Liver disease

Question 1

Define jaundice

Answer 1

Abnormal pigmentation of the skin, mucus membranes and sclera caused by deposition of bilirubin. Often only seen >20mg/L

Question 2

Describe the production of bilirubin

Answer 2

1. Haemoglobin –> heme and globin
2. Globin –> biliverdin –> unconjugated bilirubin (lipid soluble and bound to albumin)
3. Hepatic metabolism –> conjugated bilirubin (water soluble)
4. Stored as bile, released under effect of CCK in response to fatty meals
5. In gut, conjugated bilirubin is metabolised to UBG which gives poo its brown colour
6. Some UBG is reabsorbed and excreted in the urine giving it its yellow colour

Question 3

What are the common causes of unconjugated hyperbilirubinemia?

Answer 3

Caused by:

• Increased haemolysis (e.g. hemolytic disease of the newborn, sickle cell anemia, G-6-D phosphate deficiency)
• impaired hepatic bilirubin uptake (e.g. CHF, rifampicin)
• defective metabolism (e.g. Gilberts syndrome)

Question 4

What are the common causes of conjugated hyperbilirubinemia

Answer 4

Caused by reduced excretion of bilirubin, such as in:

• Biliary tract conditions (PSC, PBC)
• Biliary tract obstructions (gallstones, ascending cholangitis, cholangiocarcinoma)
• Genetic conditions (such as dubin-johnson syndrome)

Question 5

What are the complications of unconjugated hyperbilirubinemia

Answer 5

• Bilirubin encephalopathy (or kernicterus)

- Cholelithiasis (black pigmented gallstones)

Question 6

What are the symptoms associated with Gilberts Syndrome?

Answer 6

• Autosomal recessive condition
• Typically asymptomatic
• Mild haemolysis (e.g. with fasting, fevers, fatigue, stress, or exercise) will cause a mild jaundice
• NOT associated with liver disease or deranged LFTs

Question 7

Define Primary Sclerosing Cholangitis (PSC)

Answer 7

A progressive liver disease characterised by inflammation, fibrosis and INTRA & EXTRA hepatic strictures.
Associated with IBD. Can cause cholangiocarcinoma and gallbladder ca.

Question 8

Define Primary Biliary Cholangitis

Answer 8

The gradual destruction of epithelial cells lining the biliary duct causing cholestasis, jaundice and hypercholestrolemia. Exact pathophysiology unknown, but likely autoimmune, as linked to other conditions (RA, autoimmune thyoiditis).

Question 9

What labaratory signs would you expect to see for biliary tract obstruction?

Answer 9

• Hypercholestrolemia
• Vit ADEK deficiency
• Deranged LFTs (increase ALP and GGT)

Question 10

What is charcots triad of cholangitis?

Answer 10

1. Jaundice
2. Fever
3. RUQ pain

Question 11

What are the common symptoms of obstructive jaundice?

Answer 11

• Dark urine “tea stained”
• White poo
• Itchiness ++ “pruritus”
• xanthomas

Question 12

How do you differentiate unconjugated vs. conjugated jaundice

Answer 12

1. Urinalysis (of UGB)

Question 13

Define cirrhosis

Answer 13

Chronic fibrotic scarring and damage to the liver which is NOT reversible. Commonly caused by long term inflammation from alcohol, viral infection or drugs. Feels nodular.

Question 14

What are the complications of cirrhosis?

Answer 14

• Portal hypertension causing ascites, congestive splenomegaly
• Portosystemic shunts to venous anastamoses
• Poor renal perfusion and failure (hepatorenal syndrome)
• Hepatic encephalopathy (ammonia ++ and other toxins)
• Increased estrogen (causing gyneacomastia, spider angiomata and palmar erythema)
• Jaundice
• Coagulation issues

Question 15

How do you diagnose cirrhosis?

Answer 15

• Gold standard is LIVER BIOPSY

- Deranged LFT (AST>ALT and bilirubin) can be indicative

Question 16

How do you treat cirrhosis?

Answer 16

• Treat underlying cause (alcohol, antiviral HepC treatment)
• Manage complications
• Consider liver transplant if terminal