Bilirubin and Bilirubin Fractions

(redirected from Conjugated/direct bilirubin)

Bilirubin and Bilirubin Fractions

Synonym/acronym: Conjugated/direct bilirubin, unconjugated/indirect bilirubin, delta bilirubin, TBil.

Common use

A multipurpose lab test that acts as an indicator for various diseases of the liver or for disease that affects the liver.

Specimen

Serum (1 mL) collected in gold-, red-, or red/gray-top tube. Plasma (1 mL) collected in green-top (heparin) tube or in a heparinized microtainer is also acceptable. Protect sample from direct light.

Normal findings

(Method: Spectrophotometry) Total bilirubin levels in infants should decrease to adult levels by day 10 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.
AgeConventional UnitsSI Units (Conventional Units × 17.1)
Total bilirubin
 Newborn–1 dayLess than 5.8 mg/dLLess than 99 micromol/L
 1–2 daysLess than 8.2 mg/dLLess than 140 micromol/L
 3–5 daysLess than 11.7 mg/dLLess than 200 micromol/L
 6–7 daysLess than 8.4 mg/dLLess than 144 micromol/L
 8–9 daysLess than 6.5 mg/dLLess than 111 micromol/L
 10–11 daysLess than 4.6 mg/dLLess than 79 micromol/L
 12–13 daysLess than 2.7 mg/dLLess than 46 micromol/L
 14–30 daysLess than 0.8 mg/dLLess than 14 micromol/L
 1 mo–older adultLess than 1.2 mg/dLLess than 21 micromol/L
Unconjugated bilirubinLess than 1.1 mg/dLLess than 19 micromol/L
Conjugated bilirubin
 NeonateLess than 0.6 mg/dLLess than 10 micromol/L
 29 days–older adultLess than 0.3 mg/dLLess than 5 micromol/L
Delta bilirubinLess than 0.2 mg/dLLess than 3 micromol/L

Description

Bilirubin is a by-product of heme catabolism from aged red blood cells (RBCs). Bilirubin is primarily produced in the liver, spleen, and bone marrow. Total bilirubin is the sum of unconjugated or indirect bilirubin, monoglucuronide and diglucuronide, conjugated or direct bilirubin, and albumin-bound delta bilirubin. Unconjugated bilirubin is carried to the liver by albumin, where it becomes conjugated. In the small intestine, conjugated bilirubin converts to urobilinogen and then to urobilin. Urobilin is then excreted in the feces. Defects in bilirubin excretion can be identified in a routine urinalysis. Increases in bilirubin levels can result from prehepatic, hepatic, and/or posthepatic conditions, making fractionation useful in determining the cause of the increase in total bilirubin levels. Delta bilirubin has a longer half-life than the other bilirubin fractions and therefore remains elevated during convalescence after the other fractions have decreased to normal levels. Delta bilirubin can be calculated using the formula:

Delta bilirubin = Total bilirubin − (Indirect bilirubin + Direct bilirubin)

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.

This procedure is contraindicated for

    N/A

Indications

  • Assist in the differential diagnosis of obstructive jaundice
  • Assist in the evaluation of liver and biliary disease
  • Monitor the effects of drug reactions on liver function
  • Monitor the effects of phototherapy on jaundiced newborns
  • Monitor jaundice in newborn patients

Potential diagnosis

Increased in

  • Prehepatic (hemolytic) jaundice (related to excessive amounts of heme released from RBC destruction. Heme is catabolized to bilirubin in concentrations that exceed the liver’s conjugation capacity, and indirect bilirubin accumulates)
    • Erythroblastosis fetalis
    • Hematoma
    • Hemolytic anemia
    • Pernicious anemia
    • Physiological jaundice of the newborn
    • The post blood transfusion period, when a number of units are rapidly infused or in the case of a delayed transfusion reaction
    • RBC enzyme abnormalities (i.e., glucose-6-phosphate dehydrogenase, pyruvate kinase, spherocytosis)
  • Hepatic jaundice (related to bilirubin conjugation failure)
    • Crigler-Najjar syndrome
  • Hepatic jaundice (related to disturbance in bilirubin transport)
    • Dubin-Johnson syndrome (related to preconjugation transport failure)
    • Gilbert’s syndrome (related to postconjugation transport failure)
  • Hepatic jaundice (evidenced by liver damage or necrosis that interferes with excretion into bile ducts either by physical obstruction or drug inhibition and bilirubin accumulates)
    • Alcoholism
    • Cholangitis
    • Cholecystitis
    • Cholestatic drug reactions
    • Cirrhosis
    • Hepatitis
    • Hepatocellular damage
    • Infectious mononucleosis
  • Posthepatic jaundice (evidenced by blockage that interferes with excretion into bile ducts, resulting in accumulated bilirubin)
    • Advanced tumors of the liver
    • Biliary obstruction
  • Other conditions
    • Anorexia or starvation (related to liver damage)
    • Hypothyroidism (related to effect on the liver whereby hepatic enzyme activity for formation of conjugated or direct bilirubin is enhanced in combination with decreased flow of bile and secretion of bile acids; results in accumulation of direct bilirubin)
    • Premature or breastfed infants (evidenced by diminished hepatic function of the liver in premature infants; related to inability of neonate to feed in sufficient quantity. Insufficient breast milk intake results in weight loss, decreased stool formation, and decreased elimination of bilirubin)

Decreased in

    N/A

Critical findings

  • Adults and children
  • Greater than 15 mg/dL (SI: Greater than 257 micromol/L)
  • Newborns
  • Greater than 13 mg/dL (SI: Greater than 222 micromol/L)
  • Note and immediately report to the health-care provider (HCP) any critically increased values and related symptoms.

  • It is essential that critical findings be communicated immediately to the requesting health-care provider (HCP). A listing of these findings varies among facilities.

  • Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. The notification processes will vary among facilities. Upon receipt of the critical finding the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical finding, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.

  • 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 motility, phototherapy, and exchange transfusion.

Interfering factors

  • Drugs that may increase bilirubin levels by causing cholestasis include anabolic steroids, androgens, butaperazine, chlorothiazide, chlorpromazine, chlorpropamide, cinchophen, dapsone, dienoestrol, erythromycin, estrogens, ethionamide, gold salts, hydrochlorothiazide, icterogenin, imipramine, iproniazid, isocarboxazid, isoniazid, meprobamate, mercaptopurine, meropenem, methandriol, nitrofurans, norethandrolone, nortriptyline, oleandomycin, oral contraceptives, penicillins, phenothiazines, prochlorperazine, progesterone, promazine, promethazine, propoxyphene, protriptyline, sulfonamides, tacrolimus, thiouracil, tolazamide, tolbutamide, thiacetazone, trifluoperazine, and trimeprazine.
  • Drugs that may increase bilirubin levels by causing hepatocellular damage include acetaminophen (toxic), acetylsalicylic acid, allopurinol, aminothiazole, anabolic steroids, asparaginase, azathioprine, azithromycin, carbamazepine, carbutamide, chloramphenicol, clindamycin, clofibrate, chlorambucil, chloramphenicol, chlordane, chloroform, chlorzoxazone, clonidine, colchicine, coumarin, cyclophosphamide, cyclopropane, cycloserine, cyclosporine, dactinomycin, danazol, desipramine, dexfenfluramine, diazepam, diethylstilbestrol, dinitrophenol, enflurane, ethambutol, ethionamide, ethoxazene, factor IX complex, felbamate, flavaspidic acid, flucytosine, fusidic acid, gentamicin, glycopyrrolate, guanoxan, haloperidol, halothane, hycanthone, hydroxyacetamide, ibuprofen, interferon, interleukin-2, isoniazid, kanamycin, labetalol, levamisole, lincomycin, melphalan, mesoridazine, metahexamide, metaxalone, methotrexate, methoxsalen, methyldopa, nitrofurans, oral contraceptives, oxamniquine, oxyphenisatin, pemoline, penicillin, perphenazine, phenazopyridine, phenelzine, phenindione, pheniprazine, phenothiazines, piroxicam, probenecid, procainamide, pyrazinamide, quinine, sulfonylureas, thiothixene, timolol, tobramycin, tolcapone, tretinoin, trimethadione, urethan, and verapamil.
  • Drugs that may increase bilirubin levels by causing hemolysis include aminopyrine, amphotericin B, carbamazepine, cephaloridine, cephalothin, chloroquine, dimercaprol, dipyrone, furadaltone, furazolidone, mefenamic acid, melphalan, mephenytoin, methylene blue, nitrofurans, nitrofurazone, pamaquine, penicillins, pentaquine, phenylhydrazine, piperazine, pipobroman, primaquine, procainamide, quinacrine, quinidine, quinine, stibophen, streptomycin, sulfonamides, triethylenemelamine, tyrothricin, and vitamin K.
  • Drugs that may decrease bilirubin levels include anticonvulsants, barbiturates (newborns), chlorophenothane, cyclosporine, flumecinolone (newborns), and salicylates.
  • Bilirubin is light sensitive. Therefore, the collection container should be suitably covered to protect the specimen from light between the time of collection and analysis.

Nursing Implications and Procedure

Potential nursing problems

ProblemSigns & SymptomsInterventions
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 Assess skin for patches of itching; monitor liver function tests; monitor bilirubin levels; assess for yellowing of the sclera and skin; provide mitts to decrease scratching; assess patient’s perception of self related to current medical status; monitor for self-criticism; acknowledge normal response to changed appearance
Nutrition (Related to poor eating habits; excessive alcohol use; altered liver function; nausea; vomiting)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 elasticityDocument food intake with possible calorie count; assess barriers to eating; consider using a food diary; monitor continued alcohol use as it is a barrier to adequate nutrition; monitor glucose levels; check daily weight; perform dietary consult with assessment of cultural food selections; consider a high-carbohydrate diet; administer multivitamin as prescribed; administer parenteral and enteral nutrition as needed; assess liver function tests (ALT, AST, ALP, total protein, albumin, bilirubin), folic acid, glucose, thiamine, and electrolytes
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 affectMonitor blood ammonia level; determine last alcohol use; assess for symptoms of hepatic encephalopathy such as confusion, sleep disturbances, incoherence; protect the patient from physical harm; administer lactalose as prescribed
Gas exchange (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 hypoxiaMonitor respiratory rate and effort based on assessment of patient condition; assess lung sounds frequently; monitor for secretions; suction as necessary; perform pulse oximetry to monitor oxygen saturation; collaborate with physician to administer oxygen as needed; elevate the head of the bed 30 degrees; monitor IV fluids and avoid aggressive fluid resuscitation; monitor degree of abdominal ascites

Pretest

  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in assessing liver function.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s hepatobiliary system, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medication, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.

Intratest

  • Potential complications:
  • There are several types of jaundice 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. Intervention may include early frequent feeding to stimulate gastrointestinal motility and phototherapy. 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 in neonates who do not nurse well or if the mother’s milk is slow to come in; the bilirubin levels are elevated relative to the decreased total fluid volume. The goal is to provide adequate fluid and nutrition to the breastfeeding neonate by providing water or formula between feedings and until the mother’s milk supply is adequate. Phototherapy may also be ordered in order 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 than breastfeeding jaundice, occurs in about 2 percent of breastfed neonates after the first week of life, takes up to 12 wk to resolve, and is believed to have a familial relationship; assessment for family history is very helpful. Hyperbilirubinemia occurs due to substances in the mother’s milk that interfere with development of enzymes required to break down bilirubin. The main goals are to increase fluids by more frequent feeding or additional fluids given orally or by IV and through the use of phototherapy. Fiberoptic blankets and special beds that shine light up from the mattresses are available.
  • Severe jaundice may occur as the result of an ABO or Rh incompatibility between the mother and baby. The jaundice occurs as the result of hemolysis or RBC breakdown due to the incompatibility.
  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Protect the specimen from light and promptly transport the specimen to the laboratory for processing and analysis.

Post-Test

  • Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
  • Nutritional Considerations: Increased bilirubin levels may be associated with liver disease. Dietary recommendations may be indicated depending on the condition and severity of the condition. Currently, for example, there are no specific medications that can be given to cure hepatitis, but elimination of alcohol consumption and a diet optimized for convalescence are commonly included in the treatment plan. A high-calorie, high-protein, moderate-fat diet with a high fluid intake is often recommended for the patient with hepatitis. Treatment of cirrhosis is different because a low-protein diet may be in order if the patient’s liver has lost the ability to process the end products of protein metabolism. A diet of soft foods may also be required if esophageal varices have developed. Ammonia levels may be used to determine whether protein should be added to or reduced from the diet. Patients should be encouraged to eat simple carbohydrates and emulsified fats (as in homogenized milk or eggs) rather than complex carbohydrates (e.g., starch, fiber, and glycogen [animal carbohydrates]) and complex fats, which require additional bile to emulsify them so that they can be used. The cirrhotic patient should be carefully observed for the development of ascites, in which case fluid and electrolyte balance requires strict attention. The alcoholic patient should be encouraged to avoid alcohol and also to seek appropriate counseling for substance abuse.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.
  • Patient Education

    • Educate the patient regarding the cause of the hyperbilirubinemia. Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP.
    • Recognize anxiety related to test results, and answer any questions or address any concerns voiced by the patient or family.
    • Assist patient to identify coping strategies that have worked in the past to manage disease-related anxiety
    • Explain the importance of adhering to scheduled laboratory appointments to monitor liver function and disease progress.
    • Explain the importance of adequate fluid intake and teach the patient skin care for the neonate.
  • Expected Patient Outcomes

    • Knowledge
    • Recognizes that jaundice may resolve with treatment of the liver disease
    • Relates the importance of nutritional supplements to help prevent malnutrition
    • Skills
    • Follows dietary recommendations to gain and maintain adequate weight
    • Naturally verbalizes feelings about changed appearance in a positive manner
    • Attitude
    • Resolves to take proactive steps to ensure positive health maintenance
    • Complies with the recommendation to attend support groups to assist in adapting to changed physical appearance

Related Monographs

  • Related tests include ALT, albumin, ALP, ammonia, amylase, AMA/ASMA, α1-antitrypsin/phenotyping, AST, biopsy liver, cholesterol, coagulation factor assays, CBC, cholangiography percutaneous transhepatic, cholangiography post-op, CT biliary tract and liver, copper, ERCP, GGT, hepatobiliary scan, hepatitis serologies, infectious mononucleosis screen, lipase, liver and spleen scan, protein total and fractions, PT/INR, US abdomen, US liver, and UA.
  • See the Hepatobiliary System table at the end of the book for related tests by body system.