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Overview

Normally, when old red blood cells break down, the contained hemoglobin proteins that carry oxygen to the tissues and organs of the body are converted into bilirubin. The bilirubin that is produced through this process is then converted to bile by the liver, stored in the gallbladder, and secreted by the latter into the small intestine to help digest lipids that are ingested by humans.

Bilirubin has a yellow/brown pigmentation to it and travels through the digestive tract where it is excreted via the stool and this is where the fecal matter gets its characteristic color from.

A small amount of the bilirubin ends up in the bloodstream and circulates throughout the vascular system of the body without causing any issues.

Conditions and scenarios causing increased bilirubin levels

Hemolytic anemia

Hemolytic anemia is a blood disorder characterized by premature damage and destruction of the red blood cells. The rate at which the red blood cells are destroyed is high which means that excessive bilirubin is secreted into the bloodstream when hemoglobin proteins are released as a result of the damage to the red blood cells.1

Conditions that may result in hemolytic anemia include:

·         Inherited conditions such as sickle cell anemia.

·         Autoimmune hemolytic anemia where the body’s immune system produces antibody proteins that attack and damage the normal red blood cells.

·         Systemic lupus erythematosus.

·         Epstein-Barr viral infections.

·         Certain lymphomas and leukemia’s.

Liver diseases

Diseases that affect the liver cause the organ to become dysfunctional which means that a process such as conversion of bilirubin to bile is negatively impacted. Therefore, the result of this problem is that bilirubin levels start to rise in the bloodstream because the organ cannot convert the by-product into its more extractable form.

Conditions that cause the liver to become dysfunctional include:

·         Viral hepatitis.

·         Liver cirrhosis as a complication of excessive alcohol intake or viral hepatitis.

·         Gilbert syndrome.

·         Dubin-Johnson syndrome.

Diseases of the gallbladder and bile ducts

Diseases or conditions that affect the gallbladder and bile ducts of the biliary system may cause a decreased flow of bile (cholestasis) due to obstruction in these mentioned organs. The result is that bile cannot flow from the liver which results in increased bilirubin flowing back into the blood causing the level of the by-product to increase in the bloodstream.2

Conditions that can affect the gallbladder and bile ducts include:

·         Gallstones partially or completely obstructing the ducts.

·         Internal blockage of the ducts due to bile duct tumors, or external compression of the ducts by conditions such as tumors of the gallbladder, liver, or pancreas.

Medications

Certain medications can elevate bilirubin levels by reducing the absorption of bilirubin by the liver to convert it to bile. Examples of medications that can cause this include:

·         Probenecid used to manage gout.

·         Rifampin used to treat tuberculosis.

Cholestasis can be caused by medications such as:

·         Chlorpromazine.

·         Erythromycin.

·         Anabolic steroids.

·         Hormone replacement therapy such as those used to manage menopausal symptoms.

Certain medications can affect the function of the liver. One of the most important medications that can be toxic to the liver is taken in excessive amounts is acetaminophen/paracetamol.

Clinical presentation

Affected individuals may experience symptoms and signs such as:

·         Yellow discoloration of the white of the eyes and/or skin. This is called jaundice.

·         Itching of the skin due to excess bilirubin in the bloodstream.

Symptoms and signs which may indicate the involvement of the liver, gallbladder, and or bile ducts can include:

·         Upper right-sided abdominal pain.

·         Sudden abdominal enlargement.

·         Nausea and vomiting.

·         Changes in bowel habits.

·         Dark-colored urine and pale stools.

Blood-related disorders that may result in hemolytic anemia can cause issues such as:

·         Unexpected weight loss.

·         Unexplained fevers of swollen glands.

·         Anemia causing paleness of the skin, fatigue, dizziness, heart palpitations, and shortness of breath.

Conclusion

Individuals who notice yellow discoloration of their skin or white of their eyes should consult with their primary care doctors to rule out the possibility of jaundice.

This can be done by performing a blood test to check the bilirubin levels in the bloodstream and if they are elevated, the affected individual will be assessed and investigated further to determine the cause of the problem.

Once the diagnosis is confirmed, the patient will be managed accordingly.

Reference

1. Nouraie M, Lee JS, Zhang Y, et al. The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe. Haematologica. 2013;98(3):464-472. doi:10.3324/haematol.2012.068965.

2. Beckingham IJ, Ryder SD. Investigation of liver and biliary disease. BMJ : British Medical Journal. 2001;322(7277):33-36.