In hyperbilirubinemia, the blood concentration of bilirubin exceeds the normal value. The result is jaundice, as the yellowish substance is deposited in the skin. Treatment depends on the causative disease.
What is hyperbilirubinemia?
Bilirubin corresponds to a yellowish breakdown product derived from the heme portion of the red blood pigment hemoglobin. Thus, bilirubin is a bile pigment. Red blood cells have a lifespan of about 120 days, after which they are broken down within the liver and spleen. After intermediate stages, the red blood pigment becomes bilirubin. The bilirubin produced daily amounts to about 300 milligrams and about 80 percent of it comes from the degradation processes of the erythrocytes. In the blood, bilirubin is brought to non-covalent binding to albumin. Protein-coupled bilirubin corresponds to unconjugated bilirubin. In covalent binding with albumin, we are talking about delta-bilirubin. In so-called hyperbilirubinemia, the bilirubin concentration in the blood increases to values above 1.1 mg/dl. When the serum level of the degradative substance is elevated, symptoms such as jaundice occur because the bilirubin is deposited in the skin. Depending on the cause and type of bilirubin increase, additional symptoms may occur. Hyperbilirubinemia is not itself a disease in its own right. Rather, it is a symptom of a superordinate disease that manifests itself in the form of a degradation disorder of bilirubin. In the context of elevated total bilirubin, indirect is distinguished from direct hyperbilirubinemia. Indirect bilirubin has poor solubility. It is only after processes of biotransformation that more soluble bilirubin is formed within the liver, which is detectable as direct bilirubin.
Causes
The cause of hyperbilirubinemia is always a disorder in the breakdown of the waste product. The degradation disorder is considered a symptom of various diseases. Therefore, hyperbilirubinemia can have multiple causes. For example, indirect hyperbilirubinemia with more than 80 percent of total bilirubin inform of indirect hyperbilirubin may refer to hemolysis. However, this symptom may equally well be related to rhabdomyolysis, burns, or neonatal icterus. In newborns, an elevated level is physiologic and is considered normally elevated to some degree. Their liver is not yet fully functioning and for this reason breaks down much less bilirubin. From the just mentioned causes of hyperbilirubinemia with more than 80 percent of total bilirubin inform of indirect hyperbilirubin must be distinguished the causes of indirectly emphasized hyperbilirubinemia with a small amount of direct bilirubin and intrahepatic jaundice. In this context, Gilbert’s disease, Crigler-Najjar syndrome, Dubin-Johnson syndrome, or Rotor syndrome may be possible causes. The same is true for hepatitis, cirrhosis of the liver, or severe intoxication with alcohol, drugs, or aflatoxins. Salmonellosis, cholangitis, and leptospirosis must also be considered causative for this form of hyperbilirubinemia. In contrast, in directly accentuated hyperbilirubinemia with little indirect component and occlusive jaundice, causes such as cholelithiasis, pancreatic carcinoma, bile duct carcinoma, or biliary atresia are sometimes considered the most common.
Symptoms, complaints, and signs
Hyperbilirubinemia can manifest itself in clinically different symptoms. In principle, an asymptomatic course is quite possible, for example, in the context of diseases such as Meulengracht’s disease. Normally, however, at least the symptom of icterus is present. Icterus corresponds to jaundice and may be prehepatic, intrahepatic or posthepatic depending on the disease. The stage of hyperbulirubinemia influences the degree of icterus present. Thus, initially, mainly a gel coloration of the sclera presents, which is due to the deposition of the increased bilirubin. Depending on the cause and type of hyperbilirubinemia, other symptoms and complaints may occur, for example nausea and vomiting, abdominal pain, and diarrhea. Some patients suffer from fever and fatigue. The symptoms usually appear immediately after the onset of the causative disease and persist for several days to weeks.Over time, the breakdown product is also deposited in the rest of the skin and can cause discoloration all over the body. In later stages, deposition occurs in the internal organs and all other tissues of the body. Thus, in late hyperbilirubinemia, the internal tissues of the affected person also turn yellowish. If the bilirubin crosses the blood-brain barrier in the context of various diseases, developmental disorders can develop as accompanying symptoms to the deposits. The deposition in vital organs can also be accompanied symptomatically by functional impairment of the affected organs. Depending on the causative disease, additional disease-specific symptoms may be present, such as skin itching.
Diagnosis and course of the disease
Bilirubin is determined in serum. Determination in EDTA blood or heparin whole blood is also possible. When diagnosing hyperbilirubinemia, the physician compares total bilirubin with normal values. If it is more than 1.1 mg/dl, hyperbilirubinemia is present. The physician must then determine whether the hyperbilirubinemia is direct or indirect. For direct bilirubin, limits of 0.25 mg/dl apply. For indirect bilirubin, they are 0.8 mg/dl. For infants, other reference ranges apply. Determination of the cause takes place depending on the clinical general picture and usually involves further imaging.
Complications
Hyperbilirubinemia, an excess of bilirubin above normal, occurs primarily in the setting of jaundice (icterus). Icterus can have various causes and complications. Prehepatic jaundice, for example, is often caused by increased hemolysis, i.e., a breakdown of red blood cells, which can lead to anemia. This is characterized by a severe drop in performance, fatigue and weakness. In hepatic icterus, the problem lies in the liver. In addition to some harmless enzyme defects, hepatitis or liver cirrhosis can also be the cause of hyperbilirubinemia. If left untreated, hepatitis can in some cases lead to cirrhosis of the liver, which can subsequently degenerate into liver cancer. Liver cancer is a dangerous tumor that is fatal if diagnosed too late. The 5-year survival rate is just 10 percent. Posthepatic jaundice is most often due to cholestasis, which is a backlog of bile. The permanent backlog can thus lead to inflammation and also possibly to bile duct carcinoma. In newborns, an elevated bilirubin level is usually normal and disappears after a few days. However, if it does not normalize further and increases, it can lead to kernicterus. This is a severe damage to the central nervous system and can lead to weakness, reluctance to drink and absence of reflexes. If left untreated, the condition can later lead to psychomotor sequelae and seizures.
When should you see a doctor?
Hyperbilirubinemia is expressed via jaundice. Like jaundice, hyperbilirubinemia is not a disease in its own right, but a symptom. In hyperbilirubinemia, there is an underlying disease in which the breakdown of bilirubin derived from red blood cells is impaired. Numerous different diseases can be considered as possible triggers, for example:
- Hepatitis
- Cirrhosis of the liver
- Gallstones
- Bile duct carcinoma
- Bile duct inflammation
- Pancreatic cancer
- Salmonellosis
- Alcohol poisoning
- Drug abuse
Hyperbilirubinemia may also occur in neonatal jaundice. As diverse as the underlying disease of hyperbilirubinemia is also the course of treatment. The obvious first step is to consult the family doctor. After initial examinations, he or she decides which other specialists to consult for therapy. These are mainly internists, gastroenterologists and oncologists. Furthermore, there are a few hereditary diseases that result in hyperbilirubinemia, such as Rotor syndrome, Dubin-Johnson syndrome and Crigler-Najjar syndrome. People who suffer from a loss of their usual level of performance or general weakness should consult a physician. If the symptoms persist over a long period of time or increase in intensity, a follow-up visit to a physician is necessary.Tiredness despite sufficient night sleep, a lack of concentration or attention, and a feeling of illness are reasons to see a doctor. Discoloration of the skin and especially a yellow complexion should be examined and treated. If there are clay-colored stools or dark-colored urine, a doctor should be consulted. The changes indicate diseases that need to be investigated and treated. Persistent lassitude, loss of appetite, or a loss of participation in social life, should be sought medical attention. Unwanted weight loss should be seen as a warning sign from the organism. A physician should be consulted if it occurs and causes discomfort. If daily duties or activities can no longer be performed, a doctor is needed. If there are disturbances of consciousness, the disease is already advanced. An emergency physician must be called as soon as there is a loss of consciousness. First aid measures are necessary to ensure the survival of the affected person. If heart failure, abnormalities of the circulatory system or circulatory disorders occur, a visit to the doctor must be made.
Treatment and therapy
In many cases, therapy for hyperbilirubinemia is not necessary. In principle, attention is usually directed to the causative primary disease. If this disease corresponds to Rotor or Dubin-Johnson syndromes, for example, therapeutic steps are generally not required. If hepatitis is present, treatment can range from conservative drug therapy with antiviral medications to immunosuppressants to liver transplantation. If the cause of hyperbilirubinemia can be resolved, the excess concentration of the substance in the blood will decrease. If the deposits do not clear from the skin, phototherapy can be given. The bilirubin deposited in the skin is converted to a water-soluble substance during this phototherapy. This water-soluble substance corresponds to lumirubin, which can be easily excreted from the body thanks to its solubility.
Outlook and prognosis
Hyperbilirubinemia causes jaundice in most people. This can occur due to many different causes, which is why a general prognosis is not possible. If hyperbilirubinemia occurs due to abuse of alcohol and drugs, the drugs must be discontinued and withdrawal may be necessary. In other cases, hyperbilirubinemia occurs due to gallstones or bile duct inflammation, which must be treated by a physician. The anemia usually causes a feeling of weakness. Often the affected person feels listless and tired and can no longer perform physical activities. This can lead to underweight and damage to the extremities. During treatment, the causative disease is always treated. If it is hepatitis, liver transplantation may be performed or medication may be administered. As a rule, this limits the hyperbilirubinemia relatively well. In many cases, however, no treatment is necessary if there is no underlying disease that poses a health risk and leads to hyperbilirubinemia. In any case, the affected person should still see the family physician so that the cause of hyperbilirubinemia can be determined.
Prevention
Hyperbilirubinemia can be prevented only to the extent that the causative diseases can be prevented.
Follow-up
The person affected by hyperbilirubinemia usually has very few measures and options for aftercare. In this disease, the first priority should be to contact a doctor at an early stage, so that there is an early diagnosis and treatment of the disease. Therefore, a doctor should be consulted at the first signs and symptoms of the disease. Self-cure cannot occur, so that treatment by a doctor is always necessary for this disease. A therapy is not necessary only in very few cases. However, even without therapy, regular examinations of the internal organs by a doctor are very important to prevent further complications. In many cases, patients are dependent on taking medication due to this disease. When taking this medication, care should be taken to ensure that it is taken correctly and, above all, regularly. In case of questions or doubts, a doctor should always be contacted first.However, in serious cases, organ transplantation is necessary. After such an operation, bed rest must be observed. The affected person must not exert himself unnecessarily and usually also needs the care and support of the family.
What you can do yourself
Because hyperbilirubinemia occurs as a symptom of a wide range of underlying diseases, no general advice can be given. What is important is strict adherence to medical instructions, regular medication, or avoidance of triggering substances. In the case of prognostically benign causes such as Gilbert’s disease or Rotor’s syndrome, it is also possible to live without any impairment in everyday life. The greatest impact on quality of life results from jaundice, i.e. visible bilirubin deposits in the sclera of the eyes and the epidermis. This is usually a purely cosmetic problem. Not every patient is affected, as this symptom only develops when bilirubin concentrations exceed 2 µg/dl in the blood. It is completely reversible in underlying diseases that can be successfully treated. Exposure to light on the skin can make a contribution, albeit small, to the breakdown of bilirubin visible on the surface. For this reason, it is advisable not to cover the affected areas with make-up or to cover them constantly in the open air. In the case of hyperbilirubinemia due to substance abuse, self-responsible steps can be sought in addition to therapeutic measures. Attending relevant support groups and participating in abstinence programs can be an important pillar in the treatment that the patient undertakes independently of physicians.
