Liver CPC Flashcards
Causes of high BR (3)
Pre-hepatic (unconjugated) = haemolysis (e.g. drug induced aka rifampicin, hereditary, DIC)
Hepatic
- hepatitis (viral, AI)
- liver failure (drugs like ethanol/paracetamol/halothane/methyldopa/barbiturates, ALD)
- gallstones
- cirrhosis
Post-hepatic (obstruction)
- cholecystitis
- pancreatic cancer
- cholangiocarcinoma, PSC, PBC
Sinusoid anatomy
Space of Disse = space between hepatocytes and discountuous endothelium of the sinusoids where blood comes into contact with all the liver enzymes
zones:
- Zone 1: closest to the portal tract and it has the highest oxygen concentration
- Zone 3: most susceptible to hypoxia
- The cells in zone 3 are the most metabolically active cells in the liver
ix for high BR
Pre-hepatic (unconjugated) e.g. haemolysis (-> do a FBC and blood film)
Hepatic: repeat the LFTs
Post-Hepatic: obstructive jaundice
- Liver is fine, but something is blocking the bile duct (e.g. gallstone, cancer)
Measuring fractions of BR
This is done using the van den Bergh reaction
The van den Bergh reaction measures serum bilirubin via fractionation
A direct reaction measures conjugated bilirubin
The addition of methanol causes a complete reaction, which measures total bilirubin (conjugated plus unconjugated); the difference measures unconjugated bilirubin (an indirect reaction)
Unconjugated bilirubin is highly albumin bound and does not enter the urine
Conjugated means the liver is working, and the problem is post-hepatic
Paediatric jaundice
usually normal
unconjugated hyperbilirunaemia as liver immature
What should we look for if paediatric jaundice does not settle
hypothyroidism, causes of haemolysis
- TFT
- Coombes terst/DAT for haemolytic anaemia
- BR fractions
How do we manage paediatric jaundice
light (phototherapy); the skin can help to conjugate some of the bilirubin.
- Phototherapy converts bilirubin into two other compounds: lumirubin and photobilirubin
- These are isomers that do NOT need conjugation for excretion
Gilbert’s syndrome
benign and common
normal LFTs
Autosomal recessive
worsened on fasting (more yellow more BR)
Gilbert’s syndrome pathophysiology
UDP glucuronyl transferase enzyme activity is reduced to 30% - causes slight jaundice
Unconjugated bilirubin is tightly albumin bound and does not enter the urine
So, they do not have bilirubinuria (unconjugated BR does not enter the urine)
Urobilinogen is always present in the urine of normal people
- This comes from the enterohepatic circulation
The bilirubin you make goes through the biliary tree and into the bowel (if GI tract is healthy)
Here, bacteria convert some of the bilirubin to stercobilinogen and urobilinogen
This is then reabsorbed into the circulation and you pee it out
So, the presence of urobilinogen in the urine tells you that the enterohepatic circulation is intact
Negative urobilinogen is suggestive of biliary obstruction
GILBERT’S URINE: THERE IS NO BILIRUBIN (UNCONJUGATED), BUT THERE IS UROBILINOGEN
Gilbert’s syndrome management
phenobarbital reduce BR levels
Liver function
- most reperesentative marker of liver function (why not albumin)
- paracetamol overdose
- which other markers
- are enzymes markers
PT (12-14 seconds) as liver makes all clotting factors
- albumin good (represents synthetic function) but PT better
if PT is higher than number of hours since paracetamol overdose -> transfer patient to liver unit for liver transplant
other markers = albumin, clotting factors (PT,PTTK), BR
enzymes not true test of liver function = tells us that there is some liver damage
liver enzymes
Hepatitis A serology
exposure to virus required (travel hx)
faeco-oral
asymptomatic but infectious for long time (incubation period)
after IgG made -> cured and immune (NO RECURRENCE)
Havrix vaccine = antigens of hep A
Hepatitis B serology: acute infection
hep B can be acute/chronic
we often measure HBs Ag and HBe Ag
When your immune response mounts and you produce antibodies, the HBeAg titre decreases
Once HBeAg levels go all the way down, you will be able to detect anti-HBe antibodies
Similarly, when HBsAg reaches the bottom, anti-HBs antibodies become detectable
In the end, you will have three antibodies and no antigens
What does anti-HBc tell us?
you have been exposed to hep B int he past but we don’t have the capability to measure this
Hepatitis B serology: chronic carrier
this patient never clears the virus
Although the HBeAg declines (and hence infectivity declines), the HBsAg remains for years
Some of these people never become jaundiced and so do not realise that they have the virus
These people are actively antigenic and can spread the virus
histology of hepatitis (2)
lots of cells contianing fat
- swollen/balloon cells containing Mallory;’s hyaline
- inflmattory cells (neutrophil polymorphs)
alcohol hepatitis
if alcohol abuse persist
neutrophils infiltrate liver and balloon cells seen
megamutochondria
fatty change
damage may not be revrsible
cirrhosis
end stage of all liver isease
bile accunulation in liver
hepatocytes swollen and full of Mallory hyaline blocking the flow of bile through the liver
bile levels mirrored by raised BR in blood
collagen fibres surrounding individual liver cells
what does this show?
blue is collagen
collagen fibres around individual cells characteristic of alcohol abuse
this scarring is typical of cirrhosis
features of nodules
You can see around the nodules very clearly because they have a cuff of fibrous tissue
Alcoholic livers tend to have small nodules (micronodular cirrhosis)
intrahepatic shunting
In this condition you get scarring between the portal tracts and the central veins
This bridge of fibrosis means that blood doesn’t get in close contact with the hepatocytes
Hence, the blood does not get filtered
This is i_ntrahepatic shunting of the blood_
