Synonym/Acronym
Conjugated/direct bilirubin, unconjugated/indirect bilirubin, delta bilirubin, TBil.
Rationale
A multipurpose laboratory test that is an indicator for various diseases of the liver or conditions associated with RBC hemolysis.
A small group of studies in this manual have been identified as Core Lab Studies. The designation is meant to assist the reader in sorting the basic “always need to know” laboratory studies from the hundreds of other valuable studies found in the manual—a way to begin putting it all together.
Normal, abnormal, or various combinations of core lab study results can indicate that all is well, reveal a problem that requires further investigation with additional testing, signal a positive response to treatment, or suggest that the health status is as expected for the associated situation and time frame.
Bilirubin is included in the liver function test panels (LFTs) and in the comprehensive metabolic panel (CMP). LFTs are used to identify liver disease, assess severity of injury, or monitor disease process and response to treatment. CMPs are used as a general health screen to identify or monitor conditions such as bone disease, diabetes, hypertension, kidney disease, liver disease, or malnutrition.
Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction.
Normal Findings
(Method: Spectrophotometry) Total bilirubin levels in infants should decrease to adult levels by day 15 as the development of the hepatic circulatory system matures. Values in breastfed infants may take longer to reach normal adult levels. Values in premature infants may initially be higher than in full-term infants and also take longer to decrease to normal levels.
| Age | Conventional Units | SI Units (Conventional Units × 17.1) |
|---|
| Total Bilirubin | | | | Newborn–1 d | Less than 6 mg/dL | Less than 103 micromol/L | | 1–2 d | Less than 10 mg/dL | Less than 171 micromol/L | | 3–5 d | Less than 12 mg/dL | Less than 205 micromol/L | | 7–14 d | Less than 15 mg/dL | Less than 256 micromol/L | | 15 d–17 yr | Less than 1 mg/dL | Less than 17 micromol/L | | 18 yr–older adult | Less than 1.2 mg/dL | Less than 21 micromol/L | | Conjugated (direct) bilirubin | | | | 1 yr–older adult | Less than 0.3 mg/dL | Less than 5 micromol/L | | Unconjugated (indirect) bilirubin | Less than 1.1 mg/dL | Less than 19 micromol/L | | Delta bilirubin | Less than 0.2 mg/dL | Less than 3 micromol/L |
The use of different equipment and reagents between laboratories can produce variability in results. |
Adults and Children (TBil)
- Greater than 15 mg/dL (SI: Greater than 257 micromol/L)
Newborns (TBil)
Consideration may be given to verification of critical findings before action is taken. Policies vary among facilities and may include requesting recollection and retesting by the laboratory.
Sustained hyperbilirubinemia can result in brain damage. Kernicterus refers to the deposition of bilirubin in the basal ganglia and brainstem nuclei. There is no exact level of bilirubin that puts infants at risk for developing kernicterus. Symptoms of kernicterus in infants include lethargy, poor feeding, upward deviation of the eyes, and seizures. Intervention for infants may include early frequent feedings to stimulate gastrointestinal (GI) motility, phototherapy, and exchange transfusion.
Study type: Blood collected in gold-, red-, red/gray-, or green-top [heparin] tube; related body system: Digestive system. A heparinized Microtainer is also acceptable. Protect sample from direct light.
References to the various forms of bilirubin can be confusing. One way of expressing bilirubin fractions relates to the process of how each fraction is formed. First, the unconjugated form is made by the spleen; it then travels to the liver where it becomes conjugated to glucuronic acid, the form that is excreted from the body under normal circumstances. The other way of expressing bilirubin fractions relates to how laboratory instruments measure the fractions. The conjugated bilirubin in a sample reacts directly with reagents while the unconjugated bilirubin has to be combined with a solubilizing reagent in addition to the other reagents before it can be measured. Since it’s clearer to explain the physiology in terms of formation and excretion, the terms unconjugated and conjugated will be used in this study, except in the table of normal findings, where the terms used in laboratory reports are presented.
In practice, most total bilirubin assays are set up with a solubilizing reagent included in the reaction such that both the direct and indirect fractions are measured together. Results from a separate direct bilirubin reaction can be subtracted from the total bilirubin result to estimate the indirect fraction using the formula: Indirect bilirubin = (Total bilirubin – Direct bilirubin).
When old or damaged RBCs are removed from circulation and destroyed, the cellular contents are recycled (e.g., iron from hemoglobin) or excreted (e.g., heme from hemoglobin). Eighty percent of bilirubin is a normal by-product of heme catabolism and is primarily produced in the cells of the reticuloendothelial system (spleen). The other portion is recovered from heme containing proteins found mainly in the Kupffer cells (tissue macrophages) of the liver, and by other phagocytes in muscle tissue.
Normally the majority of circulating bilirubin is in the unconjugated prehepatic form until it is carried to the liver by albumin, where it is conjugated with glucuronic acid (hepatic). Conjugated bilirubin is water soluble and more easily excreted. Most of the conjugated posthepatic bilirubin enters the bile and is transported directly into the small intestine; a small portion of the conjugated bilirubin remains in the bile and is stored in the gallbladder.
Bacteria in the small intestine convert the conjugated bilirubin to urobilinogen, which is then converted to stercobilin and urobilin. Stercobilin, a pigmented waste product of bilirubin, is excreted in feces; stercobilin gives feces its normal brown color. Small amounts of urobilin, another pigmented waste product of bilirubin, are excreted in urine; urobilin gives urine its characteristic yellow color. Defects in bilirubin excretion can be identified by a greater than normal presence (e.g., cirrhosis, hemolysis, toxic hepatitis, viral hepatitis) or less than normal presence (e.g., cholestasis) of urobilinogen in a routine urinalysis.
The terms direct bilirubin and conjugated bilirubin are not interchangeable. There is a seldom-mentioned bilirubin fraction—albumin-bound conjugated bilirubin—also known as delta bilirubin. Most direct bilirubin methods measure conjugated bilirubin (unconjugated bilirubin + glucuronic acid) and delta bilirubin. Delta bilirubin appears in the serum when the normal process for hepatic excretion of conjugated bilirubin is impaired (e.g., a prolonged case of cholestasis). Normally when unconjugated bilirubin is carried to the surface of liver cells (hepatocytes) it dissociates from albumin and enters the hepatocytes. When excretion of conjugated bilirubin from hepatocytes is impaired, as in the case of a biliary obstruction, irreversible binding to albumin takes place. The albumin-bound delta bilirubin complex is not filtered by the kidneys and it remains in the plasma. Delta bilirubin is metabolized with its albumin component so the half life is similar to albumin (12–14 days). Conjugated bilirubin has a much shorter half life—it turns over in 2 to 4 hours—and unconjugated bilirubin turns over in a matter of minutes. Laboratory findings that correlate to the scenario of prolonged cholestasis would include increased blood levels of direct bilirubin and negative urine urobilinogen (normal is up to 1 mg/dL, sensitivity is 0.2 mg/dL). Delta bilirubin can be measured directly by some laboratory methods, but it is not a routinely reported test. Delta bilirubin can also be estimated using this formula 
where direct (conjugated) bilirubin and indirect bilirubin are both measured values (e.g., Ortho Clinical’s Tbil, Bu, Bc studies). Delta bilirubin = Total bilirubin – (Direct bilirubin + Indirect Bilirubin).
Increases in levels of bilirubin or its metabolites can result from prehepatic, hepatic, and/or posthepatic conditions, making fractionation useful in determining the cause of the increase in total bilirubin levels. Prehepatic refers to increased production of bilirubin (where less than 20% of the total bilirubin is from the conjugated fraction); higher levels of unconjugated bilirubin usually would be expected from:
- an RBC-related condition (e.g., abnormal RBC synthesis, RBC hemolysis)
- a condition that impairs clearance of bilirubin from the liver (congenital or acquired portosystemic shunts, congestive heart failure, certain drugs)
- defective conjugation of bilirubin (inherited disorders)
- circumstances brought about by the simultaneous interactions of multiple conditions
Hepatic refers to a dysfunction or injury associated with the liver; posthepatic refers to some type of blockage in the bile ducts. Higher levels of conjugated bilirubin would be expected (more than 50% of the total bilirubin is from the conjugated fraction) in hepatic or posthepatic conditions.
When bilirubin concentration increases, the yellowish pigment deposits in skin and sclera. This increase in yellow pigmentation is termed jaundice or icterus. Bilirubin levels can also be checked using noninvasive methods. Hyperbilirubinemia in neonates can be reliably evaluated using transcutaneous measurement devices.
| Examples of Possible Patterns Between TBil Levels and Other Core LFT Levels in Specific Hepatic Conditions |
|---|
| Diagnosis | TBil level (Other Core LFTs) |
|---|
| Cholestasis | ↑Normal to Mild (Alb N, ALP ↑↑↑, ALT ↑, AST ↑) | | Cirrhosis | ↑Normal to Mild (Alb ↓, ALP ↑ to ↑↑, ALT ↑ to ↑↑, AST ↑↑↑) | | Hepatitis, viral, acute | ↑to ↑↑ Normal to Mild or Moderate (Alb ↓, ALP ↑ to ↑↑, ALT ↑↑↑, AST ↑↑↑) | | Hepatitis, toxin- or drug-related | ↑↑Mild to Moderate (Alb ↓, ALP ↑ to ↑↑, ALT ↑↑↑, AST ↑↑↑) | | Infarction, acute necrosis of the liver, or cancer | ↑↑Mild to Moderate (Alb ↓, ALP increased, ALT ↑↑↑, AST ↑↑ to ↑↑↑) | | Jaundice, hepatic origin | ↑to ↑↑ Normal to Mild or Moderate (Alb ↓, ALP ↑ to ↑↑, ALT ↑↑ with ALT rising before AST and TBil, AST ↑↑) | | Relative ALT and TBil levels in non-hepatic jaundice | | Jaundice, RBC (prehepatic) origin | ALT ↑ Normal to Mild and TBil ↑↑ Mild to Moderate or ↑↑↑ Marked, in proportion to the degree of hemolysis |
N=Normal, ↓ Normal to Mild decrease, ↑ Normal to Mild increase, ↑ to ↑↑ Normal to Mild or Moderate, ↑↑ Mild to Moderate, ↑↑↑ Marked. Study levels will vary with degree and progression of liver damage. ALT levels remain elevated longer than AST levels. |
Factors That May Alter the Results of the Study
- Drugs and other substances that may increase bilirubin levels include acarbose, ACE inhibitors, acetaminophen (toxic), acetylsalicylic acid, allopurinol, amoxicillin, amiodarone, ampicillin, amytriptyline, ARBs, asparaginase, azathioprine, beta-blockers, baclofen, bupropion, carbamazepine, cephalosporins, chloramphenicol, chlordiazepoxide, chlorpromazine, chlorpropamide, clindamycin, cloxacillin, clopidogrel, codeine, cyproheptadine, cytarabine, danazol, desipramine, dicumarol, doxepin, enflurane, erythromycin, estrogens, ethambutol, ethionamide, ethotoin, ethyl alcohol, fibrates, gentamicin, gold salts, imipramine, isoniazid, ketoconazole, low-molecular-weight heparin, methyl dopa, metaxalone, methotrexate, nafcillin, naladixic acid, nitrofurans, nortriptyline, NSAIDs, omeprazole, oral contraceptives, oxacillin, phenobarbital, phenytoin, probenecid, procainamide, propoxyphene, pyrazinamide, quinidine, rifampin, risperidone, sulfonamides, terbinafine, tetracyclines, trazadone, trimethoprim, valproic acid, verapamil, vitamin K, and zidovudine.
- Drugs and other substances that may decrease bilirubin levels include antimicrobials (penicillins), barbiturates, caffeine, and salicylates.
- Bilirubin is light sensitive. Failure to suitably protect the collection container from light between the time of collection and time of analysis may decrease bilirubin levels.
- Hemolyzed specimens may cause falsely elevated results (total and direct).
Potential Nursing Problems: Assessment & Nursing Diagnosis
| Problems | Signs and Symptoms |
|---|
| Bleeding, risk (related to altered clotting factors) | Cool extremities, delayed capillary refill, decreased distal pulses, altered mental status, hypotension, tachycardia, decreased level of consciousness. Bruises easily, hematemesis, weakness, shortness of breath, bloody or black stools. PT prolonged greater than 13.5 seconds. | | Body image (related to jaundice; ascites; dry, flaky, itchy skin) | Yellowing of sclera and skin, open sores due to aggressive itching, repeated self-criticism, refusal to discuss altered physical appearance, withdrawal from social situations, conceals physical self with clothing | | Confusion (altered sensory perception—related to hepatic encephalopathy, acute alcohol consumption, hepatic metabolic insufficiency) | Altered attention span; unable to follow directions; disoriented to person, place, time, and purpose; inappropriate affect; mood changes; aberrant behavior; incoherence | | Fall, risk (related to impaired mobility, assistive device use, acute or chronic disease process, dizziness, confusion, history of previous falls) | Unsteady gait, decreased ability to complete activities of daily living independently, decreased visual acuity or hearing, fatigue, weakness, difficulty following instructions, improper assistive device use, altered color perception, changed center of gravity, delayed response and reaction times | | Gas exchange (ineffective—related to accumulation of pleural fluid, atelectasis, ventilation perfusion mismatch, altered oxygen supply) | Irregular breathing pattern, use of accessory muscles, altered chest excursion, adventitious breath sounds (crackles, rhonchi, wheezes, diminished breath sounds), copious secretions, signs of hypoxia | | Nutrition(insufficient—related to poor eating habits, excessive alcohol use, altered liver function, nausea, vomiting; metabolic dysfunction; inability to ingest or digest food) | Known inadequate caloric intake, weight loss; muscle wasting in arms and legs; stool that is pale or gray-colored; skin that is flaky with loss of elasticity; hair loss; pale mucous membranes; symptoms of vitamin deficiency | | Skin, risk (related to elevated serum bilirubin levels and excess bile salt resulting in tissue irritation and histamine release, jaundice associated with liver disease) | Reports itchy skin (dermatitis/pruritis); chronic scratching; dry, scaly skin; yellow skin and sclera; visible scratch marks with or without scabbing; rash |
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Before the Study: Planning and Implementation
Teaching the Patient What to Expect
- Discuss how this test can assist in assessing liver function and conditions that cause jaundice.
- Explain that a blood sample is needed for the test.
After the Study: Implementation & Evaluation Potential Nursing Actions
Avoiding Complications
- Severe jaundice may occur as the result of an incompatible blood product transfusion. It may also occur as an ABO or Rh incompatibility between a mother and baby. An ABO incompatibility can occur if a mother with blood type O blood is carrying a baby with blood type A, type B, or type AB. An Rh incompatibility can occur if a mother with Rh negative blood is carrying a baby with Rh positive blood. The jaundice occurs as the result of hemolysis or RBC breakdown of the baby’s RBCs due to the incompatibility.
- There are several other types of jaundice, unrelated to blood type, that may occur in the neonate, and it is important to quickly determine the cause so effective treatment can be initiated.
- Physiologic jaundice occurs as a normal response to the neonate’s limited ability to excrete bilirubin in the first days of life. Early interventions may include phototherapy and frequent feeding to stimulate GI motility. This type of jaundice usually lasts 10 to 14 days (premature neonates may take up to a month) and resolves in reverse to the pattern of development with the legs looking normal first and the face remaining yellowish longer.
- Breastfeeding jaundice is seen in breastfed neonates during the first week of life, peaking during the second or third week. It occurs due to dehydration related to a neonate’s inability to nurse adequately or if the mother’s milk comes in slowly. Bilirubin levels are elevated relative to the decreased total fluid volume. The interventional goal is to provide the breastfeeding neonate with adequate fluid and nutrition. This is achieved by providing water or formula between breastfeedings until the mother’s milk supply is adequate. Phototherapy may also be ordered to accelerate the breakdown of bilirubin and prevent accumulation to dangerous levels. Skin turgor, input and output, vital signs, and number/quality of stools should be frequently monitored. Total bilirubin and fractions should be monitored regularly until levels decrease to normal neonatal values.
- Breast milk jaundice is different from breastfeeding jaundice and occurs in about 2% of breastfed neonates after the first week of life. Breast milk jaundice takes up to 12 wk to resolve and is believed to have a familial relationship. A complete assessment of family history is helpful to determine future risk. Occurrence of hyperbilirubinemia is related to substances in the mother’s milk that interfere with development of enzymes required to break down bilirubin. The interventional goals are to increase fluids intake by more frequent feeding or additional use of oral or IV fluids; and use of phototherapy. Fiberoptic blankets and special beds that shine light up from the mattresses are available.
Treatment Considerations
General
- Monitor and trend TBil and DBil. Compare with LFTs (Alb, ALT, ALP, AST, TP) or other related studies to track the course of disease and response to treatment.
- Note that PT will be prolonged and INR increased if liver function is significantly damaged.
- Also monitor and trend gamma-glutamyltransperase (GGTP), bilirubin, total protein, iron, electrolytes, folic acid, vitamin K, and thiamine in the presence of hepatitis.
- Note that currently, specific drugs are being used to treat different types of viral hepatitis.
- For example, there are a number of drugs used to treat hepatitis B such as pegylated interferon (adults only), interferon alfa (adults and children), and lamivudine (adults and children); Harvoni (a combination of ledipasvir and sofosbuvir), Mavyret (a combination of glecaprevir and pibrentasvir), and Solvaldi (sofosbuvir) are examples of drugs used to treat hepatitis C.
- There are also drugs that can be given to treat and reverse the symptoms of nonviral hepatitis once the primary cause of hepatic inflammation is identified.
Bleeding, Risk
- Frequently monitor vitals signs for changes outside of the patient’s baseline.
- Monitor for bleeding symptoms (stools, emesis, bruising).
- Monitor for shortness of breath; administer oxygen as ordered.
- Administer ordered blood per facility protocol.
Body Image
- Assess for yellowing of the sclera and skin.
- Assess skin for patches of itching, and provide mitts to decrease scratching and skin damage.
- Use tepid water when cleansing the skin, avoid alkaline soaps, and keep the skin well moisturized to decrease itching.
- Assess patient’s perception of self related to current medical status, monitor for self-criticism, and acknowledge normal response to changed appearance.
Confusion
- Facilitate management of altered sensory perception.
- Monitor blood ammonia level, determine last alcohol use, and assess for symptoms of hepatic encephalopathy such as confusion, sleep disturbances, and incoherence.
- Monitor for altered attention span; orientation to person, place, time, and purpose; and inappropriate behavior.
- Protect confused patients from physical harm.
- Administer ordered lactulose.
Fall, Risk
- Assess fall risk on admission, transfer, post-fall, and change of condition.
- Follow established organizational fall prevention protocols.
- Identify previous fall history and frequency.
- Assess for disease-related symptoms such as orthostatic hypotension, urinary incontinence.
- Move the patient closer to the nurses station for easier observation.
- Enlist the support of reliable family members as partners in preventing falls.
- Move frequently used items close to the bed to decrease desire to get up.
- Answer call lights in a timely manner to decrease risk of getting up.
- Place the bed in the lowest possible position.
- Raise side rails judiciously as the situation requires.
- Encourage the use of well-fitting shoes with nonskid soles.
- Ensure the room is well lit to prevent tripping.
- Review medications to identify any pharmacological contributors to fall risk.
- Encourage the use of eyeglasses and hearing aids.
Gas Exchange
- Facilitate management of inadequate gas exchange.
- Monitor respiratory rate and effort based on assessment of patient condition.
- Frequently assess lung sounds, and monitor for secretions and suction as necessary.
- Perform pulse oximetry to monitor oxygen saturation, collaborate with the HCP and respiratory therapy to administer oxygen as needed.
- Elevate the head of the bed 30 degrees.
- Monitor IV fluids, and avoid aggressive fluid resuscitation.
- Monitor and document degree of abdominal ascites and abdominal girth.
Skin, Risk
- Assess the skin’s general condition, noting any scratches, bruises, excoriation, rash.
- Monitor bilirubin level, as a level greater than 3 mg/dL facilitates jaundice and increases itching risk.
- Discuss ways to protect the skin such as use of tepid water, alkaline soap, and emollient lotions.
- Suggest keeping short fingernails and the use of mittens to discourage scratching.
- Encourage loose-fitting cotton clothing, cool room temperatures, and administration of antihistamines to help decrease itching.
- Assess for easy bruising.
Nutritional Considerations
- Facilitate management of insufficient nutrition.
- Increased bilirubin levels may be associated with liver disease.
- Dietary recommendations may be indicated depending on the condition and its severity.
- Assess barriers to eating and consider using a food diary.
- Consider documenting food intake with a calorie count.
- Consider a consult with a registered dietitian and assessment of cultural food selections.
- Administer ordered multivitamin and parenteral or enteral nutrition.
- Monitor and trend glucose levels and daily weight.
- Assess and trend other tests related to nutrition, e.g., Alb, TP, folic acid, glucose, thiamine, and electrolytes.
- Correlate laboratory values with IV infusion and collaborate with the HCP and pharmacist to adjust to patient needs.
- Monitor continued alcohol use, as it is a barrier to adequate nutrition.
- Eliminating alcohol consumption and encouraging a diet optimized for convalescence are commonly included in the treatment plan.
- Patients who are diagnosed with substance use disorder (alcohol) should be encouraged to avoid alcohol and also to seek appropriate counseling.
- Increased bilirubin levels may be associated with liver disease. In general, patients should be encouraged to eat a well-balanced diet that includes foods high in fiber. Dietary recommendations will vary depending on the condition and its severity. For example, recommend a diet of soft foods if esophageal varices develop, fat substitutes for bile duct disease, or limitations on salt intake if ascites develop.
- Ensure adequate pain control to improve caloric intake.
- Monitor vital signs for alterations associated with metabolic imbalances.
Clinical Judgement
- Consider which interventions are most likely to get patient buy in and facilitate improved overall health.
Follow-Up and Desired Outcomes
- Understands the cause of the hyperbilirubinemia and that jaundice may resolve with treatment of the liver disease.
- Acknowledges the importance of adhering to scheduled laboratory appointments to monitor liver function and disease progress.
- Agrees with the importance of adequate fluid intake and demonstrates how to perform skin care for the neonate.
- Accepts therapeutic management plan and strictly adheres to HCP care strategy.
- Agrees to alcohol cessation and attends support group to prevent relapse.