Fluid FIltration In The Microcirculation
The capillary wall (here taken to include the wall of postcapillary venules) is very permeable to water. However, although individual water molecules can move freely between the plasma and the tissue spaces, the net flow of water across the capillary wall is very small. This flow is determined by a balance between two forces or pressures that are exerted across the wall of the capillaries. These are hydrostatic pressure, which tends to drive water out of the capillary, and colloid osmotic pressure, which tends to draw water into capillaries from the surrounding tissue spaces. The sum of these two pressures at each point along the capillary is equal to a net pressure that will be directed either out of or into the capillary, and the net flow of water is proportional to this net pressure. The classic Starling equation describes the relationship between net flow (Jv) and the hydrostatic and osmotic pressures:
JV ∞[ (PC - Pi) - s(πp-πi)]
The hydrostatic force (Pc − Pi) is equal to the difference between the blood pressure inside the capillary (Pc) and the pressure in the interstitium around the capillary (Pi). Pc in blood-perfused capillaries ranges from about 35 mmHg at the arteriolar end of the capillaries to about 15 mmHg in the venules. Pi is slightly subatmospheric in many tissues (−5 to 0 mmHg), due to a suction of fluid from the interstitium by the lymphatic capillaries. The greater pressure inside the capillary tends to drive filtration, the movement of water out into the tissues.
As described in Chapter 20, the capillary wall acts as a semipermeable membrane or barrier to free diffusion, across which electrolytes and small molecules pass with much greater ease than plasma proteins. A substance dissolved on one side of a semipermeable membrane exerts an osmotic pressure that draws water across the membrane from the other side. This osmotic pressure is proportional to the concentration of the substance in solution, and is also a function of its permeability. Substances that can easily permeate a barrier (in this case the capillary wall) exert little osmotic pressure across it, whereas those that permeate less readily exert a larger osmotic pressure. For this reason, the osmotic force across the capillary wall is largely a result of the relatively impermeant plasma proteins, in particular albumin. The osmotic pressure exerted by plasma proteins is referred to as the colloid osmotic or oncotic pressure.
The osmotic force across the capillary wall tends to cause absorption, the movement of water into capillaries. This force has classically been equated with the difference between the colloid osmotic pressure of the plasma (πp) and that of the interstitium (πi), multiplied by the reflection coefficient (σ), a factor that is a measure of how difficult it for the proteins to cross the capillary
wall. Substances that cannot cross the membrane at all have a reflection coefficient of 1, while those that pass freely have a reflection coefficient of zero. σ ranges from 0.8 to 0.95 for most plasma proteins, while (πp − πi) is typically about 13 mmHg.
Given the balance of hydrostatic and osmotic pressures acting on fluid in the microcirculation, capillaries and venules that are perfused with blood will be mainly filtering plasma (Figure 21a), so that normally there is a slight predominance of filtration over absorption in the body as a whole. Therefore, of about 4000 L plasma entering the capillaries daily as the blood recirculates, a net filtration of 8 L occurs. This fluid is returned from the interstitium to the vascular compartment through the lymphatic system.
On the other hand, certain sites such as the kidneys or the intestinal mucosa are specialized for water reabsorption. Here the osmotic pressure term is large, because plasma proteins are continually being washed out of the interstitium, so that net reabsorption occurs.
It is also the case that the balance between filtration and reabsorption is a dynamic one, mainly because the hydrostatic pressure within the capillaries is variable. Arteriolar vasodilatation, which increases intracapillary hydrostatic pressure, increases filtration, while arteriolar vasoconstriction favours absorption. For example, arterioles often demonstrate vasomotion (i.e. random opening and closing). During periods of arteriolar constriction, capillary pressure falls, favouring the absorption of interstitial fluid. This absorption tends to be transient, however, because as fluid is absorbed into the capillaries, local Pi falls and πi increases. These effects progressively diminish absorption.
Assumption of the upright posture increases the transcapillary hydrostatic pressure gradient in the lower extremities, thereby immediately increasing filtration in these regions. However, this effect is partially compensated for by a rapid constriction of the arterioles of the leg, which is mediated by a local sympathetic axon reflex. This reduces blood flow and attenuates the rise in capillary hydrostatic pressure in these areas.
By the same token, fluid tends to accumulate in the tissue spaces of the upper body and face during the night, because assumption of the supine position increases capillary hydrostatic pressures above the heart. This causes morning ‘puffiness’.
Although the principle on which the Starling equation is based is universally accepted, studies in many types of tissue have shown that net filtration is less than would be predicted from measurements of πi. This discrepancy is explained by the Michel Wein baum hypothesis (Figure 21). According to this proposal, the glycocalyx coating the luminal endothelial wall constitutes the semipermeable diffusion barrier described above. Because water crosses the endothelium mainly through the glycocalyx and inter- cellular clefts, it is not the osmotic pressure exerted by the [protein] in the tissue interstitium (πi), but rather the osmotic pressure exerted by the [protein] within the intracellular clefts just beneath the glycocalyx, which should be used to calculate the osmotic force term in the Starling equation. Importantly, this ‘subglycocalyx’ protein concentration (πsg) is lower than that in the bulk interstitium because as water streams out through the clefts, it is funnelled through narrow gaps in the junctional strands that hold the walls of the clefts together, creating a current that opposes the diffusion of interstitial protein into the cleft which also occurs through these gaps. Modifying the Starling equation by replacing πi with πsg increases the size of the osmotic term in the equation (i.e. σ(πp − πsg) is larger than σ(πp − πi) because πsg < πi) meaning that net filtration will be smaller than is predicted by the classic Starling equation.
Pulmonary And Systemic Oedema
The hydrostatic and osmotic pressures in the capillaries of the pulmonary circulation are atypical. Both Pc (∼7 mmHg) and Pi (∼8 mmHg) are low, while πi is high (∼18 mmHg), because these vessels are highly permeable to plasma proteins. The balance of forces slightly favours filtration. In congestive heart failure, the output of both the left and right ventricles is markedly reduced (see Chapter 46). Failure of the left ventricle results in an increase in left ventricular end-diastolic pressure. This pressure backs up into the lungs, causing increased pulmonary venular and capillary pressures. This promotes filtration in these vessels, causing an accumulation of fluid in the lungs (pulmonary oedema), which dramatically worsens the dyspnoea (breathlessness) and inadequate tissue oxygenation characteristic of congestive heart failure. Similarly, failure of the right ventricle increases systemic venous and therefore capillary pressure, leading to systemic oedema, particularly of the lower extremities.
Oedema of the legs is also caused by varicose veins, a condition in which the venous valves are unable to operate properly because the veins become swollen and overstretched. By interfering with the effectiveness of the skeletal muscle pump, the incompetence of the valves leads to increases in venous and capillary hydrostatic pressure, resulting in the rapid development of oedema during standing.