Histopathology 4: Liver Disease CPC Flashcards
Describe the arrangement of hepatocytes within the liver
Hepatocytes are arranged in trabeculae with sinusoids between them
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 different zones of the liver?
Zone 1:
Closest to the portal tract and it has the highest oxygen concentration
Zone 3:
most susceptible to hypoxia
Because the blood would have lost oxygen by the time it passes through other zones + cells in zone 3 are the most metabolically active cells in the liver
Ix if pre-hepatic cause of jaundice 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
Inheritance of Gilberts syndrome?
Drug used to reduce bilirubin levels?
What can worsen bilirubin levels?
Autosomal recessive
Phenobarbital
Fasting
Pathophysiology of Gilberts?
UDP glucuronyl transferase activity is reduced to 30% of normal
Unconjugated bilirubin is tightly albumin bound and does not enter the urine
Describe how urobilinogen is formed.
What is the significance of absent urobilinogen in the urine?
- Bacteria in colon converts bilirubin 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?
Another good marker of synthetic function?
Prothrombin time (normal = 12-14 seconds)
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
Hep A vaccine?
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)
Mx of alcoholic hep?
Supportive
Stop alcohol
Nutrition (vitamins especially thiamine)
Occasionally steroids (controversial but may have useful anti-inflammatory effects)
What is the issue with regeneration of hepatocytes following alcohol-related damage?
They regenerate in a disorganised manner and produce lots of nodules
The disorganised growth interferes with blood flowing through the liver leading to a rise in portal pressure
Why is Pabrinex yellow?
Presence of riboflavin (B2)
What does B1, B3 deficiency cause?
B1 - Beri Beri
B3 - Pellagra
Features of chronic alcoholic liver disease?
Palmar erythema
Spider naevi
Gynaecomastia (due to failure of liver to break down oestradiol)
Dupuytren’s contracture
Features of portal HTN?
Visible veins (oesophageal, rectal, umbilical)
Ascites
Splenomegaly
What is flapping tremor caused by?
Hepatic encephalopathy
What features is liver failure defined by?
Failed synthetic function → Failed clotting factor + albumin production
Failed clearance of bilirubin → jaundice
Failed clearance of ammonia → encephalopathy
Which type of cirrhosis is alcohol typically associated with?
Micronodular cirrhosis
NOTE: this is because the hepatocytes regenerate within a fibrous cuff
What is intrahepatic shunting?
The bridge of fibrosis between portal tracts and central veins means that blood does not come into close contact with hepatocytes and get filtered
Which type of jaundice is associated with itching? What causes the itching?
Obstructive jaundice - may see scratch marks on pt
This is because the itching is caused by bile salts and bile acids
State Courvoisier’s law.
If the gallbladder is palpable in a jaundiced patient, the cause is unlikely to be gallstones (i.e. more likely to be pancreatic cancer)
Where does pancreatic cancer metastise to and why?
Liver - because the portal vein transports blood from the cancer to the liver
How can you tell that a paracetamol OD is bad enough to need transplant?
PT in seconds is > hours since OD
What is the key histological finding that is pathognemonic for alcoholic hepatitis?
Megamitochondria
For how long following exposure to hep A should the virus be discoverable in faeces?
from 2-4 weeks
