Chem Path 4 -Liver Disease CPC Flashcards
Describe the arrangement of hepatocytes within the liver.
Hepatocytes are arranged in trabeculae with sinusoids between them
What are the three components of a portal triad?
Portal vein
Hepatic artery
Bile duct
Describe the arrangement of endothelial cells within the hepatic sinusoids.
The endothelial cells are discontinuous
There are spaces between the hepatocytes and the endothelium of the sinusoids called the space of Disse
This space allows blood to come into contact with liver enzymes
Describe the differences between zone 1 and zone 3.
Zone 1 – receives the highest oxygen concentration
Zone 3 – receives the lowest oxygen concentration, therefore it is most vulnerable to hypoxia. It is the most metabolically active zone.
Which investigations are performed if a pre-hepatic cause of jaundice is suspected?
FBC
Blood film
What reaction is used to measure fractions of bilirubin? Describe how this works.
Van den Bergh reaction
The direct reaction measures conjugated bilirubin
Methanol is added which completes the reaction and gives you a value for total bilirubin
The difference between these two values is used to measure the unconjugated bilirubin (indirect reaction)
What is the most common cause of paediatric jaundice?
Neonates have immature livers that cannot conjugate bilirubin fast enough resulting in a UNconjugated hyperbilirubinaemia
Describe how phototherapy for jaundice works.
Phototherapy converts unconjugated bilirubin into lumirubin and photobilirubin which are soluble and do not require conjugation for excretion
What is the inheritance pattern of Gilbert’s syndrome?
Autosomal recessive
Which drug can reduce bilirubin levels in Gilbert’s syndrome?
Phenobarbital
Outline the pathophysiology of Gilbert’s syndrome.
UDP glucuronyl transferase activity is reduced to 30% of normal
Unconjugated bilirubin is tightly albumin bound and does not enter the urine
What can worsen bilirubin levels in Gilbert’s syndrome?
Fasting
Describe how urobilinogen is formed. What is the significance of absent urobilinogen in the urine?
Bilirubin released into the bowels will be converted by bacteria in the colon, into urobilinogen and stercobilinogen
Some urobilinogen will be absorbed and transported via the enterohepatic circulation to the liver
Some of this urobilinogen will then be excreted in the urine
The presence of urobilinogen in the urine is NORMAL
The absence of urobilinogen in the urine is suggestive of biliary obstruction
What is the most representative marker of liver function?
Prothrombin time (normal = 12-14 seconds)
What is another good marker of liver synthetic function?
Albumin
NOTE: bilirubin is also a decent marker
Outline how hepatitis A serology changes over time.
As viral titres start to drop following initial infection, there will be a rise in IgM antibodies (during this time you will be unwell with jaundice)
After a few weeks, you will start to produce IgG antibodies (leading to cure and ongoing protection from Hep A)
NOTE: hepatitis A does NOT recur
Name the vaccine for hepatitis A
Havrix (contains some antigens)
Outline the features of hepatitis B serology in acute infection.
Initial rise in HBeAg and HBsAg
Eventually you will develop HBeAb and HBsAb resulting in a decline in HBeAg and HBsAg
You will also develop HBcAb which suggests previous infection
NOTE: there is currently no way of directly measuring HBcAg
Outline the features of hepatitis B serology in someone who has been vaccinated.
They will have HBsAb but no other antibodies
This is because the vaccine consists of administering HBsAg only
Outline the features of hepatitis B serology in a chronic carrier.
The patient will mount an immune response but will never clear the virus
HBeAg will decline but HBsAg will persist
Describe the histology of hepatitis
Hepatocytes will become fatty and swell (balloon cells), containing a lot of Mallory hyaline
There will also be a lot of neutrophil polymorphs
What are the defining and associated histological features of alcoholic hepatitis?
Defining: liver cell damage, inflammation, fibrosis
Associated: fatty change, megamitochondria
List a differential diagnosis for fatty liver disease.
NASH (most common cause of liver disease in the Western world)
Alcoholic hepatitis
Malnourishment (Kwashiorkor)
Outline the treatment of alcoholic hepatitis.
Supportive
Stop alcohol
Nutrition (vitamins especially thiamine)
Occasionally steroids (controversial but may have useful anti-inflammatory effects)
