Jaundice

Jaundice (icterus) is a yellow discoloration of tissues that we see on the skin, mucous membranes and in the eyes. Jaundice is just a symptom, it is not a disease. Yellow color of body tissues is caused by accumulation of a substance known as bilirubin.

 

Bilirubin has a close relation to hemoglobin. Everyone knows that red blood cells (erythrocytes) carry breathing gases like oxygen and carbon dioxide. Oxygen transfer is enabled by a compound located inside erythrocytes known as hemoglobin. Average life of an erythrocyte is about 120 days. During break down of an individual erythrocyte, its hemoglobin is released and divided into two compounds - heme and globin. Heme is converted to biliverdin and biliverdin is turned into the unconjugated bilirubin.

 

Unconjugated bilirubin is then bound to blood proteins are transported to the liver tissue where it is conjugated. Conjugated bilirubin becomes water soluble; it is transported to bile ducts and excreted with bile into the small intestine. In bowels bilirubin is transformed by intestinal microflora into substance known as urobilinogen that causes brownish stool coloration.


The above mentioned metabolic process can be described as follows:
heme -> biliverdin -> unconjugated bilirubin -> liver + conjugation -> conjugated bilirubin -> bile -> stool -> conversion to urobilinogen

 

If for any reason bilirubin (either conjugated or unconjugated) accumulates in the body, the jaundice occurs.

Causes

I. Increased destruction of red blood cells (hemolysis)

It is quite logical. If more red blood cells disintegrate, more hemoglobin is released and bigger amount of bilirubin is produced. When liver tissue is unable to conjugate and excrete this amount of bilirubin, it starts to accumulate and turns our tissues yellow. Such conditions related to increased hemolysis are for example severe septic conditions, malaria, autoimmune hemolytic anemia, sickle-cell anemia, thalassemia and others.

 

Neonatal jaundice is quite a specific condition. It is caused by breakdown of red blood cells induced by the natural replacement of erythrocytes containing fetal hemoglobin to erythrocytes with neonatal hemoglobin. Some forms of neonatal jaundice can be fatal; especially the so-called hemolytic disease of the newborn, when severe jaundice is caused by the mother's immune system damaging the red blood cells of the newborn.

II. Liver tissue damage

Damage to liver tissue may reduce its capability to conjugate and excrete bilirubin. Both conjugated and unconjugated bilirubin accumulates in the body and cause jaundice. Conjugated bilirubin may be excreted into urine and gives it characteristic dark color.

Liver alcohol damage

Excessive chronic abuse of alcohol damages the liver and gradually leads to cirrhosis. Jaundice is a rather late and very severe symptom of liver failure in alcoholics.

Infectious hepatitis

Infectious hepatitis is usually caused by viral microorganisms, we differentiate hepatitis A, B, C, D and E. Jaundice in acute stage is typical mainly for hepatitis A and less frequent hepatitis E.

Hepatotoxic substances (excluding alcohol)

There are many toxic substances that kill liver cells. These include high doses of paracetamol and mushroom poison (e.g. amanitin and phalloidin in amanita phalloides also known as “death cap”). Jaundice may accompany acute liver failure in poisoning by all these substances.

Wilson's disease

This rare metabolic disease is related to storage of copper in the liver. Copper behaves as an irritant substance; it damages liver tissue and may cause cirrhosis.

Liver malignancies

Advanced primary liver cancer and metastases of other tumors may be associated with jaundice. Tumor damages surrounding healthy liver tissue and so interferes wit liver functions

Autoimmune hepatitis

This autoimmune condition occurs when our own immune system attacks and gradually kills the liver cells. The consequences are serious as the process may end up in severe cirrhosis.

Genetic disorders

There are two genetic disorders that disrupt bilirubin conjugation - a rare Crigler-Najjar syndrome and more common Gilbert's syndrome. Gilbert's syndrome usually manifests in young men and it is rather a positive condition than a real disease. See more in relevant article.

III. Biliary tract obstruction

If there is a problem in bile flow, conjugated bilirubin can not be excreted into intestine and accumulates in liver and other body tissues. Because there is no urobilinogen in stool, it looses its natural brown color and becomes pale. In addition, bile absence causes problems in fat absorption; the stool becomes oily, yellowish and unpleasantly smells. Bile acids accumulating in skin cause itching. Urine is dark because of the presence of conjugated bilirubin.

Pancreas cancer

Pancreatic tumors can compress the bile duct, thus blocking the bile flow. Sudden painless jaundice is its classic symptom that should never be underestimated.

Gallbladder cancer

Gallbladder tumor can also compress the bile duct causing similar symptoms as pancreatic cancer.

Effects of alcohol

Alcohol has a complex effect on liver. It directly damages liver tissue and its ability to conjugate bilirubin. Further, alcohol prevents liver cells to release bile and thus causes a condition similar to the classic biliary obstruction.

Complication of gallstones

If a gallstone blocks the bile duct, painful colic pain occurs followed by jaundice. This condition is closely linked with infections of gallbladder (cholecystitis) and biliary tree (cholangitis).

Autoimmune diseases of bile ducts

These conditions cause immune system reaction against cells of small bile ducts in the liver and cells of extrahepatic biliary tree. We differentiate primary biliary cirrhosis and primary sclerosing cholangitis.

Genetical inherited disorders

There are two rare inherited diseases that cause disorder of bilirubin excretion into the bile. It is the so-called Dubin-Johnson syndrome and Rotor syndrome.

Diagnostic approach

Medical history should focus on known diseases, other present symptoms (loss of appetite, nausea, pain, fever, pale stool, itchy skin, dark urine), current medication, attitude to alcohol, etc. Blood tests are of a great importance as they help us to evaluate liver tests, bilirubin (both conjugated and unconjugated) serum level and serologically prove different types of viral infectious hepatitis. Elevated serum unconjugated bilirubin informs us about the increased breakdown of red blood cells and conjugated about liver damage or impaired bile flow. The examination is supplemented by imaging methods. The liver and bile duct is well-examinable by simple abdominal ultrasound. Gastroenterologists use a special examination method known as ERCP that allows visualizing biliary tract strictures and gallstones and treating them. Further use of diagnostic methods depends on the outcome of previously mentioned examinations.