Applied cardiovascular & respiratory physiology

Overview & definition

The applied cardiovascular and respiratory physiology is the substrate on which every anaesthetic acts. The anaesthetic drugs and the controlled ventilation alter the cardiac output, the vascular tone, the respiratory mechanics, and the gas exchange in the predictable ways that the anaesthetist must master. This topic integrates the cardiovascular determinants of the flow, the oxygen delivery, the lung mechanics, and the ventilation-perfusion matching into a coherent framework that explains the perioperative hypoxaemia, the hypotension, and the rationale for the monitoring and the fluid and the vasoactive therapy.[1][2]

The cardiac output and its determinants

The cardiac output (the CO) is the volume of the blood ejected by the heart per minute — the product of the stroke volume and the heart rate. The four determinants are the heart rate, the preload, the contractility, and the afterload:[1][2]

• The heart rate. The CO rises with the rate up to a point; beyond about 160 beats per minute, the shortening of the diastole reduces the filling time and the CO falls. The autonomic nervous system is the principal control.
• The preload. The end-diastolic ventricular wall tension (the stretch of the myocytes before the contraction). By the Frank-Starling mechanism, the stroke volume rises with the preload up to the optimal sarcomere length, then plateaus. The preload is determined by the venous return (the volume status, the venous tone, the position, the intrathoracic pressure).
• The contractility (the inotropy). The intrinsic force of the contraction at a given preload. Increased by the sympathetic stimulation, the catecholamines, the calcium, and the inotropes; decreased by the hypoxia, the acidosis, the myocardial disease, and most anaesthetics.
• The afterload. The wall tension against which the ventricle ejects, principally determined by the systemic vascular resistance (the SVR). A high afterload increases the cardiac work and reduces the stroke volume (in the failing heart).[1]

The Frank-Starling mechanism and the Guyton venous return

The Frank-Starling curve relates the stroke volume (the cardiac function) to the preload. The heart ejects what it receives: the cardiac output equals the venous return over time. The venous return is driven by the systemic filling pressure (the mean circulatory filling pressure, raised by the venous tone and the volume) minus the right atrial pressure, divided by the resistance to the venous return. The positive-pressure ventilation raises the intrathoracic pressure, raises the right atrial pressure, and therefore REDUCES the venous return and the cardiac output — the basis of the anaesthetic hypotension at the induction.[1]

The curve is shifted upward by the increased contractility and downward by the decreased contractility. The failing heart operates on the flat portion of the curve (the preload reserve is exhausted); the fluid challenge in the preload-dependent patient increases the CO, while in the non-dependent patient it only causes the pulmonary oedema.[2]

The arterial pressure and the systemic vascular resistance

The mean arterial pressure is the product of the cardiac output and the systemic vascular resistance (the MAP equals the CO times the SVR, plus the central venous pressure). The SVR is determined by the arteriolar radius (the fourth-power relationship in the Poiseuille law — a small radius change has a large effect) and the blood viscosity. The arteriolar tone is controlled by the sympathetic nervous system, the local metabolites, the hormones (the renin-angiotensin, the vasopressin), and the endothelial factors (the nitric oxide). The anaesthetics reduce the SVR (the vasodilation) and the contractility, the dual effect that produces the anaesthetic hypotension.[1][2]

The oxygen delivery and the Fick principle

The oxygen delivery (the DO2) is the total oxygen delivered to the tissues per minute — the product of the cardiac output and the arterial oxygen content:[2]

DO2 = CO x CaO2, where CaO2 = (1.34 x Hb x SaO2) + (0.003 x PaO2). [1]

The dissolved oxygen term (0.003 x PaO2) is small at the normal PaO2; the bound haemoglobin term dominates. The DO2 is therefore governed by the cardiac output, the haemoglobin, and the saturation. The tissues extract about 25 per cent of the delivered oxygen at rest (the oxygen extraction ratio); the DO2 can fall by about half before the anaerobic metabolism (the lactate) develops, the critical DO2 threshold. The optimisation of the DO2 (the fluid, the inotropes, the transfusion, the oxygen) is the goal of the goal-directed haemodynamic therapy. The Fick principle (the VO2 equals the CO times the arteriovenous oxygen difference) allows the cardiac output to be measured.[2][3]

The oxygen cascade and the alveolar gas equation

The oxygen partial pressure falls from the inspired gas (about 160 mmHg in the room air) through the airways, the alveolus (about 100 mmHg), the arterial blood (about 95 mmHg), the capillary, the mitochondrion (about 1 to 2 mmHg) — the oxygen cascade. The alveolar partial pressure (the PAO2) is given by the alveolar gas equation: [1]

PAO2 = FiO2 x (Patm - PH2O) - PaCO2 / RQ, [1]

where the Patm is 760 mmHg, the PH2O is 47 mmHg, and the RQ (the respiratory quotient) is about 0.8. The PAO2 falls with the hypoventilation (the rising PaCO2) and the reduced FiO2, and rises with the supplemental oxygen. The preoxygenation (the denitrogenation with the 100 per cent oxygen) builds the alveolar and the functional-residual-capacity oxygen reserve that sustains the apnoeic patient.[4]

The oxyhaemoglobin dissociation curve and its shifts

The oxyhaemoglobin dissociation curve (the sigmoid relationship between the PaO2 and the SaO2) reflects the cooperative binding of the oxygen to the haemoglobin. The curve is shifted RIGHT (the lower affinity, the easier unloading) by the increased hydrogen ion, the increased PaCO2, the increased temperature, and the increased 2,3-diphosphoglycerate (the 2,3-DPG) — the metabolic regulator of the oxygen affinity that rises in the chronic hypoxia, the anaemia, and the high altitude. The curve is shifted LEFT (the higher affinity, the harder unloading) by the alkalosis, the hypothermia, the low PaCO2, the low 2,3-DPG (the stored blood), and the fetal haemoglobin.[6]

The inhalational anaesthetics have a small effect on the curve, but the relevant shifts in the anaesthetic practice include the alkalosis (the left shift, the impaired unloading) and the transfusion of the stored blood (the low 2,3-DPG, the left shift, resolving over 24 hours).[7]

The lung volumes, the compliance, and the surface tension

The static lung volumes are the tidal volume, the inspiratory reserve, the expiratory reserve, and the residual volume; the capacities (the combinations) include the functional residual capacity (the FRC) — the volume in the lungs at the end of the expiration, the equilibrium of the inward lung recoil and the outward chest-wall recoil. The FRC is the oxygen reservoir and the determinant of the apnoea tolerance.[4]

The compliance (the change in the volume per unit change in the pressure) is determined by the tissue elasticity and the surface tension. The Laplace law (the pressure equals 2 times the surface tension divided by the radius) means the small alveoli would collapse into the large ones without the surfactant; the pulmonary surfactant (the type II pneumocyte product) lowers the surface tension at the small radius, stabilising the alveoli. The loss of the surfactant (the ARDS, the neonatal respiratory distress) lowers the compliance and causes the atelectasis.[4]

The ventilation-perfusion matching and the dead space

The gas exchange depends on the matching of the ventilation (the V) and the perfusion (the Q) in each lung unit. The ideal V/Q is about 0.8. The mismatched units produce the shunt (the perfusion without the ventilation, the V/Q of zero — the atelectasis, the pneumonia, the oedema; the hypoxaemia that does NOT improve with the supplemental oxygen) and the dead space (the ventilation without the perfusion, the V/Q of infinity — the pulmonary embolus, the emphysema; the wasted ventilation with the preserved oxygenation). The alveolar dead space fraction (the dead space divided by the tidal volume) is a marker of the V/Q mismatch and predicts the weaning.[5]

The anaesthesia increases the shunt (the atelectasis) and the dead space (the reduced pulmonary perfusion), both contributing to the impaired gas exchange.[5]

The control of breathing

The breathing is controlled by the brainstem centres (the medullary, the pontine) that integrate the chemoreceptor and the mechanoreceptor inputs. The central chemoreceptors (the medulla) respond to the CSF hydrogen ion (driven by the CO2), the principal drive to breathe. The peripheral chemoreceptors (the carotid bodies) respond to the arterial PaO2, the PaCO2, and the pH, and provide the rapid response to the hypoxia. The anaesthetics and the opioids depress both the central and the peripheral drives, producing the hypoventilation and the apnoea; the residual opioid effect is a cause of the postoperative respiratory depression.[8]

The effect of the anaesthesia on the respiratory system

The general anaesthesia has several adverse respiratory effects:[4][5]

• The fall of the FRC by about 15 to 20 per cent at the induction, from the loss of the diaphragmatic tone, the supine position, and the chest-wall relaxation. The FRC may fall below the closing capacity (which rises with the age and the disease), causing the airway closure and the atelectasis in the dependent lung.
• The atelectasis in the dependent regions, the shunt, and the rapid desaturation.
• The reduced compliance and the increased work of breathing.
• The inhibited hypoxic pulmonary vasoconstriction by the volatile agents, worsening the V/Q mismatch.
• The depressed ventilatory drive by the anaesthetics and the opioids. [1]

These effects are opposed by the preoxygenation, the protective ventilation (the PEEP, the recruitment), and the supine-to-head-up positioning.[4]

The effect of the anaesthesia on the cardiovascular system

The general anaesthesia reduces the cardiac output and the arterial pressure through the vasodilation (the reduced SVR), the reduced contractility, the blunted baroreflex, and the raised intrathoracic pressure (the positive-pressure ventilation reducing the venous return). The induction is the high-risk moment — the simultaneous vasodilation, the myocardial depression, and the positive-pressure ventilation can precipitate the severe hypotension in the hypovolaemic, the elderly, and the vasculopathic patient. The goal-directed haemodynamic therapy (the cardiac index and the DO2 targets, the individualised) aims to maintain the tissue oxygen delivery.[2][3]

The applied integration — the perioperative hypoxaemia

The perioperative hypoxaemia integrates the respiratory effects: the reduced FRC, the atelectasis (the shunt), the V/Q mismatch, the depressed drive, and the airway obstruction. The prevention and the management — the preoxygenation (the denitrogenation and the FRC reserve), the apnoeic oxygenation (the THRIVE), the protective ventilation (the low tidal volume, the PEEP, the recruitment), the head-up position, and the reversal of the opioids — follow directly from the physiology. The recognition of the shunt (the oxygen-refractory hypoxaemia) versus the V/Q mismatch (the oxygen-responsive) guides the response.[4][5]

[1] [1]

Red flags

[1] [1] [1] [1] [1]

References

1. [1]Miller A. Energy, flow and pressure in the cardiovascular system: a narrative review of how the circulation works Anaesthesia, 2026.PMID 42157570
2. [2]Mirus M, et al. Hemodynamic monitoring: basic principles in operation room and intensive care unit J Clin Monit Comput, 2026.PMID 41493520
3. [3]Flick M, et al. Personalized hemodynamic management targeting preoperative baseline cardiac index in high-risk patients having major abdominal surgery: rationale and design of the international multicenter randomized PELICAN trial Trials, 2026.PMID 41904483
4. [4]Nimmagadda U, et al. Preoxygenation: Physiologic Basis, Benefits, and Potential Risks Anesth Analg, 2017.PMID 28099321
5. [5]Nakamura S, et al. Association Between Intraoperative Alveolar Dead Space Fraction and Early Extubation After Glenn and Fontan Procedures J Cardiothorac Vasc Anesth, 2026.PMID 42225457
6. [6]Jaafar LS. 2,3-Diphosphoglycerate: the forgotten metabolic regulator of oxygen affinity Br J Nutr, 2025.PMID 41070558
7. [7]Kumar A, et al. Effects of inhaled anaesthetic agents on the oxygen dissociation curve: An updated discussion J Perioper Pract, 2025.PMID 39991860
8. [8]Honing M, et al. Cholinergic Chemotransmission and Anesthetic Drug Effects at the Carotid Bodies Molecules, 2020.PMID 33348537