This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
The cardiac effects of digitalis extend further and may be seen in the action of the kidneys. With an unobstructed ureter a normal kidney will secrete more urine if more blood flows through it. And the factors which affect the amount of blood flowing through the kidney are: the general arterial pressure, the degree of contraction of the kidney arteries, and the freedom of the venous outflow. Venous back pressure, however slight, or contraction of the kidney arterioles, or a fall in general arterial pressure, will have a tendency to lessen the amount of urine; while a reversal of these conditions favors an increase in the amount of urine.
As measured by the oncometer, the normal kidney of an animal shrinks after a laboratory (poisonous) dose of digitalis. This diminution in size is synchronous with the vasoconstriction in other parts of the body and with the rise in arterial pressure, hence it may be assumed that the kidney arterioles, in the same way as the other arterioles, are constricted by poisonous amounts of digitalis. But in human therapeutics, as we have seen, there are presumably no essential constriction of arteries and no striking rise in arterial pressure. It is a fact also that the digitalis principles apparently reach the kidney in such diluted form that, in therapeutic amounts, they have no direct irritant action upon the kidney structures. Therefore the output of urine in persons with normal circulation is unaffected.
Hedinger (1910) gave digipuratum and digalen to rabbits intravenously, and when the kidneys were normal, obtained a slight increase in the volume of the kidney, but a scarcely perceptible diuresis. In the early stages of tubular nephritis he obtained increase in kidney volume (dilatation of the arterioles) and a greater diuresis. In more severe tubular nephritis and in vascular nephritis there was no diuresis. Jonnescu and Loewi obtained a small diuretic effect from digitalis in normal animals. They believed that the drug could cause a local dilatation of the kidney arterioles, as do most diuretics. In cases with normal rhythm and without edema, Cohn emphatically states that diuresis does not follow digitalis.
But in cases with low general arterial pressure, venous engorgement and edema, i. e., in persons with failing circulation, there is regularly very little urine formed; and in these cases the administration of digitalis may be followed by a great increase of the kidney excretion. In response to digitalis, in cases with failure of the circulation we have seen a urine output of 15 or 20 ounces a day change to one of 100 or 200 ounces, at least for two or three days. So digitalis is diuretic only when it brings about improvement in a poor circulation.
Digitalis diuresis is dependent upon - (a) improvement in the general circulation, through which accumulated tissue fluid passes into the blood to make hydremic plethora, and (b) improvement in the kidney circulation. It is not due to a direct action of the drug upon the kidney cells. Consequently the marked diuresis lasts only until the excess of fluid in the body brought about by venous stagnation is removed.
The urine is very dilute and poorly colored on account of the high proportion of water, but, at least for the first few days, contains an actual increase in the total solids, and particularly in the salts and urea. It is probable that this is due to the washing out of stored-up material.
In severe poisoning, digitalis may result in the appearance of albumin and blood in the urine. This is due either to a remote local irritant action resulting in nephritis, or to excessive vasoconstriction. Either of these may also be a cause of suppression of the urine. (Suppression is a term to be distinguished from retention. It signifies failure of the kidneys to secrete urine, while retention applies to the bladder, signifying failure of the bladder to empty itself.)
In cases with failing circulation there is regularly some degree of venous engorgement, i. e., venous back pressure. And venous engorgement means:
1. Increased general capillary transudation. This results in increased formation of tissue fluid.
2. Obstruction to the flow of lymph; because the lymphatics empty into the veins. This checks the removal of tissue fluid.
3. Lessened capillary absorption of tissue fluid, because of sluggish blood-flow.
4. A lessened amount of urine. This results in lessened excretion of water.
The effect of the combined action of these factors is accumulation of fluid in the tissue spaces and serous cavities of the body, i. e., edema and dropsy. There is "water retention" in the body, and the patient becomes water-logged. Edema is a condition in which there is an abnormal amount of fluid in the tissue spaces. Dropsy implies edema, but especially refers to abnormal collections of transuded fluid in serous cavities.
By improvement in the circulation digitalis removes the venous engorgement. As a result, the general capillary transudation, i. e., the formation of tissue fluid, is lessened, while at the same time improved capillary absorption and a proper flow of lymph remove the excess of tissue fluid. The result is the reduction of the amount of accumulated fluid in the tissue spaces and serous cavities. This fluid passes to the blood, swells its volume, and makes a condition of hydremic plethora. At the same time the rapidity of the renal blood-flow is increased, and this, together with the hydremic plethora, results in diuresis. Thus the excess of fluid is removed from the blood and eliminated from the body. The ultimate result is the disappearance of the dropsy and edema, without the loss to the body of its albuminous elements.
So digitalis tends to overcome dropsy and edema, not by simply removing the accumulated blood from the veins into the arteries, nor by directly stimulating the kidneys, but - (1) By lessening general capillary transudation; (2) by increasing the lymph-flow and promoting capillary absorption, and (3) by increasing the excretion of urine. All these depend upon its power to activate the circulation; or, in other words, its power to lessen venous engorgement.
The early stages of edema are not always obvious, for a human being can store a great amount of liquid beyond the normal before edema begins to show. But a greater or less degree of water-logging or water-storage is a regular accompaniment of a failing heart, so that even when the edema is not apparent, digitalis may prove diuretic.
Digitalis is of no value as a diuretic in the removal of serous exudations due to inflammatory or local causes, as in cirrhosis of the liver, peritonitis, etc., unless these are accompanied by circulatory inefficiency.