APD Hepatobiliary Physiology & Liver Metabolic Functions (Lecture 10)

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110 Terms

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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?
What is indicated by number 1 in the image?
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D cell (somatostatin)
What is indicated by number 2 in the image?
What is indicated by number 2 in the image?
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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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LDL
_______ is the breakdown product of VLDL.
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LDL
What lipoprotein deposits cholesterol in cells & vessels?
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Apolipoproteins
________________ bind & transport triacylglycerides & cholesterol.
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Chylomicrons, VLDL, IDL, LDL
What lipoproteins contain more triacylglycerides than cholesterol?
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HDL
What lipoprotein contains more cholesterol than triacylglycerides?
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Apopoliportein CIII
What transports triglycerides from the liver to other organs?
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LDL
What lipoprotein transports cholesterol & triglycerides from the liver to peripheral organs using apopoliprotein B100?
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HDL
What lipoprotein transports fat from peripheral tissue to the liver using ApoA-I and ApoA-II?
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cholesterol
What lipid molecule is needed for cell membranes?
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cholesterol
What is needed for the synthesis of steroid hormones?
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To produce energy
What is the main purpose of breaking down triglycerides?
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HDL > 50
What are the normal levels of HDL in the body?
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LDL < 100
What is the normal level of LDL in the body?
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Triglycerides < 150 (think 50 x 3)
What is the normal level of triglycerides in the body?
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LDL < 70
What is the best with disease level of LDLs?
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Patients with a history of cardiovascular disease
In what patients should LDL levels be lower than the norm?