Endocrine Pancreas Pathology Flashcards
Where do the majority of the islets of Langerhans exist within the endocrine pancreas?
In the neck and tail
What is secreted by the following cells of the endocrine pancreas?
Alpha cell Beta cell Delta cell D1 cell PP cell
Alpha cell - glucagon Beta cell - insulin Delta cell - somatostatin D1 cell - VIP PP cell - pancreatic polypeptide
What is the step-by-step mechanism of insulin release? (5)
- GLUT-2 takes up glucose into beta cells
- Glucose metabolism generates ATP
- ATP inhibits the membrane K+ channel
- Depolarization results in Ca++ influx
- Ca++ influx results in insulin release
What is the marker of endogenous insulin levels? How is it produced?
C-peptide (helps differentiate what is produced vs. what is ingested). It is produced when proinsulin is cleaved to insulin and C-peptide.
Effects of insulin on adipose (3)
Increased glucose uptake
Increased lipogenesis
Decreased lipolysis
Effects of insulin on striated muscles (3)
Increased glucose uptake
Increased glycogen synthesis
Increased protein synthesis
Effects of insulin on the liver (3)
Decreased gluconeogenesis
Increased glycogen synthesis
Increased lipogenesis
What does oral glucose intake stimulate the release of?
What do they do?
What inactivates them?
Incretins (GLP-1, GIP, etc.).
Incretins stimulate insulin release and inhibit glucagon release resulting in lower blood glucose.
DPP-4 inactives incretins.
What is the onset like in T1DM vs. T2DM?
T1DM: childhood and adolescence typically
T2DM: usually adult
Which antibodies are circulating in T1DM?
Islet antibodies (anti-insulin, anti-GAD, anti-ICA512)
What is the pathogenesis of T1DM vs. T2DM?
T1DM: dysfunction in T-cell selection and regulation leading to breakdown in self-tolerance to islet auto-antigens.
T2DM: insulin resistance in peripheral tissues, failure of compensation by beta cells.
What pathological features are seen in the endocrine pancreas in T1DM vs. T2DM?
T1DM: insulitis (inflammatory infiltrate w/ T-cells and Mo); beta cell depletion; islet atrophy.
T2DM: no insulitis; amyloid deposition in islets; mild beta cell depletion.
Which genes are associated with the susceptibility loci in T1DM?
Which chromosome?
MHC class II genes
Chr. 6p21 (approx. 50% of T1DM)
At what point destruction of islet cells does T1DM ensue?
> 90% of islet cells destroyed
What 2 features must be present to cause T2DM?
Insulin resistance + beta cell dysfunction
What is Maturity-onset diabetes of the young (MODY)?
What are 3 features?
What is the genetic linkage?
It resembles T2DM, but in youth.
- increased blood insulin
- NO auto-Abs
- non-ketotic
Mutations causing a loss of function of glucokinase.
Classic triad of T1DM includes what?
Polyphagia, Polyuria, Polydipsia
How is T2DM usually identified?
On screening; may have vision changes, fatigue.
Why is T1DM more difficult to diagnose in AA and Hispanic children?
What HLA typing can be helpful?
Because auto-antibodies exist in <50% of AA and Hispanic children (90% in Caucasian).
HLA DR/DQ on chr. 6
What type of DM does diabetic ketoacidosis usually occur in?
What is the most common cause?
What is common as a precursor to its onset?
What is the triad?
T1DM
Non-compliance is most common etiology
Precursor infections: pneumonia, UTIs
Hyperglycemia, ketonemia, metabolic acidosis
What are 5 steps to developing diabetic ketoacidosis?
- Body cannot use glucose, so it accumulates in blood (epinephrine released).
- Glucagon is released, promoting GNG.
- Insulin deficiency promotes FFA release, generating ketones.
- Shock, dehydration (more epinephrine).
- Kidneys dump glucose and ketones, causing an osmotic diuresis.
Which 2 ketones accumulate in diabetic ketoacidosis?
How is ketoacidosis diagnosed?
Acetoacetic acid + Beta-hydroxybutyrate
Test for ketones in urine
DKA uniting pathophysiology (3)
Resulting in (3)
Presenting sings/symptoms (3)
Pathophysiology: hyperglycemia, ketonemia, acidosis
Resulting in: dehydration, polydipsia, polyuria/ketonuria
Presenting signs/symptoms: N/V, tachycardia, Kussmaul respirations
What are Kussmaul respirations?
Compensatory alkalosis for metabolic acidosis (a decrease in PCO2 decreases the [H+]; pH increases)
