Endocrine Pancreas Pathology Flashcards
Which ethnicities are more likely to develop DM?
Native Americans
African Americans
Hispanics
What are the criteria for Dx of DM?
Fasting glucose ≥ 126
Random glucose ≥ 200
2-hour glucose ≥ 200 during OGTT
HbA1C ≥ 6.5%
What is the pathogenesis of DM1?
Islet cell destruction caused by immune effector cells reacting against endogenous ß-cell Ags
What are the potential autoAg targets in DM1?
Insulin
ß-cell enzyme Glutamic Acid decarboxylase (GAD)
Islet cell autoAg 512 (ICA512)
What HLA’s are associated with DM1?
HLA-DR3, HLA-DR4
Which other HLA mutation gives the highest risk for DM1?
HLA-DR8
Which chromosome are the HLA’s on for DM1?
Chrom 6p21
Which polymorphisms are seen in DM1?
CTLA4
PTPN22
AIRE
Wasinsulin
What is the classic Sx triad for DM1?
Polyuria
Polydipsia
Polyphagia
What is the “honeymoon” period?
Endogenous insulin secretion is enough to need little exogenous insulin
Is DKA more likely in DM1 or DM2?
DM1
When does DM1 typically present?
< 18 yo
What is the biggest risk factor for DM2?
Central/Visceral obesity
What is the pathogenesis of DM2?
Insulin resistance –> decreased response of peripheral tissues to insulin
How does insulin resistance affect the liver?
Failure to inhibit gluconeogenesis –> high fasting blood glucose
How does insulin resistance affect the SkM?
Failure of glucose uptake and glycogen synthesis after a meal –> high post-prandial blood glucose
How does insulin resistance affect adipose tissue?
Failure to inhibit activation of lipase –> excess TG breakdown and high circulating FFA’s
When does DM2 typically present?
> 40 yo
What are the main Sx’s of DM2 at presentation?
Fatigue
Dizziness
Blurred vision
What is Hyperosmolar Hyperosmotic Syndrome (HHS)?
Severe dehydration from sustained osmotic diuresis
What type of pts typically get Hyperosmolar Hyperosmotic Syndrome?
Older pts disabled by stroke or infection
What is the blood glucose range for pts with Hyperosmolar Hyperosmotic Syndrome?
600-1200 mg/dL
What is Lipoatrophic diabetes?
Hyperglycemia along with loss of adipose tissue in subQ fat
Pregnant women with pregestational DM that isn’t controlled put their fetuses at increased risk for?
Stillbirth
Congenital malformations
Why do pregnant women develop gestational DM?
Pregnancy is a diabetogenic state where the hormones favor a state of insulin resistance
Do pregnant women who get gestational DM have a increased risk of developing overt DM?
Yes, 10-20 years later
What factors can trigger DKA?
Failure to take insulin*
Infection, Illness
Trauma
Drugs
What is the typically serum glucose level in DKA?
250-600 mg/dL
What are the major Sx’s of DKA?
Fatigue, N/V, ab pain, fruity breath, labored breathing (Kussmaul), CNS depression
What is the MOA of DKA?
Insulin deficiency –> stimulation of lipases –> increased FFA’s in serum –> increased fatty acyl-CoA production in liver –> oxidation of fatty acyl-CoA into ketone bodies
What are the two ketone bodies of concern in DKA?
Acetoacetic acid
ß-hydroxybutyric acid
How does metabolic ketoacidosis occur?
Dehydration –> decreased urinary excretion of ketone bodies
What is the Tx for DKA?
Insulin administration
Correct metabolic acidosis
Tx precipitating factor
What is the most common acute metabolic complication in either type of DM?
Hypoglycemia
What are the Sx’s of hypoglycemia?
Dizziness, confusion, sweating, palpitations, tachycardia
What is used to assess glycemic control?
HbA1C
Why does HbA1C help assess glycemic control?
The more glucose that has been around an RBC, the more HbA1C will be present
What is the most common cause of death in DM pts?
MI
Pts with DM have increased PAI-1 enzyme, meaning…
Increased inhibition of fibrinolysis = acts as procoagulatin
Morphology = diffuse thickening of basement membranes of vessels with paradoxical increased leakiness of vessels
Diabetic microvascular disease
What is the first sign of diabetic nephropathy?
Microalbuminuria
What is a urinary marker for increased CV risk?
Albumin
Which ethnicities (with DM2) are at greater risk for developing diabetic nephropathy?
Native Americans
African Americans
Hispanics
What are the 3 major lesions seen in the kidney in diabetic nephropathy?
Glomerular lesions
Nodular Glomerulosclerosis
Pyelonephritis (necrotizing papillitis)
What glomerular lesion is seen in diabetic nephropathy?
Thickening of the basement membrane
What is seen in Diffuse Mesangial Sclerosis?
Increase mesangium with thickend GBM
In Diffuse Meesangial Sclerosis, the matrix will stain + for?
PAS
What is the name for nodules that enlarge and eventually obliterate the glomerular tuft in the kidney?
Nodular Glomerulosclerosis (Kimmelstiel-Wilson) disease
What can happen to the afferent and efferent hilar arterioles in diabetic nephropathy?
Hyalinosis due to ischemia
Which type of pyelonephritis is more common in pts with diabetic nephropathy?
Necrotizing papillitis
Sx’s = motor and sensory dysfunction of the distal LE’s and UE’s
Diabetic neuropathy
What are the Sx’s of autonomic neuropathy?
Bowel, bladder, and ED
What are the Sx’s of mononeuropathy?
Sudden foot drop, wrist drop, or isolated CN palsies
What is the pathogenesis of diabetic ocular complications?
Neovascularization from hypoxia-induced overexpression of VEGF in the retina
What type of cells are involved in pancreatic neuroendocrine tumors?
Islet cells
Islet cell tumors secreting insulin are mostly _____ while islet cell tumors secreting other hormones are mostly _____
Benign
Malignant
What mutations are commonly seen in Pancreatic Neuroendocrine tumors?
MEN1, PTEN, TSC2
A-Thalaseemia/Mental retardation syndrome, X-linked (ATRX)
Death-domain Associated protein (DAXX)
What is the most common pancreatic endocrine neoplasm?
Insulinoma
What are the Sx’s of an Insulinoma?
Hypoglycemia with confusion, stupor, and LOC
Morphology = small cells that look like giant cells with amyloid deposition
Insulinoma
What lab value would indicate and Insulinoma?
High circulating insulin
High insulin:glucose ratio
What is the Tx for an Insulinoma?
Surgical removal
Sx’s = peptic ulcers, diarrhea, possible MEN1 syndrome
Gastrinoma (ZE)
Sx’s = mild DM with skin rash and anemia in perimenopausal and postmenopausal women
a-cell tumors (Glucagonomas)
Sx’s = DM, cholelithiasis, steatorrhea, and hypochlorhydria
d-cell tumors (Somatostatinomas)
Sx’s = watery diarrhea, hypokalemia, achlorhydria (WDHA syndrome)
VIPoma