August 11, 2005
Interpreting Laboratory Values In Older Adults
Results of common laboratory tests must be interpreted with care in older adults. Laboratory results that vary with age are presented, along with possible causes and interpretations of results.
John Doe, 83 years old, comes to the clinic complaining of increasing fatigue and weakness. His past medical history includes diabetes mellitus, chronic anemia, and hypertension. The 5'10" man is thin (148 pounds) with small muscle mass. His skin color is pale pink. A battery of diagnostic tests reveals the following: hemoglobin 11.2 g/dL, hematocrit 40%, white blood cells 5,000/ml, fasting blood sugar 183 mg/dL, blood urea nitrogen 30 mg/dL, serum creatinine 1.9 mg/dL, and serum albumin 2.3 g/dL. The nurse is uncertain which laboratory values are significant in considering Mr. Doe's care plan.This case illustrates the difficulty in interpreting laboratory values for older adults, which is a complex task with varied opinions about what is normal. Multiple confounding factors make interpretation and use of laboratory results in older patients challenging. Some of the factors include (a) physiologic changes associated with aging, (b) the high prevalence of chronic conditions, (c) changes in nutrition and fluid consumption, (d) lifestyle changes, and (e) pharmacologie regimes (Brigden & Heathcote, 2000). Laboratory test results also may be affected by many factors other than aging. Influencing factors may include gender, body mass, alcohol intake, diet, and stress (Fischbach, 2004). Technical factors such as collection site, collection time, tourniquet application, and specimen transportation also can affect results but usually can be controlled by following standardized laboratory procedures (Brigden & Heathcote, 2000).
Results of diagnostic testing in older adults may have different meanings from the results found in younger individuals. Nurses should recognize that no general trend exists for the direction of change in laboratory values for older adults. For some tests, older adults have higher than normal values and for others, lower values; some remain unchanged. Changes in laboratory values can be classified in three general groups: (a) those that change with aging; (b) those that do not change with aging; and (c) those for which it is unclear whether aging, disease, or both influence the values (Tripp, 2000). Common laboratory tests with interpretations for older adults are presented.
Interpreting Reference Ranges
The accepted, normal ranges of values typically reported may not be applicable for older adults. Reference ranges may be more appropriate. Normal ranges are obtained by determining the mean of a random sample of healthy individuals, usually ages 20 to 40 years, in order to identify two standard deviations on either side of the mean. The concept of normal range, however, is not useful in determining age-related norms for older adults (Luggen, 2004).
Reference ranges or reference values are preferred concepts. Reference ranges or reference values are those intervals within which 95% of the values fall for a specific population (Lab Tests Online, 2001). For example, geriatric reference ranges are those intervals within which 95% of values for persons over 70 years of age would fall. It must be cautioned, however, that some researchers recommend not using reference ranges for laboratory test parameters pertaining to older adults because it is difficult to differentiate whether results are a sign of a disease or are related to normal aging (Luggen, 2004). However, reference ranges are useful in some situations. The use of reference ranges allows for recognition of the special needs of the population in question. Reference ranges are calculated not just for older adults, but also for neonates (especially low-birthrate infants), adolescents, and pregnant women. In addition, specific reference ranges are known for tests for other special populations (for example, serum erythropoietin in adult athletes such as marathon runners).
Laboratory values falling outside the normal ranges may indicate benign or pathologic conditions in the older adult (Fischbach, 2004). Values within the expected normal reference ranges, however, may also indicate new or progressing pathologic conditions in certain older adults. Nurses working with older adults should consider the total assessment rather than simply relying on laboratory diagnostic testing. For example, goals of management of diabetes should be individualized. The principal goal would be to enhance quality of life without undue risk of hypoglycemia. It usually is best to achieve fasting blood glucose levels of less than 140 mg/dl. However, in the frail elderly, it is best to avoid fasting or bedtime plasma glucose levels of less than 100 mg/dl if the patient is on insulin or sulfonylurea treatment (Reed & Mooradian, 1998).
Serum creatinine is a second example of a laboratory test in which results may be within the specified reference range and yet indicate pathology for the older adult. Creatinine is a product of creatine phosphate, used in skeletal muscle contraction. Endogenous creatinine production is constant as long as muscle mass remains constant (Pagana & Pagana, 2002). The mechanisms that regulate the older individual's serum creatinine levels within the accepted reference range tend to overestimate renal functioning as a measure of glomerular filtration rate. Serum creatinine and blood urea nitrogen (BUN) levels in the high-normal category may represent significant renal dysfunction in the older adult who has inadequate protein intake (Daniels, 2002).
Specific Laboratory Tests
Hemoglobin (HGB). While the results of studies of the effects of aging on the hematologic system vary (Brigden & Heathcote, 2000; Nilsson-Ehle, Jagenburg, Landahl, & Swanborg, 2000), research does indicate that older individuals may have changes in hemoglobin and erythrocyte synthesis caused by changes in iron and vitamin B12 absorption (Giddens, 2004). Impaired erythrocyte production, blood loss, increased erythrocyte destruction, or a combination of conditions have also been identified as causes for lowered hemoglobin (Giddens, 2004). Kee (2002) defines hemoglobin as abnormal if less than 13.5 gm/dl for males and 12.0 gm/dl for females. Recent studies with older adults, however, suggest lower levels may be acceptable. The currently reported lowest acceptable value for older adults is 11.5 gm/dl for males and 11.0 gm/dl for females (Brigden & Heathcote, 2000) (see Table 1).
Hemoglobin may be lower in older adults due either to normal aging changes or illnesses such as anemia. Manson and McCance (2004) identify impaired erythrocyte production, blood loss, increased erythrocyte destruction, or a combination of conditions as causes for anemia. Most instances of anemia are associated with chronic conditions such as renal insufficiency or gastric bleeding (Giddens, 2004). Anemia may be a serious condition because it places the older individual at greater risk for circulatory and oxygenation problems (Tripp, 2000). A reduction of hemoglobin can result in a decrease in oxygen content and an increase in fatigue. Signs of anemia may not be noticed if the anemia is mild, but some individuals may present with shortness of breath, fatigue, and paresthesia (Manson & McCance, 2004). A combination of vague symptoms and an unclear clinical picture may lead the health care provider to attribute the symptoms to "old age" and not to a treatable condition.
Hematocrit (HCT). Changes in hematocrit may reflect fluid and/or nutritional status in the older adult (Fischbach, 2004; Giddens, 2004). An increase in the hematocrit may signal volume depletion, while a decrease may be a result of conditions accompanied by fluid overload or dietary deficiencies. Hematocrit, the percentage of total blood volume that represents erythrocytes, may be normal if values are 30% to 45% for older males and 36% to 65% for older females (Desai & Isa-Pratt, 2002) (see Table 1).
Geriatric Laboratory Values and Interpretations of Hematology
White blood cells (WBC). Whether total leukocyte count is affected by aging is controversial. However, there are definite changes in that the T cells are less responsive to infection (Fulop et al., 2001; Sester et al., 2002). Immunity gradually declines after age 30 to 40 years (Rybka et al., 2003) (see Table 1). A decreased WBC value may result from specific disease (myeloma, collagen vascular disorders), infection or sepsis (pneumonia, urinary tract infections), or medications (cytotoxic agents, analgesics, phenothiazides), and should not be attributed to advancing age (Fischbach, 2004). This lowered WBC count in a healthy individual may result in an absence of elevated white blood cells in the presence of severe infection. Medications such as steroids also may influence the immune response (Giddens, 2004). Because of the slower immune response, common symptoms of infections, such as enlarged lymph glands, fever, or pain, may be decreased in severity or absent in the older adult (Beers & Berkow, 2000). Nurses should be vigilant in efforts to detect other signs of infections in the older adult, such as confusion. Because of the concern for serious undetected infection, nurses should educate older adults about infection prevention techniques, such as hand washing and timely vaccination for influenza and pneumonia.
Platelets (Pit). Aging usually causes a decl\ine in bone marrow function, which may contribute to lowered platelet counts and decreased platelet function (Luggen, 2004). Studies also suggest that platelet adhesiveness increases with age, with no changes in numbers (Thibodeau & Patton, 2004). The ability of the older adult's body to respond to major blood loss by regenerating platelets may be inadequate, leading to inadequate clotting (Beers & Berkow, 2000) (see Table 1). The patient also must be assessed for potential or hidden blood losses, such as occult blood in stools and emesis.
Geriatric Laboratory Values and Interpretations of Erythrocyte Sedimentation Rate, Iron Metabolism, and Vitamin B12
Erythrocyte sedimentation rate (ESR). Brigden (1999) noted that the erythrocyte sedimentation rate increases with age, but the cause of this increase is unknown. ESR measures the rate at which red blood cells (RBCs) settle in 1 hour. An annual rate of increase in time of sedimentation rate for older adults has been quantified at 0.22 mm/hour/year from age 20 years (Duthie & Abbasi, 1991). An elevated ESR may indicate the presence of inflammation. Inflammation causes an alteration in blood proteins, making the RBCs heavier and causing them to settle faster (Fischbach, 2004). The acceptable reference range for the older adult is 40 mm/hour for males and 45 mm/hour for females (Brigden & Heathcote, 2000) (see Table 2). Because a slight elevation may or may not reflect the presence of an underlying inflammation, confirmation of a clinical problem may be difficult. Nurses should rely on other assessment factors, such as visible inflammation, pain, or fever, to determine a possible clinical condition.
Serum iron. Serum iron is decreased in many older adults, resulting in iron deficiency anemia as the most common form of anemia seen in older adults (Tripp, 2000) (see Table 2). One possible explanation is an agerelated decrease in hydrochloric acid (HCl) in the stomach (Beers & Berkow, 2000). HCI is important for facilitating iron absorption in the intestines. Serum iron, total iron-binding capacity, and iron stores decrease with age (Daniels, 2002). When there is a decrease in iron stores, serumferritin increases and serum transferrin decreases. The decrease in transferrin levels may indicate a decrease in liver synthesis (Lab Tests Online, 2004). Decreased iron storage and irondeficiency anemia, however, commonly are caused by inadequate dietary intake of iron or loss of iron through chronic or acute blood loss (Beers & Berkow, 2000). Nursing assessment should include a dietary assessment for reduced intake of iron-containing foods and assessment of occult bleeding from the gastrointestinal tract.
Geriatric Laboratory Values and Interpretations of Serum Proteins
Vitamin B12. Brigden and Heathcote (2000) report that serum vitamin B12 levels may decrease slightly with age (see Table 2). The deficiency in B12 may be due to chronic atrophie gastritis, an immune dysfunction that occurs more often in older adults, or from a deficiency of HCl, both leading to insufficient intrinsic factor and insufficient absorption of vitamin B12 (Beers & Berkow, 2000). The low end of the reference range for vitamin B12 is 150 pg/mL in the older adult as opposed to 190 pg/mL in a younger adult (Brigden & Heathcote, 2000) (see Table 2). Assessment for pernicious anemia, including checking for neuropathies, such as weakness, difficulty walking, and numbness or tingling, should be considered whenever anemia is present.
Total protein and albumin. Some serum protein levels, such as albumin and total protein, decline in older adults (Beers & Berkow, 2000). Changes in protein may reflect decreased liver functioning or inadequate nutritional intake (Beers & Berkow, 2000). While all serum proteins are reduced, albumin is the most significantly influenced by aging (Beers & Berkow, 2000). Albumin levels decrease each decade over the age of 60, with a marked decrease over 90 years of age (Daniels, 2002). In addition to being an indicator of disease or malnutrition, low serum albumin is the most common cause of a low serum calcium level in older adults, because most serum calcium is protein-bound (Beers & Berkow, 2000) (see Table 3).
Renal function. As mentioned previously, relying on commonly accepted laboratory values in determining renal function in the older adult is difficult. The age-related 30% to 45% decrease in functioning renal tissue and the glomerular filtration rate (GFR) leads to a decline in the creatinine clearance (Brigden & Heathcote, 2000). Commonly occurring reduction in lean body mass, decreased dietary protein intake, or decreased hepatic function may lead to decreases in the end products of metabolism, BUN, and creatinine (Brigden & Heathcote, 2000). BUN and creatinine levels overestimate renal functioning, as measured by GFR or creatinine clearance, because of the changes in body composition (Engelberg, McDowell, & Lovell, 2000; Luggen, 2004). A decrease in the lean body mass, relatively common in older adults, results in reduced protein degradation and nitrogen byproducts of metabolism (BUN). The decline in muscle mass also results in less creatinine production; serum creatinine values thus remain within normal limits despite diminished renal clearance capacity (Brigden & Heathcote, 2000) (see Table 4).
When considering age-related changes, most physicians and advanced practice nurses question the adequacy of BUN and creatinine as indicators of renal function (Kennedy-Malone, Fletcher, & Plank, 2004). Therefore, measurement of urinary creatinine clearance takes on special significance in the older adult. Serum creatinine is affected by both decreased GFR and body mass, while urinary creatinine clearance is affected only by glomerular filtration (Lewis et al., 2004). Determining renal function by creatinine clearance examination is especially useful when treating the older adult with medications because of the potential for the development of drug toxicity, even with usual doses (Daniels, 2002). Because it may be difficult to perform a creatinine clearance on the older patient, a formula can be used to estimate creatinine clearance values. For men, the formula is shown in Table 5 (Brigden & Heathcote, 2000). For women, the value determined from the formula is multiplied by 0.85. Normal ranges for creatinine clearance are 104 to 140 ml/minute for men and 87 to 107 ml/minute for women (see Table 4). Nurses should not assume that all changes in renal function are due to aging. Chronic urinary tract infections, benign prostatic hypertrophy, prostatic tumors, and diabetic neuropathy are also causes and should be ruled out (Lewis et al., 2004).
Geriatric Laboratory Values and Interpretations of Selected Renal Function Tests
Estimating Creatinine Clearance Values for Men
Geriatric Laboratory Values and Interpretations of Hepatic Enzymes
Geriatric Laboratory Values and Interpretations of Blood Lipids
Geriatric Laboratory Values and Interpretations of Glucose, Selected Electrolytes
Hepatic enzymes. The aging process does not significantly influence most hepatic laboratory test values (for example, bilirubin, ammonia, and lipids.) While lactic dehydrogenase (LDH) is not affected by aging, the enzymes gamma-glutamyl-transferase (GGT), serum aspartate aminotransferase (AST, SCOT), and alkaline phosphatase are affected (Brigden & Heathcote, 2000). GGT levels increase with aging (Tietz, Shuey, & Wekstein, 1997). AST increases slightly for individuals 60 to 90 years of age to 18 U/L to 30 U/L (Tietz et al., 1997). Serum alanine aminotransferase (ALT, SGTP) levels peak about 50 years of age and gradually fall to levels below those of younger adults by age 65 (Kelso, 1990). Alkaline phosphate (AP) increases with age to a level of 30 U/L to 140 U/L and is associated with age-related malabsorption, bone disorders, or decreased liver or renal functioning (Brigden & Heathcote, 2000) (see Table 6).
Geriatric Laboratory Values and Interpretations of Selected Blood Gases
Lipid profile. Lipid-related changes in aging adults younger than 70 years old are initially noted as increases in cholesterol, high- density lipoproteins (HDL), very low-density lipoprotein (VLDL), and triglycerides. Serum cholesterol increases as much as 40 mg/dl by age 60 in men and age 55 in women (Brigden & Heathcote, 2000). No increase is seen in adults over 90 years old; in fact, some very old adults will have decreased cholesterol levels (Tietz et al., 1997). The mean HDL increases 30% in men but decreases 30% in women between ages 30 and 80 (Brigden & Heathcote, 2000). Triglyceride levels increase by 30% in men and 50% in women between the ages of 30 and 80 years (see Table 7).
Glucose. Serum glucose levels increase slightly but steadily with age in parallel with a decrease in glucose tolerance. The normal reference range for serum glucose is broader for older adults, from 70 mg to 120 mg/100 ml (Tripp, 2000) (see Table 8). Older individuals may have lower glucose levels, reflecting poor nutritional status or overall loss in body mass (Kennedy-Malone et al, 2004). However, higher serum insulin levels are more commonly seen in older adults and may suggest insulin resistance, which is responsible for impaired glucose tolerance in 25% of individuals over age 75 (Kennedy-Malone et al., 2004). If insulin receptors do not respond to the same fasting level of glucose in old age as they did when the patient was younger, glucose intolerance without insulin-secretion changes could be the explanation. A reference value for the 2-hour postprandial glucose tolerance blood sugar test (PPBS) is calculated with the following formula (Brigden & Heathcote, 2000):
* 2-hr PPBS (mg/dl) = 100 + age in years (for patients over age 40)
Serum electrolytes. In most reports, electrolyte values remain well within the standard reference values \for older adults. Calcium levels increase in older patients (ages 60 to 90) but decrease in the very old over age 90 (Martin, Larsen, & Hazen, 1997). The initial increase can be explained by a decrease in serum pH and an increase in parathyroid hormone levels found in older individuals (Tietz et al., 1997). If the individual has a low serum albumin, however, the serum calcium level will most likely be low as mentioned previously. Serum potassium has been reported to increase slightly with age (Kennedy-Malone et al., 2004); however, most researchers use the same reference values as for younger adults (see Table 8).
Arterial blood gases (ABGs). Reference values for ABGs differ in older adults from those of younger adults. Stiffening of the elastic lung structures, decreased number of functioning alveoli, and decreased strength of the diaphragm are age-related changes that decrease respiratory functioning (Martin et al., 1997). The decreased respiratory functioning results in a decrease in the partial pressure of arterial oxygen tension (PaO^sub 2^). The arterial pressure decreases approximately 5/6 every 15 years starting at age 30 (Brigden & Heathcote, 2000). A formula (Brigden & Heathcote, 2000) has been devised to estimate arterial oxygen in older adults:
Geriatric Laboratory Values and Interpretations of Thyroxine, Triiodothyronine, Prostate-Specific Antigen
* PaO^sub 2^ (mmHg) = 100.1 - (0.325 X age in years)
Additionally, a corresponding increase in the carbon dioxide pressure (pCO^sub 2^) of approximately 2% per decade occurs after age 50. The bicarbonate-ion concentration also increases with age, balancing out the pO^sub 2^ and maintaining a normal blood pH (Brigden & Heathcote, 2000) (see Table 9).
Thyroid function tests. Changes in thyroid function in the older adult may be the most challenging problem for nurses as they try to separate disease from aging changes. Hypothyroidism is seen in 2% to 6% of the general population over age 70 (Kennedy-Malone et al., 2004). Free thyroxine (FT4) levels decrease progressively with age (Kennedy-Malone et al., 2004). Triiodothyronine (T3) shows substantial decreases in ages 30 to 80 years. Typically, a 20% change in T3 occurs during the lifetime of the older adult (Beers & Berkow, 2000) (see Table 10).
Prostate-specific antigen (PSA). Relevance of PSA values to support aggressive treatment is controversial (National Cancer Institute, 2004). Because an elevation in the PSA could be indicative of benign prostatic hypertrophy or prostate cancer, results from this test alone should not drive therapy. Because of false positives and false negatives, the agerelation variation of PSA increases difficulty in treatment decisions. Reference ranges for PSA with age are (a) 60 to 69 years: 0.0 to 5.0 ng/ml, and (b) 70 to 79 years: 0.0 to 6.3ng/ml. Men who have had a radical prostatectomy are expected to have values of 0.0 to 0.3 ng/ml (Daniels, 2002) (see Table 10).
Laboratory test results inform health care providers of a patient's changing condition. The presence of multiple diseases, as well as the incidence of polypharmacy, may be a source of confusion in the clinical interpretation of laboratory results. Often, nurses must ask, "What test results are significant and suggest the presence of disease? Which results suggest changes in patient conditions that require further assessment or interventions?" Greater understanding of how to interpret laboratory test values in relation to the clinical picture for the older adult allows nurses to provide age-appropriate assessments and interventions.
Mr. Doe's laboratory reports illustrate the confusion surrounding evaluating laboratory data for the older adult. Are his diagnostic test results helpful in explaining his fatigue and weakness? What really is happening with him? Perhaps the slightly elevated renal function tests indicate normal changes of aging. However, they also might be due to protein malnutrition, which is suspected because of his low body weight and recent weight loss. Obtaining serum protein and urinary creatinine studies as well as a thorough nutritional assessment might assist in defining the diagnosis.
Interpretation of laboratory test results allows nurses to rule out diagnoses that are not pertinent, but also assists in the examination of a broad spectrum of possibilities. Each laboratory may have variations in the reference ranges due to techniques and equipment. Nurses must work closely with laboratory personnel and pathologists to be informed about changes in reference ranges for older adults in a specific laboratory. Nurses also should educate other health care professionals about age-related variations in acceptable laboratory values. Better understanding of interpretation of diagnostic test results in older adults will allow nurses to feel confident about the care they provide.
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Nancy Edwards, PhD, RN,C, is an Associate Professor, Purdue University School of Nursing, West Lafayette, IN.
Carol Baird, DNS, APRN, BC, is an Associate Professor, Purdue University School of Nursing, West Lafayette, IN.
Copyright Anthony J. Jannetti, Inc. Aug 2005