LFT's Flashcards
What are the main synthetic functions of the liver ?
- Conjugation and elimination of bilirubin
- Synthesis of albumin
- Synthesis of clotting factors
- Gluconeogenesis
What investigations are mainly done to assess the synthetic function of the liver ?
- Serum bilirubin
- Serum albumin
- PT/INR
What type of jaundice cases prolonged PT/INR and why?
- 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
What are the other causes of a prolonged PT/INR besides intrahepatic pathology ?
- Anti-coagulant drugs (inc Warfarin)
- Bile malabsorption causing relative Vit K deficiency
- Consumptive coagulopathies
- Congenital coagulopathy
What are the enzymes produced by the liver ?
- AST & ALT
- ALP
- gamma-GGT
What is AST/ALT and what do they usually represent ?
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
Which is better for assessing liver damage AST or ALT ?
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
Where does ALP originate and ==> what is it a useful marker of ?
- 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
List the causes of a solo raised ALP
- Bony metastases / primary bone tumours (e.g. sarcoma)
- Vitamin D def
- Recent bone fractures
- Renal osteodystrophy
Define what jaundice is
This is yellowing of the skin and sclera
What causes jaundice ?
It results from high levels of bilirubin in the blood.
What levels of bilirubin usually result in jaundice ?
usually >40 umol/l
What is bilirubin the normal breakdown product of ?
Haemoglobin
Describe the normal breakdown pathway and excretion of bilirubin
- Normally haemoglobin is broken down into unconjugated bilirubin
- It is then goes to the liver where it undergoes conjugation (to make it water soluble)
- 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
What are the indices of intrinsic function of the liver ?
- Albumin
- PT/INR
- Bilirubin
What are the 3 main types of jaundice ?
- Pre-hepatic
- Hepatocellular (hepatic)
- Post-hepatic.
What is the underlying pathogenesis of pre-hepatic jaundice ?
- 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.
List the potential causes of pre-hepatic jaundice
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
What is the underlying pathogenesis of pre-hepatic jaundice ?
- 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
List the causes of intrahepatic jaundice
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
What is the underlying problem causing all post-hepatic jaundice (obstructive)?
There is obstruction of biliary drainage stopping conjugated bilirubin being both excreted out in the faeces and urine
List the potential causes of post-hepatic jaundice
- Gall stones (cholelisthesis)
- PSC
- Cholangiocarcinoma
- Head of pancreas mass
- Acute/Chronic Pancreatitis
What does the colour of stool and urine tell you about the cause of jaundice ?
- Normal urine + normal stools = pre-hepatic cause
- Dark urine + normal stools = hepatic cause
- 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.
What are the LFT results suggestive of a pre-hepatic cause of jaundice ?
