SFP: endocrine pancreas Flashcards
What is a major cause of death in those with diabetes?
MI
What are islets of Langerhans?
Structures in the pancreas with endocrine function
Beta islet cells make ___
Insulin
Alpha islet cells make ___
Glucagon
Delta islet cells make ___
Somatostatin
Insulin is formed as a ___
Inactive hormone; proinsulin has the C peptide removed to form insulin
What is the main negative feedback for islet B cell production of insulin?
Somatostatin
What 3 tissues does insulin have the greatest effect on?
Adipose, liver, striated muscle
Briefly describe type 1 diabetes.
Autoimmune disease resulting in B cell destruction that leads to absolute insulin deficiency
Briefly describe type 2 diabetes.
Results from either a resistance to insulin or secretion problems
CTLA4 is associated with…
T1DM, Hashimoto’s, graves’ disease. Bunch of autoimmune issues since CTLA4 is supposed to be in charge of T cell response
What gene category is associated with T1DM?
HLA
What do we see histologically in T1DM?
T cells attacking islets (mostly CD8), autoantibodies, cytotoxic granule release and activated cell death pathways
Which type of diabetes is largely associated with obesity?
T2DM
Describe how obesity can be related to T2DM.
Obesity results in more FFAs, inflammation, and adipokines that may lead to insulin resistance. Over time, beta cells try to compensate via secreting more insulin. As this goes on, the B cells begin to fail due to essentially being overworked
In which type of diabetes do we see amyloid?
T2DM
What are classic signs of diabetes mellitus?
Polyuria, polyphagia, polydipsia, weakness/fatigue
What potentially fatal presentation is seen with T1DM?
Diabetic ketoacidosis
What fatal presentation is seen with T2DM?
Hyperosmolar hyperglycemic state
What are the 3 big pathogeneses of diabetes mellitus?
- Formation of advanced glycosylation end products
- Activation of protein kinase c
- Disturbance of polyol pathways
Describe formation of advanced glycosylated end products in diabetes.
The sugar can bind to receptors such as pro-inflammatory cytokines or ROS and lead to vascularization and destruction, coagulation, or smooth muscle hyperplasia. They can also cross-link and enhance LDL, thicken kidney basement membranes, and alter plasma proteins
What is the issue with activation of protein kinase c?
This increases neovascularization and basement membrane thickening
What is the issue with disturbing polyol pathways?
Tissues that don’t use insulin use an alternate pathway for glucose. This process on overdrive results in a lack of NAD/NADH that causes us to get stuck with a lot of sorbitol that lodges places like nerves
What is diabetic microangiopathy?
Diffuse small vessel membrane thickening, making them leakier than normal
What is diabetic nephropathy?
Depositions in the mesangium of the kidney leading to nephrotic syndrome
What is diabetic retinopathy?
Thickened basement membrane in the retinas results in poor transport ability that leads to microaneurysms and neovascularization; can be proliferative or non-proliferative
What is diabetic neuropathy?
Involves sensory and autonomic systems and often impacts sensory functioning in the lower extremities (ulcers!!). Huge cause of morbidity
What is the best way to prevent diabetic ulcers?
Strict glucose control, daily foot care, proper footwear
What is the HgA1C range for diabetes?
5.7-6.4
What is the glucose range for prediabetes?
100-125
What is the oral glucose tolerance test?
A patient is given something with a known amount of sugar. If they’re normal, they should see an initial spike in blood sugar that goes down. If they’re pre-diabetic, their blood sugar will continue to go up after the initial spike
What blood sugar readings are needed to diagnose diabetes?
Two separate readings of 126 or random reading of 200
In what instances is Ha1c not a good tool?
- Anemia 2. Recent blood transfusion 3. Hemoglobinopathies
How do we diagnose insulin-secreting tumors?
Hypoglycemia in a fasting state
How do we determine metastatic potential in pancreatic endocrine tumors?
We don’t; it can’t be determined
What is seen in pancreatic endocrine tumors?
A salt and pepper nucleus
What is an insulinoma?
A tumor presenting with hypoglycemia, confusion/loss of consciousness, and precipitated by fasting or exercise
What are gastrinomas?
Tumors of cells producing gastrin result in oversecreting, causing severe peptic ulcers
What is Zollinger-Ellison syndrome?
Hypersecretion of gastric acid causing severe peptic ulcers due to gastrin secretion
One quarter of gastrinomas are associated with what syndrome?
MEN-1 syndrome
