QuestionSBA
QuestionChoice
Ipratroprium bromide does not commonly cause cholestatic jaundice
34208
d
Ipratroprium bromide 40 micrograms INH TDS
QuestionChoice
Clarithyomycin does not cause cholestatic jaundice
34205
a
Clarithromycin 500mg BD PO
QuestionChoice
Clindamycin does not commonly cause cholestatic jaundice
34207
c
Clindamycin 300mg QDS PO
QuestionChoice
Salbutamol does not commonly cause cholestatic jaundice
34209
e
Salbutamol 200 micrograms INH QDS
QuestionChoice
Fusidic acid is associated with elevated liver enzymes, hyperbilirubinaemia and jaundice with systemic use. These effects are usually reversible following withdrawal of therapy.
34206
b
Fusidic acid  250mg BD PO
QuestionComment
jaundice is listed as a side effect of clindamycin with paraenteral use though?
40532
QuestionComment
Yeah but PO fusidic acid has its own section on jaundice, deranged LFTs and hyperbilirubinemia. 
42718
User
subscriber
Anterior Gallbladder
QuestionComment
and it is also listed as a SE for clindamycin for oral use as well
61367
User
subscriber
Patient Power
User
subscriber
Axillary Stasis
Concept
Chapter
# Summary

# Definition

Jaundice is yellowing of the skin, sclerae and mucosae due to raised plasma bilirubin. The causes of jaundice can be split up into pre-hepatic, hepatic and post-hepatic causes.

# Epidemiology

Prevalence varies globally, with regions such as Africa experiencing higher rates due to infectious causes like malaria. In the UK, annual incidence estimates range from 5 to 10%, with age, gender, and socioeconomic factors influencing prevalence.

# Normal physiology

Jaundice can be classified according to whether it is pre-hepatic, hepatic or post-hepatic. 

- Normal bilirubin metabolism: red blood cells contain haemoglobin; haemoglobin is made up of haem and globin. 
- Haem is metabolised to unconjugated bilirubin. Unconjugated bilirubin is insoluble and is formed into a water-soluble conjugated bilirubin in the liver to aid excretion. 
- Conjugated bilirubin then passes into the common bile duct into the gut and is either re-taken up by the liver (enterohepatic circulation) or is converted to urobilinogen by gut macrophages. 
- Uribilinogen is reabsorbed and excreted by the kidney or is converted to stercobilin (leading to brown faeces). 
- Jaundice occurs when there is disruption to the above pathway at some point and leads to key distinguishing features.

[lightgallery]

# Aetiology

## Pre-hepatic

- Increased breakdown of haemoglobin into haem and globin – liver cannot conjugate bilirubin ‘fast’ enough, leading to raised unconjugated bilirubin. 
- Unconjugated bilirubin is not water soluble and so cannot enter the urine. It is therefore also known as acholuric jaundice.

Causes:

- Conjugation disorders, such as Gilbert's disease and Crigler-Naajjar
- Haemolysis (such as malaria or haemolytic anaemia)
- Drugs, such as contrast or rifampicin

## Hepatic

- The liver is unable to/has reduced capacity for forming unconjugated and conjugated bilirubin, resulting in a mixed conjugated/unconjugated hyperbilirubinaemia. 

Causes of hepatocellular dysfunction include:

- Viruses (hepatitis, CMV, EBV)
- Drugs, including paracetamol overdose, nitrofurantoin, halothane, valproate, statins, tuberculosis antibiotics
- Alcohol
- Cirrhosis
- Liver mass (abscess or malignancy)
- Haemochromatosis
- Autoimmune hepatitis
- Alpha-1 antitrypsin deficiency
- Budd-Chiari
- Wilson's disease
- Failure to excrete conjugated bilirubin (Rotor and Dubin-Johnson syndromes)
 
## Post-hepatic
 
- The liver able to conjugate bilirubin, but unable to excrete it. 
- This results in a rise in insoluble conjugated hyperbilirubin, which is then unable to pass into gut (so no there is stercobilin and no urobilinogen production) which causes pale stools and dark urine. Bile salts are also then deposited in the skin, resulting in pruritus.

Post-hepatic causes include:

- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Common bile duct gallstones or Mirrizi's syndrome (CBD compression from a gallstone in the cystic duct)
- Drugs, including coamoxiclav, flucloxacillin, steroids, sulfonylureas
- Malignancy, such as head of the pancreas adenocarcinoma, cholangiocarcinoma
- Caroli's disease
- Biliary atresia

# Signs and Symptoms

- **Pre-hepatic:** haemolysis, anaemia (fatigue, chest pain, palpitations, lightheadedness)
- **Hepatic:** RUQ pain, fever, viral illness, risk factors include: IVDU/tattoo, UPSI
- **Post-hepatic:** dark urine, pale stools, itch 

NB: Courvoisier’s law – jaundice and palpable painless gallbladder not due to gallstones. Painless jaundice – red flag for **pancreatic cancer or cholangiocarcinoma**


# Investigations


Bedside:

- Urobilinogen is normally found in the urine. This is decreased or absent in cases of obstructive jaundice, but increased in cases of pre-hepatic causes of hyperbilirubinaemia or hepatocellular disease.

| Urinalysis   | Normal  | Prehepatic disease | Hepatic disease | Posthepatic disease |
| ------------ | ------- | ------------------ | --------------- | ------------------- |
| Bilirubin    | Absent  | Absent             | Present         | Present             |
| Urobilinogen | Present | Increased          | Increased       | Decreased / absent  |

Bloods:

- FBC, U&E, LFTS (and split bilirubin to show conjugated/unconjugated amounts), reticulocytes, DAT, haptoglobin (goes down in pre-hepatic jaundice as it mops up free haem) 
- In LFTs - hepatocellular picture (raised AST/ALT), and cholestatic picture (raised GGT/ALP)
- Synthetic function of the liver - albumin, INR/coagulation screen

Imaging:

- 1st line is abdominal USS (to look for duct dilatation)
- 2nd line is MRCP 
- CT/MRI may be done if the presentation is suspicious for malignancy
- Liver biopsy may also be considered if there is diagnostic doubt

# Management

- Management of jaundice depends on the underlying cause. See separate management sections on the aetiologies described above in this chapter.

# NICE Guidelines

[NICE CKS - Jaundice in Adults](https://cks.nice.org.uk/topics/jaundice-in-adults/)
737
Picture
Evan Worse, CC BY-SA 4.0
2759
Bilirubin metabolism.png
images/r9q79a481710927187820.jpg
images/r9q79a481710927187820_256.jpg
images/r9q79a481710927187820_512.jpg
PQgCBgBRkNZlpzmnp5Z1KadW/8z63s0=
2784
Cholestatic Jaundice
Topic
9
Internal Medicine
6852
Case Presentation: A 70-year-old man was admitted to the respiratory ward two days ago following a recent chest infection. PMH Community acquired pneumonia, Mild COPD, TB, Diabetic foot infection. DH His current regular medicines are listed (below).


On examination
There is visible yellowing of his sclera and evidence of pruritus on his arm.
Investigation

||||
|---------------------------|:-------:|--------------------|
|Alanine Aminotransferase (ALT)|150 IU/L|10 - 50|
|Aspartate Aminotransferase (AST)|50 IU/L|10 - 40|
|Alkaline Phosphatase (ALP)|450 IU/L|25 - 115|
|Bilirubin|60 µmol/L|< 17|
|Gamma Glutamyl Transferase (GGT)|50 U/L|9 - 40|


Question: Select the prescription that is most likely to contribute to his cholestatic jaundice.
b