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.