GI 4 - Accessory GI Organs- Pancreas, Liver and Gall Bladder Flashcards
more than ____% of the pancreas is exocrine
90
what cells make up the exocrine pancreas
-acinar cells
- duct cells
what do acinar cells do
-synthesize and secrete hydrolases for digestion
-necessary for luminal digestion of carbohydrate, protein and fat
what do duct cells do
-secrete bicarbonate and water
-neutralizes gastric H+ by secreting HCO3- into the duodenum up to 145 mEq/L so acinar cells can function
what does impaired function of acinar cells result in
maldigestion and malabsorption
why doesnt the pancreas digest itself
proteolytic enzymes synthesized, stored and secreted as inactive precursors
what are proteolytic enzymes activated in the intestinal lumen by
enterokinase and trypsin
when is trypsin inhibitor secreted and what does it do
synthesized, stored and secreted with precursors
- prevents activation of trypsin while still in pancreas
what are the two stimuli for acini cell enzyme secretion
-CCK
- AcH/GRP (vagovagal reflex)
what are the effects of CCK
- gallbladder -> contraction
- pancreas -> acinar secretion
- stomach -> stimulates receptive relaxation, reduces emptying, reduce HCl secretion
- sphincter of Oddi -> relaxation
- all of these result in protein, carbohydrate, lipid absorption and digestion. And matching of nutrient delivery to digestive and absorptive capacity
what releases CCK
I cells
what are the two stimuli for I cells
- monitor peptide released by the pancreas
- CCK-RP stimulated by protein and amino acids in the lumen
what inhibits CCK release and how
trypsin by inhibiting CCK-RP and monitor peptides
what are the two stimuli for ductal cell secretion of H2O and HCO3-
-secretin
- Ach (M3 receptor) through vasovagal reflex
what is the mechanism of ductal cell secretion and where is the negative feedback occurring
- increased acid from stomach -> increased secretin secretion -> increased plasma secretin -> increased bicarbonate secretin from ductal cells in pancreas
-> increased flow of bicarbonate into small intestine -> neutralization of intestinal acid - negative feedback on secretin secretion
what does secretin directly result in
- increased cAMP
- phosphorylation of CFTR
- Cl- conductance
- HCO3- secretion
what is the mechanism in the pancreatic duct cell for secretion of bicarbonate
- H+ is returned to the blood and Na+ is pumped into the cell via the H+ Na+ active antiporter
- HCO3- is moved into the cell actively through the Na+ HCO3- symporter
- HCO3- is moved across the apical membrane in exchange for Cl-
- Cl- diffuses out the apical membrane into the lumen
- Na+ and water follows
when is secretin released
when pH is less than 4.5
when is secretin release maximal and what does further release depend on
below ph of 3. further release depends on area of small intestine affected
what is the maximal bicarbonate response
30 mEq/hour
during a meal pH is rarely below ____
3.5 or 4
what is the relationship between secretin release and HCO3 release
secretin release shows HCO3- release
what are the 3 phases of pancreatic secretion and what percentage accounts for secretion in each phase
- cephalic - 20%
- gastric- 5-10%
-intestinal - 70-80%
what are the cephalic and gastric phases of pancreatic secretion mediated by
vagovagal reflex - low volume, high enzyme secretion such as Ach and GRP
what is secreted in the intestinal phase of pancreatic secretion in response to acid? fat/protein?
-acid: secretin -> HCO3- and water
- fat/protein -> CCK -> enzymes
what is secretion rate proportional to
[secretin], [Ach], and [CCK]
what are the levels of bicarbonate and chloride at low secretion rates
-bicarbonate: low
- chloride: high
what are the levels of bicarbonate and chloride at high secretion rates
- bicarbonate: high
- chloride: low
what are the levels of sodium and potassium concentrations in response to varying secretion rates
they remain the same as the plasma
pancreatic juice is always ____
isotonic
describe what happens in cystic fibrosis
- abnormal sweat composition
- decreased pulmonary and pancreatic secretion
- mendelian autosomal recessive occurrence - single AA substitution
- defective CTFR: sweat Cl- reabsorption, pancreatic duct cell function, pulmonary mucus clearance
what are the types of pancreatitis and what happens
-acute and chronic
- trypsin activation causes pain and inflammation
- chronic disease destroys acini
- consequences reflect decreased digestive enzyme production
what can cause pancreatic duct obstruction
gallstones and tumors
what is the effects on absorption without pancreatic enzymes
- 60% of fat not absorbed- steatorrhea
- 30-40% protein and carbohydrates not absorbed
what is the functional unit of the liver
the liver lobule
what is the function of the liver
- cleansing and storage of blood
- metabolism of nutrients
-synthesis of proteins - metabolism of hormones, chemicals
- storage of energy, vitamins, iron
- excretion of lipid soluble waste products
- large capacity for cell regeneration
- secretion of bile
what proteins does the liver make
coagulation factors, plasma proteins, angiotensinogen
how much bile is secreted by the liver per day
600-1000 ml/day
what is the total blood input into the liver and what is percentage of resting CO
1,350mL/min
-27% of resting CO
describe resistance of blood flow in liver
very low
what increases resistance in the liver
cirrhosis and causes portal hypertension
what percentage of lymph production does the liver account for
50%
what does increased vascular resistance cause
ascites
what are the 2 roles of bile
-bile salts (acids) and lecithin required for digestion (emulsification) and absorption (micelles) of dietary fat
- excretion of lipophilic metabolites (bilirubin), excess cholesterol, other waste products, drugs and toxins
what do the body cholesterol pools come from and how much
dietary cholesterol (0.2 g/day) and hepatic and extrahepatic synthesis (0.8-1 g/day)
what is cholesterol excreted as from the liver and how much
bile acids (0.2-0.4 .day)
what do hepatocytes do
secrete bile salts, cholesterol, lecithin, bilirubin and many other lipophilic substances
what do duct epithelial cells do
modify primary secretion and add HCO3-
where is bile stored and concentrated
gallbladder
where is some bile reabsorbed
in the ileum of the small intestine
where do hepatocytes secrete organic components of bile
into bile ducts
what are bile salts produced from
cholesteol
what do bile duct cells secrete
water, Na+ and HCO3-
where is bile transported
-small intestine for fat digestion
- gall bladder for storage
what is the max volume of the gall bladder
30-60 mL
where are electrolytes and water reabsorbed from bile
while in the gall bladder
what substances are reabsorbed from bile
water, Na+, Cl-, and HCO3-
describe what happens in a cholecystectomy
- no problems with fat digestion
- bile flow directly into duodenum
what is the mechanism of bile flow into the duodenum
- fatty acids in the duodenum causes CCK secretion -> increased plasma CCK ->
- gallbladder contraction -> increased bile flow into common bile duct -> increased bile flow into duodenum
- AND relaxation of the sphincter of Oddi -> increased bile flow into duodenum
where is the sphincter of oddi located
- controls opening of pancreas into the small intestine
how does enterohepatic circulation conserve bile salts
-substance secreted into bile by hepatocytes
-delivered to lumen of ileum then reabsorbed
- transported to hepatocytes via sinusoids
- 94% of bile salts recirculated
-bile salts circulate 17x before lost in feces
which is greater in the liver about bile salts: secretion or synthesis
secretion»_space; synthesis
what transporter actively absorbs bile salts and where
-apical sodium dependent bile salt transporter (ASBT) in the ileum and in the renal PT
what are BARI and what does it stand for
- bile acid reabsorption inhibitors
- drugs that inhibit bile recycling
- used to lower LDL levels in the blood
- hepatocyte production of bile increases 6-10x if bile salt recycling reduced
- LDL taken up from blood via hepatocytes as source of cholesterol for bile salts
what are the types of BARI and what doe they do
- bile acid sequestrants: bind to bile salts in intestinal lumen and block transport
- ABST inhibitors: prevents bile salts from recirculating
what are the benefits of BARI
drugs work in intestinal lumen so they dont need to be reabsorbed which reduced harmful side effects
what is low ASBT activity associated with
-chrons disease
-congenital primary bile acid malabsorption
- idiopathic chronic diarrhea
- IBS
what are the disorders of biliary secretion
- hepatocyte dysfunction impairs bilirubin, bile salt secretion
- duct obstruction
- intestinal mucosal defects impair bile salt reabsorption
what causes hepatocyte dysfunction to impair bilirubin and bile salt secretion
-drugs (acetominophen), viral hepatitis, toxins
- fibrosis, cirrhosis
what stimulates and inhibits gastrin and what is its function
- stimulates: amino acids and peptides and distention
- inhibits: H+
- function: increased histamine release (ECL cell), increased H+ secretion (parietal cell), increased gastric emptying, trophic affects on mucosa
what stimulates and inhibits ghrelin and what is its function
stimulates: absence of nutrients
inhibits: stretch
-function: increases hunger
what stimulates secretin and what is its function
-H+
- increases pancreatic and biliary HCO3- secretion
- trophic affects on exocrine pancreas
- decreased gastric acid secretion
- decreased gastric emptying
what stimulates CCK and what is its function
- amino acids and peptides
-fatty acids - indirectly via secretion of CCK-RP and monitor peptide
- increases pancreatic enzyme secretion
- increased gall bladder contraction
- trophic effects on exocrine pancreas
- decreased gastric emptying
- decreased gastric acid secretion
- relaxation of sphincter of oddi
- gastric receptive relaxation
what stimulates GIP and GLP-1 and what is its function
glucose
- increased insulin response to glucose
- decreased gastric acid secretion
- decreased gastric emptying
what stimulates motilin and what is its function
- unknown might be alkaline pH in duodenum
- increases gastric motility (MMC/fasting)
- increases intestinal motility (MMC/fasting)
