T28 



NATURE 



[September 23, 1920 



dardised carefully by Haldane, and we now know 

 that the man who shows loo on the scale has an 

 oxygen capacity of 0185 c.c. of oxygen for every c.c. 

 of blood. We can, therefore, in cases of carboxy- 

 haemoglobin or methEemoglobin poisoning, express 

 the absolute amount of oxyhaemoglobin pressure 

 either by stating the oxygen capacity and so getting 

 an absolute measurement, or in relative units by 

 dividing one hundred times the oxygen capacity by 

 0185, and thus getting a figure on the ordmary 

 hsemoglobin metre scale. 



The Mechanism of Anoxaemia. 



Perhaps the most difficult phase of the discussion 

 is that of how anoxEemia produces its baneful results. 

 Before you discuss whether a certain effect is due to 

 cause A or cause B, be clear in your own mind that 

 A and B are mutually exclusive. 



Let me take an example and suppose 

 (i) That the energy of muscular contraction in the 

 long run depends in some way on the oxidation of 

 sugar ; 



(2) That in the absence of an adequate supply of 

 oxygen the reaction CjH,30,+60j = 6COj+6HiO can- 

 not take place in its entirety ; 



(3) That in such circumstances some lactic acid is 

 formed as well as carbonic acid ; 



(4) That the hydrogen-ion concentration of the 

 blood rises and the total ventilation increases. On 

 what lines are you to discuss whether the increased 

 ventilation is due to "acidosis," by which is meant in 

 this connection the increased hydrogen-ion concentra- 

 tion of the blood, or to "anoxaemia"? Clearly not 

 on the lines that it must be due to one or other, for 

 in the above instance anoxaemia and acidosis are, to 

 some extent, dependent variables. 



I have chosen the above case because measure- 

 ments have been made throughout which make the 

 various assumptions fairly certain, and tell us pretty 

 clearly in what sort of chain to string up the events, 

 what is cause and what is effect. Clearly it would 

 be ridiculous to start a discussion as to whether the 

 breathlessness was due to "acidosis " or "anoxEemia." 

 Each has its place in the chain of events, but 1 have 

 heard discussions of whether other' phenomena of a 

 more obscure nature were due to oxygen want or to 

 acidosis. Such discussions tend to no useful end. 



Nor is this the onlv problem with regard to oxygen 

 want concerning which my warning is needed. 

 Oxygen want may act immediately in at least two 

 ways : 



(i) In virtue of absence of oxygen some oxidation 

 which otherwise might take place does not do so, 

 and therefore something which might otherwise 

 happen may not happen. For instance, it may be 

 conceived that the respiratory centre can go through 

 the rhythmic changes of its activity only as the 

 result of the oxidation of its own substance. 



(2) \ deficient supply of oxygen may produce, not 

 the negation of a chemical action, but an altered 

 chemical action which in its turn produces toxic pro- 

 ducts that have a secondary effect on such an 

 organism as the respiratory, centre. 



Now these effects are not mutually exclusive. In 

 the same category are many arguments about whether 

 accumulations of carbonic acid act specifically as 

 such or merely produce an effect in virtue of their 

 effect on the hydrogen-ion concentration. Here again 

 the two points of view are not, strictly speaking, 

 alternatives, and, in some cases at all events, both 

 actions seem to go on at the same time. 



It will be evident that in any balanced action in 

 which CO2 is produced its accumulation will tend to 

 retard the reaction ; but, on the other hand, the same 



NO. 2656, VOL. 106] 



accumulation may very likely raise the hydrogen-ion 

 concentration, and in that way produce an effect. 



It is rather fashionable at present to say that " the 

 whole question of acidosis and anoxaemia is in a 

 hopeless muddle." To this I answer that if it is in 

 a muddle, I believe the reason to be largely because 

 schools of thought have rallied round words and have 

 taken sides under the impression that they have no 

 common ground. The "muddle," in so far as it 

 exists, is not, I think, by any means hopeless; but 

 I grant freely enough that we are rather at the 

 commencement than at the end of the subject ; that 

 much thought and much research must be given, 

 first, in getting accurate data, and, secondly, on 

 relating cause and effect, before the whole subject 

 will seem simple. No effort should be spared to re- 

 place indirect by direct measurements. My own infer- 

 ence with regard to changes of the reaction of the 

 blood, based on interpretations of the dissociation 

 curve, should be checked by actual hydrogen-ion 

 measurements, as has l>een done by Hasselbach and 

 is being done by Donegan and Parsons.* Meakins 

 also is, I think, doing great work by actually testing 

 the assumptions made by Haldane, Priestley, and him- 

 self as regards the oxygen in arterial blood. 



T}ie Compensations for Anoxaemia. 



For the anoxic type of ano.xaemia two forms of 

 compensation at once suggest themselves. The one 

 is increased haemoglobin in the blood; the other is 

 increased blood-flow through the tissues. Let us, 

 along the lines of the calculations already made, 

 endeavour to ascertain how far these two types of 

 compensation will really help. To go back to the 

 extreme anoxic case already cited, in which the 

 hsemoglobin was 66 per cent, saturated, let us, first, 

 see what can be accomplished by, an increase of the 

 haemoglobin value of the blood. Such an increase 

 takes place, of course, at high altitudes. Let us sup- 

 pose that the increase is on the same grand scale 

 as the anoxaemia, and that it is sufficient to restore 

 the actual quantity of oxygen in i c.c. of blood to 

 the normal. This, of course, means a rise in the 

 haemoglobin value of the blood from 100 to 150 on 

 the Gowers scale. Yet even so great an increase in 

 the haemoglobin will increase the oxygen taken up 

 in the capillary from each c.c. of blood only from 

 0031 to 0036 c.c, and will, therefore, leave it far 

 short of the 006 c.c. which every cubic centimetre 

 of normal blood was giving to the tissue. So much, 

 then, for increased haemoglobin. It gives a little, but 

 onlv a little, respite. Let us turn, therefore, to 

 increased blood-flow. 



In the stagnant typ>e of anoxaemia the principal 

 change which is seen to take place is an increase in 

 the quantity of haemoglobin per cubic millimetre of 

 blood. 



This increase is secondary to a loss of water in the 

 tissues, the result in some cases, as appears from the 

 work of Dale, Richards, and Laidlaw,' of a forma- 

 tion of histamine in their cells. Whether this 

 increase of haemoglobin is to be regarded as merely 

 an accidental occurrence or as a compensation is 

 difficult to decide at present. Roughton's calcula- 

 tions rather surprised us by indicating that increased 

 haemoglobin acted less efficiently as a compensatory 

 mechanism than we had expected. This conclusion 

 mav have been due to the inaccuracy of our assump*- 

 tions. I must therefore remind you that much 

 experimental evidence is required before the assump- 



8 Donesan and Parsons. Jmmatof Physlolegy, vol. lii., p. 315, I9'9. 



9 Dale and Richards. Journal of Physiology, vol. lii., p. no, I9'9- 

 Dale and Laidlaw. Ibid., p. 355. 



