ChemPath 4s: Liver CPC Flashcards
What does this show?
- hepatocytes arranged in a trabecula with sinusoids between them;
- the portal triad then consists of an artery, vein and bile duct
What is the space of Disse?
The ‘Space of Disse’ –
the spaces between the hepatocytes and the endothelium (discontinuous organisation) of the sinusoids meaning that the blood comes into contact with the all the liver enzymes
Label this image. Which zone (1-3) is the most oxygenated?
Portal tract → zone 1 (periportal) → 2 → 3 (centrilobular) → central vein
zone 1 has most oxygenated blood, zone 3 has least
Which zone (1-3) can be damaged by substances that are directly damaging
- Zone 1 (periportal)
- Directly hepatoxic substances
Which zone (1-3) can be damaged by substances that require bioactivation
- Zone 3 (centrilobular)
- Metabolised hepatotoxic substances (zone 3 = most metabolically active cells in the liver)
Which zone (1-3) can be damaged by hypoxia?
- Zone 3 (centrilobular)
- Hypoxic damage (blood lost quite a lot of oxygen by the time it passes through zones 1 and 2)
Damage to which zone can make ALP rise more due to close proximity to the bile ducts?
Zone 1 (periportal)
What are the Causes of a high bilirubin?
- Pre-hepatic (unconjugated)
- Haemolysis (Ix: FBC and blood film)
- Hepatic (Ix: repeat LFTs)
- Post-Hepatic (i.e. obstructive jaundice)
When does bilirubin conjugate?
once it has passed through the liver
How is Fractions of Bilirubin / ‘Split Bilirubin measured?
o This is done using the van den Bergh reaction
What does a DIRECT van den Bergh reaction measure?
conjugated bilirubin
How do you measure the uncongugated bilirubin?
Add methanol to van den Bergh reaction
which
→ complete reaction to allow you to measure total bilirubin
→ difference between two values gives the unconjugated bilirubin (i.e. an INDIRECT reaction)
Describe Paediatric Jaundice. What type of hyperbilirubinaemia is considered normal in children?
- This is usually NORMAL → usually caused by liver immaturity
- it should be an UNCONJUGATED hyperbilirubinaemia (because the liver cannot conjugate the bilirubin fast enough)
What should be done if high UNCONJUGATED bilirubin levels do not resolve in a child?
- other causes should be considered such as:
- hypothyroidism
- other causes of haemolysis
- perform a Coombs’ test (autoimmune haemolytic anaemia)
- measure unconjugated bilirubin levels
What does Phototherapy do?
- Converts bilirubin into lumirubin + photo-bilirubin
- These are isomers that do NOT need conjugation for excretion
What is the genetics behind Gilbert’s syndrome?
- Gilbert’s syndrome is autosomal recessive
- 50% carry the gene
- → 6% (1 in 20) have Gilbert’s
Is Gilbert’s syndrome malignant? is a biopsy needed for diagnosis?
- This is an entirely benign condition
- no need for a liver biopsy – identify from history
When might jaundice in Gilbert’s syndrome worsen?
periods of physiological stress e.g. fasting, , illness, dehydration, overexertion, menses
When might jaundice in Gilbert’s syndrome worsen?
periods of physiological stress e.g. fasting, , illness, dehydration, overexertion, menses
What can reduce bilirubin levels in Gilbert’s syndrome?
Phenobarbital
Outline the pathophysiology of Gilbert’s syndrome
UDP glucuronyl transferase activity is reduced to 30%
Unconjugated bilirubin is tightly albumin bound and does NOT enter the urine
So, they do NOT have bilirubinuria
Urobilinogen is ALWAYS present in the urine of normal people – this comes from the enterohepatic circulation
The bilirubin that you make will go through the biliary tree and into the bowel, where bacteria will convert bilirubin to stercobilinogen and urobilinogen – this is then reabsorbed into the circulation and you excrete it
So, the presence of urobilinogen in the urine tells you that the enterohepatic circulation is intact
Negative urobilinogen is suggestive of biliary obstruction
Which marker is most representative of liver function
• Prothrombin time is the most representative marker of liver function
What is the normal PT time?
normal PT is about 12-14 seconds
any higher, and its telling you that the liver is failing to make clotting factors
Is albumin a good marker of liver function?
Albumin is also a good marker (because it is representative of the liver’s synthetic function) but PT is better
What do AST and ALT tell you?
ALT and AST are enzymes that tell you that there is damage rather than telling you how your liver is actually functioning
Do NOT truly test the liver’s synthetic function
How is function of the liver assessed?
Function of the liver is measured by:
- Albumin
- Clotting factors (PT, PTTK)
- Bilirubin
Where is alkaline phosphatase (ALP) show? What is it usually used as a marker of (when in the presence of raised GGT)?
- ALP is particularly concentrated in the liver, bile duct and bone tissues.
- ALP is often raised in liver pathology due to increased synthesis in response to cholestasis.
- As a result, ALP is a useful indirect marker of cholestasis.
What does a raised ALP and GGT show?
- raised GGT can be suggestive of biliary epithelial damage and bile flow obstruction.
- It can also be raised in response to alcohol and drugs such as phenytoin.
- A markedly raised ALP with a raised GGT is highly suggestive of cholestasis.
What does an isolated raised ALP show? (no raised GGT)
A raised ALP in the absence of a raised GGT should raise your suspicion of non-hepatobiliary pathology. Alkaline phosphatase is also present in bone and therefore anything that leads to increased bone breakdown can elevate ALP.
- Bony metastases or primary bone tumours (e.g. sarcoma)
- Vitamin D deficiency
- Recent bone fractures
- Renal osteodystrophy
What does an isolated raised bilirubin indicate? (ALT and AST are normal)
An isolated rise in bilirubin is suggestive of a pre-hepatic cause of jaundice.
Causes of an isolated rise in bilirubin include:
- Gilbert’s syndrome: the most common cause.
- Haemolysis: check a blood film, full blood count, reticulocyte count, haptoglobin and LDH levels to confirm.
What does this clinical picture show?
- These LFTs suggest a hepatic cause of jaundice (high bilirubin)
- The AST and ALT are very high → suggest hepatocyte damage
- The ALP is marginal (it is usually highest in times of biliary obstruction)
What are the causes of abnormal LFTs?
- Pre-hepatic – Gilberts, haemolysis
- Hepatic – viral hepatitis, alcoholic hepatitis, cirrhosis
- Post-hepatic – gallstones, pancreatic