URÆMIA.*

BY E. P. SWIFT, M. D.

The study of uræmia, with an effort to determine its etiology, reveals the fact that of the many theories advanced to account for the phenomena described under this general term, none are wholly satisfactory. In view of our imperfect knowledge of the mechanism of the physiological functions of the healthy kidney it is not surprising that pathological conditions more or less dependent upon derangement of those functions should also be imperfectly understood.

A patient under my care, suffering from abscess of one kidney, was passing, prior to operation, 76 oz. of urine of sp. gr. 1010. The removal of the diseased kidney was followed by increase of the urinary secretion, which when he left the hospital, seven weeks later, was 140 oz. per diem, with sp. gr. of 1008; the remaining organ having thus nearly doubled the amount of work previously done by both.

Equally difficult of explanation is the fact, demonstrated by Bradford, in experiments on dogs, that if two-thirds of both kidneys are removed there will result an increased secretion, both of urine and of urea, and the animal will continue to live; but if three-fourths are removed, death always results, the increased secretion of urea being accompanied by rapid wasting and breaking down of muscular and other tissues.

The mechanical process by which the chlorides are eliminated from the kidney secretions in certain acute diseases, and that by which the varying proportions of the sulphates and phosphates are controlled, remains undiscovered. But while there. is still much that is obscure in the field of physiology as related to the kidney and its functions, there are some clinical facts from which reasonably accurate conclusions may be drawn in determining the cause of certain pathological states.

The set of symptoms known as uræmia, was formerly taught to be due to an excessive accumulation of urea in the blood as a result of defective elimination. That urea alone is not accountable for the production of the phenomena is proved by the fact * Read before the Clinical Club, November 20, 1903.

that many cases in which the excretion of this substance is markedly deficient, do not have the clinical evidence of uræmia.

Neither can it be said that the retention in the system of the entire urinary secretion is always followed by uræmic symptoms.

Of forty-one cases of complete anuria, due to blocking of both ureters, convulsions occurred in only five, headache in only six, and vomiting in only twelve. Consciousness is usually retained, there is very little discomfort, and death occurs, unless prevented by surgical interference, in from four to fourteen days, apparently as a result of asthenia.

The theory of Traube that the condition was the result of cardiac hypertrophy, hydræmic conditions of the blood, and cerebral edema, has some arguments in its favor, but must be discarded as not applicable to all cases.

Carleton, quoting a French authority, concludes that there is, first: a dominating toxic element caused by failure of the diseased kidney to perform satisfactory elimination of the débris of the organism. Second: a mechanical factor, cerebral anæmia, the localization of which in the motor zones may cause convulsions.

In explanation of the frequent occurrence of uræmia during the puerperal periods there is a corresponding diversity of opinion.

Dienst thinks that, as a cause of maternal intoxication, some unknown poison is formed in the fetus, which passes into the maternal blood, and that this fetal poison acts upon the maternal tissues because the kidneys are unable to excrete it He asserts that the poisons produced result from the metamorphosis of albuminous bodies.

Fehling agrees with him that eclampsia is caused by an over-production of toxins in the fetus due to metabolism.

Manton believes that during pregnancy the maternal secretory organs undergo functional and anatomic changes, and that when their limit of work is reached improper functionating begins. If the maternal organs can secrete this added amount of waste products then the mother remains well, but if for any cause these organs do not eliminate these substances they accumulate in the system and a vicious circle results.

H. Müller considers eclampsia to be the result of the absorption of bacterial toxins which have their habitat in the genital

tract.

Schmorl reports three autopsies upon women who died during the latter half of pregnancy from eclampsia, in two of whom the kidneys were diseased and in one not. All three showed evidences of severe intoxication of the nervous system. Albert believes that eclampsia results from the absorption of the metabolic products of bacteria in the decidua.

And so the opinions of other observers might be enumerated, each differing from the others, but all practically agreeing upon one point: that there is a condition of auto-intoxication due either to the retention of normal waste products which are imperfectly eliminated, or to the results of an abnormal metabolism. Assuming the correctness of this view, the question at once suggests itself: What is it that so demoralizes the working forces of the body and permits it to become surcharged with toxic material of its own manufacture? As a possible aid in arriving at a satisfactory solution of this problem, I wish to refer to a case reported by Dr. W. H. Thompson, in May of the present year.

The patient, a lady, sixty years of age, previously wellnourished and healthy-looking, suddenly became dizzy and fell from her chair. This attack was followed by pronounced symptoms of uræmia which persisted in spite of all the usual methods of treatment for two months. By that time her condition had become critical, with alarming attacks of dyspnoea, and syncope, mild delirium, pains in the head and convulsive twitching of the muscles of the face and extremities. The left ventricle was much dilated and the aortic sound accentuated. The radial artery felt small but smooth, with no signs of thickening or atheroma. The pulse was irregular, but of very high tension. The urine was scanty with a faint trace of albumin, and with granular and hyaline casts, but no blood cells.

A thorough trial of the nitrite group of vasodilators and heart stimulants having had no effect, it was decided to give full doses of aconite; 5 drops of the tinct. every 3 hours, with the object or reducing the arterial pressure.

In a few days improvement in all her symptoms were per

ceptible; her digestion became better, mental and nervous symptoms vanished; the arterial tension disappeared; the daily output of urea rose from 120 to 480 grains; the character of the heart action improved, apical impulse became perceptible and slowly increased in force, and the pulse became regular and fuller. Within a week the patient sat up, supported by a bed-rack, for ten minutes, without marked change in the pulse.

The aconite was continued for six months in the same doses. The patient slowly improved and sat out of bed from 6 to 8 hours daily, going out to drive, etc. Twice the dose of the aconite was reduced, but the return of high tension and diminution of the urea output to 200 grains, with return of cardiac weakness, caused the resumption of the original dosage. At the end of six months the aconite was discontinued, and the nitrites substituted for it for one month. Cardiac weakness and high tension developed again and the urea fell to 150 grains daily. Aconite was again substituted, and again the heart action and pulse improved, arterial tension lessened, and the urea increased to 450 grains. After four months more the aconite was discontinued, as vasodilators seemed to be no longer indicated. The patient continues to lead a carefully regulated life, makes and receives visits, takes walks and drives, and has steadily improved in strength and appearance.

I have quoted this case at length because I believe that it furnishes a clew to the true cause of uræmia and a valuable suggestion as to its treatment. To Brown Sequard is due the credit of suggesting that the kidney has an internal secretion and that many of the symptoms of uræmia are due to its disturbance. The effects of the secretion of the adjacent suprarenal glands upon the vasoconstrictors is well known, and it is easily possible that a similar action may result from disturbance of the functions of the kidney itself. Overbach made the observation that simple clamping of the renal artery in dogs for forty minutes was followed by albuminuria for twenty days. Inflammatory accumulation in the cellular tissue would result in restriction of the supply of arterial blood to the glomeruli by compression. I think we are warranted in assuming that interference with the normal supply of arterial blood to the kidney from any cause will result not only in a

derangement of its functions, but in the discharge into the circulation of an excessive amount of the internal secretion of the gland. Since it has been shown that the removal of a large part of the kidney results in increased output of urea and waste products, it is evident that this internal secretion must exert an inhibitory influence upon the metabolic process, and when excessive in amount, its effect would be to cause diminished elimination with ischemia. The high arterial tension reduces still further the blood-supply of the kidney, produces, first, hypertrophy, then dilatation of the heart, and by inducing cerebral anæmia is in itself a cause of headache and dizziness, and many of the other symptoms included under uræmia.

Shaffer's experiments have shown that the injection of suprarenal extract, with the vagi cut, or paralyzed by atropia, results in high vascular tension, accompanied by violent heart action; the intra-cranial blood pressure being thus greatly increased with resulting epileptiform convulsions.

In puerperal eclampsia an analogous condition is present. The kidneys, which may or may not have been previously diseased, have their normal blood supply restricted by pressure of the gravid uterus, there is an excessive secretion of the vasoconstrictor substance by the kidney, the inhibitory influence of the vagi upon the heart action is overcome and convulsions and coma ensue. The same is true in post-scarlatinal cases in which acute parenchymatous congestion of the organ has affected its blood supply. It is probable that the paralysis of the vagi in these cases is due to the action of accumulated poisons, resulting from metabolism, which the kidneys are unable to eliminate.

My conclusions, then, briefly stated, as to the etiology of uræmia are:

First: deficient blood supply to the kidney.

Second: the secretion by the kidney of a substance resembling in its effects the extract of the suprarenal gland.

Third: high arterial tension with diminished excretion of

urea.

Fourth excessive intracranial vascular pressure, with increased heart action, resulting in uræmic headaches, paralyses, or eclampsia.