Liver disease CPC Flashcards
Medical student
Incidentally find abnormal LFTs
Bilirubin: 32 [5-17]
ALT, ALP, AST, GGT: normal
Repeat fasting LFTs-> Bilirubin- 45, all other LFTs still normal
FBC
Hb- 14. 7 [normal]
WCC- normal
Platelets- normal
Doesn’t drink alcohol
No PMH
FH: cousin had an episode of jaundice once
What is the diagnosis?
Gilbert’s syndrome
Not haemolytic- b/c normal FBC and blood film
Not post hepatic -b/c normal ALP
What does a high GGT indicate?
Alcohol abuse
What is ALT?
Alanine aminotransferase Product of gluconeogenesis Should only be inside liver, pathogenic when in blood
What does this liver biopsy show?
NORMAL LIVER
First pic on right: hepatic vein [white circle] surrounded by hepatocytes
Second pic: Portal tract on left hand side- [from portal vein from small intestine] draining into central vein which takes blood back to heart [on the right hand side]
How does hepatic blood flow work?
What is the space of disse?
In via portal vein down sinusoid into central vein Space of disse = space between sinusoid and endothelial cells/hepatocytes- allows blood to go all the way up to the hepatocytes- increases metabolic efficiency
How do hepatocytes and the blood supply to hepatocytes change going from the portal vein to the central vein?
Oxygen supply is best next to hepatic portal vein, then decreases along the way to central vein, where pO2 is low
- This is fine for normal people
- But dangerous if alcoholic liver disease
Hepatocytes are different colour around portal vein [on left hand side of pic] because they are newly generated here and therefore most metabolic here [all drug metabolism is happening here], then as you go along to central vein, they get older and die
What does a liver lobule look like?
What does this biopsy show?
Hint: it shows the portal triad
What happens to liver architecture in liver damage?
The lobules are destroyed and lose their hexagonal structure when they regrow
How do you investigate suspected Gilbert’s syndrome?
LFTs have been done:
All but bilirubin are normal, bilirubin is high
Patient is asymptomatic
What is the next most appropriate step?
FBC- low Hb, look for signs of haemolytic anaemia- pre hepatic
Repeat bilirubin - fasting- fasting makes bilirubin higher in Gilbert’s syndrome
Viral serology- hepatitis- hepatic jaundice
Repeat bilirubin - fasting- fasting makes bilirubin higher in Gilbert’s syndrome
Used to give phenobarbitone- induces enzyme that is faulty in Gilbert’s syndrome [UDP glucuronyl transferase] and reduces bilirubin- not done anymore because unethica
If ALP abnormal, consider:
US abdo- Might see physical obstruction of biliary duct/bile duct dilation [cancer of pancreas, gallstones, cholangiocarcinoma]- post hepatic
- but not needed if normal ALP + no other symptoms
Not liver biopsy= dangerous [though absolute diagnostic]
Not CT- because extra radiation- and unnecessary at this stage
What are the causes of high bilirubin, and how do you investigate them?
Pre hepatic = haemolysis
- FBC, blood film
Hepatic = hepatitis
- Repeat LFTs, viral serology
Post hepatic= cancer, gallstones
- Imaging- US abdo
How can you tell if bilirubin is conjugated or unconjugated?
In which group of people is this especially important?
Can use the van der Bergh reaction
Direct reaction= conjugated bilirubin
Adding methanol= total bilirubin- so unconjugated bilirubin can be worked out
Neonates
Why does jaundice happen in neonates?
What type of bilirubin should they have if this is the case?
How can you treat the jaundice?
What alternative diagnoses should you consider if jaundice persists?
Underdeveloped liver, fall
Unconjugated
Light- phototherapy- breaks down bilirubin so it doesn’t need to be conjugated for excretion
Hypothyroidism, haemolytic anaemia [including Coombes/DAT for autoimmune]
How common is Gilbert’s syndrome?
Common
6% of population
How is Gilbert’s syndrome inherited- pattern of inheritance?
Autosomal recessive
50% of people are carriers
Pathophysiology of Gilbert’s syndrome?
Enzyme- UDP glucuronyl transferase- in liver- does not function
Activity of enzyme reduced to 30%
Why does pre hepatic jaundice not affect urine colour?
Unconjugated bilirubin doesn’t go into urine
Because it is tightly bound to albumin
Which LFT is most representative of liver function?
Synthetic factors
So:
PT [prothrombin time]/Clotting factors
Also useful: [but not the best tests, because change more slowly]
- Albumin
- Bilirubin
If PT rises by more than one sec per hour= need liver transplant
Other liver tests look at enzymes, which is not truly a test of liver function
35 year old patient
Chronic alcohol intake
Frequently presents drunk at A and E
Nausea, abdo pain, jaundice
Abnormal LFTs
Bilirubin: 90 [v high]
ALP: 200 [<130]
AST: 1500 [<50]
ALT: 750 [<50]
What is the most likely diagnosis?
What is the treatment?
Hepatitis [probably alcoholic, could also be viral, possible but unlikely to be autoimmune]
More inflammation of liver than obstruction= hepatic
AST:ALT- 2:1
Treatment
Supportive:
- alcohol cessation
- nutrition
- vitamins- thiamine and B1/Pabrinex
Sometimes steroids occasionally
How long does Hepatitis A take to present with jaundice after infection?
How does the antibody reponse/serology work?
Can you be a carrier for Hep A?
Four weeks
Cannot be a carrier- immune after one exposure
How does Hep B serology work if:
- Currently infectious?
- Cleared infection?
- Carrier for infection?
How long are carriers infectious for?
Which antibody is formed through vaccination?
When does patient present with jaundice?
Antigens
HBs Ag= currently infectious
HBe Ag= currently highly infectious
Antibodies
If cleared infection:
Anti-HBc antibodies get rid of HBe antigen
Anti-HBs= indicates immunity [natural or vaccine]
Anti-HBe= indicates natural immunity [no vaccine]
If carrier:
Illness subclinical- may or may not have jaundice
Secrete active virus for ten-twenty years after infection
HBs Ag
HBe Ag
Have antibodies against:
Anti-HBe
Anti- HBc
[but NO Anti-HBs]
- HBs antigen used in vaccine
- Present with jaundice three or four months after infection
What does this biopsy show?
What does the left hand arrow point to?
Large droplet fatty liver disease + alcoholic hepatitis
Left arrow: Mallory-Denk bodies- pink dots= cytoskeleton clumping due to acetaldehyde from alcohol metabolism linking to lysine residues
Right arrow: Neutrophils + ballooning cells- indicates hepatitis [inflammation]
Also accumulation of bile in bile canaliculi- cholestasis [can be seen better on close up below]
What does this show?
Micronodular cirrhosis
- Nodules [of regenerating hepatocytes] separated by scar tissue [collagen]
- Pallor- fat deposited everywhere
- Involves whole liver- diffuse
What is intrahepatic shunting?
What type of liver disease does it indicate + what does it indicate about progression of disease?
Fibrosis between portal vein and central vein
Blood goes down these fibrous scars, misses hepatocytes
Toxins can no longer be cleared- increased risk of encephalopathy
Indicates cirrhosis
First sign of irreversible disease
What usually causes micronodular cirrhosis?
Alcohol
What does this liver biopsy show?
Tumour- adenocarcinoma- forming glands
Primary colon cancer- has metastasised to liver
Normal liver has no glands
What does this liver biopsy show?
Poorly differentiated melanoma metastasised to liver
What do these post mortems show?
Liver mets
