Jaundice

Jaundice is the term used to describe the yellow appearance of skin and membranes due to the deposition of bilirubin, which is a toxic substance.

Causes and associated conditions
Bilirubin (BR) is a pigment derived from the breakdown of haeme, which is found in haemoglobin of red blood cells (and accounts for 80 percent of the daily production), myoglobin (in muscle cells) and several other proteins and enzymes. The degradation of haeme is a complex, multistage process, involving the liver, kidney, blood transport, enzymes and the intestines. Problems can arise at any of these stages.

Part of the processing of BR is to render it water-soluble, so that it may be eliminated from the body by the gut and kidneys. At any given time, there is a known normal ratio between the amount of water-soluble BR (called conjugated BR, or CBR) and unprocessed BR (unconjugated BR or UBR). Certain disease states disrupt this pattern, and this can be used to interpret blood tests for diagnosis.

Because of the complexity of the BR metabolism, it is clinically convenient to classify disorders into two major groups according to the predominant type of BR in the serum.

Predominantly UBR, due to overproduction of BR, impaired liver uptake or impaired conjugation, such as:

• Excess red cell breakdown in bleeding, auto-immune diseases, thalassaemia, malaria.


• Impaired liver uptake of BR, as in heart failure and after exposure to certain drugs.


• Faulty conjugation, for instance some congenital syndromes, hyperthyroidism, cirrhosis, and in newborn babies (temporary), and Gilbert’s syndrome.

Predominantly CBR, due to liver cell disease, problems with liver excretion at cell level, or obstruction to the bile duct system.

Problems outside the liver tissue – mainly obstructions:

• Tumours


• Strictures after surgery or other procedures


• Parasitic infection, like liver flukes and roundworms


• Stones in the bile ducts

• Hepatitis – viral, alcoholic


• Primary biliary cirrhosis


• Drugs/toxins like herbal medicines, and some steroids. Drug-induced conditions my clear within 48 hours of stopping the drug, unless permanent damage has been caused.


• Sepsis – especially post-operative


• Infiltrative diseases – TB, lymphoma and sarcoidosis


• Sickle cell crisis


• Some rare cases induced by pregnancy

Symptoms, signs and diagnosis
A markedly jaundiced patient is obvious, even in dark-skinned persons, because the whites of the eyes appear yellow. In lighter-skinned persons, all body tissues look yellowish.

Relevant points to establish are:

• Rash, itch, joint pain, weight loss, pain, fever or changes in urine or stool


• Exposure to possibly toxic substances, whether oral (prescription or herbal) or injected (tattoos, blood transfusions, intravenous drug use, or sexual activity)


• Alcohol consumption


• Recent travel, for instance malaria contact


• Work exposure to liver toxins (like benzene)

Examination may reveal signs of associated causes, like liver enlargement, abdominal tumours, evidence of alcoholic liver disease, enlarged regional lymph nodes, ascites, signs of heart failure, and enlarged spleen.

The most important first step is to measure the total amount of BR in the blood, and the amounts of CBR and UBR. This simple blood test will immediately place the diagnosis in one of the two categories above. Complete liver function tests (LFTs) will also show the pattern of liver damage by measuring enzymes released when liver cells are destroyed. A full blood count (FBC) and smear will detect abnormalities in the quantity, quality and morphology of red blood cells.

BR in the urine may be an early sign of liver disease, though some forms of kidney disease may permit even albumin-bound BR (a large molecule) to “leak” through the normally impermeable kidney membrane.

Blood tests and the clinical examination may lead to other investigations, like scans, ultrasound, or X-rays to establish the underlying cause, such as tumours or gallstones.

Treatment and outcome
The choice of treatment and its outcome will depend on the cause of the jaundice. It may be as simple as stopping a certain drug, or as complex as surgery (such as for removal of gallstones) or chemotherapy (for malignancies).

Physiological neonatal jaundice can be helped by simple phototherapy, in which the baby (with eyes covered for protection) is exposed to light of a certain wavelength, which speeds up the breakdown and excretion of BR. This is important because high levels of BR can lead to some being deposited in the brain and nervous system, causing a permanent condition known as kernicterus whose features include:

• Cerebral palsy with choreoathetosis


• Deafness


• Abnormal eye movement


• Abnormal dental enamel

Jaundice always warrants investigating.