Pathology of the endocrine pancreas Flashcards
what is MODY? what is the cause?
maturity onset diabetes of the young
- genetic abnormalities which cause a primary defect in beta cell function
features of MODY
- no loss or change in beta cell numbers**
- usually AD with high penetrance
- early onset usually under 25 years old
- no obesity
- no insulin resistance and no antibodies to glutamic acid decarboxylase**
diagnosing criteria for diabetes
which need to be repeated?
what is definitively diagnostic?
- HbA1c over 6.5%
- fasting plasma glucose over 126 mg/dL
- 2 hour OGTT plasma glucose over 200 mg/dL
- random glucose over 200 mg/dL in symptomatic patient
lab results need to be repeated
symptoms + one other sign is diagnostic
what is the pathogenesis of viral infection mediated T1DM?
molecular mimicry
is there inflammation in T1DM? what about in T2DM?
T1DM - yes (insulitis)
T2DM - no
T1DM histology - early insulitis
acute insulitis - infiltrate of neutrophils, degranulation and death of beta cells
T1DM - histology - chronic insulitis
- reduction in number and size of islets, thus loss of beta cells
- infiltration of an islet by lymphocytes
- hyalinization
- fibrosis
early T2DM - insulin changes, insulitis?
- normal insulin secretion and plasma levels, but loss of pulsatile, oscillating pattern of secretion
- NO insulitis
late T2DM - insulin changes
- mild / moderate insulin deficiency, may be due to beta cell damage (beta cells may be ‘exhausted’ due to chronic hyperglycemia (“glucose toxicity”)
- insulin resistance in peripheral tissues also seen in obesity and pregnancy
what is amylin?
insulin, abnormally packaged and secreted, tends to accumulate outside beta cells and resembles amyloid
what is the most common underlying cause in the pathognesis of complications in DM?
glycation (non-enzymatic glycosylation) of extracellular matrix
what are the potentially pathogenic effects of AGEs (advanced glycation end-products)?
- plasma proteins can bind to glycated basement membranes
- induction of cross linking in type IV collagen in basement membranes (becomes thick and leaky)
- trap LDL particles in artery walls
- bind to receptors on numerous cell types
what occurs when AGEs bind to receptors on numerous cell types?
- release of cytokines and growth factors from macrophages
- increase in endothelial permeability
- increase in endothelial procoagulant activity (ischemia)
- increase in ECM production by vascular smooth muscle cells as well as increased proliferation
where does diabetic microangiopathy occur?
small vessels (retina, glomeruli)
what underlies the development of diabetic nephropathy / retinopathy / neuropathy?
microangiopathy
