A text book on uric acid and its congeners, with special reference to its physical and chemical properties, its metabolism and accumulation in the organism, together with the disease processes arising therefrom and their ætiological therapy

Front matter

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Preface

This volume is offered as a means of enabling physicians and students to better acquaint themselves with the fundamental principles of uric acid and its accumulation in the organism: a subject which every doctor is supposed to be somewhat familiar with, though one which is barely touched upon in any of our standard text-books. The need of such a work at the present time is almost imperative, not only on account of the vital bearing of the subject upon the ills of human kind, but in order that applicants for license to practice medicine may possess some medium for acquiring the specific information so often demanded of them. For instance, atone of the examinations, held not long ago by the New York State Medical Examining Board, among other interesting questions propounded in the Physiology paper occurred the following: " How is uric acid 'developed in the human system? What class of foods increases the development of uric acid?" A few years ago, physiologists would have been obliged to give quite different answers to these two questions than are given to-day. Yet the physician is supposed so keep himself fully abreast of the times and explain such mooted points satisfactorily. To do so, however, he must, perforce, seek assistance from various rare sources outside his library. He must have access to scores of foreign and domestic scientific medical journals, which have been issued from time to time during the past four or five years. Scattered throughout their numerous pages, he may, iv PREFACE.

if sufficiently patient and persevering, find some highly instructive papers on the subject, written by professional chemists and other experts. But he must be able to sift the "wheat" from the "chaff" — the "truth" from the "poetry." Many of the older chemical theories have been exploded; therefore, it is only by extensive and painstaking research through this form of literature that a proper understanding of the present status of the uric acid question can be formed.

It is partly to fill thismanifest want that the present work has been published. In it have been brought together from all available sources the results of the experimental work of competent Swedish, French, German, Russian, English and American investigators, the deductions from whose findings are presented as far as may be in a simple straightforward manner and from the most practical viewpoint.

Few vital questions before the medical profession to-day possess greater interest than does this of uric acid; and it has therefore been the aim here to furnish needed information along such lines as will enable the physician or student to better comprehend the subject and apply his added knowledge to some practical use. G. A. G.

179 Main St., Danbury, Conn.

CHAPTER I. Its Place in Nature. page

As a Nitrogenous Excrement 7

As a Plant Food 8

Anabolism vs. Catabolism 8

Location in Vegetable Food 9

Location in Flesh Foods 10

Its Cumulative Action 10

Its Power for Good or Evil 11

CHAPTER II. Historical Review

Discovery of Uric Acid (1776) 13

Early Chemical Findings (1 793-1848) 13

The Early Medical Theory (1 797-1870) 14

Garrod's Discovery (1848-1854) 16

Garrod's Theory 17

Early Xanthin Findings (1851-1889) 17

Early Theory Exploded (1868-1893) 18

Recent Findings (1 895-1905) 20

CHAPTER VIII. Accumulation in the Organism

Purin Removal 68

Normal Finding of Uric Acid 68

Its Presence a Menace 69

Toxicity of the Purins 69

Why Not Urea? 70

Uric Acid Excess 70

Purin Foods 72

Tables of Exogenous Purins 73

Meats 73, 74

Vegetables , 74

Beverages 74

Miscellaneous 75

White vs. Dark Meats 75

CHAPTER IX. Accumulation in the Organism {Continued)

Blood Alkalescence 77

Urinary Acidity "... 78

Weakened Reaction of Blood 79

Deposition of Urates 80

Effect of Alcohol 82

CHAPTER X. Disease Processes

Purin Excess 84

Its Three Stages 84

(1) Uricacidremic Stage.

Names 85

Increased Viscosity 86

Capillary Obstruction 86

Localization of Symptoms 87

Faulty Metabolism 87

(2) Rheumatic Stage.

Names 88

Transition Period 88

Localization of Symptoms 89

(3) Gouty Stage. page

Formative Period ^ 90

Localization of Deposits 91

CHAPTER XL (ij Uricacid/emic Manifestations.

Pain 95

Headache 96

"Next Morning" Headache 97

Fits of Blues 98

Insomnia 99

Headache Powders 100

The Neuroses 102

Periodicity of Symptoms 102

CHAPTER XVI. Uric Acid Tests

Murexid Test 139

Approximate Test 140

Heat and Acetic Acid Test 140

Heintz' Test 141

Harley's Test 142

Schiff's Test 142

Dimrock and Branson's Method 142

PAGE

Microscopic Examination 143

The Complicated Tests 144

The Uricometer 144

Hall's Purinometer 145

A Simple Test 145

CHAPTER XXXIII. Final Word

Autotoxemia Due to a Non-toxic Factor, 289; The Uric Acid Diathesis, 290; Extent of Investigation, 290; Uric Acid Destruction, 291; Experiments Extra Corpus, 291; Croftan on the Rationale of the Alkaline Treatment, 292; Minkowski and von Noorden on Treatment, 293; Prof. Mendel's Discovery, 294; Classification into Three Stages, 294; Uric Acid an Intermediate Product, 295; Urea the End Product of Purin Catabolism, 295.

URIC ACID

AND

ITS CONGENERS.

Chapter I Its Place In Nature

As a Nitrogenous Excrement. — Nitrogenous metabolism is recognized to be one of the most important of life's vital processes, of which, in the animal kingdom, uric acid is one of the two essential end products. Though man and many other vertebrate animals give off their urinary nitrogen principally in the form of urea (86 per cent.), birds, insects and reptiles excrete theirs almost entirely as uric acid.

Why uric acid should be the end product of tissue metamorphosis in some animals, and not in others, has long remained a mystery to the physiologist. It would seem only rational, however, in the light of modern evolutionary science, to conclude that the excretions of animals must necessarily correspond with the individual structural environments of such excretions — i. e., their respective anatomical organs. The mammal, with its kidneys and accessory genital organs, has reached an anatomical evolutionary development which necessitates its nitrogenous waste being presented in a more soluble form — i. e., urea. In other words, a morphological structure like the kidney, and a physiological excretion like urea, necessarily go hand in hand— evolve pari passu.

The fowl and serpent, and other oviparous animals (those that spawn or lay eggs), have never been evolved to the stage requiring a special urinary apparatus, therefore there is no necessity of their nitrogenous excreta being presented in the more highly oxidized form of urea; for, inasmuch as the ureters end in a common cloaca with the rectum, it may pass out with the feces in the less soluble form of uric acid. It has been noted, too, that the red blood corpuscles of all oviparous animals contain nuclei — not observed in the red globules of mammals.

As a Plant Food. — The complementary and antithetical relationship existing between the metabolic processes of the animal and vegetable kingdoms is often very strikingly illustrated. The animal, for instance, exhales carbon dioxid, and inhales oxygen: the plant absorbs the former and gives off the latter. One furnishes what the other needs.

In a similar manner the fruits of plants serve as a food for animals, while the excrement of animals serves as a food for plants. For years, guano has been used by the agriculturist as a fertilizer. The guano of commerce is obtained from the islands off the coast of Peru, to which large flocks of sea-birds resort. It is chiefly composed of their excrement in a decomposed state and consists principally of uric acid in the form of ammonium urate.

Anabolism vs. Catabolism. — The nitrogen, or ammonium content (NH 4 ), of uric acid (probably nitrate of ammonium), is utilized bv the plant as a food-essential which either is combined with, or is instrumental in the combining of other elements, to form and elaborate tissue

ITS PLACE IN NATURE. 9

structure. It is a singular fact that plants have the power of building up or forming from the simple inorganic elements in Nature, the complex organic structures of which they are composed and which serve as food for animals. In short, their metabolic process is chiefly a synthetic process.

Animals do not possess this power. On the contrary, they take the complex substances already built up by plants, which, in becoming a part of the animal organism (i. e., digested, absorbed and assimilated), are decomposed into their original elementary parts. The metabolic process in animals is chiefly an analytical process.

The plant, as may be seen, utilizes uricacid as a food constituent; while the animal excretes it as useless waste. In this way, this substance has become an important factor in the cycle of life: in the anabolism of vegetable tissue and the catabolism of animal tissue.

Location in Vegetable Food. — Uric acid does not, of course, occur, as such, in plants. It is synthesized to an allied form of purin or xanthin. It is located where we would naturally expect: in the vitalizing or fecundating organs of the plant, i. e., in the germinating seeds, ovules and leaves — as in coffee and tea, peas and beans. In short, it is found in the parts analogous to the secreting organs of animals — the vegetative or reproductive parts: where it appears, in one, an active source of metabolism, and in the other as a passive result.

The uric acid or ammonia derivative, in plants, exists as an "alkaloid"; as theobromin (from cacao beans and seeds of theobroma cacao); caffein or theophyllin (from seeds of the coffee tree or from tea leaves) ; morphin ; codein; narcotin; quinin; strychnin; veratrin; atropin; etc. In animals, the analogous bases from which uric acid is metabolized, are guanin, xanthin, hypoxanthin, adenin, etc.

Location in Flesh Foods. — By "flesh food," we mean the flesh or meat of dead animals. The blood and tissue-juices of these dead animals contain the waste debris salts (uric acid, xanthins, etc.), which the animal was about to excrete, and would have excreted as useless had it not been killed. This waste, therefore, cannot be considered as a food proper, since it has already been cast off from the disintegrating or dying cells of the animal.

Again, the nuclein of the cellular tissues of the animal (composing muscle-fibers and glands) must also be decomposed after ingestion, into its cleavage products, the xanthins, thus serving as another food-source for uric acid. In one case, the xanthins already exist as free bases in the tissue-juices of the dead animal; in the other, they are organically combined with the nucleinic acid of the nuclein, but are, of course, set free during the analytic process of digestion. Like the alkaloids of the plant (which are often taken in the form of drugs), these flesh xanthins or purins can only serve to stimulate or irritate temporarily, by causing extra effort on the part of the metabolic organs to oxidize them (into uric acid or urea) and effect their removal from the system.

Its Cumulative Action. — From what has been said, it will be seen that uric acid is obtained from the foods of the vegetable kingdom, as an alkaloid, xanthin, purin, or extractive of plants; and from foods of the animal kingdom, as an alkaloid, xanthin, purin, or extractive of meat. When introduced into the system, by ingestion of flesh food or of vegetable food of the character described, it acts much like any other alkaloid, in the form of a drug: not as a food

ITS PLACE IN NATURE. 11

proper. Like morphin and certain other alkaloids, it has a cumulative action, so that the person who has been accustomed to eating flesh, drinking coffee, etc., may become suddenly and unexpectedly poisoned from an "explosion" of its effects, and he will also, probably, become an habitue — that is, his sympathetic nervous system will crave its accustomed irritant or stimulant. It is, therefore, a difficult matter, or perhaps impossible, for the meat eater to turn at once into a vegetarian. It is like giving up the "drink" habit or "drug" habit.

Its Power for Good or Evil. — Of course, the human organism is obliged to rid itself of the uric acid resulting from the breaking down of its own bodily cells, as well as of that of the cleavage products derived from the nuclein of flesh ingested as food; so that the metabolic and excretory organs are made sufficiently active in performing their essential duty, without introducing gratuitously more work of a similar character by means of free xanthins, ready formed, which can serve no useful purpose as. food. We are prone to ingest substances into the organism, in this way, which are quite unnecessary and superflous, thus causing extra eliminative effort to get rid of them — as in the case of alcohol, drugs, tobacco, etc.

The power of uric acid for good or evil probably resides chiefly in its nitrogen or ammonia content, which will be beneficial to the plant and injurious to the animal. An analogous power is inherent in carbon dioxid, which the animal exhales as poisonous and the plant absorbs as a nutrient.

It will be seen, then, that, though uric acid has an important place in Nature, this place is not as a food for man. On the contrary, like carbon dioxid, and like ammonia in other combinations than that of the ureids proper, it is excreted from the animal body as useless waste, which becomes harmful if retained. In fact, it may be decomposed into carbon dioxid, ammonia and glycocoll. Its true office, then, is to serve as an excrement for animals and a fertilizer for the reproduction and growth of plants. It is a nitrogenous ash, thrown off by the analytical processes (catabolic) of animal life, to be taken up and utilized by the synthetic processes (anabolic) of vegetable life.

In conclusion, it may be stated that the excreta of plants are altogether of gases, so that waste substances resulting from the cell life of the plant must remain in its tissues. Such products are always removed to parts in which they cannot interfere with the vital activities of the plant; so that such "extractives" are found in the bark of plants, skins of seeds, etc.

Chapter II. Historical Review

Discovery of Uric Acid (1776).— Though the history of uric acid, during its 130 years' ups and downs* contains (until very recently) but few American names of note, the year that marks its beginning has a distinct American sound.

In 1776, two years after his discovery of oxygen, Karl Wilhelm Scheele discovered uric acid in a concrement; and, in the same year, Prof. T. Olof Bergman found the substance in a cystitic calculus. Both were well-known Swedish chemists, whose names have become famous for their important discoveries in chemical science. The collected works of the latter were published in 1779-84; those of the former, in 1793.

Early Chemical Findings, (1 793-1848). — For a number of years after this discovery of uric acid, chemical experts were interested in its study, and it was soon found to be a normal constituent of human urine.

In the same year that Scheele published his voluminous work, (1793), Comte de Fourcroy, a well-known French chemist, found urea to be one of the decomposition products of uric acid; and, four years later (1797), William Hyde Wollaston, the celebrated English chemist and physicist (who afterward discovered the ultraviolet rays of light), found uric acid in the form of its insoluble salts in the concretions of gout.

The next two names to be connected with these earlier uric acid studies are familiarly known to physicians and students in every part of the civilized world; viz., Prof.

Friedrich Wohler and Baron Justus von Liebig, the two illustrious German chemists, who associated themselves together for scientific research in the early part of the 19th century. Wohler, who is generally recognized as the "Father of Organic Chemistry," demonstrated, in 1828, the possibility of forming a product of the living organism (i. e., urea) from inorganic material (ammonium cyanate). Liebig was professor of chemistry at Giessen, where he established his laboratory for researches in organic chemistry, and afterwards published his famous "Dictionary of Chemistry." In 1838, these two scientists, by their combined investigations, were enabled to point out conclusively the singularly close relationship borne by uric acid toward urea, allantoin and alloxan.

Ten years later (1848), it was shown by Wohler and Frerichs that when uric acid was introduced as such into the organism, some of it was transformed into urea, on excretion.

The Early Medical Theory (1 797-1 870). — The knowledge gained concerning uric acid and its intimate relationship to urea, soon set medical men to speculating on the probable similarity of origin of the two substances and their probably analogous mode of formation in the body. As urea was known to be the end product of albumin metabolism, as well as an oxidation product of uric acid, it was reasonable to suppose that the latter was also derived from albumin and represented an intermediate stage in the process. For many years it was believed by medical men, and was so taught by physiologists (and even many physicians today have not learned to the contrary) that normally all albumin passes through a uric acid stage in being oxidized into urea.

HISTORICAL REVIEW. 15

From this, it was only a step further to believe that any increase of uric acid must result from faulty albumin metabolism, the process being interrupted at the uric acid stage owing to insufficient oxygenation. Anything which interfered with the normal oxidizing processes of the body, such as disturbances of the circulation or of respiration, was considered responsible for the increase of uric acid.

This theory obtained so firm a foothold that experimental investigators were, as a rule, prone to make the mistake of looking only for such clinical evidence as seemed to be confirmatory. In other words, facts were made to harmonize with the theory, rather than vice versa.

In support of this suboxidation theory, Virchow, in 1847, directed notice to the abnormal amount of uric acid in leukaemia. Six years later, Lehmann's popular i Text-book of Physiological Chemistry" appeared, in which it was taught that uric acid is a half-way stage in the oxidation of albumin into urea. In Vol. I, of the German Archives of Clinical Medicine, published in 1866, Bartels advanced his famous hypothesis of the "relative" insufficiency of oxygen as in pneumonia and certain fevers to account for the increase of uric acid, known to be present in these conditions.

About this time, numerous feeding experiments by different investigators corroborated Wohler's finding that uric acid, when fed to dogs and man, is given off in the urine largely as urea. This experimental finding was considered convincing proof of the correctness of the albumin-metabolism theory. The fact did not seem to be appreciated then, as it is now, that though the experiment proved that uric acid may be burned into urea, this does not necessarily mean that all uric acid is thus burned, or that all urea is thus derived. As a matter of fact, it is known that only a small proportion of urea represents burned up uric acid, and only a certain proportion of uric acid is burned into urea.

Garrod's Discovery (1848-1854). — The uric acid finding, to which we have now come, is one which has profoundly influenced all subsequent studies and investigations of the subject. Though, as already mentioned, Wollaston had discovered uric acid salts in the concretions of gout, fifty years previously, the connection between uric acid and gout was not worked out. To Sir Arthur Garrod, the palm must be awarded for showing the relationship between the two.

In 1848, in a paper on "The Blood and Urine in Gout, Rheumatism, and Bright's Disease," read before the Medico-Chirurgical Society of London, Garrod demonstrated that the blood of gouty patients contains urate salts in excess. In determining the presence of an excess of uric acid in the blood, he introduced his famous "thread test"; to wit: — A little blood is collected in a watch crystal and some dilute acetic acid added; in this mixture a linen thread is immersed and the whole set aside to stand for twenty-four hours, evaporation being prevented. At the end of this time, if there is an excess, crystals of uric acid are thrown out, adhere to the thread, and can be easily recognized under the microscope.

By the application of this test, it was shown by Garrod that the blood of gouty patients contains uric acid in an abnormally large amount. His findings were subsequently confirmed by several well-known investigators (Ranke, Charcot, Bence-Jones, Salomon, and others) and more recently by Klemperer and Strauss, who used the more

HISTORICAL REVIEW. 17

accurate Ludwig-Salkowski method, for determining uric acid in the blood by gravimetric analysis.

Garrod's Theory. — Though the knowledge of the mode of formation of uric acid in the body was still incomplete and faulty at the time of Garrod's discovery, yet the theory he formed concerning the aetiology and pathology of gout is accepted by many authorities even today. He considered that the gouty nodes and tophi are derived primarily from an excess of uric acid in the blood, and that the tissue lesions in the affected parts are caused by the deposition of urates. He held that, in gout, there is deficient elimination on the part of the kidneys, the alkalinity of the blood plasma is lessened, and consequently the blood is no longer able to hold the uric acid combination in solution. The latter, in the form of the biurates, is suddenly deposited in and about the joints, where an inflammatory action of the contiguous soft tissues is effected.

Early Xanthin Findings (1851-1889). — As early as 1 85 1, Scherer published his findings of hypoxanthin in the .spleen and in the blood of leukaemic subjects; and, during the next four or five years, experts began to recognize the chemical resemblance between uric acid and the xanthins. In 1858, Ranke suggested that inasmuch as uric acid and hypoxanthin were both present in splenic juice and were increased in amount in leukaemia, the two substances possibly had a similar origin, hypoxanthin being an earlier stage than uric acid in the metabolic process. In 1 87 1, the expert, Salkowski, put forth strong arguments against the albumin-metabolism theory and offered in its stead the hypothesis that uric acid is derived from xanthin bases and the spleen; but the time was not yet ripe for the acceptance of this new doctrine.

Pure chemists now began those remarkable experiments with nucleins and their cleavage products. In 1874, Miescher isolated nucleinic acid from the sperm of salmon and showed that xanthin bases resulted as decomposition products. Again, in 1879, Kossel obtained xanthin, hypoxanthin, adenin and guanin from nuclein; showing, moreover, that they are not present in nuclein as free bases, but organically combined with the nucleinic acid. Two years later he suggested that these bases were probably forestages of uric acid; and, the following year, he offered as an argument that the muscles of birds and reptiles (whose chief metabolic end product is known to be uric acid) are much richer in hypoxanthin than are the muscles of mammals.

It will be seen that these studies were gradually leading up to the discovery of the fact that uric acid is derived from the nucleins and xanthin bases, as demonstrated by Horbaczewski in 1889, when he performed his classic experiment of squeezing spleen pulp, mixing with it defibrinated blood, passing air through it and finding large amounts of uric acid formed. He believed that he was warranted in declaring that uric acid was an oxidation product of nuclein (only of leucocytes, he thought) through its xanthin cleavage products. This was an important finding, inasmuch as it led to the discovery of the true origin and mode of formation of uric acid in the body.

Early Theory Exploded (1 868-1 893). — Little attention was at first paid to those experimental findings which threatened in any way to disprove the theory that albumin, in being metabolized in the body, passes through a uric acid stage, and that the latter is increased whenever there is deficient oxidation. Increase of uric acid excretion

HISTORICAL REVIEW. 19

following the ingestion of meat, pointed to a nitrogenous origin; and, until certain chemical discoveries were made, that origin was naturally thought to be albumin.

As early as 1868, Senator cast some doubt on the suboxidation theory, by showing that permanently constricting the thorax of animals, thus limiting their oxygen intake, did not increase the uric acid excretion. In short, interference with respiration did not necessarily mean uric acid increase, though it did mean deficient oxygenation. Again, it was shown by other investigators that anaemia, produced experimentally, did not cause increased uric acid excretion; and, furthermore, that there was no evidence of the oxidizing processes being diminished in leukaemia.

It was also shown by Minkowski and others that the feeding of pure albumin foods had no direct relation toward uric acid increase. The death-knell to the albumin theory was not sounded, however, until Kossel (1893) demonstrated that meat increased uric acid excretion owing to the abundance of free xanthins it contained. In other words, it finally became understood that uric acid was not derived from the albumin of meat, but, as shown by Kossel, Burian and Schur, and others, from the nuclein and free xanthin bases, especially of glandular meats (sweetbread, liver, etc.).

Horbaczewski had been the first to point out, by his feeding experiments, that nuclein produced an increase of uric acid excretion within two hours after its ingestion. Professional chemists now abandoned the albumin theory — they recognized the fact that uric acid metabolism and albumin metabolism were carried out along two entirely different lines; but it took medical men some time to learn that the old established theory had been exploded.

Recent Findings (1895-1905). — During the last decade many important discoveries have been made concerning the origin, destruction, and mode of formation of uric acid in the body, under normal conditions. It has also been shown how the metabolism of uric acid becomes changed under certain pathological conditions and thus gives rise to disease. These various findings, relating to the precipitation of urates out of solution, their faulty excretion, retention and accumulation in the organism, will be considered in detail under their proper headings in the body of this work.

Chapter III. Physical Characteristics

Isolation of Uric Acid. — The most convenient way of isolating uric acid in its purity, is to submit the excrement of snakes to a simple chemical process, the details of which may be found described in any text-book of physiological chemistry. It can also be separated from human urine by the employment of a somewhat more complicated though similar analytic method — i. e., by concentration and addition of hydrochloric acid.

It was first prepared synthetically by Horbaczewski, in 1882, by treating a mixture of glycocoll and urea at a high temperature. It has also been obtained synthetically by heating a mixture of urea and trichlorlactic acid.

Its Appearance. — Pure uric acid is tasteless and inodorous. It is a glistening, snow-white, crystalline powder, which, under the microscope, appears to consist of minute (though regular) transparent, colorless crystals, in the form of rhombic plates, with rounded angles, and often united in pretty rosettes. They may be whetstone, dumb-bell, paddle, and spiculated shaped, and of a reddish or yellow-brown color, due to the accompanying pigment (usually purpurine). They may be seen by the naked eye in the urine, as "sand," " gravel, " "brick-dust," and "red pepper grains."

Reaction. — Uric acid slightly reddens blue litmus, as it is a tasteless, weak acid.

Solubility. — Uric acid itself is less soluble than most of its salts. It is practically insoluble in dilute acids, alcohol, ether water, or strong solutions of alkaline carbonates. It dissolves in i : 40,000 parts, cold water, and in 1 : 1,800 parts, boiling water.

It is soluble in weak alkaline solutions: therefore, alkaline urine and blood hold uric acid in solution.

In a solution containing both uric acid and the soda phosphates (as in the urine and blood), the uric acid is precipitated by the acid phosphates, and held in solution by the basic or neutral phosphates.

Uric acid does not occur, as such, in the normal urine, but rather in the form of its more soluble salts or urates — principally with the alkali metals, sodium and potassium. Being a dibasic acid, it is capable of forming two series of these salts — neutral urates and acid urates, the former being more soluble than the latter. The urates, therefore, that we see precipitated from urine, passed in normal quantity, are the acid urates.

Uric acid may be precipitated in the form of its characteristic crystals, owing to its liberation from union with sodium or potassium, during the period of the so-called "acid fermentation," when the urine reaches its. greatest acidity (i. e., a few hours after voidance). The neutral urates may also, at the same time, be converted into acid urates and thus precipitated. Even in fresh urine, if the urates are excessive in amount, or if the urine be too acid or too small in quantity to hold the urates in solution, the latter will be deposited in the form of sediment. Under the same conditions, they may be precipitated in the bladder before voidance, thus being passed as. gravel.

Heat dissolves the urates; cold precipitates them. Thus being more soluble in warm than in cold solutions,

PHYSICAL CHARACTERISTICS. 23

the urine may be clear on voiding, but deposit quite a sediment on cooling. This precipitate will be dissolved by heating the urine, which will serve to differentiate it from other precipitates.

The urinary urates are usually spoken of as the " amorphous," or " acid," or " mixed " urates. They rarely appear in crystalline form, though small needles are sometimes found. As one author says: "The usual form is a rather dense, sandy deposit, cream-colored, yellow, pink or rose-colored, or even brown, depending on the color of the urine. Under the microscope, small sandy particles are seen, usually yellowish or brownish, with now and then a crystal of uric acid. A drop of caustic soda or potash added to the sediment on the slide, will cause it to dissolve immediately. On the other hand, a drop of hydrochloric acid added to the sediment will in two or three minutes produce very small colorless crystals of uric acid."