20/21: Pathology of the Endocrine Pancreas - Fang Flashcards
“bronze diabetes”
hemochromatosis
due to hemosiderin deposition in pancreas
b-cell destruction leading to absolute insulin deficiency
type 1 DM
immune-mediated
idiopathic
insulin resistance with relative insulin deficiency
type 2 DM
MODY =
maturity onset diabetes of the young
genetic abnormalities which cause a primary defect in b-cell function
no obesity
no insulin resistance
no antibodies to gluatmic acid
MODY
-just a defect in b-cell function
normal blood glucose range
70-120
any one of four criteria for diabetes diagnosis :
- A1c greater of equal to 6.5%
- Fasting plasma glucose greater than 126 mg/dL
- 2h plasma glucose greater than 200 mg/dL during an oral glucose tolerance test
- random glucose greater than 200 in patient with symptoms
- in the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed
most common COD in pt with DM
MI
inflammation, degranulation of b-cells, and death of b-cells
acute islitis
early change in type I DM
following this acute inflammation, there will eventually be a reduction in number and size of islets; thus loss of b-cells. later will be hyalinized.
there is a _______ lack of insulin in type 2 DM
relative
normal levels of insulin re circulating but cells are not appropriately responding to the insulin
primary beta cell defect and peripheral tissue insulin resistance –> hyperglycemia —> _______ —> type 2 DM
beta cell exhaustion
insulin, abnormally packaged and secreted, accumulating outside beta cells
amylin (because resembles amyloid)
sign of type 2 DM
does early type 2 DM show insulinitis?
no insulinitis present
“glucose toxicity”
later stage of Type 2 DM
mild/moderate insulin deficency due to beta cell damage/exhaustion due to chronic hyperglycemia
amorphous “cracked plate glass”
histological type II DM
amylin
***_____________ is the MOST common underlying cause in the pathogenesis of complications in DM
non-enzymatic glycosylation of extracellular matrix
4 pathogenic effects of AGEs
- plasma prtns can bind to glycated BM
- can induce cross linking in type IV collagen in BM
- can trap LDL particles in artery walls
- can bind to receptors on numerous cell types
AGEs =
advanced glycation end-products
AGEs binding to cell receptors can cause (4)
- release of cytokines and growth factors from macrophages
- increased endothelial permeability
- increased endothelial procoagulant activity
- increased extracellular matrix production by vascular smooth muscle cells as well as increased proliferation
AGEs play a role in damage of BM by (2)
- prtn accumulation thickening of BM
- trapping of LDL in artery wall, oxidation
most consistent morphologic feature of diabetes
diffuse thickening of BM
most evident in capillaries of retina and renal glomeruli
despite increase in thickness of BM, diabetic capillaries are _______ than normal to plasma prtns
more leaky
microangiopathy underlies the development of …
diabetic nephropathy
diabetic retinopathy
some forms of neuropathy
thick, narrow, and leaky SMALL blood vessels
diabetic microangiopathy- especially in kidneys and eyes
due to glycosylation
BM damage leak
AGE deposition
how would you describe peripheral neuropathy caused by DM nerve damage?
symmetric , bilateral progressive, irreversible paraesthesia pain muscle atrophy
damage to blood vessels in eyes is described as
exudative and proliferative retinopathy
diabetic nephrosclerosis =
nodular kimmelstiel-wilson glomerulopathy
gram negative bacilli –>
staphylocci –>
pyelonephritis
cortical infection
what are some effects of visceral neuropathy?
CN - diplopia, bell palsy
GIT - constipation, diarrhea
CVS- orthostatic hypotension
diabetic macroangiopathy =
accelerated atherosclerosis
due to nonenzymatic glycosylation of lipoprtns
ischemia due to microangiopathy and atherosceleroiss serves as a stimulus for neovascular proliferation
diabetic retinopathy
3 changes in retina with diabetic retinopathy
edema
hemorrhagic foci
neovascularization
no insulinitis
yes amyoid
type 2 DM
more concordance in twins
type 2 DM
2 pancreatic neuroendocrine tumors NETs
- insulinoma
- zollinger-ellison syndrome
- wermer syndrome
hyperinsulinism NET
insulinoma
most common pancreatic NET
hypergastrinemia NET
zollinger-ellison syndrome
MEN1 syndrome NET
wermer syndrome
**Whipple triad of hypoglycemia
- blood glucose less than 45 mg/dL
- CNS confusion/stupor
- precipitated by fasting or exercise and relieved by food
describe insulinomas
- benign
- solitary
- small
- encapsulated
- “giant islets”
- amyloid can be found
- 10% carcinomas
multiple peptic ulcerations in stomach, duodenum and even jejunum —>
suspect zollinger-ellison syndrome
result of elevated gastric acid secretion caused by a gastrinoma
risks of zollinger-ellison syndrome
- 1/2 metastasized at time of diagnosis
- 25% associated with other endocrine tumors (MEN1 syndrome)
