Jaundice

Question 1

What are the three steps of bilirubin metabolism?

Answer 1

Production of unconjugated bilirubin
Conjugation of bilirubin
Excretion of bilirubin

Question 2

How does unconjungated bilirubin travel to the liver?

Answer 2

Bound to albumin

Question 3

Where are blood cells normally broken down?

Answer 3

In the spleen by splenic macrophages

Question 4

What is bilirubin conjugated with in the liver?

Answer 4

Glucuronic acid

Question 5

What is conjugated bilirubin converted to within the intestines and what happens to these products?

Answer 5

Urobilinogen and stercobilinogen
Some of the urobilinogen is reabsorbed by the intestines and excreted by the kidneys
Stercobilinogen gets converted to stercobilin, which gives faeces its brown colour

Question 6

What are the three main types of jaundice?

Answer 6

Pre-hepatic
Hepatic
Post-hepatic (obstructive)

Question 7

What characteristic clinical features are associated with obstructive jaundice?

Answer 7

Dark urine

Pale stools

Question 8

What are the two mechanisms of unconjugated hyperbilirubinaemia?

Answer 8

Increased production of bilirubin (increased haemolysis)

Decreased capacity to conjugate bilirubin

Question 9

Why might patients who are undergoing intravascular haemolysis have dark urine?

Answer 9

Free haemoglobin from the haemolysis is degraded into haemosiderin, which is water soluble and very dark

Question 10

List some congenital causes of intravascular haemolysis.

Answer 10

G6PD deficiency
Pyruvate kinase deficiency
Sickle cell disease
Thalassemia

Question 11

List some acquired causes of intravascular haemolysis.

Answer 11

Artificial heart valves
Blood group mismatch
DIC 
Malaria 
Medications

Question 12

What might be seen on the blood film of a patient undergoing intravascular haemolysis?

Answer 12

Schistocytes

Question 13

Which clinical sign is likely to be seen in patients undergoing extravascular haemolysis?

Answer 13

Splenomegaly

Question 14

List a congenital and acquired cause of extravascular haemolysis.

Answer 14

Congenital – hereditary spherocytosis

Acquired – autoimmune haemolytic anaemia

Question 15

What can cause reduced uptake of bilirubin by the liver?

Answer 15

TIPS (transjugular intrahepatic portosystemic shunt)

Question 16

Name two congenital enzymatic problems that lead to unconjugated hyperbilirubinaemia.

Answer 16

Gilbert’s syndrome

Crigler-Najjar syndrome

Question 17

Name a congenital cause of obstructive jaundice.

Answer 17

Dubin-Johnson syndrome

Question 18

Using the surgical sieve, list causes of obstructive jaundice.

Answer 18

Infection – hepatitis, ascending cholangitis, liver abscess
Neoplasia – HCC, cholangiocarcinoma, pancreatic cancer
Vascular – Budd-Chiari syndrome
Inflammation/Autoimmune – PBC, PSC, autoimmune hepatitis, pancreatitis
Trauma – gallstones, strictures
Endocrine – intrahepatic cholestasis of pregnancy
Degenerative
Metabolic – haemochromatosis, Wilson’s disease
Drugs – alcohol, paracetamol, sodium valproate, co-amoxiclav

Question 19

List some key features of the history of presenting complaint that you should ask a patient with jaundice.

Answer 19

Acute or chronic
RUQ pain, nausea and vomiting – suggests hepatobiliary
Fever and diarrhoea – suggest infection
Steatorrhoea, dark urine, pruritus – suggests obstructive
Weight loss, fever, night sweats – systemic features of malignancy
Bronzed skin and signs of diabetes mellitus – haemochromatosis

Question 20

List three diseases, exclusive to pregnancy, that can cause jaundice.

Answer 20

Acute fatty liver of pregnancy
Intrahepatic cholestasis of pregnancy
HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)

Question 21

Why is it important to check for signs of diabetes mellitus?

Answer 21

Haemochromatosis can lead to diabetes mellitus

Question 22

List some key features of the past medical history and explain why they might be significant.

Answer 22

Gallstones
Liver disease
Haemophilia – may have received contaminated blood products
Recent blood transfusion or surgery – possible transfusion reaction
Ulcerative colitis
Diabetes mellitus
Emphysema
Psychosis – may result from Wilson’s disease

Question 23

List some drugs that increase the risk of jaundice by the following mechanisms:
Intravascular haemolysis
Autoimmune, extrvascular haemolysis
Hepatitis
Cholestasis

Answer 23

- Intravascular haemolysis
Sulphonamides
- Autoimmune, extravascular haemolysis
Methyldopa
- Hepatitis
Paracetamol overdose 
- Cholestasis
Co-amoxiclav

Question 24

List some features of the social history that would be significant in a patient with jaundice.

Answer 24

Alcohol abuse 
IV drug use 
Tattoos 
Unprotected sex with multiple partners
Recent foreign travel

Question 25

List some features that you might see on examination of a patient with jaundice.

Answer 25

``` Signs of dehydration Fever Conjuctival icterus Cachexia Scratch marks Needle tracks Signs of chronic liver disease (spider naevi, palmar erythema, clubbing, bruising and gynaecomastia) Bronzed tan Kayser-Fleischer rings ```

Question 26

Which causes of jaundice are supported by RUQ tenderness?

Answer 26

Hepatitis | Gallbladder disease – cholecystitis, ascending cholangitis

Question 27

List some blood tests that may be useful in a patient with jaundice.

Answer 27

FBC and reticulocyte count Serum bilirubin levels Liver enzymes (AST, ALT, ALP, GGT) Serum amylase or lipase

Question 28

``` State which liver disease is likely if: Elevation of AST > ALT Elevation of ALT > AST Elevation of ALP + GGT Isolated elevation of GGT ```

Answer 28

``` - Elevation of AST > ALT Alcoholic liver disease - Elevation of ALT > AST Viral hepatitis - Elevation of ALP + GGT Biliary pathology - Isolated elevation of GGT Recent alcohol consumption ```

Question 29

What does the finding of bilirubin in the urine indicate?

Answer 29

Post-hepatic obstruction

Question 30

Which test must be performed in young women presenting with jaundice?

Answer 30

Pregnancy test – there are some causes of jaundice that are exclusive to pregnant women

Question 31

List the components of the haemolysis screen.

Answer 31

Haptoglobins – these bind to free Hb and, hence, will be low in haemolytic states Lactate dehydrogenase (LDH) – released by red cells when they lyse Direct Antiglobulin test (Coombs test) – tests for autoantibodies against red cells (AIHA) Blood film – look for schistocytes, sickle cells, spherocytes, malaria

Question 32

Which diseases are tested for in viral serology?

Answer 32

Hepatitis A, B and C EBV and CMV HIV

Question 33

Which antibodies should be tested for in an autoimmune screen of a jaundice patient?

Answer 33

Anti-smooth muscle antibodies (ASMA) – type 1 autoimmune hepatitis Anti-mitochondrial antibodies (AMA) – primary biliary cirrhosis Anti-nuclear antibodies (ANA)

Question 34

Which test results would be consistent with: Haemochromatosis Alpha-1 anti-trypsin deficiency Wilson's disease

Answer 34

``` - Haemochromatosis High ferritin High transferrin saturation - Alpha-1 anti-trypsin deficiency Low alpha-1 anti-trypsin - Wilson’s disease High serum copper Low caeruloplasmin ```

Question 35

What is the earliest maker of compromised liver function?

Answer 35

Prolonged clotting times

Question 36

What are the four possible outcomes for patients with acute viral hepatitis B?

Answer 36

Full clinical recovery (virus is rarely completely cleared) Carrier status Chronic hepatitis B (some will end up developing cirrhosis and HCC) Fulminant hepatitis (rare but 80% mortality)

Question 37

Describe the typical presentation of a patient with obstructive jaundice.

Answer 37

``` Jaundice RUQ pain Steatorrhoea + dark urine Nausea Raised ALP + GGT ```

Question 38

Which investigation can be performed to visualise gallstones?

Answer 38

Biliary ultrasound

Question 39

Which intervention can be performed to remove gallstones from the CBD and drain pus?

Answer 39

ERCP

Question 40

Describe the presentation of acute cholecystitis.

Answer 40

Constant, unresolving fever (> 6 hrs) Tender abdomen Positive Murphy’s sign Nausea and (maybe) vomiting

Question 41

Outline the management of acute cholecystitis.

Answer 41

Antibiotics NBM IV fluids Cholecystectomy

Question 42

What is Charcot’s triad?

Answer 42

RUQ pain Jaundice Fever with rigors

Question 43

Outline the management of ascending cholangitis.

Answer 43

``` EMERGENCY Blood cultures Careful monitoring Broad-spectrum antibiotics ERCP if necessary – to drain pus from the CBD ```

Question 44

What is Primary Biliary Cirrhosis (PBC)?

Answer 44

Autoimmune disorder characterised by T-cell mediated destruction of the biliary ducts

Question 45

Which liver enzymes will be deranged in PBC?

Answer 45

High ALP + GGT

Question 46

Which autoantibody is the hallmark of PBC?

Answer 46

Anti-mitochondrial antibodies (AMA)

Question 47

Outline the management of PBC.

Answer 47

``` Confirm diagnosis – MRCP and biopsy Immunosuppression Bile salt replacement Fat-soluble vitamin supplementation Pruritus management – with cholestyramine Liver transplantation ```

Question 48

What is Primary Sclerosing Cholangitis (PSC)?

Answer 48

Autoimmune disorder that lead to T-cell mediated destruction of biliary epithelial cells, leading to multifocal scarring of biliary ducts

Question 49

Which disease is PSC strongly associated with?

Answer 49

Ulcerative colitis