12. Jaundice and LFTs

Question 1

What is jaundice?

Answer 1

A yellowing of the skin and eyes, due to raised bilirubin

Question 2

What is bilirubin and where is it produced?

Answer 2

Breakdown product of haem, produced in the spleen

Question 3

What is unconjugated bilirubin bound to?

Answer 3

albumin

Question 4

Where and why is bilirubin conjugated?

Answer 4

In the liver, to make it more water soluble so can be excreted in urine and faeces

haem –> biliverdin –> bilirubin –> conjugated

Question 5

What are the 3 routes for conjugated bilirubin?

Answer 5

option 1 - go in circles in hepatic circulation as part of bile
option 2 - travel to duodenum where it is oxidised to stercobilin - pigmented part of faeces
option 3 - goes in bloodstream to kidneys and releases as urobilinogen in urine

Question 6

What are the 3 types of jaundice and what is the general mechanism that causes them?

Answer 6

• Pre-hepatic, too much haem
• hepatic, reduced hepatocyte function
• post-hepatic, obstructive causes

Question 7

What is pre-hepatic jaundice caused by and what type of bilirubin is raised?

Answer 7

Caused by increased degradation of haemoglobin, overwhelms livers ability
- raised unconjugated bilirubin

◦ Liver conjugating ability is fine
◦ Excretion pathway is fine

Too much demand on the liver so not able to conjugate

Question 8

Give examples of conditions that cause pre-hepatic jaundice.

Answer 8

Haemoglobinopathies
e.g. Sickle cell, Thalassaemia, Spherocytosis
Damage to red blood cells
e.g. Haemolysis

Question 9

What is hepatic jaundice caused by and what type of bilirubin is raised?

Answer 9

Reduced conjugating ability of the liver due to damage to hepatocytes

◦ Amount of bilirubin is fine
◦ Excretion pathway is usually fine
Therefore, you get a mix of conjugated and unconjugated bilirubin

Question 10

Give examples of conditions that lead to hepatic jaundice.

Answer 10

Causes of cirrhosis:
e.g. alcoholic liver diease, NAFLD, Viral hepatitis, autoimmune, Wilson’s, Haemochromatosis, medications, etc.

Can also occur in acute liver damage e.g. paracetamol toxicity, acute viral hepatitis

Question 11

What is post-hepatic jaundice caused by and what type of bilirubin is raised?

Answer 11

Obstruction to the excretion pathway

◦ Amount of bilirubin is fine
◦ Conjugating ability of the liver is usually
fine
Therefore, the raised bilirubin tends to be conjugated

Question 12

What happens levels of bilirubin excreted in urine in post-hepatic jaundice?

Answer 12

Conjugated therefore water soluble, more is excreted in the kidney, making the urine darker

Question 13

What effect does post-hepatic jaundice have on stool and urine?

Answer 13

pathologically high levels of conjugated bilirubin can lead to dark urine and pale stools

Question 14

Give examples of conditions that can cause post-hepatic jaundice.

Answer 14

Gallstones(in common bile duct), Biliary stricture, Pathology of the head of the pancreas

Intrahepatic pathology can compress the intrahepatic bile ducts
◦ Oedema e.g. inflammation (autoimmune conditions) - PBC, PSC
◦ Growth e.g. primary or metastatic malignancy
◦ Scarring e.g. cirrhosis - non expandable so compress bile ducts

Question 15

What is measured in LFTs?

Answer 15

Bilirubin, Conjugated vs unconjugated
Albumin
Alanine transaminase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)

Question 16

What does measuring albumin tell us?

Answer 16

Assess synthetic function of the liver
◦ i.e. if liver function is reduced, it makes less albumin
◦ Usually seen in chronic cases

Question 17

WHAT DOES LOW ALBUMINM CONTRIBUTE TO?

Answer 17

Ascites

Question 18

What is AST and ALT and what do they indicate?

Answer 18

These are hepatic enzymes

◦ If hepatocytes are damaged, these enzyme levels go up

Question 19

What rises more in acute and chronic liver damage AST or ALT?

Answer 19

ALT rises > AST in acute liver damage

AST > ALT in cirrhosis & alcoholic hepatitis

Question 20

WHich is more specific to liver AST or ALT?

Answer 20

ALT is more specific to the liver

◦ AST is also found in cardiac/skeletal muscle and red blood cells

Question 21

An increase in what along with increase AST indicate skeletal muscle damage?

Answer 21

CK

Question 22

An increase in what along with increase AST indicate cardiac muscle damage?

Answer 22

troponins

Question 23

Where is ALP found and when might there be increased ALP?

Answer 23

Found in the cells lining the bile ducts

◦ Levels therefore go up in cholestasis (bile duct obstruction) but also when there is increases bone turn over

Question 24

What can be used to confirm ALP increase due to bile duct obstruction?

Answer 24

Gamma-Glutamyl Transferase (“Gamma GT”)

- increases

Question 25

What do abnormal LFTs tell you?

Answer 25

◦ Tell you about the underlying liver pathology
◦ Give a pattern or picture;
◦ Hepatocellular damage
◦ Obstructive (cholestasis)
◦ Mixed; damage to hepatocytes and an element of obstruction

Question 26

When might you see a mixed picture of hepatic and post-hepatic jaundice?

Answer 26

Obstruction AND hepatocellular damage

◦ Damage to hepatocytes leads to obstruction (e.g. cirrhosis, cancers, oedema)
◦ Obstruction leads to hepatocellular damage

Question 27

Describe how the LFTs might be in pre hepatic jaundice?

Answer 27

Raised levels of unconjugated bilirubin
Associated anaemia
Other LFTs NAD

Question 28

Describe how the LFTs might be in hepatic jaundice?

Answer 28

Likely to see mixed picture bilirubin
High levels of ALT and AST (‘hepatocellular damage’)
Usually normal ALP

Question 29

Describe how the LFTs might be in post hepatic jaundice?

Answer 29

Raised levels of conjugated bilirubin
Raised ALP (‘obstructive pattern’)
Associated increase in 𝛾-GT
Usually normal ALT/AST