Weakness
• Peripheral demyelinating neuropathy (cats)
• Cataracts (dogs)
• Hepatic lipidosis/cirrhosis
• Secondary infections - impaired PMN leukocyte (neut) fxn
• Diabetic nephropathy

Question 15

Peripheral demyelinating neuropathy

Answer 15

Cats!

• Plantigrade stance
• Glycation of myelin sheaths

Question 16

Cataracts

Answer 16

Dogs!

• Glucose –> sorbitol
• • cats have less of the converting enzyme, so they rarely get cataracts
• Sorbitol accumulation in the lens
• • lens fiber swelling (osmotic)/degeneration
• • precipitation of lens proteins

Question 17

Hepatic lipidosis/cirrhosis

Answer 17

• increased lipid mobilization
• hepatocyte injury (ketones)
• dec lipid utilization

Question 18

Secondary infections

Answer 18

(Impaired neut fxn)

• Cystitis
• • emphysematous: causes a “lumpy bumpy” appearance
• • glycosuria
• Prostatitis
• Bronchopneumonia
• Dermatitis

Question 19

Diabetic nephropathy

Answer 19

• Glycogen deposition in tubules
• thickened basement membranes
• CRD/CKD
• Hyperglycosylation of proteins –> alters protein fxn
  (can also lead to vascular changes in the retina)

Question 20

Name 6 Insulin Antagonists

Answer 20

1. Glucagon
   - - opposite effect of insulin in liver
   - - may contribute to DKA
2. Progesterone
3. GH
4. Estrogen
5. Catecholamines/thyroxine
6. Glucocorticoids (e.g. Cushing’s)

Question 21

DKA - Clin Path

Answer 21

1. Severe hyperglycemia
2. Metabolic acidosis
3. ketones - blood and urine
4. Hyponatremia/hypokalemia, hypomagnesemia
5. Pre-renal azotemia

• Dehydration and hypovolemia
• Both DM and DKA are assoc’d with thrombosis (hyper coagulable state)

Question 22

Hyperfunction of Islet Cells

Answer 22

Neoplasia of the pancreas
* Insulinoma 
-- hyperinsulinemia, hypoglycemia 
-- Dogs: carcinoma > adenoma 
(mets readily to liver, LNs, and mesentery) 
-- also common in ferrets 

• Gastrinoma
• Glucagonoma

Iatrogenic

Question 23

Insulinoma Clinical Signs

Answer 23

1. Hypoglycemia
2. Weakness/fatigue
3. Muscle tremors
4. Seizures
5. Tumors are large, and extend beyond the pancreas
   - readily metastasize in dogs (liver, LNs, and mesentery)