Physiology of Ageing

Renal Changes

•    ↓ Renal mass and ↓ nephron number:

o    GFR declines ~1 mL/min/year after age 40

•    Reduced tubular function:

o    Impaired ability to concentrate and dilute urine → predisposition to dehydration, hyponatraemia, hyperkalaemia

•    Clinical implications:

o    Increased susceptibility to acute kidney injury (AKI)

o    Increased risk of drug accumulation (e.g., digoxin, NSAIDs, aminoglycosides)

o    Lower renin and aldosterone → impaired sodium conservation

Hepatic Changes

•    ↓ Hepatic blood flow (~30–40% by age 80)

•    Reduced phase I metabolism (oxidation, reduction via cytochrome P450 enzymes)

•    Preserved phase II metabolism (conjugation)

•    Clinical implications:

o    Reduced first-pass metabolism → higher bioavailability of certain drugs (e.g., morphine, propranolol)

o    Potentially prolonged half-lives of benzodiazepines (esp. diazepam)

Cardiovascular Changes

•    ↓ Baroreceptor sensitivity:

o    Increased risk of orthostatic hypotension → dizziness, falls, syncope

•    ↑ Arterial stiffness:

o    Leads to isolated systolic hypertension

o    ↑ Pulse pressure (difference between systolic and diastolic BP)

•    ↓ β-adrenergic responsiveness:

o    Blunted heart rate response to stress, exercise, or hypovolaemia

Musculoskeletal Changes

•    ↓ Bone density (osteopenia, osteoporosis):

o    Increased risk of vertebral, hip, wrist fractures

o    Accelerated by menopause (loss of oestrogen)

•    ↓ Muscle mass and strength (sarcopenia):

o    Contributes to frailty, immobility, and falls

o    Increased risk of disability and institutionalisation

•    Joint changes:

o    Cartilage thinning → osteoarthritis

Body Composition Changes

•    ↑ Body fat:

o    Alters volume of distribution for lipophilic drugs (e.g., diazepam) → prolonged sedation

•    ↓ Total body water:

o    Alters distribution of hydrophilic drugs (e.g., digoxin, ethanol) → higher plasma levels

•    ↓ Serum albumin:

o    Increases free fraction of protein-bound drugs (e.g., warfarin, phenytoin)

Immune System Changes

•    Immunosenescence:

o    Decreased naive T-cell production (thymic involution)

o    Reduced B-cell function → impaired humoral response

o    Diminished NK cell activity

•    Clinical implications:

o    Atypical infection presentations (e.g., no fever or localising signs)

o    Increased susceptibility to infections (e.g., pneumonia, UTIs, zoster)

o    Poorer vaccine responses (e.g., influenza, pneumococcus)

Extra Revision Pearls

•    Dehydration risk: reduced thirst sensation + reduced renal concentrating ability

•    Falls risk: multifactorial (orthostatic hypotension, sarcopenia, visual impairment, medications)

•    Anaemia of ageing: mild normocytic anaemia common; always exclude iron deficiency and malignancy

•    Delayed recovery from stressors: reduced physiological reserve → concept of frailty