JAUNDICE

Left: “Nude with a Dove” oil on canvas, Tamara de Lempicka, 1928. Right: “Nu Aux Voiles”, (“Nude with Sails”) oil on canvas, Tamara de Lempicka, 1931.

“But then as Turner’s oils became more ambitious, more visionary, the dismissive humour became more aggressive. The jokes about accidents in the kitchen started. Once he had been attacked by Sir George Beaumont for initiating the “white school”. Now he was said to be the victim of “yellow fever”. (Mortlake Terrace of 1827, washed in a peachy gold light that hung over the Thames, was said to be a case in point). Told at Petworth that it would be impossible to paint a figure against a yellow background,

Turner responded with his stunning “Jessica”, 1830 (from the Merchant of Venice) a Romantic take of Rembrandt, as ravishingly beautiful as any head and shoulders painted in the entire 19th century. It was met with hoots of helpless laughter and predictable remarks about women leaning out of mustard pots. The poet William Wordsworth joining in the culinary fun, said, “It looks to me as though the painter has indulged in raw liver until very unwell”.

“Painting up a Storm”, in “Power of Art”, Simon Schama, BBC, 2006.

What makes a painter great - technical skill, the ability to evoke powerful emotional responses perhaps? Its ultimately in the eye of the beholder, however, there is one aspect that truly sets the great apart from “the rest”, and that is innovation - a “breaking of the mold”, that changes the game forever. Turner was a painter far ahead of his time. In the early Nineteenth century, he was the prophet of the “Impressionist” school of the latter years of that century. Many of his works can be described as early examples of impressionism, although this expression did not even exist in the1830s. Turner broke the mold of the dogma that all art should follow strict “lines of engagement”, he heralded the age of the Impressionists, which in turn laid the foundation of the fantastic radiation of genres in the twentieth century that would change our concepts of “art” forever.

Of these radiations, few were more stunning than the brilliant period of “Art Deco” of the 1920s and 30s. And one of its most brilliant exponents, the Polish female painter, Tamara de Lempicka, had no hesitation in using the colour yellow in her works. Not only backgrounds could be yellow - but people as well! Even “lemon yellow” could be beautiful! Comparing her two works “Nude with a Dove” and “Nude with Sails” one readily appreciates the striking sign that “jaune” is to both the artistic as well as the medical eye! One wonders what William Wordsworth would have made of “Nude with Sails”!

“Self Portrait”, pencil on paper, Tamara de Lempicka, c.1930

JAUNDICE

Introduction

Jaundice of the sclera. The sclera is the site where this clinical sign first becomes apparent.

Jaundice (also sometimes referred to as icterus) is an important and common sign seen in the Emergency Department.

The word itself comes from the French “jaune” - meaning yellow.

It is the yellow discoloration of the sclera, skin and mucous membranes caused by the deposition of bilirubin in the tissues.

Jaundice may be the first or indeed the only sign of liver disease; thus its detection and evaluation is of critical importance.

Its causes can be divided into pre-hepatic, hepatic and post-hepatic.

Treatment will depend on the underlying pathology.

For the assessment of jaundice in infants, see RCH Guidelines.

Physiology

Bilirubin is a normal metabolite of heme catabolism.

It is the principal pigment in bile.

RBC breakdown

Haemoglobin → Heme + Globin

Biliverdin

Unconjugated bilirubin - (sometimes also called indirect bilirubin) - a water soluble compound.Unconjugated bilirubin does not appear in the urine - “acholuric jaundice”)This is bound to albumin in the blood stream

Taken up by hepatocytes, where glucuronyl transferases conjugate bilirubin with glucuronide, to form Conjugated bilirubin, (sometimes also called direct bilirubin)

Conjugated bilirubin is excreted into the small bowel. → converted to Urobilnogen in the bowel → in turn converted to Stercobilinogen.

Up to 20% of urobilinogen is reabsorbed from the bowel, to then be re-excreted via the urine.

Pathophysiology

The normal serum bilirubin level is < 17 µmol/litre.

When serum bilirubin levels rise to about twice the upper limit of normal (about 34 µmol/litre) it is deposited in the tissues of the body, particularly those which contain elastin. 1

The skin, and particularly the sclera, (which is rich in elastin), begins to stain yellow.

Causes of hyperbilrubinaemia

The board groups of causes of jaundice include:

1. Pre-hepatic causes: (elevated unconjugated bilirubin)

Excessive bilirubin production:

● Hemolysis (from any cause)

♥ Intravascular

♥ Extravascular

● Gilberts syndrome

♥ A genetic disorder with impairment of conjugation of bilirubin.

● Severe CCF:

♥ Secondary to hepatic congestion, with a failure of bilirubin uptake by the hepatocytes.

● Extravasation of blood into tissues.

2. Hepatic causes, (elevated conjugated and unconjugated bilirubin)

Hepatocellular failure (i.e. damage at the level of the hepatocyte cell) from any cause:

● Chronic hepatic cirrhosis

● Infections:

♥ Viral, bacterial, protozoal

♥ Severe sepsis in general (from any cause) can cause jaundice via a number of different mechanisms, including intrahepatic cholestasis, and impaired hepatic function.

● Malignancy

● Infiltrative

● Drugs

● Toxins

3. Post hepatic causes, (elevated conjugated bilirubin):

This is often referred to as cholestatic jaundice.

These are essentially any of the causes of obstruction to the flow of bile from the microscopic bile canaliculi or larger extrahepatic bile ducts.

● Intrahepatic bile flow obstruction (i.e. within bile microscopic canaliculi):

♥ Drugs

♥ Alcoholic hepatitis

♥ Intrahepatic cholestasis of pregnancy 

● Extrahepatic bile flow obstruction:

♥ Biliary tract stones

♥ Scarring of the bile ducts, (from any cause):

♥♥ Primary sclerosing cholangitis

♥♥ Strictures from pervious infection or surgery

♥ External compressive lesions of the bile ducts:

♥♥ Carcinoma of the pancreas, (most commonly)

♥♥ Carcinoma of the bile ducts, (cholangicarcinoma).

♥♥ Porta-hepatis malignant lymph nodes, lymphoma, metastatic carcinoma.

Complications

Jaundice is of course simply a sign of underlying disease and so the major complications experienced by a patient will primarily relate to the underlying cause of the jaundice.

With respect to high bilirubin levels of itself, apart from the sometimes startling cosmetic effects of jaundice, high levels of bilirubin deposition in the tissues can also result in:

● Pruritis, (which can be intense)

● Interference with cardiac conduction fibres, leading to bradycardia, (in severe cases only). 1

Clinical assessment

Important points of history:

1. Pruritus:

● Bilirubin in the skin can lead to intense pruritus.

2. Pain:

● Abdominal pain in association with jaundice is usually due to biliary tract stones.

● Painless jaundice is more commonly associated with extrahepatic obstructive lesions such as carcinoma of the pancreas.

3. Pale stools and darkened urine occur with obstructive (or cholestatic) jaundice.

● Dark urine (excess conjugated bilirubin) is caused by obstructive lesions

● Pale stools, (reduced or absent stercobilinogen) is also caused by obstructive lesions.

4. Always keep in mind the possibility of malaria, and enquire about any recent travel to a malaria endemic region, when the cause of the jaundice is unclear.

Important points of examination:

1. Sclera:

● Jaundice may be the first or indeed the only sign of liver disease; thus its detection and evaluation is of critical importance

● The sclera are usually the earliest site of yellow discolouration.

In more subtle cases this is best appreciated in natural sunlight.

2. Vital signs:

Assess for the usual signs of septicaemia

Fever is an important association with jaundice.

Contrary to popular perception jaundice in a febrile patient is only uncommonly caused by viral hepatitis.

The patient should be assessed for both medical and surgical causes for the jaundice and fever. A number of these causes are life-threatening, such as falciparum malaria and cholangitis from an obstructing stone.

As a broad generalization, younger patients (< 40) will more commonly have an infective cause, whilst older patients (> 40) will more commonly have a surgical cause.

In addition to medical and surgical causes of fever and jaundice, drug reactions and acute severe haemolysis can also cause this combination of signs.

3. Skin:

Initially there is a pale-lemon discoloration of the sclera and skin, and as the jaundice becomes more severe the discoloration becomes a darker and darker yellow and may even become a dark orange in very severe cases.

Haemolysis (or pre-hepatic causes) usually only result in milder jaundice with levels rarely rising above 70 micromol/L

Scratch marks may be evident on the skin

4. Signs of chronic liver disease:

5. Abdominal tenderness/ guarding:

● Raises suspicion for a surgical condition.

The clinical triad of right upper quadrant pain/ tenderness with fever and jaundice, strongly suggests the surgical emergency of obstructive cholangitis.

Differential diagnoses:

The sclera are rarely affected by other pigments, and in fact jaundice is the only condition causing a yellow discolouration of the sclera. 1

The skin can be yellow stained not only by jaundice, but also by:

● Carotenaemia (excess consumption of carotene)

● Acriflavine

● Flourescein

● Picric acid ingestion

...but none of these will affect the sclera.

Investigations

These will be guided by the index of suspicion for any given condition, but in broad outlines the following will need to be considered:

Blood tests

1. FBE

2. CRP

3. U&Es/ glucose

4. LFTs and INR:

● Liver transaminases

● Albumin and globulin levels

● INR

● Bilirubin levels to confirm the diagnosis of "jaundice"

Somewhat arbitrarily the ratio of unconjugated and conjugated bilirubin helps to determine cause of hyperbilirubinemia

Predominantly unconjugated (<20% bilirubin conjugated)

Predominantly conjugated (>50% bilirubin conjugated)

Others as clinically indicated, such as:

5. Blood cultures

6. Viral serology of the known causes of infectious hepatitis

7. Malaria screens, in returned travellers.

8. Paracetamol levels:

● For either acute intention overdose, or unintentional supra-therapeutic dosing.

9. Blood alcohol levels.

10. Haemolysis screens:

● Coombs test

● LDH

● Haptoglobin levels

Urinalysis

Normally there is no bilirubin in the urine, only small amounts of urobilinogen.

Conjugated bilirubin is (virtually) all excreted into the small bowel.

In obstruction however, conjugated bilirubin leaks from hepatocytes into the blood stream and from there can be excreted in the urine - this results in dark urine (excess conjugated bilirubin).

In Hepatocellular disease there is diminished hepatocyte function which can be associated with both conjugated hyperbilirubinemia and unconjugated hyperbilirubinemia (due to an impaired ability to conjugate bilirubin).

Substance Haemolysis Hepatocellular liver disease Obstruction or cholestasis

Urine:

Bilirubin (conjugated)

Bilirubin (unconjugated)

Urobilinogen

Absent

Raised

Raised

Present

Present

Present

Present

Present

Decreased or Absent

Faeces:

Stercobilinogen Raised Present Decreased or Absent

Ultrasound

This is an excellent initial investigation for obstructive lesions and biliary tract disease, especially for gall stones.

A key finding will be dilation of the bile ducts.

Unless the diagnosis is clearly viral hepatitis, an ultrasound screen should be done. The urgency will depend on such aspects as underlying risk factors, fever, how unwell the patient is.

CT Scan

A CT scan of the abdomen is most commonly done to assess for intra-abdominal malignant disease, most commonly lesions of the pancreas or lymph node involvement around the porta-hepatis

MRCP

This is a good imaging alternative, when IV contrast material required in a CT scan is best avoided, (allergies, renal impairment).

ERCP

Although an invasive procedure, this modality had the added benefit of being able to perform therapeutic interventions, such as stone removal and/or biliary tract stenting.

Management

Treatment depends on the cause of the jaundice.

Important general considerations will include:

1. Initial resuscitation

2. The need for urgent empirical antibiotics

3. The need for urgent surgical intervention.

4. Is NAC required for severe paracetamol poisoning?

“Jessica”, oil on canvas, Joseph Mallord William Turner, 1830

References

1. Talley NJ, O’Conner S, Clinical Examination, 4th ed 2001.

2. Yung A. et al. Fever and Jaundice, in Infectious Diseases, a clinical approach, 2nd ed, 2005.

Dr J. HayesMarch 2012