Liver disease CPC

Question 1

What does the portal triad consist of?

Answer 1

Hepatic vein, artery, bile duct

Question 2

What is the Space of Disse?

Answer 2

The spaces between the hepatocytes and the endothelium (discontinuous organisation) of the sinusoids meaning that the blood comes into contact with the all the liver enzymes

Question 3

What is Zone 1 damage and what substances cause it?

Answer 3

Periportal damage, caused by directly hepatotoxic substances

Question 4

What is Zone 3 damage and what substances cause it?

Answer 4

Centrilobar damage, caused by metabolised hepatotoxic substances i.e. those that require bioactivation. Hypoxic damage as most oxygen lost by the time the blood reaches Zone 3

Question 5

In which zone are the most metabolically active cells in the liver?

Answer 5

Zone 3

Question 6

ALP rises more when which zone is damaged? Why?

Answer 6

Zone 1 due to proximity to bile ducts

Question 7

What is Zone 2 damage?

Answer 7

Midzonal

Question 8

Name 2 substances that cause Zone 1 damage

Answer 8

Iron salts, white phosphorus

Question 9

Name 3 substances that cause Zone 2 damage

Answer 9

Furans, ngaione (myosporum spp.), beryllium

Question 10

Name 4 substances that cause Zone 3 damage

Answer 10

Acetaminophen, aflatoxin, microcystin, ricin

Question 11

How do you measure the split bilirubin? (conjugated and unconjugated)

Answer 11

van den Bergh reaction

Direct reaction to measure conjugated BR

Indirect reaction to measure unconjugated BR: add methanol which completes the reaction, allows measurement of total BR, so minus the conjugated value to get unconjugated value

Question 12

Is the hyperbilirubinaemia conjugated or unconjugated in paediatric jaundice? Why?

Answer 12

Unconjugated in normal paediatric jaundice as caused by liver immaturity- cannot conjugate the BR fast enough.

Question 13

What does phototherapy convert bilirubin to? Why is this helpful to treat paediatric jaundice?

Answer 13

Lumirubin and photo-bilirubin. These isomers do not need to be conjugated to be excreted.

Question 14

What is the inheritance pattern of Gilbert’s syndrome?

Answer 14

Autosomal recessive

Question 15

What do you see in LFTs in Gilbert’s?

Answer 15

Raised unconjugated bilirubin with otherwise normal LFTs

Question 16

What makes the bilirubin levels worse in Gilbert’s?

Answer 16

Fasting

Question 17

Pathophysiology of Gilbert’s

Answer 17

UDP glucuronyl transferase activity is reduced to 30%

Question 18

What is the most representative marker of liver function?

Answer 18

Prothrombin time (if raised, shows liver isn’t making clotting factors so isn’t working properly)

(Albumin and BR also good)

Question 19

Why are the enzyme LFTs (AST, ALT) not true markers of the liver’s synthetic function?

Answer 19

They tell you that there is damage rather than telling you how your liver is actually functioning

Question 20

What do high AST and ALT indicate?

Answer 20

Hepatocyte damage e.g. hepatitis

Question 21

In what type of hepatitis is AST > ALT?

Answer 21

Alcoholic hepatitis

Question 22

In what type of hepatitis is ALT > AST?

Answer 22

All other heps other than alcoholic

Question 23

What does high ALP indicate?

Answer 23

Biliary obstruction

Question 24

3 key features of hepatitis

Answer 24

Fever, jaundice, raised ALT/AST

Question 25

Causes and findings in pre-hepatic jaundice

Answer 25

Causes: haemolysis, congestive heart failure Findings: Raised unconjugated BR, raised LDH, reduced haemoglobin and haptoglobin

Question 26

Causes and findings in hepatic jaundice

Answer 26

Causes: acute or chronic liver failure, Gilbert's, viral/alcoholic hep, PBC Findings: raised unconjugated BR, raised ALT/AST, ~synthetic dysfunction

Question 27

Causes and findings in post-hepatic jaundice

Answer 27

Causes: anything causing biliary tree obstruction e.g. stones, inflammation (PBC/PSC), strictures, masses, extra-luminal masses e.g. pancreatic cancer/cholangiocarcinoma Findings: raised conjugated BR, raised urinary BR, dark urine and pale stools

Question 28

Route of transmission of hep A

Answer 28

Faeco-oral

Question 29

Hep A presentation

Answer 29

ACUTE Asymptomatic, or nausea, D+V, fever, jaundice, RUQ pain

Question 30

Hep A onset and symptom duration

Answer 30

2-6 wks, symptoms last ~8wks

Question 31

Explain natural history of hep A in terms of antibodies

Answer 31

After viral titres drop, get rise in IgM (--> unwell, jaundice) After first few weeks, IgM drops and IgG rises --> immunity, cured

Question 32

Hep A treatment

Answer 32

Supportive

Question 33

Routes of transmission of hep B

Answer 33

Sexually, vertically, blood-to-blood

Question 34

Hep B presentation

Answer 34

Normally acute presentation (can be acute ± chronic) Hepatitis symptoms – fever, jaundice, N+V, RUQ pain) But a chronic infection follows in ~10% of people

Question 35

Hep B duration of onset

Answer 35

2-6 wks

Question 36

What percentage of hep B infections become chronic?

Answer 36

5-10%

Question 37

Antigens measured in hep B

Answer 37

HBsAg and HBeAg Once these go down, produce antibodies against them (anti-HBs and anti-HBe)

Question 38

How could you distinguish between someone who has immunity to hep B through vaccinated and someone who has actually had hep B?

Answer 38

Vaccination contains HBsAg, so they will have anti-HBs antibodies but not anti-HBeAg

Question 39

Which antigen is never cleared in chronic hep B?

Answer 39

HBsAg (but levels decrease with time)

Question 40

Management of hep B

Answer 40

Acute: supportive Chronic: antiviral therapy

Question 41

Which heps are associated with hepatocellular carcinoma?

Answer 41

B and C

Question 42

Route of transmission of hep C

Answer 42

Blood-to-blood

Question 43

Hep C duration of onset

Answer 43

6-8 wks

Question 44

Hep C presentation

Answer 44

Normally results in an asymptomatic presentation leading to a chronic infection (60-80%)

Question 45

Hep C management

Answer 45

Antiviral therapy (can be treated and eradicated)

Question 46

Which hep must hep D co-infect with?

Answer 46

Hep B

Question 47

Route of transmission of hep E

Answer 47

Faeco-oral

Question 48

Hep E presentation

Answer 48

Acute – asymptomatic, or – nausea, D+V, fever, jaundice, RUQ pain

Question 49

Hep E duration of onset

Answer 49

Onset = 2-6 weeks; symptoms last = ~8 weeks

Question 50

Which groups are at higher risk of hep E?

Answer 50

``` Expectant mothers Immunocompromised patients (“E-mmunocompromised”) ```

Question 51

Key histological features of hepatitis (3)

Answer 51

Liver cell damage: Balloon cells (ballooning degeneration) containing mallory hyaline, Mallory-Denk bodies Inflammation Fibrosis

Question 52

What causes nutmeg liver?

Answer 52

Venous congestion (Budd-Chiari, congestive HF etc)

Question 53

What is Courvoisier's Law?

Answer 53

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