A direct study of the isolated rat liver perfused with oxygenated blood containing amino acids and lysine-ϵ-C14 has yielded facts indicating that the liver synthesizes practically all the plasma fibrinogen, the albumin fraction, and probably more than 80 per cent of the plasma globulin fraction. The response of the isolated perfused liver in protein synthesis is qualitatively and quantitatively analogous to that of the intact animal, notably in (a) the ability to discriminate between natural L-lysine and D-lysine, (b) the per cent of isotopic amino acid converted to CO2, (c) the per cent utilized in liver and plasma protein synthesis. The results obtained with the perfused liver are compared and contrasted with those reported for tissue homogenates, minces, and slices.

Iron absorption is a function of the gastro-intestinal mucosal epithelium. The normal non-anemic dog absorbs little iron but chronic anemia due to blood loss brings about considerable absorption—perhaps 5 to 15 times normal. In general the same differences are observed in man (1). Sudden change from normal to severe anemia within 24 hours does not significantly increase iron absorption. As the days pass new hemoglobin is formed. The body iron stores are depleted and within 7 days iron absorption is active, even when the red cell hematocrit is rising. Anoxemia of 50 per cent normal oxygen concentration for 48 hours does not significantly enhance iron absorption. In this respect it resembles acute anemia. Ordinary doses of iron given 1 to 6 hours before radio-iron will cause some "mucosa block"—that is an intake of radio-iron less than anticipated. Many variables which modify peristalsis come into this reaction. Iron given by vein some days before the dose of radio-iron does not appear to inhibit iron absorption. Plasma radio-iron absorption curves vary greatly. The curves may show sharp peaks in 1 to 2 hours when the iron is given in an empty stomach but after 6 hours when the radio-iron is given with food. Duration time of curves also varies widely, the plasma iron returning to normal in 6 to 12 hours. Gastric, duodenal, or jejunal pouches all show very active absorption of iron. The plasma concentration peak may reach a maximum before the solution of iron is removed from the gastric pouch—another example of "mucosa block." Absorption and distribution of radio-iron in the body of growing pups give very suggestive experimental data. The spleen, heart, upper gastro-intestinal tract, marrow, and pancreas show more radio-iron than was expected. The term "physiological saturation" with iron may be applied to the gastro-intestinal mucosal epithelium and explain one phase of acceptance or refusal of ingested iron. Desaturation is a matter of days not hours, whereas saturation may take place within 1 to 2 hours. We believe this change is a part of the complex protein metabolism of the cell.

1. Application of the principles of hydrodynamics to the problem of blood flow and blood volume indicates that the calculation of blood volume and cell volume from the venous hematocrit and plasma volume (as determined by the dye method) is subject to considerable error. 2. This conclusion is borne out by determinations of total cell volume by viviperfusion and with the use of radioactive iron tagged erythrocytes, which have shown the erythrocyte volume to be only 70 to 75 per cent of the volume indicated by the previously mentioned calculations. 3. The average hematocrit of the entire vascular system is considerably lower than the hematocrit of the large vessels, and the cell-plasma ratio of the smaller vessels is still less. 4. In the dog there are no considerable stores of immobilized erythrocytes, and the total erythrocyte volume and circulating erythrocyte volume are identical. 5. The "rapidly circulating blood volume" can be determined by dividing the erythrocyte volume by the venous hematocrit, and is found to be considerably less than the total blood volume. 6. The concept of the "rapidly circulating plasma volume" is introduced, and it is found to be approximately 80 per cent of the total plasma volume. 7. The volume of plasma in the peripheral, cell free, sluggishly moving plasma films, plus that contained in small vessels in which no red cells are present, is also determined and found to be approximately 20 per cent of the entire plasma volume. 8. The existence and magnitude of these fractions of the blood plasma volume should receive consideration in studies of blood flow and blood volume.

Sodium has received considerably less attention in the study of tissue electrolytes than chloride, undoubtedly because of the difficulty of sodium micro-chemical methods. It has been generally assumed to be in the extracellular phase because of the evidence that most of the chloride in muscle is cxtracellular (7) and because of the fact that in some tissues the sodium: chloride ratios are the same as in plasma. The tendency to extend to all tissues, concepts which may aptly describe muscle, was criticized by Amberson et al. (1) and by Manery and Hastings (18), the latter showing that the sodium: chloride ratio differed appreciably in many tissues from that in plasma. An %xcess" chloride was reported (18) in rabbits in blood, connective tissues, testes, gastric mucosa and in the liver of rats (13a, and this paper), and an "excess" sodium in cart,ilage, spinal cord and intestinal wall (18) which suggests the existence of both intracellular sodium and chloride. It is of some interest, too, that in certain muscles a small "excess" sodium has been reported but t*his is not true for all muscle tissue. It was located in frog (6) and in dog skeletal muscle (11, 12) but not in the skeletal muscles of the rabbit (11, 18). To conform to the simple morphological division into intra-and extracellular phases, this excess sodium has been allocated to the intracellular phase. In view of these findings and of the fact that the red cells of many species (15) contain sodium instead of potassium, it seems possible for sodium to function as an intracellular ion. This report shows how radioact.ive isotopes were used to investigate such a possibility. The general scheme of dividing the tissues into two phases, intra-and extracellular, has been adopted. The limitations of this simple procedure are fully realized but its lack of complexity makes it useful. The following studies have been carried out and are reported herein: a. The rate and extent of the penetration of radioactive sodium into a JEANNE F, Mr\NERY AND WXLLIrlM F. BALE

With the production of radioactive isotopes by the physicists and the concentration of naturally occurring isotopes by the chemists, the grateful physiologists have been presented with what may prove to be the "Rosetta Stone" for the understanding and study of body metabolism. The radioactive isotopes are "marked" elements which behave precisely like their inactive replicas in the physiology of the body but can be readily recognized as distinct entities wherever found. The radioactive isotope of iron used fortunately has a long life (half life 47 days) which covers ample time for prolonged study of iron metabolism and gives assurance to the student that this iron found in tissues, bones, or fluids is the iron introduced and not some other iron coming from body storage depots, hemolysis, or red cell wastage.The literature on iron metabolism is enormous but the net results are disappointing to say the least. Every hypothetical possibility has been championed by students but very few points have been settied to the satisfaction of all workers. One can scarcely suggest a single possibility without finding that it has been more or less vigorously supported by physiologists or physicians in the past. We feel that radioactive iron will be a means of settling many of these disputes but it is impossible at this time to review all these interesting hypotheses.