OVERVIEW
Bilirubin is a waste product of the metabolism of hemoglobin from red blood cells in the blood. Bilirubin is mainly converted from hemoglobin, one gram of which produces 34 mg of bilirubin. When red blood cells age (red blood cell life cycle of 120 days), they will be destroyed by the spleen and processed to produce bilirubin. Bilirubin will be excreted by the liver and through the bile ducts to the duodenum, and most of the bilirubin will be excreted in the feces. A normal person produces 250-350mg of bilirubin per day, of which 80%-85% comes from senescent red blood cells in the blood circulation, and the remaining 15%-20% comes from the bone marrow and the liver, which is called bypass bilirubin. Bilirubin is a waste product to the body. High serum bilirubin reveals abnormalities such as liver disease or bile duct obstruction, and the level of serum bilirubin represents the severity of the abnormality. Generally speaking, a serum bilirubin value of 0.5mg/dl or less for Bilirubin Direct and 1.3mg/dl or less for Bilirubin Total is considered normal. Bilirubin is an important basis for clinical determination of jaundice and an important indicator of liver function. Normal serum total bilirubin concentration is 1.7-17.1μmol/L, with one-minute bilirubin below 3.4μmol/L. When bilirubin exceeds the normal value, it is considered to be in the range of 1.3mg/dl.
When bilirubin exceeds the normal value, it is considered high bilirubin (hyperbilirubinemia). Jaundice can be detected clinically when the total bilirubin is 34 μmol/L. If the total serum bilirubin exceeds the normal range and jaundice is not visible to the naked eye, it is known as hidden jaundice. Jaundice is most commonly seen in liver and gallbladder diseases, but it can also occur in other systemic diseases.
Questions you may be concerned about
What is hyperbilirubinemia?
Hyperbilirubinemia is a common condition characterized by elevated bilirubin, most often seen in patients with liver and gallbladder diseases.
Bilirubin is the product of metabolism of hemoglobin in red blood cells, which is mainly converted from hemoglobin. One gram of hemoglobin produces 34mg of bilirubin, and the normal serum bilirubin concentration ranges from 1.7 to 17.1 umol/L. When serum bilirubin exceeds the normal value, it is called hyperbilirubinemia.
Hyperbilirubinemia is usually caused by intrahepatic or extrahepatic obstructive jaundice, acute jaundice hepatitis, chronic active hepatitis, toxic hepatitis and other diseases that cause damage to the liver cells, resulting in bilirubin not being able to be converted to bile normally, causing hyperbilirubinemia to occur. It is often characterized by increased serum bilirubin, splenomegaly, and yellowing of the skin and sclera.
Laboratory tests include laboratory tests and imaging tests, which may reveal a marked increase in alkaline phosphatase, decreased cholesterol lipids, or abnormal liver function. Imaging tests include ultrasonography and CT scan, which can determine whether the liver, gallbladder and pancreas are diseased, and then clarify the cause of hyperbilirubinemia.
If you are diagnosed with hyperbilirubinemia, it is recommended that you go to a regular hospital in a timely manner and under your doctor’s guidance, you should undergo the relevant medical tests, such as blood routine, liver function, ultrasound, etc., to identify the cause of the disease and actively cooperate with your doctor’s treatment.
Causes
The life span of human red blood cells is generally 120 days. After the death of red blood cells, they turn into indirect bilirubin, which is converted into direct bilirubin by the liver and forms bile, which is excreted into the biliary tract and finally through the stool. The sum of indirect and direct bilirubin is total bilirubin. A disorder in any of the above can cause a person to become jaundiced. Hemolytic jaundice can occur if too many red blood cells are destroyed and too much indirect bilirubin is produced, and the liver is unable to convert it completely into direct bilirubin; hepatocellular jaundice occurs when the liver cells become diseased because bilirubin cannot be converted into bile normally, or when bile ducts in the liver are pressurized by swollen liver cells, which obstructs the excretion of bile and raises the bilirubin in the blood; and once a tumor occurs or stones appear in the extra-hepatic biliary system, it will cause jaundice to occur. Tumors or stones occur, blocking the bile ducts, bile can not be excreted smoothly, and obstructive jaundice occurs. Jaundice in patients with hepatitis is generally hepatocellular jaundice, with elevated direct bilirubin and indirect bilirubin, while direct bilirubin is predominantly elevated in patients with biliary hepatitis.
1. High direct bilirubin
If the liver cells are damaged, bilirubin can not be converted into bile normally, or the excretion of bile is obstructed, which will cause high direct bilirubin. Common causes of high direct bilirubin include intra-hepatic and extra-hepatic obstructive jaundice, pancreatic head carcinoma, capillary bile duct hepatitis, and other bile stasis syndromes;
2. Total bilirubin, direct bilirubin and indirect bilirubin are all elevated
See acute jaundice hepatitis, chronic active hepatitis, hepatic cirrhosis, toxic hepatitis, etc.
3. Increased total bilirubin and direct bilirubin
See intrahepatic and extrahepatic obstructive jaundice, pancreatic head cancer, capillary bile duct hepatitis and other bile stasis syndromes.
4. Increased total bilirubin and indirect bilirubin.
See hemolytic anemia, blood group incompatibility transfusion, malignant disease, neonatal jaundice, etc.
5. Red blood cell rupture factor
Liver injury can lead to massive death and rupture of erythrocytes in the liver, which can cause hemolytic jaundice when the metabolism of the liver is not enough to convert them into direct bilirubin.
6. Hepatocellular lesion factor
When hepatitis B patients have liver cell lesions or bilirubin can not be converted into bile, it can lead to liver enlargement, intrahepatic bile ducts are compressed and bile excretion is impaired, which will lead to elevated bilirubin content in the blood.
7. Bile excretion obstruction factors
For example, if hepatitis B patients suffer from gallstones, the gallstones can block the excretion of bile in the liver, making the bile cannot be discharged from the liver smoothly, which can lead to the elevation of bilirubin in the blood.
8. Increased total bilirubin
(1) Liver diseases Acute jaundice hepatitis, acute yellow liver necrosis, chronic active hepatitis, cirrhosis, etc.
(2) Extrahepatic diseases: hemolytic jaundice, blood transfusion reaction with incompatible blood groups, cholecystitis, cholelithiasis, etc.
(3) Others See toxic or viral hepatitis, hemolytic gangrene, pernicious anemia, paroxysmal hemoglobinuria. Erythrocytosis, neonatal jaundice, internal hemorrhage, hemolytic gangrene after blood transfusion, acute yellow liver atrophy.
9. Elevated indirect bilirubin
(1) Hemolytic jaundice Increase of indirect bilirubin in blood due to excessive destruction of red blood cells by some hemolytic diseases;
(2) Hepatocellular jaundice When the liver cells are diseased, the bilirubin in the blood is elevated because bilirubin cannot be converted into bile normally and because the swelling of the liver cells compresses the bile ducts in the liver and obstructs the excretion of bile.
(3) Blood transfusion error Blood group incompatibility transfusion leads to hemolysis, which destroys a large number of red blood cells and results in the release of a large amount of indirect bilirubin into the blood.
(4) Neonatal-type jaundice is mainly due to elevated indirect bilirubin in the blood caused by incompatibility of blood groups between mother and child or congenital biliary malformations in newborns. Regardless of the classification, the occurrence of hyperbilirubin (jaundice) ultimately stems from a disorder in one or more of the metabolic processes of bilirubin.
Symptoms
1. Hemolytic jaundice
When a large number of red blood cells are destroyed (hemolysis), an excessive amount of unconjugated bilirubin is produced, which exceeds the ability of the liver cells to take up, bind, and excrete, resulting in the retention of unconjugated bilirubin in the blood and the occurrence of jaundice. Characteristics:
(1) Mild jaundice of the sclera, with fever and backache in acute episodes (hemolytic crisis), and the skin and mucous membranes are often markedly pale;
(2) There is no itching of the skin;
(3) There is splenomegaly;
(4) There are signs of exuberant bone marrow proliferation, such as increased peripheral blood reticulocytes, the presence of nucleated red blood cells, and active proliferation of the bone marrow erythrocyte system;
(5) Increased serum total bilirubin, usually not more than 85 μmol/L, mainly unconjugated bilirubin;
(6) Increased urobilinogen without bilirubin in urine, hemoglobinuria in acute attack, increased ferritin in urine in chronic hemolysis.
2. Hepatocellular jaundice
Due to hepatocellular lesions, the function of bilirubin uptake, binding and excretion is impaired, so that a considerable amount of unconjugated bilirubin is retained in the blood; at the same time, due to damage to hepatocytes and/or destruction of the structure of liver lobules, the conjugated bilirubin can not be discharged normally into the small bile ducts, and flows back into the hepatic lymphatic fluids and the blood, and as a result, jaundice occurs. Characteristics:
(1) The skin and sclera are pale yellow to deep golden yellow, and the skin is sometimes itchy;
(2) Both unconjugated and conjugated bilirubin are increased in the blood;
(3) Urine bilirubin is positive and urobilinogen is often increased, but at the peak of the disease, urobilinogen is reduced or absent due to intrahepatic sludge;
(4) Serum aminotransferases are significantly increased;
(5) Hepatitis virus markers in the blood are often positive;
(6) Liver biopsy is important for the diagnosis of diffuse liver disease.
3. Cholestatic jaundice
Intrahepatic cholestasis refers molecularly and cytologically to a decrease in bile production and secretion, as well as bile stasis and concentration. Intrahepatic cholestasis occurs either alone or in conjunction with hepatic parenchymal damage. Characteristics:
(1) Dark yellow, yellow-green, or greenish-brown skin color;
(2) Remarkable itching of the skin, often occurring before the appearance of jaundice;
(3) Increased blood bilirubin, predominantly conjugated bilirubin, with a direct response to a qualitative bilirubin test;
(4) Urine bilirubin is positive, but urobilinogen is reduced or absent;
(5) Decreased or absent urobilinogen in feces, with light gray or clay-colored feces;
(6) Increased serum total cholesterol, alkaline phosphatase, gamma-glutamyl transpeptidase, and positive lipoprotein-X.
4. Congenital non-hemolytic jaundice
(1) Gilbert’s syndrome is caused by impaired uptake of free bilirubin by hepatocytes and insufficient glucuronosyltransferase in particles. Unconjugated bilirubin is elevated in the serum, liver function tests are normal, erythrocyte fragility is normal, the gallbladder is well visualized, and there is no abnormality in liver biopsy.
(2) Dubin-Johnson syndrome is caused by the impaired excretion of bound bilirubin and other organic anions (indocyanine green, X-ray contrast medium) by hepatocytes into the capillary bile ducts, resulting in an increase in serum bound bilirubin, but normal bilirubin uptake and binding. The gallbladder is often not visualized with oral cholecystography. The liver has a greenish-black appearance (black liver), and liver biopsy reveals diffuse tan pigment granules (melanin or adrenaline metabolite polymorphs) in the hepatocytes.
(3) Rotor syndrome Due to congenital defects in the uptake of free bilirubin and excretion of conjugated bilirubin by the hepatocytes, there is a predominant increase in conjugated bilirubin in the blood, and there is a decrease in the indocyanine green (ICG) excretion test. Cholangiography was mostly well visualized, and a few were not. Liver biopsy is normal, and there are no pigmented particles in the hepatocytes.
(4) Crigler-Najjar syndrome is due to the lack of glucuronosyltransferase in the hepatocytes, resulting in the inability to form conjugated bilirubin, thus the concentration of non-conjugated bilirubin in the blood is very high, and it may be complicated by kernel jaundice; the prognosis is very poor.
Examination
1. Laboratory examination
(1) Alkaline phosphatase (ALP) In extrahepatic and intrahepatic obstructive jaundice and intrahepatic cholestasis, ALP is obviously increased.
(2) Serum total cholesterol, cholesteryl ester, and lipoprotein-X (LP-X) measurements In cholestatic jaundice, total cholesterol is increased; in hepatocellular jaundice, especially with extensive necrosis, cholesteryl ester is decreased.
(3) Prothrombin time In hepatocellular and cholestatic jaundice, the production of prothrombin is reduced, and thus the prothrombin time is prolonged. 24 hours after injection of vitamin K 2-4mg, the prothrombin time is rechecked, and if there is a significant shortening of prothrombin time compared with that before injection, it indicates that the liver function is normal, and the jaundice may be cholestatic. If there is no change, it indicates that the liver’s ability of producing thrombin is impaired, and the jaundice may be hepatocellular.
2. Ultrasonography
If dilatation of intrahepatic bile ducts is found, jaundice is definitely caused by obstruction of extrahepatic bile ducts.
3. Barium esophageal swallow, barium gastrointestinal examination
If varicose veins are found in the esophagus or gastric fundus, cirrhosis can be diagnosed.
4. Transduodenoscopic retrograde cholangiopancreatography (ERCP)
It is important for diagnosing chronic pancreatitis, pancreatic cancer and understanding the biliary system.
5.CT examination
It has great diagnostic value for the diagnosis of hepatobiliary and pancreatic diseases and the site, scope and nature of extrahepatic obstruction.
6. Liver puncture biopsy and laparoscopy
It can help to diagnose hepatocellular jaundice, intrahepatic cholestasis and Dubin-Johson syndrome.
Diagnosis
Jaundice is an important symptom and sign of many diseases. The cause of jaundice originates from the abnormality of bilirubin metabolism, through the analysis of bilirubin, urobilinogen and fecal bilirubin, the nature of jaundice can be initially categorized, but an accurate determination of the cause of jaundice still relies on the clinician’s comprehensive analysis and judgment on the basis of the history of the disease, the signs and symptoms, and the results of laboratory and other auxiliary examinations in order to obtain the correct diagnosis. The correct diagnosis can only be made after comprehensive analysis and judgment by the clinician based on the results of history, signs and laboratory and other auxiliary examinations.
Complications
Bilirubin encephalopathy, also known as kernel jaundice, is a hemolytic disease of the newborn. As unconjugated bilirubin passes through the blood-brain barrier, it inhibits the utilization of oxygen by brain tissue, affects cellular oxidation, and inhibits energy production in brain cells leading to brain damage. Due to the destruction of red blood cells, a large amount of bilirubin is produced. At the same time, about one week after birth, the defense function of brain tissue is poor, and free bilirubin easily enters the brain, mainly damaging the basal ganglia and the cerebellum, as well as the nuclei of nerves related to hearing. The child’s jaundice deepens, with lethargy, decreased muscle tone, which soon develops into increased muscle tone, screaming, followed by hearing impairment, eye movement disorders, intellectual backwardness, and bradykinesia. The treatment of such children is poor, but the damage to the cerebral cortex is mild, so these children may have better intelligence. Therefore, perinatal care must be done to prevent kernicterus from occurring. Once hyperbilirubinemia occurs in the first week of life, it should be detected early, and blue light irradiation, medication, and blood exchange therapy should be used to prevent kernicterus from occurring.
Treatment
Patients with high bilirubin are advised to check the alanine aminotransferase (AST) and aliquot aminotransferase (AAT), if these two items are elevated, it is necessary to find out the original cause of the disease and carry out hepatoprotection and other treatments; if the AST and AAT are within the normal range, then high bilirubin does not need to be treated for the time being. Rest, reasonable diet, and regular liver function tests are necessary to monitor the development of the disease. For the treatment of hyperbilirubinemia, it is recommended to go to a regular hospital for treatment because the underlying cause has to be identified while treating the symptoms.
Prognosis
Hyperbilirubinemia is a condition in which the liver’s ability to metabolize and convert bilirubin decreases after liver damage, resulting in bilirubin not being excreted normally and flowing back into the bloodstream. Hyperbilirubinemia is very harmful to human body, because bilirubin itself has certain toxicity, a large amount of bilirubin gathered in the blood, which may lead to severe jaundice in mild cases, and in serious cases, it may also jeopardize the life of the patient. Hyperbilirubinemia may indicate that the patient has hemolytic jaundice, hepatocellular jaundice, obstructive jaundice and so on, when the patient’s liver has a lesion or the bile ducts are blocked, which leads to a drastic increase of bilirubin in blood. Bilirubin increases dramatically. In severe jaundice, the liver is damaged, the metabolic function decreases, and a large amount of bilirubin gathers in the liver, which will surely further aggravate the damage of the liver. The patient develops indigestion, itchy skin, abdominal pain and other symptoms, accompanied by changes in the color of urine and feces. At this time, the patient should seek medical attention without delay and, if necessary, undergo the necessary hemodialysis to alleviate the symptoms.
Prevention
Reasonable arrangement of diet, regular life, happy spirit, pay attention to the combination of static and dynamic, do not have a disease indiscriminately abuse of drugs. Please pay attention to the following points:
1. A light diet rich in vitamins A, B, C and E, with good antioxidant function and easy to be digested and absorbed, such as bean products, fish, vegetables and fruits, is recommended.
2. Eat seafood, mushrooms, sesame seeds, walnuts, jujubes, lean meat and animal liver and other foods.
3. Avoid drinking alcohol and excessive sweets.
4. It is advisable to rest in bed for 1 to 2 hours after meals to ensure that the liver gets sufficient blood supply, which is conducive to liver cell repair.