The body (and in most cases, the brain) is always monitoring every physiological function. If staying alive is the body's goal, then homeostasis is one major strategy that the body uses to achieve that goal. In simple terms, if any change in any body function is detected by the brain, many mechanisms are activated to correct the change. As mentioned previously, this detection and correction process is almost always done using negative feedback mechanisms. If the kidney detects too little of something (oxygen, for instance, which is an indicator of too few RBCs), the kidney sends a message to the body to release more of something else (the hormone erythropoietin, for instance) to correct the situation. In our example, the erythropoietin travels to the bone marrow to stimulate increased production of RBCs. That is, the erythropoietin causes the "RBC faucet" to increase its flow. Conversely, too much oxygen (indicating too many RBCs) will cause less erythropoietin to be released, causing the "RBC faucet" to decrease its flow.

Now, it must be noted here that the homeostatic condition of the body on Earth is different from the homeostatic condition of the body in space. To state this in terms that you have heard before, the "Earth-normal" condition of the body is different from the "space-normal" condition of the body. The body goes through a natural process of adaptation when it senses the new environment of space. The brain develops a new set of criteria from which to judge the condition of the body, and the feedback mechanisms operate differently to reflect the new criteria. Therefore, the PV, RBCM, and TBV changes that we looked at in the previous section are normal changes for the body to undergo in space. And the space flight changes in erythropoietin levels and reticulocyte counts that you will look at in this section are also normal adaptive measures undertaken by the body in response to the new environment of space.

Figure 13. Preflight inflight and postflight erythropoietin (EPO) levels.

In Dr. Alfrey's study, erythropoietin levels were measured from blood samples taken preflight, six times inflight, and postflight. The inflight blood samples were frozen to assure their preservation for later analysis on Earth. As you can see from Figure 13, the inflight erythropoietin levels are lower compared to preflight levels. In fact, they are significantly lower (at times by up to 50%) until the end of the mission. The reduction in erythropoietin levels indicates where at least some of the responsibility rests for the reduction in RBCM seen in the last section. One day after landing, erythropoietin levels increased to twice preflight levels, presumably in response to the body's immediate need to replace the RBCM that decreased in space. At this point, the brain has had to reprogram itself to respond to the needs of the body under the conditions of Earth's gravity.

Figure 14. A smear slide showing selectively stained reticulocytes.

In the normal process of RBC production, there are certain precursor cells that must first develop in order to become full-grown RBCs. Precursor cells are the "babies" that eventually mature into full-grown RBCs. The bone marrow always has a supply of "RBC embryos," called stem cells, that wait for the signal from erythropoietin before they begin to develop. Once the erythropoietin signal arrives, these stem cells mature into the "RBC babies" known as reticulocytes. There are always a small number of reticulocytes that are released regularly by the bone marrow into the bloodstream, but if RBC production is increased for any reason, there are proportionally more reticulocytes circulating in the blood. If RBC production is decreased for any reason, there are then less reticulocytes released into the bloodstream. Therefore, the number of reticulocytes in the blood can indicate an increase or decrease in the production rate of RBCs that is occurring in the bone marrow.

The number of circulating reticulocytes in the bloodstream was determined before and after the mission in order to understand if the rate of production of RBCs is affected by space flight. This was done by taking a drop of blood from each of the four astronauts, adding a methylene blue dye that selectively marks the reticulocytes, and smearing the dyed sample on a glass slide. Under a microscope, the number of reticulocytes in the blood sample can be counted (Figure 14) and this number can be converted to a relative volume overall. Dr. Alfrey's results are shown in Table 5.

Table 5. Preflight and postflight reticulocyte counts.

Reticulucyte Count
	1g		Postflight
	Mean	Standard Deviation	R + 0	R + 14
Crew Member 1	0.8	0.08	0.6	1.3
Crew Member 2	1.1	0.15	0.5	1.8
Crew Member 3	1.1	0.07	0.7	1.8

What do these results indicate? That is, why do the erythropoietin levels and the number of reticulocytes decrease? Well, for one thing, the plasma volume decreases inflight. If the RBCM did not also decrease, the blood would be too thick with RBCs. Therefore, in order for the RBCM to decrease, the brain must signal the kidneys to slow down the release of erythropoietin. The consequence of decreased erythropoietin levels is a decrease in erythropoiesis. This means that there are less RBCs "born," which also means that the number of "baby RBCs," or reticulocytes, released by the bone marrow would decrease. It should be expected, then, that the decreased erythropoietin level was accompanied by a lowered reticulocyte count.

Another point to remember is that the body's oxygen requirement probably decreases inflight because astronauts do not utilize their muscles in the same way that they must on Earth, where we must always work against gravitational forces. Since RBCs carry the oxygen and there is less oxygen needed, then there are fewer RBCs needed by the body while in space.

We have talked about the negative feedback mechanism involving erythropoietin that is responsible for "turning on" or "turning off" the RBC production faucet. We have also looked at one of the factors (the number of reticulocytes) that indicate the rate of RBC production. In the next section we will look at the RBC production process more deeply and how other factors may become involved to either influence the rate of production or to affect the survival of RBCs.