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C HAPTER 9 / Physiologic Adaptations With Aging 209
As a result of changes in airway closure, diffusing capacity, The limited ability of the kidney to regulate salt balance is
lung volumes, and lung structure, a lower arterial oxygen tension compounded by changes in water regulation. The aging kidney
is seen in older adults. The arterial oxygen (Pa O2 ) decreases and exhibits a modest age-related impairment in the ability to dilute
alveolar–arterial oxygen difference (A a O2 ) widens, whereas arte- urine and excrete a water load. Inability to dilute urine maximally
rial carbon dioxide (Pa CO2 ) and pH remain unchanged. is related to decreased GFR and an inability to suppress antidi-
In summary, although the lung undergoes some structural and uretic hormone. The ability to concentrate urine declines moder-
functional changes, the nondiseased respiratory system continues ately also, with the usual value specific gravity of 1.032 decreasing
to be capable of supporting daily function throughout life. The ef- to 1.024 at age 80 years. 25 Therefore, the older person has more
fect of changes in the respiratory system may become evident un- difficulty retaining fluid when it is necessary, as in situations of de-
der situations of high physiologic demand. creased circulating fluid volume (e.g., dehydration), and in ex-
creting fluid, as in situations of excess circulating fluid volume
(e.g., congestive heart failure).
RENAL CHANGES Although baseline homeostasis of fluids and electrolytes is
maintained with normal aging, there is a progressive loss of renal
The kidney is an organ with complex functions that are intimately reserve. Vitamin D hydroxylation in the kidney is decreased and
related with other organ systems, such as the cardiovascular, en- may contribute to a decreased intestinal absorption of calcium.
docrine, and neurological systems. In discussing the aging kidney, Decreased renal reserve manifests in older patients’ vulnerability
changes are discussed as they relate to intrinsic changes in the kid- to renal failure during acute illness. There are many functions of
ney as well as those adaptive changes that result from the effects the kidney (e.g., erythropoietin production, hormone metabo-
of other systems. lism) that have yet to be thoroughly studied. Of those changes
that have been described, the clinical effects on drugs and their ex-
Structural Changes cretion and on fluid balance are of primary importance.
The volume and weight of the kidney reach maximum in the
third decade of life, start to decline during the fourth decade, and HEPATIC CHANGES
continue to decline throughout the remainder of the lifespan.
Most of the decline in volume and weight is in the cortex, with a Structural Changes
steady decline in the number of nephrons. Renal arteries undergo
age-related thickening, producing a decline in renal blood flow The proportion of liver to body weight remains constant through
26
and an increase in vascular resistance with age. middle age and decreases gradually after age 70 years. Liver his-
tology in older adults shows more lipofuscin pigment and giant
hepatocytes than in younger individuals. In healthy subjects, liver
Functional Changes size, blood flow, and perfusion decrease by 30% to 40% between
the third and tenth decade. 26
Average renal blood flow decreases approximately 10% per
decade, and the majority of older adults lose approximately 10%
of glomerular filtration rate (GFR) per decade after the fourth Functional Changes
decade. The reduced renal blood flow and decreased number of There is no change in level of serum bilirubin, aminotransferases,
nephrons contribute to the reduction of GFR. Because of the de- or alkaline phosphatase with aging. Age-related change in liver
crease in muscle mass with aging, increased serum creatinine does function is small and, with the exception of some enzymes in-
not correspond with reduced GFR. Creatinine clearance, not volved in drug metabolism, is not clinically significant. There is a
serum creatinine, should be the criterion for assessing renal func- decrease in the hepatic clearance of drugs, particularly those that
tion in older people. The Cockcroft–Gault equation predicts cre- have a low-extraction ratio and whose elimination is dependent
atinine clearance from serum creatinine. For men: creatinine on the cytochrome P450 system.
clearance (140 – age) (weight in kg)/(72 serum creatinine
measured in mg/dL). The results are adjusted for women by mul-
tiplying by 0.85. EFFECTS OF AGING ON
The clinical importance of this formula is apparent when de- PHARMACOKINETICS
terminations about kidney function and appropriate drug dosage
need to be made. The steady decline in renal function impairs the Drug Absorption
ability of the kidney to excrete a salt or water load and decreases
the renal clearance of those medications normally removed by the Little is known about absorption of oral drugs from the intestines,
kidney. 24 but it seems to be mildly decreased or unchanged with age. Ab-
The aging kidney’s tendency to lose salt is related to nephron sorption appears to be the pharmacokinetic parameter least af-
loss, with increased osmotic load per nephron leading to mild os- fected by advancing age.
motic diuresis and the age-related changes in the renin–aldos-
terone system. Lower levels of renin (decreased by 30% to 50% in Drug Distribution
older adults) are related to 30% to 50% reductions in plasma con-
centration of aldosterone. When these lower levels are combined Decreased serum albumin concentration is linked to decreased
with the decreased GFR, older people are at risk for expansion of binding capacity of drugs. Drugs that are bound are inactive in
extracellular fluid volume when faced with an acute salt load terms of therapeutic effect. Unbound, or free, drug is free to exert
(from diet, drugs, or intravenous fluids). therapeutic effects. This is one reason why a smaller dosage of