Pancreas-Usera Flashcards
THe endocrine pancrease is made up of a million clusters of cells called the (blank)
islets of langerhans
What are the four main cells types of the islets of langerhans?
- β: secretes insulin
- α: secretes glucagon
- δ: secretes somatostatin
- PP: secretes pancreatic polypeptide
What are the 2 minor cell types of the islets of langerhans?
- D1: secrete VIP (slows muscle contraction)
* Enterochromaffin cells: secrete serotonin
What does glucagon look like?
alpha granules-round, dense, with a thin halo
What does insulin look like?
beta granules-crystalline core with a wide halo
What does somatostatin look like?
delta granules-round, less dense core with a thin halo (somastostatin)
What does pp look like?
small, hyperdense cores
What is diabetes mellitus?
- dysfunction or loss of pancreatic B-cells
- decreased secretion of insulin
What is a pancreatic endocrine tumor?
abnormal proliferation of pancreatic islet cells
Diabetes mellitus (DM) is not a single disease entity, but rather a (blank) of metabolic disorders sharing the common underlying feature of hyperglycemia
group
DM results from defects in (Blank)
insulin secretion or insulin action OR more commonly both
Chronic hyperglycemia and associated metbaolic dysregulation may be associated with secondary organ damage, especially in the (Blank x 4)
kidneys
eyes
nerves
blood vessels
DM affects greater than (blank) million children and adults
20
App. (blank) million cases of DM are diagnoses each year
1.5
DM is the leading cause of (blank), adult onset (blank) and non-traumatic lower extremity amputation
end-stage renal disease
adult onset blidness
(blank) million adults are pre-diabetic (elevated blood sugar not meeting criteria for diagonsis of DM
54
For individuals born in the US, the estimated lifetime risk of being diagnosed with diabetes mellitus is (blank) in males and (blank) in females
1/5
2/5
DM is 2 to 5 times higher in the (blank X) population as compared to non-hispanic whites
AA, hispanic, native americans
It is one of the most common noncommunicable disease?
DM (number of affected individual is expected to double)
How can you make the diagnosis of DM?
Random blood glucose> 200 mg/dL with classical signs and symptoms
Fasting blood glucose>126 mg/dL
Abnormal glucose tolerance test w/ blood glucose > 200 mg/dL after a standard carb load
What is normal blood sugar?
less than 100 mg/dL fasting
less than 140 mg/dL for a glucose tolerance test
What is prediabetic blood sugar?
greater than 100 but less than 126 mg/dL fasting
greater than 140 and less than 200 mg/dL glucose tolerance test
What is type 1 DM?
- absolute deficiency of insulin caused by an autoimmune destruction of B cell mass
- T-lymphocytes mount an immune response against pancreatic B cell antigens
What is type 2 DM?
-peripheral resistance to insulin action
-relative insulin deficiency (inadequate secretion by pancreatic B cells)
Accounts for 90-95% of
-most are overweight -but its not necessary
(blank) locus on 6P21; contributes over 50% of the genetic susceptibility for type I diabetes
HLA
90-95% of whites with DM type I have either (blank or blank) haplotypes
HLA-DR3 or HLA-DR4
What are the non-HLA genes that can have mutations and cause Type I diabetes?
- insulin (VNTR)
- CTLA4 (cytotoxic T lymphocyte antigen 4)
- PTPN22 (protein tyrosine phosphatase)
- CD25 (decreases activity of IL2R)
Viral infections can cause type I DM, what infections can cause this?
How?
- Mumps, rubella, coxsackie B, CMV, and others
- viral infection induces islet cell injury/inflammation
- molecular mimicry
- precipitating virus
How does a viral infection induce islet cell injury/inflammation?
leading to exposure of self B cell antigens and activation of autoreactive T-cells
How does molecular mimicry cause type I DM?
viral proteins mimic B cell antigens and the immune response cross reacts
How does a precipitating virus cause type I DM?
viral infection early in life could persist in tissue; subsequent infection with a similar virus could elicit an immune response against infected islet cells
What is this: Slow progressive destruction of islet cells prior to any signs or symptoms Greate than (blank)% of the B cells have been destroyed before hyperglycemia and ketosis occur
Type 1 diabetes
90%
What is the fundamental immune abnormality in type 1 diabetes?
failure of tolerance to self
NOTE: autoantibodies to islet cells are present in patients and their family members.
What is the pathogenesis of type 2 DM?
-environmental factos:
sedentary lifestyle, diet, obesity
-Genetic factors
What are the genetic factors that contribute to type 2 DM?
- 35-60% concordance in monozygotic twins
- risk more than doubled if both parents affected
- strongest association to TCF7L2 (10q)
- not linked to HLA genes
What are the 2 metabolic defects of type 2 diabetes
- Insulin resistance
- B cell dysfunction (relative insulin deficiency)
What is insulin resistance?
decreased ability of peropheral tissues to respond to insulin
What is b-cell dysfunction (relative insulin deficiency)?
inadequate insuline secretion in the face of hyperglycemia
In type 2 diabetes, usually (blank) is the primary event and predates hyperglycemia, followed by increasing degrees of b-cell dysfunction
insulin resistance
What is the normal function of insulin on adipose tissue?
increased glucose uptake
increased lipogenesis
decreased lipolysis
what is the normal function of insulin on striated muscle?
increased glucose uptake
increased glycogen synthesis
increased protein synthesis
What is the normal function of insulin on liver?
decreased gluconeogensis
increased glycogen synthesis
increased lipogenesis
Visceral obesity is present in (blank) percent of diabetic patients. Insulin resistance is present in obesity unaccompanied by hyperglyemia
80%
What is this:
failure of target tissues to respond normally to insulin
insulin resistance
In states of insulin resistance, insulin secretion is initially higher for each level of (blank)
glucose
When (blank) compensation becomes inadequate, diabetes develops
B cell
What can cause B cell compensation to become inadequate?
- intrinisc predisposition
- TCF7L2 allelic variants associated with reduced insulin secretion
- Amyloid replacement of islet cells
Diabetes genes, adipokines, inflammation, hyperglycemia, FFAs all cause (blank)
b cell dysfunction and insulin resistance
Obesity will lead to adipocytes secreting.. (blank X 3). This will result in (blank)
adipokines, FFAs and inflammation
-insulin resistance
What is persistant hyperglycemia?
glucotoxicity
What is the best assessment of glycemic control?
HGBA1C (glycosylated hemoglobin)
What is this:
• Formed by nonenzymatic covalent addition of glucose moities to hemoglobin in RBCs
• Provides a measure of glycemic control over the lifespan of a RBC (120 days)
HGBA1C
A non-diabetic patient has a HGBA1C of less than (blank)
6.5%
What is this:
form when non-enzymatic reaxns occur b/w glucose and the amino groups of intra and extracellular proteins
The rate of age formation is accelerated in (blank)
Advanced Glycosylation End (AGE) products
Hyperglycemia
AGES can directly cross-link to extracellular matrix proteins and cause….?
decreases vascular elasticity
enhances protein deposition
entrap non-glycated plasma and interstitial proteins (LDL)
Tissues that do not require insulin for glucose transport are most affected by (blank)
hyperglycemia
Increased intracellular glucose-> reduced (blank) production-> increased susceptibility to (blank)
glutathione
oxidative stress
In neurons, hyperglycemia causes (blank)
diabetic neuropathy (glucose neurotoxicity)
In DM, accelearted atherosclerosis involving (blank) and (blank) arteries, (blank) of the lower extremities, (blank) arteriosclerosis associatd with HTN
aorta and large-medium sized arteries
gangrene
hyaline
What is the most common cause of death in diabetic patients?
myocardial infarctions due to atherosclerosis of coronary arteries (equally common in diabetic women and men, increased ris of prediabetics)
What is this:
diffuse thickening of the BM, most evident in the capillaries
Diabetic microangiopathy
Diabetic capillaries are more leakly than normal to (Blank)
plasma proteins
What underlies development of diabetic nephropathy, retinopathy, and some forms of neuropathy?
diabetic microangiopathy (diffuse thickening of BM)
Renal failures is the (blank) most common cause of death in DM
2nd
What are these found in:
glomerular lesions
renal vascular lesions (primarily arteriolosclerosis)
Diabetic nephropathy
What are glomerular lesions?
Where do you find glomerular lesions? Where do you find diffuse mesangiosclerosis?
capillary BM thickening-> widespread thickening of glomerular capillary basement membrane
- Present in all cases of diabetic nephropathy
- nephrotic syndrome
If you have nodular diabetic glomerulosclerosis what can you see histologically?
kimmelsteil-wilson nodules
What are the 2 stages of diabetic retinopathy?
proliferative and non proliferative
What are the oral manifestations of DM?
Dental caries (diet, decreased salivary flow)
Salivary dysfunction (Xerostomia)
Oral mucosal diseases (lichen planus, apithous stomatitis)
Gingivitis and periodontal disease
Taste and othe rneurosensory disorders
Candidiasis and periodontal disease are common in (blanK)
Diabetes mellitus
What are the long term complications of DM?
- microangiopathy, cerebrovascular infarcts, hemorrhage
- retinopathy, cataracts, glaucoma
- HTN
- MI
- Islet cell loss (type 1 (insulitis) type 2 (amyloid)
- atherosclerosis
- nephrosclerosis (glomerulosclerosis, arteriosclerosis, pyelonephritis)
- peripheral neuropathy
- autonomic neuropathy
- gangrene
- infections
- peripheral vascular atherosclerosis
What are the clinical features of Type 1 DM?
- occurs in the young
- polyuria, polydipsia, polyphagia and ketoacidosis are the dominant clinical features.
Since insulin is a major anabolic hormone, insulin deficiency results in a catabolic state affecting (blank X 3). What happens to glucose protein and fat?
glucose, protein and fat metabolism
increased blood glucose
muscle breakdown-> protein breakdown
Increased lipolysis
What are the clinical features of type 2 DM?
patients are older (>40 ) and obese
-diagnosis is usually made after routine blood or urine testing in an asymptomatic patient
Ketoacidosis is infrequent in type 2 DM because in type 2 you have (blank) levels that prevents unchecked (blank) and keeps formation of (blank) in check.
higher portal vein insulin
FA oxidation
ketone bodies
Ketoacidosis is infrequent in type 2 DM because in type 2 you have (blank) levels that prevents unchecked (blank) and keeps formation of (blank) in check.
higher portal vein insulin
FA oxidation
ketone bodies
Type 1 DM patients get (blank) comas
TYpe 2 DM patients get (blank) comas
DKA
hyperosmotic nonketotic coma
Hyperosmotic nonketotic coma develops in type 2 DM because you get dehydrated from (blank)
hyperglycemic polyuria
In type 2 DM does N/V and respiratory symptoms occur?
NO, this happens in type 1 pnts because it occurs with ketoacidosis
What is this:
- a young patient
- not obese
- absolute lack of insulin
- autoantibodies HLA linkage
- Ketotic hyperosmolar coma DKA
- insulitis, B-cell depletion, islet atrophy
Type I diabetes
What is this:
- adults (usually > 40 yrs)
- obese
- relative lack of insulin
- no autoantibodies
- no HLA linkage
- Usually not DKA
- amyloid deposition within islets
Type 2 DM
What are the major signs of hypoglycemia?
disorientation, confusion
What are the most common causes of pancreatic endocrine neoplasms?
neoplastic proliferation of B cells (insulinomas)
Pancreatic endocrin neoplasms may produce enough insulin to cause (blank0
clinical hypoglycemia
Patients with an insulinoma have increased levels of (blank and blank) which differentiates this cause of acute hypoglycemia from exogenous injection of insulin
c-reactive peptide and insulin
What are rare pancreatic endocrine neoplasms?
alpha-cell tumors (glucagonomas)
delta-cell tumors (somatostatinomas)
vipoma
What does a Pancreatic Endocrine Neoplasm Islet cell tumor look like histologically?
salt and pepper chromatin
eosophilic
-vomit lesions
