Flashcards in Usera: Endocrine Pancreas Deck (63):
The endocrine pancreas is made up of 1 million clusters of cells called the (blank)
islets of langerhans
What are the four main cells types found in the endocrine pancreas, and what does each secrete?
beta cells: secrete insulin
alpha cells: secrete glucagon
delta cells: secrete somatostatin
PP cells: secrete pancreatic polypeptide
What are the two minor cells found in endocrine pancreas, and what does each secrete?
D1 cells: secrete VIP
enterochromaffin cells: secrete 5HT
Round, dense granules with a thin halo
alpha granules (secrete glucagon)
Crystalline core with a wide halo
beta granules (secrete insulin)
Round, less dense core with a thin halo
delta granules (secrete somatostatin)
Small, hyperdense cores
What are the two main disorders of the pancreatic islet cells?
pancreatic endocrine tumors
Dysfunction or loss of pancreatic B-cells
Decreased secretion of insulin
Abnormal proliferation of pancreatic islet cells
pancreatic endocrine tumors
Not a single disease entity, but rather a group of metabolic disorders sharing the common underlying feature of hyperglycemia.
Results from defects in insulin secretion, insulin action or most commonly, both.
Chronic hyperglycemia and associated metabolic dysregulation may be associated with secondary organ damage, especially in these organs...
Diabetes mellitus is the leading cause of these three conditions
end-stage renal disease
non-traumatic lower extremity amputation
What is the estimated lifetime risk of being diagnosed with DM in individuals born in the US, males vs females?
1 in 3 males
2 in 5 females
What are 3 ways to diagnose DM?
1. random blood glucose greater than 200mg/dL with classical signs & symptoms
2. fasting blood glucose greater than 126mg/dL more than once
3. abnormal glucose tolerance test with blood glucose greater than 200mg/dL after a carb load
What is the fasting blood glucose of a prediabetic? What is the glucose tolerance testing like?
fasting blood glucose: 100-126 (less than 100 in healthy individuals)
glucose tolerance testing: 140-200 (less than 140 in healthy individuals)
What is type 1 DM?
absolute deficiency of insulin caused by autoimmune destruction of beta-cell mass
T-lymphocytes mount an immune response against pancreatic beta-cell antigens
What is type 2 DM?
peripheral resistance to insulin action or relative insulin deficiency (inadequate secretion by pancreatic B cells)
This makes up 90-95% of diabetes cases
type II DM
Most people with type II DM are (blank)
What is the major gene associated with type I DM?
HLA-DR3 and HLA-DR4
**HLA contributes to over 50% of the genetic susceptibility
90-95% of whites with DM type 1 have either HLA DR3 or DR4 haplotypes
40-50% of DM type i are combined DR3 & DR4 heterozygotes
Some non-HLA genes associated with DM 1 include the following...
CD25 (decreases activity of IL2R)
This is one way that you can get type 1 DM...
viral infection induces islet cell injury & inflammation --> leads to exposure of self B cell antigens and activation of autoreactive T-cells
Two ways in which a virus can lead to type 1 DM...
molecular mimicry: viral proteins mimic B cell antigens & the immune response cross reacts
precipitating virus: viral infection early in life could persist in tissue --> subsequent infection with a similar virus could elicit an immune response against infected islet cells
In type 1 DM, there is slow, progressive destruction of islet cells. About what percentage of the beta cells must be destroyed before hyperglycemia & ketosis occur?
greater than 90%
These are present in patients with type 1 DM and in their family members
autoantibodies to islet cells
What are some environmental factors contributing to type 2 DM?
What are some genetic factors contributing to type 2 DM?
strongest association with TCF7L2
35-60% concordance in monozygotic twins!!
lifetime risk for offspring is more than doubles if both parents are affected
not linked to HLA genes
What are the TWO metabolic defects of type 2 diabetes? Which happens first?
1. insulin resistance - decreased ability of peripheral tissues to respond to insulin
2. beta-cell dysfunction - inadequate insulin secretion in the face of hyperglycemia
**the insulin resistance is usu the primary event
What effects does insulin have on the following?
adipose tissue: increases glucose uptake & decreases lipolysis
striated muscle: increases glucose uptake & glycogen synthesis, increases protein synthesis
liver: decreases gluconeogenesis & increases glycogen synthesis & lipogenesis
(blank) is present in about 80% of type 2 DM patients
(blank) is present in obesity unaccompanied by hyperglycemia. In other words, in states of fatty excess, there is a fundamental abnormality in (blank)
insulin resistance; insulin signaling
The failure of target tissues to respond normally to insulin
Discuss how beta cell dysfunction evolves with insulin resistance leading to diabetes
in states of insulin resistance, insulin is initially higher for each level of glucose
higher levels of insulin compensate for peripheral insulin resistance to maintain normal blood glucose levels
once beta cell compensation becomes inadequate, diabetes developes
(blank) allelic variants associated with reduced insulin secretion
So initially, pancreatic beta cells secrete normal amounts of insulin, and blood glucose remains normal. Then, as insulin resistance begins to develop, beta cells compensate by producing more insulin. Ultimately, the beta cells will (blank), leading to decreased insulin production & (blank)
fail; diabetes mellitus
What is the best assessment of glycemic control in DM?
What is HgbA1c? What does it tell you?
formed by nonenzymatic covalent addition of glucose moities to hemoglobin in RBCs
**provides a measure of glycemic control over the lifespan of the RBCs (120 days)
What should the HgbA1c be in non-diabetics?
less than 7%
Form when nonenzymatic reactions occur between glucose and the amino groups of intra- and extracellular proteins
advanced glycosylation end products (AGEs)
The rate of AGE formation is accelerated in hyperglycemia. When AGEs directly cross-link to extracellular matrix proteins, what happens?
Decreases vascular elasticity
Enhances protein deposition
Entrap non-glycated plasma and interstitial proteins (LDL)
What happens to peripheral tissues (tissues that do not require insulin for glucose transport i.e. nerves, lenses, kidneys, blood vessels) with persistent hyperglycemia?
increased intracellular glucose --> reduced glutathione production --> increased susceptibility to oxidative stress
In neurons, hyperglycemia causes (blank)
This is a hallmark of DM
Accelerated atherosclerosis involving aorta and large- and medium-sized arteries
This is most common cause of death equally common in diabetic women and men
There is an increased risk in prediabetics
Myocardial infarction due to atherosclerosis of coronary arteries
What types of symptoms would you see when you have macrovascular disease in DM?
gangrene of the lower extremities
hyaline arteriolosclerosis --> HTN
Diffuse thickening of the basement membranes, most evident in the capillaries
Diabetic capillaries are more leaky than normal to plasma proteins
Underlies development of diabetic nephropathy, retinopathy and some forms of neuropathy
(blank) secondary to microvascular disease is 2nd most common cause of death in DM
So what are the top two leading causes of death in diabetic patients?
1. MI due to atherosclerosis of coronary arteries
2. renal failure
What type of vascular problems do you see in the kidneys of diabetic patients?
glomerular lesions - capillary basement membrane thickening
You will see these histologically in the glomerulus of diabetic patients
What happens to the eyeballs in DM?
What happens to the mouth in DM?
dental caries --> due to diet & decreased salivary flow
oral mucosal diseases --> lichen planus, aphthous stomatitis
oral infections --> candidiasis
gingivitis & periodontal disease
taste & other neurosensory disorders
Recap the longterm complications of DM
microangiopathy, cerebral vascular infarcts
retinopathy, cataracts, glaucoma
peripheral vascular atherosclerosis --> gangrene
What are the dominant clinical features of type 1 DM?
occurs in the young
polyuria, polydipsia, polyphagia, ketoacidosis
What are the dominant clinical features of type 2 DM?
ketoacidosis is infrequent
How is the diagnosis of type 2 diabetes usu made?
after routine blood or urine testing in an asymptomatic patient
Why don't you usu see ketoacidosis in type 2 DM?
higher portal vein insulin levels prevents unchecked fatty acid oxidation, keeps formation of ketone bodies in check
This occurs in type 2 diabetics when they are severely dehydrated from hyperglycemic polyuria, and they are not compensating
Do not experience nausea, vomiting, resp symptoms that occur in ketoacidosis though
hyperosmotic nonketotic coma
Finally, compare type 1 to type 2 diabetes...everything you know...
type 1: young patient, not obese, absolute lack of insulin, autoantibodies, HLA linkage, ketoacidosis, insulitis, beta cell depletion, islet atrophy
type 2: adults, obese, relative lack of insulin, no autoantibodies, no HLA linkage, nonketotic hyperosmolar coma (usu not DKA), amyloid deposition within islets
Most common of the pancreatic endocrine neoplasms
May produce enough insulin to cause clinical hypoglycemia
Most common of pancreatic endocrine neoplasms
May produce enough insulin to cause clinical hypoglycemia
insulinoma (neoplastic proliferation of beta cells)
What differentiates hypoglycemia caused by an insulinoma from exogenous insulin injection?
with an insulinoma, you will get elevation in both insulin & C peptide levels
If exogenous insulin, no C peptide
**proinsulin is cleaved into insulin & C-peptide