Age-related changes in physiology

Question 9 from the first paper of 2012 asked the candidates to list the cardiovascular, respiratory and pharmacological influences of old age on human physiology. One can really go to town on this question (indeed, somebody already has) but the college did not seem to expect a senior geriatrician level answer. They were happy with something like "Lungs work poorly. Heart works poorly. Everything breaks down and starts failing." The specifics were the increased chest wall stiffness, reduced medullary responsiveness to CO2, and the decrease in cardiac response to sympathetic stimulation.

Age-related changes in cardiovascular function

Everyone always talks about ischaemic heart disease and CCF, but there are age-related changes which occur in everyboy, but which do not related to any sort of disease process, other than ageing itself. From an often-cited article on geriatric cardiology, I quote a few physiological (non-pathological) cardiovascular changes associated with age:

  • A decrease in elasticity and an increase in stiffness of the arterial system. Thus:
    • Increased afterload on the left ventricle
    • left ventricular hypertroph
    • Increase in systolic blood pressurey,
    • Changes in the left ventricular wall that prolong relaxation of the left ventricle in diastole; thus diastolic dysfunction and the propensity towards pulmonary oedema
    • Aortic valve calcification
  • Dropout of atrial pacemaker cells resulting in a decrease in intrinsic heart rate.
  • With fibrosis of the cardiac skeleton there is calcification at the base of the aortic valve and damage to the His bundle as it perforates the right fibrous trigone.
  • Decreased responsiveness to β-adrenergic receptor stimulation
  • Decreased reactivity to baroreceptors and chemoreceptors,
  • Increase in the levels of circulating catecholamines.

Age-related changes in respiratory function

slightly older article from Europe sets a nice scene for the age-related changes in respiratory physiology. It hastens to add that "in spite of these changes, the respiratory system remains capable of maintaining adequate gas exchange at rest and during exertion during the entire lifespan, with only a slight decrease in arterial oxygen tension, and no significant change in arterial carbon dioxide tension".

  • Decrease in exchange surface area ("senile emphysema"):
    • Dilatation of alveoli
    • Enlargement of airspaces
    • loss of supporting tissue for peripheral airways
    • Carbon monoxide transfer decreases with age, reflecting mainly a loss of surface area.
  • Decreased static elastic recoil of the lung, thus
    • Increased residual volume
    • Increased functional residual capacity.
  • Decreased expiratory flow rates (especially small airways)
    • The ventilation/perfusion ratio heterogeneity increases, with low V/Q zones appearing as a result of premature closing of dependent airways.
  • Decreased compliance of the chest wall, thus increased work of breathing
  • Decreased respiratory muscle strength (though this depends on the heart, and on nutrition)
  • Decreased sensitivity of respiratory centres to hypoxia and hypercapnia

Is age an independent predictor of adverse drug reactions? Well, much of this part of the question seems to have been lifted out of the abstract for this opinion piece, which goes on about how the elderly have polypharmacy problems and forgetfully fail to coordinate their complex medication cocktails. However, a much older study suggests that age might not be an independent risk factor in hospitalised elderly patients. Perhaps its a matter of somebody more responsible and organised looking after these people.

Age-related changes in pharmacokinetics and pharmacodynamics

(see also the chapter on the pharmacology and toxicology of old age)

Changes in pharmacokinetics:

  • Reduction in first-pass metabolism, thus increased oral bioavailability of a few drugs.
  • Body fat increases, body water decreases; thus:
    • Hydrophilic drugs have a smaller volume of distribution
    • lipophilic drugs have an increased volume of distribution and a longer half-life
  • Drugs with a high hepatic extraction ratio decrease in systemic clearance
  • Activities of cytochrome P450 enzymes are preserved in normal ageing
  • Renal clearance may be decreased due to age-related changes in renal function

Influence of old age on intensive care management

Changes in airway management:

  • Intubation may be easier due to the patient being edentulous
  • Intubation may be more difficult due to C-spine and TMJ arthritis
  • Bag-mask ventilation may be more difficult because of missing teeth and wasting of facial soft tissues
  • Swallowing may be impaired and aspiration is more likely
  • Mechanisms maintaining airway patency are impaired, and extubation failure is more likely
  • Greater risk of post-induction cardiovascular collapse

Changes in respiratory management and ventilation

  • Decrease in expectations: SpO2 goals may be lowered (~ 92%, due to "senile emphysema")
  • Chest physiotherapy becomes more important (decreased respiratory muscle strength)
  • Early extubation is favoured (to prevent deconditioning)
  • There is decreased sensitivity of respiratory centres to hypoxia and hypercapnia, which must be considered.

Changes in approach to cardiovascular support

  • Responsiveness to β-adrenergic receptor stimulation is decreased; higher doses of vasopressors may be required
  • Baroreceptors and chemoreceptors are less reactive
  • Levels of circulating catecholamines are increased
  • An increased blood pressure goal is therefore appropriate when titrating vasopressors: chronic hypertension is almost assured, and with this, organ bloodflow autoregulation is impaired (i.e. more closely tied to pressure).

Changes in assessment of neurological function

  • Increased risk of delirium (therefore, greater vigilance in screening for delirium)
  • Decreased expectation of neurological performance, eg. when assessing for extubation (pre-existing dementia)
  • Parkinson disease (unusual response to antidopaminergic drugs)
  • Pre-existing weakness may produce a "difficult to wean" scenario

Changes in approach to the support of renal function

  • Age-related decrease in GFR is to be expected
  • Renal blood flow decreases; the kidneys are more susceptible to fluctuations of blood pressure
  • Renal blood flow autoregulation undegoes a left-shift; thus a higher perfusion pressure may be required (eg. a MAP of 75-80)
  • Because of these factors, old kidneys are more susceptible to dialysis-associated renal dysfunction. This influences the decision as to whether one does or does not offer dialysis.

Changes in approach to nutrition

  • Albumin is expected to be low (due to age-related decrease in albumin synthesis)
  • Decreased glycogen reserve means greater vigilance in monitoring for hypoglycaemia
  • Decreased metabolic rate means nutritional requirements may be lower than predicted by crude approximations of caloric requirements
  • Likelihood of premorbid malnutrition is greater - thus, more susceptible to refeeding syndrome

Changes in approach to blood transfusion

  • Age-related hanges in haematological function influence your expectations: these patients are more likely to be chronically anaemic, and well adapted to anaemia.
  • Decreased marrow cellularity results in a diminished response to anaemia and EPO.
  • Chronic anaemia of malnutrition may pre-date ICU admission

Changes in interpetation of the clinical features of sepsis

  • There is diminished immune response, both cellular and humoural.
  • The elderly may not mount a febrile response, and may actually be hypothermic with sepsis
  • Decreased synthetic function of the liver may result in diminished synthesis of CRP

Changes in pharmacology

  • Drug levels may not represent the effective "free" fraction due to changed in protein binding and volume of distribution
  • Dose adjustments need to be made to account for decreased hepatic and renal clearance


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Shi, Shaojun, and Ulrich Klotz. "Age-related changes in pharmacokinetics."Current drug metabolism 12.7 (2011): 601-610.

Corsonello, A., C. Pedone, and R. Antonelli Incalzi. "Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions." Current medicinal chemistry 17.6 (2010): 571-584.

Carbonin, P., et al. "Is age an independent risk factor of adverse drug reactions in hospitalized medical patients?.Journal of the American Geriatrics Society39.11 (1991): 1093-1099.

Timiras, Paola S., ed. Physiological basis of aging and geriatrics. CRC Press, 2013.

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Solh, Ali A. El, et al. "Extubation failure in the elderly." Respiratory medicine 98.7 (2004): 661-668.

Linton, Phyllis Jean, and Kenneth Dorshkind. "Age-related changes in lymphocyte development and function." Nature immunology 5.2 (2004): 133-139.

Muschler, George F., et al. "Age‐and gender‐related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors." Journal of Orthopaedic Research 19.1 (2001): 117-125.

Grady, C. L., et al. "Age-related changes in brain activity across the adult lifespan."Cognitive Neuroscience, Journal of 18.2 (2006): 227-241.