We may devise a fluid containing practically all the inorganic diffusible constituents of the blood except calcium, and use it to dialyze normal blood in such a way as to remove from it a large part of its calcium. The dialyzed blood when perfused through an isolated extremity produces an extreme hyperexcitability of the nerves quite like that observed in tetany. Since perfusion with blood dialyzed in precisely the same way against a fluid of the same composition, but containing calcium in the proportion found in the normal blood, causes no hyperexcitability of the nerves, it is evident that the hyperexcitability is due to the lack of calcium. This effect can be attained in only a slight degree by replacing the blood of a whole animal with the dialyzed blood, since under the conditions of the experiment the tissues cannot be sufficiently depleted of their calcium. It seems probable that the parathyroid secretion is not removed by dialysis, but is returned to the body with the dialyzed blood. To bring this result into relation with the condition in tetany following parathyroidectomy, animals in tetany were bled and the blood was replaced in one case with normal blood, in the other with dialyzed blood poor in calcium. The normal blood immediately relieves the tetany and lowers the excitability, while the dialyzed blood does not. We therefore believe that this is a further proof that in the tetany of parathyroidectomy also the twitching and hyperexcitability of the nerves is due to lack of calcium in the blood and tissues.
It has been our aim to determine in what particular the blood is altered during tetany so that it can produce hyperexcitability of the motor nerves. As a working hypothesis it has been assumed that (1) there may be a lack of calcium in the blood and tissues; (2) there may be a circulating poison which like an oxalate could render inactive the circulating calcium; and (3) there may be a substance in circulation vaguely resembling strychnia in its action upon the nervous system and directly causing the hyperexcitability. It is impossible to decide with our present knowledge which, if any, of these explanations is the true one, but certain experimental results are brought forward. If tetany blood be used to perfuse a normal leg the excitability of the nerves rises to a characteristically high level and the addition of parathyroid extract to the blood has little or no effect in lowering this excitability. Parathyroid extract whether from the ox or the dog fails when injected into the circulation of an animal in tetany to reduce the excitability of the nerves markedly or permanently, although it seems to affect the more sensitive ganglion cells thus cutting off excessive impulses to the periphery. Although the nerves remain hyperexcitable, tetany is usually much diminished or abolished entirely. This seems to be analogous to the action of ether or any other anesthetic which may inhibit the activities of the ganglion cells, although it leaves the nerves excitable and able to conduct impulses. An animal in tetany relaxes instantly on being given ether although the excitability of the nerves to electric currents is little changed. Bleeding followed by the replacement of the blood with an indifferent solution free from calcium stops tetany and lowers the excitability of the nerves. Probably this cannot be ascribed to the removal of a circulating poison, but rather to a general disturbance of the nutrition of the nervous system. Oxalate-like substances introduced into the circulation rapidly, and for a short time only, may kill the animal, but they seem to produce no change in the excitability of the nerves. If the solution is injected very slowly and over a long period the protective action of the body seems to be overcome and the excitability of the nerves rises to high levels. This seems to resemble somewhat the latent period after the destruction of the parathyroid before tetany begins. Direct analysis of the blood shows that as compared with the normal, the blood of an animal in tetany is very poor in calcium. Administration of parathyroid extract does not increase this calcium content. On the contrary, if the extirpation of the parathyroids has been incomplete so that tetany does not appear, the calcium content of the blood is that of the normal animal. Even yet, therefore, in spite of our efforts to shake it, the theory that tetany is closely dependent upon a disturbance of the calcium content of the blood is supported by stronger evidence than any other idea, but much remains to be done before a clear conception of the process is reached.