Reply to Pavithran's question: Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?

E.S.Prakash, Editor, Medical Physiology Online, e-mail: medicalphysiologyonline@gmail.com

I refer to Pavithran's question [1]: Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?

The study by Mullin et al [2] specifically investigated the effects of directly lowering CSF calcium levels without altering serum ionized calcium or pH on neuromuscular responses. In these experiments, the authors note that the tetanic phenomena in the animals could have been caused by calcium levels in the CSF as low as 0.1 mM (normally CSF [Ca] is 1.2 mM). They also observed that exposing the lower spinal cord to a calcium poor solution did not produce a noticeable change in muscular tension indicating that the low concentration of calcium in brain interstitial fluid bathing cell bodies of neurons (and not plasma ionized calcium) was the cause for the increased neuromuscular excitability in these experiments. I do not know of clinical states in which CSF calcium levels would reduce to this extent without changes in serum calcium.

Edmonson and colleagues [3] compared the effects of rapid intravenous infusion of ethylene glycol tetraacetate (EGTA) alone versus hypocapnic alkalosis in thyroparathyroidectomized animals and the interaction between hypocalcemia and alkalosis on the "onset of tetany". Their data indicate that hypocapnic alkalosis reducing arterial PCO2 to between 10-20 mmHg alone is associated with tetany even if it is not accompanied by a significant lowering of ionized calcium in serum. However, in the presence of significant hypocalcemia (serum ionized calcium between 0.5 and 0.9 mM) induced by rapid infusion of EGTA, tetanic symptoms are evident at a slightly higher PCO2 (20-30 mmHg). There is a clear time lag of the order of hours for equilibration of calcium ions across the blood brain barrier. In contrast, changes in minute ventilation produce changes in CSF pH instantly. The authors also note that ventilation with a gas containing 5% CO2 was a more rapid and effective means of terminating tetany produced by EGTA and thyroparathyroidectomy than administration of calcium. Thus, this study by Edmonson et al [3] provides clear evidence of an interaction between serum hypocalcemia and respiratory alkalosis in the genesis of tetany and that CSF pH is a key modulator of neuronal excitability.

Conflict of interests: none

Note: This submission was not peer reviewed.

References:

[1] Pavithran P. Which is more important in the genesis of tetanus and tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis? Medical Physiology Online [serial online] article 3.7, volume 1, 2008, available from http://medicalphysiologyonline.blogspot.com

[2] Mullin FJ, Hastings AB, and Lees WM. Neuromuscular responses to variations in calcium and potassium concentrations in the cerebrospinal fluid. Am J Physiol 1938; 121: 719-727

[3] Edmondson JW, Brashear RE, Li TK. Tetany: quantitative interrelationships between calcium and alkalosis. Am J Physiol 1975; 228: 1082-1086