is a direct ratio between the two. As a rule, the temperature is highest and the quantity of urea greatest in the early stages of a continued fever, and when there is an unusual elevation of temperature there is an unusual amount of urea. There are no doubt exceptions. The temperature is modified by the amount of evaporation going on from the surface of the skin, and the urea may be lessened by albuminoid matter more or less changed being retained in the blood. In badly nourished persons also it has been found that comparatively little urea is eliminated, notwithstanding the rise of temperature; but the latter is also less than in the robust and well-fed, and is probably due to an increased formation of carbonic acid. In one respect the temperature of fever differs in its origin from that of health. In health the elimination of nitrogen is entirely regulated by the amount entering the body with the food; but the increased nitrogen of fever does not come from the food, for it is out of all proportion to it. The fixed albumen of the muscles, brain and nerves, breaks down into circulating albumen, to be in its turn transformed into urea and other nitrogenous excreta. Hence it is that in fever the muscles waste and the brain becomes atrophied. The large amount of cerebral fluid so common in protracted fevers is merely thrown out to fill the space vacated by brain. The disintegration of the nitrogenous tissues in fever is confirmed by microscopic observation; the granular and waxy degenerations of the muscles found by Zenker in enteric fever occur in all fevers of a severe type, while Beveridge has found a quantity of amorphous granular matter in the cervical ganglia of typhus. The only parts of the body that do not waste in fevers are the glandular organs, and especially the liver, spleen, kidneys, and lymphatic glands, which become enlarged and congested from the increased functions thrown upon them, the enlargement being greatest in the young and robust who have most tissue to spare for conversion into urea. The gland-cells of these organs become swollen with minute granules, and a similar appearance is often presented by the white corpuscles of the blood, which are usually increased in number. It is important to note that while the nitrogenous solids of the urine are thus increased in fever, the water and the chlorides are usually diminished, and the latter may wholly disappear. The large amount of nitrogenous detritus formed in fevers PARKES, 1871. may be all eliminated by the kidneys or bowels, or a portion may be retained in the blood, either as urea or as some halftransformed albuminoid matter, and then the temperature may be elevated without a corresponding augmentation of urea in the urine. The urea, or other less oxidized products of metamorphosis, circulating in the blood and permeating the tissues, gives rise to symptoms of uræmic poisoning (typhoid symptoms)." Every practitioner must have been struck with the remarkable resemblance between a case of typhus in its advanced stage, and one of uræmia dependent on renal disease; in fact, the two conditions are very often mistaken for one another. It is highly probable that the symptoms in both cases are due to the circulation of the same morbid materials in the blood, the difference being that in fevers these materials are generated in excess, while in renal disease the kidneys are unable to The exact pathology of uræmia is still a subject of discussion. According to Frerichs, the simple accumulation of urea in the blood will not give rise to so-called uræmic symptoms, and the real toxic agent is carbonate of ammonia resulting from the decomposition of the retained urea by some ferment in the blood (Die Brightsche Nierenkrankheit, 1851). Hammond and Richardson, on the other hand, have more recently supported the old view, according to which the urea itself is capable of exciting uræmic symptoms (HAMMOND, in Americ. Journ. of Med. Sc., January 1861, and Edin. Med. Journ., October 1861; RICHARDSON's Asclepiad, 1862). Oppler, of Berlin, opposes the view that uræmic symptoms are due to urea in the blood, because Bright, Christison, and Owen Rees have shown that urea may exist in large quantities in the blood without any symptoms of uræmia, and because certain French observers have injected a large amount of urea into the blood without producing any other effect than diuresis. He also objects to Frerichs's theory, because he did not find that the injection of carbonate of ammonia produced the heaviness and drowsiness of uræmia, and because, after extirpating the kidneys and tying the ureters of animals, he found much urea, but no carbonate of ammonia, in the blood. He observed, that when the functions of the kidneys were arrested, products of retrograde metamorphosis (Kreatíne and Leucine) were formed and accumulated largely in the muscles, and that the extractive matters of the blood were greatly increased. He concludes that a similar increased metamorphosis occurs in the central organs of the nervous system, and that this chemical change accounts for the symptoms of uræmia. Oppler also adduces experiments to show that the kidneys have the power of transforming kreatine into urea. (VIRCHOW's Archiv. Bd. xxi. Heft 3.) But, whatever theory be adopted, the clinical fact remains, that the symptoms of 'uræmia' are produced by whatever interferes with the excreting function of the kidneys. T Dr. Richardson has attempted to distinguish between the symptoms produced by urea, and those caused by ammonia in the blood. The typhoid state of continued fevers he believes to be due to the latter substance, and to differ from true uræmia in the occurrence of jactitations in place of paroxysmal convulsions; in the tendency to the hæmorrhagic diathesis, as evidenced by petechial eruptions and fluxes of blood: and in the absence of prolonged coma, which is the leading symptom of uræmia cannot admit the, applicability of these distinctive characters in practice. Long experience at the London Fever Hospital, where cases of renal disease were constantly being sent in as examples of typhus, leads me to say, that the first and last points of distinction would of themselves afford no aid in diagnosis. The presence of the specific eruption would of course decide in favour of typhus; but, failing the eruption, the sole point of difference is the temperature, which is elevated in typhus, but at or below the normal standard in uræmia. Dr. Richardson admits that the morbid appearances of the blood and internal organs after death are identical in both states. (RICHARDSON'S Asclepiad, 1862, p. 191.) C eliminate the normal quantity. This is not a mere conjecture. It will be shown in a subsequent part of this work, that in the different continued fevers with cerebral symptoms, no lesions are to be found in the brain or its membranes, but that urea is present in the blood, while the occurrence of epileptiform convulsions and other severe head-symptoms is often accompanied by a great diminution in the amount of urine. It is difficult to say why the nitrogenous matter is excreted in some cases, and retained in others; but its elimination appears to be often prevented by some morbid condition of the large glands, and especially of the kidneys, either of old standing, or consequent on the febrile attack. Disease of the kidneys, indeed, is an almost fatal complication of typhus and of many other fevers. There is also reason to believe that the half-changed albuminoid matter circulating in the blood may be deposited in the different organs, and thus cause secondary inflammations in the course of fever. Cases of idiopathic fever have been observed, where a sudden diminution in the amount of excreted urea was followed by an attack of pleurisy or other local disease, the quantity of urea again increasing as the local complication receded." It is important to add that critical deposits are chiefly observed in the urine in cases, where it might be inferred from the symptoms that the nitrogenous products of metamorphosis have been retained in the system. After convalescence is fairly established, and the patient is regaining weight, the elimination of nitrogen and also the temperature are found to be diminished below the normal standard. As the metamorphosis of albumen which occurs during health is under the control of the nerves, so the augmented metamorphosis of fever is probably, in great measure, due to some abnormal condition of the nervous system. According to the well-known experiment of Claude Bernard, an elevation of temperature to the extent of from 7° to 11° Fahrenheit is produced on one side of the face of an animal, when the trunk uniting the sympathetic ganglia of the neck on the corresponding side is divided, the sensibility of the part becoming greatly excited and the vessels dilated and hyperæmic. This elevation of temperature must be referred to the hyperæmia and the increased metamorphosis in the part, which had before been held in check by the sympathetic nerve. The converse of this experiment has been performed by Waller, who found that con See PARKES, 1855. traction of the dilated vessels, diminution of vascular injection, and reduction of temperature followed the irritation of the divided sympathetic by the transmission of an electric current. Experiments on the vagus nerves have been attended with equally important results. Weber ascertained that section of the vagus was followed by increased rapidity of the heart's action, the number of beats being again reduced on passing an electric current through the cut nerve. Volkmann and Fowelin observed that section of the vagus caused an increased lateral pressure of the blood in the arteries, whilst Ludwig and Hoffa found the lateral pressure diminished by irritation of the nerve.' These and other observations make it probable that the increased metamorphosis, the elevated temperature, and the accelerated action of the heart in fever are due to paralysis of the sympathetic nerves and the vagus. W Many facts indicate that the nervous system exercises a powerful influence on the early phenomena of fever, such, for example, as the rigors, pain, languor and prostration usually complained of from the first, and the occasional occurrence of sudden death at the onset. In Simple Continued Fever, which is independent of a specific poison, the nervous system seems to be affected primarily. The best illustration is to be found in the fever that occasionally results from sheer nervous exhaustion, consequent on mental or bodily fatigue. But, as regards the other continued fevers which are due to some poison, the poison is probably in the first place absorbed into the blood, and through this medium produces its effects on the nerves. The facts recorded by Sir Henry Marsh and others, to the effect that persons may be seized with symptoms of fever immediately on exposure to the poison, do not prove that the poison acts directly on the nerves without being absorbed into the blood, for hydrocyanic acid may prove fatal in a few seconds after its application to the tongue, and be detected after death in the blood of the heart.* The muscles being deprived in the manner described of their healthy nervous stimulus, the patient naturally suffers from a feeling of incapacity for exertion or motion; at the same time, the muscular and other tissues begin to waste. The amount of metamorphosis, or the severity of the case, will ▾ See Brit. and For. Med. Chir. Rev. Ap. 1856, p. 398. See for example, GEE, 1871, p. 390. * CHRISTISON, On Poisons, 3rd ed. p. 697. depend, not so much on the primary poison, as on the vitality, or the power of resistance of the recipient, and his richness in muscle and fat. The blood sooner or later becomes contaminated by the débris of the disintegrated tissues in addition to the original fever-poison. These morbid materials may be eliminated by the natural channels, and so be productive of no injury; but if there be any impediment to their excretion, they give rise to the symptoms already referred to. When stupor, delirium and coma present themselves in the course of fever, it is the custom to refer them to the action of the fever-poison on the brain; but the cerebral functions are more probably deranged, not by the fever-poison, which was the first and necessary link of the pathological chain, but by the accumulation in the blood of the products of metamorphosis, and by the perverted and defective nutrition of the brain. Hence it is, that the symptoms in the advanced stages of many fevers (the typhoid state') are closely assimilated, although the primary poisons have been perfectly distinct. Since the appearance of the first edition of this work, two new theories as to the cerebral symptoms of fevers have been proposed. It is contended by Liebermeister and others, that they are due to the direct action of the elevated temperature on the central organs of the nervous system; but this view appears to me to be negatived by the fact that in relapsing fever the temperature often reaches 106° or 107° Fahrenheit without any cerebral symptoms, that in typhus there may be most severe cerebral symptoms although the temperature has at no time exceeded 103° Fahrenheit, and that cerebral symptoms identical with those of fevers may result from disease of the kidneys, when the temperature does not exceed the normal standard. The other view is that of Dr. Charlton Bastian, who attributes the delirium and stupor of the typhoid state to plugging of minute vessels in the grey matter of the brain with masses of white corpuscles; but these coagula, if constant, are probably only one of the results of the morbid state of the blood and circulation above referred to. a According to the present extent of our information, the phenomena of idiopathic fevers may be summed up as follows: 1. The fever-poison enters the blood. MURCHISON, Clinical Lecture on the Pathology of the Typhoid State, Brit. Med.. Journ. January 4, 1868. Deutsch. Arch. für klin. Med. vol. i. p. 174, 1866. BASTIAN, 1869. |