Interaction of Load, Capacity, and Resistance in Body Processes

INTERACTION OF LOAD, CAPACITY, AND RESISTANCE IN BODY PROCESSES JOHN H. FRENSTER, H.D.* Adaptation is the result of a steady interaction between an animal and its external environment, in which those individuals or populations undergoing changes which best fit them to their immediate environment display greater survival than those undergoing less useful changes (i). Genetic mutation may induce hereditary changes within a population which are irreversible and which are random in their occurrence; the external environment may induce physiologic changes within an individual which are reversible, and which seem usefully specific in their occurrence (I'2)· It is nowevident that the subunits ofan individual organism—its organs, its cells, its sub-cellular particles, and its enzymes—are similarly engaged in a constant interaction with their immediate micro-environments within the organism (3-6). As a result of such interaction, these organs, cells, particles, and enzymes undergo changes in response to their microenvironments , and in turn produce changes in those environments. One ofthe most interesting ofsuch interactions is the ready adjustment ofthe work capacity ofa body process to the work demands presented to that process (7). The mechanisms mediating such ready responsiveness are of interest because ofwhat they reveal about normal useful growth and its control in the organism. To study such mechanisms, it is useful to analyze the individual body process under scrutiny into its components. Any single body process, whether ofthe organ, cell, particle, or enzyme level, can be viewed as the functional interaction of an imposed load presented to the process for action, the available capacity ofthe process to accomplish its action, and * The Rockefeller Institute, New York 21, N.Y. I52 fohn H. Frenster · Load, Capacity, and Resistance Perspectives in Biology and Medicine · Winter 1961 the resistances opposing completion oftheaction (8). Such ananalysis permits quantitation of each of the components determining the action of the process. I.Loads The nature ofthe imposed load presented to a body process is as diverse as the nature or the level of the process examined. For example, at the organ level, the load imposed upon the heart is the quantity ofblood presented to the heart for propulsion (8). The load imposed upon the liver includesthe quantity ofbilirubinpresentedtotheliverfor biliaryexcretion (9). At the cellular level, the load imposed upon each body cell includes the quantity of glucose presented to the cell membrane for transport into the interior ofthe cell (10). The load imposed upon a renal tubular cell includes the quantity of glucose presented to the lumen surface of the cell for renal reabsorption (11). At the sub-cellular particle level, the load imposed upon a mitochondrion includes the quantity of phosphorylated carbohydrate presented to the mitochondrial membrane for further oxidative phosphorylation (12). The load imposed upon a cell nucleus includes the quantity of amino acids presented to the nuclear membrane for transport into the interior of the cell nucleus (13). At the enzyme level, the imposed load is the quantity of specific substrate presented to each enzyme molecule for its action (14). In biosynthetic processes which are forming new molecules, new particles , or new cells, thermodynamic and specific stimuli are presented to the process which tend to promote the new synthesis (15). The load imposed upon such biosynthetic processes is equal to the magnitude and intensity of such thermodynamic and specific stimuli imposed upon the process. II.Resistances The natures of resistances opposing the successful action of a body process are also diverse. Biophysical resistances include such factors as inertial resistance to propulsion, frictional and pressure resistances to air and liquid flow, gravitational resistance to elevation, elastic resistance to deformation, and viscous resistance to shearing (16). The most common typeofbiochemicalresistance isthethermodynamicrequirement for some 153 minimal activation of the chemical reactants in a process before thenenergy level permits the reaction to proceed (14). Other biochemical resistances include the resistance offered to a reaction by the wide distribution of its reactants at some distance from the active site of the reaction. Their dispersion is often overcome by active trapping (17), pumping (18), or concentrating (19) mechanisms, as displayed by the thyroid in concentrating iodide ion for further thyroxin synthesis (17). In addition, enzyme reactions are resisted by the requirement for some minimum time...