Jaundice

[lakshmidr]

Title: Jaundice – Types, Causes, Signs and Symptoms, Diagnosis and Treatment

Description: Jaundice is characterised by yellowish discolouration of the skin and eyes, and occurs when the bilirubin levels in the blood increase.

Keywords: jaundice, yellow skin and eyes, hepatic, hemolysis, obstructive, hepatocellular, bilirubin, liver, gallbladder, bile ducts, cancer, viral hepatitis, alcohol, infection, drugs

Overview of Bilirubin Metabolism
Jaundice refers to yellowish discolouration of the skin and the eyes and occurs when the bilirubin levels in the blood increase.

To understand how jaundice occurs, a brief outline of bilirubin metabolism is given below.

Bilirubin is the end product of red cell (RBC) breakdown which occurs as part of recycling of old or damaged RBCs. The bilirubin thus formed is carried in the bloodstream to the liver where it mixes with bile in a process called conjugation.

The bilirubin in the liver is then transported from the liver via the bile ducts and reaches the intestines where most of it is eliminated in the stools. A small amount is however excreted in the urine.

What are the Causes of Jaundice?
From the above discussion, it is evident that any disruption in the metabolism of bilirubin can lead to jaundice. The causes of jaundice therefore include the following

I. Increased formation of bilirubin (hemolytic jaundice)
II. Defective conjugation of bilirubin in the liver (hepatocellular jaundice)
III. Defective transport and excretion of bilirubin in the intestines (obstructive or post-hepatic jaundice) and backflow into the bloodstream

Hemolytic jaundice
Increased formation of bilirubin occurs when there is increased destruction of RBCs which occurs due to the various hemolytic anaemias eg sickle cell anaemia, thalassemia and drug induced haemolysis.

Hepatocellular jaundice
In hepatocellular jaundice, the conjugation of bilirubin is impaired because the conjugation function of the liver cells is affected by various causes such as:
• Viral infections eg hepatitis A B and C
• Alcohol abuse
• Cirrhosis liver
• Autoimmune liver disease
• Drugs eg acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), mushroom poisoning
• Gilbert syndrome

Obstructive (Cholestatic) jaundice:
In obstructive jaundice, the transport of bilirubin to the intestines to be excreted is affected due to a blockage of the bile ducts within the liver (intrahepatic cholestasis) or outside (extrahepatic cholestasis).

The accumulated bilirubin spills over into the blood. The causes include:
• Tumor or inflammation in the bile ducts or gallbladder
• Stones in the gallbladder or bile ducts
• Pancreatic cancer
• Congenital disorders of bile ducts

What is Conjugated and Unconjugated Hyperbilirubinemia?
When the increase in serum bilirubin is predominantly unconjugated bilirubin the type of jaundice is referred to as unconjugated hyperbilirubinemia. If the increase is predominantly conjugated bilirubin, then it is conjugated hyperbilirubinemia.

• Generally, unconjugated hyperbilirubinemia occurs in haemolytic jaundice where there is increased formation of unconjugated bilirubin (refer bilirubin metabolism) and hepatic causes of jaundice where the bilirubin has not undergone conjugation due to liver cell damage, resulting in increased blood levels of unconjugated bilirubin.

• In post-hepatic or obstructive jaundice the bilirubin is conjugated in the liver but unable to be transported to the intestine to be excreted resulting in backflow of the conjugated bilirubin into the bloodstream and conjugated hyperbilirubinemia.

What are the Symptoms and Signs Of Jaundice?
It should be emphasised that jaundice is in itself a symptom of an underlying disease. The clinical features will therefore depend on the underlying cause. The associated clinical features depending on the underlying cause may include the following:

• Fever
• Abdominal pain
• Loss of appetite
• Nausea
• Severe itching or pruritis
• Varying degrees of anaemia (in haemolytic jaundice)
• Liver enlargement
• Weight loss
• Signs of liver failure such as ascites, spider naevi, gynaecomastia, flapping tremor

How is Jaundice Evaluated?
A complete and thorough history and physical examination is essential to give a clue to the possible cause. The doctor will ask about the onset and duration of symptoms, history of weight loss, family history, history of blood transfusion, and history of drug ingestion or IV drug use. During physical examination, he will look for signs of anaemia, fever, presence of liver enlargement, enlarged lymph nodes etc to rule in or rule out certain causes.

Laboratory tests: to confirm the diagnosis:.

Blood tests
The following tests may be useful in confirming the diagnosis

• Estimation of serum bilirubin level comprising total, conjugated and unconjugated bilirubin. The normal value of total serum bilirubin is 0.3-1.9 mg/dL.

• Tests to rule out haemolytic anaemia such as complete blood count including
reticulocyte counts, blood film examination, and autoantibody screen.

• Liver enzymes – Serum transaminases (ALT and AST) are typically elevated in liver or hepatocellular injury. Serum alkaline phosphatase is elevated in obstructive jaundice though this is not specific for liver disease (bone disease also shows elevated alkaline phosphatase). In alcoholic liver disease, gamma-GT is elevated.

• Viral serology for hepatitis B and C and blood culture to check for infectious causes such as leptospirosis.

Urinalysis:Urine is checked for presence of bile salts and bile pigments

Diagnostic imaging:
Ultrasound of the abdomen may reveal an enlarged liver, presence of gallstones, or tumor. In some cases a CT-scan or MRI may be necessary. Occasionally specialised tests such as endoscopic retrograde cholangiopancreatography (ERCP) will be done to look for any disease in the pancreas or the biliary tree.

Liver biopsy: It involves inserting a needle through the skin of the abdomen to enter the liver and obtain a sample of liver tissue for microscopic examination. It is performed under radiological guidance. It is only indicated when the results of other tests are not helpful or further information is needed. A liver biopsy carries some risk of bleeding and infection.

How is Jaundice Treated?
The treatment of jaundice involves management of the underlying cause and providing symptomatic relief.

• Analgesics and antipyretics to relieve symptoms of pain and fever
• Cholestyramine for relief of pruritis
• Liver supplements in hepatocellular jaundice to improve liver function in viral hepatitis A which is usually self-limiting.
• Anti-viral medication for Hepatitis B and C
• Management of haemolytic anaemia
• Surgery to remove gallstone or bile duct stone.
• Appropriate management of tumor in the liver, gallbladder, biliary tree or pancreas

How can Jaundice be Prevented?
Not all causes of jaundice can be prevented. However infectious and drug induced causes can be prevented.

• Proper hygienic practices such as regular handwashing before eating, after empting bowels
• Avoid sharing personal items such as razors and toothbrushes
• Thorough check before transfusion of blood and blood components for Hepatitis B and C
• Hepatitis B vaccination in high risk individuals such as doctors and lab personnel who handle blood and blood products
• Practising safe sex
• Avoid sharing IV needles
• Ensure clean and sterile needles are used while getting tattooed
• Avoiding alcohol abuse
• Avoid abuse of painkillers such as NSAIDs and acetaminophen

Frequently Asked Questions:

How long will it take to recover from jaundice?
The duration depends on the cause of jaundice. Usually hepatitis A infection is self-limiting and the patient recovers in 4-6 weeks. In cases of obstruction, the jaundice disappears once the obstruction is relieved eg bile duct stones. In malignancy the disease course may be prolonged. In liver failure eg alcoholism, jaundice may be progressively worse.

What diet is recommended in jaundice?
A diet filled with fresh fruits and green vegetables is essential. Avoid oily and spicy foods. Alcohol intake should be avoided. Liver supplements will help.

Can jaundice be fatal?
Most cases of jaundice recover completely. In instances of liver failure or incurable cancer, it could be life-threatening.

What is kernicterus?
This condition when severe jaundice occurs in the newborn. The excess bilirubin gets deposited in the brain causing brain damage.

What is pseudojaundice?
In pseudojaundice, the yellowish discolouration of skin is not due to bilirubin, but due to excess intake of beta carotene containing foods such as carrots.

Are there inherited causes of jaundice?
Certain enzyme deficiencies can result in jaundice due to excess unconjugated bilirubin such as Gilbert and Criggler Najjar syndrome. In Dubin Johnson and Rotor syndrome, there is excess conjugated bilirubin because the liver is unable to excrete the conjugated bilirubin. Fortunately these conditions are rare.

[uamohammed]

Thank you, Dr Lakshimi, for an update on Jaundice.

One cause of haemolytic jaundice is falciparum malaria. Of course we don't encounter that many cases of malaria as we had seen some decades ago, but it is still present here and there. World health authorities are warning us that it is going to re-emerge soon.
It is usually seen in non-immune or semi-immune individuals. Immune individuals who have lost their immunity due to stay in a non-malarious area may also develop the complication if they happen to get malaria on their return to malarious area.
The intravascular hemolysis can be due to non-immune destruction of parasitized red cells in case of high parasitemia or due to immune mediated destruction of parasitized as well as non-parasitized red cells.
In malaria if the jaundice is due to haemolysis it is unconjugated form. The mild elevation in serum bilirubin level usually returns to normal within 3-5 days of effective antimalarial treatment.

However, hepatic dysfunction may also be seen in cases of severe falciparum malaria. Such patients have conjugated hyperbilirubinemia, marked elevations of aspartate aminotransferase and alanine aminotransferase and prolongation of prothrombin time. Massive haemolysis, disseminated intravascular coagulation and hepatic dysfunction may all contribute to this picture. A term ‘malarial hepatitis’ has been used to describe this entity.

The haemolysis can occur so rapidly that the haemoglobin may drop significantly within a few hours and it may recur periodically at intervals of hours or days. Patient presents with head ache, nausea, vomiting and severe pain in the loins and prostration. Fever up to 39.40C with a rigor is also seen. Urine is dark red to almost black. Patient may have tender hepatosplenomegaly. The urine becomes darker and the output slowly drops. Renal failure and peripheral circulatory failure are the usual causes of death in these patients.
I used to tell my juniors whenever you come across a severe intractable anemia and jaundice, don't forget to look for malaria. Unfortunately, sometimes 'looking for' malaria may not get you any where. You should have a strong suspicion and sometimes you have to treat malaria empirically.

UA Mohammed

[Badri]

Thank you Mohammed for that useful update. Lakshmi has covered the topic well and she had mentioned haemolysis. Haemolysis can occur from a variety of diseases and causes. I suppose we should never forget Malaria, particularly in India where it is becoming a problem again.