Clinical meaning
The clinician differentiates normal age-related physiological changes from pathological processes to avoid both over-investigation of normal aging and failure to diagnose treatable disease in older adults. Cardiovascular: increased arterial stiffness (collagen cross-linking, elastin degradation) causing widened pulse pressure and isolated systolic hypertension, decreased maximal heart rate (220 minus age), increased left ventricular wall thickness (concentric remodeling), decreased diastolic filling (increased reliance on atrial contraction -- explains why AF is poorly tolerated in elderly). Respiratory: decreased chest wall compliance (costal cartilage calcification), decreased alveolar surface area (loss of elastic recoil), increased closing capacity (small airway closure during normal tidal breathing, causing V/Q mismatch and reduced PaO2 -- expected PaO2 = 100 - 0.3 x age), decreased mucociliary clearance. Renal: progressive nephron loss (GFR decreases approximately 1 mL/min/year after age 30), decreased renal concentrating ability, decreased renin and aldosterone secretion, reduced drug clearance requiring dose adjustment for renally cleared medications (use CKD-EPI equation, not Cockcroft-Gault which overestimates in elderly). Neurological: brain volume decreases approximately 5% per decade after age 40, decreased processing speed and working memory, preserved crystallized intelligence and vocabulary, decreased deep tendon reflexes, reduced proprioception. Pharmacological implications: decreased hepatic first-pass metabolism (increased bioavailability), decreased albumin (increased free drug fraction), increased body fat percentage (increased volume of distribution for lipophilic drugs), decreased total body water (increased peak levels of hydrophilic drugs). The clinician applies Beers Criteria for potentially inappropriate medications in older adults.