4 Hepatobiliary Function Flashcards
Main functions of the liver
Bile production and secretion
Metabolism of carbs, proteins, and lipids
Bilirubin production and excretion
Detoxification of substances
Three metabolic functions of the liver
Carbohydrate metabolism
Protein metabolism
Lipid metabolism
Carbohydrate metabolism of the liver includes ______, release of ______, and storage of glucose as ______.
Gluconeogenesis
Glucose
Glycogen
Protein metabolism of liver includes synthesis of ______ amino acids
Modification of _____ for use in biosynthetic pathways for carbohydrate
Synthesis of plasma proteins including _____ and _____
Conversion of ammonia to _____
Nonessential
Amino acids
Albumin and clotting factors
Urea
Lipid metabolism of the liver includes synthesis of _____, ______, and _____, and fatty acid oxidation.
Lipoproteins
Cholesterol
Pospholipids
The more blood vessels in parallel, the _____ the resistance.
The more in series, the _____ the resistance.
Lower
Greater
Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue (fibrosis)
Most common causes is ____.
Cirrhosis
Alcohol abuse
Alcohol abuse leads to an accumulation of _____ in hepatocytes.
_____ is a fatty liver with inflammation, leading to scarring of the liver and cirrhosis.
Fat
Steatohepatitis
Chronic disease that causes the bile ducts in the liver to become inflamed, damaged, and eventually lost
Primary biliary cirrhosis
What is one of the most common causes of portal hypertension?
Why?
Cirrhosis
Liver cirrhosis is caused by fibrosis of the liver-> increases resistance to portal blood flow -> portal hypertension
Clinical consequences of portal hypertension due to liver cirrhosis
Hepatic encephalopathy
Esophageal varies
Splenomegaly
Caput medusae (ascites)
Hemorrhoids
Testicular atrophy (less testosterone)
Composition of bile
Bile salts
Bile pigments
Cholesterol
Phospholipids (lecithin)
Ions
Water
Function of bile
Vehicle for elimination of substances from the body
Solubilizes lipids that are normally insoluble
How does the parasympathetic innervation of the _____ nerve affect bile secretion?
What opposes this innervation?
Vagus nerve
Increases bile flow
Includes contraction of the gallbladder
Sympathetics
This hormone is the primary regulator of bile secretion.
What does it stimulate?
Other hormones and fx
CCK
Gallbladder contraction directly
Relax the sphincter of Oddi
Gastrin
Secretin stimulates liver ductal secretion (antagonize CCK actions)
Pancreatic polypeptide and somatostatin (decrease gallbladder contractility)
Primary bile acids are synthesized in _____ by ____.
Secondary bile acids are synthesized in _____ by _____.
Secondary acids are _____ in the liver and form bile salts.
Bile salts form _____.
Hepatocytes; 7 alpha-hydroxylase
Small intestine; 7 alpha-dehydroxylase
Conjugated
Micelles
Cirrhosis liver leading to portal hypertension causes _____ albumin production-> ______ oncotic pressure and ____ hydrostatic pressure.
Also causes ______ aldosterone and Na reabsorption in the kidney
Decreased
Decreased
Increased
Increased
Enterohepatic circulation plays a role in the biliary system by ____.
Regulated by what two hormones?
It recycles bile acids to decrease the amount need to be synthesized (90% of bile acids delivered recycled to portal blood; the rest excreted in feces)
CCK and secretin
Some bile is lost in ____.
This changes the amount of bile ____.
Feces
Synthesis
Bile is secreted across what kind of membrane?
By what cells?
Canalicular (have active and passive secretions)
Ductile cells
Bile salt transporters:
into the hepatocyes
Into canaliculi
Into enterocytes
Exiting enterocytes
NTCP: Na dependent transport protein
OATPs: organic anion transport protein
BSEP: bile salt excretory pump
MRP2: multidrug resistance protein 2
ASBT: apical Na dependent bile acid transporter
OSTalpha/beta: organic solution transporter
Increased bile secretion ____ the rate of return
Cholesterol 7 alpha-hydroxylase is inhibited by ____ (negative feedback).
Increases
Bile salts
How does ileal resection affect enterohepatic circulation?
Increases bile salt synthesis levels by 10 fold
Because not longer able to reabsorb bile into the portal blood through the enterocytes in the ileum
What does secretin stimulate during bile acid secretion?
HCO3 and water secretion form ductile cells
Increase volume, increases pH, decreases bile salt concentration
What does it meant to be bile acid-dependent and independent?
Almost all bile formation is driven by bile acids
Small portion of bile is stimulated by secretin
What happens to bile secretion between meals?
What happens when food is ingested and what mediates this?
Gallbladder fills with bile and relaxes
Sphincter of Oddi is closed
Contraction of gallbladder
Relaxation of sphincter of Oddi—mediated by CCK
Bilirubin is made from hemoglobin from RBC-> bilirubin combines with ____ and goes to the liver-> bilirubin is ____ in the liver by ______ enzyme-> some conjugated bilirubin is excreted in the ____-> the rest goes to the small intestine where it is converted into urobilin and stercobilin to make _____.
Albumin
Conjugated
UDP-glucuronyl transferase
Urine (yellow because of conjugated bilirubin or bilirubin glucuronide)
Dark colored stools (feces)
What is jaundice a sign of?
How do you measure jaundice?
Direct vs indirect?
Hyperbilirubinemia
Measure total serum bilirubin to see levels of direct (conjugated) and indirect (unconjugated) bilirubin
Form of anemia due to hemolysis of RBC
Increased ____ bilirubin.
Hemolytic anemia
Unconjugated bilirubin
Increased unconjugated bilirubin in blood during the 1st week of life
What causes it?
Neonatal jaundice
Elevated bilirubin production due to breakdown of fetal erythrocytes
Low activity of UDP glucuronyl transferase
Gilbert’s syndrome has increased levels of _____ bilirubin in the blood.
Appears during adolescence because has episodes of _____ brought on by stress.
Caused by mutation in gene coding for ____.
Mild; ____ of people have no signs or symptoms
Unconjugated bilirubin
Hyperbilirubinemia
UDP glucuronyltransferase
30%
Crigler-Najjar Syndrome has increased levels of ____ bilirubin in the blood.
Mutation in gene coding for ____.
Type 1 is ____.
Type 2 is ____.
Unconjugated
UDP glucuronyltransferase
Very severe
Less severe
____ is a form of brain damage caused by the accumulation of unconjugated bilirubin and develops in the 1st year.
Symptoms of cerebral palsy, sensory neural hearing loss, and gaze abnormalities.
Due to untreated _____ with a build up of ____ bilirubin?
Kernicterus
Crigler-Najjar Syndrome Type 1
Unconjugated
What treats type 2 crigler-najjar syndrome?
How?
Can it help type 1?
Phenobarbitol
Helps conjugate the bilirubin
NO
What treats type 1 crigler-najjar syndrome?
Phototherapy up to 12 hr/day
Heme oxygenate inhibitors
Oral calcium phosphate
Carbonate
Liver transplant
Dublin-Johnson syndrome has increased levels of ____ bilirubin.
Why?
Mutation in ____.
Liver has a ____ pigmentation.
Conjugated bilirubin
Defect in the ability of hepatocytes to secrete conjugated bilirubin in bile
MRP2
Black
Rotor Syndrome has a buildup of _____ bilirubin but most is _____.
Mutation in genes ____.
Unconjugated and conjugated
Conjugated
OATP1B1 and OATP1B3
Phototherapy is the main treatment in babies with ____.
How?
Unconjugated hyperbilirubinemia
Isomerization that changes trans-bilirubin into water-soluble cis-bilirubin isomer
Bile duct obstruction (stones) causes an increase in ____ bilirubin.
Small stones blocking the cystic duct cause ____.
Conjugated bilirubin
Acute cholecystitis
Causes of gallstones
Too much absorption of water and bile acids from bile
Too much cholesterol in bile
Inflammation of epithelium
Liver enzymes can modify drugs and toxins to make them ____.
This allows excretion of theses substances through _____.
Phase 1 processed by _____.
Phase 2 includes ____ with glucoronide, sulfate, AA, or glutathione
Water-soluble
Bile or urine
P450 enzymes
Conjugation
Liver function tests measure what liver enzymes?
Serum aminotransferases: ALT and AST
Alkaline phosphatase
Elevated aminotransferases mean what?
Elevated alkaline phosphatases mean what?
Hepatocytes injury
Cholestasis
Measures the liver’s ability to detoxify metabolites and transport organic anions into bile
Bilirubin function test
Low levels of _____ mean severe impairment in liver function/hepatocyte function like during cirrhosis.
Why?
Albumin (hypoalbuminemia)
Because albumin is synthesized in the liver
Increases as the ability of cirrhotic liver to synthesize clotting factors decreases
Reflects the degree of hepatic synthetic dysfunction
Prothrombin time/INR
