The general oscillator theory pertinent to frequeacy stability is presented, and the superiority of the bridge oscillator is demonstrated.
The hematologist has pursued the subject because of difficulties of diagnosis in certain hematological diseases, while the control engineer has found it a challenging example of a physiological control system for which a completely satisfactory model has not been derived. The work described here evolved from a collaboration of physicians and engineers following both these interests. A digital simulation and an optimum search program that should have broad application in simulation problems were implemented in the course of the investigation. BACKGROUNDThe human body of the normal adult male contains about 4.0 grams of iron. About 2.5 grams are found in the hemoglobin of red blood cells, a vital part of the oxygen-transporting mechanism of the blood. About one gram is tied up in storage sites, primarily in the liver and spleen. Small amounts are found in various other tissues of the body. Finally, about 2 to 4 milligrams are found in the blood plasma, bound in a carrier called transferrin. This latter amount, small in quantity, is the key to any study of ferrokinetics.In the normal adult male, the assumption is generally made that the only iron transport pathways of any importance in magnitude can be represented in Figure 1. Figure 1 -Principal pathways for iron transportWith a normal life span of red blood cells of approximately 110-120 days, the production of new red blood cells requires that about 20 to 23 mg. of iron pass from plasma to marrow every day. It can be seen that the intake and loss of about 1 mg/day are minor perturbations on the system and these are generally ignored in analysis of normals. The system is then considered as essentially a closed one for reasonably short periods of experimentation. z If plasma iron turnover is estimated using only the initial disappearance rate following an injection of tracer, the result exceeds the known uptake by marrow in normal subjects by 30 to 50%. Further study, using a sensitive tracer, Fe59, reveals a second component in the disappearance curve implying exchange of iron between plasma and another pool of iron as well as simple outflow to marrow. 1 Succeeding investigators have tried to place the exchange compartment at different sites, to relate the appearance of tracer in red cells to the model parameters, and to relate normal models to interpretations of data in pathologic cases. [2][3][4][5] In general all of these studies, and our own, have relied on some version of a compartmental model to represent ferrokinetics. Figure 2 is a representation of the compartmental model as we have used it; other investigators would rearrange the compartments and pathways topologically.Compartment 1 is the plasma iron, in which measures of iron and radioiron may be made by taking a blood sample and processing it in the laboratory. Compartment 2 lumps together iron in red cells and iron in the red-cell-producing sites in marrow. Radioiron introduced into plasma does not appear in redcells for about 24 hours and not in large amounts ACKNOWLEDGEMENT
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