Liver and biliary apparatus

Question 1

What are the elements of the portal tract?

Answer 1

3 elements:

• artery
• vein
• bile duct

Question 2

How do drugs enter the systemic circulation?

Answer 2

Either directly eg. by intravenous injection or indirectly following absorption from the site of administration, typically from the small intestine following oral administration.

Question 3

Why is Digoxin an unusual drug when it comes to the volume of distribution?

Answer 3

It has a large volume of distribution even though it is not very lipid soluble. It binds to Na+/K+ ATPase in cardiac and skeletal muscle and therefore plasma concentrations are very low relative to the amount of drug in the body.

Question 4

What sort of patient characteristics can alter clearance and maintenance dose requirements?

Answer 4

Age, wight, pregnancy, renal diseases, hepatic disease, cardiac disease, drug interactions and more.

Question 5

What is the correction factor for clearance for someone who is a smoker?

Answer 5

x1.6 (increased)

Question 6

What is the correction factor for clearance for someone with cirrhosis of the liver?

Answer 6

x-0.5 (decreased)

Question 7

What is bioavailability (F)?

Answer 7

The fraction of the oral administered dose that reaches the systemic circulation. Can be high eg. Theophylline (F=1) or low for drugs that are poorly absorbed eg. Gentamicin (F<0.01) or are extensively metabolised on “first pass” through the liver before they reach the systemic circulation eg. Lidocaine (F=0.3).

Question 8

What is cirrhosis?

Answer 8

3 fold definition: diffuse process with fibrosis and nodule formation. End result of chronic inflammation and scarring of the liver. Leads to altered circulation and function. Causes: alcohol, viruses, toxins/drugs/inherited conditions.

Question 9

Name some signs and symptoms of cirrhosis.

Answer 9

Encephalopathy, sparse body hair, muscle wasting, spider angioma, ascites and dilated blood vessels on abdomen, jaundice.

Question 10

What causes ascites?

Answer 10

Develops in 50% of cirrhotics within 10 years of diagnosis. System vasodilation, leading to renal vasoconstriction and activation of the renin-angiotensin system and increased sodium retention.

Question 11

What is the innervation of the gallbladder?

Answer 11

Vagus and splanchnic nerves.

Question 12

What is the composition of bile?

Answer 12

Water, electrolytes, phospholipids, bile salts or acid, bile pigments, cholesterol, haem waste products and other substances from blood.

Question 13

Where is the major site of bile salt reabsorption?

Answer 13

Ileum

Question 14

What are the two main metabolic pathways in hepatic alcohol metabolism?

Answer 14

1) Cytoplasmic alcohol dehydrogenase (ADH).

2) Microsomal ethanol oxidising system (MEOS).

Question 15

When does alcoholic hepatitis develop?

Answer 15

After 3-5 years of alcohol abuse but occurs in only 1/3 of alcoholics. Females are at greater risk. Genetic susceptibility.

Question 16

What are some of the complications of alcoholic cirrhosis?

Answer 16

• Portal hypertension (portal-systemic shunts, ascites, splenomegaly).
• Liver failure.
• Hepatocellular carcinoma in 3-6% of patients

Question 17

What is Gilbert’s syndrome?

Answer 17

Gilbert’s syndrome is an inherited (usually autosomal recessive) metabolic disorder that causes intermittent, isolated raised unconjugated bilirubin levels, due to defective conjugating enzymes in the liver. There is otherwise normal liver function, and no evidence of haemolysis. Most common cause of unconjugated hyperbilirubinaemia.