Chemical Pathology - Liver Disease CPC Flashcards
what does the portal triad consist of?
artery
vein
bile duct
what is the space of disse?
spaces between hepatocytes and endothelium of sinusoids
blood comes into contact with liver enzymes
what causes zone 1 damage (periportal)?
directly hepatoxic substances
damage to zone 1 makes ALP rise more due to close proximity to bile duct
what causes zone 3 damage (centrilobular)?
hypoxic damage (blood lost quite a lot of O2 by time it passes through zones 1 and 2) metabolised hepatotoxic substances (zone 3 = most metabolically active cells in liver)
where does bilirubin conjugate?
as passes through liver
what are the causes of a high bilirubin?
- pre-hepatic (unconjugated) –> haemolysis
- hepatic (look at LFTs)
- post-hepatic (obstructive jaundice)
how do you measure the fractions of bilirubin?
Van den bergh reaction
- DIRECT: conjugated bilirubin
- INDIRECT: add methanol, reaction completed and allows you to measure total bilirubin
what causes paediatric jaundice?
NORMAL
caused by liver immaturity
unconjugated bilirubinaemia
how do you treat paediatric jaundice?
phototherapy
inheritance pattern of Gilbert’s
autosomal recessive
what can improve jaundice in Gilbert’s?
phenobarbital
what is the pathophysiology of Gilbert’s?
decreased UDP glucuronyl transferase activity
unconjugated bilirubin is tightly bound to albumin so does not enter urine
what does the presence of urobilinogen tell you?
enterohepatic circulation is intact
urobilinogen is always present in urine of normal people
bilirubin –> biliary tree –> into bowel –> bacteria convert it into stercobilinogen and urobilnogen
this is reabsorbed into circulation and you excrete it
what is the most representative function of liver function?
PT
what is the general rule about PT and paracetamol overdose?
if the PT is higher than the number of hours since the OD, pt should be transferred for transplant
what are the 3 ways that the function of the liver can be measured by?
- albumin
- clotting factors
- bilirubin
what does high AST and ALT suggest? what if one is higher than the other?
AST and ALT high = hepatocyte damage
ALT > AST = other forms of hepatitis
AST > ALT = alcoholic hepatitis
what are the causes of abnormal LFTs?
Pre-hepatic: Gilbert’s, haemolysis
Hepatic: viral hepatitis, alcoholic hepatitis, cirrhosis
Post-hepatic: gallstones, pancreatic
causes of pre-hepatic jaundice
haemolysis
CHF
causes of hepatic jaundice
liver failure gilbert syndrome crigler-naijar syndrome viral hepatitis alcoholic hepatitis PBC
causes of post-hepatic jaundice
obstruction of biliary tree
- intraluminal: stones, strictures
- luminal: mass, neoplasm, inflammation (PSC/PBC)
- extra-luminal: pancreatic Ca, cholangiocarcinoma
what are the features of hepatitis?
- fever
- jaundice
- raised ALT/AST
how is Hep A transmitted?
- faeco-oral (food, men-on-men sex)
- contaminated water, recent shellfish
how does Hep A present? time period?
acute: asymptomatic OR nausea, D+V, fever, jaundice, RUQ pain
onset: 2-6 weeks, symptoms last 8 wees
infectious when asymptomatic
how do the antibodies respond in Hep A?
- viral titres start to drop
- get a rise in IgM antibodies, become unwell with jaundice
- if you survive initial few weeks, produce IgG antibodies
- this point onwards, cured and immune
how do you treat Hep A?
supportive
avoid alcohol
Vaccine (Havrix) - contaisn some Hep A antigens
what are the routes of infection of Hep B?
- sex
- vertically (mother to child)
- blood products
how does Hep B infection normally present?
normally acute presetnation
chronic infection follows in 10%
hepatitis symptoms: fever, jaundice, N+V, RUQ pain
what are the 2 main antigens measured in Hep B?
HBsAg
HBeAg (highly infectious)
after these antigens go down, you can detect antibodies against
end with 3 antibodies and no antigens
what will be seen in the blood if you have been vaccinated against Hep B?
vaccine contains HBsAg
if vaccinated, you will have anti-HVs but no HBeAg or anti-HBe
what will chronic carriers have?
chronic carriers never clear the HBsAg
but infectivity decreases with time
what is the tx of Hep B?
acute - supportive
chronic - anti-viral therapy
what can HBV and HCV be associated with?
- hepatocellular carcinoma
- history of thalassaemia –> blood transfusions
what are the features of HCV?
- blood products spread
- normally asymptomatic leading to chronic infection
what is important to remember about Hep D?
requires co-infection with Hep B to invade liver cells
how is Hep E transmitted?
- faecal oral (food, men on men sex)
- shellfish
- uncooked pork
how does Hep E present?
asymptomatic OR nausea, D+V, fever, jaundice, RUQ pain
onset = 2-6 weeks
symptoms = 8 weeks
who has an increased risk for Hep E?
expectant mothers
immunocompromised patients
what is the histology of alcoholic hepatitis?
- too much alcohol = fat deposit in liver = reversible
- if alcohol abuse continues = alcoholic hepatitis (neutrophils will infiltrate liver)
- when hepatocytes get damages, see balloon cells containing mallory hyaline
defining histological features of alcoholic hepatitis
- liver cell damage
- inflammation
- fibrosis
- fatty change
- megamitochondria
what are the different differential diagnoses for fatty liver disease?
- NASH (looks like alcoholic hepatitis)
- alcoholic hepatitis
- malnourishment (Kwashiorkor)
what are the treatments for alcoholic hepatitis?
- supportive
- stop alcohol
- occasionally steroids
- nutrition
- Vits (B1 and thiamine)
what happens if alcohol is stopped?
- liver can regenerate
- will heal in disorganised fashion
- difficult for blood to flow through
- inc BP
= PORTAL HTN
what are the features of chronic STABLE alcoholic liver disease?
- palmar erythema
- gynaecomastia
- spider naevi (>5)
- dupuytren’s contracture
what are the features of portal HTN?
- visible veins
- ascites
- splenomegaly
what is liver failure defined as?
- failed synthetic function
- failed clotting factor and albumin production
- failed clearance of bilirubin
- failed clearance of ammonia (encephalopathy)
what do nodules represent in fatty liver?
regenerating hepatocytes
what are the sites of portosystemic anastomoses?
- oesophageal varices
- rectal varices
- umbilical vein recanalizing
- spleno-renal shunt
what are the examination findings in obstructive jaundice?
- jaundice
- cachectic
- palpable gall bladder
- scratch marks (bile salts and acids that appear in blood stream when bile duct is blocked)
how will your gallbladder present with gall stones?
small
fibrotic
non palpable
different causes of micronodular vs macronodular hepatitis
micronodular: alcoholic hepatitis, biliary tract disease
macronodular: viral hepatitis, Wilson’s disease, A1AT
antibodies in AI hepatitis
Type 1: ANA, anti-SMA, anti-actin Ig, anti-soluble liver antigen Ig
Type 2: anti-LKM Ig
what scoring system is used to calculate prognosis in liver cirrhosis?
modified Child Pugh Score
