Endocrine Pancreas Pathology Flashcards
1
Q
What is glucose homeostasis regulated by?
A
- Hepatic release of glucose
- Tissue utilization of glucose
- Hormonal control of glucose by insulin and glucagon
2
Q
What is the regulation of insulin release?
A
- GLUT-2 takes glucose into beta cells
- Glucose metabolism generates ATP
- ATP inhibits the membrane K+ channel
- Depolarization results in Ca2+ influx
- Ca2+ influx results in insulin release
3
Q
How is insulin processed?
A
- Proinsulin is cleaved in the beta cell to form insulin and C-peptide
4
Q
What is C peptide?
A
- A marker of endogenous insulin
- Can differentiate from insulin administered as a pharmaceutical agent
5
Q
What does insulin do in adipose tissue?
A
- Increase glucose uptake
- Increase lipogenesis
- Decrease lipolysis
6
Q
What does insulin do in striated muscle?
A
- Increase glucose uptake
- Increase glycogen synthesis
- Increase protein synthesis
7
Q
What does insulin do in the liver?
A
- Decrease gluconeogenesis
- Increase glycogen synthesis
- Increase lipogenesis
8
Q
What are the incretins?
A
- Glucagon like peptide (GLP-1)
- Glucose-dependent insulin-releasing polypeptide (GIP)
9
Q
What is the MOA of incretins?
A
- Stimulate insulin release and inhibit glucagon release resulting in lower blood glucose
10
Q
What inactivated incretins?
A
- Dipeptidyl peptidase-4 (DPP-4)
11
Q
What causes type 1 diabetes?
A
- Autoimmune disease due to failure of T-lymphocyte self tolerance
- T-lymphocytes directed against antigens on the pancreatic beta cells
- After initial insult, damaged beta cells evoke autoimmune reponse
12
Q
What is a major link in type 1 diabetes?
A
- MHC class II genes –> susceptibility loci
- HLA gene cluster on chromosome 6p21, responsible for as many as 50% of T1DM
13
Q
How do genetics and environment affect type 2 diabetes?
A
- Majority of patients with T2DM have a first degree relative with T2DM
- Major risk factor is obesity
14
Q
What is maturity-onset diabetes of the young (MODY)?
A
- Resembles T2DM clinically, but happens in youth
- Blood insulin may be high, normal, or low
- No autoantibodies
- Nonketotic
15
Q
What is the genetic linkage in MODY?
A
- Most often caused by mutations resulting in loss of function of glucokinase
16
Q
What are some risks to the fetus in gestational diabetes?
A
- Neonatal hypoglycemia causing seizures and brain damage
- Macrosomia
- Congenital malformations
- Stillbirth
17
Q
What is a risk to the mother in gestational diabetes?
A
- Cesarean section
18
Q
What is the classic triad fo T1DM?
A
- Polyphagia
- Polyuria
- Polydipsia
- Severe: diabetic ketoacidosis
19
Q
How is T2DM usually identified?
A
- On screening
- Fatigue, vision changes
20
Q
Who are the autoantibodies checked for diabetes?
A
- Present in >90% of caucasian children
- Present in <50% of african american and hispanic children
21
Q
What HLA typing is done for diabetes?
A
- HLA DR/DQ on chromosome 6
22
Q
What is the triad of diabetic ketoacidosis?
A
- Hyperglycemia
- Ketonemia
- Metabolic acidosis
23
Q
Who has diabetic ketoacidosis most often?
A
- More typical of T1DM
24
Q
What are some causes of diabetic ketoacidosis?
A
- Non-compliance most common underlying etiology
- Precursor infections common (pneumonia or UTI)
25
What is a way to test for diabetic ketoacidosis?
- Test for ketones in the urine
- Acetoacetic acid
- Beta-hydroxybutyrate
26
What are some presenting signs of DKA?
- Nausea/vomiting
- Tachycardia
- Kussmaul respirations
27
What is hyperglycemic hyperosmotic syndrome (HHS)?
- Acute hyperglycemic crisis in T2DM
28
What causes HHS?
- Culmination of prolonged insulin deficiency
- Increased gluconeogenesis
- Decreased glucose uptake in peripheral tissues
29
What are the presenting symptoms of HHS?
- Glucose >600 mg/dL
- Severe dehydration
- Hyperosmolality --> obtundation, coma
- Impaired renal function
30
What is hemoglobin A1C?
- Irreversible glycosylation of the hemoglobin tetramer
| - Measure of long term diabetic control, since binding takes over 1 month
31
What is a target A1C?
- 6.5-6.7 or lower
32
What does chronic hyperglycemia increase the risk of?
- Stroke
- MI
- Lower extremity gangrene
33
What is the most common cause of death in diabetics?
- MI
34
What is the screening done in diabetic nephropathy?
- Use albumin:creatinine ratio in urine
35
What are the three primary pathologic conditions that could occur due to diabetes?
- Glomerular sclerosis
- Renal vasculature lesions
- Pyelonephritis
36
What is glomerular sclerosis?
- Thickening of the basement membrane
- Disruption of the protein cross-linkage that normally makes the membrane an effective filter
- In consequence, there is a progressive leak of large molecules into the urine
37
What occurs in diabetic retinopathy?
- Neovascularization
- Hypoxia leads to VEGF overexpression
- Hemorrhage
- Blindness
- Cataracts
- Glaucoma
38
What is a chronic diabetic complication?
- Neuropathy
- Distal symmetric polyneuropathy
- Autonomic neuropathy
- Diabetic mononeuropathy
39
What are diabetics are an increased risk for?
- Cellulitis
- Pneumonia
- Pyelonephritis
40
What are some unifying features of pancreatic neuroendocrine tumors?
- Gross appearance --> solid, tan-yellow
- Predilection for the pancreatic neck and tail
- Histology --> well-differentiated neuroendocrine tumors
- EM -- secretory granules
41
What is an insulinoma?
- Small tumors that can produce episodes of symptomatic hypoglycemia
- Amyloid is a common finding
- C peptide levels can make diagnosis
42
What is the triad for a gastrinoma?
- Islet cell tumor
- Gastric acid hypersecretion
- Peptic ulceration
43
What is a clue to clinical diagnosis for a gastrinoma?
- Ulcers do not respond to conventional therapy
44
What is a gastrinoma also called?
- Zollinger-Ellison syndrome
45
What is seen in somatostatinomas?
- Diabetes
- Cholelithiasis
- Steatorrhea
46
What are manifestations of a somatostatinoma? Why?
- Reduced insulin
- Reduced gallbladder motility
- Reduced exocrine pancreatic secretions
- This is all due to somatostatin being a paracrine regulator (usually inhibitory)
47
What is seen in a glucagonoma?
- Mild diabetes
| - Necrolytic migratory erythema (groin and LE)
48
What are the 4 D's of glucagonomas?
- Diabetes
- Dermatitis
- Depression
- DVT's
49
What is seen in VIPomas?
- Watery diarrhea
- Hypokalemia
- Achlorhydria
- WDHA syndrome
- Flushing
50
What cell of the pancreas is involved with an insulinoma?
- beta
51
What cell of the pancreas is involved with a gastrinoma?
- G
52
What cell of the pancreas is involved with a somatostatinoma?
- Gamma
53
What cell of the pancreas is involved with a glucagonoma?
- alpha
54
What cell of the pancreas is involved with a VIPoma?
- D1
