Response
Division of Nephrology
St Michael's Hospital
University of Toronto
Toronto
ON, Canada
Sir,
We thank Dr Rosival for his interesting comments. It is true that important authorities, such as those he cited, do state that a low pH in arterial blood can lead to a decreased level of consciousness. Nevertheless, one must ask: ‘What is the compelling evidence to believe that this is ‘cause-and-effect’, rather than an association’. Paraphrasing Beveridge,1 one can never prove anything to be correct experimentally. Rather the scientific principle is that one ‘flawless’ experiment with an ‘ugly fact’ will disprove a ‘beautiful hypothesis’, even if the association is observed in many situations’. In this context, since the blood pH can fall below 7.0 during a sprint2 while there is no obvious ‘deterioration in CNS status’, these data are not consistent with a direct linkage between a decreased level of consciousness and a very low blood pH.
Our impression is that a decrease in CNS function may be seen when metabolic acidosis is accompanied by a low ECF volume with poor haemodynamics.3 The essence of the argument is as follows. While it may seem obvious that the severity of the metabolic acidosis (indicated by how low the concentration of 
in plasma was) is the most important determinant of the H+ load to be removed by the brain, the novel features of the bicarbonate buffer system described in reference 3 prompts us now to think otherwise.
Our view is that the expected physiological response to a large H+ load is to have H+ removed by the bicarbonate buffer system;4 this requires a low pCO2 in capillaries in the location where most of the bicarbonate buffer system exists (in the interstitial fluid and in cells of skeletal muscle). If this capillary pCO2 rises unduly due to a slow blood flow rate in response to the contracted ECF volume, the majority of in the body is not available to remove most of these new H+. Hence the brain will be presented with a much higher H+ load. If, in addition, the haemodynamic state is compromised sufficiently to undermine the autoregulated cerebral blood flow rate, the pCO2 in capillaries at the blood–brain barrier should rise and this will divert H+ from the bicarbonate buffer system in brain cells. The resulting high intracellular H+ concentration will force more H+ to bind to intracellular proteins, which will change their charge and perhaps, their shape and function, with potentially devastating results.
Infusing enough isotonic saline to improve the blood flow to skeletal muscles is perhaps the most effective way to ensure that buffering by the bicarbonate buffer system in the interstitial fluid and in cells of skeletal muscles has improved; this is indicated by a fall in the brachial venous pCO2. As a result, fewer H+ will bind to proteins in brain cells, and their ‘ideal charge’ should be restored.5 On the other hand, a low arterial pCO2 is necessary, but not sufficient for this ideal, non-cerebral, buffering of H+.
References
1. Beveridge WIB. (1951) Art of Scientific investigation Penguin Books.
2. Cheetham M, Boobis L, Brooks S, Williams C. (1986) Human muscle metabolism during sprint running. J Appl Physiol 61 54–60.
3. Halperin ML, Kamel KS, Maccari C, Carlotti ACP, Bohn D. (2006) Strategies to reduce the danger of cerebral edema in a pediatric patient with diabetic ketoacidosis. Ped Diabetes 7 191–5.[CrossRef]
4. Vasuvattakul S, Warner LC, Halperin ML. (1992) Quantitative role of the intracellular bicarbonate buffer system in response to an acute acid load. Am J Physiol 262 R305–9.[Medline]
5. Zalunardo N, Lemaire M, Davids MR, Halperin ML. (2004) Acidosis in a patient with cholera: A need to redefine concepts. Q J Med 97 681–96.
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