Endocrien Pancreas Flashcards
Describe etiology of type I diabetes
Genetic factors, genes encoding class II MHC on 6p21 (HLA-D)
Environemental factors especially infections mumps, rubella, coxB, may be an initial trigger by antigenic mimcry
Mention the 2 two metabolic effects of type 2 diabetes with explanation
- Insulin resistance: obesity has a relation probably mediated by cytokines.
- B cell dysfunction: beta cell compensation becomes inadequate leading to hyperglycemia, this can lead to secretion of pro-inflammatory cytokines from beta cells into islets, ultimaletly leading to their death. Amyloid replacement is a chch finding in ling standing cases.
Describe diabetic morphological changes in:
1. Pancreas
2. Microvasculature
- Reduction in number & size of islets (type 1), leukocytic infiltration in islets in both types. Amyloid replacement is a chch finding in ling standing cases.
- Accelerated atherosclerosis affecting aorta & large & medium-sized arteries.
Describe pathogenesis of long term diabetes complications.
- Formation of AGEs: accelerate atherosclesis + basement membrane thicking leading to diabetic microangiopathy.
- Activation of intracellukar PKC: produce proangiogenic molecules as VEGF (retinopathy), & profibrogenic factors as TGFB.
- Disturbance in polyol pathway leading to oxidative stress.
Describe morphology & significance of diabetic microangiopathy
-Diffuse thickening of basement membranes either in capillaries or nonvascular structures. Basal lamina is thickened by concentric layers of hyaline material composed of collagen IV. Diabetic capillaries are leaky.
-This underlies diabetic nephropathy, retinopathy & some types of neuropathy.
List features of diabetic nephropathy
- Glomerulosclerosis (12 yrs or more, either diffuse or nodular called Kimmelsteil-Wilson lesion)
- Renal arteriosclerosis
- Pyelonephritis with necrotizing papillitis & papillary necrosis.
………..are the major contributor to mortality in diabetic
MI, renal vascular insufficiency & CVA
Describe features of eiabetic neuropathy
- “Glove & stocking” pattery of polyneuropathy
- Autonomic neuropathy of bowel or bladder or sexual impotency
- Mononeuropathy
…….are PanNETs with LEAST malignant potential.
Insulinomas
…..is the most common metastatic site for PanNETs
Liver
…….is one of the best correlates of outcome in PanNETs
Proliferative rate (measured by either mitotic counts or nuclear labeling with proliferator marker Ki-67)
Describe morphology of insulinoma
G: majority are solitary, small, localized to pancreas
M: benign tumors look like giant islets with preservation of regular cords of monotonous cells & their orientation to the vasculature. Not even malignant lesions present much evidence of anaplasia & they may be deceptively encapsulated. Deposition of amyloid in ECT.
List features of Zollinger-Ellison syndrome
- Pancreatic islet cell tumor “Gastrinoma”
- Gastric acid hypersecretion
- Peptic ulceration the stomach, duodenum & jejunum (multiple & unresponsive)
Describe morphology of gastrinoma
G: single in sporadic cases, multifocal in MEN1
M: bland looking cells, rare marked metaplasia
With respect diabetes, Genetic predisposition is stronger in……
Type 2
