Chapter XVIII: Part 18

_Degenerations of the Kidneys_ are to be largely traced to the same hepatic source. The uric acid diathesis, and the oxalic acid diathesis, both the result of imperfect liver function, are among the most frequent causes of irritation of the kidneys, by which channel they are eliminated from the body. Hence acute and chronic nephritis, as well as nephritic calculi result from morbid conditions which have their starting point in the imperfect function of the liver. Again fatty degeneration of the kidney is very liable to result from derangement of the glycogenic function of the liver, the tendency to the formation of fat and the constant irritation caused by the passage of the sugar contributing to the tissue degradation. In such cases albuminuria is a not uncommon accompaniment.

_Derangements of the Digestive Organs_ may be said to be a necessary result of hepatic disorder. Excessive secretion of bile stimulates peristalsis and may induce diarrhœa, while diminished secretion tends to constipation, light colored, fœtid stools, intestinal fermentations and poisoning by the irritant products. A torpid hepatic circulation means congestion of the whole portal system, indigestions, colics, chronic muco-enteritis, intestinal hemorrhages, hemorrhoids, etc.

_Derangements of the Nervous System._ In this connection may be named the lameness of the right shoulder which accompanies certain disorders of the liver, the extreme dullness and depression that attends on others, the sluggish pulse that appears in certain types, the unsteadiness of gait (giddiness) in others, the muscular cramps, and irritability in still others. These appear to be due in some instances to the nervous sympathy of one part with another, whilst at other times they as manifestly depend on the circulation in the blood of partially oxidized and other morbid products of hepatic disorder which prove direct poisons to the nervous system.

Derangements of the circulation, like extreme rapidity, or slowness of the pulse, irregularities in rhythm and intermissions, may be charged more directly on the nervous affection, though primarily determined by hepatic disorder.

On the part of the _Respiratory Organs_, affections of a chronic type, like sore throat and bronchitis may often be traced to hepatic torpor or disorder.

_Skin Diseases_ are notoriously liable to come from inactive or disordered liver, the irritant products circulating in the skin or sweating out through it, giving rise to more or less irritation. The result may be a simple pruritus, an urticaria, an eruption of papules, vesicles or even pustules. In any such cases it is proper to look for other indications of liver disease,—pale color and offensive odor of the fæces, muco-enteritis, indigestion, icterus or yellow patches on the mucous membranes, tenderness on percussion over the asternal ribs, muscular neuralgia, nervous disorder, the passage of bile, hæmoglobin, albumen, sugar or other abnormal elements in the urine, etc.

TREATMENT OF SECONDARY AND FUNCTIONAL DISEASES OF THE LIVER.

_Diet._ Many hepatic disorders, and especially those that are exclusively or mainly functional may be corrected by diet alone. Prominent among dietary influences is the abundant supply of water. The succulent grasses of spring and early summer constitute the ideal diet, hastening and increasing elimination, and lessening the density of the bile, even to the extent of dissolving biliary calculi and concretions. Upon dry winter feeding such calculi are common especially in ruminants, whereas after a month or two at pasture they are extremely rare. In winter the same good may be arrived at by the use of ensilage, brewer’s grains, roots, fruits, or even scalded hay or bran. The two extremes of highly albuminous and highly carbonaceous or saccharine food are to be avoided or used only in limited amounts. In the one class are clover, alfalfa, sainfoin, vetches, cowpea, lespedeza, especially in the form of hay, beans, peas, cotton seed, gluten-meal, rape and linseed cake. In the other are wheat, buckwheat, Indian corn, sorghum, sweet-corn and cornstalks. Some agents like beets which are rich in saccharine matter may be actually beneficial by reason of their laxative and cholagogue action. In the carnivora the food should be largely of simple mush of oatmeal, wheat seconds, or barley meal, skimmilk or buttermilk. If it is needful to tempt the appetite in a fleshfed animal this should not be done by rich, fat gravies, highly spiced animal food, or rich saccharine puddings, but rather by the addition of a little pure juice of lean meat, or some well skimmed beef tea.

It is as important to regulate the quantity as the quality of the food as the heavy feeder will over-charge the liver as much by an excess of otherwise wholesome food, as will the ordinary animal by the indigestible and unwholesome articles. As a rule the improved breeds of meat producing animals, have acquired such facility in fat production that much of the surplus is largely and profitably disposed of in this way, and in their short lives little obvious evil comes of the overfeeding, but in cases in which this outlet proves insufficient, as in horses and dogs that are highly fed on stimulating or saccharine diet, and which are kept for the natural term of their lives, with little exercise, the evil tends to reach a point of danger. Nursing mothers and dairy cows find a measure of safety in the free flow of milk and the yield of butter, but breeding cows that have been improved till they have no longer a capacity for milking, but must have their calves raised on the milk of other and milking strains are correspondingly liable to suffer.

_Exercise in the Open Air._ As enforced idleness, on a full diet and in a warm and moist environment is a main cause of hepatic disorder, so abundant exercise in the open air and especially in a cool season is beneficial in a marked degree. Beside the bracing effect on the digestive organs and the improvement of the general tone of the system, the action of the muscles in hastening the circulation greatly favors the removal and elimination of waste matters. Still more advantageous is the increased activity of the respiration and the aspiratory power of the chest in at once unloading the portal system and the liver by hastening the progress of the hepatic blood into the vena cava and right heart, and in furnishing an abundant supply of oxygen for the disintegration of the albuminoids and amylaceous products. Such exercise must of course be adapted to the condition of the animal and its power of sustaining muscular work, but judiciously employed, it is one of the most effective agencies in correcting and improving hepatic disorder or hepatic torpor. Idle horses, the victims of obstinate habits of constipation, muco-enteric irritation, indigestion, nervous, urinary or cutaneous disorders will often be greatly benefited or entirely restored by systematic exercise. This is one of the great advantages of a run at pasture, as the subject secures at once the laxative cholagogue diet, an abundant supply of oxygen, a better tone of the muscular and general system, and a more perfect disintegration of albuminoids. Sea air with its abundance of ozone is especially advantageous.

In the carnivora while we cannot send them to grass, much can be done in the way of systematic exercise, and in the case of city dogs a change to the country, where they can live out of doors and will be tempted to constant exercise and play, will go far to correct a faulty liver.

_Laxatives._ _Cholagogues._ When a free action of bowels and liver cannot be secured by succulent food and exercise, we can fall back on medicinal laxatives. These are advantageous in various ways. Some laxatives like podophyllin, aloes, colocynth, rhubarb, senna, jalap, and taraxacum act directly on the liver in increasing the secretion of bile. These may be used for a length of time in small doses and in combination with the alkalies. Other aperients act directly on the bowel carrying away the excess of bile, the albuminoids and saccharine matter that would otherwise be absorbed, and by a secretion from the portal veins, abstracting nitrogenous and saccharine elements which would otherwise overtax the liver to transform them. Thus indirectly these also act as cholagogues by withholding the excess of material on which it has to operate, and by rousing its functions sympathetically with those of the bowels. Thus sulphates of magnesia and soda, and tartrates and citrates of the same bases, given in the morning fasting, dissolved in a large quantity of warm water and conjoined with sodium chloride, ammonium chloride, sodium carbonate or other alkaline salts, or with one or more of the vegetable cholagogues above mentioned, may be continued for a length of time until the normal functions have been re-established, and will maintain themselves irrespective of this stimulus.

Calomel (and even mercuric chloride in small doses), though it is not experimentally proved to be a direct cholagogue, is one of the very best correctives of impaired hepatic function. It expels the bile from the duodenum and bowels generally, thereby preventing its reabsorption; it proves antiseptic to the ingesta; it eliminates much of the peptone, saccharine and fatty matter from the intestines and portal system thus relieving the liver materially; and it is supposed further to modify the other liver functions by a direct action on the hepatic cells, and by reducing the cohesion of fibrine, and promoting the disintegration of albumen. Certain it is that calomel gives most substantial relief in many torpid and other disorders of the liver and as it is not in itself an active liver stimulant but has rather a soothing action on that gland it can be safely resorted to in states of hepatic irritation in which the more direct cholagogues would prove more or less hurtful.

In some forms of hepatic disorder where a speedy and abundant secretion is demanded, pilocarpin may be employed, with great caution so as not to reduce the strength unduly by the attendant diaphoresis, diuresis, salivation or diarrhœa.

_Alkalies_ have long been recognized as of great clinical value in hepatic disorders. Though carbonate of soda decreases the secretion of bile, (Nasse, Röhrig), yet the alkalies generally appear to promote oxidation, and to hasten the disintegration of albumen and the albuminoids. They increase the disintegration of sulphur compounds materially adding to the sulphates and urea in the urine. They further tend to increase the hippuric acid, carbonate of soda (2 drs.) even determining the abundant excretion of this acid in man (Nasse). It may be concluded that the acknowledged value of alkalies in these diseases, is largely due to their hastening of the metabolic processes in albuminoids. Small doses of sodium carbonate further stimulate the gastric secretion and may thus benefit by rendering the process of digestion more complete and satisfactory.

_Chlorine, Iodine, Bromine and their Salts._ These halogens are of great value in many hepatic disorders. The universal craving for sodium chloride indicates the need of its elements in the animal body, and whether this is mainly the supply of chlorine for the hydrochloric acid of the gastric juice, or to fulfill its uses in favoring the oxidation and disintegration of the nitrogenous matters in the blood and tissues, or for other more or less obscure uses, it is well to recognize and act upon the indication. The various mineral waters which are held in high esteem in liver affections contain a large proportion of sodium chloride. As a medicinal agent ammonium chloride maintains an equally high position. Large doses thrice a day, so as to induce diaphoresis and diuresis greatly relieve hepatic congestions. This agent determines a great increase in the urea eliminated so that it is even more effective in the same direction, than sodium chloride. Free chlorine is also effective in hepatic torpor and congestion, and to this in part may be attributed the great value of nitro-muriatic acid.

Bromide and iodide of potassium have been found to be effective in reducing hepatic enlargement and thus in conducing to a more healthy activity of the liver.

_Ipecacuanha, Euonymus, etc._ These agents are more or less hepatic stimulants and may be found beneficial as combined with the laxative or alkaline agents in securing a better functional activity in cases of torpor or deranged function.

_Tonics, Bitters._ Tonics are often useful when the health has been undermined by long continued hepatic disorder. The iron tonics are as a rule contraindicated as tending to check secretion of bile, unless they can be given with alkalies. Iron sulphate or chloride, combined with sodium or potassium carbonate so as to establish a mutual decomposition will obviate this objection. The vegetable bitters (gentian, cascarilla, calumba, salicin, serpentaria, aloes, nux vomica) combined with alkalies are often of great value. Quinia, like opium, checks secretion and is to be avoided or used with judgment and in combination with cholagogues.

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.