Respiratory failure in pulmonary anoxaemia
(a) The Ventilation in Pulmonary Hypoxemia The role played by chemical constituents of the blood in controlling pulmonary ventilation has been the subject of numerous investigations for over one hundred years since Kussmaul and Tenner in 1857 showed that a chemical stimulus was involved by experiments in which a large increase in ventilation was produced by breathing low oxygen mixtures and by re breathing from a bag. The earliest theory which attempted to account for these observations was put forward by Rosenthal in 1862, and again in 1882, He suggested that the oxygen content of the blood determined the ventilatory response. He discounted any place for CO2 in the regulation of ventilation on the basis of experiments showing that inhalation of high concentrations of CO2 (20 to 30$) did not affect the breathing, Pfluger had shown in 1868, however, that both excess of C02 provided it was not too great, and oxygen lack stimulated the ventilation. In a series of brilliant cross circulation experiments on dogs, Fredericq (1901) appeared to confirm the then prevalent assumption that the influence of these factors was a direct one upon the brain, but the Heymans (1927),father and son, were later to show that there were chemosensitive areas of the aortic arch and carotid sinus capable of responding to alterations in the concentrations of C02 and oxygen in the perfusate,and that these receptors transmitted impulses to the respiratory centres by the vagus nerves. Further studies by Heymans and Riglant (1933) and v. Euler, Liljestrand and Zotterman (1939) showed in anaesthetised cats that the carotid sinus nerves were in a state of continuous tonic excitation. When the oxygen saturation of the blood fell even slightly below the normal of 96$ this chemoreceptor discharge of nervous impulses increased. Gesell, Lapides and Levin showed in 19^0 that blocking these sinus nerve impulses in animals by the application of cold to the nerves depressed the ventilation when the animals were breathing room air at rest. These observations were confirmed by Marshall and Rosenfeld (1936). All of these workers agreed that hypoxaeinia was more effective than CO^ excess in increasing the peripheral chemoreeeptor activity, whereas CCg excess in the arterial blood was the major factor in stimulating the central respiratory control mechanism. The relative importance of the central and peripheral mechanisms in maintaining the pulmonary ventilation under varying conditions was estimated in a quantitative way by Gesell et al. (v.s.) using the cold block technique. The part played by the peripheral chemoreceptors in controlling the ventilation in response to a fixed degree of hypoxaemia varied between 0 and 100$ according to the concentration of C02 which the animals breathed. The greater the amount of C02 in the inspirate the less was the effect on the ventilation of blocking the nerves. When 5 or 6$ CO^ was inspired nerve blocking had no effect, showing that in these circumstances respiration was 100$ controlled by a central mechanism which was presumably insensitive to liypoxaenia. Bjurstedt (19*»-6) and Gernandt (19*+6) confirmed these observations and found that the greater the acidity of the blood, the less was the effect upon respiration of blocking the sinus nerves. Bjurstedt also showed that in the early stages of acute hypoxia, the peripheral chemoreceptors played a large part in controlling the respiration; but this part gradually decreased with time until, over a period of six to ten hours, it became slight as the pK of the blood fell towards normal. The maximum hypoxaemic stimulus to respiration coincided with the time at which the pH was most raised due to CO,, washout. The mechanism of the compensatory decrease in plasma bicarbonate which resulted in the return of the blood pH towards normal was assumed to be a renal one due to diminished tubular reabsorption of bicarbonate. This renal compensatory phenomenon had been studied by Haliane (J.S.), Kellas and Kennaway in 1919 and also by Haldane (J.B.S.) in 1921. They observed that the initial alkalinity of the blood upon acute exposure to hypoxia gradually decreased with time, the pH of the blood becoming less upon continued exposure. Y. Henderson in studying the same process in 1919 showed that the 'hypocapnia \*as followed by a hypocarbia Winterstein (1956) noted that hypoxaemie human subjects given 100$ oxygen to breath in the early stages of the period of oxygen lack reacted by becoming apnoeic. If the anoxaemia was continued over a longer time the duration of apnoea due to breathing oxygen decreased. All of these observations point to a direct relationship between the magnitude of the hypoxaemic stimulus to respiration and the pH of the blood. It would appear to be reasonable to test the implication that hypoxaemic emphysematous subjects with marked C0^ retention and lowered blood pH should show little or no immediate decrease in pulmonary ventilation on breathing high concentrations of oxygen.