daibetes

Question 1

where is the pancreas located?

what kind of gland is it?

Answer 1

mixed endocrine and exocrine gland
retroperitoneal between duodenum and spleen,
anterior to aorta and inferior vena cava
(its hard to surgically remove bc of its close proximity to important things)

Question 2

what are the islets of langerhans?

what are the types? what are their hormone products?

Answer 2

functional units of the pancreas that secrete hormones directly into the blood
alpha cells: glucagon (15?20% islet cell population, located along periphery of islet)
beta cells: insulin (60?70% of total iselt cell pop? located throughout islet)
D cells: somatostatin (sparsely distributed throughout islet)
enterochromaffin cells: serotonin
epsilon cells: grehlin

Question 3

differences between type 1 and type 2 DM:
age?
onset?
pathology?
insulin level?

Answer 3

type 1: onset before age 20, abrupt onset, often with ketoacidosis, autoimmune, beta cell mass becomes markedly reduced, ciruculating insulin level is reduce

type 2: onset usu after age 20, gradual, asymptomatic onset, multifactorial cause (genetics), beta cell mass normal or slightly reduced, circulating insulin level can be normal or elevated (due to resistance)

Question 4

diabetes type 1 path

Answer 4

inulitis: lymphocytic infiltrate in and aorund islets of langerhans
disease manifests when 90% of beta cells are lost
islet fibrosis is seen late in disease

Question 5

path of type 2 DM

Answer 5

islet amyloid deposition (composed of amylin)

but amyloid depo can also be seen in older invididuals without clinical evidence of DM

beta cell mass is normal/slightly reduced
islet fibrosis

Question 6

what do pancreatic endocrine tumors arise from?

what types of tumors do not metastasize?

Answer 6

arise from pluripotent cells in the pancreatic ducts

insulinomas dot not metastasize, but other functioning tumors usually behave in aggressive manner

Question 7

MEN1?? what is involved

Answer 7

parathyroid glands
pituitary gland
endocrine pancreas
loss of men 1 tumor suppressor gene

Question 8

distinguish between a microadenoma and a pancreatic endocrine tumor

Answer 8

microadenoma: less than 0.5 cm in diameter, benign, found incidentally

pancreatic endocrine tumor: 0.5 cm and greater, often found in body or tail of pancreas
(ADENOCARCINOMAS are likely found in pancreatic head)
usually well circumscribed
occasionally show gross evidence of invasion/mets

Question 9

which pattern is characteristic of neuroendocrine differentiation?
what can confirm it?

Answer 9

salt and pepper chromatin pattern by H&E stain, can be confirmed by immunohistochemical stains

Question 10

what is required for a dx of malignant pancreatic endocrine tumor?

Answer 10

direct invasion into peripancreatic tissues or presence of metastatic disease

Question 11

insulinoma

tx?

Answer 11

most common functioning pancreatic endocrine tumor
can induce severe hypoglycemia (bc secretion of insulin not regulated by blood glucose level)
most are not aggressive, usually 3 cm or less in diameter

10% malignant, 10% multiple, can occur w/MEN1
SURGERY is tx of choice?? pre op imaging can be hard (CT+ transabdominal)
medical therapy: diazoxide?? inhibits insulin secreiton, opens the ATP sensitive K channel in beta cell
or somatostatin (octreotide), small frequent meals

Question 12

gastrinoma

what are the 3 parts of the zollinger?ellison syndrome?

Answer 12

second most common functioning pancreatic endo tumor
gastrin secreting cells?? not typically found in islets
induce gastric acid secretion

3 parts of ZE: intractible gastric hypersecretion, severe peptic ulceration of duodenum and jejunum, high blood gastrin levels

most are malignant!

Question 13

glucagonoma

symptoms?

Answer 13

assoc w/ mild diabetes
necrolytic migratory erythema (rash with blisters), anemia, venous thrombosis, severe infections
most are malignant, often large, invade surrounding structures

Question 14

somatostatinoma
what is it associated with?
malignant or benign?

Answer 14

rare
assoc w/ mild diabetes, gallstones, steatorrhea, hypochlorhydia
most are malignant

Question 15

VIPoma

what are symptoms?

Answer 15

explosive and profuse watery diarrhea
hypokalemia, hypochlorydia
usually large tumors, malignant

Question 16

which hormones counteract hypoglycemia?

which hormones counteract hyperglycemia?

Answer 16

inc glucagon, epinephrine, GH, cortisol

insulin combats hyperglycemia

Question 17

what level do you get autonomic symptoms?

neuro symptoms

Answer 17

autonomic: BG<55
diaphoretic, shaky/tremulous, palpitaitons, anxious, tingling/paresthesia, hungry

neuroglycopenic: weak, tired, diff concentrating, faint, dizzy, difficulty speaking, altered mental status, blurred vision, coma, seizure

Question 18

what is the whipples tirad of hypoglycemia?

Answer 18

symptoms of hypoglycemia
confirmed lab measurement of hypoglycem
resolution of symptoms with admin of glucose

Question 19

what is the ddx of fasting hypoglycemia in neonates/children when insulin is low

Answer 19

inborn erros of metabolis (FA oxidation disorders, glycogen storage disease, galactosemia)
hormonal deficiency (GH, cortisol)
prematurity: low AA stores
drugs (salicylates)
sepsis, severe illness

Question 20

what is the ddx of fasting hypoglycemia in neonates/children when insulin is high

Answer 20

maternal diabetes
congenital hyperinsulinism (mutation in K?ATPase or sulfonylurea receptor gene
inuslinoma
drugs (surreptitious ingestion of insulin)

Question 21

what is the ddx of fasting hypoglycemia in adults when insulin is high

Answer 21

drugs (insulin, sulfonylurea), insulinoma, autoimmune (rare? insulin AB or insulin receptor AB)

Question 22

what is the ddx of fasting hypoglycemia in adults when insulin is low

Answer 22

drugs (alcohol, quinine, salicylates, pentamidine)
hormonal deficiency (cortisol, GH)
critical illness (liver failure, renal failure, sepsis)
non?islet cell tumors?? can secrete IGF?2

Question 23

what are issues with collection when measuring glucose levels?

Answer 23

glucose decreases rapidly in whole blood
greater fall with leukocytosis
will continue without cryopreservation

you can also have pharmacy dispensation errors
factitious hypoglycemia

Question 24

what labs do you check while someone is hypoglycemic?

screening labs?

Answer 24

glucose, insulin, C peptide, sulfonylurea screen

otherwise: glucose, insulin, cortisol, TSH, IGF?1, creatinine, LFT, CBC

Question 25

what is the goal of fasting hypoglycemia?

Answer 25

demonstrate whipples triad
asses role of insulin in genesis of hypoglycemia
72 hours is gold standard

Question 26

how do you distinguish insulinoma from surreptitious insulin?

Answer 26

insulinoma: insulin is high, C peptide is high, sulfonylurea screen is negative

exogenous insulin: insulin is very high, c peptide (which is cleaved with insulin from proinsulin) is low, sulfonylurea is negative

sulfonylurea induced: insulin is high, c peptide is high, screen is positive

Question 27

postprandial hypoglycemia

3 causes

Answer 27

1. postgastrectomy (rapid gastric emptying and influx of CHO to intestine stimulates overproduction of incretins and hyperinsulinemia
   typically occurs 2 hrs after meals
   tx w/ small frequent meals w/ avoidance of concentrated CHO
   meds (acarbose) that delay CHO absorption may be helpful
2. early type 2 diabetes: dleayed but exaggerated response in early diabetes?? typically 4?5 hrs after a meal
   same tx as above
3. idiopathic posprandial symdrome: common, ill defined, no identifiable cause, dietary tx or meds can be beneficial (poor correlation between symptoms and plasma glucose)

Question 28

what is hbA1c?

where can error come from?

Answer 28

function of of glucose concentration surrounding RBCs
average life of RBC is 120 days
correlates with blood glucose over previous 8?12 weeks
change of 1% reflects change of 35 mg/dL average blood glucose
(can be error with decresaed RBC survival or increased or Hb variants)

Question 29

what is fructosamine?

Answer 29

glycated albumin (half life of albumin is 20 days)