Chemistry Studies

Chemistry Studies


Blood chemistry testing identifies many chemical blood constituents. It is often necessary to measure several blood chemicals to establish a pattern of abnormalities. A wide range of tests can be grouped under the headings of enzymes, electrolytes, blood sugars, lipids, hormones, proteins, vitamins, minerals, and drug investigation. Other tests have no common denominator. Selected tests serve as screening devices to identify target organ damage. When collecting specimens for chemistry studies, refer to Standard Precautions for Prevention and Control of Infection in Appendix A, Guidelines for Specimen Transport and Storage in Appendix B, and Effects of Drugs on Laboratory Tests in Appendix E.

General Biochemical Profiles

Profiles are a group of select tests that screen for certain conditions. Some of the more common profiles or panels are listed in Table 6.1.

Use of the Autoanalyzer

Sophisticated automated instrumentation makes it possible to conduct a wide variety of chemical tests on a single sample of blood and to report results in a timely manner. Numerical results may be reported with low, high, panic (or critical values), toxic, or D (i.e., fails Delta check) comments along with normal reference range. Computerized interfaces allow direct transmission of results
between laboratory and clinical settings. Not only does this method of record keeping provide a baseline for future comparisons, but it can also allow unsuspected diseases to be uncovered and can lead to early diagnosis when symptoms are vague or absent. Chemistry tests may be grouped into lipid, basic metabolic, comprehensive metabolic, hepatic, or electrolyte panels. A list of standard panels appears in Table 6.2.

TABLE 6.1 Common Screening Profiles

Group Headings

Tests Suggested

Cardiac markers (MI)

Troponin, myoglobin

Electrolyte panel

Na, K, Cl, CO2

Kidney functions, disease

BUN, phosphorus, LDH, creatinine, creatinine clearance, total protein, A/G ratio, albumin, calcium, glucose, CO2

Lipids (coronary risk)

Cholesterol, triglycerides, HDL, LDL

Liver function, disease

Total bilirubin, alkaline phosphatase, GGT, total protein, A/G ratio, albumin, AST, LDH, viral hepatitis panel, PT

Thyroid function

Free T4, TSH

Basic metabolic screen

Cl, Na, K, CO2, glucose, BUN, creatinine

A/G ratio, albumin-to-globulin ratio; AST, aspartate aminotransferase; BUN, blood urea nitrogen; GGT, γ-glutamyl transpeptidase; HDL, highdensity lipoprotein; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; MI, myocardial infarction; PT, prothrombin time; T4, thyroxine; TSH, thyroid-stimulating hormone.

Adapted from Expert panel on detection, evaluation and treatment of high blood cholesterol in adults. Executive summary of NCEP-ATP III. JAMA 285:2486-2497, 2001


• Fasting Blood Glucose (FBG); Fasting Blood Sugar (FBS); Fasting Plasma Glucose (FPG); Casual Random Plasma Glucose (PG)

Glucose is formed from carbohydrate digestion and conversion of glycogen to glucose by the liver. The two hormones that directly regulate blood glucose are glucagon and insulin. Glucagon accelerates glycogen breakdown in the liver and causes the blood glucose level to rise. Insulin increases cell membrane permeability to glucose, transports glucose into cells (for metabolism), stimulates glycogen formation, and reduces blood glucose levels. Driving insulin into the cells requires insulin and insulin receptors. For example, after a meal, the pancreas releases insulin for glucose metabolism, provided there are enough insulin receptors. Insulin binds to these receptors on the surface of target cells such as are found in fat and muscle. This opens the channels so that glucose can pass into cells, where it can be converted into energy. As cellular glucose metabolism occurs, blood glucose levels fall. Adrenocorticotropic hormone (ACTH), adrenocorticosteroids, epinephrine, and thyroxine also play key roles in glucose metabolism.

TABLE 6.2 Standard Panels

Panel Tests

Specimen Collection

Arthritis Panel (ARTH PN)

Uric acid, ESR, ANA (antinuclear antibody screen), rheumatoid factor

Two 7-mL red-topped tubes and 1 lavender-topped tube

Basic Metabolic Panel (BC MET)

Creatinine, CO2, chloride, glucose, potassium, sodium, BUN, calcium

1-mL unhemolyzed serum (red-topped tube or SST tube)

Comprehensive Metabolic Panel (CM MET)

Albumin, alkaline phosphatase, ALT, AST, total bilirubin, calcium, CO2, chloride, creatinine, glucose, potassium, sodium, total protein, BUN

1-mL unhemolyzed serum (red-topped tube or SST tube)

Electrolytes (LYTES)

CO2, chloride, potassium, sodium

1-mL unhemolyzed serum (red-topped tube or SST tube)

Hepatic Function Panel (HEPFUN)

ALT, albumin, alkaline phosphatase, AST, direct bilirubin and total bilirubin, total protein

1-mL unhemolyzed serum (red-topped tube or SST tube)

Acute Hepatitis Panel (ACUTE HEP)

Hepatitis A Ab-IgM, hepatitis B core Ab-IgM, hepatitis B surface antigen-IgM, hepatitis C Ab

7-mL red-topped tube

Lipid Panel (LIPID PN)

Cholesterol, HDL, triglycerides (LDL and CHOL/HDL ratio included, as calculated values)

2-mL serum (red-topped tube or SST tube)

Obstetric Panel (OB PN)

Type and Rh, antibody screen, RPR, rubella Ab-IgG, hepatitis B surface antigen

One 7-mL red-topped tube, one lavender-topped tube, and SST tube

Prenatal Screen (PRESCP)

Type and Rh, antibody screening and studies if indicated, RPR for syphilis, rubella Ab-IgG, hepatitis B surface antigen

One lavender-topped tube, one 7-mL red- topped tube, and SST tube

Ab, antibodies; Ab-IgG, antibodies for immunoglobulin G; Ab-IgM, antibodies for immunoglobulin M; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CHOL, cholesterol; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; RPR, rapid plasma reagin; SST, serum separator tube.

There are four categories of diabetes:

  • Type 1 (formerly known as insulin-dependent diabetes mellitus or juvenile-onset diabetes mellitus), due to destruction of pancreatic β cells which leads to deficiency in insulin, accounts for about 5% to 10% of individuals diagnosed with diabetes.

  • Type 2 (formerly known as non-insulin-dependent diabetes mellitus or adult-onset diabetes mellitus), a progressive form of insulin deficiency concomitant with insulin resistance, accounts for 90% to 95% of individuals diagnosed with diabetes.

  • Due to other causes (e.g., genetic defects [see Chapter 11 for genetic causes]), disease of the pancreas, drug- or chemical-induced, and so forth.

  • Gestational (i.e., diagnosed during pregnancy)

The American Diabetes Association (ADA) uses the term prediabetes, also known as impaired glucose tolerance or impaired fasting glucose. Individuals with prediabetes demonstrate higher levels of blood plasma glucose (PG) (100 to 125 mg/dL or 5.6 to 6.9 mmol/L) than normal subjects
(<100 mg/dL or <5.6 mmol/L) and, if left untreated, go on to develop type 2 diabetes within 10 years.

Diagnosing latent autoimmune diabetes in adults (LADA) early in the course of the disease process is critical because of the high risk for developing insulin dependency. It has been found that most patients with LADA have at least two of the following: age of onset <50 years, body mass index (BMI) <25 kg/m2, personal history of autoimmune disease, acute symptoms before diagnosis, or family history of autoimmune disease.

Fasting blood glucose is a vital component of diabetes management. The term random/casual is defined as any time of day without regard to time since the last meal. Fasting is defined as no caloric intake for at least 8 hours. Abnormal glucose metabolism may be caused by inability of pancreatic islet β cells to produce insulin, reduced numbers of insulin receptors, faulty intestinal glucose absorption, inability of the liver to metabolize glycogen, or altered levels of hormones (e.g., ACTH) that play a role in glucose metabolism.

In most cases, significantly elevated fasting plasma glucose (FPG) levels (i.e., >140 mg/dL or >7.77 mmol/L; hyperglycemia) are, in themselves, usually diagnostic of diabetes. However, mild, borderline cases may present with normal fasting glucose values. If diabetes is suspected, a glucose tolerance test (GTT) can confirm the diagnosis. Occasionally, other diseases may produce elevated PG levels; therefore, a comprehensive history, physical examination, and workup should be done before a definitive diagnosis of diabetes is established.

Normal Findings

FPG, adults: ≤100 mg/dL or ≤5.6 mmol/L

Fasting, children (2 to 18 years): 60 to 100 mg/dL or 3.3 to 5.6 mmol/L

Fasting, young children (0 to 2 years): 60 to 110 mg/dL or 3.3 to 6.1 mmol/L

Fasting, premature infants: 40 to 65 mg/dL or 2.2 to 3.6 mmol/L

Interfering Factors

  • Elevated glucose

    • Steroids, diuretics, other drugs (see Appendix E)

    • Pregnancy (a slight blood glucose elevation normally occurs)

    • Surgical procedures, anesthesia, and hospitalization in intensive care unit (ICU)

    • Obesity or sedentary lifestyle

    • Parenteral glucose administration (e.g., from total parenteral nutrition)

    • Intravenous (IV) glucose (recent or current)

    • Heavy smoking

    • The dawn phenomenon occurs in both non-insulin-dependent and insulin-dependent diabetes mellitus. There is an increase in blood glucose, typically between 4:00 a.m. and 8:00 a.m., due to counter-regulatory hormones, including growth hormone, cortisol, and glucagon.

  • Decreased glucose

    • Hematocrit >55%

    • Intense exercise

    • Toxic doses of aspirin, salicylates, and acetaminophen

    • Other drugs (see Appendix E), including ethanol, quinine, and haloperidol

• Hemoglobin A1c (HbA1c); Glycohemoglobin (G-Hb); Glycated Hemoglobin (GhB); Diabetic Control Index; Glycated Serum Protein (GSP)

Glycohemoglobin (G-Hb) is a normal, minor type of hemoglobin. Glycosylated hemoglobin is formed at a rate proportional to the average glucose concentration by a slow, nonenzymatic process within the red blood cells (RBCs) during their 120-day circulating life span. G-Hb is blood glucose bound
to hemoglobin. In the presence of hyperglycemia, an increase in G-Hb causes an increase in HbA1c (formed as a result of irreversible attachment of glucose to an amino acid in the β chain of the adult hemoglobin molecule). If the glucose concentration increases because of insulin deficiency, then glycosylation is irreversible.

Glycosylated hemoglobin values reflect average blood sugar levels for the 2- to 3-month period before the test. This test provides information for evaluating diabetic treatment modalities (every 3 months), is useful in determining treatment for juvenile-onset diabetes with acute ketoacidosis, and tracks control of blood glucose in milder cases of diabetes. It can be a valuable adjunct in determining which therapeutic choices and directions (e.g., oral antihypoglycemic agents, insulin, β-cell transplantation) will be most effective. A blood sample can be drawn at any time. The measurement is of particular value for specific groups of patients: diabetic children; diabetic patients in whom the renal threshold for glucose is abnormal; unstable type 1 diabetic patients (taking insulin) in whom blood sugar levels vary markedly from day to day; type 2 diabetic patients who become pregnant; and persons who, before their scheduled appointments, change their usual habits, dietary or otherwise, so that their metabolic control appears better than it actually is.

Normal Findings

Results are expressed as percentage of total hemoglobin. Values vary slightly by method and laboratory.

G-Hb: 4.0% to 7.0% or 0.04 to 0.07

HbA1c: 5.0% to 7.0% (100 to 170 mg/dL or 5.5 to 9.3 mmol/L)

Plasma blood glucose (mg/dL) = (HbA1c × 35.6) − 77.3

Plasma blood glucose (mmol/L) = (HbA1c × 1.98) − 4.29

Interfering Factors (varies by method)

  • Presence of HbF and H causes falsely elevated values.

  • Presence of HbS, C, E, D, G, and Lepore (autosomal recessive mutation resulting in a hemoglobinopathy) causes falsely decreased values.

• Gestational Diabetes Mellitus (GDM)

Glucose intolerance during pregnancy (gestational diabetes mellitus [GDM]) is associated with an increase in perinatal morbidity and mortality, especially in women who are aged >25 years, overweight, or hypertensive. In addition, more than one half of all pregnant patients with an abnormal GTT do not have any of the same risk factors. It is therefore recommended by the ADA that all pregnant women be screened for GDM as follows: Women with presence of risk factors should be screened at the first prenatal visit, and women with no known prior diabetes should be screened at 24 to 28 weeks.

A diabetes risk assessment should be done at the first prenatal visit. Screening for very-high-risk pregnancies should be done as soon as possible. At this stage, screening can be done using standard criteria. An OGTT is done to detect GDM and screen nonsymptomatic pregnant women. During pregnancy, abnormal carbohydrate metabolism is evaluated by screening all pregnant women at the first prenatal visit and then again at 24 to 28 weeks.

Two approaches may be followed for GDM screening at 24 to 28 weeks:

  • Two-step approach:

    • Perform initial screening by measuring plasma or serum glucose 1 hour after a 50-g load of 140 mg/dL identifies 80% of women with GDM, whereas the sensitivity is further increased to 90% by a threshold of 130 mg/dL.

    • Perform a diagnostic 100-g OGTT on a separate day in women who exceed the chosen threshold on 50-g screening.

  • One-step approach (may be preferred in clinics with high prevalence of GDM): Perform a diagnostic 100-g OGTT in all women to be tested at 24 to 28 weeks. The 100-g OGTT should be performed in the morning after an overnight fast of at least 8 hours.

Reference Values

To make a diagnosis of GDM, at least two of the following PG values must be found:

  • FPG >95 mg/dL (>5.3 mmol/L)

  • 1-hour >180 mg/dL (>10.0 mmol/L)

  • 2-hour >155 mg/dL (>8.6 mmol/L)

  • 3-hour >140 mg/dL (>7.8 mmol/L)

• Glucose Tolerance Test (GTT); Oral Glucose Tolerance Test (OGTT)

In a healthy individual, the insulin response to a large oral glucose dose is almost immediate. It peaks in 30 to 60 minutes and returns to normal levels within 3 hours when sufficient insulin is present to metabolize the glucose ingested at the beginning of the test. The test should be performed according to WHO guidelines using glucose load containing the equivalent of 75 g of anhydrous glucose dissolved in water or other solution.

If fasting and postload glucose test results are borderline, the GTT can support or rule out a diagnosis of diabetes mellitus; it can also be a part of a workup for unexplained hypertriglyceridemia, neuropathy, impotence, renal diseases, or retinopathy. This test may be ordered when there is sugar in the urine or when the fasting blood sugar level is significantly elevated. The GTT/OGTT should not be used as a screening test in nonpregnant adults or children.

Indications for Test

The GTT/OGTT is done on certain patients, with the following indications (few indications still meet wide acceptance):

  • Family history of diabetes

  • Obesity

  • Unexplained episodes of hypoglycemia

  • History of recurrent infections (boils and abscesses)

  • In women, history of delivery of large infants, stillbirths, neonatal death, premature labor, and spontaneous abortions

  • Transitory glycosuria or hyperglycemia during pregnancy, surgery, trauma, stress, MI, and ACTH administration

Normal Findings


Adults: 100 mg/dL or 5.6 mmol/L

120-Minute (2-Hour GTT Test) 2-Hour PG after 75-g Glucose Load

Adults: ≤200 mg/dL or ≤11.1 mmol/L

Adults: 140 to 199 mg/dL (7.8 to 11.0 mmol/L), IGT

Interfering Factors

  • Smoking increases glucose levels.

  • Altered diets (e.g., weight reduction) before testing can diminish carbohydrate tolerance and suggest “false diabetes.”

  • Glucose levels normally tend to increase with aging.

  • Prolonged oral contraceptive use causes significantly higher glucose levels in the second hour or in later blood specimens.

  • Infectious diseases, illnesses, and operative procedures affect glucose tolerance. Two weeks of recovery should be allowed before performing the test.

  • Certain drugs impair glucose tolerance levels (this list is not all inclusive; see Appendix E for other drugs):

    If possible, these drugs should be discontinued for at least 3 days before testing. Check with the healthcare provider for specific orders.

    • Insulin

    • Oral hypoglycemics

    • Large doses of salicylates, anti-inflammatory drugs

    • Thiazide diuretics

    • Oral contraceptives

    • Corticosteroids

    • Estrogens

    • Heparin

    • Nicotinic acid

    • Phenothiazines

    • Lithium

    • Metyrapone (Metopirone)

  • Prolonged bed rest influences GTT results. If possible, the patient should be ambulatory. A GTT in a hospitalized patient has limited value.

• Lactose Tolerance; Breath Hydrogen Test

Lactose intolerance often begins in infancy, with symptoms of diarrhea, vomiting, failure to thrive, and malabsorption. The patient becomes asymptomatic when lactose is removed from the diet. This syndrome is caused by a deficiency of sugar-splitting enzymes (lactase) in the intestinal tract.

This test is actually a GTT done to diagnose intestinal disaccharidase (lactase) deficiency. Glucose is measured, and it is the increase or lack of increase over the fasting specimen that is used for the interpretation. Breath samples reveal increased hydrogen levels, which are caused by lactose buildup in the intestinal tract. Colonic bacteria metabolize the lactose and produce hydrogen gas.

Normal Findings

Change in glucose from normal value >30 mg/dL or >1.7 mmol/L

Inconclusive: 20 to 30 mg/dL or 1.1 to 1.7 mmol/L

Abnormal: <20 mg/dL or <1.1 mmol/L

Hydrogen (breath):

Fasting: <5 ppm or <5 × 10-6

After lactose ingestion: <12 ppm or <12 × 10-6 increase from fasting level

• Related Tests That Influence Glucose Metabolism


C-peptide is formed during the conversion of proinsulin to insulin. Proinsulin is cleaved (holds α- and β-insulin chains together in the proinsulin molecule) into insulin and biologically inactive C-peptide. C-peptide assay provides distinction between exogenous and endogenous circulating insulin.

The main use of C-peptide is to evaluate hypoglycemia. C-peptide levels provide reliable indicators for pancreatic and secretory functions and insulin secretions. In a patient with type 1 diabetes mellitus, C-peptide measurements can be an index of insulin production and mark endogenous β-cell activity. C-peptide levels can also be used to confirm suspected surreptitious insulin injections (i.e., factitious hypoglycemia). Findings in these patients reveal that insulin levels are usually high, insulin antibodies may be high, but C-peptide levels are low or undetectable. This test also monitors the patient’s recovery after excision of an insulinoma. Rising C-peptide levels suggest insulinoma tumor recurrence or metastases.

Normal Findings

Fasting: 0.51 to 2.72 ng/mL or 0.17 to 0.90 mmol/L

Values vary with laboratory.

Interfering Factors

Increased C-Peptide

  • Renal failure

  • Ingestion of sulfonylurea


Glucagon is a peptide hormone that originates in the α cells of the pancreatic islets of Langerhans. This hormone promotes glucose production in the liver. Normally, glucagon is a counterbalance to insulin. Glucagon provides a sensitive, coordinated control mechanism for glucose production and storage. For example, low blood glucose levels cause glucagon to stimulate glucose release into the bloodstream, whereas elevated blood glucose levels reduce the amount of circulating glucagon to about 50% of that found in the fasting state. The kidneys also affect glucagon metabolism. Elevated fasting glucagon levels in the presence of renal failure return to normal levels following successful renal transplantation. Abnormally high glucagon levels drop toward normal once insulin therapy effectively controls diabetes. However, when compared with a healthy person, glucagon secretion in the person with diabetes does not decrease after eating carbohydrates. Moreover, in healthy persons, arginine infusion causes increased glucagon secretion.

This test measures glucagon production and metabolism. A glucagon deficiency reflects pancreatic tissue loss. Failure of glucagon levels to rise during arginine infusion confirms glucagon deficiency. Hyperglucagonemia (i.e., elevated glucagon levels) occurs in diabetes, acute pancreatitis, and situations in which catecholamine secretion is stimulated (e.g., pheochromocytoma, infection).

Normal Findings

Adults: 20 to 100 pg/mL or 20 to 100 ng/L

Children: 0 to 148 pg/mL or 0 to 148 ng/L

Newborns: 0 to 1750 pg/mL or 0 to 1750 ng/L

Normal ranges vary with different laboratories.


Insulin, a hormone produced by the pancreatic β cells of the islets of Langerhans, regulates carbohydrate metabolism together with contributions from the liver, adipose tissue, and other target cells. Insulin is responsible for maintaining blood glucose levels at a constant level within a defined range. The rate of insulin secretion is primarily regulated by the level of blood glucose perfusing the pancreas; however, it can also be affected by hormones, the autonomic nervous system, and nutritional status.

Insulin levels are valuable for establishing the presence of an insulinoma (i.e., tumor of the islets of Langerhans). This test is also used for investigating the causes of fasting hypoglycemic states and neoplasm differentiation. The insulin study can be done in conjunction with a GTT or FBG test or a FPG test.

Normal Findings


Adults: 0 to 35 µIU/mL or 0 to 243 pmol/L

Children: 0 to 10 µIU/mL or 0 to 69 pmol/L


Adults: 0 to 17 µIU/mL or 0 to 118 pmol/L

Children (prepubertal): 0 to 13 µIU/mL or 0 to 90 pmol/L

Interfering Factors

  • Surreptitious insulin or oral hypoglycemic agent ingestion or injection causes elevated insulin levels (with low C-peptide values).

  • Oral contraceptives and other drugs cause falsely elevated values.

  • Recently administered radioisotopes affect test results.

  • In the second to third trimester of pregnancy, there is a relative insulin resistance with a progressive decrease of PG and immunoreactive insulin.


• Ammonia (NH3)

Ammonia, an end product of protein metabolism, is formed by bacteria acting on intestinal proteins together with glutamine hydrolysis in the kidneys. The liver normally removes most of this ammonia through the portal vein circulation and converts the ammonia to urea. Because any appreciable level of ammonia in the blood affects the body’s acid-base balance and brain function, its removal from the body is essential. The liver accomplishes this by synthesizing urea so that it can be excreted by the kidneys.

Blood ammonia levels are used to diagnose Reye’s syndrome, to evaluate metabolism, and to determine the progress of severe liver disease and its response to treatment. Blood ammonia measurements are useful in monitoring patients on hyperalimentation therapy.

Normal Findings

When Measured as NH3

Adults: 15 to 60 µg/dL or 11 to 35 µmol/L

10 days to 2 years: 70 to 135 µg/dL or 41 to 80 µmol/L

Birth to 10 days: 170 to 340 µg/dL or 100 to 200 µmol/L

When Measured as N

Adults: 15 to 45 µg/dL or 11 to 32 µmol/L

>1 month of age: 30 to 70 µg/dL or 21 to 50 µmol/L

Birth to 14 days: 80 to 130 µg/dL or 57 to 93 µmol/L

Values test somewhat higher in capillary blood samples. Values can vary with testing method used.

Interfering Factors

  • Ammonia levels vary with protein intake and many drugs.

  • Exercise may cause an increase in ammonia levels.

  • Ammonia levels may be increased by use of a tight tourniquet or by tightly clenching the fist while samples are drawn.

  • Ammonia levels can rise rapidly in the blood tubes.

  • Hemolyzed blood gives falsely elevated levels.

• Bilirubin

Bilirubin results from the breakdown of hemoglobin in the RBCs and is a byproduct of hemolysis (i.e., RBC destruction). It is produced by the reticuloendothelial system. Removed from the body by the liver, which excretes it into the bile, bilirubin gives the bile its major pigmentation. Usually, a small amount of bilirubin is found in the serum. A rise in serum bilirubin levels occurs when there is excessive destruction of RBCs or when the liver is unable to excrete the normal amounts of bilirubin produced.

There are two major forms of bilirubin in the body: conjugated bilirubin and unconjugated bilirubin, sometimes termed direct and indirect bilirubin, respectively. Unconjugated bilirubin circulates freely in the blood until it reaches the liver, where it is conjugated with glucuronide transferase and then excreted into the bile. An increase in unconjugated bilirubin is more frequently associated with increased destruction of RBCs (hemolysis) as well as in neonatal jaundice. An increase in freeflowing bilirubin is more likely seen in dysfunction or blockage of the liver. A routine examination measures only the total bilirubin. A normal level of total bilirubin rules out any significant impairment of the excretory function of the liver or excessive hemolysis of red cells. Only when total bilirubin levels are elevated will there be a call for differentiation of the bilirubin levels by conjugated and unconjugated types.

The measurement of bilirubin allows evaluation of liver function and hemolytic anemias. For infants younger than 15 days of age, a neonatal, or more specifically an unconjugated, bilirubin measurement may be necessary.

Normal Findings


Total: 0.3 to 1.0 mg/dL or 5 to 17 µmol/L

Conjugated (direct): 0.0 to 0.2 mg/dL or 0.0 to 3.4 µmol/L

Interfering Factors

  • A 1-hour exposure of the specimen to sunlight or high-intensity artificial light at room temperature will decrease the bilirubin content.

  • No contrast media should be administered 24 hours before measurement; a high-fat meal may also cause decreased bilirubin levels by interfering with the chemical reactions.

  • Air bubbles and shaking of the specimen may cause decreased bilirubin levels.

  • Certain foods (e.g., carrots, yams) and drugs (see Appendix E) increase the yellow hue in the serum and can falsely increase bilirubin levels when tests are done using certain methods (e.g., spectrophotometry).

  • Prolonged fasting and anorexia raises the bilirubin level.

  • Nicotinic acid increases unconjugated bilirubin.

• Neonatal Bilirubin, Total and Fractionated (“Baby Bili”)

In newborns, signs of jaundice may indicate hemolytic anemia or congenital icterus. If bilirubin levels reach a critical point in the infant, damage to the CNS may occur in a condition known as kernicterus. Therefore, in these infants, the level of bilirubin is the deciding factor in whether or not to perform an exchange transfusion.

Neonatal bilirubin is used to monitor erythroblastosis fetalis (hemolytic disease of the newborn), which usually causes jaundice in the first 2 days of life. All other causes of neonatal jaundice, including physiologic jaundice, hematoma or hemorrhage, liver disease, and biliary disease, should also be monitored. Normal, full-term neonates experience a normal, neonatal, physiologic, transient hyperbilirubinemia by the 3rd day of life, which rapidly falls by the 5th to 10th day of life.

Normal Findings

Newborns (0 to 7 days)

Interpretation of newborn bilirubin concentrations should be done using a nomogram comparing the age of the infant in hours to the bilirubin concentration. This nomogram provides the risk for a subsequent bilirubin result to be consistent with hyperbilirubinemia. See Figure 6.2.

Cord Blood Total

Full term: <2.5 mg/dL or <43 µmol/L

Premature: <2.9 mg/dL or <50 µmol/L

FIGURE 6.2. Nomogram for designation of risk in 2840 well newborns at 36 or more weeks’ gestational age with birth weight of 2000 g or more, or at 35 or more weeks’ gestational age and birth weight of 2500 g or more, based on the hour-specific serum bilirubin values. The serum bilirubin level was obtained before discharge, and the zone in which the value fell predicted the likelihood of a subsequent bilirubin level exceeding the 95th percentile (high-risk zone). (Used with permission from Bhutani VK, Johnson L, Sivieri EM: Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 103:6-14, 1999. Reprinted from American Academy of Pediatrics: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 114:297-316, 2004.)

See Table 6.4 for a comparison of premature and full-term infants.

• Blood Urea Nitrogen (BUN, Urea Nitrogen)

Urea forms in the liver and, along with CO2, constitutes the final product of protein metabolism. The amount of excreted urea varies directly with dietary protein intake, increased excretion in fever, diabetes, and increased adrenal gland activity.

The test for blood urea nitrogen (BUN), which measures the nitrogen portion of urea, is used as an index of glomerular function in the production and excretion of urea. Rapid protein catabolism and impairment of kidney function will result in an elevated BUN level. The rate at which the BUN level rises is influenced by the degree of tissue necrosis, protein catabolism, and the rate at which the kidneys excrete the urea nitrogen. A markedly increased BUN is conclusive evidence of severe impaired glomerular function. In chronic renal disease, the BUN level correlates better with symptoms of uremia than does the serum creatinine.

Normal Findings

Adults: 6 to 20 mg/dL or 2.1 to 7.1 mmol/L

Older adults (>60 years): 8 to 23 mg/dL or 2.9 to 8.2 mmol/L

Children: 5 to 18 mg/dL or 1.8 to 6.4 mmol/L

Interfering Factors

  • A combination of a low-protein and high-carbohydrate diet can cause a decreased BUN level.

  • The BUN is normally lower in children and women because they have less muscle mass than adult men.

  • Decreased BUN values normally occur in late pregnancy because of increased plasma volume (physiologic hydremia).

  • Older persons may have an increased BUN when their kidneys are not able to concentrate urine adequately.

  • IV feedings only may result in overhydration and decreased BUN levels.

  • Many drugs may cause increased or decreased BUN levels.

• Albumin

Albumin (along with total protein) is a part of a diverse microenvironment. Its primary function is the maintenance of colloidal osmotic pressure (COP) in the vascular and extravascular spaces (e.g., urine, cerebrospinal fluid, amniotic fluid). Albumin is a source of nutrition and a part of a complex buffer system. It is a “negative” acute-phase reactant. It decreases in response to acute inflammatory infectious processes.

Albumin is used to evaluate nutritional status, albumin loss in acute illness, liver disease and renal disease with proteinuria, hemorrhage, burns, exudates or leaks in the GI tract, and other chronic diseases. Hypoalbuminuria is an independent risk factor for older adults for mortality—admission serum albumin in geriatric patients is a predictor of outcome.

Normal Findings

Using Bromcresol Green Dye

Children: 3.8 to 5.4 g/dL or 38 to 54 g/L

Adults: 3.5 to 5.2 g/dL or 35 to 52 g/L

Older than age 40 years and in persons living in subtropics and tropics (secondary to parasitic infections), level slowly declines.

Interfering Factors

Albumin is decreased in:

  • Pregnancy (last trimester, owing to increased plasma volume)

  • Oral birth control (estrogens) and other drugs (see Appendix E)

  • Prolonged bed rest

  • IV fluids, rapid hydration, overhydration

• Prealbumin (PAB)

The proteins most often used in nutrition assessment include albumin, prealbumin (PAB), C-reactive protein, and retinol-binding protein. When used in combination, they can very accurately reflect a subclinical deficit and assess response to restorative therapy.

For years, albumin was the widely accepted marker for malnutrition. However, mounting evidence points to PAB as the better choice. Because albumin has a half-life of 21 days, it is slow to respond to a patient’s recent increase in nutrients and, therefore, is not a good indicator of recent changes in protein levels. In contrast, PAB responds more rapidly and gives a timelier picture of a change in dietary status. Because of its short half-life (2 days), PAB responds quickly to a decrease in nutritional intake and nutritional restoration. It reflects the current nutritional status within a patient’s body, not the status from 3 weeks ago.

Normal Findings

19 to 38 mg/dL (190 to 380 mg/L) by nephelometry

• Cholinesterase, Serum (Pseudocholinesterase); Cholinesterase, Red Blood Cell (Acetylcholinesterase)

The cholinesterase of serum is referred to as pseudocholinesterase to distinguish it from the true cholinesterase of the RBC. Both of these enzymes act on acetylcholine and other cholinesters. Alkylphosphates are potent inhibitors of both serum and RBC cholinesterase.

Patients who are homozygous for the atypical gene that controls serum cholinesterase activity have low levels of cholinesterase that are not inhibited by dibucaine. Persons with normal serum cholinesterase activity show 70% to 90% inhibition by dibucaine (an amino amide). The red cell (true cholinesterase) enzyme is specific for the substrate acetylcholine.

These are two separate tests. The primary use of serum cholinesterase measurement (pseudocholinesterase) is to monitor the effect of muscle relaxants (e.g., succinylcholine), which are used in surgery. Patients for whom suxamethonium anesthesia is planned should be tested using the dibucaine inhibition test for the presence of atypical cholinesterase variants that are incapable of hydrolyzing this widely used muscle relaxant.

The RBC cholinesterase test is used when poisoning by pesticides such as parathion or malathion is suspected. Severe insecticide poisoning causes headaches, visual distortions, nausea, vomiting, pulmonary edema, confusion, convulsions, respiratory paralysis, and coma.

Normal Findings

Acetylcholinesterase: 7 ± 3.8 (SD) U/g Hb or 2 ± 0.2 mU/mol Hb

Serum cholinesterase: 4.9 to 11.9 U/mL or 4.9 to 11.9 kU/L

Dibucaine inhibition: 79% to 84% or 0.79 to 0.84

Fluoride inhibition: 58% to 64% or 0.58 to 0.64

RBC cholinesterase: 30 to 40 U/g Hb

Values vary with substrate and method. These are two different tests. Values are low at birth and for the first 6 months of life.

• Creatinine and Estimated Glomerular Filtration Rate

Creatinine is a byproduct in the breakdown of muscle creatine phosphate resulting from energy metabolism. It is produced at a constant rate depending on the muscle mass of the person and is removed from the body by the kidneys. Production of creatinine is constant as long as muscle mass remains constant. A disorder of kidney function reduces excretion of creatinine, resulting in increased blood creatinine levels. Thus, creatinine levels give an approximation of the glomerular filtration rate (GFR).
An estimated GFR (eGFR) can be calculated using the Modification of Diet in Renal Disease (MDRD) study equation, which requires a serum creatinine result, gender, age, and race.

eGFR (mL/min/1.73 m2) = 186 × (Scr)-1.154 × (age)-0.203 × (0.742 if female) × (1.210 if African American) (conventional units)

Many labs are reporting the eGFR with the creatinine result.

This test diagnoses impaired renal function. It is a more specific and sensitive indicator of kidney disease than BUN, although in chronic renal disease, both BUN and creatinine are ordered to evaluate renal problems because the BUN-to-creatinine ratio provides more information.

Normal Findings

Adult men: 0.9 to 1.3 mg/dL or 80 to 115 µmol/L

Adult women: 0.6 to 1.1 mg/dL or 53 to 97 µmol/L

Children (3 to 18 years): 0.5 to 1.0 mg/dL or 44 to 88 µmol/L

Young children (0 to 3 years): 0.3 to 0.7 mg/dL or 27 to 62 µmol/L

BUN-to-creatinine ratio: 10:1 to 20:1

Interfering Factors

  • High levels of ascorbic acid and cephalosporin antibiotics can cause a falsely increased creatinine level; these agents also interfere with the BUN-to-creatinine ratio.

  • Drugs that influence kidney function plus other medications can cause a change in the blood creatinine level (see Appendix E).

  • A diet high in meat can cause increased creatinine levels.

  • Creatinine is falsely decreased by bilirubin, glucose, histidine, and quinidine compounds.

  • Ketoacidosis may increase serum creatinine substantially.

• Cystatin C

Cystatin C is a low-molecular-weight protein inhibitor found in blood serum and is an indicator of glomerular filtration in kidney function.

This test is done to assess GFR. Cystatin C may be a more reliable indicator of renal function than creatinine. Cystatin C is independent of muscle mass and age and is not reabsorbed in the kidney. Measurements of cystatin C are not as common as creatinine measurements.

Normal Findings

Young adults: <0.70 mg/mL (<2.9 µmol/mL)

Older adults (>60 years): <0.85 mg/mL (<3.5 µmol/mL)

• Uric Acid

Uric acid is formed from the breakdown of nucleonic acids and is an end product of purine metabolism. Uric acid is transported by the plasma from the liver to the kidney, where it is filtered and where about 70% is excreted. The remainder of uric acid is excreted into the GI tract and degraded. A lack of the enzyme uricase allows this poorly soluble substance to accumulate in body fluids.

The basis for this test is that an overproduction of uric acids occurs when there is excessive cell breakdown and catabolism of nucleonic acids (as in gout), excessive production and destruction of cells (as in leukemia), or an inability to excrete the substance produced (as in renal failure). Measurement of uric acid is used most commonly in the evaluation of renal failure, gout, and leukemia. In hospitalized patients, renal failure is the most common cause of elevated uric acid levels, and gout is the least common cause.

Normal Findings

Men: 3.4 to 7.0 mg/dL or 202 to 416 µmol/L

Women: 2.4 to 6.0 mg/dL or 143 to 357 µmol/L

Children: 2.0 to 5.5 mg/dL or 119 to 327 µmol/L

Interfering Factors

  • Stress and strenuous exercise will falsely elevate uric acid.

  • Many drugs cause increase or decrease of uric acid (see Appendix E).

  • Purine-rich diet (e.g., liver, kidney, sweetbreads) increases uric acid levels.

  • High levels of aspirin decrease uric acid levels.

  • Low purine intake, coffee, and tea decrease uric acid levels.

• Lead (Pb)

Lead is absorbed into the body through both the respiratory and GI tracts. It also moves transplacentally to the fetus. Absorption through these different routes varies and is affected by age, nutritional status, particle size, and chemical form of the lead. Absorption is inversely proportional to particle size; this factor makes lead-bearing dust important. Adults absorb 6% to 10% of dietary lead and retain very little of it; however, children from birth to 2 years of age have been shown to absorb 40% to 50% and to retain 20% to 25% of dietary lead. Spontaneous excretion of lead in urine by infants and young toddlers is normally about 1 µg/kg/24 hours, which may increase somewhat in cases of acute poisoning. Dietary intake of lead is <1 µg/kg of lead, which provides a margin of safety in the sense that a child goes into positive lead balance when intake exceeds 5 µg/kg of body weight. Early symptoms of lead poisoning include anorexia, apathy or irritability, fatigue, and anemia. Toxic effects include GI distress, joint pain, colic, headache, stupor, convulsions, and coma. Another, less sensitive test that may be used to evaluate lead intoxication is free erythrocyte protoporphyrin. However, a blood lead assay is the definitive test.

The blood lead assay is used to screen adults and children for lead poisoning (plumbism). In adults, high levels are caused mainly by industrial exposure to lead-based paints, gasoline, and ceramics. Highrisk children usually are ages 3 to 12 years and live in or visit old or dilapidated housing with lead-based paint. A single paint chip can contain as much as 10,000 µg of lead.

Normal Findings


0 to 10 µg/dL or 0 to 0.48 µmol/L

24-hour urine: <80 µg/L or <0.39 µmol/L


Adult: <155 µg/g dry weight or <0.75 µmol/g dry weight

Child: <70 µg/g dry weight or <0.34 µmol/g dry weight

Interfering Factors

  • Failing to use lead-free Vacutainer tubes invalidates results.

  • An elevated level should be confirmed with a second specimen to ensure that the first specimen was not contaminated.

TABLE 6.6 U.S. Centers for Disease Control and Prevention Classifications of Blood Lead Levels


Blood Leada



<10 µg/dL or 0.48 µmol/L

Not lead poisoned


10-14 µg/dL or 0.48-0.68 µmol/L

Rescreen frequently and consider prevention activities


15-19 µg/dL or 0.72-0.92 µmol/L

Institute nutritional and educational interventions


20-44 µg/dL or 0.97-2.1 µmol/L

Evaluate environment and consider chelation therapy


45-69 µg/dL or 2.17-3.33 µmol/L

Institute environmental intervention and chelation therapy


>69 µg/dL or >3.33 µmol/L

Medical emergency

a Owing to possible contamination during collection, elevated levels should be confirmed with a second specimen before therapy is instituted.

TABLE 6.7 Effects of Increased Blood Lead Levels on Children

Blood Lead Level

Effects in Children

>10 µg/dL or >0.48 µmol/L

Reduced IQ, hearing, and growth

>20 µg/dL or >0.97 µmol/L

Impaired nerve function

>30 µg/dL or >1.45 µmol/L

Reduced vitamin D metabolism

>40 µg/dL or >1.93 µmol/L

Damage to blood-forming system

>50 µg/dL or >2.41 µmol/L

Severe stomach cramps

>60 µg/dL or >2.90 µmol/L

Severe anemia

>80 µg/dL or >3.86 µmol/L

Severe brain damage

>125 µg/dL or >6.04 µmol/L


From the President’s Task Force on Environmental Health Risks and Safety Risks to Children: Federal strategy to eliminate childhood lead poisoning, March 2002 (Online). Available at

• Osteocalcin (Bone G1a Protein)

Osteocalcin, also referred to as bone G1a protein, is a protein produced by the osteoblasts and dentin and has a function in bone mineralization and calcium ion homeostasis. A small amount of osteocalcin, an integral part in bone formation, is released into the blood and therefore can serve as a marker for recent bone formation. Osteocalcin levels are influenced by age (rapid growth) and gender (males somewhat higher) and are increased during menopause. This test is used to screen for osteoporosis in postmenopausal women, assess risk for fractures, and determine eligibility for treatment for osteoporosis. The U.S. Preventive Task Force recommends screening for osteoporosis in women over the age of 65 years, and in women under age 65 years who have a risk of fracture that is equal to or greater than that of a 65-year-old white woman. Screening is not recommended for men. Osteocalcin is a specific marker for bone formation and is regulated by 1,25-dehydroxyvitamin D.

Normal Findings

Osteocalcin: 8.1 ± 4.6 µg/L or 1.4 ± 0.8 nmol/L

Carboxylated osteocalcin: 9.9 ± 0.5 µg/L or 1.7 ± 0.1 nmol/L

Undercarboxylated osteocalcin: 3.7 ± 1.0 µg/L or 0.6 ± 0.2 nmol/L

Normal Using RIA

Adult male: 3.0 to 13.0 ng/mL or 3.0 to 13.0 µg/L

Premenopausal female: 0.4 to 8.2 ng/mL or 0.4 to 8.2 µg/L

Postmenopausal female: 1.5 to 11.0 ng/mL or 1.5 to 11.0 µg/L

There is a diurnal variation, a peak during the night and a decrease in the morning.

Interfering Factors

  • Increased during bed rest and no increase in bone formation.

  • Increased with impaired renal function and no increase in bone formation.


• Androstenedione

Androstenedione is one of the major androgens produced by the ovaries in females and, to a lesser extent, in the adrenal gland in both genders. This hormone is converted to estrogens by hepatic enzymes. Levels rise sharply after puberty and peak at age 20 years.

This hormone measurement is helpful in the evaluation of conditions characterized by hirsutism (excessive hair growth in women) and virilization. In females, there is poor correlation of plasma levels with clinical severity.

Normal Findings

Newborns: 20 to 290 ng/dL or 0.7 to 10.1 mmol/L

Prepuberty: 8 to 50 ng/dL or 0.3 to 1.7 mmol/L

Women: 75 to 205 ng/dL or 2.6 to 7.2 mmol/L

Men: 85 to 275 ng/dL or 3.0 to 9.6 mmol/L

Postmenopausal women: <10 ng/dL or 0.35 mmol/L (abrupt decline at menopause)

Different laboratories may have variation in reference values.

• Aldosterone

Aldosterone is a mineralocorticoid hormone produced in the adrenal zona glomerulosa under complex control by the renin-angiotensin system. Its action is on the renal distal tubule, where it increases resorption of sodium and water at the expense of increased potassium excretion.

This test is useful in detecting primary or secondary aldosteronism (also called hyperaldosteronism). Patients with primary aldosteronism characteristically have hypertension, muscular pains and cramps, weakness, tetany, paralysis, and polyuria. This test is also used to evaluate causes of hypertension or low blood potassium levels and to check for adrenal tumors.

Normal Findings

In Upright Position

Adults: 7 to 30 ng/dL or 0.19 to 0.83 nmol/L

Adolescents: 4 to 48 ng/dL or 0.11 to 1.33 nmol/L

Children: 5 to 80 mg/dL or 0.14 to 2.22 nmol/L

In Supine Position

Adults: 3 to 16 ng/dL or 0.08 to 0.44 nmol/L

Adolescents: 2 to 22 ng/dL or 0.06 to 0.61 nmol/L

Children: 3 to 35 mg/dL or 0.08 to 0.97 nmol/L

Low-sodium diet: values 3 to 5 times higher

Interfering Factors

  • Values are increased by upright posture.

  • Recently administered radioactive medications affect test outcomes.

  • Heparin therapy causes levels to fall. See Appendix E for drugs that increase or decrease levels.

  • Thermal stress, late pregnancy, and starvation cause levels to rise.

  • Aldosterone levels decrease with age.

  • Many drugs—diuretics, antihypertensives, progestogens, estrogens—and licorice should be terminated 2 to 4 weeks before test.

• Antidiuretic Hormone (ADH); Arginine Vasopressin Hormone

Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Its major physiologic function is regulation of body water. In the dehydrated (hyperosmolar) state, ADH release results in decreased urine excretion and conservation of water. ADH increases blood pressure.

When ADH activity is present, small volumes of concentrated urine are excreted. When ADH is absent, large amounts of diluted urine are produced. Higher secretion occurs at night, with erect posture, and with pain, stress, or exercise. Measurement of the level of ADH is useful in the differential diagnosis of polyuric and hyponatremic states. ADH testing aids in diagnosis of urine concentration disorders, especially diabetes insipidus, SIADH, psychogenic water intoxication, and syndromes of ectopic ADH production.

Normal Findings

<2.5 pg/mL or <2.3 pmol/L

Sep 25, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Chemistry Studies

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