Part 76

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.