Richard M. Pearce

THE ELIMINATION OF IRON AND ITS DISTRIBUTION IN THE LIVER AND SPLEEN IN EXPERIMENTAL ANEMIA. II.

In the continuous blood destruction, essentially a chronic experimental anemia, caused by injecting the dog with Trypanosoma equiperdum, no increased elimination of iron is observed in the feces. The storage of iron in the liver and spleen under these experimental conditions is somewhat greater in amount, but of the same general character as in transient experimental anemia. Splenectomy before or after infection, i.e. the development of anemia, influences neither the elimination of iron in the feces nor its storage in the liver. The retardation of the course of the trypanosome infection and thus the production of a more chronic anemia by treatment with a trypanocide, arsenobenzol, likewise does not affect iron storage. These experiments have therefore failed to reproduce the changes in iron metabolism seen in certain of the chronic hemolytic anemias of man. In the presence of a bile duct-ureter fistula the iroh content of the mixture of urine and bile is not appreciably greater than that of the urine alone. In the dog, therefore, the elimination of iron in the the bile would not appear to be an important factor. On the other hand, when bile is excluded from the intestine an unusual storage of iron occurs in the spleen. For this no explanation is offered.

THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE : XI. THE INFLUENCE OF THE SPLEEN ON IRON METABOLISM.

In the splenectornized dog the anemia caused by hemolytic poisons (hemolytic immune serum and sodium oleate) and by bleeding is of a severer grade, runs a longer course, and is accompanied by a less rapid regeneration of the blood than is the case in the normal dog. Also in the splenectomized dog, especially after the use of hemolytic serum, the leucocytosis is greater than in the normal animal. The splenectomized dog almost uniformly exhibits an increased resistance of the red cells to hypotonic salt solution, but after the administration of hemolytic poisons, and especially hemolytic serum, this increased resistance disappears and a decreased resistance persists for long periods of time. The same change occurs in the normal dog, but in the latter the return to the previous degree of resistance is more rapid than in the splenectomized animal.

An experimental study of the influence of kidney extracts and of the serum of animals with renal lesions upon the blood pressure

1. Extracts of the rabbits kidney injected into the rabbit cause a slight increase in blood pressure which is barely more than that due to the mechanical effect of the injection. 2. Extracts of the dogs kidney injected into the dog cause a decided fall in pressure; an equal fall may be caused by the dogs urine. A series of control experiments indicates that the fall caused by the kidney extract may be due to the urinary salts which it contains. 3. Extracts of cats kidney cause a rise in pressure; as the cats urine causes a fall, this rise in pressure indicates the possibility of a kidney extract containing a pressor substance which cannot be influenced by the depressor substance of the urine. 4. Rabbits kidney which in the rabbit produces a slight rise when injected into the dog causes a drop comparable to that caused by the dogs kidney itself. Similarly the dogs kidney, which injected into the dog causes a drop, produces in the rabbit a rise analogous to that produced by rabbits kidney. It is evident therefore that these pressor and depressor substances of the kidneys in question do not have a constant effect on all animals as do the extracts of the adrenal gland.

Experimental cirrhosis of the liver

The experimental studies upon which this communication is based were suggested by an investigation of the necrosis produced in the liver of the dog as the result of injecting hemolytic immune sera of high hemagglutinative power. 1 These necrotic lesions, which are due apparently to an obstruction of the circulation by thrombi composed of fused red blood-corpuscles, vary in position and extent, according to the dose of serum administered. Small doses cause more or less isolated lesions which may occupy any portion of the lobule; large doses produce a diffuse necrosis which spares only the tissue about the larger portal spaces. The uniformity of this necrotic lesion suggested the importance of a study of the repair process which would naturally follow in animals recovering from the acute toxic effects of the injected serum. The extent of the destruction precluded complete regeneration of liver parenchyma, and if the defect was repaired by connective-tissue proliferation, the resulting histological picture would be, except for a difference in the relation between the new tissue and the remainder of the lobule, analogous to cirrhosis in man. Methods.— Dogs were injected either in the smaller branches of the femoral vein, or in the abdominal cavity, with serum obtained from rabbits which had received repeated injections of red blood-corpuscles of the dog. The dose usually employed was I c.c. of serum to from 500 gm. to 800 gm. of body-weight, and the animals were killed at intervals varying from 48 hours to 36 days Results.— A majority of the animals die after intervals varying from 4 minutes to 48 hours. In those surviving, hemoglobinuria was a constant phenomenon usually appearing within 18 to 24 hours, persisting 3 to 4 days, and followed for several days by the presence of bile pigment in the urine. The first evidence of repair was mitosis of the liver cells lying at a slight distance from the necrotic areas. The earliest period at which this was seen was 38 hours after injection.