Journal of IiME Volume 2 Issue 1 www.investinme.org WHO GETS ME AND WHY - The role of impaired capillary blood flow in ME (continued) consider cure, as an endpoint and my objective in treatment is simply to improve the quality of life of sufferers. To a large extent it seems that clinicians take red cells for granted, ignoring the fact that the loss of the nucleus as the cell leaves the bone marrow, renders it incapable of independent existence, and at the mercy of its environment. There are many published reports which record the different ways in which red cells respond to change in their environment, both in vivo and in vitro, with the change in shape associated with reduced deformability. The significance of the reduction in deformability is that the average diameter of capillaries lies between 3.5 and 5 microns, whereas the diameter of a red cell is between 7.5 and 8 microns. Therefore, in order to traverse a capillary bed, red cells must be able to deform and any reduction in red cell deformability will increase the resistance to flow in the microcirculation. A 1970 editorial (5) titled, “The importance of erythrocyte deformability,” concluded that, “ …the remarkable deformability of normal mature erythrocytes appears to depend on at least three factors: (1) maintenance of the biconcave shape which in turn depends on a high ratio of surface area to cell volume; (2) normal internal fluidity of the cell which in turn depends primarily on the properties of normal haemoglobin; and finally (3) intrinsic membrane deformability which is significantly affected by the relationship between intracellular ATP, calcium and magnesium and may be affected by pH and oxygen tension in local regions of the microcirculation.” Therefore it can be expected that any change in the cell environment which alters any of those three factors will lead to a reduction in cell deformability. Although viral infections, which will alter the internal environment, are considered to be key factors in the aetiology of ME, other infections, inoculations, vaccinations, severe emotional upsets, herbicidal sprays and heavy physical activity have been reported as causal factors in ME. All those factors will alter the red cell environment. However, it needs to be emphasised that although everyone exposed to such changes will show shapechanged red cells, only a small proportion will go on to develop the symptoms of ME. So those who are at risk of developing ME have some physiological difference which leads to a reduced ability to restore red cell shapes to normal. of the unknown factor or factors involved may persist for 15 to 20 years or longer. WHO GETS ME? (Continued on page 27) As the problems of poorly deformable red cells in Invest in ME (Charity Nr. 1114035) Page 26/34 The action traversing a capillary bed will be greatest in small capillaries, it is proposed that a key factor in determining who gets ME is the anatomical feature of smaller than usual capillaries. The random distribution of clusters of small capillaries provides a basis for understanding the idiosyncratic nature of the symptoms of ME. This implies that some cases may exhibit only a few regions which become symptomatic, whereas other cases may have symptoms in many regions of the body. While the presence of smaller than usual capillaries may have little functional effects when red cells exhibit normal deformability, their presence will become obvious after exposure to an agent which alters the internal environment and stimulates change in the shape populations of red cells. Furthermore, during remissions, when red cell shape populations return to normal, normal functional status indicates normal rates of capillary blood flow. Because a requirement for normal tissue function is a normal rate of capillary blood flow which delivers sufficient oxygen and nutrient substrates to sustain normal function and to remove metabolic wastes, it is clear that when shape-changed, poorly deformable red cells are in the circulation, capillary blood flow will not be normal. The severity of the consequences of impaired capillary blood flow will be determined by the tissue involved. Muscles, the central nervous system and secreting glands are particularly sensitive to oxygen deprivation which may lead to body wide dysfunction. It is not surprising that in ME most symptoms relate to those tissues. Therefore it is proposed that those people who develop the chronic condition we call ME, share the common anatomical feature of having smaller than usual capillaries, the distribution of which will be marked by the development of symptoms when some agent induces change in red cell shape which makes them poorly deformable. Because many other chronic disorders exhibit changes in the shape populations of red cells, the presence of such cells is not diagnostic for ME. A 1992 paper (6) noted that, “ Subjects with the characteristic (of smaller than usual capillaries) would always be at risk of developing red cell shaperelated impairment of capillary blood flow.” Thus, those who will get ME are the small proportion of the population who by chance have smaller than usual capillaries. The severity of the symptoms which develop in the presence of poorly deformable red cells will reflect the extent to which small capillaries are present in the microcirculation. Limited observations have left me with the impression that black and brownskinned races have a lower incidence of small capillaries.
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