Liver- Jones

based off pp

What are the functions of the liver?

• filtration and storage of blood

• metabolism

• bile synthesis

• storage of vitamins and iron

• formation of coagulation factors

What vitamins are stored in the liver?

A,D,E,K

What cell type of the liver lobule is the epithelial layer and separates the internal from external environment?

hepatocyte

What are the role of Kupffer cells in liver lobules?

macrophage—> identify bacteria

What does this entire structure refer to?

acinus

What the roles of Stellate cells?

• Vit A storage

• secrete GF

What is the Space of Disse?

• interstitial space between blood and hepatocytes

What is a Cholangiocyte?

cells that make up the bile duct

How does blood flow from the GI tract back to the heart?

1. GI tract

2. Portal vein

3. Sinusoid

4. space of disse

5. hepatocytes

6. back out into sinusoid and into central vein to the heart

The lobule of the liver is split into how many zones? What zone receives the most oxygen? In what zone is most of the metabolism done?

• 3 zones (zone 1, zone 2, zone 3)

• zone 1 receives the most oxygen

• zone 1 is where most of the metabolism is done

What artery brings oxygen rich blood from the heart?

hepatic artery

How do the sinusoids in the liver lobules respond to meals?

during meals—> dilate to allow for increased metabolism

fasting—> collapse/ smaller

During portal hypertension:

• What happens to flow to the liver?

• What happens to pressure within the portal vein?

• What happens to resistance within the portal vein?

• What happens to flow in the surrounding areas?

• flow is obstructed/less than normal

• INCREASED PRESSURE

• INCREASED RESISTANCE

• INCREASED FLOW to surrounding areas

What are the 3 classifications of portal hypertension? What are the common causes of each?

1. pre-hepatic: portal/splenic vein thrombosis

2. intra-hepatic: fibrosis in the liver, cirrhosis, hepatitis, alcohol abuse

3. post-hepatic: right-sided HF, vena cava clot

Why is splenomegaly seen in pre-hepatic portal hypertension?

bc of a blockage/clot fluid can’t flow into the liver and flows into the spleen. results in enlarged spleen or splenomegaly

What are the symptoms of portal hypertension?

• ascites

• jaundice

• development of varices

• vomiting, diarrhea

In portal hypertension, how does our body react to the increased resistance in the portal vein?

excessive vasodilation to surrounding areas (this becomes a problem)

How does cirrhosis lead to ascites?

1. cirrhosis causes portal hypertension

2. we vasodilate to counter the increased resistance

3. vasodilation increases the pressure in the capillaries and causes lymph to leak out of into the IS = ascites

4. AT THE SAME TIME—> because all the fluid is leaking out, our body thinks we have arterial hypovolemia

5. therefore, our body activates the RAAS system, vasoconstricts the arterioles and that leads to more fluid retention, worsening the ascites

When the RAAS system is activated in portal hypertension by conditions like cirrhosis, what hormones are increased?

↑ Aldosterone, ↑ Ang II, ↑ ADH

Bile is synthesized from __________________.

cholesterol

How are primary bile acids converted into secondary bile acids?

primary bile acids are synthesized in the liver and go to the GI where they are converted into secondary bile acids by bacteria

When bile acids are being reabsorbed/recycled, they are conjugated in the liver into what 2 things? Why?

• conjugated into Glycine or Taurine

• conjugated to make them more soluble

How are conjugated and non-conjugated bile acids brought into the HEPATOCYTE from the SINUSOID?

conjugated—> NTCP transporter

un-conjugated—> OATP1B 1/3

How do conjugated bile acids get from the HEPATOCYTE into the BILE?

BSEP transporter

Explain the process of how bilirubin is formed?

1. RBC dies and is converted to Hgb

2. In a macrophage, Hgb is converted to bilirubin

In the blood, bilirubin is bound to ___________.

albumin

How does bilirubin get into the HEPATOCYTE from the BLOOD? What happens once bilirubin enters the hepatocyte?

• gets into the cell using the OATP transporter

• once inside the cell—> conjugated by the UGT enzyme

Once conjugated, how is bilirubin moved from the HEPATOCYTE into the BILE? Where is bilirubin stored thereafter?

• bilirubin moves into bile using MRP2 transporter

• then store in the gallbladder with bile

Once bilirubin is secreted into the intestine, what happens? What happens after it’s turned into Urobilinogen?

• deconjugated and metabolized by bacteria into urobilinogen

• THEN either converted into STERCOBILIN and excreted into feces OR returned to plasma

What condition is a yellowing of the skin and tissue as a result of bilirubin accumulation?

jaundice

What are some causes of jaundice?

• overproduction—> RBC/hemolysis

• genetics:

  • reduced liver uptake

  • impaired conjugation

  • decreased hepatic excretion

• impaired bile flow—> gallstone

How can the cause of jaundice be determined?

looking at the form of bilirubin aka is there high unconjugated or conjugated bilirubin

For each cause of jaundice, determine whether there would be higher conjugated or unconjugated bilirubin:

• overproduction

• reduced uptake

• impaired conjugated

• decreased hepatic excretion

• impaired bile flow

• overproduction- ↑ both but more unconjugated

• reduced uptake- ↑ unconjugated

• impaired conjugated- ↑ unconjugated

• decreased hepatic excretion- ↑ conjugated

• impaired bile flow- ↑ conjugated

Unconjugated Hyperbilirubinemia can be caused by:

• hemolytic anemia

• drugs inhibiting uptake into the liver

• Gilberts

• Crigler-Najjar

Gilbert’s is impaired _____________ function.

UGT1A1

Crigler-Najjar is impaired ____________ function.

UGT1A1

Conjugated Hyperbilirubinemia can be caused by:

• Dubin-Johnson

• Rotor’s

• obstruction in ducts

Dubin-Johnson is a mutation in _____________

MRP2/ ABCC2 transporter

Rotor’s is a mutation in _______________.

OATP1B1/3

Ammonia is toxic to the CNS and can cause what if there is high amounts?

Hepatic encephalopathy (altered mental status)

Hepatocytes play a role of converting ammonia into ______ and _______ to be excreted from the body.

urea and ornithine

A person with Rotor’s will have a problem doing what? (ex: conjugating bilirubin)

transporting conjugated bile into the hepatocyte

A person with Gilbert’s will have a problem doing what? (ex: conjugating bilirubin)

conjugating bilirubin

A person with Crigler-Najjar will have a problem doing what? (ex: conjugating bilirubin)

conjugating bilirubin

A person with Dubin-Johnson’s will have a problem doing what? (ex: conjugating bilirubin)

moving bilirubin from the hepatocyte into the bile