17. Endocrine Pancreas Pathology Flashcards
4 cell types of the islets of langerhans and their phormone products
Beta cells — insulin
Alpha cells — glucagon
Delta cells — somatostatin
PP cells — pancreatic polypeptide
Hormone product of D1 cells of the pancreas
Vasoactive intestinal polypeptide (VIP)
______ is the transporter responsible for glucose uptake into beta cells. Glucose metabolism generates ATP which inhibits the membrane K+ channel, allowing ____ influx, which results in insulin release
GLUT-2; Ca++
During processing, proinsulin is cleaved to form insulin and ____, which a marker of endogenous insulin
C peptide
Oral glucose stimulates the release of ______ which stimulate insulin release and inhibit glucagon release resulting in lower blood glucose
Incretins
What are examples of incretins?
Glucagon-like peptide-1 (GLP-1)
Glucose-dependent insulin-releasing polypeptide (GIP)
Incretins are inactivated by _______
Dipeptidyl peptidase-4 (DPP-4)
Difference in age of onset between T1D and T2D
T1D: usually childhood and adolescence
T2D: usually adult, increasing incidence in childhood and adolescence
Difference in autoantibodies between T1D and T2D
T1D: presence of circulating islet autoantibodies (anti-insulin, anti-GAD, anti-ICA512) [major linkage to MHC class II genes — specifically HLA gene cluster on Chr6p21]
T2D: no islet antibodies [no HLA linkage]
Difference in pathogenesis between T1D and T2D
T1D: dysfunction in T cell selection and regulation, leading to breakdown in self-tolerance to islet autoantigens
T2D: insulin resistance in peripheral tissues, failure of compensation by beta cells; multiple obesity-associated factors
What is insulitis, and which type of DM is it associated with?
Insulitis = inflammatory infiltrate of T cells and macrophages — associated with T1D
[T2D is NOT associated with insulitis, but may show amyloid deposition in islets]
What disease resembles T2DM clinically, but happens in youth — presenting with increased blood insulin but NO autoantibodies and is nonketotic?
Maturity-onset diabetes of the young (MODY)
Maturity-onset diabetes of the young (MODY) is most often caused by mutations resulting in loss of function of _______
Glucokinase
Risks to mom vs. risks to fetus with gestational diabetes
Mom: cesarean section (usually due to large size of fetus)
Fetus: neonatal hypoglycemia may lead to seizures and subsequent brain damage; macrosomia, congenital malformations, stillbirth
What are the 2 opportunities for gestational diabetes screening?
Screen at first prenatal visit for pre-existing DM — measure fasting plasma glucose (FPG), HgbA1c, or random plasma glucose
Screen at 24-28 weeks gestation with oral glucose tolerance test (OGTT) — glucose levels measured while fasting, 1 hour post-oral glucose, and 2 hours post-oral glucose
Classic triad of T1DM
Polyphagia
Polyuria
Polydipsia
Severe = diabetic ketoacidosis
[T2DM usually identified on screening — fatigue, vision changes, etc.]
Signs/symptoms of T1DM
Increased thirst and frequent urination
Extreme hunger
Weight loss
Fatigue
Irritability or behavior changes
Fruity-smelling breath
How is T1DM distinguished from T2DM based on lab results?
Autoantibodies — present in T1DM only
HLA typing — HLADR/DQ on Chr6
[note that autoantibodies are more reliably detected in caucasian children with T1DM than AA and hispanic children]
Clinical triad of DKA
Hyperglycemia (usually of T1DM)
Ketonemia
Metabolic acidosis
[presenting signs/symptoms include dehydration, polydipsia, polyuria/ketonuria, N/V, tachycardia, and Kussmaul respirations]
Pathogenesis of DKA
Body can’t use flucose, so it accumulates in the blood
Glucagon is released, promoting gluconeogenesis
Kidenys dump glucose and ketones, osmotic diuresis occurs
Shock, dehydration, more epinephrine
Insulin deficiency promotes FFA release generating ketones
DKA treatment
Insulin
Hydration
Potassium
[hypokalemia will rapidly occur when you give insulin, so you must also give K+]
What is hyperglycemic hyperosmotic syndrome (HHS)?
Acute hyperglycemic crisis in T2DM
Culmination of prolonged insulin deficiency —> increased gluconeogenesis and decreased glucose uptake in peripheral tissues
Presenting signs/symptoms of hyperglycemic hyperosmotic syndrome (HHS) — note which sign makes it different from DKA!
Glucose >600 mg/dL
Severe dehydration
Hyperosmolality (>350 mOsm/L) leading to obtundation, coma
Impaired renal function
[NO KETONES! — distinguishes it from DKA]
What lab provides a measure of long-term diabetic control?
Hemoglobin A1c
