Histopathology 4: Liver Disease CPC

Question 1

Describe the arrangement of hepatocytes within the liver

Answer 1

Hepatocytes are arranged in trabeculae with sinusoids between them

Question 2

Components of a portal triad?

Answer 2

Portal vein

Hepatic artery

Bile duct

Question 3

Describe the arrangement of endothelial cells within the hepatic sinusoids

Answer 3

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

Question 4

Describe the different zones of the liver?

Answer 4

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

Question 5

Ix if pre-hepatic cause of jaundice suspected?

Answer 5

FBC

Blood film

Question 6

What reaction is used to measure fractions of bilirubin?

Describe how this works

Answer 6

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)

Question 7

What is the most common cause of paediatric jaundice?

Answer 7

Neonates have immature livers that cannot conjugate bilirubin fast enough resulting in a UNconjugated hyperbilirubinaemia

Question 8

Describe how phototherapy for jaundice works.

Answer 8

Phototherapy converts unconjugated bilirubin into lumirubin and photobilirubin which are soluble and do not require conjugation for excretion

Question 9

Inheritance of Gilberts syndrome?

Drug used to reduce bilirubin levels?

What can worsen bilirubin levels?

Answer 9

Autosomal recessive

Phenobarbital

Fasting

Question 10

Pathophysiology of Gilberts?

Answer 10

UDP glucuronyl transferase activity is reduced to 30% of normal

Unconjugated bilirubin is tightly albumin bound and does not enter the urine

Question 11

Describe how urobilinogen is formed.

What is the significance of absent urobilinogen in the urine?

Answer 11

• 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

Question 12

What is the most representative marker of liver function?

Another good marker of synthetic function?

Answer 12

Prothrombin time (normal = 12-14 seconds)

Albumin
NOTE: bilirubin is also a decent marker

Question 13

Outline how hepatitis A serology changes over time

Answer 13

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

Question 14

Hep A vaccine?

Answer 14

Havrix - contains some antigens

Question 15

Outline the features of hepatitis B serology in acute infection

Answer 15

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

Question 16

Outline the features of hepatitis B serology in someone who has been vaccinated

Answer 16

They will have HBsAb but no other antibodies

This is because the vaccine consists of administering HBsAg only

Question 17

Outline the features of hepatitis B serology in a chronic carrier

Answer 17

The patient will mount an immune response but will never clear the virus
HBeAg will decline but HBsAg will persist

Question 18

Describe the histology of hepatitis.

Answer 18

Hepatocytes will become fatty and swell (balloon cells), containing a lot of Mallory hyaline

There will also be a lot of neutrophil polymorphs

Question 19

What are the defining and associated histological features of alcoholic hepatitis?

Answer 19

Defining: liver cell damage, inflammation, fibrosis

Associated: fatty change, megamitochondria

Question 20

List a differential diagnosis for fatty liver disease.

Answer 20

NASH (most common cause of liver disease in the Western world)

Alcoholic hepatitis

Malnourishment (Kwashiorkor)

Question 21

Mx of alcoholic hep?

Answer 21

Supportive

Stop alcohol

Nutrition (vitamins especially thiamine)

Occasionally steroids (controversial but may have useful anti-inflammatory effects)

Question 22

What is the issue with regeneration of hepatocytes following alcohol-related damage?

Answer 22

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

Question 23

Why is Pabrinex yellow?

Answer 23

Presence of riboflavin (B2)

Question 24

What does B1, B3 deficiency cause?

Answer 24

B1 - Beri Beri

B3 - Pellagra

Question 25

Features of chronic alcoholic liver disease?

Answer 25

Palmar erythema

Spider naevi

Gynaecomastia (due to failure of liver to break down oestradiol)

Dupuytren’s contracture

Question 26

Features of portal HTN?

Answer 26

Visible veins (oesophageal, rectal, umbilical)

Ascites

Splenomegaly

Question 27

What is flapping tremor caused by?

Answer 27

Hepatic encephalopathy

Question 28

What features is liver failure defined by?

Answer 28

Failed synthetic function → Failed clotting factor + albumin production

Failed clearance of bilirubin → jaundice

Failed clearance of ammonia → encephalopathy

Question 29

Which type of cirrhosis is alcohol typically associated with?

Answer 29

Micronodular cirrhosis

NOTE: this is because the hepatocytes regenerate within a fibrous cuff

Question 30

What is intrahepatic shunting?

Answer 30

The bridge of fibrosis between portal tracts and central veins means that blood does not come into close contact with hepatocytes and get filtered

Question 31

Which type of jaundice is associated with itching? What causes the itching?

Answer 31

Obstructive jaundice - may see scratch marks on pt

This is because the itching is caused by bile salts and bile acids

Question 32

State Courvoisier’s law.

Answer 32

If the gallbladder is palpable in a jaundiced patient, the cause is unlikely to be gallstones (i.e. more likely to be pancreatic cancer)

Question 33

Where does pancreatic cancer metastise to and why?

Answer 33

Liver - because the portal vein transports blood from the cancer to the liver

Question 34

How can you tell that a paracetamol OD is bad enough to need transplant?

Answer 34

PT in seconds is > hours since OD

Question 35

What is the key histological finding that is pathognemonic for alcoholic hepatitis?

Answer 35

Megamitochondria

Question 36

For how long following exposure to hep A should the virus be discoverable in faeces?

Answer 36

from 2-4 weeks