APD Hepatobiliary Physiology & Liver Metabolic Functions (Lecture 10)

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basolateral membrane

Hepatocytes uptake substances from capillary via what membrane?

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apical membrane

Hepatocytes modify compounds/material before excretion across what membrane?

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  1. Chenodeoxycholic acid

  2. Cholic acid

  3. Protonated form

What are 3 examples of bile acids?

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  1. Glucoronate

  2. Glycine

  3. Sulfate

  4. Taurine

What are 4 examples of bile salts?

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heme

Free iron in the blood; travels with transferrin in the blood

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biliverdin

Reduced to bilirubin

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bilirubin

Transported with albumin--not soluble in blood

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jaundice

Build up of bilirubin causes ____________.

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urobilinogen

Bilirubin in the small intestine is metabilized to _____________ by microbes in the natural flora.

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stercobilin; urobilin

Urobilinogen is metabolized to ________ to be excreted through the feces and is oxidized to ____________ to be excreted as urine.

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  1. Heme

  2. Biliverdin

  3. Bilirubin (w/ albumin)

  4. Conjugated bilirubin (in liver)

  5. Urobilinogen (GI bacteria)

  6. Urobillin (urine)

Using numbers 1 through 6, list the metabolism of heme when converted to bilirubin to be excreted in the urine.

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  1. Heme

  2. Biliverdin

  3. Bilirubin (w/ albumin)

  4. Conjugated bilirubin (in liver)

  5. Urobillinogen (GI bacteria)

  6. Stercolbin (feces)

Using numbers 1-6, list the metabolism of heme when converted to bilirubin to be excreted in feces.

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  1. Heme

  2. Biliverdin

  3. Bilirubin (w/ albumin)

  4. Conjugated bilirubin (in liver)

  5. urobilinogen (GI bacteria)

  6. Reabsorption in small intestine (made to bile)

Using numbers 1-6, list the metabolism of heme when converted to bilirubin to be reabsorbed in GI tract.

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Make molecules more water soluble

During biotransformation in the liver, what is the overall purpose of this process?

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3

How many phases make up biotransformation in the liver?

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P-450 cytochromes

What catalyzes phase 1 of biotransformation in the liver?

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Adds oxygen

What is the mechanism of action for P-450 cytochromes?

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Conjugation; makes product more water soluble

What major process occurs in phase 2 of biotransformation? What does this do to the phase 1 product?

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excretion of phase 2 product into blood or bile

What major process is occurring in phase 3 of biotransformation in the liver?

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Reduced glutathione (GSH)

What is the starting material of mercapturic acids (phase 2 conjugation)?

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1/2

Out of all the bile produced from hepatocutes, how much bile (relatively) is diverted to the gallbladder between meals (instead of the small intestine through the duodenal papilla)?

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cholesterol

What do hepatocytes make bile acids from?

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  1. Bilirubin

  2. Cholesterol

What are the 2 major organic solutes that make up bile?

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Normal lipid absorption and digestion

What is the primary function of bile?

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mixed micelles

Bile salts form soluble ___________________ with fat to aid in passage from lumen.

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Cholestyramine (Questran)

What increases excretion of bile in the feces?

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  1. Heavy metals

  2. Lipophilic compounds

What are 2 main bile excretory products?

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bacteria

Secondary bile acids are formed by dehydroxylation by __________.

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cholesterol

What levels decrease within the blood due to bile acid production?

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secretin

What major player is responsible for secretion of bicarbonate rich fluid?

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somatostatin

What major player is responsible for inhibiting the cAMP pathway in bile duct secretion?

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Secretin; Somatostatin

___________ increases bile duct secretion. ______________ inhibits bile duct secretion.

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cystic fibrosis

What condition decreases bicarbonate in bile secretions?

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Glucagon (pancreatic alpha cells)

What is indicated by number 1 in the image?

<p>What is indicated by number 1 in the image?</p>
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D cell (somatostatin)

What is indicated by number 2 in the image?

<p>What is indicated by number 2 in the image?</p>
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  1. Cystic duct to gallbladder

  2. Common bile duct to duodenum

What are the 2 parts of the common hepatic duct bifurcation?

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CCK

What mediator relaxes the sphincter of Oddi?

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False

True/False: CCK decreases bile secretion.

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True

True/False: Most bile acids are recycled.

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terminal ileum & colon

What parts of the GI system reabsorb bile acids?

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fat; blood

Bile is used to absorb ____. Bile helps this be absorbed then drops it off in the __________ and cycles back to help more be absorbed.

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gluconeogenesis; glycogenolysis

Between meals in low blood glucose conditions, ____________ occurs to make glucose from amino acids. In addition, _______________ can also occur to breakdown glycogen to glucose.

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glycogen synthesis; fat

After meals, during high glucose conditions, ________ can occur to store glucose for later usage (glycogen). After glycogen is made, unused carbohydrates are converted to _____.

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False

True/False: Glucose entry into the liver depends on insulin.

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glycolysis

Excess glucose can be used in what process?

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fat

During lipogenesis, excess glucose is converted to what?

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  1. Albumin

  2. Globulins

  3. C-reactive protein (CRP)

  4. Glutathione

What are 4 major plasma proteins produced by the liver?

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systemic inflammation

C-reactive protein is used to measure what within the body?

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Removing free radicals

What is glutathione responsible for?

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  1. Protein S

  2. Protein C

  3. anti-thrombin III

What are 3 major coagulation inhibitors in hemostasis/fibrinolysis (anti-clot)?

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plasminogen

What is a major player of fibrinolysis?

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angiotensinogen

What is a prohormone plasma protein made by the liver?

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ApoA-I & ApoA-II

What type of apolipoproteins are present with HDL?

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Apo-B100

What type of apolipoproteins are present with LDL?

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Metabolism of amino acids

What is the liver’s role in dealing with amino acids?

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urea

The liver converts amino acids to _______ for excretion in the urine.

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glycogenolysis

What glucose metabolic pathway occurs during fasting?

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  1. Amino Acids & urea

  2. Angiotensinogen

  3. Bile

  4. C-Reactive protein

  5. Coagulation factors

  6. Glucose & Glycogen

  7. Cholesterol

  8. Glutathione

What are the 8 primary components produced from the liver (think ABCG)?

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cholesterol

4 ring lipid molecule

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triglyceride

Glycerol with 3 fatty acid chains

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cholesterol ester

Cholesterol linked to fatty acid with ester bond

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HMG CoA reductase

What is the rate limiting step of cholesterol synthesis?

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The -statins

Cholesterol synthesis is inhibited by what drugs?

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True

True/False: The liver makes cholesterol endogenously.

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dietary fat

Fat that hasn’t yet entered the liver

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lipoprotein lipase (LPL)

Chylomicrons are cleaved by what?

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  1. Triglycerides

  2. Fatty acids

  3. Cholesterol

When chylomicrons are cleaved, what 3 components are left over?

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VLDL

Remnants of chylomicrons that have been cleaves enter the liver and are converted to _______.

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False--dietary fat

True/False: Chylomicrons are made of endogenous fat.

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thoracic duct

Chylomicrons travel into the blood via the _______________.

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fatty acids; glycerol

LPL breaks down triglycerides into ____________ and ____________.

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VLDL

The liver packages endogenous fat (& chylomicron remnants) as _______.

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lipoprotein lipase

What breaksdown VLDL?

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apolipoproteins

What is responsible for transporting lipoproteins?

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triacyglycerides

Release of ________________ leads to more and more densely packed cholesterol molecules.

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triglycerides

Both chylomicrons & VLDL carry ______________ to tissues.

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ketone bodies; kidney

Fatty acids metabolize to ___________ in β oxidation. They are then sent to the brain, muscle, & __________.

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HDL

Which is healthier: HDL or LDL?

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HDL

What lipoprotein is responsible for removing lipids from blood vessels?

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cholesterol

What is present in higher quantities within HDL: cholesterol or triacylglycerides?

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ApoA-1 & ApoA-2

What apolipoproteins aid in the transport of HDL?

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chylomicrons

Dietary fat is transported as _______________.

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  1. Cholesterol

  2. Triglycerides

  3. Phospholipids

What are the 3 main components of chylomicrons?

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Lipoprotein lipase; apolipoprotein CII

________________ breaks down triglycerides to release fatty acids to tissues. _______________ inhibits this from occuring.

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