Red blood cells: Centerpiece in the evolution of the vertebrate circulatory system

American Zoologist, Apr 1999 by Snyder, Gregory K, Sheafor, Brandon A

Red Blood Cells: Centerpiece in the Evolution of the Vertebrate

Circulatory System1

SYNOPSIS. All vertebrates except cold-water ice fish transport oxygen via hemoglobin packaged in red blood cells (RBCs). Vertebrate RBCs vary in size by thirtyfold. Differences in RBC size have been known for over a century, but the functional significance of RBC size remains unknown. One hypothesis is that large RBCs are a primitive character. Agnathans have larger RBCs than do mammals. However, the largest RBCs are found in urodele amphibians which is inconsistent with the hypothesis that large RBCs are primitive. Another possibility is that small RBCs increase blood oxygen transport capacity. Blood hemoglobin concentration ([Hb]) and mean RBC hemoglobin concentration (MCHC) increase from Agnatha to birds and mammals. However, the changes in [Hb] and MCHC do not parallel changes in RBC size. In addition, RBC size does not affect blood viscosity. Thus, there is no clear link between RBC size and oxygen transport capacity. We hypothesize that RBC size attends changes in capillary diameter. This hypothesis is based on the following observations. First, RBC width averages 25% larger than capillary diameter which insures cell deformation during capillary flow. Functionally, RBC deformation minimizes diffusion limitations to gas exchange. Second, smaller capillaries are associated with increased potential for diffusive gas exchange. However, smaller capillaries result in higher resistances to blood flow which requires higher blood pressures. We propose that the large capillary diameters and large RBCs in urodeles reflect the evolutionary development of a pulmonary vascular supply. The large capillaries reduced systemic vascular resistances enabling a single ventricular heart to supply blood to two vascular circuits, systemic and pulmonary, without developing high pressures on the pulmonary side. The large RBCs preserved diffusive gas exchange efficiency in the large capillaries.

INTRODUCTION

Hemoglobins were the first of the oxygen carriers (Mangum, 1992). They are the most widely distributed of the respiratory pigments and may be found in cells (the tissue hemoglobins) or circulating in one or more fluid compartments. Tissue hemoglobins have a single polypeptide chain with a core structure that appears to be ubiquitous in all but the archebacteria (Wittenberg, 1992). Circulating hemoglobins are derived from tissue hemoglobins and generally have multiple polypeptide chains. Circulating hemoglobins may occur in solution or they may be packaged in red blood cells (Snyder, 1992). Often overlooked is the fact that red blood cells (RBCs) are found in seven phyla and they seem to have appeared very shortly after the first circulating body fluids evolved (Mangum, 1992). Hemoglobin appears to have arisen only once. However, the RBCs that carry the respiratory pigment may have arisen once or multiple times.

With one major exception (Ruud, 1954), all vertebrates have circulating hemoglobins packaged in RBCs. The vertebrate RBCs vary tremendously in size. At one extreme, RBCs of the mouse deer (Order Artiodactyla) are approximately spherical and average 2 (mu)m in diameter (Snyder and Weathers, 1977). At the other extreme, RBCs of the amphibian Amphiuma (Order Caudata) are biconvex oval discs with dimensions around 66 (mu)m by 37 (mu)m diameter and 15 (mu)m at the greatest thickness (Wintrobe, 1933; Chien et al., 1971). The presence of RBCs in the vertebrate circulation was described over 300 years ago by Antonie van Leeuwenhoek (Dobell, 1932; Schierbeek, 1959) and the tremendous range in RBC size was described over 150 years ago (Gulliver, 1870; see also Wintrobe, 1933). Since these early descriptions there has been considerable interest in the structural and functional characteristics of vertebrate RBCs. However, the significance of the variation in RBC size remains enigmatic.

Few studies have attempted to make broad surveys of RBC size in the vertebrates. However, sufficient information is now available to provide a reasonable summary of the trends. In Table 1 we show averages for RBC size and selected blood characteristics by class, and the number of species in each class for which data are available. We feel that this information is important because it should demonstrate major trends in RBC size for the major vertebrate taxa. Obviously, hidden in this approach are variations on the general scheme which often provide important insights into the adaptive significance of any character. We will deal with these more specific variations after looking at the broader aspects of RBC size.

A number of trends are obvious from the data in Table 1. First, the vertebrates that appeared first have larger RBCs than do the birds and mammals. But, by far the largest RBCs are found in the Amphibia. The only other vertebrate with large RBCs is the lungfish. A more subtle, but obvious, change is a reduction in RBC size from Agnatha to Osteichthyes and again from Amphibia to Mammalia (Table 1).