| Core Lab |
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 red blood cell (RBC) hemolysis.
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)
Newborns (TBil)
Timely notification to the requesting health-care provider (HCP) of any critical findings and related symptoms is a role expectation of the professional nurse. A listing of these findings varies among facilities.
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: .) 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 is clearer to explain the physiology in terms of formation and excretion, the terms unconjugated and conjugated are 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 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:
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 nonhepatic 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.
Increased In
Unconjugated Bilirubin
Conjugated Bilirubin
Decreased In
N/A
Potential Problems: Assessment & Nursing Diagnosis/Analysis
| 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 sec. | ||
| 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 |
Before the Study: Planning and Implementation
Teaching the Patient What to Expect
After the Study: Implementation & Evaluation Potential Nursing Actions
Avoiding Complications
Treatment Considerations
Bleeding, Risk
Confusion
Safety Considerations
Nutritional Considerations
Clinical Judgement
Follow-Up Evaluation and Desired Outcomes