Figure 1

Topological Scheme of Steady-State Iron Flux into and out of the main Body Organs of the Mouse. All compartments receive iron from plasma/Extravascular Fluid (EVF) via the transferrin receptor endocytosis. The peripheral compartments return iron probably mainly via the ferroportin transporter. An exception is bone marrow the iron of which is rapidly channelled into haemoglobin synthesis of the maturing erythrocytes [13, 59]. The depicted direct flow into the spleen represents red blood cell production (a particular feature of this organ in mice [53]) and possibly the iron uptake by spleen macrophages due to "ineffective erythropoiesis" [15]. Tracer iron bound as freshly synthesized heme may also be recycled (e.g. FLCVR-mediated) circumventing the passage through the vast red blood cell compartment. These different fluxes cannot be distinguished in a compartment clearance model as formulated here. For the red blood cell compartment we assume a component of random elimination of cells into spleen/RES, independent of cell age. The removal of senescent cells after their life span cannot be seen in the earlier stages of pulse-labelling of the iron compartments. Some of the compartments loose iron out of the body by way of cell exfoliation or desquamation (intestinal tract, skin integument), by production of bile (liver) and urine (kidney), or by bleeding. These compartments have double exits. For the purpose of parameter estimation of steady-state ⁵⁹Fe flux the quantitatively less important elements of these double exits have been neglected (dotted arrows). Heme flow as enterohepatic absorption-secretion cycle has not been included into the figure. It would not be visible in the tracer experiment due to onset of tracer dilution over the whole body.