Oxygen transport in the microcirculation and its regulation

Abstract

Objective: Cells require energy to carry out their functions and they typically use oxidative phosphorylation to generate the needed ATP. Thus, cells have a continuous need for oxygen, which they receive by diffusion from the blood through the interstitial fluid. The circulatory system pumps oxygen-rich blood through a network of increasingly minute vessels, the microcirculation. The structure of the microcirculation is such that all cells have at least one nearby capillary for diffusive exchange of oxygen and red blood cells release the oxygen bound to hemoglobin as they traverse capillaries.

Methods: This review focuses first on the historical development of techniques to measure oxygen at various sites in the microcirculation, including the blood, interstitium, and cells.

Results: Next, approaches are described as to how these techniques have been employed to make discoveries about different aspects of oxygen transport. Finally, ways in which oxygen might participate in the regulation of blood flow toward matching oxygen supply to oxygen demand is discussed.

Conclusions: Overall, the transport of oxygen to the cells of the body is one of the most critical functions of the cardiovascular system and it is in the microcirculation where the final local determinants of oxygen supply, oxygen demand, and their regulation are decided.

Figure 1

Schematic diagram of an unbranched segment (length = L) of a microvessel for which the convective inflow and outflow of oxygen (QO₂^conv) are computed from the variables diameter (d = 2R_i), velocity (v), hemoglobin concentration ([Hb]) and oxygen saturation (SO₂) according to Eq. 7. Their difference is equal to the rate of oxygen diffusion (QO₂^diff) from the segment across the wall of thickness w = R_o − R_i, according to Eq. 8. The oxygen consumption of the wall can be computed from the mass-specific consumption, M, and the volume of the wall. This figure originally appeared in Pittman (124).

Figure 2

Compilation of oxygen consumption data for various vascular tissues: endothelial cells, smooth muscle cells (SMC), isolated segments of vessels, large in vivo vessels, and in vivo microvessels (from oxygen flux values computed from measurements similar to those associated with Eqs. 7 and 8). The horizontal line labeled M_mt represents the maximum oxygen consumption expected for these tissues based on their mitochondrial content. The value represented by the open square labeled 1 comes from Tsai et al (168) and the hatched bar on the right side of the plot represents data from numerous studies and reveals the widespread finding of an order of magnitude discrepancy between measured and predicted oxygen flux from microvessels. This figure originally appeared in Vadapalli et al (180). See original article for more details.

Figure 3

Demonstration of erythrocyte-associated transients (EATs) in PO₂ at upstream (upper trace) and downstream (lower trace) sites in the same capillary using the scanning PQM approach. The excitation spot switched back and forth between the two sites at a frequency of 100 Hz for 1 sec. There was a systematic difference between PO₂ values at the two sites, indicating a longitudinal gradient in PO₂ along the capillary. Note also that the magnitude of the fluctuations was larger at the downstream site, as expected for a relatively uniform efflux of oxygen along the capillary and lower oxygen content at the downstream site. This figure originally appeared in Pittman (125).

Figure 4

Typical plot of the oxygen dependence of respiration for the in situ resting rat spinotrapezius muscle. These data points were obtained using Eq. 6 (with corrections as described in ref 55) to compute oxygen consumption and the PO₂ values are corresponding interstitial values on the surface of the fibers at the measurement site. The data were partitioned between hypoxic and normoxic regions in the muscle and the resulting curve fits are shown as solid lines. For this muscle K_m was 9.4 mmHg and the PO₂ difference within the muscle was about 3 mmHg. This figure originally appeared in Golub and Pittman (58). See original article for more details.

Figure 5

Schematic diagram of the terminal microvasculature (arterioles, capillaries and venules) depicting the movement of oxygen by convection (arrows within vessels) and diffusion (arrows between vessels). The concept from Krogh’s writings was that diffusive oxygen exchange occurred between neighboring capillaries, but other vessels were not involved in oxygen diffusion. The current view is that the highly diffusible oxygen can move by diffusion between any vessels in close proximity, so long as a PO₂ gradient exists between them. Such diffusive exchange is represented in this diagram. The PO₂ values in any region are the result of the interactions of local diffusion and consumption as found in numerous computational modeling studies. This figure originally appeared in Ellsworth et al (40).