Pathology of the Endocrine Pancreas Flashcards
What is a defining features of all types of diabetes mellitus?
Hyperglycemia
What other major disease is diabetes mellitus associated with?
- Renal Failure
- Heart Disease
- Stroke
What are the requirements for a Dx of diabetes from a random glucose test?
Classical signs of diabetes mellitus - polyuria, polydypsia, unexplained weight loss with a random glucose level greater than 200 mg/dL
What are the requirements for a Dx of diabetes from a fasting glucose test?
Fasting glucose greater than or equal to 126 mg/dL
What level of HbA1C is Dx for DM?
HbA1C greater than or equal to 6.5
DM Type I
Autoimmune and is due to pancreatic beta cell destruction that leads to insulin deficiency
What is the pathogenesis of DM Type I?
– Failure of self‐tolerance in T‐cells
– Activated T‐cells cause ‐cell injury
• CD8 CTLs directly injure cells
• TH1 cell injury via cytokines
What can trigger DM Type I onset?
Stressing factors such as illness can turn someone on the verge to having full DM.
What will be seen in the islets for a patient with DM Type I?
Lymphocytes
DM Type II
Peripheral Insulin RESISTANCE - the beta cells are initially in tact and crank up insulin production due to the decreased peripheral response, but over time, the increased production wears the beta cells out.
What is the function of adiponectin?
Adiponectin sensitizes tissues to insulin
What are the function of adipokines?
Adipokines cause insulin resistance
How do FFAs affect insulin?
They increase insulin resistance
What will be seen in the islets in DM Type II?
Amyloid deposition of the protein amylin
Nonketotic Hyperosmolar Coma
Seen rarely with extreme hyperglycemia (greater than 600) more often in nursing home patients
What is the age of patients in Type I VS II DM?
Type I - young children or adolescents
Type II - adults
What happens to DM Type I patients in the absence of insulin therapy?
Diabetic Ketoacidosis
Nonenzymatic Glycosylation (AKA Glycation)
Glucose covalently attaches to multiple proteins nonenzymatically like cellular basement membrane proteins in the ocular lens
Over time labile products of glycaion undergo complex chemical rearrangements to form _________________.
Advanced Glycosylation End-Products (AGEs)
What happens due to non enzymatic glycosylation to the vasculature?
- Deposition of extracellular matrix
- Increase vascular stiffness
- Increase vascular permeability
What are the effects of hyperglycemia on PKC?
Intracellular hyperglycemia results in activation of Protein Kinase C which causes:
• Production of VEGF
• Decreased expression of endothelial nitric oxide
synthase
• Production of profibrinogenic factors(TGF‐beta)
What is the effect of increased intracellular glucose?
Excess glucose metabolized by aldose reductase to sortibol via NADPH co‐factor which depletes NADPH, an antioxidant and can also mediate cell damage via sorbitol.
Diabetic Retinopathy
Microvascular changes lead to increased production of VEGF and retinal angiogenesis with retinopathy caused by new vessel formation on disc, retina, and elsewhere
Insulinoma
Arise in beta cells and most are benign and solitary
What is Whipple’s triad for insulinomas?
- Hypoglycemia (less than 50)
- CNS symptoms
- Symptoms resolve with feeding or glucose
What are the lab findings for insulinoma?
- Hypoglycemia
- High circulating levels of insulin
- High insulin:glucose ratio
Gastrinoma
Gastrin producing cells found in pancreas, duodenum, and in peripancreatic tissue
Zollinger‐Ellison Syndrome
Hypergastrinemia causes gastric acid secretion and peptic ulceration often in unusual places like the jejunum
Alpha‐cell tumors presenting with diabetes, a skin rash, often middle aged and older women, anemia, high glucagon levels.
Glucagonoma
Diabetes and malabsorption associated with d‐cell tumors, very hard to localize pre-op.
Somatostatinoma
Severe secretory diarrhea‐‐‐can be associated with neural crest tumors
VIPoma
