Ex 4 - Pathology of the endocrine Pancreas Flashcards Preview

742 - Biology of Disease III > Ex 4 - Pathology of the endocrine Pancreas > Flashcards

Flashcards in Ex 4 - Pathology of the endocrine Pancreas Deck (23):
1

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

1. Alpha --> glucagon

2. Beta --> Insulin, islet amyloid polypeptide (IAPP)
**most prominent cells

3. Delta --> somatostatin

2

What stimulates release of insulin? How is it secreted?

Hyperglycemia

Exocytosis

*requires appropriate ECF conc of Ca++

3

What effects does insulin have on carbohydrate metabolism?

* Facilitates uptake of glucose by mm, adipose, etc.

* Stimulates storage of glycogen in liver

* Dec blood glucose

4

What effects does insulin have on lipid metabolism?

* Stimulates synthesis of fatty acids in liver

* inhibits breakdown of fat

* Storage/accumulation of fat

5

Overall function of insulin

Functions are anabolic

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

--> blood glucose levels decreased

6

Overall function of glucagon

Functions are catabolic

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

--> blood glucose levels increased

7

Type 1 vs Type 2 DM

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)

8

Hypofunction of islet cells (DM) - Primary

* Developmental
- aplasia/hypoplasia --> keeshonds, chows, goldens

* Destructive
- DEGENERATIVE, atrophy, INFLAMMATORY, neoplasia

9

Hypofunction of islet cells (DM)- Secondary

Insulin antagonists

10

Hypofunction of islet cells (DM) - Insulin Resistance

Decreased effectiveness of insulin (resistance)
- anti-insulin Abs
- inactive insulin complexes
- dec sensitivity of target tissues

11

Islet cell degeneration - dogs

dogs = islet destruction
- more like a Type 1 diabetes
- chronic relapsing pancreatitis occurs more freq. than acute pancreatic necrosis

12

Islet cell degeneration - cats

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

13

How can obesity lead to insulin resistance?

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

14

Clinical Signs of DM

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

15

Peripheral demyelinating neuropathy

Cats!
* Plantigrade stance
* Glycation of myelin sheaths

16

Cataracts

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

17

Hepatic lipidosis/cirrhosis

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

18

Secondary infections

(Impaired neut fxn)

* Cystitis
-- emphysematous: causes a "lumpy bumpy" appearance
-- glycosuria

* Prostatitis

* Bronchopneumonia

* Dermatitis

19

Diabetic nephropathy

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

20

Name 6 Insulin Antagonists

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)

21

DKA - Clin Path

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)

22

Hyperfunction of Islet Cells

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

* Gastrinoma

* Glucagonoma

Iatrogenic

23

Insulinoma Clinical Signs

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)