Liver and Gallbladder Function - Lopez Flashcards
Function of liver
bile production and secretion, metabolism of carb/protein/lipid, bilirubin production, detoxification
Carb metabolism by liver
gluconeogenesis, storage of glucose as glycogen, release of glucose
Protein metabolism by liver (4)
synthesize nonessential amino acids, modify amino acids, synthesize plasma protein, convert ammonia to urea
Liver failure can result in…
hypoalbuminemia –> edema
Lipid metabolism by liver
fatty acid oxidation, synthesis of lipoproteins, cholesterol, and phospholipids
Majority of bile is….
bile salts
Where is bile produced and secreted
liver
Cirrhosis
chronic liver disease where normal liver cells are damaged and replaced by scar tissue
How can cirrhosis occur
excessive alcohol intake
Why does alcohol lead to cirrhosis
alcohol abuse causes accumulation of fat in hepatocytes causing fatty liver and steatohepatitis
Steatohepatitis
fatty liver with inflammation leading to scarring
Relative amounts of the four bile acids
cholic acid > chemodeoxycholic acid > deoxycholic acid > lithocholic acid
Location of primary bile acids
hepatocytes
Location of secondary bile acids
lumen of small intestine
Location of bile salt conjugation
liver
Bile salt structure
amphiphathic
Role of bile salts
emulsify lipids and form micelles
Phospholipid structure
amphipathic molecules but not soluble in H2O
How are micelles formed?
bile salts solubilize phospholipids
Cholesterol structure
weakly polar molecule on interior micelle
Most important bile pigment
bilirubin
T/F Bile pigments play a major rile in micellar formation
F- do not take part in micellar formation
What is the predominant cation of bile
Na+
Predominant anion of bile
Cl- and HCO3-
What does the behavior of bile salts depends on…
bile salt concentration
Decreased concentration of bile salts
no aggregation of bile salts
Increased concentration of bile salts
increased concentration of micelle formation
Critical micellar concentration
hydrophobic portion of bile salt, phospholipds, and fatty acids interact in interior of micelles
5 components of biliary system
liver, gallbladder and bile duct, duodenum, ileum, portal circulation
What is secreted into the bile canaliculi
the returning bile salts
What secretes canalicular bile
ductule cells in response to osmotic effects of anion transport
What happens via enterohepatic circulation
bile salts are recirculated to the liver
3 steps of enterohepatic circulation
1bile salts transported from ileum to portal blood 2. bile salts back to liver 3. Synthesis of bile salts to replace amount that was lost
What membrane do the bile salts get taken up through
basolateral membrane of hepatocytes
2 systems of bile salt uptake by liver
1Na+ dependent transport protein, sodium taurocholate cotransporting polypeptide, 2. Na+ independent transport protein, organic anion transport protein
Ileal transport process
highly efficient at carrying bile acids to portal blood
Effect of increase in bile secretion on returning rate of bile acids
increase bile acid to liver via portal blood
What is inhibited by bile salts
cholesterol 7a-hydroxylase
Secretin effect on bile salts
stimulates HCO3 secretion and H2O from ductile cells cause an increase in bile formation and decrease in bile salt concentration
Secretion of bile acids in relation to cations
accompanied by passive movement of cations into conaliculus
What is canalicular bile
ultrafiltrate of plasma
Bile flow between periods of digestion: gallbladder
relaxed gallbladder, sphincter of Oddi closed
Interdigestive period
between periods of digestion
CCK mediated when…
eating
CCK function on gallbladder
contraction of gallbladder and relaxation of sphincter of Oddi
UDP glucuronyl transferase
synthesized slowly after birth
- can potentially cause jaundice
Conjugated bilirubin is called..
bilirubin glucuronide
What accounts for the urine’s yellow color
conjugated bilirubin
What causes stool dark color
Urobilin and stercobilin
Physiological neonatal jaundice
increase level on unconjugated bilirubin in blood during first week of life
Two main causes of physiological neonatal jaundice
1bilirubin production is elevated 2. Low activity of UDP glucuronyl transferase
Why would bilirubin be elevated
increased breakdown of fetal erythrocytes
UDP glucuronyl transferase
enzyme responsible for binding bilirubin to glucuonic acid to mae bilirubin more soluble
Jaundice
yellowing of skin beginning at face
Crigler-Najjar syndromes
can’t conjugate bilirubin
Gilbert’s syndrome
can’t uptake unconjugated bilirubin in liver
Dubin-Johnson syndrome
can’t secrete conjugated bilirubin into bile
Rotor syndrome
can’t secrete conjugated bilirubin into bile
same as Dubin-Johnson
Hemolytic anemia
form of anemia due to hemoylsis
Hemolytic anemia affect on bilirubin
increase bilirubin production
T/F Hemolytic anemia is related to both unconjugated bilirubin and conjugated bilirubin
F- Hemolytic anemia is related to conjugated bilirubin
Constitutional hepatic dysfunction/familial nonhemolytic jaundice
aka Gilbert’s syndrome
Level of unconjugated bilirubin for Gilbert’s syndrome
increased in blood ( unconjugated hyperbilirubinemia)
What causes Gilbert’s syndrome
mutation in gene that codes for UDP glucuronyl transferase
Level of unconjugated bilirubin for Crigler-Najjar syndrome
increased in blood (unconjugated hyperbilirubinemia)
Type I Crigler-Najjar syndrome
early in life
- no function of UDP glucuronyl transferase
- with kernicterus
Kernicterus
form of brain damage caused by accumulation of unconjugated bilirubin in brain
Babies with kernicterus
lethargic and weak muscle tone
Type II Crigler-Najjar syndrome
starts later in life
- less that 2-5 function of UDP glucuronyl transferase
- less likely to develop ketnicterus
Treatment for Crigler-Najjar
- light treatment (phototherapy) but doesn’t work after the age of 4 due to thickening of skin
- blood transfusions
- oral calcium
Treatment for only Type I CN
liver transplant
Treatment for only Type II CN
phenobarbitol drug
Level of unconjugated bilirubin for Dubin-Johnson syndrome
increase of unconjugated bilirubin IN SERUM without liver enzyme elevation
Cause of Dubin-Johnson
defect in ability of hepatocytes to secrete conjugated biliruin
Mutation in Dubin-Johnson
multidrug resistance protein 2 (MRP2)
Function of MRP2
transport bilirubin out of liver cells into bile
Staple sign of Dubin-Johnson
liver has black pigmentation
Dubin-Johnson incidence rate
more common among iranian and moroccan jews living in Israel
Rotor syndrome bilirubin levels
build up of both unconjugated con conjugated bilirubin in blood
Gene associated with Rotor syndrome
abnormally short OATP1B1 and OATP1B3
Function of OATP1B1 and OATP1B3
transport bilirubin from blood to liver to be cleared from body
Liver appearance with Rotor syndrome
not pigmented
How does phototherapy work
transformation of trans-bilirubin into cis-bilirubin allowing the newborn to excrete bilirubin in urine and stools
Cholelithiasis
excess of pigmented bilirubin breakdown or cholesterol
Choledocholithiasis
small gallstomes pass to biliary duct and get stuck leading to inflammation and crampy pain
How can jaundice form from gallstone
if stone passes to common bile duct and obstructs it
How can pancreatitis form from gallstone
if stone pass to entrance of duct at duodenum and obstruct pancreatic duct
Gallstone ileus
stone pass into duodenum and obstruct it
Phase I of drug metabolism by liver
cytochrome P450 enzyme oxidation
Phase II of drug metabolism by liver
conjugation phase
