Optimal hematocrit: Theory, regulation and implications

American Zoologist, Feb 1997 by Geoffrey F Birchard

SYNOPSIS. Hematocrit is likely to be optimized because of its influences on oxygen transport. However, optimal hematocrit must also change because shear rates and blood vessel radii within circulations change temporally. Blood vessel endothelia regulate shear stress on their walls by changing their radius. Wall shear stress is dependent on shear rate and viscosity. Because there is regulation of vessel radius by the endothelium it is hypothesized that hematocrit may be regulated near optimal by changes in plasma volume. The implication of such regulation is that changes in vascular volume (blood volume) would occur with alterations in red blood cell mass. Data are presented which indicate that regulation of optimal hematocrit normally occurs through changes in plasma volume. The regulation of optimal hematocrit has significant implications for processes that depend on oxygen transport (e.g., exercise) because of the effect of blood volume on cardiac output.

Optimal Hematocrit: Theory, Regulation and Implications1 Two major principles have been applied to the theoretical understanding of physiological systems: (1) maintenance of steady states, and (2) the principle of minimum work (Murray, 1926; LaBarbera, 1990). The study of oxygen transport is among the oldest quantitative fields in physiology and thus optimization models (models which incorporate principles one and two above) have been applied many times to this system (Murray, 1926; LaBarbera, 1990). The steady state maintained by the oxygen transport system is the partial pressure of oxygen at the mitochondria for aerobic production of ATP. The work involved (energy used by the system), which theoretically should be minimized within the limits of maintaining the steady state, includes cardiac muscle contraction (for pressure generation) and the construction and maintenance of the vasculature and blood.

The Poiseuille-Hagen equation is a fundamental component of most models examining optimization in the cardiovascular system (Murray, 1926; Crowell and Smith, 1967; LaBarbera, 1990): oxygen transport and hematocrit being parabolic in shape (Murray et al., 1963; Erslev, 1966; Crowell and Smith, 1967; Snyder, 1971; Usami, 1982). Oxygen transport is maximized at some particular hematocrit and at lower and higher hematocrits oxygen transport decreases due to reduced oxygen carrying capacity and increased viscosity, respectively. Crowell et al. (1959) coined the term "optimal hematocrit" for the maximum for this function; the theoretical relationship between hematocrit and oxygen transport was subsequently derived mathematically (Crowell and Smith, 1967). The analysis by Crowell and Smith (1967) continues to be the basis of hypotheses on this subject (Wells and Baldwin, 1990; Withers et al., 1991; Gallaugher et al., 1995).

Many analyses of optimal hematocrit have been based solely on measurements of viscosity, hemoglobin concentration, and/or hematocrit (e.g., Erslev, 1966; Wells and Baldwin, 1990). Optimal hematocrit occurs at the maximum in the relationship between oxygen flow (oxygen carrying capacity/ viscosity) or (hematocrit/viscosity) and hematocrit (Fig. 1). This type of analysis generally assumes or ignores three factors: (1) shear rate within the circulations are equal (interspecific comparisons) or do not change with treatment (intraspecific comparisons); (2) the geometry of the circulation, which affects vascular resistance is the same in different species or is unchanged by treatment; and (3) the optimal hematocrit is equal throughout the circulation. This review examines some of these assumptions in light of existing data and our current understanding of vascular regulation. A revised view of optimal hematocrit as a "regulated variable" is proposed and some of the implications for exercise physiology are briefly discussed.

Blood viscosity decreases exponentially with increasing shear rate. Shear rate within circulations depends primarily on flow rate. Therefore, a single oxygen transport-hematocrit curve (optimal hematocrit) cannot exist for a circulatory system because flow (cardiac output) does not remain constant within circulatory systems. A family of oxygen transport-hematocrit curves exists where optimal hematocrit increases with increasing shear rate (Fig. 1). This relationship between optimal hematocrit and shear rate is significant because cardiac output increases with increasing metabolic rate. Thus, it is consistent with the theory of optimal function theory that hematocrit increases with elevations of temperature in ectotherms or during exercise in all animals (e.g., Persson, 1967; Snyder, 1971; Frangioni and Borgioli, 1994; Gallaugher et al., 1995). Under these circumstances a rise in the shear rate likely compensates for any increase in viscosity due to hematocrit. In fact, the infusion of additional red blood cells by splenic contraction during exercise can be regarded as a strategy to increase oxygen carrying capacity and perhaps increase hematocrit towards a new optimal hematocrit. With regard to exercise it should be noted that at high shear rates blood viscosity is minimally affected by hematocrit (Schmid-Schonbein, 1996). Because blood viscosity is not highly dependent on hematocrit at high cardiac outputs it may not be possible to define an optimal hematocrit at high work rates (e.g., Gallaugher et al., 1995).