HISTO: Liver CPC Flashcards
Why is the endothelium in the liver special compared to the rest of the body?
The cells are discontinuous in the liver, spaces in between so that blood can come in between. This space where the blood comes in is called Space of Disse.
The blood can come into contact with the endothelial cells this way and all the liver enzymes.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/707/a_image_thumb.png?1628091837)
Which zone of the hepatocytes is the blood least oxygenated in? Where are the most metabolically active cells located?
Both in Zone 3
-
Zone 1 damage (periportal) – damage for substances that are directly damaging…
- Directly hepatoxic substances
- N.B. damage to zone 1 makes ALP rise more due to close proximity to the bile ducts
-
Zone 3 damage (centrilobular) – damage for substances that require bioactivation…
- Hypoxic damage (blood lost quite a lot of oxygen by the time it passes through zones 1 and 2)
- Metabolised hepatotoxic substances
- Zone 1 and 2 cells look similar at first but zone 3 are the most metabolically active cells in the liver
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/709/a_image_thumb.png?1628092128)
What does the portal triad consist of?
- Artery
- Vein
- Duct
They are hexagonal with trabecula with sinusoids between them
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/710/a_image_thumb.png?1628091980)
What substances can damage each of the zones of hepatocytes?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/711/a_image_thumb.png?1628092068)
How do you categorise and investigate the causes of a high bilirubin?
- Pre-hepatic (unconjugated) BR conjugates once it has passed through the liver
- Haemolysis (Ix: FBC and blood film)
- Hepatic (Ix: repeat LFTs)
- Post-Hepatic (i.e. obstructive jaundice)
How do you assess fractions of bilirubin/measure the split bilirubin?
- This is done using the van den Bergh reaction
- A DIRECT reaction measures conjugated bilirubin
- Add methanol which –> complete reaction to allow you to measure total bilirubin –> difference between two values gives the unconjugated bilirubin (i.e. an INDIRECT reaction)
In a prehepatic cause would you have more unconjugated or conjugated bilirubin?
More conjugated bilirubin because the liver is fine to conjugate it.
In children, what forms should most of the bilirubin be in and why?
This is usually NORMAL –> usually caused by liver immaturity and it should be an UNCONJUGATED hyperbilirubinaemia (because the liver cannot conjugate the bilirubin fast enough)
How do you manage high bilirubin in a child first line?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/716/a_image_thumb.png?1628092296)
How does phototherapy work? What should you do if it doesn’t help?
- Converts bilirubin into lumirubin + photo-bilirubin
- These are isomers that do NOT need conjugation for excretion
If the bilirubin does NOT resolve, other causes should be considered such as hypothyroidism and other causes of haemolysis (perform a Coombs’ test and measure unconjugated bilirubin levels)
How common is Gilberts and how is it inherited?
Gilbert’s syndrome is autosomal recessive
50% carry the gene –> 6% (1 in 20) have Gilbert’s
(25% risk of child having it if two carriers)
How do you know it is Gilberts syndrome using investigations?
- This is an entirely benign condition (no need for a liver biopsy – identify from history)
- If all the other enzymes are normal on LFTs, it tells you that there aren’t any other problems in the liver
- It’s probably Gilbert’s
What exacerbates Gilberts syndrome? What can reduce bilirubin levels (not done anymore)?
The bilirubin in Gilbert’s is worsened by fasting
Phenobarbital can reduce bilirubin levels in Gilbert’s syndrome
What is the pathophysiology of Glberts? Is unconjugated bilirubin found in urine and if so why? Is urobilinogen present in urine?
- UDP glucuronyl transferase activity is reduced to 30%
Unconjugated bilirubin is tightly albumin bound and does NOT enter the urine
- So, NO 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/gall bladder 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
What does absence of urobilinogen in the urine indicate?
Negative urobilinogen is suggestive of biliary obstruction
What does ALT, ALP and AST stand for?
Alanine aminotrasferase - ALT
Alkaline phosphatase - ALP
Aspartate aminotransferase - AST
Which investigation is the most representative of liver function?
- Prothrombin time is the most representative marker of liver function
- This is telling you that the liver is failing to make clotting factors (hence, it is not functioning well)
- Albumin is also a good marker (because it is representative of the liver’s synthetic function) but PT is better
What is the normal PT? How is this important in liver failure?
Normal PT is about 12-14 seconds
General rule: if the PT (s) is higher than the number of hours since the overdose, the patient should be transferred to a liver unit for a transplant
Which investigations are best at indicating that there is liver damage?
- ALT and AST are enzymes that tell you that there is damage rather than telling you how your liver is actually functioning
- Function of the liver is measured by:
- Albumin
- Clotting factors (PT, PTTK)
- Bilirubin
What are 6 causes of abnormal LFTs?
- Pre-hepatic – Gilberts, haemolysis
- Hepatic – viral hepatitis, alcoholic hepatitis, cirrhosis
- Post-hepatic – gallstones, pancreatic
When is AST>ALT? What are the other general rules for liver enzymes?
- ALT > AST = other forms of hepatitis
- AST > ALT = alcoholic hepatitis
- S = Stella
- High ALP = obstructive jaundice e.g. jaundice or cancer or head of the pancreas
Name 3 causes of hepatitis.
- Viral causes – check viral titres
- Autoimmune
- Alcoholic
What are the 3 features of hepatitis clinically?
Fever
Janudice
Raised ALT/AST
What is the route of transmission of Hep A? What are the most common sources?
- fAEco-oral transmission route – food or men-on-men sex
- Contaminated water is often the major source
- E.G. Recent shellfish consumption (improper washing)
What are the symptoms of hepatitis A and when are carriers infectious? How long is the course of infection?
Acute – asymptomatic, or – nausea, D+V, fever, jaundice, RUQ pain
Onset = 2-6 weeks;
Symptoms last = ~8 weeks
Often infectious whilst asymptomatic
What is the antibody response pattern to hepatitis A?
After viral titres start to drop, you get a rise in IgM antibodies and you become unwell with jaundice
If you survive the initial few weeks, you will produce IgG antibodies and from that point onwards you are cured, and you are immune - KILL OR CURE.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/829/734/a_image_thumb.png?1628093169)
How is hepatitis A managed? What is the vaccine against it called?
Treatment supportive (alcohol avoided) – vaccine called Havrix exists that contains some antigens of hepatitis A
What percentage of hepatitis B becomes chronic?
5-10%
What are the two antigens which can be detected in Hep B infection?
HBe and HBs (surface) antigens. HBe antigen is highly infectious. Cannot measure core Ag.