Microvascular Hematocrit

It is evident that microvascular hematocrit may be the dominant determinant of apparent viscosity in microvessels. Because of the particulate nature of blood, three hematocrits

Shear Rate Tube

Figure 1 Apparent viscosity (h) versus shear rate (g) at various levels of hematocrit was obtained in a large scale cone-plate viscometer. The cross-hatching delineates the typical range in microvessel hematocrit, h, and g found in the microcirculation in the normal flow state. Redrawn from a study of cat blood by Lipowsky et al. (1980). Microvasc. Res. 19, 297-319.

Figure 1 Apparent viscosity (h) versus shear rate (g) at various levels of hematocrit was obtained in a large scale cone-plate viscometer. The cross-hatching delineates the typical range in microvessel hematocrit, h, and g found in the microcirculation in the normal flow state. Redrawn from a study of cat blood by Lipowsky et al. (1980). Microvasc. Res. 19, 297-319.

must be considered when describing blood flow in smallbore tubes or microvessels: (1) the feed hematocrit (^FEED), (2) the discharge hematocrit (^DiSCh), and (3) the tube or microvessel hematocrit (^TUBE or ^MICRO). The feed hematocrit represents the packed cell fraction contained in the suspension that supplies the small blood vessels and is equivalent to the red cell fraction present in large vessels of the macrocirculation, typically larger than 100 mm in diameter. The discharge hematocrit is the volume fraction of red cells found in a hypothetical collection container that receives flow from the exit of a microvessel or small tube. In the absence of any cell screening events at the tube entrance, HFEED = Hdisch. The tube or microvessel hematocrit is defined as the packed cell fraction resident within the lumen of the tube at any instant of time and is determined by suddenly stopping the flow and assaying the packed cell fraction of RBCs within the tube. Given that RBCs flow through a tube with an average velocity of FRBC, it has been shown that VRBCHTUBE = VMEAN^ISCยป where VMEAN is ^

mean velocity of blood (cells plus plasma) calculated by dividing the volumetric flow rate (Q) by the cross-sectional area (A) of the tube, that is, VMEAN = Q/A. These relationships lead to a hypothetical minimum value for HMICRO if it is assumed that Poiseuille's law governs the flow of blood. That is, for Poiseuille flow with a parabolic velocity profile within the tube, VMEAN is 1/2 the maximum velocity that occurs along the tube center line, VCL. Hence, if all RBCs were infinitesimally small and traveled along the vessel centerline, the lowest value of HMICRO attainable would be 1/2 that of Hdisch. In contrast, the theoretical maximum value

Rat Microvessel Endothelial Cells

Figure 2 Representative distribution of microvessel hematocrit (HMICRO), normalized with respect to systemic values (HSYS), measured in the cremaster muscle of the rat for microvessels ranging from arterioles to venules of the indicated luminal diameter. HMICRO falls below HSYS because of the Fahraeus effect and plasma skimming at arteriolar branches. From the data of House and Lipowsky (1987). Am. J. Physiol. 252, H211-H222.

Figure 2 Representative distribution of microvessel hematocrit (HMICRO), normalized with respect to systemic values (HSYS), measured in the cremaster muscle of the rat for microvessels ranging from arterioles to venules of the indicated luminal diameter. HMICRO falls below HSYS because of the Fahraeus effect and plasma skimming at arteriolar branches. From the data of House and Lipowsky (1987). Am. J. Physiol. 252, H211-H222.

particle, the maximum volume fraction would be about 53 percent, whereas for a rigid RBC it would be about 64 percent.

Within the microvasculature, HMICRO has been shown to span a much broader range of values under normal and pathological conditions. Direct measurements of HMICRO reveal that as microvessel diameter falls throughout successive divisions, Hmicro falls to on the order of 25 percent of systemic values (HSYS) as blood approaches microvessels comparable in diameter to the characteristic size of an RBC. The average capillary hematocrit has been found to vary among tissues as a result of different topographical patterns of blood vessels and luminal diameters within a given microvascular division, as illustrated in Figure 2 for the cremaster muscle (rat). Two processes give rise to this fall: the Fahraeus effect and plasma skimming.

Since the pioneering studies of Robin Fahraeus (1929; see Ref. [2]) it has been recognized that hematocrit in tubes comparable in size to that of the red cell may be reduced dramatically below the feed hematocrit that supplies a tissue. This behavior has been attributed to rapid changes in the mean velocity of red cells relative to that of plasma, as summarized by Cokelet [3]. As tube diameter is diminished toward the size of a red cell, the velocity of red cells increases relative to the mean velocity of plasma. Hence, to maintain conservation of red cell flux, the tube hematocrit falls and fewer red cells travel through the tube at a faster than normal speed (relative to plasma) to maintain the same red cell volumetric flow. With further reductions in tube diameter to the point where red cells must undergo large deformation to gain entry to the tube, the Fahraeus effect reverses, as evidenced by increasing HTUBE with diminishing diameter as the motion of RBCs becomes hindered and their sequestration in the tube leads to increases in HMICRO

of Hmicro that could be attained within a tube is governed above HS

by packing considerations for rigid particles of volume equivalent volume to that of red cells. For a rigid spherical

Direct measurements of HMICRO by cell counting or spectrophotometry within single microvessels have revealed a heterogeneous distribution of HMICRO within any given division of the network [4] indicative of hematocrit reductions due to other effects. The principal mechanism leading to further reductions in HMICRO is that of skimming off of plasma by daughter branches at bifurcation points within the network, as first observed by Poiseuille [5]. It has been suggested that HMICRO is relatively uniform across the lumen (radial direction) of an arteriole or venule, compared with the heterogeneity associated with successive branchings. However, the presence of a thin annulus of plasma surrounding the core of RBCs within a microvessel facilitates an uneven distribution of RBCs at arteriolar branchings [3]. The proportions of RBCs from the core, and the cell-free plasma layer that is captured by an arteriolar branch at a bifurcation, is dependent upon the relative magnitudes of total volumetric flow from parent to daughter branch at a bifurcation. At the final ramifications of the arteriolar network, red cell entry into capillaries is dependent upon the presence of a sufficient pressure gradient that can sustain red cell deformations at the capillary entrance and hence the capillary branch with the fastest stream (greatest pressure gradient) captures the majority of red cells. In concert with the Fahraeus effect, plasma skimming contributes to the markedly lower than systemic hematocrits in the capillary network.

Other mechanisms of hematocrit reduction have been implicated as a source of the low capillary hematocrit. It has been suggested that irregularities in the capillary lumen, due to departures from a circular cross-section, introduce substantial errors in computing HCAP that may result in systematically low values. Uncertainties in observing the luminal surface of the capillary endothelium may also introduce significant errors in estimating HCAP. The presence of a thick (~ 0.5 mm) surface layer of carbohydrates and proteins on the surface of the endothelium (the glycocalyx) may also affect estimation of HCAP. Removal of the endothelial surface layer by enzymatic degradation of the glycocalyx (see review by Pries et al. [6]) has resulted in a substantial rise in capillary hematocrit.

The observed low capillary hematocrits have raised critical questions on the role of hematocrit in oxygen transport to tissue. It is generally accepted that the potential for oxygen transport from blood to tissue is related to the concentration of RBCs within the microvasculature. However, the low levels of microvessel hematocrit are inconsistent with the fact that for a given level of oxyhemoglobin, oxygen content is proportional to the product of mean corpuscular hemoglobin concentration and HMICRO. Attempts to account for all of the factors contributing to reduced hematocrit (Fahraeus effect, plasma skimming, uncertainties in capillary diameter, and so on) have not resolved the disparity between HSYS and HCAP. This situation may have persisted because hematocrit measurements do not consider the flow-weighted flux of red cells within individual microvessels. In contrast, the flow-weighted estimates of red cell fraction obtained using techniques of indicator dilution (with fluo-rescently labeled RBCs and plasma) have revealed average tissue hematocrits approaching systemic values, which are substantially greater. Nonetheless, the importance of HMICRO rests in that it remains a major determinant of the apparent viscosity of blood in microvessels, and hence of resistance to blood flow.

In addition to the dynamic processes that affect RBC apportionment at branch points, RBC mechanical properties may dramatically affect capillary hematocrit. Pathologically stiff red cells (e.g., in sickle cell disease, the thalassemias, or hereditary spherocytosis) may affect the distribution of cells. Because of cell-cell interactions, less deformable RBCs have a tendency to become trapped within networks with nontube-like vessels, such as the lung, spleen, liver, or bone marrow. The permeability characteristics of the microvessel wall may also affect hematocrit. In the classical study of disruption of the permeability of the small blood vessels leading to complete vascular stasis, as first described by August Krogh [1], the hyperpermeable vessel wall may allow compaction of RBCs to hematocrits approaching 100 percent.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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