4 Hepatobiliary Function Flashcards by Abby Finder

Main functions of the liver

Bile production and secretion

Metabolism of carbs, proteins, and lipids

Bilirubin production and excretion

Detoxification of substances

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Three metabolic functions of the liver

Carbohydrate metabolism

Protein metabolism

Lipid metabolism

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Carbohydrate metabolism of the liver includes ______, release of ______, and storage of glucose as ______.

Gluconeogenesis

Glucose

Glycogen

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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

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Lipid metabolism of the liver includes synthesis of _____, ______, and _____, and fatty acid oxidation.

Lipoproteins

Cholesterol

Pospholipids

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The more blood vessels in parallel, the _____ the resistance.

The more in series, the _____ the resistance.

Lower

Greater

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Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue (fibrosis)

Most common causes is ____.

Cirrhosis

Alcohol abuse

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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

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Chronic disease that causes the bile ducts in the liver to become inflamed, damaged, and eventually lost

Primary biliary cirrhosis

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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

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Clinical consequences of portal hypertension due to liver cirrhosis

Hepatic encephalopathy

Esophageal varies

Splenomegaly

Caput medusae (ascites)

Hemorrhoids

Testicular atrophy (less testosterone)

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Composition of bile

Bile salts

Bile pigments

Cholesterol

Phospholipids (lecithin)

Ions

Water

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Function of bile

Vehicle for elimination of substances from the body

Solubilizes lipids that are normally insoluble

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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

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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)

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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

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Cirrhosis liver leading to portal hypertension causes _____ albumin production-> ______ oncotic pressure and ____ hydrostatic pressure.

Also causes ______ aldosterone and Na reabsorption in the kidney

Decreased

Increased

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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

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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