The exchange of gases, nutrients, water, and waste material occurs at the capillary level and is governed by the interplay of two opposing but balanced forces. At the proximal end of a capillary, intravascular pressure slightly exceeds tissue pressure. The gradient in hydrostatic pressure results in hydraulic ultrafilration, a process characterized by the movement of fluid through the capillary wall and into the extracellular compartment. Composed of a single layer of endothelial cells, the capillary acts as a selective filter. The degree of selectivity varies with the physical properties of the endothelium in different tissues. Passage of relatively large molecules (e.g., proteins) is largely impeded, although some leakage occurs with subsequent reabsorption into lymphatic vessels and a return to the circulation. As a result of ultrafiltration, the concentration of solute (plasma osmolarity) increases along the length of a capillary, and the associated force (termed oncotic pressure) acts to pull extracellular fluid back into the capillary lumen through a process of reabsorption. This fundamental concept was first described by Ernest Starling in 1896 and is therefore known as the Starling hypothesis, mathematically expressed as follows:
where Qf is fluid movement across the capillary wall, Pc is capillary hydrostatic pressure, p is interstitial fluid oncotic pressure, P i is interstitial fluid hydrostatic pressure, pp is plasma oncotic pressure, and k is a filtration constant for capillary membrane.
A positive Qf value indicates net filtration, whereas a negative value connotes net reabsorption. In general, if filtration exceeds reabsorption, an edematous state develops; conversely, if reabsorption exceeds filtration, plasma volume expands (primarily on the venous side), and cellular/extracellular volume decreases. It should be noted, however, that not every capillary behaves in the idealized fashion predicted by the Starling hypothesis. For example, in the renal glomerulus, hydrostatic pressures are elevated along the entire length of the capillary; hence filtration predominates. In the intestinal mucosa, the elevated oncotic forces result primarily in reabsorption, with little or no filtration.
Transcapillaryexchange is modulated by a series of integrated mechanisms ranging from central neural control of CO and total peripheral resistance (the primary determinants of blood pressure) to local mechanisms within the microcirculation that modulate capillary pressure and regional blood flow. During the last decade, our appreciation of the latter has increased substantially, and it is now clear that metabolic and myogenic factors within the microcirculation play a major role in determining upstream resistance and, hence, pressure within a capillary bed.
The presence of actin and myosin in some endothelial cells, particularly those of postcapillary venules (also a site of fluid exchange), argues for the existence of a cytoskeletal mechanism for governing the geometry of interendothelial pores or clefts.ili The state of the cytoskeleton is, in turn, regulated by physical and chemical signals that impinge on the capillary. A number of molecules, such as histamine, adenosine, and
NO, are able to alter the permeability characteristics of the endothelium and lead to rapid and significant changes in permeability. For example, vascular endothelial growth factor (VEGF) is a peptide that binds to receptors on the endothelium and initiates a series of intracellular signal-transduction events that result in greatly augmented permeability. Recent observations suggest that this pathway involves a receptor tyrosine kinase that is coupled to phospholipase C, an enzyme whose activation leads to the generation of second messengers that modulate both enzymatic and ionic events within the endothelial cell, including activation of protein kinase C, generation of NO, and changes in the endothelial cytoskeleton.i72 Finally, in some organs such as the brain or kidney, transcapillary exchange may be subject to modulation by pericytes, specialized cells that encircle the capillary endothelium and contribute to permeability/barrier functions by mechanisms that are as yet poorly defined. Under normal conditions, it is essential that the vascular resistance upstream of the capillary bed be regulated in such a way so as to maintain capillary pressure at levels at which normal fluid exchange may occur. The remainder of this section therefore is devoted to reviewing the principal mechanisms by which the cells of the arterial and arteriolar wall regulate arterial tone and hence vascular resistance and capillary pressure.
Was this article helpful?