4s: 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 (periportal): closest to the portal tract and it has the highest oxygen concentration, directly hepatic substances, damage makes ALP rise more due to close proximity to bile ducts
- Zone 3 (centrilobular): most susceptible to hypoxia
- The cells in zone 3 are the most metabolically active cells in the liver, metabolised hepatotoxic substances
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 resolve
hypothyroidism, causes of haemolysis → do ix:
- 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
What drug can reduce BR levels in Gilber’s syndrome
Phenobarbital = UDPGT enzyme inducer
Liver function
- What is most representative 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
ALP <130
AST <50
ALT <50
Hepatitis A serology
exposure to virus required (travel hx)
faeco-oral (food, MSM, contaminated water e.g. recent shellfish consumption)
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 in the past but we don’t have the capability to measure this
What does the Hep B vaccine contain?
HBsAg (virulent) so you will not have HBeAg or Anti-HBe or Anti-HBc
If you see a patient who has HBsAb present and nothing else, this is consistent with a health worker who has been vaccinated. If you can measure both antibodies, this is consistent with someone who has had the infection.
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 containing fat
- swollen/balloon cells containing Mallory’s hyaline
- inflammatory cells (neutrophil polymorphs)
fatty liver disease
If anyone drinks too much alcohol, they get fat deposits in their liver. This is due to metabolic overload. However, these fatty deposits will go away if the patient stops drinking alcohol.
alcoholic hepatitis
- associated histological feature = iif alcohol abuse persist neutrophils infiltrate liver and balloon cells (with Mallory-Den bodies seen)
- megamitochondria
- fatty change
Liver cell damage, inflammation, fibrosis
damage may not be reversible
cirrhosis
end stage of all liver isease
bile accumulation 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 staining collagen
collagen fibres around individual cells characteristic of alcohol abuse
this scarring is typical of cirrhosis
FLD -> Alcoholic hepatitis -> cirrhosis
FLD = fat deposits
AH = neutrophils, balloon cells w/ Mallory hyaline, fat deposits, megamitochondria
cirrhosis = all of the above with bile, raised BR, and collagen fibres surrounding indiviual liver cells (scarring)
DDx for FLD
Non-alcoholic steatohepatitis (NASH)
- This looks exactly like alcoholic hepatitis (history is important)
- It is the most common cause of liver disease in the Western world
Alcoholic hepatitis
Malnourishment (Kwashiorkor)
tx for a patient with alcoholic hepatitis
how regeneration leads to portal hypertension
fluids
stop alcohol intake
- regeneration -> little nodules -> portal hypertension
nutrition (B1 thiamine aka pabrinex)
occasionally steroids (controversial)
B1, B2, B3 vitamins names and deficiency names
B1 (thiamine, pabrinex) + B2 riboflavin = dark yellow urine
- B1 deficiency = Beri-Beri
B3 (niacin) deficiency = Pellagra
B12 (cobalamin) → B12 deficiency/SCD
Chronic Stable Liver Disease (features)
are they unwell?
what can you develop?
- Palmar erythema
- Spider naevi (>5)
- Gynaecomastia: due to failure of the liver to break down oestradiol
- Dupuytren’s contracture
These patients are not necessarily unwell. If they stop drinking, they will be absolutely fine.
develop portal hypertension (caused by cirrhosis)
- caput medusae (visible veins)
- splenomegaly
- shifting dullness (ascites)
- scrotal oedema
features of liver failure
Failed synthetic function
Failed clotting factor and albumin production (easy brusing and bleeding)
Failed clearance of bilirubin (hyperbilirubinaemia)
Failed clearance of ammonia (leads to encephalopathy)
- flapping tremor (asterixis) = manifestation of hepatic encephalopathy
mx of liver failure
This is managed by minimising the work done by the liver (difficult to do this).
- Avoid protein intake
- Avoid GI bleeding
- Provide supportive care
Only true cure is a liver transplant.
features of nodules (fatty liver)
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 (fatty liver)
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_
alcohol abuse pathway
Alcoholic hepatitis
Chronic stable liver disease
Resultant portal hypertension
Liver failure (asterixis)
Portosystemic Anastomoses: importance
Places where the portal blood meets the systemic circulation. These occur in many places; if you have high portal pressure in the stomach, this can result in varices. Varices have very thin walls (have no muscle in the vessel); if they tear, this can lead to death:
- Oesophageal varices
- Rectal varices
- Umbilical vein recanalising
- spleno-renal shunt
TIPSS: Transjugular intrahepatic portosystemic shunt
Done through the jugular vein by a radiologist. From SVC to IVC. Go through JVP to hepatic vein. Hole drilled from portal vein to hepatic vein. Prevents death but causes jaundice and liver failure
what makes you itchy
obstructive jaundice (gallstones, pancreatic cancer)
- Gallstones or cancer of the pancreatic head can block the bile duct
- Bile is made up of bilirubin and bile salts (which emulsify fats and are reabsorbed)
- Bile salts/acids only appear in the blood stream when the bile duct is physically blocked
- Both bile salts and bile acids cause itchiness
What is Courvoisier’s Law
if the gallbladder is palpable in a jaundiced patient, the cause is unlikely to be gallstones (i.e. it is more likely to be pancreatic cancer).
This is because a gall bladder with stones is usually small and fibrotic and incapable of being large.
where does pancreatic cancer typically metastaise to
what ix result would you see in this metastasis
liver because the portal vein transports blood from the cancer to the liver
high ALP
USS = dilated bile ducts (means metastasis)
pancreatic carcinoma
Formation of ducts in pancreas
Liver cells form units
Sarcoma are muscle cells
Melanoma will have pigment
Each met grows in round nodules
What is normal BR?
5-17 mmol/L
How do we treat Hep B
Acute = supportive
Chronic = anti-viral therapy
Hep C (RNA virus)
60-80% go chronic = asymptomatic presentation leading to chronic infection
Associated with HCC (hepatocellular carcinoma) = “Hx of jaundice, hepatomegaly, weight loss” “RAISED AFP”
Blood product spread = Hx of thalassaemia (recurrent blood transfusions)
Hep D
- REQUIRES CO-INFECTION WITH HEPATITIS B, HDV needs HBV surface antigen to invade liver cells
Hep E
- Faeco-oral (food, MSM, shellfish, uncooked pork)
- Acute = asymptomatic or N+D+V, fever, jaundice, RUQ pain
Increased risk in: expectant. Others, immunocompromised patients
Give 3 features of portal HTN (usually caused by cirrhosis)
Visible veins
Ascites
Splenomegaly
Acute vs Chronic hepatitis
- Acute hepatitis → spotty necrosis
- Chronic hepatitis → piecemeal necrosis, hepatocyte necrosis, fibrosis, nodules of regenerating hepatocytes
- Portal Inflammation
- Interface hepatitis (PIECEMEAL NECROSIS) – cannot see the border between the portal tract and parenchyma
- Lobular inflammation
- Bridging from the portal vein to central vein (critical stage in the evolution of hepatitis to cirrhosis)
Micronodular vs marconodular hepatitis
- Micronodular = alcoholic hepatitis, biliary tract disease
- Macronodular = viral hepatitis, Wilson’s disease, A1AT
Causes of chronic hepatitis
Causes of chronic hepatitis
How do score the prognosis in liver cirrhosis?
Modified Child-Pugh Score
