"Splenism" - the function of spleen, as the organ conducting the interrelation of the circulatory system and hematopoiesis

Abstract

The term “hypersplenism” has long been entrenched firmly in clinical practice; it is defined as the enlargement of the spleen (splenomegaly), as a consequence of difficulties of blood outflow from the spleen, accompanied by the development of pancytopenia. Most frequently and "clean" such - secondary splenomegaly develops as a result of difficulties of blood outflow in the liver cirrhosis (in 30-50% of patients) (12). In this case, the phenomenon of hypersplenism, which manifests itself in pancytopenia, is observed in more than half of these patients (11, 18, 19, 20). However, the mechanism of anemia needs to be clarified, as a rule the emphasis is only on blood cell destruction in the congestive spleen or blood loss from the varicose veins. (14, 16, 18).Previously we (5) had found that in most of the 25 studied patients with secondary splenomegaly (cirrhosis and splenic vein thrombophlebitis) potent inhibitor of blood was detected in serum. Splenectomy led to the disappearance of the inhibitor and the activation of erythropoiesis.Materials and methods. The experiments were performed on Wistar rats, weighing 200-250 g; several models of experiments were involved. Splenomegaly was created either by ligation of splenic vein or intraperitoneal infusion of 80% saline suspension of washed red blood cells (3.5 ml/100 g body weight). In part of this group of animals spleen was tightly sheathed with capron a week before transfusion of red blood cells in order to deprive of the opportunity to deposit the excess of red blood cells. Red blood cells count, hemoglobin level and concentration of reticulocytes were studied in the dynamics. We determined the concentration of serotonin in blood and kidneys.Results and Discussion. Ligation of the splenic veins as well as deposition of the part of the transfused red blood cells in it, as evidenced by the almost two-fold increase of its mass (from 1.0-1.2 g to 2.0-2.5 g), led to the weakening of erythropoiesis. The inhibition of erythropoiesis is evidenced by the sharp decrease of the concentration of young red cells - reticulocytes and the gradual reduction of erythrocytes. Transfusion of large number of red blood cells results in the same effect.In plasma of these animals there is an active factor, which leads to inhibition of erythropoiesis. This can be concluded on the basis of the fact that the introduction of the blood serum of these animals resulted in inhibition of blood in recipients: as evidenced by the reduction in the concentration of reticulocytes. In contrast, the reproduction of erythrocytosis against the deprivation of spleen’s possibility to deposit the excess of red blood cells, in spite of the decrease in the activity of erythropoiesis, did not lead to the appearance of active inhibitor of erythropoiesis in the blood of these animals: after the introduction of serum erythropoietic activity of the recipient did not change (the concentration of reticulocytes count remained at the level of the control animals). Polyglobulia itself leads to the reduced formation of erythropoiesis stimulator - erythropoietin.Thus, we have found that enlargement of the spleen (splenomegaly), both after ligation of its veins and when depositing excess of erythrocytes in case of erythrocytosis, leads to anemia due to the formation of the active inhibitor. We believe that the active inhibitor exerts its effect through inhibition of the formation of erythropoietin in the kidney rather than by direct blocking of the bone marrow. Such inhibitor is serotonin, as its blood level increased with splenomegaly. In patients with splenomegaly source of serotonin is apparently the destruction of platelets. Increased serotonin level was found in those parts of kidneys, which are the structures that synthesize erythropoietin. Removal of the spleen leads to the significant reduction of serotonin level both in blood and kidneys.Conclusions:1. Pancytopenia develops in patients with congestive splenomegaly, it is caused not only by the destruction of blood cells, but also by active suppression of hemopoiesis.2. Serotonin is apparently the erythropoiesis depressing factor; its high concentration in the blood is detected in case of blood stagnation in the spleen.3. Hyperserotoninemia inhibits the production of erythropoietin in kidneys despite the presence of anemia. 4. Polycythemia in rats, which spleen is deprived of the possibility to deposit the blood excess, does not lead to the appearance of the inhibitor of erythropoietin.5. Spleen, performing the function of depositary, provides the connection of the circulatory system and blood formation. Taking part in deposition of excess of red blood cells in the circulatory system, spleen blocks the formation of erythropoietin, thereby reducing the formation of red blood cells. This functional mechanism of the spleen could be called "splenism". And the excessive increase of this function leads to the pathology - hypersplenism.