Capillary Endothelium and Data Processing: A Hypothesis

CAPILLARY ENDOTHELIUM AND DATA PROCESSING: A HYPOTHESIS RICHARD J. KONES, M.D.* The stability and security of biological systems is assured in large part by self-regulation mediated by feedback control. This critical unifying principle in biology is operational from the molecular level to population dynamics and may be applied to most systems in man. Such servomechanisms can be regarded as information flow sheets and in fact may be analyzed mathematically with techniques developed in communications theory. A generalized schema for a servomechanism with a simple negative feedback loop is presented in figure 1 [1-6]. The output signal is monitored by a sensing device which feeds a modified signal back to an input detector element. Subtraction of the feedback signal from the command signal results in an actuating error, from which corrective steps ensue to minimize variation in the controlled (output) variable . Hence, negative feedback decreases uncertainty in the output and stabilizes the overall stimulus-response curve of the system. As an illustration, no more direct example may be cited of biological feedback stabilization than the simple reflex arc and gamma-fiber system. The constraint of anatomy must be accounted for when constructing servomechanisms representing biological phenomena—pathways must physically exist to carry impulse traffic in postulated loops. Conversely , when recognized pathways exist, it is distinctly unusual for them to serve no useful purpose. An attempt may be made to correlate possible malfunctions in servomechanisms representing biological systems with known pathology. Thus, an aberration of the sensor, improper function of the transducer, delay or saturation of the amplifier , and difficulty in integrating the feedback signal with the command signal are potential sources of servomechanism failure. When * Cardiology Section, Department of Medicine, New York Medical College, New York, New York 10029. Address for reprints: 250 E. 87 Street, New York, New York 10028. 288 I Richard J. Kones · Capillary Endothelium afferent channel efferent chorrel memory bridges MEMORY BANK Fig. 1.—A single-loop servomechanism, activated by a perturbating agent (X), with a memory bank. a hierarchy of channels exist, as is common, confusion among signals and dyssynergy of outputs may result [7]. For instance, a delay in insulin release in high-output (maturity onset) diabetes may be construed as a transducer abnormality [8]. Faulty response of the adenyl cyclase system may result in inadequate discrimination or amplification of a stimulus [9]. Further examples of interpretation of pathological events in terms of servomechanism element failure in biological systems are numerous but beyond the scope of this paper. The capillary has been regarded as a relatively passive structure (e.g., as in the lung): a diffusion barrier responding to pressure differences and electrochemical gradients [10]. Yet the anatomical location of capillaries, their differentiation in various organs, and their unique topology in relation to the parenchyma they serve define a potential role as a data sensor. In some organs, specialized vascular network anatomy contributes to regulation by virtue of the architectural constraint alone. Thus, the countercurrent apparatus of the kidney provides osmotic conservation, vascular networks of the bone marrow regulate ratios of various cell types [11], cutaneous arteriovenous anastomoses [12] create countercurrent thermal flow [13], and hepatic sinusoidal arrangement obviously permits liver function. Evidence , however, is accumulating to imply a more active role of capillaries quite apart from these resulting from the effects of organ morphology mentioned above. Hence the postulate of capillary endothelial function as a sensor in control of small lymphocyte proliferation [14], and of receptors governing endothelial function in considering a molecular model of the lung [15]. Specially differentiated cells may exist in the glomerular capillaries to liberate an erythropoietin -inducing substance, if not erythropoietin itself or a precursor. Such an intimate location would serve ideally to biologically monitor oxygen saturation. Last, an endothelial contribution to lipid metaboPerspectives in Biology and Medicine · Winter 1973 | 289 lism and blood coagulation have also been suspected by hématologiste . As a corollary of the fundamental position of capillary endothelium , specific aberration in disease would be expected to have significant and varied effects. In viremia, for example, in which information transfer and energy production are widely disrupted, the role of endothelium in pathogenesis is unclear. Similarly for systemic lupus erythematosus and diabetes mellitus, in...