PATHOLOGY 387 trouble. As to the acute yellow atrophy of the pregnant state the circumstances are doubly complex. In all the incidents of preg nancy we must take into account the placental function, a meta bolism almost as great for the time as that of the liver itself; and, if we are to find any link of connexion between the seemingly diverse conditions here in question, we should have to resort to the somewhat vague generality that, in a rare concurrence of circum stances, the placental function makes demands upon the maternal blood and tissues, or upon the ordinary metabolisms of the mother, which are of an upsetting kind, the incidence falling sometimes on the metabolic functions of the liver.
- umin- Albuminuria. The waste of albumen in the course of the
t .. urinary excretion is a much more frequent and hardly less serious factor in disease than the sugar - waste ; but albuminuria differs from diabetes in two important respects : firstly, the albumen which escapes is, in great part at least, the proper albumen of the blood (serum-albumin and globulin); and secondly, there goes hand in hand with the error of function a series of progressive structural changes fatal to the general efficiency of the kidney itself. Albuminuria is the functional error that corresponds on the whole closely to fright s disease ; but it would be a mistake to suppose that Bright s disease can be measured by the amount of albumen lost. A con sideration of these complex forms of constitutional disturbance may proceed, however, from the side of albuminous leakage, and from the point of view of the adaptations in the kidney whereby the leakage is ordinarily prevented or reduced to a minimum. The problem, as it maybe called, of the renal excretion is how to discharge from the blood and from the body absolutely the wash ings of the tissues, or the waste-matters of metabolism, without allowing other dissolved substances of the blood to be discharged at the same time. In adaptation hereto, the kidney is in part a secreting organ and in part a mechanical filter. Those parts or regions of its structure where its epithelium is in the form of very large and richly protoplasmic cells have a true secretory function, so that nothing passes from the blood to be cast out from the body except through the interior of a very considerable cell, and in all probability through a metabolic selective process therein. This is known to be the urea-region of the kidney ; and the separation of urea from the blood may be said to be the greatest of the renal functions. But by far the largest part of the urine, namely the water of it, is strained off from the blood by another kind of kidney- structure, which is more truly a mechanism ; not all the water of the urine, but the greater part of it, is filtered from the blood as it passes through the remarkable coils or glomeruli of small vessels which are placed at the farther end of the tubular system. In these the structural adaptations all point to mechanical filtration and not to selective secretion. The circulation in the vascular coils of the kidney is unique as regards the balance of driving force and resisting force ; the lateral pressure in these spherical coils of small vessels is greater than in any other capillary region of the body. It is indeed great enough to cause a transudation of water ; but is it so nicely balanced as not to allow an escape of albumen ? P-sio- There can be no question that albumen does often find its way into If cal the urine without amounting to a serious functional error or to a
- i iiuiii- clinical condition of disease; and it is equally certain that the
u .. leakage takes place at the glomeruli. Albumen is found so often in the urine when it is looked for systematically from day to day that we may admit, with Senator, that any one may be more or less albuminuric from time to time. In 119 healthy soldiers, 19, or 16 per cent., had albumen in the urine ; in 200 seemingly healthy persons examined for life assurance there were 24 with albumen, or 12 per cent. ; in 61 healthy children, 7, or 11 - 5 per cent ; in 32 hospital attendants in good health, 14, or 44 per cent. Add to these experiences the difficulty of detecting small quantities of albumen in ordinarily dilute urine and the impossibility of detecting certain varieties of albumen (known to occur in the urine) except by special tests, and we may safely conclude that the filtration of water from the blood in the renal capillaries is very apt to be attended with a slight leakage of albumen also. The adaptation that water should drain off, but not albumen, is a very nicely balanced one, and therefore very easily upset. As a matter of fact it is frequently upset ; the physiological albuminuria, like the physiological glycosuria, and like the small admixture of colourless cells among the multitude of blood -disks proper, is the narrow margin of non- perfect adaptation which meets us frequently in the economy of living organisms. The nicely-adjusted balance of driving .force and resisting force in the vascular tufts is constantly exposed to disturbing influences, so that one may reckon to find a certain small average of albuminous leakage. The great occasion of this leakage is sluggish circulation through the glomeruli, whether from over-distension of the veins beyond or from other cause. The faster the blood passes through these capil laries the greater the quantity of water drained off, and the more minimal the quantity of albumen that escapes ; but when the blood travels slower there is absolutely less water filtered off in a given time, and the proportion of albumen that passes with it is increased from a minimal quantity to something considerable. Thus a con gested state of the kidney, whether the embarrassment be traced to the side of influx or of efflux, to the arterial or the venous side, is favourable to the leakage of albumen, and a large part of all the albuminuria of medical practice is of that nature. The congested state has been often experimentally induced in animals by various devices, and the laws of albuminous leakage have thus been determined with an exactitude which is very considerable. In these experiments the embarrassment of the circulation has been induced in various ways by clamping the renal vein so as to dam up the blood in the kidney, by clamping the renal artery, by inter fering with the nervous mechanisms, either at the spot or more centrally, and by introducing toxic substances into the circu lating blood. Probably all of these forms of experimental inter ference have their analogies in disease, although the gross mechan ical impediments are a rare type. The albuminuria of the pregnant state not certainly an invariable occurrence, but rather a liability of that condition may be referred in great part, if not altogether, to embarrassed venous reflux, for there are analogous cases of tem porary albuminuria in which the cause is not the gravid uterus, but a uterine or ovarian tumour. In pregnancy it is specially apt to occur in primipar.ie and in cases of twins, and in the later months. Again, the albuminuria of some forms of heart-disease, of emphy sema, and of chronic bronchitis is an affair of difficult venous reflux. It is on the arterial side that we have to place the deter mining forces of a considerable number of albuminuric cases, and these the most insidious. In all those cases where the congestion of the kidney is " inflammatory " there are the irregularities of circulation usual in inflammation, the parenchymatous cellular changes of inflammation, and the somewhat difficult correlation between these two factors in the process.. These cases may be said to exhaust the instances of albuminuria due to heightened blood- pressure. The albuminuria of cachectic subjects is known to be dependent mostly on the impaired integrity of the glomerular vessel-walls, on an amyloid change in them which permits the transudation of albumen under the ordinary conditions of pressure. But there is still a third determining cause of albuminuria, namely, a changed state of the blood when both the pressure and the state of the vessel-walls are constants. It has been mentioned that there are two instructive points of contrast between the drain of sugar and the drain of albumen ; the sugar is not ordinarily present in the blood, and its discharge by the kidney is unattended with structural changes in that organ. The albumen of albuminuria is to a great extent the ordinary albu men of the blood (serum-albumin and globulin) ; but in the urine there are other albumins found which are not ordinarily present in the blood, such as the variety identical with pepton, and another variety, hemialbumose, or " propepton. " The latter is found in cases of osteomalacia, and it may be detected under other circum stances as well. Even when there are no new and specially diffus ible albumins in the blood, it is probable that some alteration in the relative composition of the blood in the proportion of its salts and the like will make its albumen more liable to transude in the renal glomeruli. The albuminuria of phosphorus-poisoning and of acute yellow atrophy of the liver raises another possibility, the possibility, namely, that the albumen is produced in the course of the meta bolic process in the proper secreting epithelium of the kidney- tubules. Certainly the large epithelial cells of the kidney in these two conditions are filled with peculiar granules of "albuminous" matter. The question has to be at least entertained, whether certain cases of albuminuria may not be due to a primary disorder of the renal metabolism, to some interference with its "ferment." Four factors, then, are concerned in the waste of albumen, and they may act either singly or in combination. In the order of their importance they are : (1) disorder of the vascular pressure, whereby the nicely-adjusted filtering mechanism in the glomeruli is deranged ; (2) states of the blood exceptionally favourable to the diffusion of its albumen, or even the presence in the blood of pecu liar forms of albumen with high difl usibility ; (3) a more perme able condition of the vessel-wall (as in amyloid disease) ; and (4) an error in the proper metabolism of the secreting epithelium where by an albuminous by-product is formed from it. It now remains to consider briefly the other distinctive point in the acquired habit of albuminous waste, namely, the associated structural changes. Structural Changes in the Kidney. If the kidneys be examined Large from a case in which the symptoms, sometimes lasting for years, white had been albumen in the urine (with cylindrical casts of the kid- kidiiey. ney-tubules), a more or less scanty amount of urine, and a small proportion of urea, together with dropsy and marked anaemia, they will most likely be found to be enormously enlarged, and of a pale fawn colour, compared by Watson to the cut surface of a parsnip. This is the "large white kidney" of chronic Bright s disease, the enlargement being in the outer zone of the organ, in the region of the glomeruli and secreting tubules. "The incised surface gives one the notion of some deposit whereby the original texture of the part is obscured." How comes it that an attack of congestion at some more or less remote period, or repeated congested states of the
