LFT's

Question 1

What are the main synthetic functions of the liver ?

Answer 1

• Conjugation and elimination of bilirubin
• Synthesis of albumin
• Synthesis of clotting factors
• Gluconeogenesis

Question 2

What investigations are mainly done to assess the synthetic function of the liver ?

Answer 2

• Serum bilirubin
• Serum albumin
• PT/INR

Question 3

What type of jaundice cases prolonged PT/INR and why?

Answer 3

• Liver is responsible for synthesis of most clotting factors.
• When there is reduced synthetic function of the liver it therefore doesnt produce these factors as well and results in prolonged PT/INR
• ==> in the absence of other potential causes of a prolonged PT/INR then it suggests an intrahepatic pathology

Question 4

What are the other causes of a prolonged PT/INR besides intrahepatic pathology ?

Answer 4

• Anti-coagulant drugs (inc Warfarin)
• Bile malabsorption causing relative Vit K deficiency
• Consumptive coagulopathies
• Congenital coagulopathy

Question 5

What are the enzymes produced by the liver ?

Answer 5

• AST & ALT
• ALP
• gamma-GGT

Question 6

What is AST/ALT and what do they usually represent ?

Answer 6

These are hepatic enzymes that are usually intracellular, but when the liver is damaged they are released from hepatocytes ==> become raised when liver is damaged

Question 7

Which is better for assessing liver damage AST or ALT ?

Answer 7

ALT because it is specific to the liver whereas AST can be increased due to other disorders as it is also present in the heart, pancreas, skeletal muscle, lungs, RBC’s & WBC’s

==> ALT is the most useful marker of hepatocellular injury

Question 8

Where does ALP originate and ==> what is it a useful marker of ?

Answer 8

• ALP is particularly concentrated in the liver, bile duct and bone tissues.
• It is a useful marker of intrahepatic and post-hepatic jaundice - in particular tho for post-hepatic jaundice

Note it can also be increased in bone disease, during pregnancy, and certain malignancies

Question 9

List the causes of a solo raised ALP

Answer 9

• Bony metastases / primary bone tumours (e.g. sarcoma)
• Vitamin D def
• Recent bone fractures
• Renal osteodystrophy

Question 10

Define what jaundice is

Answer 10

This is yellowing of the skin and sclera

Question 11

What causes jaundice ?

Answer 11

It results from high levels of bilirubin in the blood.

Question 12

What levels of bilirubin usually result in jaundice ?

Answer 12

usually >40 umol/l

Question 13

What is bilirubin the normal breakdown product of ?

Answer 13

Haemoglobin

Question 14

Describe the normal breakdown pathway and excretion of bilirubin

Answer 14

1. Normally haemoglobin is broken down into unconjugated bilirubin
2. It is then goes to the liver where it undergoes conjugation (to make it water soluble)
3. Conjugated bilirubin is then excreted via the bile into the GI tract (as urobilinogen and stercobilin) which is then excreted out of the body

Around 10% of urobilinogen is reabsorbed into the bloodstream and excreted through the kidneys ==> bilirubin gives urines its darker colour

Question 15

What are the indices of intrinsic function of the liver ?

Answer 15

• Albumin
• PT/INR
• Bilirubin

Question 16

What are the 3 main types of jaundice ?

Answer 16

1. Pre-hepatic
2. Hepatocellular (hepatic)
3. Post-hepatic.

Question 17

What is the underlying pathogenesis of pre-hepatic jaundice ?

Answer 17

• There is excessive RBC breakdown which overwhelms the liver’s ability to conjugate bilirubin.
• This causes an unconjugated hyperbilirubinaemia.
• Any bilirubin that manages to become conjugated will be excreted normally, yet it is the unconjugated bilirubin that remains in the blood stream to cause the jaundice.

Question 18

List the potential causes of pre-hepatic jaundice

Answer 18

Increased bilirubin production:

• Extra/intravascular haemolysis
• Extravasation of blood into tissues

Impaired hepatic bilirubin uptake:

• Heart Failure
• Drugs; Rifampicin, Probenecid

Impaired bilirubin conjugation

• Gilbert’s/Crigler-Najjar Syndrome
• Hyperthyroidism
• Advanced Liver Disease

Question 19

What is the underlying pathogenesis of pre-hepatic jaundice ?

Answer 19

• There is dysfunction of the hepatic cells. The liver loses the ability to conjugate bilirubin (acute hepatocellular injury)
• In other cases it may become cirrhotic, where it compresses the intra-hepatic portions of the biliary tree causing a degree of obstruction. This leads to both unconjugated and conjugated bilirubin in the blood, termed a ‘mixed picture’. (chronic hepatocellular injury)

For simplisity know that intrahepatic causes a conjugated hyperbilirubinaemia

Question 20

List the causes of intrahepatic jaundice

Answer 20

Causes of acute hepatocellular injury include:

• Poisoning (paracetamol overdose)
• Infection (Hepatitis A and B)
• Liver ischaemia

Causes of chronic hepatocellular injury include:

• Alcoholic fatty liver disease
• NAFLD
• Chronic infection (Hepatitis B or C)
• Primary biliary cirrhosis
• Others; alpha-1 antitrypsin deficiency, Wilson’s disease, Haemochromatosis

Question 21

What is the underlying problem causing all post-hepatic jaundice (obstructive)?

Answer 21

There is obstruction of biliary drainage stopping conjugated bilirubin being both excreted out in the faeces and urine

Question 22

List the potential causes of post-hepatic jaundice

Answer 22

• Gall stones (cholelisthesis)
• PSC
• Cholangiocarcinoma
• Head of pancreas mass
• Acute/Chronic Pancreatitis

Question 23

What does the colour of stool and urine tell you about the cause of jaundice ?

Answer 23

1. Normal urine + normal stools = pre-hepatic cause
2. Dark urine + normal stools = hepatic cause
3. Dark urine + pale stools = post-hepatic cause (obstructive)

If bile and pancreatic lipase’s are unable to reach the bowel because of a blockage (e.g. in obstructive post-hepatic pathology), fat is not able to be absorbed, resulting in stools appearing pale, bulky and more difficult to flush.

Question 24

What are the LFT results suggestive of a pre-hepatic cause of jaundice ?

Answer 24

Question 25

What is the most common cause of a isolated raised jaundice ?

Answer 25

Gilberts syndrome

Question 26

What is the relevence of AST/ALT ratios?

Answer 26

AST \> ALT is seen in cirrhosis and acute alcoholic hepatitis **(basically think alcohol if AST/ALT ratio \> 2)**

Question 27

Describe the LFT results you would expect for intrahepatic and then post-hepatic jaundice

Answer 27

Intrahepatic jaundice: * Expect a markedly increased ALT comapred to ALP (which is also raised), also PT/INR increased Post-hepatic: * Expect a markedly increased ALP compared to ALT (which is also raised). If so check GGT because if also increased then very likely post-hepatic. If not then consider other causes of rasied ALP

Question 28

What investigations should be done for a patient presenting with jaundice

Answer 28

Any patient presenting with jaundice should have the following bloods taken: * LFT's * Coagulation studies (PT can be used as a marker of liver synthesis function) * FBC (anaemia, raised MCV, and thrombocytopenia all seen in liver disease) and U&Es * Specialist blood tests, as summarised below as part of a liver screen

Question 29

What does a liver screen include ?

Answer 29

* LFTs * Coagulation screen * Hepatitis serology (A/B/C) * Epstein-Barr Virus (EBV) * Cytomegalovirus (CMV) * Anti-mitochondrial antibody (AMA) * Anti-smooth muscle antibody (ASMA) * Anti-liver/kidney microsomal antibodies (Anti-LKM) * Anti-nuclear antibody (ANA) * p-ANCA * Immunoglobulins – IgM/IgG * Alpha-1 Antitrypsin – Alpha-1 Antitrypsin deficiency * Serum Copper – Wilson’s disease * Ceruloplasmin – Wilson’s disease * Ferritin – Haemochromatosis * Tissue transglutaminase antibody (TTG) - for coeilacs