Laboratory assessment considerations for the aging individual

Christine Stabler

Introduction

Of all people who have ever lived to the age of 65, over half are alive today. This striking statement has significant implications for the ongoing care of the elderly. Until now, little research has been conducted to evaluate the specific differences seen in the laboratory assessment of the older individual.

The Human Genome Project has finally been completed and the genetic basis of many biological functions has been identified; however, there is still much to learn about the biology of aging. It is known that cells and tissues have finite lifespans, and that growth and replication slows with age. However, it seems that many metabolic and biological functions remain constant over the lifetime of humans. Extrapolating these data from tissue to human is somewhat risky but it is accurate to do so in that aging itself is not marked by predictable biochemical changes. As people age they become more dissimilar, belying any stereotype of aging. Abrupt declines in system functions or marked changes in laboratory values should be attributed to the effects of disease, not normal aging. Finally, in the absence of disease or modifiable risk factors, the concept of healthy old age is absolutely valid. This chapter will review the laboratory differences between the well young adult and the well older individual and identify the known variations that occur in the absence of disease.

Age-related considerations

Certain basic tenets apply when evaluating the elderly patient. In the process of aging, there is a decline in metabolic reserves in most organ systems, particularly in the cardiovascular, central nervous, gastrointestinal, hematopoietic and endocrine systems. Disease states will affect these vulnerable systems and become evident through laboratory value changes more rapidly than in younger adults. The fragile renal and hepatic systems of older adults are more susceptible to the effects of pharmacological agents and less tolerant of their side-effects.

Normal laboratory values are derived from analyses of what are considered to be disease-free healthy populations (Huber et al., 2006). Normal ranges are based on plus or minus 2 standard deviations (SD) from the mean value. The populations analyzed are heterogeneous for age and assume that aging individuals are the same as young adults. In many cases this may be true, but adequate reference ranges for laboratory testing in the elderly are generally lacking (Brigden & Heathcote, 2000). Specific differences may be caused by the loss of certain biological reserves in those aged over 75, ironically the fastest-growing segment of the elderly population. There are some predictable changes in laboratory values that occur with age which can be attributed to the normal aging process and not to disease states. Although there is significant variation from one individual to the next, these changes begin in the fourth decade of life and continue in a linear fashion into old age. With these exceptions, it is important to understand that most laboratory values in the elderly are similar to those of the healthy young (Coresh et al., 2003).

In blood chemistry, the level of serum alkaline phosphatase, an enzyme found in bone and liver, increases with age. In men, it increases by up to 20% between the ages of 40 and 80. In women, slightly greater increases (0–37%) are seen. Serum albumin, traditionally a marker of nutrition, decreases slightly with age, despite adequate nutrition. Levels of serum prealbumin, a marker of current nutrition, should be equivalent to those of healthy young individuals (16–35 mg/dl) (Kubota et al., 2012). In healthy individuals, serum magnesium decreases by about 15% between the ages of 30 and 80. Uric acid, a metabolic product of purine metabolism, increases slightly in normal aging individuals without disease. Other chemistries, such as serum electrolytes, serum bilirubin, liver enzymes and total proteins, remain unchanged with age (Feld & Schwabbauer, 2000).

Lipid values also change with aging. In both women and men, total cholesterol levels increase by 30–40 mg/dl from 30 to 80 years of age. High-density lipoprotein (HDL), which is thought to be protective against atherosclerosis, increases by approximately 30% in men, but falls by up to 30% in women after menopause. This is attributed to the fact that, during the reproductive years, women have significantly higher levels of HDL than men because of the positive effect of estrogen on lipid production in the liver. Triglycerides, or blood fats, increase by 30–50% in both men and women from age 30 to 80. Serum levels of low-density lipoprotein (LDL), cholesterol molecules associated with accelerated atherosclerosis, are unchanged by age (Kubota et al., 2012).

Fasting blood glucose levels increase by 2 mg/dl for each decade over the age of 30. Glucose metabolism, as measured by postprandial glucose levels, increases by up to 10 mg/dl for each decade over the age of 30. The risk of developing diabetes mellitus in individuals with insulin resistance caused by either genetic predilection or obesity increases with age.

Thyroid function is measured by serum triiodothyronine (T3) and thyroxine (T4) levels as well as levels of the pituitary hormone thyroid-stimulating hormone (TSH). Both TSH and T3 levels may decrease slightly with age; a marked or progressive development of abnormal values indicates a disease state in the elderly. Serum T4 levels remain unchanged in healthy elderly individuals.

Levels of serum creatinine do not change with age but less creatinine is produced and serum creatinine clearance, a measurement of renal function, declines by approximately 10 ml/min/1.73 m² for each decade over the age of 40. This phenomenon is explained by an age-related reduction in muscle mass in older individuals and by a decrease in protein byproducts like creatinine being delivered to the kidney. It is exacerbated by the age-related loss of renal tissue, parenchyma, that begins in the fifth decade (Coresh et al., 2003). Creatinine clearance can be calculated using a simple formula including the patient’s serum creatinine value, gender, weight and age. Therefore, a normal serum creatinine level does not necessarily indicate normal renal function. Like creatinine, many drugs require renal clearance during metabolism; the age-related decline in renal function therefore necessitates adjustments in the dosing of these drugs. If too large a dose of medication is delivered to an even minimally impaired kidney, incomplete clearance occurs leaving potentially toxic metabolites in the kidney tissue (parenchyma). This can build up and further damage the kidney in a process called interstitial nephritis. This can be reversed with immediate withdrawal of the drug but, occasionally, permanent impairment can occur. The most common drugs responsible for this phenomenon are nonsteroidal anti-inflammatory agents and antibiotics (Mantha, 2005).

Hematological assessment of the elderly is achieved by white blood cell, hemoglobin, hematocrit, platelet and red blood cell counts. White blood cell counts may decrease slightly in the healthy older individual, whereas it is thought that hemoglobin, hematocrit and platelet counts should remain constant with aging. However, anemia is quite common in the elderly. It can be associated with many chronic diseases of aging such as arthritis, diabetes, renal impairment and bone marrow suppression by drugs and environmental chemicals. The World Health Organization has established norms of 13 g/dl or more for men and 12 g/dl for women for hemoglobin levels. In the elderly, some experts accept slightly lower values as normal (11.5 g/dl in men and 11 g/dl in women); if they remain constant, these values should not trigger extensive investigations (Thein et al., 2009).

Serum vitamin B₁₂ levels may decrease with age (Park & Johnson, 2006). Normal values in young adults are>190 pg/ml; levels of>150 pg/ml are acceptable in older adults in the absence of macrocytic changes to the red blood cells. Levels of vitamins C, E, D and B₆ also show a slight age-related decrease.

The erythrocyte sedimentation rate (ESR) increases with age by approximately 22 mm/h from a norm of 20–25 mm/h to acceptable rates of up to 40 mm/h (in men) and 45 mm/h (in women) in the elderly. Levels greater than these are indicative of inflammatory or neoplastic conditions, which commonly occur in the geriatric population. Isolated increases in ESR are associated with increases in all causes of mortality. By definition, those with elevated ESRs have a higher death rate than age-matched individuals, regardless of the cause of death. Increases in ESR mandate workup for disease states. Normal values for serum C-reactive protein (CRP), another measurement of overall inflammation, remain unchanged, regardless of age.

The assessment of nutritional status has been studied extensively. In normal healthy ambulatory elderly individuals, serum protein and albumin levels are relatively unchanged with age. Nutritional status is assessed by the measurement of serum prealbumin and albumin levels, and indirectly by the numbers of white blood cells known as lymphocytes. Nutritional deficiencies, however, are common in the elderly and are caused by a multitude of factors including poor intake, a reduction in the acuity of taste, loss of appetite, depression, malabsorption from intestinal surgery or disease, and interactions with medications. It is important to consider nutritional status when caring for the elderly to maximize the potential for rehabilitation.

Indications for laboratory assessment

When is laboratory assessment necessary? Routine laboratory testing should be determined by a patient’s presentation, history and current use of medication. For example, a patient who must use diuretics requires a regular assessment of serum electrolytes, especially serum potassium. Simple alterations in diet, such as increased sodium levels, may cause potassium wasting in the elderly kidney and precipitate hypokalemia, a cause of muscle weakness. A patient on anticholesterol medication such as the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors requires initial assessment of liver functions, whereas a patient receiving ticlopidine (Ticlid), a platelet inhibitor used in patients with transient ischemic attacks and stroke, requires a regular blood count.

Laboratory assessment is especially important in the evaluation of a patient who presents with new physical findings. The workup for dementia and delirium is particularly vital. Neurosyphilis, vitamin B₁₂ and folic acid deficiencies, and acute infection can be detected by laboratory assessment and are precipitants of acute delirium and dementia. Radiological findings and other physical diagnostic tests such as lumbar puncture can quickly identify reversible causes for a patient’s neurological changes.

Lethargy and altered levels of consciousness may also be presenting symptoms in a patient with abnormal laboratory values. Hypoglycemia, hyponatremia, acidosis, hypoxia and hypocalcemia are direct causes of central nervous system depression and can be identified through commonly used laboratory tests. Neuromuscular irritability, tetany and muscle spasms may present in severe cases of hypocalcemia.

A patient who presents with peripheral, sensory or motor deficits may be suffering from a disease that is identifiable by analysis of blood chemistries. Peripheral neuropathies are caused by diabetes mellitus (hyperglycemia), heavy metal ingestion and medication toxicities, Vitamin B₁₂ deficiency and biochemical assessment can identify these problems.

Deteriorating renal function as indicated by an elevation in the levels of serum creatinine and blood urea nitrogen may place the patient at a greater risk of medication toxicity. Frequent assessment of drug serum levels and adjustment of doses is the hallmark of safe continued usage in the face of renal insufficiency. Abnormalities in thyroid hormone levels may present differently in the elderly than in younger adults. Cardiac arrhythmias and weight loss may be the presenting symptoms of hyperthyroidism in the elderly, whereas hypothyroidism may present more insidiously, with the typical symptoms of myxedema occurring less frequently. Alterations in mental status, lethargy, weight gain and thought disorders may be caused by hypothyroidism in the elderly.

Table 13.1 indicates the normal values of routinely used laboratory assessments and Box 13.1 shows the possible age-related effects on these values. Significant deviations from these values may indicate the presence of disease or deterioration of organ systems.

Table 13.1

Selected normal laboratory values

	Normal Values
Serum electrolytes
Carbon dioxide	23–31 mEq/l
Chloride	98–107 mEq/l
Potassium	3.5–5.1 mEq/l
Sodium	136–145 mEq/l
Metabolic indicators
Calcium	8.6–10.0 mg/dl
Cholesterol	240 mg/dl
Creatinine	0.8–1.5 mg/dl
Free thyroxine (T₄)	0.8–2.3 mg/dl
Glucose, fasting	80–110 mg/dl
Glucose, 2 h postprandial	80–110 mg/dl
Protein
Total	6.0–8.0 g/dl
Albumin	3.5–5.5 g/dl
Globulin	2.0–3.5 g/dl