Chemoreceptor Chapter-the Control of Breathing

After 100 years of research, nature has been astonishingly reluctant to reveal how breathing is controlled in any mammal.
Following the award of the Nobel Prize for the discovery of arterial chemoreceptors in 1938, it was believed only a matter of
time before someone sorted out the details of how they might account for the control of breathing. But now it is more obvious than
ever before that they cannot. Instead, what must be one of the most fundamental questions in physiology remains unanswered.
There is no absolute definition of “control” in the context of breathing. To a physiologist, its key element is whatever mechanism
matches breathing to metabolic rate so well between rest and maximum exercise. “Control” has more subtle connotations too. For
instance, a specified minute ventilation can be achieved with a number of difference combinations of breathing frequency, tidal
volume and drive. But why any one particular combination is chosen too is beyond the scope of this review. Furthermore for a busy
clinician, exercise (raising metabolic rate) is irrelevant and the concern is diagnosis and management of sinister changes in arterial
blood gases and the distressing symptoms of dyspnoea in bed ridden patients (at low and unchanging metabolic rates). This article
will focus only on trying to understand how breathing matches metabolic rate in exercise (as metabolic rate rises). It will not
deliberately review the clinical implications of blood gas changes at constant metabolic rate.
Here the words control and matching will be used interchangeably. We believe breathing is controlled to regulate something.
This something has always been presumed to be arterial blood gas levels. But, as explained below, it could be something entirely
different, with the stability of arterial blood gases being just a fortuitous coincidence. Control might be achieved either via a classic
feedback mechanism (potentially slow but accurate) or feedforward (instantaneous but potentially inaccurate). We have so little
understanding even of how breathing is controlled in utero (where fetal breathing movements do not influence the oxygen supply to
the fetal brain), or about what initiates breathing at birth. With these issues in mind, there is little benefit to the next generation of
scientists in simply repeating the old shibboleths about the control of breathing that appear in every textbook. It is not sensible to
presume even that all mammals (that fly, or dive, are quadrupeds or bipeds) must share the same control mechanism. Neither is it
always sensible to speculate about control mechanisms in humans just by mixing disparate observations from a range of other
species. From what little knowledge we have about how breathing matches metabolic rate, it is also remarkably difficult to provide
clinicians with any useful information to assist in understanding, diagnosis or treatment of disorders of breathing at resting
metabolic rate (e.g., Sudden Infant Death Syndrome, Cheynes Stokes breathing or Chronic Central Hypoventilation Syndrome).
A more critical evaluation of the current limitations of our knowledge in humans of how breathing matches metabolic rate might
therefore be useful. The next generation of scientists might then be in a better position to identify the key ideas to pursue and to
appreciate more quickly the relevance or otherwise of new information.
Whilst extensive citation of references here is inappropriate, a few key references are given and the detailed arguments discussed
here are fully referenced in the reviews cited under further reading.