Bilirubin is a heme-containing pigment compound released during the breakdown of red blood cells.
It is excreted from the human body as part of the bile fluid, therefore it belongs to bile pigments.
- Bile pigment formation
- Metabolic path
- Types of bilirubin
- The rate of different fractions of bilirubin
- The level of bile pigments in children
- Bilirubin levels during pregnancy
- How is the increase in bilirubin manifested?
- How to lower bilirubin?
- What is hyperbilirubinemia associated with?
- What are the symptoms?
- How many types of jaundice are there?
- Pathological jaundice in newborns
- What does low bilirubin levels indicate?
Bile pigment formation
Bilirubins are located in the spleen from biliverdin during the process of hemolysis (destruction of erythrocytes), it accounts for 85% of the newly formed pigment, the remaining 15% are synthesized during the cleavage of other heme-containing compounds – myoglobin, cytochromes.
As a result of heme catabolism, the non-protein part of hemoglobin, indirect bilirubin (unconjugated) is formed, a hydrophobic toxic water-insoluble substance that is transported by carrier proteins – albumin through the blood plasma.
In order to study this fraction, bilirubin must be separated from albumin by their precipitation, therefore it is called indirect.
After that, the pigment is transported by the portal vein system to the hepatocytes, where it is utilized by the conjugation (binding) reaction with UDP-glucuronate under the influence of the enzyme UDP-glucuronyl-bilirubin transferase.
This is how the process of neutralizing the toxic substance occurs, as a result of which a direct (conjugated) fraction of bilirubin is formed – hydrophilic, low toxic and water-soluble.
The bound bilirubin is excreted (excreted) by the bile stream into the small intestine, where it is converted into urobilinogen. This bile pigment is partially absorbed by enterocytes and utilized through the portal vein system into hepatocytes.
Most of the urobilinogen is transported to the large intestine and forms fecal stercobilin, which gives it a specific color. The remainder of the pigment compound is converted to urine stercobilin, which provides a straw-yellow color, and is filtered in the kidneys.
This means that only stercobilin should be in the urine and feces, the rest of the bile pigments are not normally excreted by these pathways.
Types of bilirubin
There are three types of bilirubin:
- General – all bilirubin circulating in the bloodstream. Its designation also looks like this Bilirubin total,
- Indirect – a toxic compound, the place of formation directly during the destruction of erythrocytes.
- Direct – associated with glucuronic acid bilirubin, excreted by the liver.
The rate of different fractions of bilirubin
Normal indications of bilirubin vary by gender and age.
Indicator In women (μmol/l) In men (μmol/l)
|Indirect fraction||5,6 – 17||Not more than 20,0|
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The level of bile pigments in children
The normal level of bilirubin in newborns differs from the results of analyzes in an adult. The bilirubin level is 22 μmol/L in the first hours of life, but soon this figure can become high up to 190 μmol/L.
Indicator 1-3 days after birth (μmol/L) 3-6 days after birth (μmol/L) After a month (μmol/L) Adults (μmol/L)
|Total bilirubin||24 – 190||28 – 210||3,5-20,4||8-20,5|
|Indirect fraction||23,5-179,8||27-197,6||Not more than 16,5||Not more than 16,5|
This is due to the fact that at birth, a baby may experience a transient (transitional) state – physiological jaundice of newborns. Intrauterine fetal hemoglobin is formed in the fetus, and when it is born, it begins to be replaced by an “adult”.
Increased hemolysis will be observed, and physiological immaturity of hepatocytes also plays an important role.
This transient state manifests itself 2-3 days after birth, and lasts no more than 10 days. Differences between physiological jaundice and pathological changes: it does not affect the general condition of the child and goes away on its own without medication.
Symptoms of jaundice in newborns: yellowness begins on the skin of the face and head, palms and feet, then goes down, changing the color of the whole body.
Bilirubin levels during pregnancy
During the period of gestation with a biochemical blood test, the bilirubin level in women may be slightly increased. This is due to the compression of the uterus of the liver, gallbladder.
To protect yourself from unwanted consequences, you need to undergo diagnostics and do an ultrasound scan. Hyperbilirubinemia in pregnant women can be triggered by stress, malnutrition, emotional and psychological stress.
They can reveal:
- Fatty hepatic dystrophy,
- Acute viral hepatitis,
- Gallstone disease
- Infectious diseases,
- Dyskinesia of the biliary tract (a problem with the removal of bile from the body).
Any changes in the functioning of the mother’s body affect the future baby, you should not close your eyes to these conditions.
How is the increase in bilirubin manifested?
An increase in bilirubin levels is called hyperbilirubinemia. Only one of the bilirubin fractions may increase, which will indicate pathological disorders in one of the internal organs. How can hyperbilirubinemia be diagnosed?
A condition that develops as a result of an increase in heme-containing pigment compounds is jaundice.
Jaundice is characterized by yellowness of the skin and mucous membranes. Initially, the sclera, the oral cavity acquire a yellow color, after that the skin of the face, palms and feet. The rest of the body turns yellow last.
In people with a large weight, the symptoms of hyperbilirubinemia are not as pronounced as in thin people.
An unhealthy skin color may indicate various diseases that are not tied to the work of the liver: diabetes mellitus, hypothyroidism, food preferences for carrots and red tomatoes.
Bile pigments are not normally found in urine and feces. If conjugated bilirubin is elevated, which is associated with liver disease, levels may be elevated in urine.
Scheme of the formation and removal of bilirubin from the body
How to lower bilirubin?
To lower the level of bilirubin, it is necessary to diagnose the cause that triggered the development of this condition. After that, dietary food and drug therapy are prescribed.
The dietary table includes the following foods:
- Vegetable broths,
- Fermented milk products,
- Fruits and vegetables,
- Lean meat dishes,
- Herbal teas,
- Cereals: rice, oatmeal, buckwheat,
All food should be served warm, in small portions, and divided into three to five meals a day.
There are also foods that you need to exclude from your diet:
- Fried and smoked dishes,
- Black bread,
- Coffee and tea,
- Carbonated drinks,
- Hot sauces and seasonings
- Sweets and bakery products,
- Wheat porridge
Drug treatment is represented by the following groups of drugs:
- Homeopathic remedies,
What is hyperbilirubinemia associated with?
Among the reasons leading to hyperbilirubinemia are:
- Liver disease – cirrhosis of various etiologies and hepatitis,
- Problems with the outflow of bile through the biliary tract,
- Pathological changes in the hematopoietic system,
- Gallbladder disease
- Blood transfusion (blood transfusion),
- Organ transplant,
- Hypo- and avitaminosis,
- Toxic intoxication.
Hereditary hyperbilirubinemia can also cause elevated bile pigment levels.
- Gilbert’s syndrome is a pathology directly related to the insufficient production of the enzyme glucuronidase, which takes part in the reaction of the formation of glucuronic acid. In a blood test, the level of direct bilirubin is markedly lowered. This disease has no unfavorable prognosis for life, work and physical activity, since there will be no destruction of hepatocytes. Patients need to adhere to a healthy lifestyle, a balanced diet, avoid physical activity and the use of alcoholic beverages.
- Dabin-Johnson syndrome is a congenital autosomal recessive disorder characterized by mutational changes in the gene responsible for the organic anion transporter protein. As a result, there is a violation of the excretion of bilirubin and organic anions from hepatocytes – the content of direct bilirubin in the blood is increased.
- Crigler-Nayyar syndrome is a hereditary pathology transmitted in an autosomal recessive way. It arises due to the complete absence or reduced activity of the enzyme glucuronyl transferase, which ensures the neutralization of the indirect fraction of bilirubin. Chronic intoxication of the nervous system appears with subsequent degenerative changes in the body.
What are the symptoms?
With an increase in total bilirubin, one can think of accelerated hemolysis associated with blood diseases, the presence of parasitic infections, primary biliary cirrhosis, the formation of stones in the hepatobiliary system, pregnancy, neoplasms that block the outflow of bile fluid.
Symptoms indicating an increase in direct bilirubin indicators: yellowness of the sclera and skin, dyspeptic symptoms, itching, poor appetite, bouts of hepatic colic, dark urine.
The reason for this is the obstructed outflow of bile, pathological changes in hepatocytes and the spread of the pigment compound throughout the body by the blood stream.
Unbound bilirubin is higher than normal in case of disorders associated with the conjugation process and the formation of a non-toxic direct pigment fraction.
The patient’s complaints will be slightly different: discomfort and pain in the right hypochondrium, high fever, splenomegaly (enlargement of the spleen), rapid fatigue and weakness, dizziness, pale skin, belching with bitterness, headache, dark urine.
How many types of jaundice are there?
There are three types of jaundice. Let’s take a closer look at each of them.
Type of jaundice; Characteristic; Development reasons
|Hemolytic (suprahepatic)||The manifestations of this disease are not associated with liver function. Most often, increased hemolysis occurs, in which an excess amount of indirect bilirubin accumulates in the body, which is toxic to the body. In this condition, there is an increase in the level of stercobilin in urine and feces, which gives them an intense color. Suprahepatic jaundice is extremely difficult to treat.||1. Abnormal changes in erythrocytes: congenital thalassemias, sickle cell anemia and acquired B12-deficiency anemia,|
|2. Infectious diseases: malaria, typhoid fever, sepsis,|
|3. Intoxication with snake venom, salts of heavy metals, plant toxins with subsequent destruction of red blood cells,|
|5. Hemotransfusion of an incompatible blood group and Rh-conflict during pregnancy,|
|6. Blood cancer.|
|Hepatic (parenchymal)||Occurs due to liver failure. There are two mechanisms for the development of such pathological changes. First, the capture of indirect bilirubin by glucuronic acid is disrupted, due to which only this fraction will be increased in the blood test. Second, with the development of severe forms of hepatitis, direct bilirubin can enter the bloodstream and its level also increases along with the unconjugated fraction. This condition characterizes the cytolytic syndrome.||1. Viral infections|
|2. Alcohol intoxication|
|With hepatic jaundice, urine and feces stercobilin decreases due to a violation of bilirubin excretory function. Urobilin will be found in the discharge, which normally should not be there, this bile pigment will determine the color of the discharge: clay-colored feces, urine the color of beer (a medical term).||3. Drug intolerance|
|4. Food poisoning|
|5. Hepatitis and cirrhosis.|
|Mechanical (subhepatic)||This condition is an indicator of a violation of the excretion of direct bilirubin from the body. The reasons leading to such conditions are: cholelithiasis, biliary dyskinesia, neoplasms of the pancreatic head.||1. Congenital and acquired anomalies of the biliary tract,|
|In the blood test, an increase in direct bilirubin is noted, since the liver works unchanged. The feces will be acholic (complete absence of bile), or partially discolored due to a decrease in the level of stercobilin. Stercobilin urine is also lowered, or absent, which determines its color – the color of meat slops (medical term).||2. Cholecystitis,|
Pathological jaundice in newborns
Pathological jaundice manifests itself immediately after the baby is born, lasts more than two weeks, and affects the general condition of the baby.
Crying of a child, refusal to eat, muscle hypertrophy, lack of a sucking reflex, discoloration, or excessive color of urine and feces may indicate the presence of the onset of irreversible processes.
There are two types of pathological jaundice in newborns:
- Nuclear – develops in the absence or lack of substances of an enzymatic nature, with the help of which free bilirubin is rendered harmless. This may be due to premature birth, large hemorrhages on the head of the newborn.
Due to the fact that toxic bile pigment can enter the brain by the bloodstream system, kernicterus can lead to impaired physical and intellectual development, cerebral palsy, deafness, blindness, paralysis, damage to the liver and biliary tract.
- Hemolytic – observed when a Rh-conflict occurs, when the child is positive, and the mother is negative. This condition also leads to great intoxication of the body, especially the central nervous system, which can lead to disastrous consequences.
Treatment of pathological jaundice in newborns consists in phototherapy, the use of droppers with special drugs that remove bilirubin from the body.
Blood transfusion is recommended.
What does low bilirubin levels indicate?
A low bilirubin level signals insufficient production of red blood cells and decreases the level of their destruction.
Hypobilirubinemia is quite rare, therefore, its diagnosis indicates pathological changes in the body, which are worth paying attention to:
- Blood cancer,
- Coronary heart disease,
- Renal failure
- Tuberculous changes
- Aplastic anemia.
Hypobilirubinemia is also promoted by the use of excessive doses of alcohol, caffeine drinks, weight loss against the background of inappropriate nutrition, drug intoxication due to the intake of glucocorticoids, vitamin C, phenobarbital, antibiotics, violation of preparation for the test.
The level of bilirubin is checked during the delivery of a biochemical blood test, which is taken on an empty stomach by drawing venous blood.
A person who considers himself completely healthy should donate blood for a biochemical analysis for bilirubin once or twice a year for preventive purposes.
Prevention of an increase in the level of bilirubin includes the timely diagnosis and treatment of diseases, one of the symptoms of which is hyperbilirubinemia.
You also need to lead a healthy lifestyle, make sure that your diet is rational, get rid of bad habits (smoking, drinking alcoholic beverages), take a responsible approach to the choice of drugs for treatment, paying attention to the timing of production, side effects.
Indicators of bilirubin fractions can change their value in physiological conditions and pathological changes.
However, in order to differentiate, you need to seek specialized medical care, where you will be prescribed tests and, based on their results, will select an individual treatment, if required.
The level of bilirubin is directly related to the work of the hepatobiliary system, therefore, errors in nutrition, an unhealthy lifestyle, bad habits can significantly weaken your body and provoke hyperbilirubinemia.