Chem Path 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

What are the three 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 differences between zone 1 and zone 3.

Answer 4

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.

Question 5

Which investigations are performed if a pre-hepatic cause of jaundice is 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

What is the inheritance pattern of Gilbert’s syndrome?

Answer 9

Autosomal recessive

Question 10

Which drug can reduce bilirubin levels in Gilbert’s syndrome?

Answer 10

Phenobarbital

Question 11

Outline the pathophysiology of Gilbert’s syndrome.

Answer 11

UDP glucuronyl transferase activity is reduced to 30% of normal

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

Question 12

What can worsen bilirubin levels in Gilbert’s syndrome?

Answer 12

Fasting

Question 13

Describe how urobilinogen is formed. What is the significance of absent urobilinogen in the urine?

Answer 13

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

Question 14

What is the most representative marker of liver function?

Answer 14

Prothrombin time (normal = 12-14 seconds)

Question 15

What is another good marker of liver synthetic function?

Answer 15

Albumin

NOTE: bilirubin is also a decent marker

Question 16

Outline how hepatitis A serology changes over time.

Answer 16

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 17

Name the vaccine for hepatitis A

Answer 17

Havrix (contains some antigens)

Question 18

Outline the features of hepatitis B serology in acute infection.

Answer 18

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 19

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

Answer 19

They will have HBsAb but no other antibodies

This is because the vaccine consists of administering HBsAg only

Question 20

Outline the features of hepatitis B serology in a chronic carrier.

Answer 20

The patient will mount an immune response but will never clear the virus

HBeAg will decline but HBsAg will persist

Question 21

Describe the histology of hepatitis

Answer 21

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

There will also be a lot of neutrophil polymorphs

Question 22

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

Answer 22

Defining: liver cell damage, inflammation, fibrosis

Associated: fatty change, megamitochondria

Question 23

List a differential diagnosis for fatty liver disease.

Answer 23

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

Alcoholic hepatitis

Malnourishment (Kwashiorkor)

Question 24

Outline the treatment of alcoholic hepatitis.

Answer 24

Supportive

Stop alcohol

Nutrition (vitamins especially thiamine)

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

Question 25

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

Answer 25

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 26

Why is Pabrinex yellow?

Answer 26

Presence of riboflavin (B2)

Question 27

What condition is caused by B1 deficiency?

Answer 27

Beri Beri

Question 28

`What condition is caused by B3 deficiency?

Answer 28

Pellagra

Question 29

List some features of chronic alcoholic liver disease.

Answer 29

Palmar erythema

Spider naevi

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

Dupuytren’s contracture

Question 30

List some features of portal hypertension

Answer 30

Visible veins (oesophageal, rectal, umbilical)

Ascites

Splenomegaly

Question 31

What is flapping tremor caused by?

Answer 31

Hepatic encephalopathy

Question 32

What is liver failure defined by?

Answer 32

Failed synthetic function

Failed clotting factor and albumin production

Failed clearance of bilirubin

Failed clearance of ammonia

Question 33

Which type of cirrhosis is alcohol typically associated with?

Answer 33

Micronodular cirrhosis

Question 34

What is intrahepatic shunting?

Answer 34

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 35

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

Answer 35

Obstructive jaundice

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

Question 36

State Courvoisier’s law.

Answer 36

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 37

Where does pancreatic cancer tend to metastasise to?

Answer 37

Liver