Introduction
Bilirubinuria is an abnormal condition whereby conjugated bilirubin is detected in urine. Bilirubin is the end product of the process called heme catabolism that causes exchange of the bile pigments which are usually in the urine that it is not detected (Douman et al., 2013). When there are abnormal amounts of the bilirubin that is excreted through the bile then it is an indicator that someone is suffering from bilirubinuria.
Bilirubin is a tetrapyrole product by the normal break down of heme. Most bilirubin is produce during the break down of hemoglobin and other hemoproteins. Accumulation of bilirubin or its conjugates in body tissues produce jaundice (i.e. icterus),when characterized by high plasma bilirubin levels and deposition of yellow bilirubin pigments in the skin, sclerae, mucous membranes and other less visible tissues (Westwood, 2011).
Normally, even in a healthy person, red blood cells eventually reach the end of their life. They live far less than a human about 120 days in total. But the thing is that in that short space of time, they can travel upwards of a total 300 miles within our body. Once red blood cells reach their end either naturally or due to disease they either burst open in the bloodstream or are removed from circulation by spleen. Of course the spleen only retires the really old, sick and decrepit red blood cells and lets the health ones pass through. Once a red blood cell dies its haemoglobin which is a protein in red blood cells that actually carries the oxygen is broken down into parts. One part of haemoglobin is known as heme and it is this part that is broken into bilirubin. More specifically this bilirubin is known as indirect bilirubin or unconjugated bilirubin. Indirect bilirubin is a yellow pigment formed from the destruction of red blood cells. It is released into circulation but because it’s water-insoluble, it must be bound to a blood protein called albumin (Fevery, 2008).
In generally, unconjugated bilirubin is unable to pass through glomerulus and therefore does not appear in the urine (Baker and Silvertons, 2009).
Conjugated bilirubin passes into the bile canaliculi through the bile duct and into the intestine. In the terminalileum and colon the bilirubin is deconjugated and reduced by bacteria to various pigments and colourless chromogens (urobilinogen most of which are excreted in the process as stercobilinogen). Some of the bilirubin and urobilinogen from the intestine reabsorb into the portal circulation and reaches the liver where it re-enters the intestine in the bile and is excreted in the faeces. A small amount of reabsorb urobilinogen is carried in through the liver and transported to the kidney where is excreted in urine.
In a health individual about 5% of the total plasma bilirubin is conjugated and 95% or more unconjugated. Urine contains a trace of urobilinogen and in a pathological condition bilirubin is found (Cheesbrough, 2004).
Conceptual framework
Bilirubinuria is abnormal condition found in the urine, caused by high level of conjugated bilirubin. Bilirubinuria is not a disease but an abnormality that indicate a possible problem. It may indicate any of several condition including jaundice, hepatitis or other hepatic diseases, liver dysfunction or impairment, disorders involving haemolytic anaemia, bile duct obstruction, starvation or dehydration, haemolysis or pyrexia. In more rare cases it may be a system of certain cancers, or inherited disorder such as Dubin-Johnson syndrome or Rotor syndrome. It may also be caused by a certain prescribed drugs that lower the urine PH value or high levels of nitrates or ascorbic acid (Memon et al., 2015).
Bilirubinuria has been identified to be the hepatocellular disease whose symptom is normally build up of copper which is found in the liver. The traces of copper get dispersed to other areas of the body as time goes by and causes serious damage especially when they reach the brain. The sensitive tissues of the brain are affected by the copper and as a result causing tremors that cannot be controlled to the body as well as deficiencies in a person speech. When the copper reaches the liver it causes a condition called cirrhosis which causes damage to the liver (Johnston, 2006).
Because bilirubin is highly insoluble in water it may be converted into a soluble conjugated bilirubin before elimination from the body. In the liver uridin diphosphate (UDP) – glucoronyl transferase convert bilirubin to a mixture of monoglucuronides and diglucuronides, refers as conjugated bilirubin, which is then secreted into the bile by an ATP – dependent transporter. This process is highly efficient under normal conditions, so plasma unconjugated bilirubin concentration remain low.
A large number of disease slites lead to bilirubin accumulation in plasma. Diseases that increase the rate of bilirubin formation, such as haemolysis or diseases that reduce the rate of bilirubin conjugated such as Gilbert syndrome, produce unconjugated hyperbilirubinemia (Muraca et al., 2004).
Pathophysiology
Conjugated hyperbilirubinemia result from reduced secretion of conjugated bilirubin into the bile, such as occurs in patients with hepatitis, or from impaired flow of bile into the intestine as in patient with biliary obstruction. Bile formation is sensitive to various hepatic insuits including high levels of inflammatory cytokines as may occur with patients well septic shock.
High levels of conjugated bilirubin may secondarily elevate the level of unconjugated bilirubin. Although the mechanism of this effect is not fully known, likely cause is reduced hepatic clearance of unconjugated bilirubin that results from competition well conjugated bilirubin for uptake or excretion (Pejor and Cushman, 2009).
Causes of bilirubinuria
The following are the causes of bilirubinuria:
Hepatitis: due to hepatitis viruses and less frequently to other viruses (e.g. yellow fever viruses, Marburg and Ebola viruses, Epstein – Borr virus, cytomegalovirus). Bacteria such as leptospira interrogans, parasites including toxoplasma gondii and a certain drugs and toxin affect the liver resulting in obstruction the liver (Cheesbough, 2004).
Hepatocellular: in hepatocellular there is buld up of bilirubin in the plasma because it is not transported conjugated or excreted by the liver cells because they are damaged, e.g. in viral hepatitis. The excess bilirubin is usually of both the conjugated and unconjugated types with bilirubin being found in urine (Cheesbough, 2004).
Haemolytic: in haemolytic (prehepatic) more bilirubin is produced then the liver can metabolize e.g. in severe haemolysis (breakdown of red cells). The excess bilirubin which buld up in the plasma is mostly of the unconjugated type and is therefore not found in the urine (unconjugated) but in case of conjugated it may be found in urine causing bilirubinuria (Cheesbough, 2004).
Obstruction: In obstruction (posthepatic) bilirubin is build up in plasma because its flow is obstructed in the small bile channels or in the main bile duct. This can be caused by gall stones or a tumour obstructing or closing the biliary tract. The excess bilirubin is mostly of the conjugated type and is therefore found in the urine. The term cholestasis is used to describe a failure of bile flow (Cheesbough, 2004). In certain liver diseases such as biliary obstruction or hepatitis excess bilirubin can build up in the blood and is eliminated in urine. The presence of bilirubin in urine is an indicator of liver disease and can occur before clinical symptom such as, jaundice develop. A positive test for urine confirms that any raised plasma levels are from hyperbilirubinaemia (Adeoye, 2007).
Types of bilirubin
Bilirubin exist in two forms, which are the unconjugated and conjugate bilibrubin.
Unconjugated bilirubin
Unconjugated bilirubin is also known as indirect bilirubin. The haem (iron porphyrin) of the haemoglobin molecule is firstly removed from the globin. The porphyrin portion is then converted to biliverdin which is reduced to bilirubin. The bilirubin is insoluble in water, it is carried in the blood attached to albumin and it cannot be excreted by the kidney. This bilibrubin is referred to as unconjugated or indirect bilirubin. (Ochie and Kolhatkar, 2007).
Conjugated bilirubin
In the liver, bilirubin combines with glucuronic acid by the enzyme glucuronyltraferase, making it soluble water, the conjugated bilirubin is often called “direct” bilirubin. Much of it goes into the small intestine. Though most bile acid is resorted in the terminal ileum to participate in eterohepatic circulation, conjugated bilirubin is not absorbed and instead passes into the colon. Total bilirubin comprises of both conjugated bilirubin levels are measured directly in the blood, whereas indirect bilirubin level are, derived from the total and direct bilirubin measurement (Chiefetz and Adam, 2010).
Etiology of bilirubin
Some underlying conditions leading to bilirubin according to Gillott (2015) are:
- Acute inflammation of the liver: this may impair the ability of the liver to conjugate and secrete bilirubin, resulting in buildup of bilirubin.
- Inflammation of the bile duct: this prevents the secretion of bile and removal of bilirubin causing jaundice.
- Obstruction of the bile duct: it prevents the liver from disposing of bilirubin, which results in hyperbilirubinemia.
- Malaria: a blood borne infection spread by mosquitoes.
- Sickle cell anaemia and thalassaemia: an inherited blood disorder where the red blood cells develop abnormally; its most common among black Caribbean, black African and black British people.
- Najjar syndrome: a genetic syndrome where an enzyme needed to move bilirubin out of the blood and into the liver is missing.
- Hereditary spheroeytosis: a genetic that causes red blood cells to have a much shorter life span than normal.
- Viral hepatitis group of infections; hepatitis A,B and C.
- Alcohol liver disease: where the liver is damage as a result of drinking too much alcohol.
- Leptospirosis: a bacterial infection that is spread by animals, particularly rats.
- Glandular fever: a viral infection caused by Epetein-bar virus.
- Drug misuse: leading cause are ecstasy and overdoses of paracetamol.
- Primary biliary cirrhosis. A rare condition that causes progressive liver damage.
- Giberts syndrome: a common genetic syndrome where the liver has problems breaking down bilirubin at a normal rate.
- Liver cancer: a rare and usually incurable cancer that develops inside the liver.
- Exposure to substance known to be harmful to the liver: such as phenol (used in the manufacture of plastic or carbon tetrachloride).
- Autoimmune hepatitis: a rare condition where the immune system attacks the liver.
- Primary sclerosing cholangitis: a rare type of liver disease that causes long lasting (chronic) inflammation of the liver.
- Dubin-Johnson syndrome: a rare genetic syndrome where the liver is unable to move bilirubin out of the liver.
- Gall-stone: obstructing the bile duct system.
- Pancreatitis: inflammation of the pancreases, which can either be acute pancreatitis (lasting for a few days) or chronic pancreatitis (lasting for many years).
Treatment
Treatment of bilirubin depends on the type, how serious it is and its causes. It may indicate taking an underlying condition such as malarial. For genetic conditions that don’t get better, like sickle cell anemia, a blood transfusion may be given to replenish red cells in the body. If the bile duct system is blocked, an operation may be needed to unlock it.
During these procedures, measures may be taken to help prevent further problems such as removal of the gallbladder. If the liver is found to be seriously damaged, a transplant may be an option. In the case of newborn, exposing the baby to special coloured light (phototherapy) or exchange blood transfusion may be required to decrease elevated bilirubin level.
Prevention
Many conditions can cause bilirubinuria. So it is hard for doctors to give specific prevention advice in all cases. The underlying medical condition causing bilirubin,can in some cases be prevented.
Some preventive measures include the following:
- Avoid heavy alcohol use (Alcohol hepatitis, cirrhosis, and pancreatitis).
- Vaccines for hepatitis (Hepatitis A and B).
- Take medications which prevent malaria before travelling to high risk regions.
- Avoid potentially contaminated food/water and maintain good hygiene (Hepatitis A).
- Avoid medication that can cause haemolysis in susceptible individuals (such as those with G6PD deficiency, a condition that leads to red blood cell breaking down after consumption of certain substance).
- Avoid medications and toxins which can cause haemolysis or directly damage the liver (Steven, 2014).
References
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