Hyperbilirubinaemia
Disease Details
Family Health Simplified
- Description
- Hyperbilirubinemia is a condition characterized by elevated levels of bilirubin in the blood, often resulting in jaundice.
- Type
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Hyperbilirubinemia can be categorized into unconjugated and conjugated types.
1. **Unconjugated Hyperbilirubinemia**: This occurs when there is excess bilirubin in its unconjugated form, often due to increased production, decreased hepatic uptake, or impaired conjugation. Common causes include hemolytic anemias, Gilbert's syndrome, and Crigler-Najjar syndrome.
- **Gilbert's Syndrome**: Typically follows an autosomal recessive pattern.
- **Crigler-Najjar Syndrome**: Type I is autosomal recessive, and Type II can be considered less severe but also autosomal recessive.
2. **Conjugated Hyperbilirubinemia**: This results from impaired excretion of bilirubin that has already been conjugated within the liver, often due to liver diseases, obstruction of bile ducts, or inherited diseases affecting bilirubin transport.
- **Dubin-Johnson Syndrome**: Autosomal recessive.
- **Rotor Syndrome**: Autosomal recessive.
In both types, genetic transmission patterns are often autosomal recessive. - Signs And Symptoms
- The most common signs of jaundice in adults are a yellowish discoloration of the white area of the eye (sclera) and skin with scleral icterus presence indicating a serum bilirubin of at least 3 mg/dl. Other common signs include dark urine (bilirubinuria) and pale (acholia) fatty stool (steatorrhea). Because bilirubin is a skin irritant, jaundice is commonly associated with severe itchiness.Eye conjunctiva has a particularly high affinity for bilirubin deposition due to high elastin content. Slight increases in serum bilirubin can, therefore, be detected early on by observing the yellowing of sclerae. Traditionally referred to as scleral icterus, this term is actually a misnomer, because bilirubin deposition technically occurs in the conjunctival membranes overlying the avascular sclera. Thus, the proper term for the yellowing of "white of the eyes" is conjunctival icterus.A much less common sign of jaundice specifically during childhood is yellowish or greenish teeth. In developing children, hyperbilirubinemia may cause a yellow or green discoloration of teeth due to bilirubin deposition during the process of tooth calcification. While this may occur in children with hyperbilirubinemia, tooth discoloration due to hyperbilirubinemia is not observed in individuals with adult-onset liver disease. Disorders associated with a rise in serum levels of conjugated bilirubin during early development can also cause dental hypoplasia.
- Prognosis
- Hyperbilirubinemia has a varied prognosis depending on its underlying cause and the patient's overall health. In neonatal cases, the prognosis is generally good with appropriate treatment, such as phototherapy. For adults, the prognosis depends on the underlying condition causing the hyperbilirubinemia, like liver diseases (e.g., hepatitis, cirrhosis) or bile duct obstructions. Early diagnosis and treatment are crucial for a better outcome.
- Onset
- For the onset of hyperbilirubinemia, it can vary depending on the underlying cause. In newborns, it commonly appears within the first few days of life, typically around the second to third day. In adults, it may develop insidiously over a variable period depending on the cause, such as liver disease, hemolysis, or biliary obstruction.
- Prevalence
- The prevalence of hyperbilirubinemia varies based on the underlying cause and population. In newborns, it is quite common, with jaundice occurring in approximately 60% of term infants and 80% of preterm infants during their first week of life. In adults, prevalence data can vary widely due to different etiologies such as liver disease, hemolytic disorders, and genetic conditions like Gilbert's syndrome.
- Epidemiology
- Jaundice in adults is rare. Under the five year DISCOVERY programme in the UK, annual incidence of jaundice was 0.74 per 1000 individuals over age 45, although this rate may be slightly inflated due to the main goal of the programme collecting and analyzing cancer data in the population. Jaundice is commonly associated with severity of disease with an incidence of up to 40% of patients requiring intensive care in ICU experiencing jaundice. The causes of jaundice in the intensive care setting is both due to jaundice as the primary reason for ICU stay or as a morbidity to an underlying disease (i.e. sepsis).In the developed world, the most common causes of jaundice are blockage of the bile duct or medication-induced. In the developing world, the most common cause of jaundice is infectious such as viral hepatitis, leptospirosis, schistosomiasis, or malaria.
- Intractability
- Hyperbilirubinemia is typically not intractable. It is a condition characterized by elevated levels of bilirubin in the blood and can often be managed or treated effectively. The underlying cause of hyperbilirubinemia, such as liver disease, bile duct obstruction, or hemolysis, will determine the treatment approach. Addressing the root cause usually leads to a resolution of the condition.
- Disease Severity
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Hyperbilirubinemia refers to an elevated level of bilirubin in the blood. The severity of hyperbilirubinemia can vary widely, from mild cases that may not require treatment to severe cases that can lead to serious complications.
For newborns, untreated severe hyperbilirubinemia can lead to a serious condition called kernicterus, which can cause permanent neurological damage. Prompt treatment is essential in these cases.
In adults, the severity often depends on the underlying cause, which can range from liver diseases and bile duct obstruction to hemolysis (destruction of red blood cells).
Proper diagnosis and treatment, based on the specific cause and severity, are crucial for managing the condition effectively. - Healthcare Professionals
- Disease Ontology ID - DOID:2741
- Pathophysiology
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Transient neonatal jaundice is one of the most common conditions occurring in newborns (children under 28 days of age) with more than 80 per cent experienceing jaundice during their first week of life. Jaundice in infants, as in adults, is characterized by increased bilirubin levels (infants: total serum bilirubin greater than 5 mg/dL).
Normal physiological neonatal jaundice is due to immaturity of liver enzymes involved in bilirubin metabolism, immature gut microbiota, and increased breakdown of fetal hemoglobin (HbF). Breast milk jaundice is caused by an increased concentration of β-glucuronidase in breast milk, which increases bilirubin deconjugation and reabsorption of bilirubin, leading to persistence of physiologic jaundice with unconjugated hyperbilirubinemia. Onset of breast milk jaundice is within 2 weeks after birth and lasts for 4–13 weeks.While most cases of newborn jaundice are not harmful, when bilirubin levels are very high, brain damage — kernicterus — may occur leading to significant disability. Kernicterus is associated with increased unconjugated bilirubin (bilirubin which is not carried by albumin). Newborns are especially vulnerable to this damage, due to increased permeability of the blood–brain barrier occurring with increased unconjugated bilirubin, simultaneous to the breakdown of fetal hemoglobin and the immaturity of gut flora. This condition has been rising in recent years. as babies spend less time in sunlight. - Carrier Status
- Hyperbilirubinemia is a condition characterized by elevated levels of bilirubin in the blood. It is not typically categorized as a carrier status condition, as this term is usually associated with genetic disorders where an individual carries one copy of a mutated gene but does not show symptoms. Hyperbilirubinemia can result from various causes, including liver diseases, hemolysis, or genetic conditions like Gilbert's syndrome or Crigler-Najjar syndrome. The term "nan" (not a number) is not applicable in this context.
- Mechanism
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Hyperbilirubinemia is characterized by an excess of bilirubin in the bloodstream. Here is a detailed explanation of its mechanism and molecular mechanisms:
### Mechanism:
1. **Bilirubin Production**: Bilirubin is a yellow pigment formed from the breakdown of heme, a component of hemoglobin in red blood cells.
2. **Transport to Liver**: Unconjugated (indirect) bilirubin, which is lipid-soluble, is transported to the liver bound to albumin.
3. **Conjugation in the Liver**: In the liver, bilirubin is conjugated with glucuronic acid by the enzyme UDP-glucuronosyltransferase (UGT1A1), converting it into water-soluble conjugated (direct) bilirubin.
4. **Excretion**: Conjugated bilirubin is secreted into bile and then into the intestines, where it is eventually excreted in the feces.
### Molecular Mechanisms:
1. **Heme Breakdown**: Heme oxygenase catalyzes the degradation of heme to biliverdin, carbon monoxide, and free iron. Biliverdin is subsequently reduced to bilirubin by biliverdin reductase.
2. **Albumin Binding**: Unconjugated bilirubin binds to albumin in the bloodstream to be transported to the liver.
3. **Enzymatic Conjugation**: The enzyme UDP-glucuronosyltransferase (UGT1A1) in hepatocytes converts unconjugated bilirubin to bilirubin diglucuronide (conjugated bilirubin). This reaction increases bilirubin's solubility, facilitating its excretion.
4. **Bile Secretion**: Conjugated bilirubin is actively transported into bile canaliculi by transporters such as multidrug resistance protein 2 (MRP2).
5. **Intestinal Processing**: In the intestines, bacterial action converts bilirubin to urobilinogen, which is either reabsorbed and excreted in urine as urobilin or oxidized to stercobilin and excreted in feces.
### Pathophysiology:
- **Pre-hepatic (Hemolytic)**: Increased production of bilirubin due to excessive breakdown of red blood cells (e.g., hemolytic anemia).
- **Hepatic**: Impaired hepatic uptake, conjugation, or secretion of bilirubin due to liver diseases (e.g., hepatitis, cirrhosis, genetic disorders like Gilbert's syndrome).
- **Post-hepatic (Obstructive)**: Obstruction of bile ducts (e.g., gallstones, tumors) leading to impaired excretion of conjugated bilirubin.
These disruptions can lead to elevated levels of either unconjugated or conjugated bilirubin, resulting in hyperbilirubinemia and its clinical manifestation, jaundice. - Treatment
- Jaundice in newborns is usually transient and dissipates without medical intervention. In cases when serum bilirubin levels are greater than 4–21 mg/dl (68–360 μmol/L), infant may be treated with phototherapy or exchanged transfusion depending on the infant's age and prematurity status. A bili light is often the tool used for early treatment, which consists of exposing the baby to intensive phototherapy, which may be intermittent or continuous. A 2014 systematic review found no evidence indicating whether outcomes were different for hospital-based versus home-based treatment. A 2021 Cochrane systematic review found that sunlight can be used to supplement phototherapy, as long as care is taken to prevent overheating and skin damage. There was not sufficient evidence to conclude that sunlight by itself is an effective treatment. Bilirubin count is also lowered through excretion — bowel movements and urination —so frequent and effective feedings are vital measures to decrease jaundice in infants.
- Compassionate Use Treatment
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Hyperbilirubinemia, characterized by elevated levels of bilirubin in the blood, can be managed with various standard treatments depending on the underlying cause. However, in certain situations where conventional treatments may not be effective or available, compassionate use, off-label, or experimental treatments may be considered. Here are a few examples:
1. **Compassionate Use Treatments:**
- **Phenobarbital:** Sometimes used to lower bilirubin levels in newborns with jaundice, particularly those with conditions like Crigler-Najjar syndrome.
2. **Off-Label Treatments:**
- **Clofibrate:** Used off-label in newborns with severe jaundice to enhance the breakdown and elimination of bilirubin.
- **Metal-porphyrin Inhibitors:** Such as tin-mesoporphyrin or zinc-protoporphyrin, which can inhibit the production of bilirubin.
3. **Experimental Treatments:**
- **Gene Therapy:** Emerging as a potential approach for genetic disorders like Crigler-Najjar syndrome that cause severe hyperbilirubinemia.
- **Heme Oxygenase Inhibitors:** Research is ongoing into drugs that can inhibit heme oxygenase, the enzyme that produces bilirubin.
These treatments are usually considered when standard options, such as phototherapy or exchange transfusion, are insufficient or unsuitable. It is essential to consult a healthcare professional to evaluate the potential benefits and risks of these treatments. - Lifestyle Recommendations
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For hyperbilirubinaemia, here are some lifestyle recommendations:
1. **Avoid Alcohol**: Limit or avoid alcohol consumption to reduce strain on the liver.
2. **Healthy Diet**: Maintain a balanced diet rich in fruits, vegetables, lean proteins, and whole grains to support liver health.
3. **Hydration**: Stay well-hydrated by drinking plenty of water.
4. **Medication Management**: Take medications as prescribed and avoid over-the-counter drugs and supplements that can affect the liver without consulting a doctor.
5. **Exercise Regularly**: Engage in regular physical activity to maintain a healthy weight and improve overall wellness.
6. **Avoid Toxins**: Stay away from chemicals and toxins that can harm the liver, including certain household cleaning products and substances.
7. **Medical Follow-Up**: Regularly monitor liver function and bilirubin levels with your healthcare provider.
These steps can help support liver health and manage hyperbilirubinaemia more effectively. - Medication
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For neonatal hyperbilirubinemia, also known as neonatal jaundice, common treatments include:
1. **Phototherapy**: This is the most widely used treatment where the baby is exposed to a type of fluorescent light that helps to break down bilirubin in the skin.
2. **Intravenous Immunoglobulin (IVIg)**: Used in cases where jaundice is caused by blood group incompatibility between the mother and baby.
3. **Exchange Transfusion**: In severe cases, where other treatments are not effective, this procedure removes the baby's blood and replaces it with fresh donor blood to quickly reduce bilirubin levels.
Pharmacological options are usually not the first line of treatment but may include:
1. **Phenobarbital**: Sometimes used to increase liver metabolism of bilirubin though it's less common due to potential side effects.
Always consult a healthcare professional for the most appropriate treatment options based on the specific circumstances. - Repurposable Drugs
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Hyperbilirubinemia refers to elevated levels of bilirubin in the blood. This condition can be caused by various underlying issues, including liver diseases, hemolytic anemia, and bile duct obstruction. Repurposable drugs for managing hyperbilirubinemia include:
1. Phenobarbital: Typically used to treat seizures, it can stimulate liver enzyme activity to enhance bilirubin conjugation.
2. Ursodeoxycholic Acid (UDCA): Primarily used for gallstones and certain liver diseases, it can help improve bile flow and reduce bilirubin levels.
3. Probiotics: Though not a direct drug, certain probiotic strains have been explored for their role in reducing bilirubin levels by modulating gut flora.
Note: The use of any medication should be under the guidance of a healthcare provider. - Metabolites
- Hyperbilirubinaemia involves elevated levels of bilirubin, a yellow compound that is a byproduct of the normal breakdown of red blood cells. Metabolites associated with hyperbilirubinaemia include bilirubin itself, conjugated bilirubin (direct bilirubin), and unconjugated bilirubin (indirect bilirubin). Elevated levels of these bilirubin metabolites are key indicators in diagnosing and managing the condition.
- Nutraceuticals
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Nutraceuticals for hyperbilirubinemia are largely under-explored in mainstream medical literature. Hyperbilirubinemia is typically managed through phototherapy or, in severe cases, exchange transfusion. However, certain dietary supplements, which may offer general liver support and enhance detoxification processes, might be considered for mild management. These include:
- **Milk Thistle (Silybum marianum)**: Contains silymarin, which has hepatoprotective properties.
- **N-acetylcysteine (NAC)**: Boosts glutathione levels, aiding in liver detoxification.
- **Curcumin**: Found in turmeric, has anti-inflammatory and antioxidative properties.
- **Probiotics**: Can support gut health, which indirectly benefits liver function.
It's crucial to consult a healthcare provider before starting any nutraceutical regimen, particularly for conditions like hyperbilirubinemia. - Peptides
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Hyperbilirubinemia is a condition characterized by elevated levels of bilirubin in the blood. While peptides and nanoparticles (nanomedicine) are emerging fields in medical research, their application in treating hyperbilirubinemia is still primarily experimental.
Peptides: Specific peptide therapeutics for hyperbilirubinemia are not well-established in clinical practice. Research may explore peptides that modulate liver function or assist in the conjugation and excretion of bilirubin.
Nanoparticles: Nanotechnology approaches for hyperbilirubinemia may include the development of nanocarriers to deliver drugs that enhance bilirubin processing or removal. For instance, nanoparticles could be designed to improve the solubility and bioavailability of such drugs, or to target specific cells in the liver to enhance their function.
In summary, while promising, the use of peptides and nanotechnology in the treatment of hyperbilirubinemia is still largely in the research phase.