Physiological functions volume regulation

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The outline of this chapter will follow a "system s approach" to regulation of smooth muscle relaxation and will be divided into sections dealing with ion flux regulation, key protein kinases, and regulation of cyclic nucleotides. For detail on the normal biochemi-cal/physiological function of these systems, the reader is referred to Chapters 9, 11, 12, 16, 20, and 22 in this volume. Where appropriate, differences between vascular, airway, gastrointestinal, and reproductive smooth muscle will be noted. 

A low thyroid function can influence many of the neuro-humoral systems involved in vascular tone and plasma volume regulation. It has long been known that chronic hypothyroid patients show an increase in peripheral arterial resistance. This is principally due to the lack of direct T3-dependent vasorelaxation and to an increase in arterial wall thickness (Cappola and Ladenson, 2003 Rawat and Satyal, 2004), but enhanced sympathetic activity may also contribute significantly to peripheral vasoconstriction, probably as a powerful compensatory mechanism for the decreased cardiac contractility and intravascular volume which follows TH deprivation. The enhanced sympathetic efflux may eventually overcome a downregulation of post-synaptic vasoconstrictor a-adrenoreceptors, which is described in hypothyroid states, at variance with what is observed in normal physiology, where a positive relationship does exist between TH and the number and activities of noradrenergic receptors (Gomberg-Maitland and Frishman, 1998). 

Another major function of the adrenal cortex is the regulation of water and electrolyte metabolism. The principal mineralocorticoid, aldosterone, can increase the rate of sodium reabsorption and potassium excretion severalfold. This will occur physiologically in response to sodium or volume depletion or both. The primary site of... 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

Our treatment of basic principles of water-solute relationships involves a bottom-up approach that begins with a basic physical-chemical analysis of how fundamental water solute interactions have set many of the boundary conditions for the evolution of life. We discuss how the properties of macromolecules and micromolecules alike reflect selection based on such fundamental criteria as the differential solubilities of different organic and inorganic solutes in water, and the effects that these solutes in turn have on water structure these are two closely related issues of vast importance in cellular evolution. With these basic features of water-solute interactions established, we will then be in a position to appreciate more fully why regulation of cellular volume and the composition of the internal milieu demands such precision. We then can move upwards on the reductionist ladder to consider the physiological mechanisms that have evolved to enable cells to defend the appropriate solutions conditions that are fit for the functions of macromolecular systems. This multitiered analysis is intended to help provide answers to three primary questions about the evolution and regulation of the internal milieu ... 

These studies of protein structure, like those of urea and methylamine effects on enzyme kinetic parameters, reveal that physiological mixtures of counteracting solutes achieve essentially the same end result as use of compatible solutes regulating cell volume through adjusting concentrations of compatible solutes or counteracting solutes (at the appropriate ratio of concentrations) conserves critical aspects of protein structure and function as well as cell volume per se. 

A third volume addresses the interrelationships of hormones with factors in the environments of the tissues, the organs and the whole plants, within which the hormones are functioning. When this volume touches upon wide-reaching topics such as photomorphogenesis or plant movements, only those aspects that relate to principles of hormonal regulation are treated. Separate volumes of the Encyclopedia of Plant Physiology, New Series, provide comprehensive treatment of topics such as photomorphogenesis and plant movements. 

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