Jaundice, a condition that causes yellowing of the skin, eyes, and mucous membranes, is not a disease itself but rather a visible sign of various underlying medical conditions.

It is often associated with liver dysfunction, but the causes can range from blood disorders to infections. In this Blog, we will look at the underlying science behind it, its causes, mechanisms, and how it is diagnosed and treated.

What is Jaundice?

Jaundice, medically known as icterus, is the visible yellowing of the skin, the whites of the eyes (sclera), and other tissues due to the accumulation of bilirubin.

Bilirubin is a yellow pigment produced when red blood cells break down in the body. It is a natural byproduct of hemoglobin breakdown and is normally processed by the liver before being excreted through stool and urine.

However, when bilirubin builds up in the blood, it begins to accumulate in body tissues, causing jaundice.

Metabolism of BILIRUBIN

To grasp the essence of jaundice, it is essential to understand bilirubin metabolism:

• Production: Bilirubin forms when hemoglobin from old red blood cells is broken down in the spleen.
  
  
• Transport: Unconjugated (indirect) bilirubin is released into the bloodstream and travels to the liver.
  
  
• Conjugation: In the liver, bilirubin binds with glucuronic acid, converting it into a water-soluble form known as conjugated (direct) bilirubin.
  
  
• Excretion: This conjugated bilirubin is then excreted into the bile and removed from the body through feces. A small amount is also excreted through urine, giving it its yellow color.

When any part of this process is disrupted—whether through excessive production of bilirubin, liver damage, or obstruction in bile excretion—bilirubin accumulates in the body, resulting in jaundice.

Risk Factors for Jaundice

Various factors increase the risk of developing jaundice, including:

Hemolytic diseases: Can lead to increased breakdown of red blood cells.

Alcohol abuse: Damages the liver and leads to cirrhosis.

Chronic hepatitis: Causes long-term liver inflammation and damage.

Obesity: Increases the risk of developing fatty liver disease.

Causes

Jaundice can stem from a wide variety of conditions. It is typically categorized into three main types based on where the problem lies within the bilirubin metabolism pathway:

Pre-hepatic Jaundice

This type occurs before the liver processes bilirubin and is usually caused by the excessive destruction of red blood cells (hemolysis). This leads to an increase in unconjugated bilirubin in the blood, overwhelming the liver’s capacity to process it.

• Hemolytic anemia: A condition where red blood cells are destroyed faster than they are produced.
  
• Malaria: A parasitic infection that invades red blood cells.
  
• Sickle cell disease: An inherited disorder that causes red blood cells to become abnormally shaped and more prone to destruction.
  
• Thalassemia: A genetic blood disorder leading to the abnormal production of hemoglobin.

Hepatic Jaundice

In hepatic jaundice, the problem lies within the liver itself, where damage to liver cells impairs the processing of bilirubin.

• Hepatitis: Inflammation of the liver due to viral infections, alcohol, or drugs.
  
• Liver cirrhosis: Long-term damage to liver tissues, often due to chronic alcoholism or hepatitis.
  
• Liver cancer: Malignant cells in the liver disrupt its normal functions.
  
• Gilbert’s syndrome: A genetic condition where the liver has trouble processing bilirubin properly.

Post-hepatic Jaundice

Also known as obstructive jaundice, this type occurs when bilirubin cannot flow out of the liver due to blockages in the bile ducts, leading to the accumulation of conjugated bilirubin in the bloodstream.

• Gallstones: Hardened deposits in the gallbladder that block bile ducts.
  
• Pancreatic cancer: A tumor compressing the bile ducts.
  
• Primary biliary cirrhosis: An autoimmune disease that gradually destroys the bile ducts in the liver.
  
• Cholangitis: Infection or inflammation of the bile ducts.

How To Approach

Approaching jaundice in a clinical setting requires a thorough history and physical examination to help determine the underlying cause.

History

Onset and Duration:

• Ask the patient when they first noticed yellowing of the skin or eyes.
• Acute onset of jaundice may suggest hepatitis, gallstone disease, or drug-induced liver injury, while chronic jaundice could indicate conditions like cirrhosis or chronic hepatitis.

Color of Urine and Stool:

• Dark urine with pale stools suggests obstructive jaundice, which could be due to biliary obstruction (e.g., gallstones, tumors).
• Normal-colored urine with dark stools may suggest pre-hepatic causes like hemolysis.

Associated Symptoms:

• Fatigue, anorexia, and fever: These can suggest viral hepatitis or other liver infections.
  
  
• Pruritus (itching): This symptom is often present in cholestatic (obstructive) jaundice due to the buildup of bile acids.
  
  
• Abdominal pain: Right upper quadrant pain may suggest cholelithiasis or cholecystitis.

Medical and Surgical History:

• History of liver disease, hepatitis, gallbladder surgery, or blood transfusions is important.
  
  
• Ask about medications (e.g., acetaminophen, antibiotics) that could contribute to drug-induced liver injury.
  
  
• Check for alcohol use or substance abuse, which could lead to alcoholic liver disease.

Travel and Risk Factors:

• Recent travel to areas endemic for hepatitis A or E could point to a viral cause.
• History of IV drug use or unprotected sexual contact may increase risk for hepatitis B or C.

According to the Centers for Disease Control and Prevention (CDC), approximately 60-90% of people who inject drugs may contract Hepatitis C within five years of starting IV drug use due to the high risk of needle sharing .

Family History:

Ask about inherited conditions like Gilbert’s syndrome or hemolytic anemias.

Physical Examination

General Inspection:

• Look for yellow discoloration of the skin, sclera, and mucous membranes.
• Assess for cachexia (severe weight loss), muscle wasting, or other signs of chronic disease.

Palpation of the Abdomen:

• Liver: Assess for hepatomegaly (enlarged liver) which may be tender in acute liver disease (e.g., hepatitis).
• Gallbladder: Check for Murphy’s sign (pain on palpation of the right upper quadrant during inspiration), which could indicate cholecystitis.
• Ascites: Look for fluid accumulation, which may be present in cirrhosis or liver failure.

Signs of Chronic Liver Disease:

• Spider angiomas: Small, dilated blood vessels on the skin are often seen in cirrhosis.
• Palmar erythema: Redness of the palms may suggest chronic liver disease.
• Gynecomastia: Enlarged breast tissue in men can be a sign of hormonal imbalances due to liver dysfunction.
• Caput medusae: Distended veins around the umbilicus, indicating portal hypertension.

Neurological Examination:

• Assess for hepatic encephalopathy (e.g., confusion, asterixis, or tremors), which can occur in advanced liver disease.

Investigations

Laboratory Tests:

• Hemolytic tests: These include a complete blood count (CBC), reticulocyte count, and haptoglobin levels to evaluate hemolysis.
  
  
• Bilirubin levels: Total and direct (conjugated) bilirubin levels in the blood help differentiate between unconjugated and conjugated hyperbilirubinemia.
  
  
• Liver function tests (LFTs): Check for elevated liver enzymes (ALT, AST, ALP), indicating liver damage or obstruction.
  
  
• Viral markers: Tests for hepatitis A, B, and C can identify viral causes of jaundice.

Imaging:

• Ultrasound: The liver and bile ducts are often visualized to check for blockages or gallstones.
• CT or MRI: May be used if a tumor or other structural cause is suspected.

Management

In general, the goal is to resolve the cause of the bilirubin buildup.

• Pre-hepatic Jaundice: Treatment focuses on addressing the cause of hemolysis. Blood transfusions, immunosuppressive therapy (in autoimmune hemolytic anemia), or treatment for infections like malaria may be necessary.
  
  
• Hepatic Jaundice:
  • In cases of hepatitis, antiviral or steroid therapy may be used. Supportive care, such as abstaining from alcohol, eating a balanced diet, and avoiding medications that affect the liver, is essential.
  • Liver transplant may be necessary in advanced cirrhosis or liver failure.
    
    
• Post-hepatic Jaundice:
  • In cases of obstructive jaundice, the goal is to relieve the blockage. This might involve removing gallstones, surgically bypassing the bile ducts, or placing a stent to keep the bile duct open.
  • If cancer is the cause, surgical removal of the tumor or chemotherapy may be required.

Conclusion

Jaundice, though visually distinct, is a symptom with a wide range of potential causes. From the breakdown of red blood cells to liver dysfunction and bile duct obstruction, the mechanism behind jaundice is rooted in the body’s complex processing of bilirubin.

Accurate diagnosis and treatment depend on identifying the underlying cause, whether it’s a hemolytic condition, liver disease, or an obstruction in the bile ducts.