388 PATHOLOGY organ, have led to so remarkable a result ? It does not help us, for the purpose of rational analysis, to turn to "inflammation" as a last resource ; what the analysis really conducts us to is the corre lation between the disordered function and the structural changes. It is impossible not to connect the remarkable form of hyper- plasia in the large white kidney (or where there is also the amyloid complication) with the albuminous character of the exuda tion in which the organ, and more especially its cortex, is bathed. Sugar, as we have seen, has no such effect on structure, nor has uric acid, as we shall see in speaking of the kidney in gout ; the albumen has a special influence on the local centres of nutrition, on the cells and tissues of the organ. Again, the excess of nutri tion does not conduct to increase on the normal lines. There are such cases of normal increase in the kidney s bulk, as when one kidney has to do the work of two, owing to removal or congenital absence of the other. But in the large white kidney of albumin- aria the increase is of an unprofitable kind ; it is a hypcrplasia that not only does not add to the efficiency of the organ but even seri ously impairs it. The large epithelial cells of the secreting region are clouded with albuminous deposit, and their nuclei show a fainter reaction to the colouring agents ; or they fall into an unstable granular condition and into molecular detritus ; or they are shed bodily into the lumen of the tubule. The flattened cells of the Bowman s capsule are less apt to degenerate ; they are more likely to multiply in situ, and to build up an unnaturally thick wall around the capsule. Further, the interstices of the tubules and the margins of the glomeruli are occupied by collections of round nuclear cells, like the collections underlying a catarrhal mucous membrane. All this activity is misdirected ; it does not help the function, but overwhelms it. The urine is scanty and the propor tion of urea small ; and these consequences may be traced, firstly to the sluggish circulation within the organ, and secondly to the complete obliteration of some glomeruli and the cumbrous thicken ing of others, and to the degeneration of the secreting epithelium interfering with its proper metabolism. There is hardly any tendency to rcstitutio ad integrum in the large white kidney, the unprofitable overfeeding of its elements continuing to the end. Granular Contrasting with the large white kidney is the contracted kidney 2on- in another variety of chronic Bright s disease. For the present tracted purpose it is necessary to follow the broader lines of distinction, kidney. an d to avoid the transitions and finer shades in the pathology ; and it may be stated as a general truth that the large white kidney goes with scanty urine and much waste of albumen (the waxy modifica tion having only the latter), while the small granular contracted kidney is associated with even copious urine and a waste of albu men which is often small, and in any case variable. The error in these latter cases appears to lie with the arterial side of the circula tion ; the left heart is hypertrophied, and so is the muscular coat of the arteries in the kidney, if not also elsewhere. It is essen tially an interstitial disease of the kidney, leading to enormous development of its supporting tissue ; whole tubules become obli terated, but in those that remain the epithelium is not degenerated. Obliteration also overtakes the glomeruli, but there must be a compensating increase in the work done by those that survive to account for the copious urine ; it often happens, also, that num erous small cysts are produced. Shrinkage of the connective tissue after a period of revived embryonic activity is the cause of all these changes ; it is the ordinary shrinkage of cicatricial tissue, and it has the effect of com pressing the proper urinary apparatus the filtering and the secret ing to its destruction. The kidneys may be reduced even to one- fourth of their natural size, and their uneven surface shows that there has been mechanical dragging along certain lines. In the end the urea- waste accumulates in the blood to such an extent that death results, usually from unemic coma and convulsions. In some cases cerebral haemorrhage anticipates the fatal effect of uraemia. The small granular contracted kidney is usually of a reddish- brown colour, but it may be whitish, in which case the lobulation of its surface is larger. It is one of the standing difficulties of renal pathology to decide whether the small contracted kidney is not often a later stage of the large white. But there can be hardly any doubt that it is oftenest the structural manifestation of an entirely different disease, an arterial disease. That which has been emphasized by some pathologists as the distinctive process in this affection is the overgrowth of cells on the inner wall of the arteries, the so-called endo-arteritis or arterio-capillary sclerosis, whereby the lumen of the vessel tends to be occluded. But it may be made a question whether this is not really a part of the revived embry onic activity in the connective tissue, whose shrinkage gives the organ its granular contracted character. The interest would thus come to centre in the error of nutrition whereby so much activity is diverted to the connective tissue, an activity that takes the em bryonic formative direction. We have a close analogy in cirrhosis of the liver, a disease associated with the drinking of raw spirits ; and it is noteworthy that the insidious form of Bright s disease, whose morbid anatomy is summed up in the small contracted and puckered kidney, occurs most frequently in those who sustain themselves more by ardent spirits than by ordinary food, and next most frequently in the subjects of gout and of lead -poisoning, although there are a good many cases of the disease remaining to be accounted for by less obvious causes. The dropsy of Bright s disease is difficult in its pathology. The Drops watery state of the blood, or the hydrsemia, consequent on the loss of of much of its albumen does not suffice by itself. A subsidiary Bright hypothesis, adopted by Cohnheim, is that the blood-vessels of the disease skin become unusually permeable. Sometimes the dropsy appears first round the ankles, at other times it shows itself in pulliness of the eyelids and a somewhat bloated pallor of the face. Gout and the Uratic Diathesis. Many other states of the system Gout, besides podagra the disease which usually begins in the night with pain and redness of the great-toe joint are now reckoned as be longing to gout. The disease, in the extended use of the name, is indeed a widespread error of metabolism which may manifest itself in very various ways. The particular liabilities to error arise dur ing the metabolism of protcids, from the first stage of digestion in the stomach to the last stage of excretion in the kidney. Hence it is that gout, in its widest meaning, has been taken to be a form of "dyspepsia." The opportunity for going wrong may be said to depend on the fact that there are two chief forms of nitrogenous waste remaining to be got rid of in the end, which are somehow correlated to one another, the highly soluble substance urea, and the highly insoluble substance uric acid. There are remarkable differences in the proportions of these two waste-products through out the animal kingdom ; in most reptiles and in birds the fonn of nitrogenous waste is mostly uric acid, whereas in man (and other mammals) it is mostly urea. But in man the waste is still to a small extent in the form of uric acid. In normal human urine the proportions are : to 1500 grammes (52 91 ounces) of water in the urine of twenty-four hours the total of solids is 72 grammes (2 54 ounces), of which 33 18 (1 17 ounces) are urea, and only "555 ( - 019 ounce) uric acid, or not more than one-sixtieth of the quantity of urea. Whether or not we are to regard this small margin of uric acid as another of those instances of non-perfect adaptation of which we have previously found instances in the physiological traces of sugar and of albumen in the urine, and of colourless corpuscles in the blood, there can be no doubt that the adaptation, such as it is, whereby the nitrogenous waste is mostly the highly soluble urea, but to a very small amount also the less soluble uric acid, is the occasion of many and serious morbid con ditions. The liability to these gouty and calculous disorders depends partly on the increase of uric acid at the expense of the urea, together with the low solubility of the former, but it seems to depend also on an abnormally low power of the animal fluids to dissolve uric acid, or of the kidney to eliminate it when its quantity is not excessive. The peculiar liability from uric acid is sometiines called the Urati iiric-acid or uratic diathesis or constitution ; some persons have it ,ii a . much more than others, and it is exceedingly apt to be handed tliesii- down from parent to offspring, so that the stock, in countries and among classes where gout is common, may be said to be widely inoculated with it. Where the acquisition of it can be traced at first hand it is often found that the associated circumstances are high-feeding and a life of physical inaction and feeble intellectual zest. These are among the best-known conditions of gout, admitted equally by the ancients and the moderns. It is now known, how ever, that practically the same gouty constitution may be and often is induced by conditions which have hardly anything in common with luxury. Thus gout is a common liability of workers in lead, being one of the various manifestations of lead-poisoning ; it is also common among those classes of labourers, such as dock- labourers on the Thames, whose habitual drink is porter ; and it is said to have become common among the working-class in Dublin, where it was rare twenty or thirty years ago, according as they have taken to drinking porter instead of ardent spirits. There are still other cases of gouty constitution for which neither heredity, nor luxury, nor lead-poisoning, nor porter-drinking can be in voked as an explanation ; and these are the cases which justify the somewhat wide definition of gout as a form of dyspepsia. In order to have the gouty effect there need be no great increase Uric in the amount of uric acid formed in the course of the metabolism in go of proteids. During an acute attack of gout, and previous to it, the amount of uric acid in the urine will probably be much below the average ; it is the kidney that has failed in its function, so that the uric acid is retained in the blood to be deposited else where. The presence of uric acid (urato of soda) in the blood in gout is the well-known discovery of Uarrod, who has also pointed out that its proportion in the urine is at the same time reduced. But there need not even be failure of the kidney s function, al though, as a matter of fact, there often is ; the error may lie in the heightened insolubility of the uric acid. It is observed that the uric acid of urine is apt to be deposited in the form of nrates, as a brick -red sediment, even when there is no excess of it; a more acid state of the urine seems to favour the precipitation of the uric acid ; and it has been conjectured (from the success of the
