The Rhythmic Range of the White Blood Cells in Human, Pathological Leucopenic and Leucocytic States, With a Study of Thirty-Two Human Bone Marrows

Abstract

In a study of twenty clinical cases with a wide range of diagnoses, repeated total counts of the white cells at 15 minute intervals reveal a large fluctuation at various levels comparable to that found for the normal (1, 2). The granulocytes seem to follow a more or less hourly rhythm, the most marked shift to the left in the Ameth pattern and the moment of greatest percentage of motility coinciding with the peaks. The independence found existing between the peripheral blood concentrations of individual strains of white cells and the red cells, as determined by total and differential counts, their differential response to pathological and pharmacological stimuli, and their normal relative relations, all indicate some separate physiological mechanism of control for each type of cell, either working through, or independently of, their sources of origin. The many factors to which the circulation of the blood, as such, is subject, the complexity of the influences on origin, maturation, delivery, longevity, and destruction of each cell group, the limitations inherent in the present involved, indirect technics of counting, combine to make any single observation subject to grave misinterpretation. The value to the clinician must come in repeated observations, at times when the diagnosis or a therapeutic procedure is in doubt, at frequent intervals, at other times over longer or shorter periods, but always with the relation between consecutive counts, rather than the absolute values, the important point for consideration. Both the red and the white cells probably change their relative concentrations in the peripheral blood from time to time over a considerable range that is quite within normal physiological limits, so that, in theoretical considerations and in practical functional estimations, a zonal concept with adequate individual extremes should always be kept in mind for both physiological and pathological states. A cytological analysis of thirty-two bone marrows from human biopsy and autopsy material shows the striking reciprocity found to exist between the myelocytes and the mature polymorphonuclear leucocytes. This, together with the observed focal uniformity of maturation found in bone marrow, and the periodicity of the fluctuations of the neutrophils in the peripheral blood, leads to the formulation of the hypothesis of a constant functional withdrawal of granulocytes from the peripheral blood with a periodic delivery of new cells from the marrow, which in leucopenia and in leucocytosis represents a depression or a stimulation, respectively, of the normal mechanism. The nature and degree of the response are an approximate index of the cellular factor in the complex of the "resistance" of the particular individual.

A Study of the Mechanism of Nucleinate-Induced Leucopenic and Leucocytic States, With Special Reference to the Relative Rôles of Liver, Spleen, and Bone Marrow

“…This could occur either directly or through the m e d i u m of the phagocytic group of cells reducing the debris. The correlation of the showers of " n o nmotile" cells in h u m a n pathological conditions with a subsequent increase of young motile neutrophils (7) further supported the concept. This seemed to point to a thorough restudy of the effect of nucleic acid and its derivatives on the leucopoiefic system, inasmuch as these substances m u s t be constantly produced physiologically in the body.…”

“…Apparently in a state when the spleen is known to contain large numbers of myeloid cells, as illustrated in the case of Rabbit 19 (Fig. 5), any marked contraction of the organ might be expected to force out neutrophils, even as it does lymphocytes, under adrenalin stimulation in the normal (7). Barcroft's (45) conclusions with reference to the relation of spleen and the reserve of red cells would seem equally apropos for the white cells under the conditions just cited: " I t (the spleen) has a function entirely in conformity with its muscular structure, being in fact a reservoir of corpuscles at once fitted by its reticulum to detain them, and by its musculature to expel them when required to do so."…”

“…In some of the experiments the differential counts of the white cells were made with the supravital technic (6) using vital neutral red. The usual routine was employed in the takhlg of the various consecutive samples (7).…”

Mechanisms of Leukocyte Production and Release

“…A spurting delivery of leukocytes into the circulation of intact animals has been observed by Patt and M a lo n ey (36) using H3-thymidine labeling procedures. Spurting release probably contributed to the irregular fluctuations in white cell counts observed by Sabin et al (44,45), Kjennon et al (26), known to persist in human beings with leukopenia or leukocytosis (11). A plausible explanation for the spurts in leukocyte delivery is that not all areas of the marrow circulatory tree are open simultaneously.…”

The Mammalian Lymphocyte

“…I n children the count may be considerably higher (14-57y0, Joppich & Liessens, 1937). Doan & Zerfas (1927) in a 4-year-old child found the lymphocytes to be 37-3 yo of all marrow cells. Little information is available on absolute counts of nucleated cells in human marrow, but on the basis of counts such as those of Isaacs (1937) or Gordon (1939), 10% of lymphocytes would be equal to ~o,oo~-~oo,ooo cells per cu.mm.…”