Ventilation is the movement of air between the lungs and the surrounding environment.
Ventilation is key to maintaining adequate arterial oxygenation and for the removal of CO2. Under normal circumstances, breathing is a passive process controlled by centres in the brainstem. These respiratory centres are specialised groups of neurones. The complex interaction of these neuronal collections are responsible for ventilation.
Three such groups have been identified: the pons respiratory centre, the medullary respiratory centre and the pre-Bötzinger complex.
The pons (primary) respiratory centre is composed of two centres.
The medullary respiratory centre is composed of two groups.
Respiratory rhythm is thought to be generated by the pre-Bötzinger complex. The neurones here exhibit pacemaker-like activity which is thought to drive the DRG.
Central chemoreceptors exert siginifcant influence over the respiratory centres in response changes to acid/base balance.
Located on the ventrolateral surface of the medulla, central chemoreceptors are sensitive to changes in pH within the cerebrospinal fluid (CSF). The central nervous system itself is separated from the blood by the blood-brain barrier which hydrogen ions (H+) are unable to cross.
Instead, carbon dioxide (CO2) levels are responsible for pH changes in the CSF. CO2, which is lipid soluble, easily diffuses through the blood brain barrier. In the CSF, it forms carbonic acid with water. Carbonic acid then may dissociate to hydrogen ions and bicarbonate. An increase in hydrogen ions leads to a reduction in the CSF pH.
Respiratory acidosis - caused by raised CO2 - is quickly detected via the mechanism described above leading to compensatory changes. The impact of systemic metabolic acidosis on this system is not fully understood.
It is thought that a systemic metabolic acidosis like diabetic ketoacidosis or lactic acidosis stimulates central chemoreceptors. Animal studies have shown activation of central chemoreceptors in metabolic acidosis may occur, likely due to subtle changes in CSF pH.
Local cerebral hypoxaemia will also activate central chemoreceptors due to the development of a localised metabolic acidosis.
This system, though slower than the peripheral chemoreceptors, is the primary stimulus of ventilation and is estimated to provide 80% of the stimulus for a ventilatory response to a raised arterial CO2.
Peripheral chemoreceptors are able to bring about rapid changes to ventilation in response to fluctuations in arterial pH, O2 and CO2.
There are two sets of peripheral chemoreceptors:
These ‘bodies’ are bathed in blood thanks to sinusoidal capillaries. A reduction in O2 or an increase in CO2 causes an increase in ventilation.
They act more rapidly than central chemoreceptors and are estimated to provide 20% of the stimulus for a ventilatory response to raised arterial CO2.
Respiratory failure occurs when there is inadequate gaseous exchange in the lungs.
Two types of respiratory failure are traditionally described. This reflects the underlying aetiology. It should be remembered that these are not entirely distinct, instead existing on the same pathological spectrum.
See notes titled Lung function tests for more details.
Type I respiratory failure is characterised by:
Type I respiratory failure typically occurs due to a ventilation / perfusion mismatch or a shunt.
Type II respiratory failure is characterised by:
Type II respiratory failure typically occurs secondary to reduced airflow with alveolar hypoventilation.
It has long been taught that in the presence of chronic hypercapnia (for example in some COPD patients) hypoxia becomes the primary drive of ventilation. This was thought to be due to desensitisation of the respiratory centre to raised CO2. Therefore, in acute deteriorations treatment with high-flow oxygen targeting high O2 saturations would risk respiratory depression.
The reality is this theory was posited several decades ago and now represents an outdated understanding of the underlying processes. It is true that in a subset of patients with COPD, high flow oxygen during an acute exacerbation will cause oxygen-induced hypercapnia. However, any depression in ventilation in this group of patients is mild and short-lived. Any contribution to oxygen-induced hypercapnia is considered limited.
It is now understood that other mechanisms for oxygen-induced hypercapnia are in effect, namely:
The need for reduced O2 saturation targets in these patients remains. COPD patients who are CO2 ‘retainers’ should have saturation targets of 88-92%.
The exact working of these is beyond the scope of this note. For those interested details, a concise paper on the topic can be found: Abdo et al. Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care. 2012;16(5):323
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