Acidosis from capillary poisons

Abstract

In a study of pathological conditions of the capillaries, and the effects of these conditions on the body as a whole, we have sought for some agents which produce widespread capillary damage. There is a considerable number of substances classed as capillary poisons. Some of these, for example histamine, produce functional changes, others, such as uranium and diphtheria toxin, produce structural changes. If the change produced results in a damage to the capillary wall, there should be a decrease in its permeability. The tissue cells supplied by the capillary would receive less blood and oxygen, with a resulting abnormal metabolism. It seemed to us that this effect might take the direction of an acidosis. The following figures, obtained from experiments on dogs, the Van Slyke apparatus being used for the alkali reserve determination, bear out this conception.

A study of the table shows that uranium, cantharidin, arsenic, and diphtheria toxin, which cause widespread capillary damage, bring about a definite acidosis. Podophyllotoxin and emetine,

whose action is confined to the intestinal capillaries, cause no acidosis. Hydrazin, which is not classed as a capillary poison, but which produces changes confined to the liver, and comparable to those seen in phosphorus poisoning, causes no acidosis. Histamine, given by subcutaneous injection in repeated and eventually fatal doses caused an increase in alkali reserve, given intravenously to an anirnal sensitized by ether, it causes acidosis.

If our conception of the cause of the acidosis from these capillary poisons is correct, it should follow that other agents which interfere with the supply of oxygen to the tissues in other ways would also cause acidosis. This is indeed the case. Nitrites, which induce methaemoglobin formation, and cyanides, which prevent the utilization of oxygen by the tissues, bring about a marked acidosis.