6.3 Physiological Changes of Ageing and Thermoregulation

6.3 Physiological Changes of Ageing and Thermoregulation

Senescence represents the progressive structural and functional decline across all physiological systems, leading to reduced homeostatic reserve and impaired organ responsiveness to stress. In elderly surgical patients, physiological changes interact with anaesthetic agents to produce heightened drug sensitivity, hemodynamic instability, perioperative hypothermia, and neurocognitive complications. A comprehensive understanding of geriatric physiology and thermoregulation is central to perioperative safety.

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1. Cardiovascular Ageing and Haemodynamics

                  [ AGE-RELATED VASCULAR REMODELING ]
                                   |
        +--------------------------+--------------------------+
        |                                                     |
[ Loss of Arterial Elastin & Collagen Crosslinking ]  [ Left Ventricular Hypertrophy ]
        |                                                     |
  Decreased Arterial Compliance                         Impaired Diastolic Relaxation
  Elevated Pulse Wave Velocity (Early Wave Reflection)   Elevated A Wave, Inverted E/A Ratio
        |                                                     |
  Isolated Systolic Hypertension & Widened Pulse Pressure  20-30% Dependence on "Atrial Kick"
        |                                                     |
        +--------------------------+--------------------------+
                                   |
              [ Blunted Autonomic Responses & Baroreflex ]
              - Beta-1 & Beta-2 Adrenergic Desensitization
              - Maximum Heart Rate Declines: HR_max ≈ 220 - Age
              - Severe Unbuffered Hypotension on Induction

Arterial Stiffening and Pulse Wave Velocity

• Elastin Degradation and Collagen Deposition: Ageing is characterized by progressive fragmentation and loss of medial elastin fibers in large conduit arteries (particularly the thoracic and abdominal aorta), accompanied by increased deposition of disorganized collagen and advanced glycation end-product cross-linking.
• Loss of Arterial Compliance: The aorta transforms from an elastic, distensible reservoir (Windkessel effect) into a rigid conduit. As arterial compliance ($C = \Delta V / \Delta P$) declines, pulse wave velocity ($PWV$) increases markedly from ~5 m/s in young adults to $> 10-15\text{ m/s}$ in the elderly.
• Reflected Pressure Waves: In youthful elastic arteries, peripheral wave reflections return to the central aorta during diastole, augmenting coronary arterial perfusion pressure. In stiff geriatric arteries, the accelerated pulse wave reflects backward prematurely during late systole. This reflected wave augments peak systolic pressure while lowering diastolic pressure, producing isolated systolic hypertension, a widened pulse pressure, and increased left ventricular afterload that promotes concentric left ventricular hypertrophy (LVH).

Diastolic Dysfunction and Atrial Dependence

• Impaired Myocardial Relaxation: Active re-uptake of calcium ions into the sarcoplasmic reticulum via the SERCA2a pump slows with age, and myocardial fibrosis increases passive ventricular stiffness. This impairs early active diastolic relaxation.
• Echocardiographic Inversion ($E/A < 1$): On transmitral Doppler echocardiography, early passive diastolic filling (the E wave) diminishes, whereas late ventricular filling driven by active left atrial contraction (the A wave) increases to compensate, producing an inverted $E/A$ ratio ($< 1.0$).
• The Atrial Kick: While young healthy adults derive only 10% to 15% of left ventricular end-diastolic volume from atrial systole, the elderly patient depends on this active atrial contraction ("atrial kick") for 20% to 30% (or more) of end-diastolic filling.
• Haemodynamic Vulnerability: The onset of atrial fibrillation, loss of atrioventricular synchrony (e.g. junctional rhythms), or sudden tachycardia (which truncates the diastolic filling interval) leads to a precipitous drop in left ventricular preload, a sharp fall in stroke volume, profound arterial hypotension, and acute hydrostatic pulmonary congestion.

Autonomic Dysregulation and the Baroreceptor Reflex

• Beta-Adrenergic Desensitization: Ageing leads to a marked, progressive down-regulation and post-receptor uncoupling of beta-1 and beta-2 adrenergic receptors. Both chronotropic and inotropic responsiveness to endogenous catecholamines and exogenous beta-agonists (e.g. isoprenaline, dobutamine) are blunted. The maximum attainable heart rate declines reliably with age:

$\text{HR}_{\max} \approx 220 - \text{age}$

• Preserved Alpha-Adrenergic Tone: In contrast to beta-receptors, vascular alpha-1 adrenergic receptor responsiveness remains relatively intact. Systemic vascular resistance tends to be higher at baseline.
• Blunted Baroreceptor Reflex: Sclerosis of the carotid sinus and aortic arch reduces the stretch sensitivity of baroreceptor terminals. When systemic blood pressure drops during induction of general anaesthesia or following neuraxial sympathectomy, elderly patients fail to generate compensatory reflex tachycardia or swift vasoconstriction. Profound, unbuffered arterial hypotension is common, demanding preemptive vasopressor support.

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2. Respiratory Senescence and Gas Exchange Mechanics

Lung and Chest Wall Mechanics

• Loss of Elastic Recoil: Progressive enzymatic degradation of alveolar septal elastic fibers produces "senile emphysema" with destruction of alveolar walls and enlargement of distal airspaces. Loss of radial alveolar tethering diminishes the inward elastic recoil of the lung, causing lung compliance to increase.
• Chest Wall Stiffening: Calcification of costochondral articulations, chondrosternal synostosis, and progressive senile thoracic kyphosis stiffen the thoracic cage. Consequently, chest wall compliance decreases.
• Respiratory Musculature: Sarcopenia affects the diaphragm, intercostal, and accessory muscles, reducing maximum inspiratory pressure ($P_{I\max}$) and maximum expiratory pressure ($P_{E\max}$) by 30% to 50%, weakening cough efficacy and secretion clearance.

                         [ SENILE LUNG VOLUMES ]

    Total Lung Capacity (TLC): Relatively Constant or -10%
   +--------------------------------------------------------------+
   | Vital Capacity (VC)                                          |
   | Decreases by 20-25% by age 70                                |
   |                                                              |
   |------------------------------------+                         |
   | Tidal Volume                       | Functional              |
   |------------------------------------| Residual                |
   | Expiratory Reserve Volume (ERV)    | Capacity (FRC)          |
   | Decreases                          | Increases ~10% / decade |
   +------------------------------------+-------------------------|
   | Residual Volume (RV)                                         |
   | Increases by +50-100% by age 70                              |
   +--------------------------------------------------------------+

Static and Dynamic Lung Volumes

• Residual Volume (RV): Increases by 50% to 100% by age 70. Loss of elastic tethering permits smaller dependent airways to collapse earlier during expiration, trapping gas.
• Functional Residual Capacity (FRC): Increases slightly (by ~10% per decade) due to the altered balance between reduced inward lung recoil and thoracic wall stiffness.
• Vital Capacity (VC): Decreases by 20% to 25% by age 70 ($VC = TLC - RV$).
• Total Lung Capacity (TLC): Remains relatively constant or declines minimally (by ~5% to 10%) due to height loss and spinal compression.

Closing Capacity and Age-Dependent $V/Q$ Mismatch

Closing volume ($CV$) is the volume of gas remaining in the lungs above residual volume at which dependent small airways begin to collapse during expiration. Closing Capacity ($CC$) is the sum of closing volume and residual volume ($CC = CV + RV$).

• Because of progressive loss of alveolar elastic tethering, closing capacity increases steadily throughout life:
  • At ~44 years of age, Closing Capacity exceeds FRC in the supine position.
  • At ~65 years of age, Closing Capacity exceeds FRC even in the upright / seated position.
• Pathophysiological Consequence: When $CC > FRC$, dependent terminal bronchioles close during normal, resting tidal breathing. This creates micro-atelectasis, intrapulmonary right-to-left shunt, and low ventilation-perfusion ($V/Q$) units, explaining the progressive, normal decline in resting arterial oxygen tension ($P_a\text{O}_2$) with advancing age:

$P_a\text{O}_2 \approx 100 - (\text{age} \times 0.3)\text{ mmHg}\quad [\text{or } P_a\text{O}_2 \approx 13.3 - (\text{age} \times 0.04)\text{ kPa}]$

For a healthy 70-year-old breathing room air, normal resting $P_a\text{O}_2$ is roughly 79 mmHg (10.5 kPa); for an 80-year-old, it is roughly 76 mmHg (10.1 kPa).

Blunted Ventilatory Chemosensitivity

Both the central (medullary) response to hypercapnia and the peripheral (carotid body) response to hypoxaemia decline by up to 50% in the elderly. Sedative agents, opioids, and residual volatile anaesthetics blunt these responses further, creating high susceptibility to unrecognized hypoventilation, airway obstruction, and hypercapnic respiratory arrest.

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3. Neurobiology and Pharmacokinetics of Ageing

Central Nervous System and Anaesthetic Requirements

• Structural Changes: Cerebral brain mass decreases by 10% to 20% between ages 30 and 80, with preferential loss of gray matter in the frontal cortex, temporal cortex, and hippocampus. Neuronal density declines, alongside a marked reduction in dendritic synapses.
• Neurochemical Deficits: Synthesis and receptor density of key neurotransmitters—specifically acetylcholine, dopamine, serotonin, and noradrenaline—fall significantly. The central cholinergic deficit is the primary neurobiological substrate for perioperative cognitive vulnerability.
• Minimum Alveolar Concentration (MAC): The MAC for all volatile inhalational anaesthetics decreases predictably by approximately 6% per decade beyond 40 years of age. For example, a 2.0% MAC of sevoflurane in a 40-year-old decreases to approximately 1.5% to 1.6% in an 80-year-old.
• Intravenous Agent Sensitivity: Pharmacodynamic sensitivity to GABA-ergic agents (propofol, midazolam, etomidate) and opioids is markedly enhanced. Induction doses of propofol must be reduced by 30% to 50%, administered slowly to avoid unbuffered hypotension and prolonged apnea.
• Postoperative Delirium (POD) vs Cognitive Dysfunction (POCD):
  • POD: An acute, fluctuating disturbance in attention, awareness, and cognition emerging in the immediate postoperative period (days 1 to 3). Triggered by anticholinergic drugs, pain, sleep disruption, and systemic inflammation.
  • POCD: A subtle, prolonged decline in cognitive performance (memory, executive function) confirmed by objective neuropsychological testing weeks to months following surgery.

Body Composition and Distribution Volumes

                  [ AGE-RELATED BODY COMPOSITION SHIFT ]
                                     |
        +----------------------------+----------------------------+
        |                                                         |
[ Total Body Water Drops ~15% ]                       [ Adipose Mass Increases +20-40% ]
[ Skeletal Muscle Mass Declines (Sarcopenia) ]        [ Lipophilic Compartment Expands ]
        |                                                         |
Smaller Vd for Water-Soluble Drugs                   Larger Vd for Lipid-Soluble Drugs
(Higher Initial Peak Concentrations:                  (Prolonged Elimination Half-life: 
 e.g. Rocuronium, Digoxin)                             e.g. Fentanyl, Diazepam, Thiopental)

Plasma Protein Binding

• Serum Albumin: Albumin concentrations decline by 15% to 20% due to decreased hepatic synthesis. Because acidic drugs (e.g. thiopental, warfarin, phenytoin), and some others such as diazepam, bind predominantly to albumin, the free, pharmacologically active unbound fraction is increased, intensifying drug effects at standard doses.
• Alpha-1 Acid Glycoprotein ($\alpha_1$-AGP): As an acute-phase reactant, $\alpha_1$-AGP levels remain stable or increase with age. Binding of basic drugs (e.g. lidocaine, bupivacaine, many opioids) is preserved or increased.

Hepatic and Renal Elimination

• Hepatic Clearance: Hepatic parenchyma and total liver blood flow decrease by 20% to 40% with advancing age (~10% per decade). Phase I cytochrome P450 reactions (oxidation, reduction) decline significantly, whereas Phase II conjugation reactions (glucuronidation) are relatively preserved.
• Renal Clearance: Renal cortical mass declines, and functioning glomeruli are lost. Renal blood flow and GFR decrease by approximately 1 mL/min/year after age 40.
• The Sarcopenia Paradox: Because skeletal muscle mass and daily endogenous creatinine generation fall in tandem with GFR, serum creatinine often remains falsely normal (e.g. 70-90 $\mu\text{mol/L}$) despite GFR declining by 50%. Relying solely on serum creatinine leads to severe overdosing of renally cleared drugs (e.g. sugammadex, low-molecular-weight heparin, aminoglycosides, morphine metabolites). Creatinine clearance must be estimated using the Cockcroft-Gault equation:

$\text{CrCl} = \frac{(140 - \text{age}) \times \text{weight (kg)}}{72 \times \text{serum Cr (mg/dL)}} \times [0.85 \text{ if female}]$

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4. Perioperative Thermoregulation and Hypothermia

Hypothalamic Thermal Control and Anaesthetic Disruption

• The Interthreshold Range: The preoptic anterior hypothalamus regulates body temperature within a tightly controlled interthreshold range of 0.2°C to 0.4°C. Within this narrow window, no autonomic thermoregulatory defenses are active.
• Anaesthetic Widening of the Range: Both general anaesthetics (volatile agents, propofol, opioids) and neuraxial blocks widen this interthreshold range roughly 20-fold (to about 2.0°C to 4.0°C). They elevate the warm-defense (sweating) threshold while substantially depressing the cold-defense thresholds (vasoconstriction, non-shivering thermogenesis, and shivering). Consequently, the patient becomes poikilothermic, matching ambient temperature unless active warming is applied.

The Three Phases of Hypothermia Under General Anaesthesia

Core Temp (°C)
 37.0 |----
      |    \  Phase 1: Internal Thermal Redistribution
 36.0 |     \ (Core-to-peripheral heat flux via vasodilation)
      |      +-------
 35.0 |              \  Phase 2: Linear Heat Loss
      |               \ (Environmental loss > Metabolic production)
 34.0 |                +------------------ Phase 3: Thermal Plateau
      +----------------------------------------- (Vasoconstriction engaged)
      0       1       2       3       4  Time (Hours)

1. Phase 1: Internal Thermal Redistribution (First 30 to 60 minutes):
   • Core temperature drops rapidly by 1.0°C to 1.5°C.
   • General anaesthetics cause widespread peripheral vasodilation and abolish tonic pre-capillary vasoconstriction, opening arteriovenous shunts.
   • Warm blood from the central core compartment (trunk, thoracic viscera, brain) flows into the cold peripheral thermal compartment (limbs), while cooler blood returns to the core.
   • Key Mechanism: This initial drop is an internal thermal gradient redistribution, not net heat loss to the ambient environment. Active pre-warming for 15 to 30 minutes preoperatively eliminates this core-to-periphery gradient.
2. Phase 2: Linear Heat Loss (Hours 1 to 3):
   • Core temperature declines steadily at a slower, linear rate.
   • Driven by environmental heat loss exceeding metabolic heat production (which is reduced by 20% to 30% under general anaesthesia due to loss of muscle tone and decreased cellular metabolism).
3. Phase 3: Thermal Plateau Phase (Hours 3 to 5+):
   • Core temperature stabilizes and ceases falling.
   • When core temperature drops to the anaesthetic-lowered vasoconstriction threshold (typically ~34.5°C to 35.0°C), hypothalamic vasoconstriction triggers, restoring peripheral vasoconstriction, confining metabolic heat to the core, and halting further core cooling.

Physical Mechanisms of Heat Loss in the Operating Theatre

Pathophysiological Complications of Inadvertent Perioperative Hypothermia ($< 36.0^\circ\text{C}$)

• Coagulopathy and Haemorrhage: Coagulation cascade enzymatic kinetics and platelet activation/aggregation are temperature-dependent. Each 1.0°C drop in core temperature increases intraoperative blood loss by roughly 16% and elevates the relative risk of allogeneic transfusion by 22%. Importantly, standard laboratory coagulation panels (PT, aPTT) are warmed to 37.0°C in the laboratory, completely masking this in vivo hypothermic coagulopathy.
• Surgical Site Infection and Impaired Wound Healing: Core hypothermia triggers thermoregulatory peripheral vasoconstriction, causing profound subcutaneous tissue hypoxia. Tissue hypoxia impairs neutrophil oxidative bacterial killing and reduces fibroblast collagen deposition, increasing surgical site infection rates 3-fold.
• Prolonged Drug Duration: Hepatic biotransformation enzyme activity slows, and renal excretion declines. The duration of action of non-depolarizing neuromuscular blocking agents (e.g. rocuronium, vecuronium) is prolonged by over 100%, predisposing to postoperative residual curarization.
• Adverse Cardiac Events: Hypothermia triggers sympathetic activation, elevating circulating noradrenaline levels, systemic vascular resistance, and blood pressure. The incidence of morbid cardiac events (myocardial ischemia, ventricular arrhythmias) is tripled in hypothermic elderly patients.
• Post-Anaesthetic Shivering: Post-extubation shivering increases total body oxygen consumption by 100% to 400%, inducing systemic hypoxaemia, carbon dioxide retention, lactic acidosis, and dangerous spikes in intraocular and intracranial pressures. Intravenous pethidine (meperidine 12.5-25 mg) or clonidine effectively suppresses shivering via central alpha-2 and opioid receptor modulation.