ChemPath: Liver Disease

Question 1

How may the causes of high bilirubin be categorized?

Answer 1

Pre-hepatic: Liver is OK but something beforehand is increasing the through put and that is haemolysis. Haemolytic anaemia is a good cause. Do a FBC and film. Film you can see if any RBCs are lysing and FBC may show anaemia.

Hepatic disease: Repeat the LFT, gamma GT, all the enzymes the liver makes will leak out into the circulation

Post-hepatic: Liver is fine but there’s something blocking the bile duct. Commonly either a gallstone and cancer of the head of the pancreas. Block the bile duct, end up with bilirubin in the circulation.

Question 2

Where is bilirubin conjugated?

Answer 2

The liver

Question 3

How do you measure conjugated and unconjugated bilirubin?

Answer 3

Van de Bergh Reaction

A direct reaction measures conjugated bilirubin

An indirect reaction measures unconjugated bilirubin

Question 4

When may paediatric jaundice be normal and when may it be pathological?

Answer 4

Paediatric jaundice is usually normal, but the bilirubin should be unconjugated as the cause is usually liver immaturity coupled with a fall in the haemoglobin early in life. If it doesn’t settle, other rare causes should be looked for including hypothyroidism, other causes of haemolysis (including a Coombes test or DAT), and the unconjugated bilirubin will be useful.

Question 5

What therapy may be used to help bilirubin conjugation?

Answer 5

Phototherapy - skin may also conjugate bilirubin. Converts bilirubin into two other compounds, lumirubin and photobilirubin which are isomers that do not need conjugation for excretion.

Question 6

What type of inheritance pattern does Gilberts syndrome have?

Answer 6

Recessive

Question 7

How prevalent is Gilbert’s syndrome?

Answer 7

About 6% of people will have it (1 in 20) 50% carry the gene.

Question 8

What would you expect to see on LFTs for Gilberts?

Answer 8

Normal LFTs and high bilirubin. No need for liver biopsy.

Question 9

What may exacerbate a high bilirubin level in Gilberts?

Answer 9

Fasting will increase bilirubin.

Question 10

Describe the pathology of Gilberts.

Answer 10

UDP glucuronyl transferase activity reduced to 30%. This causes a slightly raised unconjugated bilirubin but this does not enter the urin and cause bilirubinurea.

Question 11

What does it mean if you have urobilinogen in the urine?

Answer 11

That the enterohepatic circulation is intact. Urobilinogen is always present in the urine of normal people. It comes from the entero-hepatic circulation. If you have a normal GIT, the bilirubin that you make goes into the biliary tree, into the bowel, then bacteria in the bowel converts a small amount of bilirubin into stercobilinogen which is the same as urobilinogen and is reabsorbed and you poo it out.

Question 12

What does a lack of urobilinogen in the urine suggest?

Answer 12

Blockage of the biliary tree. If you block the biliary tree then the bacteria cannot see the bilirubin, you get pale stools, don’t make any urobilinogen which means urine becomes negative. If urine is negative for urobilinogen but they are jaundice, suggests physical obstruction to biliary tree.

Question 13

What is the best measure of Liver Function?

Answer 13

• Prothrombin time (clotting factors PT, PTTK)
• Albumin
• Bilirubin

Question 14

What do raised levels of all liver enzymes suggest?

Answer 14

Hepatitis

Question 15

What does a high AST and ALT suggest?

Answer 15

Hepatocyte damage

Question 16

What would an extremely high Alk phos suggest?

Answer 16

• Obstructive Jaundice
• Obstructive jaundice normally causes alk phos to rise a lot. Alk phos will increase by the greatest of the enzymes with obstructive jaundice.

Question 17

What are prehepatic causes of hyperbilirubinaemia?

Answer 17

• Gilberts
• Haemolysis

Question 18

What are hepatic causes of hyperbilirubinaemia?

Answer 18

• Viral hepatitis
• Alcoholic hepatitis
• Cirrhosis

Question 19

What are post-hepatic causes of hyperbilirubinaemia?

Answer 19

• Gallstones
• Cancer of the head of the pancreas

Question 20

What are 3 main causes of hepatitis?

Answer 20

• Viral - check viral titres
• Autoimmune
• Alcoholic

Question 21

Describe Hepatitis A serology.

Answer 21

To get hep A you need to be exposed to the virus. Usually in developing country, drink contaminated water – virus replicates and you have an incubation period, Virus then excreted. Then you have immune response. IgM increases and jaundice – some people die at this point. IgG comes next. If you survive, you are cured and then immune. It is either kill or cure. Can’t get it twice.

Question 22

What are the two main antigens in Hepatitis B?

Answer 22

• Antigen E
• Antigen S

Question 23

Describe the serology of someone who has been infected with Hep B.

Answer 23

• Anti-HBc +
• Anti-HBs +
• Anti-HBe +

Question 24

What antigen does the Hep B vaccine contain?

Answer 24

HBs

Question 25

Describe the serology of someone who has been vaccinated for Hep B.

Answer 25

• Anti-HBs+
• Anti-HBe -
• Anti-HBc -

Question 26

What causes chronic hepatitis B?

Answer 26

When a patient has had Hep B and has the antibodies but never clears the virus. This person is a carrier and is infectious to others at all times.

Question 27

What are defining histology features of Alcoholic Hepatitis?

Answer 27

• Liver cell damage:
  
  • ballooning degeneration
  • Mallory-Denk Bodies
• Inflammation
• Fibrosis

Question 28

What does NASH stand for?

Answer 28

Non-alcoholic steato-hepatitis

Question 29

What is the management of alcoholic hepatitis?

Answer 29

• Supportive
• Stop alcoholic
• Nutrition
• Vitamins (B1, thiamine)
• Ocassionally steroids

Question 30

What diseases do deficiencies in these cause?

• Vit D
• Vit C
• B12
• B1
• B3
• Folic acid

Answer 30

• Vit D = Rickets
• Vit C = Scurvy
• B12 / IF = Pernicious anaemia
• B1 = Beri-beri
• B3 = Pellagra
• Folic acid = neural tube defects

Question 31

What are clinical features of chronic stable liver disease?

Answer 31

• Multiple spider naevi
• Dupuytren’s contracture
• Plamar erythema
• Gynaecomastia

Question 32

What else are you most likely to find on careful abdominal examination, given the visible vein on the anterior abdominal wall?

Answer 32

Splenomegaly. Increasing portal vein pressure goes up to the spleen. Splenomegaly is a sign of portal hypertension.

Question 33

What are 3 clinical features of portal hypertension caused by cirrhosis?

Answer 33

• Visible veins
• Splenomegaly
• Ascites

Question 34

What causes a liver flap?

Answer 34

Liver flap is due to poison toxins to the brain due to inability of the liver to clear them.

Question 35

What are the consequences of liver failure?

Answer 35

• Failed synthetic function
• Failed clotting factor and albumin
• Failed clearance of bilirubin
• Failed clearance of ammonia (encephalopathy)

Question 36

What is the management of liver failure?

Answer 36

• Minimize work done by the liver
• Minimize GI bleeding
• Wait and hope they recover OR give them a new liver

Question 37

What is intra-hepatic shunting of blood?

Answer 37

Blood comes into the portal tract via the portal vein and hepatic artery, trickles down the sinusoids and emerges through the hepatic vein. Here the patient develops scarring between the portal tract and the central vein so instead of trickling past the hepatocytes there is collagen tissue. Blood comes into the liver, it goes nowhere near the hepatocytes, it bypasses them completely, it comes in and then comes out. Nothing is done to the blood. This is called intra-hepatic shunting of the blood.

Question 38

What is a porto-systemic anastomoses?

Answer 38

Area where the portal blood meets the systemic blood.

Question 39

Where are the possible sites of porto-systemic anastamoses?

Answer 39

• Oesophageal varices
• Rectal varices
• Umblical vein recanalising
• Spleno-renal shunt

Question 40

What does scratching with jaundice suggest?

Answer 40

A post-hepatic cause

Question 41

What 2 things make up bile?

Answer 41

Bilirubin and bile salts

Question 42

What is the role of bile salts?

Answer 42

Bile salts emulsify fats. Bile salts deliberately excreted into the gut, emulsify fat then reabsorbed later downstream in the gut so there is enterhepatic circulation.

Question 43

What causes itching in post-hepatic jaundice?

Answer 43

Bile salts or bile acids. Both not in the blood stream usually but appear when you block the bile duct.

Question 44

What is Courvoisier’s Law?

Answer 44

In the presence of jaundice, if the gall bladder is palpable, the cause is unlikely to be gall stones. This is because a gall bladder with stones is usually small and fibrotic and incapable of being large.