APD Hepatobiliary Physiology & Liver Metabolic Functions (Lecture 10)

basolateral membrane

basolateral membrane

Hepatocytes uptake substances from capillary via what membrane?

apical membrane

Hepatocytes modify compounds/material before excretion across what membrane?

1. Chenodeoxycholic acid

2. Cholic acid

3. Protonated form

What are 3 examples of bile acids?

1. Glucoronate

2. Glycine

3. Sulfate

4. Taurine

What are 4 examples of bile salts?

heme

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

biliverdin

Reduced to bilirubin

bilirubin

Transported with albumin--not soluble in blood

jaundice

Build up of bilirubin causes ____________.

urobilinogen

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

stercobilin; urobilin

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

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.

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.

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.

Make molecules more water soluble

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

3

How many phases make up biotransformation in the liver?

P-450 cytochromes

What catalyzes phase 1 of biotransformation in the liver?

Adds oxygen

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

Conjugation; makes product more water soluble

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

excretion of phase 2 product into blood or bile

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

Reduced glutathione (GSH)

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

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)?

cholesterol

What do hepatocytes make bile acids from?

1. Bilirubin

2. Cholesterol

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

Normal lipid absorption and digestion

What is the primary function of bile?

mixed micelles

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

Cholestyramine (Questran)

What increases excretion of bile in the feces?

1. Heavy metals

2. Lipophilic compounds

What are 2 main bile excretory products?

bacteria

Secondary bile acids are formed by dehydroxylation by __________.

cholesterol

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

secretin

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

somatostatin

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

Secretin; Somatostatin

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

cystic fibrosis

What condition decreases bicarbonate in bile secretions?

Glucagon (pancreatic alpha cells)

What is indicated by number 1 in the image?

D cell (somatostatin)

What is indicated by number 2 in the image?

1. Cystic duct to gallbladder

2. Common bile duct to duodenum

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

CCK

What mediator relaxes the sphincter of Oddi?

False

True/False: CCK decreases bile secretion.

True

True/False: Most bile acids are recycled.

terminal ileum & colon

What parts of the GI system reabsorb bile acids?

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.

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.

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 _____.

False

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

glycolysis

Excess glucose can be used in what process?

fat

During lipogenesis, excess glucose is converted to what?

1. Albumin

2. Globulins

3. C-reactive protein (CRP)

4. Glutathione

What are 4 major plasma proteins produced by the liver?

systemic inflammation

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

Removing free radicals

What is glutathione responsible for?

1. Protein S

2. Protein C

3. anti-thrombin III

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

plasminogen

What is a major player of fibrinolysis?

angiotensinogen

What is a prohormone plasma protein made by the liver?

ApoA-I & ApoA-II

What type of apolipoproteins are present with HDL?

Apo-B100

What type of apolipoproteins are present with LDL?

Metabolism of amino acids

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

urea

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

glycogenolysis

What glucose metabolic pathway occurs during fasting?

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)?

cholesterol

4 ring lipid molecule

triglyceride

Glycerol with 3 fatty acid chains

cholesterol ester

Cholesterol linked to fatty acid with ester bond

HMG CoA reductase

What is the rate limiting step of cholesterol synthesis?

The -statins

Cholesterol synthesis is inhibited by what drugs?

True

True/False: The liver makes cholesterol endogenously.

dietary fat

Fat that hasn’t yet entered the liver

lipoprotein lipase (LPL)

Chylomicrons are cleaved by what?

1. Triglycerides

2. Fatty acids

3. Cholesterol

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

VLDL

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

False--dietary fat

True/False: Chylomicrons are made of endogenous fat.

thoracic duct

Chylomicrons travel into the blood via the _______________.

fatty acids; glycerol

LPL breaks down triglycerides into ____________ and ____________.

VLDL

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

lipoprotein lipase

What breaksdown VLDL?

apolipoproteins

What is responsible for transporting lipoproteins?

triacyglycerides

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

triglycerides

Both chylomicrons & VLDL carry ______________ to tissues.

ketone bodies; kidney

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

HDL

Which is healthier: HDL or LDL?

HDL

What lipoprotein is responsible for removing lipids from blood vessels?

cholesterol

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

ApoA-1 & ApoA-2

What apolipoproteins aid in the transport of HDL?

chylomicrons

Dietary fat is transported as _______________.

1. Cholesterol

2. Triglycerides

3. Phospholipids

What are the 3 main components of chylomicrons?

Lipoprotein lipase; apolipoprotein CII

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

LDL

_______ is the breakdown product of VLDL.

LDL

What lipoprotein deposits cholesterol in cells & vessels?

Apolipoproteins

________________ bind & transport triacylglycerides & cholesterol.

Chylomicrons, VLDL, IDL, LDL

What lipoproteins contain more triacylglycerides than cholesterol?

HDL

What lipoprotein contains more cholesterol than triacylglycerides?

Apopoliportein CIII

What transports triglycerides from the liver to other organs?

LDL

What lipoprotein transports cholesterol & triglycerides from the liver to peripheral organs using apopoliprotein B100?

HDL

What lipoprotein transports fat from peripheral tissue to the liver using ApoA-I and ApoA-II?

cholesterol

What lipid molecule is needed for cell membranes?

cholesterol

What is needed for the synthesis of steroid hormones?

To produce energy

What is the main purpose of breaking down triglycerides?

HDL > 50

What are the normal levels of HDL in the body?

LDL < 100

What is the normal level of LDL in the body?

Triglycerides < 150 (think 50 x 3)

What is the normal level of triglycerides in the body?

LDL < 70

What is the best with disease level of LDLs?

Patients with a history of cardiovascular disease

In what patients should LDL levels be lower than the norm?