pancreas disorders Flashcards
digestive functions of the pancreas
produce digestive enzymes
hormonal functions of the pancreas
islets of langerhans produce insulin that controls blood sugar levels
what is the endocrine pancreas made of
islets of langerhans
what is the exoocrine pancreas made of
acini cells
what do acini cells do
secrete pancreatic juice in the duodenum through pancreatic ducts
what is pancreatic juice important for
digestion absorption; pancreatic insufficiency and fatty stools
what does dysfunction of the pancreas cause
DM
what is islets of langerhan cells produce
insulin
4 parts of pancreas?
head, neck, body, tail
where is the ucinate process/curvature of the duodenum located?
head of pancreas
what is the exocrine pancreas drained by?
duct of wirsung
tell me about the duct of wirsung
main pancreatic duct that runs the length of the gland and is 3-4mm in diameter
where does the main pancreatic duct enter the duodenum
duodenal papilla
where does the main pancreatic duct end?
ampulla of vater
what does the sphincter of oddi surround
common bile duct and main pancreatic duct
what 2 ducts join together to form a common channel before ending at the ampulla of vater
main pancreatic duct and common bile duct
what is the duct of santorini?
separate accessory pancreatic duct pany ppl have
what are acinar cells
pyramidal epithelial cells arranged in rows; their apexes join to form the lumen of the acinus
where are zymogen granules found? what are they?
acinar cells; inactive enzymes
how are zymogens released
exocytosis from apexes of the acinar cells into the lumen
when are there more zymogen granules in the acinar cells? less?
more: fasting
less: after a meal
what enzymes are secreted by the acinar cells in their active form?
lipase, amylase, deoxyribonuclease, ribinuclease
what enzymes are secreted by the acinar cells as zymogens?
trypsinogen, chymotrypsin, prolastase, procarboxypeptidase, phospholipase 2A
where are zymogens activated?
lumen of proximal intestine
what does activation of zymogens in acinar cells lead to
acute pancreatitis and pancreatic autodigestion
what happens when pancreatic juice enters the duodenum
trypsinogen is converted to trypsin
what facilitates the conversion of trypsinogen to trypsin? where is this found?
enteropeptidase/ enterokinase; on intestinal brush border
why is trypsin important?
converts remaining zymogens to active enzymes (like a cascade)
if trypsinogen is activated in the pancreas, what are the two protective mechanisms?
pancreatic secretory trypsin inhibitor (PSTI) and trypsin autolysis
acute pancreatitis is a clinical syndrome resulting from what?
acute inflammation and autodigestion of pancreas and peripancreatic tissues
what are the clinical manifestations of acute pancreatitis?
acute upper abdominal pain, nausea, vomiting, fever
what are the 2 most common causes of acute pancreatitis?
biliary tract disease and alcohol trauma
what is common in all cases of acute pancreatitis?
activated proteolytic enzymes escape from ducts which cause local tissue injury, inflammation, necrosis, and infection in some cases
when does alcohol induced pancreatitis occur?
after a heavy episode of drinking
what is the mechanism of alcohol induced pancreatitis?
unclear how alcohol damages the gland
what is the metabolite of alcohol
acetaldehyde
what disease may have a direct toxic effect on the pancreatic acinar cells
alcohol induced pancreatitis
what may alcohol induced pancreatitis lead do?
intracellular trypsin activation and inflammation of the sphincter of oddi
what disease is associated with deficiences in zinc or selenium
alcohol induced pancreatitis and chronic pancreatitis
what occurs in biliary tract disease
gallstones or biliary sludges become lodged at ampulla of vater
what do gallstones or biliary sludges becomming lodged at ampulla of vater cause
obstruction of common bile duct and main pancreatic duct
is biliary tract disease more common in men or women? what about gallstones?
both women
key pathologic finding in acute pancreatitis?
fat necrosis
what is chronic pancreatitis?
relapsing disorder with severe abdominal pain, exocrine or endocrine pancreatic insufficiency, duct abnormalities, pancreatic calcifications
what is the major cause of chronic pancreatitis?
chronic alcoholism
what do deficiencies in zinc and selenium inhibit in chronic pancreatitis
quenching of O2 free radicals
what can long term obstruction of the pancreatic duct cause
chronic pancreatitis
what is the key panthological finding in chronic and acute pancreatitis
peripancreatic and intrapancreatic fat necrosis
what is chronic pancreatitis characterized by?
scarring and shrinkage of the pancreas
what does scarring and shrinkage of the pancreas result from
fibrosis, atrophy of acini, and stenosis/dilation of ductules
what part of the pancreas is involved in chronic pancreatitis?
usually the whole gland, but it’s localized to the head and body in 1/3 of cases
what are ductules and ducts often filled with in chronic pancreatitis?
calculi (ductal stones)
why is the pancreas hard in chronic pancreatitis?
sclerosis and calcification
why might someone need a biopsy of the pancreas
differentiate chronic pancreatitis from pancreatic carcinoma
what does chronic pancreatitis look like microscopically?
loss of acini, dilation of ductules, fibrosis, lymphocytes
what is preserved in chronic pancreatitis?
islets of langerhans
what are the clinical manifestations of chronic pancreatitis?
maldigestion and impaired fat digestion
what enzyme is essential for fat digestion
pancreatic lipase
what can absence of pancreatic lipase lead to?
steatorrhea which is a greasy, bulky, lightly colored stool
why do ppl with pancreatic insufficiency rarely present with carb and protein maldigestion?
other enzymes in gastric and intestinal juice compensate for loss of amylase and trypsin
what is pancreatic insufficiency?
syndrome of maldigestion which results from disorders interfering with effective pancreatic enzyme activity
where are islets of langerhan located?
embedded in pancreatic exocrine tissues
are islets of langerhan cells vascularized
yes
what are the 4 major islet cell types
beta, alpha, delta, and PP
what is the predominant cell in the islet
beta
what do beta islet cells secrete?
insulin
what are alpha islet cells?
glucagon secreting cells
what are delta islet cells?
somatostatin secreting cells
what are PP islet cells?
pancreatic polyeptide secreting cells
where are PP cells located?
posterior lobe of the head of the pancreas
more the 70% of the insulin secreting cells must be lost/damaged before dysfunction occurs in what?
endocrine pancreas
what supplies each islet with nutrients
one major arteriole
where does blood from the islets drain into?
hepatic portal vein
what is the major site of action of glucagon and insulin
liver
what are islets innervated directly by?
parasympathetic and sympathetic NS
what are islets innervated indirectly by?
stimulation of catecholamine release by the adrenal medulla
what plays a key role in glucose homeostasis during stress
catecholamine release by the adrenal medulla
circulator half life of insulin?
3-5 min
where is insulin catabolized
liver and kidney
what is the most potent stimulator of insulin
glucose
what is glucose enhanced by?
several enteric proteins such as glucagon like peptide 1 (GLP-1)
what is glucose inhibited by?
catecholamines and somatostatins
what is the mechanism of insulin?
it exerts its effects by binding to insulin receptors on the surface of target cells
what are the target cells of insulin
liver, muscle, fat and ovaries
what is the role of insulin in metabolism
fuel homeostasis, promote fuel storage, promote formation of precursors for fatty acid synthesis, stimulate lipogenesis, inhibit hepatic glucose output
what is anabolism
fuel storage
catabolism?
breakdown and release of fuel
how does insulin promote fuel storage in liver?
stimulating glycogen synthesis and storage
how does insulin promote formation of precursors for fatty acid synthesis?
stimulating glycolysis
how does insulin stimulate lipogenesis?
VLDL synthesis is increased
how does insulin inhibit hepatic glucose output?
inhiting gluconeogenesis and glycogenolysis
what inhibits fatty acid oxidation and production of ketone bodies
insulin
where are ketones made
liver
where and when are ketones used as fuel
in the brain when glucose isnt available
what s DM
heterogeneous disorder defined by presence of hyperglycemia
what can hyperglycemia be due to
dec in insulin secretion by pancreatic cells, dec response to insulin by target tissues, or increase in counterregulatory hormones that oppose effects of insulin
what was formerly known asIDDM and juvelile diabetes
DM type 1
what is DM type 1 characterized by
autoimmune destruction of pancreatic islet cells that results in severe insulin deficiency
why does DM type 1 mainly affect
ppl younger than 30
where is there a bimodal incidence peak in DM type 1
5-7 y/o and puberty
who is DM type 1 more common in
males
what do patients with DM type 1 present with
polyuria, polydipsia, and weight loss with high serum glucose levels
what is diabetic ketoacidosis
when ketone bodies are increased because of lack of insulin in DM type 1
is DM type 1 autoimmune
yes
what isDM type 1 caused by
destruction of pancreatic beta cells which makes autoreactive T lymphocytes
what is the early disease of DM type 1 marked by
lymphocytic infiltrates
what surrounds the necrotic beta cells in DM type 1
CD4 T cells and cytotoxic CD8 T cells
what is an important diagnostic criteria of DM type 1 ?
autoantibodies are present but are not responsible for destruction
50% of newly diagnosed DM type 1 patients have increased…
islet cell autoantibodies (ICA) and insulin autoantibody (IAA)
can screening be used to identify majority of DM type 1 ppl?
no
what alleles have the strongest influence for DM type 1 risk?
class II HLA-DR and HLA-DQ loci
what environmental factors may lead to DM type 1 ?
viral infections such as exposure to rubella
molecular mimicry is associated with the etiology of what disease
DM type 1
who does DM type 2 occur most commonly in
adults, native americans, mexican americans, and african americans
is there a stronger genetic component for DM type 1 or 2
2
this disorder is associated with an increased resistance to the effects of insulin at its sites of action and decreased insulin secretion by the pancreas
DM type 2
what can ameliorate or even terminate DM type 2
weight loss in obese or overweight ppl
what 2 metabolic defects are responsible for hyperglycemia in DM type 2
- target tissue resistance to insulin
2. inadequate pancreatic cell insulin secretion
can a genetic test identify ppl at risk for type 2 diabetes
no
what is the debate about in DM type 2
whether the primary lesion is insulin resistance or defective cell insulin secretion
what is a key factor in the link btwn obesity and DM type 2
insulin resistance
what is the primary source of mediators of insulin resistance
central/abdomoinal adiposity
how does central/abdomoinal adiposity increase insulin resistance
lipotoxicity, adipokines, and hormones
what are adipokines
dysregulated secretion of cytokines made in fat tissue
what are the toxic effects of excess free fatty acids
dec skeletal muscle insulin sensitivity
what does leptin do
controls satiety and enhances insulin sensitivity
do most ppl with type 2 DM develop diabetes
no
what kinda of disorders is DM a secondary disease?
pancreatitis, cushings syndrome, genetic beta cell defects, drugs like HIV protease inhibitors
who does gestational DM occur in?
pregnant women in their 2nd or 3rd trimester
what is gestational DM caused by
increasing levels of the hormones progesterone, cortisol, and prolactin
how is gestational DM diagnosed
oral glucose tests
when is gestational DM resolved
parturition, but 50% of these ppl develop type 2 DM later in life
