Biliary Secretion: Hepatobiliary Function Flashcards
Why is the location of the liver ideal?
it can receive absorbed nutrients and detoxify drugs/toxins
what can hypoalbuminemia lead to?
edema
what does the liver convert ammonia to?
urea
what does alcohol abuse lead to?
accumulation of fat within hepatocytes
what does fatty liver lead to?
steatohepatitis
what is steatohepatitis?
fatty liver accompanied by inflammation, which leads to scarring of the liver and cirrhosis
what can cirrhosis cause?
portal hypertension
when does portal hypertension develop?
when there is resistance to portal blood flow
what is associated with portal hypertension?
changes to the venous circulation
what are esophageal varices?
swollen connection between systemic and portal systems at the inferior end of the esophagus
what is caput medusae?
swollen connection between the systemic and portal systems around the umbilicus
what else is associated with portal hypertension besides the venous changes?
spleenomegaly and porto-systemic collaterals
how does liver dysfunction lead to hepatic encephalopathy?
the decreased hepatic urea cycle metabolism leads to the accumulation of ammonia in the systemic circulation; ammonia readily crosses the BBB and alters brain function
where is bile produced and secreted from?
the liver
where does the synthesis of the primary bile acids occur?
liver
where does the synthesis of the secondary bile acids occur?
lumen of small intestine
where does the conjugation of the bile acids occur?
liver
what are the components of the biliary system?
the liver, gallbladder and bile duct, duodenum, ileum, and portal circulation
how is bile concentrated in the gallbladder?
by the absorption of water and ions
when chyme reaches the small intestine, what is secreted?
Cholecystokinin (CCK)
what are the two separate by coordinated functions of CCK?
it stimulates the contraction of the gallbladder and the relaxation of the sphincter of Oddi (this causes the stored bile to flow from the gallbladder into the lumen of the duodenum)
what happens when lipid absorption is complete?
the bile salts are recirculated to the liver via the enterohepatic circulation
where does the absorption of bile salts take place?
in the ileum
how is the bile rediluted?
secretin stimulates the production of ions (HCO3-) and H2O in the bile duct
bile in the liver (both new and recycled) is secreted into where?
bile canaliculi
bile secretion occurs via two mechanisms. what are they?
- bile-acid dependent 2. by secretin and it is then secreted from the ducts (bile acid-independent)
what is the secretion of bile acids accompanied by?
the passive movement of cations into the canaliculus
bile salts are recirculated to the liver via what?
enterohepatic circulation
how do the bile salts move from the lumen of the ileum into the enterocyte?
via the apical sodium dependent bile acid transporter (ASBT)
how do the bile salts move into the basolateral side of the enterocyte?
via the organic solute transporter alpha/beta (OST-alpha or OST-beta)
how do the bile salts move from the portal circulation into the hepatocytes?
either via the Na+ Tauroholate Co-transporting polypeptide (NTCP) or the organic anion transporter protein (OATPs)
how do the bile salts get from the hepatocytes into the bile canaliculi?
either the bile salt excretory pump (bsep) or the multidrug resistance protein 2 (mrp2)
how does the liver “know” how much new bile acid to synthesize daily?
bile-acid synthesis is under negative-feedback control by the bile salts
what is the rate limiting enzyme in the biosynthetic pathway and what is it inhibited by?
7-alpha- hydroxylase, inhibited by bile salts
what processes senescent red blood cells?
the reticuloendothelial system
what happens when hemoglobin is degraded by the RES?
one of the byproducts is biliverdin (green-color)
what is biliverdin converted into?
bilirubin (yellow-color)
what is bilirubin bound to in the blood stream and where does it travel to?
it is bound to albumin and it travels to the liver to be taken up by hepatocytes
once in the liver, in hepatic microsomes what happens to the bilirubin?
it is conjugated with glucuronic acid via the enzyme UDP glucuronyl transferase
why do some newborns develop jaundice?
because the UDP glucuronyl transferase is synthesized slowly after birth
what could be said about the solubility of conjugated bilirubin?
it is water soluble, and therefore a portion of it is excreted in the urine
what happens when the conjugated bilirubin that is secreted into bile reaches the terminal ileum and colon?
it is deconjugated by bacterial enzymes and metabolized to urobilinogen
what is urobilinogen converted into?
urobilin and stercobilin- which are excreted in the feces
what gives stool its dark color?
urobilin and stercobilin
what is jaundice a sign of?
hyperbilirubinemia
how can you determine the quantitation of jaundice?
measurement of the total serum {bilirubin}
how are bilirubin test results expressed as?
direct (conjugated), indirect (unconjugated) or total bilirubin
any cause of hemolytic anemia could lead to what?
an increase in production of bilirubin
in hemolytic anemic patient’s, the increased bilirubin level overwhelms the liver’s capacity leading to what?
the liver cannot produce conjugated bilirubin- results in high unconjugated bilirubin levels
what is another reason why some newborns can have high levels of unconjugated bilirubin levels during their first week of life?
bilirubin production is elevated because of increased breakdown of fetal erythrocytes
what kind of bilirubin levels would you find in a patient with Gilbert’s syndrome?
increased levels of unconjugated bilirubin in the blood
when do episodes of gilbert syndrome typically occur?
when the body is under physiological stress
what causes gilbert’s syndrome?
a mutation in the UGT1A1 gene- the gene that codes for the UDP glucuronyl transferase enzyme
why is gilbert’s syndrome mild?
because the UGT1A1 gene still has about 30% activity
what kind of bilirubin levels would you find in a patient with Crigler-Najjar syndrome?
increased levels of unconjugated bilirubin in the blood
what causes crigler-najjar syndrome?
mutations in the gene that codes for the UDP glucuronyl transferase enzyme
what are the two types of crigler-najjar syndrome?
Type 1: very severe; Type 2: less severe
what would crigler Najjar syndrome Type 1 cause in patients before the availability of phototherapy?
kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nervous tissue
what are the major clinical features of kernicterus?
cerebral palsy, sensoryneural hearing loss, and gaze abnormalities
what kind of bilirubin levels would you expect to see in a patient with dubin-johnson?
high levels of conjugated bilirubin in the serum without elevation of liver enzymes
what is dubin johnson syndrome caused by?
a defect in the ability of hepatocytes to secrete the conjugated bilirubin into the bile
what gene mutation is involved in Dubin-johnson syndrome?
mutations for the gene that encodes the MRP2 drug
what does the liver look like in dubin-johnson syndrome?
it is black, which is the result of an intracellular melanin-like substance
what kind of bilirubin levels would you expect to see in a patient with rotor syndrome?
there will be a build up of unconjugated and conjugated bilirubin in the blood, but mostly conjugated
what causes rotor syndrome?
gene mutations that lead to abnormally short and nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins
what does the liver look like in Rotor syndrome?
it is normal
what is the primary treatment in neonates with unconjugated hyperbilirubinemia?
phototherapy
how does phototherapy work?
through a process of isomerization that changes trans-bilirubin into the water-soluble cis-bilirubin isomer
when do gallstones occur?
when there is excess of either pigment of bilirubin breakdown or excess cholesterol
what could contribute to pigmented stones (black stones)
hemolysis aka hemolytic anemia
what is the medical term for gallstones?
cholelithiasis
what is choledocholelithiasis?
gallstones occluding the common bile duct
what would you expect to find in a patient with choledocholelithiasis?
jaundice and conjugated hyperbilirubinemia
what is cholangitis?
infection of the bile duct
what is a patient at risk of developing if a stone is impacted in the distal bile duct?
cholangitis
what would elevated levels of aminotransferases point to?
hepatocyte injury
what would elevated alk phos point to?
this is primarily due to a bile duct injury (cholestasis)
what would abnormal serum bilirubin, albumin, and or PT point to?
impaired hepatic synthetic function
what do decreased levels of albumin point towards?
severe impairment of hepatocyte function
what does PT point to?
it is going to increase as the ability of a cirrhotic liver to synthesize clotting factors diminishes
