HÆMOGLOBINÆMIA. AZOTÆMIA. AZOTURIA. HÆMOGLOBINURIA. TOXÆMIA FROM IMPERFECT HEPATIC FUNCTION.
Definition. Theories, of hysteria, uræmia, spinal myelitis, myelo-renal congestion, rheumatic lumbago, myosito-myelo-nephritis, rheumatic chill with destruction of muscle albuminoids. Yet it occurs in our semi-tropical midsummer with a temperature of 80 or 90, in spring and autumn, and rarely even in the cold, damp stable in midwinter in the absence of exercise. Constant conditions: One or more days absolute rest, preceding steady work, a strongly nitrogenous ration, continued during the rest, sudden active exertion accelerated breathing and unloading of peptones and proteids from portal vein and liver into the general circulation. Sanguineous albuminuria from excess of albuminous food, free ingestion of water, suppressed milk secretion, forced marches. Transfusion of blood. Excess of albumen dangerous, excess of red globules not dangerous. The blood concentration of diuresis or diaphoresis is not dangerous. Continuous muscle decomposition from work bars the disease. Stable miasm untenable. Poison may be drawn suddenly from the enormous mass of blood in the liver, spleen and portal system. The absence of icterus antagonizes the bile theory. Benzoic acid, unaltered peptones, and glycogen are examples of elements destructive to blood. Normal destruction of red globules in liver, spleen and bone marrow. Sudden access of resulting hæmoglobin to the blood. Other products of disintegrated globules. Poisons from food, and antitoxic action of liver in presence of glycogen. Carbon dioxide favors solution of red globules. Theories of hæmoglobinæmia in man. Lesions: Blood black, diffluent, iridescent, has no avidity for oxygen, with excess of urea and extractives, serum of clot red, globules, small, pale, distorted, not sticky, extravasations, liver, enlarged, congested, blood gorged, spleen congested, swollen: Lumbar or gluteal muscles pale, infiltrated, with loss of striation; bone marrow congested, hemorrhagic; kidneys congested infarcted; urine dark brown or red, with excess of urea and hæmoglobin. End of spinal cord has congestion or infiltration. Symptoms: History of high condition, constant work, high feeding, a day’s rest, then exercise and attack. To full life, follows flagging, droops, moves one or both hind limbs stiffly, knuckles, drags toes, crouches, trembles, perspires, breathes rapidly, is tender on back, loins, croup or thigh, muscles firm, paretic, and drops unable to rise. Urine retained, brown, red or black, sometimes glairy, later may have casts. Appetite may return. In mild cases, stiffness, lameness, with or without visible muscular lesions or tremors. Urine glairy, dense, with excess of urea and nitrogenous products. Recover under careful feeding and exercise, and relapse under original causes. Progress: May recover under rest. In bad cases accelerated breathing and recumbency forbid rest and recovery. Recovery in a few hours or after a week. Urinary casts with renal epithelium, imply nephritis and grave conditions. In persistent paresis, muscles waste. Modes of death. Mortality 20 per cent. Diagnosis, by history of onset, etc. Prevention: When highly fed and hard worked, give daily exercise, with comparative rest, reduce ration, and give laxative or diuretic. Plenty of water. Treatment: Rest, sling, diffusible stimulants, bleeding, bromides, water ad libitum, fomentations, unload liver and portal vein, purgative, eserine, barium chloride, enemata, diuretics, for remaining paresis, derivatives, strychnia, diet, laxative, non-stimulating, restore to work gradually.
Definition. An acute auto-poisoning occurring in plethoric horse on being subjected to active exertion after a period of idleness, and manifested by great nervous excitement and prostration, paresis commencing with the hind limbs and the passage of hæmoglobin in the urine.
Nature and Causes. The most varied conclusions as to the nature of this disease have been put forward by different authors. In England, Haycock called it hysteria, mistakenly supposing that it was confined to mares, and Williams attributed it to uræmic poisoning, conveniently ignoring the fact that the sudden manifestation of the most extreme symptoms in an animal which just before was in the highest apparent health and spirits contradicted the conclusion. In France (Trasbot) and Southern Europe (Csokor) it has been looked on as a spinal myelitis, a conclusion based on the disturbed innervation of the posterior extremities in the great majority of cases, but which is not always sustained by the pathological anatomy of the cord. In Germany veterinarians have viewed the disease from widely different standpoints. Haubner calls it myelo-renal-congestion (Nièren-Rückenmarks): Weinmann, a rheumatic lumbago; Dieckerhoff defines it as an acute general disease of horses, manifested by a severe parenchymatous inflammation of the skeleton muscles, with a bloody infiltration of the bone marrow, especially of the femur, and with acute nephritis and hæmoglobinuria. He attributes the attack to exposure to cold. If this were the real cause the attack would be far more common in very cold weather when the horse is suddenly exposed to cold drafts between open doors and windows, than when he is harnessed and driven so as to generate and diffuse animal heat. Yet attacks in the stable are virtually unknown, and in almost every instance the onset occurs during a short drive. Friedberger and Fröhner say that the epithet rheumatismal may be correctly applied to almost all cases that we meet in practice. They quote Goring as having produced the disease experimentally by exposure to cold, and go on to explain that rest in the stable before the attack causes the extreme sensitiveness to cold that is generated by a warm environment. The implication of the lumbar, pelvic and femoral muscles they explain by the stimulation of the nutritive metamorphosis by the action of cold on the sensitive nerves of the skin. The effect of this cutaneous irritation is exaggerated by the heat of the stable to which they have been previously subjected. The products of the destruction of the albuminoids of the muscles, pass into the blood as hæmoglobin, and produce the ulterior phenomena. The muscles of the hind quarters especially suffer because of their greater exposure and because they are subjected to the hardest work in propelling the animal machine. In this connection they quote the experiments of Lassar and Nassaroff in which sudden exposure to cold determines parenchymatous degeneration of muscles; also the cases of paroxysmal or winter hæmoglobinuria in certain susceptible men whenever they are exposed to an extremely low temperature.
There are serious objections to the acceptance of this as the essential cause, among which the following may be named:
1st. The disease is not confined to the cold season but occurs also at midsummer when the outdoor temperature is even higher than it is in the stable.
2d. In our Northern States it appears to be more common in spring and autumn or early winter, when the extreme colds have either already passed, or have not yet set in, but when the abrupt changes of weather (rain-storms, etc.) are liable to shut up the animal indoors for a day or more at a time.
3d. The popular names quoted with approval by these authors—Monday disease, Easter disease, Whitsuntide disease—indicate the prevalence in Europe also, of the malady in the milder, or more temperate seasons rather than during the prevalence of extreme cold.
4th. The fact that the disease rarely or never occurs in the stable, no matter how cold the season, how open the wooden walls or floor, nor how strong the draft between doors or windows, shows that the theory of cold as the sole or main cause must be discarded.
It is not necessary to ignore the action of cold as a concurrent factor in certain cases, or as a stimulant to reflex vaso-motor paresis, to muscular metamorphosis and the increase of hæmoglobin in the blood. It is only necessary that this should be held as subordinate and non-essential to the final result. Several other factors that are accorded a subordinate place by these writers, are so constant and so manifestly essential that they must be allotted a much more important position in the list of causes.
A period of rest is a constant precursor of an attack. The more extended the inquiry the more certain we become that a short rest is a prerequisite to equine hæmoglobinæmia. The horse that is kept at daily steady work may be said to be practically exempt. Even the non-professional observer recognizes the fact and names the disease after the weekly or yearly holiday or rest day which was the occasion of it. To him it is the Monday morning disease, the disease of the day following Thanksgiving, Christmas, New Year, or Fourth of July. It is the disease of wet weather, of heavy snowfalls, of the blizzard, or of the owner’s absence from home, of any time that entails one or two days of absolute inactivity in the stall.
But again the affection does not appear in the horse that is absolutely idle for a length of time. It is the short period of rest in an interval of otherwise continuous work that determines it. In short the subject must be in good muscular condition and with a hearty, vigorous appetite and good digestion. The short unwonted rest interrupts the disposal of the rich products of a vigorous digestion, and tends to overload the portal veins, the liver, the blood and tissues with an excess of proteids. The condition of the animal is so far one of plethora.
Another feature that bears this out is that the attack comes only in the animal that is heavily fed on a strongly nitrogenous ration. It is not the disease of the horse kept on straw, or hay, or which receives a limited amount only of grain. It does not occur in the animal which has its grain suspended or materially reduced during the one or two days of idleness. It does not select the horse that has had a laxative either in the form of food or medicine. This last may increase the sensitiveness to cold, but it certainly lessens the tendency to hæmoglobinæmia. The most rational explanation appears to be that it affords this protection by interfering with the thoroughness of digestion and absorption, by securing elimination from the portal veins and liver, and by reducing the amount of albuminoids in the blood.
A blood abnormally rich in albuminoids, as it is in the transient plethora induced by a short period of rest, in the well-conditioned working horse, without any restriction of his diet, may therefore be set down as one of the most important factors in producing hæmoglobinæmia. Nor is this without approximate examples in human pathology. Von Bamberger has shown that “hæmatogenous albuminuria” will occur in healthy individuals when there is an excess of albumen in the blood-plasma, as after a too free use of albuminous food, or after suppression of the milk secretion (Landois). A similar result comes from increase of blood pressure, as after drinking freely, or when, under emotion or violent exertion, the heart’s action is increased in force and the blood is thrown with greater impetus into the large renal arteries. Senator has found albuminous urine to attend and follow, for several days, upon forced marches made by young recruits. Here the muscular work is added to the increased blood tension superinduced by the more active contractions of the heart.
In this connection it is interesting to trace the changes in the blood after transfusion. The dilatability of the capillaries enables the system to accommodate itself to a very great increase in the volume of blood An increase of 83 per cent. may be borne without serious results, but above this limit there is increasing risk and an increase of 150 per cent. entails immediate danger to life. In the restoration of the blood to its normal condition, the secretion of water sets in promptly leaving an excess of albuminoids and blood globules. The next change is in the albuminoids which in two days are almost entirely transformed into urea. This leaves the blood abnormally rich in globules (Panum, Lesser, Worm-Müller), the red globules break up much more slowly and may still be in excess after the lapse of a month (Tscherjew).
In this light, temporary plethora cannot of itself be accepted as the main or essential cause of the disease. It must be admitted to be a more constant and important factor than the mere exposure to cold, but of itself it is inadequate to the production of hæmoglobinæmia. In the absence of exertion the general plethora fails to produce the specific disease; again, after transfusion a plethora of albumen lasts for one or two days, but hæmoglobinæmia sets in only in the first few minutes after the animal starts out from the stable, (never after an hour or two at work): once more, excess of globules may last for a month, but with steady work there is no danger of this disease, after the first mile or two has been traversed, on the first day of the resumption of labor.
A similar plethora of albuminoids and globules may be induced in a plethoric animal by a profuse diarrhœa, diuresis or perspiration, the blood having been robbed of its watery constituents, and concentrated especially as regards its globules and albuminoids, but hæmoglobinæmia never occurs as the result of such an artificial concentration. On the contrary a free secretion by the bowels or kidneys is of the greatest value in cutting short its progress after it has set in.
The doctrine of poisoning by hæmoglobin produced by excessive work and disintegration of the muscles is equally insufficient to account for an attack. Excess of muscular work and of muscle-decomposition-products, would not reach its maximum within the first few minutes after the animal has started from the stable, but, other things being equal, would increase with the continuance of work and the accumulation in the blood of a constantly increasing amount of these products. The sharp line of restriction by which the attack is limited to the initial period of work, while it is never seen after hard work continued for hours in succession, rules out this from the list of essential causes. It may be that the products of muscular decomposition aggravate the attack, but to set them down as the cause of the attack is to beg the whole question and to contradict the truth that continuous and severe muscular work with its consequent increase of waste products is a direct bar to the development of the disease. It should be noted in this connection that the increase in the waste of nitrogenous bodies, as shown by the increase of urea, is dependent far more on the amount of nitrogenous matters ingested than on the muscle work or decomposition. In eleven hours just before ascending the Faulhorn, Fick passed 21.686 grs. of urea per hour; in eight hours ascending the hill, 12.43 grs. per hour; and in six hours after the ascent he passed 13.39 grs. per hour.
A general survey of the field shows that it is not the simple increase of any normal waste product in the blood which determines hæmoglobinæmia, and on the other hand the suddenness and severity of the attack bears all the marks of a profound poisoning. The nature of the poison has not yet been definitely ascertained, yet one or two hypothesis may be hazarded, as furnishing a working theory, in anticipation of the actual demonstration which may be expected in the early future.
The action of a stable miasm as claimed by some writers is contradicted by the fact that the disease does not develop so long as the animal is left to inhale that miasm, and on leaving the stable, the life and vigor are usually remarkable.
The morbific agent must be sought in some source from which it can be supplied with great rapidity under the stimulus of a short but active exertion. The chylopoietic viscera furnish such a source. The healthy liver contains one-fourth of the entire mass of the blood. The torpid congested liver of the vigorous high conditioned horse, after a short period of idleness, on full, rich feeding, must hold much more than this normal ratio. The spleen, the natural store-house or safety valve of the portal veins, is also gorged with this liquid in the high fed, idle animal. This organ which is always turgescent after meals, is especially so in the over-fed horse, which for twenty-four hours has been denied the opportunity of working off by exercise, the superfluous products of an active digestion and absorption. Then the whole of the portal veins and the capillaries in which they originate are surcharged with rich blood which cannot make its way with the necessary dispatch through the inactive liver.
In this condition there is incomparably more than a quarter of the entire mass of blood, enriched to the highest degree in proteids, ready to be discharged through the liver and hepatic veins into the general circulation. Under the action of the hurried breathing and circulation, caused by the sudden and active exertion, this whole mass of rich blood is speedily unloaded on the right heart, the lungs and the systemic circulation. One can hardly conceive of a more effective method of inducing a sudden plethora, with an excess of both globules and albuminoids.
The presence of actual poisons in such blood is not so easily certified.
The absorption of bile elements and especially of taurocholic acid, which is a solvent of the red blood globules, and would set free their globulin might account for the characteristic condition of the blood. The powerful aspiratory action of the chest, would speedily empty the whole of the liver blood vessels, and lessening their tension below that of the biliary radicals would determine an active absorption of bile or of the more diffusible of the bile elements. A manifest objection to this view is the absence of an icteric tint in the mucous membranes of the affected animals. The visible mucosæ are of a brownish red hue, such as might come from hæmoglobin dissolved in the blood serum, rather than the yellow tint which might be expected from bile pigment. The theory of poisoning by bile acids therefore, would require an explanation of concurrent suppression or decomposition of the bile pigments.
Other sources, however, offer solvents for hæmoglobin, benzoic acid, which is derived from a cellulose in the fodders, and forms the source of hippuric acid, dissolves red globules (Landois). In the over-fed horse with active digestion, but inactive body and liver, this must accumulate in the liver, spleen and portal system, and when suddenly drawn into the blood without time for oxidation in the liver it will contribute to the condition of hæmoglobinæmia.
Peptones, being very diffusible, are very rapidly absorbed, but they are not found, in healthy conditions, in the portal vein (Neumeister). These are manifestly transformed into albumen in the intestinal mucosa (Salvioli), or taken up by the very numerous leucocytes and transformed or carried elsewhere (Hoffmeister). But peptones injected into the blood of the dog render it incoagulable, and in large quantity are fatal (Landois). An excess of glycogen dissolves the red globules, and the conditions of heavy feeding and torpid liver, are calculated to produce this in great excess and to store it in the liver cells.
Under the extra vigorous aspiratory force of the chest, these highly diffusible agents, present in great excess, are likely to be drawn on through the mucosa, into the portal vein, liver, and cava, without an opportunity for complete transformation by leucocytes or liver cells. These would tend to rob the blood globules of their normal physiological vigor, would unfit them for maintaining the healthy functions of lungs, kidneys, brain or muscle, and would unfit the globules for successful resistance to solvents and other inimical influences.
Again it is an important function of the liver, spleen and red bone marrow to disintegrate worn out or abnormal red globules. These are taken up by the white blood corpuscles of the hepatic capillaries, by the cells of the spleen and the bone marrow and are stored up chiefly in the capillaries of the liver, in the spleen, and in the marrow of bone. They are transformed, partly into colored and partly into colorless proteids, and are either deposited in the granular form, or are dissolved (Landois). Quincke says: “That the normal red blood globules and other particles suspended in the blood stream are not taken up in this way, may be due to their being smooth and polished. As the corpuscles grow older and become more rigid, they, as it were, are caught by the amœboid cells. As cells containing blood corpuscles are very rarely found in the general circulation, one may assume that the occurrence of these cells within the spleen, liver, and marrow of bone, is favored by the slowness of the circulation in these organs.” From this chain of normal processes of blood disintegration, we may reasonably infer, a greatly exaggerated work of blood destruction when, in connection with an increased density of the plasma, and the presence in the portal blood of poisonous products of digestion, the red globules have been altered in density, in outline and in vitality, so that they become ready victims of the amœboid cells of blood and tissues. Then the stagnant condition of this altered blood in the compulsorily idle animal favors the greatest excess of this destruction and the storing up of an increased quantity of hæmoglobin and other products, to be poured suddenly into the general circulation as soon as the movement of the blood is quickened by exercise.
This destruction of the red blood globules by disintegration contributes to the formation of numerous decomposition-products, like succinic, formic, acetic, butyric and lactic acids, inosite, leucin, xanthine, hypoxanthin, and uric acid, some of which are strongly toxic. The tendency will be to lower the vitality of the red globules and thus to render them the easier victims of the leucocytes and of the liver, spleen and marrow cells. Even the freed hæmoglobin appears to exert a solvent action on the red blood globules. These are, of course, most concentrated and effective in the seat of their production, yet when drawn suddenly in large amount, into the general circulation, by the vigorous aspiratory action of the chest, they may prove seriously detrimental to the blood at large.
Again a variety of toxic matters are introduced into the system in the food and others are developed from the food in the stomach and intestine. Brieger found in the gastric peptones a potent alkaloid having the effect of urari, and which in excess would determine muscular paralysis. The alkaloidal and other poisons produced by fermentations in the intestines have to be safely disposed of. The ptomaines, if not too abundant, are arrested or even decomposed in the liver which thus stands as a guardian, at the outlet of the portal system, to protect the body at large. But this antitoxic function of the liver is only exercised in the presence of glycogen (Rogers, Landois), and forced muscular movement soon removes all glycogen from the liver of the dog (Landois). Again glycogenesis in the liver is now believed to be dependent on a ferment produced by the pancreas. If therefore, the sudden active exercise and the aspiratory action of the chest freed the liver of its glycogen, and hurried the alkaloidal and other poisons through its capillaries too rapidly to allow of the protective action of the liver cells, or if the pancreas as well as the liver had become torpid and had failed to produce the requisite amount of glycogen-ferment for the liver, the poisoning of the blood and system at large would be imminent.
Not to mention the other toxic products which come from imperfect metamorphosis in the liver, it may be noted that a venous condition of the blood or an excess of carbon dioxide contributes greatly to the solubility of the red blood globules. It also tends greatly to modify the fibrinogenous elements. Thus the blood of a suffocated animal fails to coagulate or coagulates loosely, and the blood of the portal vein of a suffocated horse is strongly toxic (Sauson). Now the conditions attendant on the onset of equine hæmoglobinæmia are such as to give free scope to both of these inimical influences. The great mass of blood in the portal vein, spleen and liver is venous blood strongly charged with carbon dioxide, and by the sudden, active exertion this is forced rapidly through the liver and lungs without time for full æration, so that the whole mass of the circulating blood is speedily reduced below par, and laid specially open to the action of blood solvents. By the same action the systemic blood is charged with poisons, direct from the food, and fermenting ingesta, and from the overworked spleen and liver whose functions are profoundly impaired, and later from other important organs, the healthy functional activity of which can no longer be maintained by the deteriorated blood supplied to them.
Hæmoglobinæmia in dogs has been produced experimentally by the injection of water into the veins the mere dilution of the plasma dissolving out the coloring matter from the red globules (Hayem); also by the inhalation of arseniureted hydrogen (Naunyn and Stadelman); by the ingestion of toluylendiamine, or phosphorus (Afanassiew, Stadelman); by snake venom, septicæmia, influenza, contagious pneumonia, petechial fever, anthrax, etc. These cannot be looked on as causes of the acute hæmoglobinæmia in the horse, but they serve as illustrations of changes in the plasma, and poisons in the blood determining the escape of hæmoglobin from the cells.
Ralfe recognizes two forms of hæmoglobinæmia in man:
1st. That in which the hæmoglobin is simply dissolved out of the blood globules, the solution taking place chiefly in parts exposed to cold.
2d. A more severe form in which the dissolution is general and probably attended by some destruction of red globules in the liver, spleen and even in the kidneys. The general opinion appears to be that the attacks are due to some nervous disturbance, which causes vaso-motor disorder and it is supposed that there is an exaggerated sensibility of the reflex nervous system. It has been suggested that peripheral irritation causes irritation of the vaso-motor centre, and in turn this causes local asphyxia in the part stimulated, under which conditions the red globules part with their hæmoglobin (Roberts).
Murri holds that the disease depends on an increased irritability of the vaso-motor reflex centre, and the formation, owing to the disorder of the blood forming organs, of corpuscles unable to withstand exposure to cold or carbon dioxide.
While it is not assumed to point out the actual poisons of hæmoglobinæmia in the horse the above suggestions may offer valuable hints as to the lines of inquiry that may be followed with the best hope of reaching definite results.
Lesions. These are especially found in the blood, liver, spleen, muscles, bone marrow and kidneys. The spinal cord and nerve trunks are occasionally affected.
The blood is charged with carbon dioxide and is black, tarry, comparatively incoagulable remaining in the veins and showing an iridescent reflection. It does not absorb oxygen readily though exposed to the air, and thus bears a strong general resemblance to the blood of anthrax. It contains an abnormal proportion of urea and allied extractive matters which greatly increase its density, and interfere with the healthy exercise of the different cell organisms and functions. These are not due to excessive muscular activity as stated by Friedberger and Fröhner, but are derived mainly from the abundant products of digestion. When the shed blood coagulates it forms a soft clot without buff and the expressed serum is reddish from the presence of hæmoglobin, and of hæmatoidin crystals. The uncoagulated blood drawn over a sheet of white paper stains it deeply by reason of the same coloring matters in solution. The red corpuscles may be paler than natural, some even entirely colorless, and they are often notched or broken up in various irregular forms. They have lost the natural tendency of the shed equine blood to stick together, to collect in rouleaux and precipitate to the bottom of the vessel, so that no buffy coat is formed, should the blood coagulate. The white corpuscles are relatively increased. Finally the coloring matters contained in the plasma are imbibed by the different tissues and give a brown or reddish tinge to such as are naturally white. Limited blood extravasations are not uncommon especially in the more vascular organs like the muscles, liver, spleen and kidneys.
The liver is more or less congested and enlarged, friable, yellow, or mottled yellow and red and exudes black blood freely when incised. The bile is thick, viscid and dark green, as in cases of experimental intravenous injection of hæmoglobin.
The spleen is also swollen and congested with blood, and the pulp is very high colored from the excess of hæmoglobin and other products of blood destruction. The muscles of the croup are usually the seat of visible lesions. There may be pallor, œdema and swelling, but not unfrequently there are blood extravasations varying in size from a pin’s head upward and giving a dark red aspect to the affected tissues. Under the microscope the affected fibres are seen to have lost their transverse striation and to have assumed a more or less granular or hyaline appearance. Next to the gluteal muscles, these changes are frequently found, in the muscles of the thigh (especially the rectus femoris, and triceps extensor cruris), and in those of the loins (psoas, ilio-spinalis, and longissimus dorsi). Exceptionally the pectoral muscles are involved or even the abdominal muscles. A considerable straw-colored œdema may be found in the intermuscular connective tissue.
The red bone marrow primarily of the large bones of the limbs (femur, tibia, humerus, radius,) and less frequently of other bones, even of the vertebræ, is often the seat of intense vascular congestion and even of hemorrhage. The medullary matter is of a deep red or black color, and there is an abnormal accumulation of red globules in various conditions of growth and destruction (red nucleated corpuscles, fragments of corpuscles, colored granules). Dieckerhoff considers the condition one of osteomyelitis, but it seems to be rather a sudden, extraordinary exaggeration of the processes of blood metamorphosis. Neumann found that when the blood regeneration process is very active even the yellow marrow may be changed into red, and this throughout all the bones of the extremities.
The kidneys are usually the seat of congestion, and black spots of infarction, when the disease has lasted for twenty-four hours. In rapidly fatal cases they may appear normal. There may be enlargement of the kidneys with softening and granular degeneration of the renal epithelium in cases that survive for some days.
The bladder contains dark brown or red glairy urine of a high density and loaded with urea, hæmoglobin, etc.
The terminal portion of the spinal cord and the lumbo-sacral plexus, or some of its branches, are sometimes blood stained, or the seat of an exudate or surrounded by one.
Symptoms. In the regular type of hæmoglobinæmia in the horse the history of the attack is highly significant. The subject is in good working condition, he may be fat, or lean, but in either case the muscles are firm and well developed, diet has been liberal, embracing a large proportion of albuminoids, work has been constant up to within a day or two preceding the attack, when the animal has been left absolutely idle in the stall without any reduction of feed. Then finally it has been suddenly subjected to active exertion which demands vigorous muscular movement, and above all activity of the respiratory muscles and the heart. This exertion usually consists in riding under the saddle or going in harness, but may attend on casting in the stall, lounging in a ring, or in a playful run when suddenly set at liberty.
Severe Cases. The attack comes on early in the course of such exercise. The patient may not have gone more than one hundred yards from the stable or he may have traveled for half an hour or an hour, but the disease rarely shows itself after a longer period of work.
The horse which left the stable full of life and spirit, suddenly flags and hangs on the bit, the ears or head may drop, and one or more limbs usually the hind ones, are moved stiffly and awkwardly, or even stagger. He knuckles over at the fetlocks, drags the toes on the ground, flexes the joints imperfectly, the muscles appearing to be rigid and uncontrollable, or he crouches, the joints remaining semiflexed the animal in vain attempting to extend them. The patient trembles violently, sweats profusely, breathes deeply and rapidly and assumes a pinched, anxious, agonized expression of countenance. The heart beats tumultuously, the pulse (in 84 per cent. Friedberger and Fröhner) is accelerated to a variable degree, and the temperature is still normal (in 80 per cent. Friedberger and Fröhner), or rarely exceeds 101.5°F. There is often tenderness on percussion and sometimes even on manipulation over the loins, short ribs, and the croup, and pinching of the loins may cause wincing. The affected muscle or muscles (lumbar, gluteal, crural) are usually firm, hard and tender, they may be the seat of spasm or of œdema and paresis. These parts may, however, have their sensitiveness lessened and even punctures or electric currents may have little effect on them.
Soon the increasing muscular weakness is incompatible with the maintenance of the standing position, the bending of the limbs and crouching become extreme, the animal makes vain efforts to control the muscles and extend the joints, and helplessly drops to the ground. When down he moves his legs convulsively, but is unable to coördinate the muscular movements and all efforts to rise are unavailing.
The spasms and paresis may attack other parts of the body such as the pectoral region the shoulders and even the abdomen, but the earliest and most persistent disorder is usually in the divisions of the lumbo-sacral plexus affecting the supra or sublumbar muscles, the gluteals, the patellar (triceps,) the adductors and the abductors. The caudal muscles are exceptionally involved. In a series of ten cases Bouley noticed that the left hind limb was always the first paralyzed (evidently a simple coincidence).
Urine may be passed freely or the bladder may be paretic so that it must be emptied with the catheter. In severe cases the urine is of a high density and of a dirty brownish gray, red or almost black color. It contains no blood clots, nor blood globules, but granular hæmoglobin, tyrosin and other waste products contribute to produce the reddish color. In some instances there is an abundant metalbumen which renders the liquid glairy, causing it to fall in fine threads or films. Urea is usually present in great excess. Hippuric and even uric acid are usually present but not in excess. When the disease has advanced to nephritis the albuminuria is complicated by the presence of casts of the uriniferous tubes, renal epithelium, white and even red blood globules.
During the violence of the attack there is no disposition nor leisure to eat, but when the more violent symptoms abate appetite is usually manifested. There may be more or less paresis of both bowels and bladder, so that neither fæces nor urine is passed yet in other cases both are discharged spontaneously.
The senses are preserved, excepting in the case of the affected muscles and the integument which covers them. There may, however, be more or less dullness and stupor in certain cases from poisoning of the cerebral centres by the poisons circulating in the blood.
Mild Cases. In the mildest cases there is stiffness and lameness in one, or less frequently in both hind limbs, coming on when put to work after a period of idleness, and not associated with any appreciable lesion of the limb in question. There may or may not be hardness and swelling of the gluteal or other muscles of the quarter or loins. This has the appearance of rigidity or spasm but may be primarily due to œdema or exudation into the substance of the muscle. In some instances the muscles of the breast, shoulder, or forearm are the seat of the trouble. Muscular trembling and perspiration may be present and if the urine is examined, it is often found to be glairy, or charged with urea, and allied nitrogenous products. These cases are not benefited by local applications, but they recover (temporarily) under rest and above all under active eliminating treatment. Under gentle and progressive exercise too they improve and get well. They recur, however, with great readiness under a rich nitrogenous diet and a temporary rest followed by sudden exertion.
Between the mildest and gravest cases there are infinite gradations of severity, one-third to one-half of the worst cases usually terminating fatally, whereas the mildest are always amenable to treatment.
Progress. The course of the disease depends on the severity of the attack but also, in no small degree, on the good judgment of the driver. Cases that develop with great suddenness, and apparently with extreme severity may subside spontaneously if the animal is placed in a condition of absolute rest. If, however, we can secure rest of the muscles of progression only, while the breathing remains rapid and labored, improvement is unlikely, as the system continues to receive large accessions of the toxic products. When the patient is down and unable to rise, the enforced rest may be beneficial, but too commonly, the greater effort with which breathing is carried on in the recumbent position, and the frequent ineffectual struggles of the limbs prevent the requisite muscular quietude.
In some cases, and especially in the mildest, recovery may seem to have been effected in a few hours, and in others it will be seen in twenty-four or forty-eight hours, while in still others the paresis and helplessness may continue for a week and yet be followed by recovery. In these cases appetite may be retained in greater or less degree, but the intestinal peristalsis is usually weak and imperfect, the fæces small in quantity and dry, and the bladder atonic so that the urine may have to be drawn off with the catheter. It usually retains the deep red color, or improvement may be heralded by a change to a dirty grayish hue. If, however, it shows an excess of albumen, cylindroid casts entangling renal epithelium and white or red globules it will indicate the access of diffuse nephritis and a prolonged or even a fatal illness.
When control of the limbs is not restored at the end of a week, the paretic muscles usually undergo marked and rapid wasting, which may last for months or years. This is especially common in the case of the patellar muscles (muscle of the fascia lata, triceps extensor cruris) in which the atrophy may become so extreme that the skin covering the inner and outer sides of the thigh may be brought virtually in contact in front of the femur. This entails an almost complete inability to sustain the body on the hind limbs. When atrophy is less extreme, there is only a weakness, stiffness, or swaying or staggering on the hind limbs in progression.
In fatal cases death may occur early in connection with the violent struggles, the excited breathing, pulmonary hypostasis and congestion, a cyanotic hue of the visible mucous membranes and a gradual increase of stupor. Though delayed for several days, there is a continuation of the muscular struggles, and the labored breathing; the red or glairy character of the urine persists or is exaggerated; the nervous irritability increases, with muscular trembling; and cyanosis, or stupor increases until death.
The mortality is always high in the severe forms of the disease, the deaths ranging from 20 per cent. upward.
After a first attack there is a strong predisposition to a second under similar exciting conditions.
Diagnosis. The peculiar symptoms of this disease and the circumstances attending its onset, are usually sufficient to distinguish it from all others. There may be danger of confounding certain cases with thrombosis of the posterior aorta, or of the iliac arteries or their branches, but the absence, in such cases, of the special history of the attack and of the morbid state of the urine, and the absence of pulsation in the arteries distal to the thrombosis will serve to prevent confusion. Spinal myelitis will be distinguished by the gradual nature of the onset, by the absence of the conditions attending on the attack of hæmoglobinæmia, and usually by the absence of hæmoglobin, urea and other nitrogenous products in excess in the urine.
Prevention. The hard worked or systematically exercised horse, which is at the same time heavily fed must not be left in a state of absolute rest in his stall for twenty-four hours. A fair amount of exercise must be given on every day in the week, and at the same time, the food should be restricted in ratio with the restriction of exercise. Turning for an hour or two daily into a yard may be a sufficient precaution. When from any cause, rest is imperative, the diet must be materially reduced and given in part in a laxative form (bran, roots), or a slight laxative (Glauber salts) or diuretic (saltpeter) may be added. Cleanliness and a free ventilation of the stable, are also of value in obviating at once auto-intoxication and the admission of poison through the lungs. In the same way a free allowance of drinking water is beneficial as favoring a general elimination from the various emunctories, and a dilution of the plethoric blood.
These precautionary measures are especially important in the case of horses which have passed through a first attack and which are in consequence strongly predisposed to a second. Horses fed liberally on highly nitrogenous food (oats, beans, peas, cotton seed meal), will also require specially careful oversight when at rest for a day or two only.
Treatment. The first and perhaps the most important consideration is absolute rest. If the subject is stopped instantly on the appearance of the first symptoms, the disease may be often aborted. It is better to avoid the exercise of walking to a stable until such time as the severity of the attack has somewhat moderated and then to move the subject only in the slowest and quietest possible way. If the patient is already down and unable to rise, he may be carried to the nearest stable in an ambulance or on a stone-boat, and there helped to his feet and supported in slings. Though he may be unable to continue in the standing position without the sling, yet if he can use his limbs at all for support, and is prevented from lying down, the breathing will be rendered so much more free and quiet, that it may greatly lessen the transfer of the poisonous elements into the general circulation and materially contribute to recovery. If, however, he cannot stand on his limbs at all, but must settle in the slings, the compression of the chest will so excite the breathing that it will induce dyspnœa, pulmonary congestion and a rapidly fatal result. In such a case a good bed must be provided and the patient made as comfortable as possible in the recumbent position.
In some cases in the earliest stages a full dose of sweet spirits of nitre or even half a pint of whiskey has seemed to assist in aborting the disease though the urine was already of a deep red color. It probably acted by supporting the already oppressed heart, and securing a prompt elimination by the kidneys.
Friedberger and Fröhner strongly recommend bleeding in all cases of dyspnœa and excited heart action, and considering the plethoric condition of the animal it would equally commend itself in other cases as well. This is the most prompt sedative of the nervous and vascular excitement, and the most speedy and certain means of removing much of the poisons accumulated in the blood, and of diluting what remains by reason of the absorption of liquids from every available source. This will more than counterbalance any temporary increase of poisons drawn from the portal system to fill up the vacuum in the systemic veins caused by the emission of blood. When the thick tarry condition of the blood seriously hinders a speedy abstraction both jugulars may be opened at once.
In some cases of great nervous excitement bromides may be useful in moderating circulatory and respiratory movement, but on the whole the advantage is greater from an immediate resort to eliminating agents.
One of the most effective agents is water. If the patient is thirsty he should have all he will drink, and if not, it may even be given from a bottle, or thrown into the rectum. A still more effective resort would be to introduce water intravenously in the form of a normal saline solution, or even to pass it into the trachea through a small cannula or large hypodermic needle. This serves to dilute the over dense blood, to stimulate the kidneys and other emunctories to active secretion, and to retain in solution the hæmoglobin, urea and other products which would otherwise cause greater irritation. This would be especially applicable after the blood tension had been diminished by phlebotomy.
Warm fomentations to the loins or croup are not without their influence. They tend to soothe the irritated parts and to solicit the action of the kidneys more particularly. The old resort of a fresh sheep skin, with the fleshy side in, may be used as a substitute.
Perhaps the most important indication is to secure depletion from the overloaded portal system and liver. Where nothing better offers, a pint or quart of castor oil, or a pound of Glauber salts, or a half drachm of podophyllin and four drachms of aloes may be given. If available 1 to 1½ grains of eserine, or 7 grains of barium chloride may be given hypodermically in distilled water or that which has been raised to the boiling point. This may be supplemented by frequent injections of hot soap suds or even of laxative saline solutions. If the bowels can be roused to free secretion the removal of toxic matters from the portal blood and the delay in the progress of similar matters through the liver will go far toward securing a favorable result. When free purgation has been secured recovery can usually be counted on.
The action on the bowels must be followed up by diuretics to eliminate the offensive matters from the general system. Colchicum has been recommended because of its action in increasing the solids of the urine, and this may be combined with saltpeter or other diuretic, or the latter may be used alone and repeated twice a day. If, however, the patient can, by the free use of common salt or otherwise, be induced to drink freely of water, the elimination through the kidneys will be sufficiently secured.
The muscular weakness and paralysis that remain after the acute symptoms have subsided must be met by stimulating liniments and even blisters to the loins or affected muscles, by the internal use of strychnia (2 grs. twice daily) until the jerking of the muscles indicates that its physiological action has been secured, and by an electric current daily for ten minutes at a time through the affected nerves and muscles. Animals that have been helpless for weeks have, in our hands, recovered under such treatment, and even cases of several months’ standing, with the most extensive atrophy of the triceps, and in which the animal could barely stand, have made a satisfactory recovery.
Any remaining nephritis must be treated according to its indications.
During recovery and in the convalescent animal the diet should be laxative and non-stimulating. Bran mashes, turnips, beets, carrots, green fodder, ensilage and scalded hay may be allowed. Oats, corn, beans, peas, vetches, etc., must be carefully avoided. If the food fails to maintain the bowels in a gently relaxed condition one, two or more ounces of sulphate of soda may be added daily.
In the mild cases a good dose of purgative medicine succeeded by a course of diuretics will serve a good purpose.
In all cases alike work must be resumed very gradually. At first the animal may be walked a few hundred yards, and the pace or load and duration of exercise may be increased day by day until full work can be safely endured. In an animal that has once suffered the same gradual inuring to labor should be followed, after any short period of rest on a fairly good ration.