Update: December 2018 Perhaps about such an indicator as bilirubin
heard, if not everyone, then most of us. Many know that
увеличение его содержания в сыворотке of blood сопровождает различные
liver disease can occur in newborn babies, and
the main clinical manifestation of disorders of its metabolism is jaundice.
What are the causes of increased bilirubin, mechanisms and consequences
of these violations? This will be discussed in our article.
What is bilirubin?
Bilirubin is referred to as the so-called hemoglobinogenic pigments.
The main amount of it (about 85%) is formed during physiological
disintegration of old, worn red blood cells. The rest, the smaller part,
appears when other hem-containing substances are destroyed –
The breakdown of red blood cells occurs mainly in the liver,
spleen, as well as in the bone marrow. A day in the body is destroyed
about 1% of red blood cells, and of the hemoglobin contained in them
forms up to 300 mg of bilirubin. This pigment is found in
of blood и в норме, однако его количество не должно превышать
maximum permissible values.
Today, the features of the structure, metabolism, and
the causes of disturbances in the exchange of bilirubin are studied and described sufficiently
OK. When jaundice occurs, which is the main symptom
hyperbilirubinemia, diagnosis in most cases is not
presents significant difficulties (see jaundice – symptoms,
diseases associated with jaundice).
The main stages of bilirubin metabolism
So, with the destruction of red blood cells formed bilirubin,
is a toxic and water-insoluble compound.
Its further transformation occurs in several stages:
- с током of blood билирубин переносится к печени – для этого
requires a carrier, in the role of which albumin protein acts,
быстро и прочно связывающий токсичный билирубин в плазме blood.
This protein-bilirubin complex is not able to penetrate
renal filter, and therefore does not enter the urine;
- penetration of bilirubin into the liver cell after separation
it from albumin on the surface of the hepatocyte membrane and further
transportation through the membranes of the endoplasmic reticulum;
- conjugation (binding) of bilirubin with glucuronic acid in
endoplasmic reticulum and the formation of bilirubin-diglucuronide.
It is in this bound state that bilirubin becomes soluble.
in water and thus can be excreted with bile and urine from
- excretion (elimination) with bile – the final stage of the exchange
bilirubin, which in the intestine turns into urobilinogen and
As stercobilinogen is excreted in the feces. Notбольшое количество
bilirubin is absorbed by the intestinal wall and, getting into the bloodstream,
filtered by the kidneys and excreted in the urine.
Based on the characteristics of the metabolism, direct and indirect
bilirubin. To assess the degree and nature of metabolic disorders
bilirubin needs to know its normal performance in healthy
- Notпрямой (несвязанный, неконъюгированный, свободный) билирубин,
being a breakdown product of heme substances, it is toxic
bilirubin. The amount of indirect bilirubin should not exceed 16.2
μmol / l.
- Direct (conjugated, bound) formed in the liver at
binding to glucuronic acid. This is bilirubin, which is already
neutralized by the liver and ready for withdrawal from the body. Straight
билирубин, норма 0 – 5,1 мкмоль/л
- Total bilirubin ranges from 0.5 to 20.5 µmol / l
In the face of trouble, it is possible to raise the level of both direct,
and indirect bilirubin, called hyperbilirubinemia.
The predominance of a particular faction depends on the causative factor,
приведшего к увеличению его содержания в сыворотке blood.
Симптоматика повышенного bilirubin в of blood (гипербилирубинемия)
in the form of, first of all, jaundice appear when it exceeds 34
umol per liter.
It happens that the content of bilirubin is ten times higher
acceptable values that endanger the life of the patient and require
provide immediate assistance.
Signs of elevated bilirubin
As is known, the primary role in the exchange of bilirubin
belongs to the liver, and jaundice is a characteristic syndrome that reflects it
defeat and manifest also in cases where the amount
bilirubin exceeds the functional ability of the liver to bind
its surplus, or there are obstacles to the outflow of bile and,
respectively, excretion of conjugated bilirubin from
Sometimes it happens that the severity of jaundice does not match the numbers
serum bilirubin. For example, with obesity, edema, yellowness
less noticeable while thin and muscular people have it
Причины высокого bilirubin в of blood весьма разнообразны и
associated either with its enhanced formation in cells
reticuloendothelial system, either in violation of one or immediately
several links of exchange in the hepato-biliary system.
From a clinical point of view, it is important to note that
hyperbilirubinemia affects the nature of staining of various
- So, most often the first get icteric shade
- Oral mucosa
- Then the face, palms, soles turn yellow, and finally all skin
It must be remembered that yellow staining of the skin is not always
consequence of hyperbilirubinemia. For example, when eating,
containing a large amount of carotene (carrots, tomatoes), sugar
diabetes, hypothyroidism (reduced thyroid function) skin
может приобретать желтый оттенок, однако в этих случаях sclera
will be normal color (intact).
List of diseases associated with high levels of bilirubin
в of blood
Diseases in which direct bilirubin is elevated:
- Acute viral hepatitis (hepatitis A, B, hepatitis with infectious
- Chronic hepatitis (hepatitis C), autoimmune hepatitis
- Bacterial hepatitis (brucellosis, leptospirosis)
- Toxic (poisoning by toxic compounds, fungi),
medicinal (taking hormonal contraceptives, NSAIDs,
tuberculosis, anticancer drugs)
- Pregnant jaundice
- Liver tumors
- Biliary cirrhosis
- Hereditary Jaundice — синдром Ротора, Дабина-Джонсона
Diseases for which indirect bilirubin rises:
- Congenital hemolytic anemia – spherocytic,
nonsferocytic, sickle cell, thallicemia, disease
- Acquired hemolytic anemia autoimmune – develop
against the background of systemic lupus erythematosus (symptoms, treatment),
rheumatoid arthritis, lymphocytic leukemia, lymphatic granulomatosis (symptoms,
- Infectious diseases – typhoid fever, sepsis, malaria
- Drug hemolytic anemia – triggered by taking
cephalosporins, insulin, aspirin, NSAIDs, chloramphenicol,
penicillin, levofloxacin, etc.
- Toxic hemolytic anemia – poisoning by poisons, bites
insects, snakes, mushroom poisoning, lead, arsenic, copper salts
- Syndromes of Gilbert, Crigler-Nayar, Lucy-Driscol.
Types of jaundice and the main causes of elevated bilirubin
в of blood
Повышению bilirubin в of blood способствуют 3 основных
- Erythrocyte destruction (accelerated or increased)
- Disruption of the normal flow of bile
- Disruption of metabolism and elimination of bilirubin
Erythrocyte destruction (accelerated or increased)
High indirect bilirubin in hemolytic jaundice due to
increased red blood cell breakdown (hemolysis), which may be
the result is not only hereditary defects of the red cells themselves
of blood (серповидно-клеточная анемия, сфероцитоз), но и ряда внешних
reasons, for example:
- infections (malaria, sepsis, typhoid fever, mycoplasmosis);
- poisoning with hemolytic poisons of various origin
(toxins of the toadstool, mercury, lead, snake venom others);
- переливание of blood, несовместимой по групповой принадлежности
or Rh factor;
- malignant tumors, in particular, hematopoietic tissue
(leukemia, multiple myeloma and others);
- massive hemorrhages (pulmonary infarction, extensive
Hemolytic jaundice has the following symptoms:
- lemon yellow staining of the skin and mucous membranes, sclera
- pallor due to anemia due to increased destruction
red blood cells
- pain in the left hypochondrium due to an enlarged spleen
- possible increase in body temperature
- a large number of sterile and
urobilin giving them dark staining
- against the background of lack of oxygen in the tissues of the body in humans
there may be palpitations, headaches, increased
Disruption of the normal flow of bile
Subhepatic jaundice develops upon return intake into
blood conjugated bilirubin due to the violation of its outflow from
bile, most commonly associated with cholelithiasis, acute and
chronic pancreatitis, hepatic artery aneurysm, cancer
pancreas or gallbladder, diverticula
duodenal ulcer. При этом состоянии в of blood высокий прямой
bilirubin. The causes of this type of jaundice can be:
- the closure of the bile duct stone, tumor, parasites;
- compression of the bile ducts from the outside, accompanying the tumor
gallbladder, pancreatic head,
- inflammatory processes in the biliary tract followed by their
sclerosis and narrowing of the lumen;
- congenital anomalies or underdevelopment of the bile ducts.
For this type of hyperbilirubinemia (with stones in the gall
bladder cancer of the gall or pancreas) is characterized by:
- the strongest icteric staining of the skin
- most patients complain of itchy skin, the result
which are scratching on the skin
- since the binding function of the liver in this case is not impaired,
в of blood будет обнаруживаться повышенное количество конъюгированного
- unlike other types of jaundice, fecal masses will be acholichic,
that is, to have almost white color, which is due to the lack of
them sterkobilina, and urine dark color
- возникают периодические боли в right upper quadrant или приступ
such pain with hepatic colic
- violation of the digestive tract – flatulence (causes, treatment), diarrhea,
constipation, nausea, loss of appetite, belching bitter
Disruption of metabolism and elimination of bilirubin
This is a violation accompanied by its excessive accumulation and as
consequence, jaundice can be hereditary –
наследственные желтухи, либо возникать на протяжении жизни
and complicate various diseases – acquired jaundice.
Abnormalities in the hepatic bilirubin metabolism
(binding, transport in the liver cell and removal from it),
cause hereditary jaundice:
- kriegler-nayar syndrome
- Gilbert’s syndrome
- Dabin-Johnson syndrome
Чаще других встречается Gilbert’s syndrome – доброкачественно
flowing hyperbilirubinemia with a favorable prognosis.
Causes of high blood bilirubin in this disease lie
lack of liver cell binding enzyme
free bilirubin with glucuronic acid, therefore
hyperbilirubinemia will be mainly due to unbound
The disease is hereditary and is accompanied by
gene defect located in the second chromosome.
The prevalence of Gilbert syndrome in the world varies. So y
Europeans, it occurs in 3-5% of cases, while residents
In Africa – in 36%, which is associated with a high frequency of occurrence in them
characteristic genetic defect.
Often the disease is asymptomatic or with episodes
jaundices of varying intensity that occur on the background
stress, excessive physical exertion, while taking alcohol.
Given the benign course and favorable prognosis,
specific treatment in such patients, as a rule, is not required.
Suprahepatic jaundice occurs when the amount
newly formed bilirubin is so great that even enhanced in
3-4 times the intensity of its binding by the liver does not lead to
remove excess serum.
Hepatic, or parenchymal, jaundice occurs as
manifestation of various diseases associated with damage
parenchyma of the liver and bile capillaries, which entails
violation of the capture, conjugation and excretion of bilirubin, as well as
its return flow into the blood from the bile duct with cholestasis
(stagnation of bile) inside the liver. This is one of the most common
developing types of jaundice at which high straight
Diseases involving hepatic jaundice are numerous.
and diverse, but most often this type of hyperbilirubinemia
observed in hepatitis and cirrhosis of the liver.
Гепатиты- представляют собой большую группу
inflammatory liver damage that may have
viral nature or caused by non-infectious agents
(drug hepatitis, autoimmune, alcohol).
In the acute course of the disease, the causative factor most often
there is a viral infection (hepatitis A, B, C, D, G), and manifestations
- signs of general intoxication with increasing body temperature
- common weakness
- muscle and joint pain
- the liver damage in this case will indicate pain in
right upper quadrant
- icteric staining of skin and mucous membranes
- discoloration of feces and urine, as well as characteristic changes in
With the progression of the disease with involvement in the process
significant volume of the hepatic parenchyma, as well as in case of difficulty
outflow of bile may cause itching, bleeding,
signs of brain damage in the form of a characteristic hepatic
encephalopathy and, ultimately, the development of hepatic-renal
life-threatening deficiency and often
cause of death of such patients.
Chronic hepatitis is quite common as a result.
acute viral, medicinal and alcoholic lesions
the liver. Their clinical manifestations are reduced to parenchymal
jaundice and changes in the biochemical analysis of blood; during exacerbation
fever, arthralgia, and skin rashes are possible.
Циррозы печени- представляют
is a heavy change with the loss of the normal histoarchitecture of her
parenchyma. In other words, there is a violation of the normal
microscopic structure: as a result of the death of hepatocytes
hepatic lobules disappear, orientation of the blood vessels is disturbed
vessels and bile capillaries appear massive foci
proliferation of connective tissue in place of damaged and dead
These processes make it impossible for the liver to perform functions
binding and removal of bilirubin from the body, as well as processes
detoxification, the formation of various proteins and coagulation factors
blood. Most often, cirrhosis of the liver completes its inflammatory
In addition to parenchymal jaundice, characteristic of cirrhosis
clinical manifestations will be an increase in the liver and spleen,
pruritus, fluid in the abdominal cavity (ascites),
varicose veins of the esophagus, rectum, anterior abdominal
Over time, signs of hepatic increase
deficiency, develops brain damage, decreases
blood clotting, and this is accompanied not only by rash on
skin, but also hemorrhages in the internal organs and bleeding
(stomach, nasal, uterine), wearing often life threatening
Elevated bilirubin in newborns
Special attention deserve hyperbilirubinemia, that is,
elevated bilirubin in newborns. It is known that in the early days
most babies have varying degrees of severity
желтухи, которая носит физиологический character
This is because the child’s body adapts to
extrauterine existence, and the so-called fetal (fetal)
hemoglobin is replaced by hemoglobin “adult” type, which
accompanied by partial destruction of red blood cells. Usually peak
yellowing is noted on 3-5 days of life, and after a short time
it is allowed without harming the child’s body.
In cases where hemolysis occurs in premature babies, either
due to rhesus conflict or other reasons
there is a significant increase in the unbound fraction of bilirubin with
its penetration through the hemato-encephalic barrier.
The result will be the development of so-called nuclear jaundice, with
which damaged brain nuclei, which is a threat
life of the baby and requires immediate intensive care.
In all cases, it is necessary to establish the exact causes of high
bilirubin in the newborn in order to avoid serious complications
timely treatment started:
- physiological breakdown of red blood cells
- liver damage
- congenital anomalies of biliary tract
- rhesus conflict, etc.
How to reduce bilirubin?
Ways to combat hyperbilirubinemia depend on the reasons
caused, however, with the appearance of jaundice is not worth doing
self-treatment, and should immediately seek medical attention. Insofar as
jaundice is only a symptom and treatment should first be
aimed at eliminating its causes.
With high numbers of bilirubin due to pronounced hemolysis
erythrocyte infusion therapy with the introduction of glucose,
albumin, as well as plasmapheresis. With jaundice
neonatal phototherapy is very effective in which radiation
skin contributes to the conversion of free toxic bilirubin to
bound, easily excreted.
When non-conjugation hyperbilirubinemia effective appointment
drugs that enhance the activity of liver enzymes, for example,
In all cases, it should be remembered that jaundice is usually
an indicator of serious disorders in the body, and therefore timely
finding out its causes increases the likelihood of a favorable outcome
and possibly a complete cure for the disease that caused it. Not
it is worth neglecting visiting the doctor even in the case of a minor
yellow staining of the skin, sclera, because timely
diagnosis and timely treatment can not only save
life to the patient, but also significantly improve its quality.