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Bile Secretion & Gall Bladder Fxn (Pathway of Bile (portal lobules…
Bile Secretion & Gall Bladder Fxn
Total bile flow
canalicular flow
dependent
depends on [(-) bile salts]
ingestion of supplemental bile acids increased biliary flow by several hundred mL/day
rising; inc. w/ bile secretion
independent
solely on osmotic force
constant
hepatocytes >> canaliculi
ductal flow
constant
mediating factors
inc. secretion (
choloretics
)
secretin
VIP
GRP
glucagon
MOA: inc. cAMP >> apical CFTR & Cl/HCO3 exchanger
dec. secretions or inc. fluid absorption
somatostatin: (-) cAMP
Bile release
CCK
stimulus: FAs in duo
causes contraction of gall bladder & relaxation of sphincter of Oddi
when fat not present in food, gallbladder empties poorly
with significant fat, gallbladder normally empties completely in ~1 hr
ACh
stimulates to a lesser extent than CCK
from both the vagus & intestinal enteric NS
6 Steps
CCK &secretin enter blood stream
bile salts & secretin inc. bile flow
vagal stimulation >> weak contractions of gall bladder
CCK >> strong contraction of gall bladder & relaxation of sphincter of Oddi >> bile enters duo
bile salts reabsorbed into blood stream >>
enterohepatic circulation of bile salts
47% diffuse thru mucosa in early SI
47%
actively
reabsorbed in
terminal ileum
portal v. >> liver >> almost entirely absorbed into hepatocytes from sinusoids on first pass
only 5% lost in stool
salts circulate thru ~17x before exiting in feces
rate of liver bile salt secretion actively controlled by amount in circulation (inc. bile salts >> inc. secretion)
supp. bile salts can inc. bile secretion by several hundred mL/day
acidic fatty chyme in duo >> CCK & secretin release from duodenal wall enteroendocrine cells
Secretin
inc. bile secretion via ductal cells (sometimes 2x for several hrs after meal)
secretin feedback mechanism for neutralizing duo acid (lesser extent)
Bile Contents
bile salts (67%)
composition
biliary bile acids
95% cholic + chenodeoxycholic + deoxycholic acids
5% lithocholic + ursodeoxycholic
fecal bile acids
2' bile acids (2/3 deoxycholic; 1/3 lithocholic)
almost entirely unconjugated d/t bacteria
cholesterol >> cholic acid + chenodeoxycholic acid =
primary bile acids
hepatocytes conjugate most 1' bile acids to glycine & taurine (to lesser extent) >> glyco- & tauroconjugated bile acids
salts of these acids (mainly Na salts) secreted in bile =
bile salts
cholesterol cholelithiasis
(gallstones)
:
cholesterol precipitates
d/t extended high-fat diet >> XS cholesterol
d/t XS H2O &/or bile acid abs.
d/t inflammation of epi or gallbladder (
cholecystitis
)
d/t abnormal bile composition, biliary stasis
bacteria in terminal ileum & colon may dehydroxylate 1' bile acids >> deoxycholic acid & lithocholic acid (toxic) =
secondary bile acids
can also conjugate some 1' & 2' bile acids to sulfate or glucuronate
Bile salts are efficiently recycled in
enterohepatic circulation
.
See Bile release section
protection from toxic bile salts
drawback: mucin associated w/ inc. development of crystal & stone >> cholesterol cholelithiasis
gall bladder epi cells secrete mucus layer
most abundant; ~1/2 total solutes; 6g/day
bilirubin
(0.3%)
breakdown product of heme (RBCs)
gives bile green/yellow/black pigment
abnormally high [bilirubin] in blood >> jaundice
stercobilin gives stool brown pigment
aka bile pigments
phospholipids (22%)
mainly lechithin
enhance bile salts solubilizing of cholesterol
cholesterol (4%)
FAs, enzymes, hormones, electrolytes (Na, K, Ca, Cl, HCO3)
proteins (4.5%)
3 functions
emuslifying/detergent fxn
bile salts emulsify dietary fats >> allow attack by lipases
inc. agitation in GI tract >> break up fat globules
waste product excretion
XS cholesterol
bilirubin (Hgb destruction)
lipophilic drugs, trace minerals, etc.
aid GI tract absorption
of FAs, monoglycerides, cholesterol, and other lipids via micelles
bile salts + lecithin + cholesterol >>
micelles
w/o bile salts: up to 40% of ingested fats not absorbed >> steatorrhea >> metabolic deficit d/t nutrient loss
Bile Secretion
disruption
results:
steatorrhea
severe pain, jaundice, & pruritus (itching)
damage to hepatocytes (liver enzymes in plasma)
dec. lipid dig & abs >> malabsorption of fat-soluble vitamins (A, D, E, K)
cholestasis
:
d/t many acute & chronic liver disease
suppression of bile secretion
obstruction of extrahepatic bile ducts or
impaired flow at hepatocytes or intrahepatic bile ducts
reflux of bile into liver parenchyma >> systemic circulation
450 ml/12 hours; 600-1000ml/day of "hepatic bile"
3 steps
1/2 is diverted to gall bladder (1/2 empties into duo)
actively diverted to the gall bladder between meals by contraction of sphincter of oddi
concentrates (5-20X) & stores bile
MOA: active transport of Na >> H2O, Cl, & other diffusibles follow via secondary active transport
minutes to several hours
max vol = 30-60ml
hepatocyte secretion
contents: bile acids, cholesterol, organic material
into bile canaliculi
actively & continuously secreted
secretory epithelial cells (ductal cells)
contents: watery solution of Na & HCO3
added as bile travels from bile canaliculi >>>> common bile duct
can increase bile volume by 100%
mixture of relatively "dilute" hepatic bile & "conc." gallbladder bile delivered to duo
active & isotonic
Pathway of Bile
portal lobules
(includes all hepatocytes drained by a bile duct)
bile canaliculi
adjacent to
sinusoids
(wide bore capillaries) w/ opposing flow
toward interlobular septa >>
terminal bile ductules
>>
perilobular ducts >> interlobular ducts >> septal ducts >> lobar ducts
R. & L. hepatic ducts
>>
common hepatic duct
common bile duct
(common hepatic & cystic duct join)
hepatopancreatic ampulla
(CBD & pancreatic duct join)>> duo via
sphincter of Oddi
if sphincter contracted, bile diverted via
cystic duct
to gall bladder
cholangitis
: inflammation of biliary ducts
Liver
fxns:
chemical factory
storage
:
glycogen, fat, iron, copper, vitamins
synthesis
:
plasma proteins, albumin, glucose, cholesterol, FAs, lipoproteins, etc.
metabolism
: carbs, proteins, lipids
excretory system
detoxification
:
exogenous (drugs & toxins)
endogenous (steroid & hormones)
inactivation
: macrophage Kupffer cells remove foreign particulate (bacteria, endotoxins, parasites, aging RBCs)
bile production
:
gall bladder stores, concentrates, acidifies, & delivers to duo
elimination of endogenous & exogenous waste
complex secretory product
bile aka gall = bitter, neutral or slightly alkaline fluid
body's major route of cholesterol elimination
inefficient excretion of cholesterol >> inc. serum cholesterol
endocrine & exocrine gland
activation
:
deiodination of thyroxine T4 to triiodothyronine T3
hydorxylation of vitamin D
energy provider to all other organs (via hepatic glycogen >> glucose)
blood supply:
hepatic a.
(25%):
O2-rich blood w/ metabolites for hepatic processing
to sinusoids >> central v. >> hepatic v.
hepatic portal v.
(75%)
deoxy. blood from stomach, GI tract, pancreas, & spleen
processing & storage of newly absorbed nutrients
to venules >> sinusoids >> central v. >> hepatic v.
leaves liver via
hepatic v.
refer to liver histo map