Transcapillary Forces and Microvascular Permeability in Normal Pregnancy

Edema is one of the features of normal pregnancy, affecting up to 80 percent of all pregnant women. Whereas edema formation could result from a disturbance of the Starling forces that govern fluid exchange between vascular and interstitial spaces, the lymphatic drainage, or changes in permeability of the microvascular endothelial barrier itself, the precise mechanisms contributing to edema formation during normal pregnancy remain unexplained. The higher incidence of peripheral and pulmonary edema is suggestive that microvascular permeability is increased in normal pregnancy. Venous occlusion plethysmography studies support this concept, as do disappearance studies using Evan's Blue (a nontoxic dye that is firmly bound to plasma albumin). The edema of pregnancy appears to be due to increases in all extracellular fluid compartments, since the ratio of intravascular to interstitial compartment remains unchanged.

Transcapillary Colloid Osmotic Gradient in Normal Pregnancy

In normal pregnancy, plasma albumin concentration decreases from nonpregnant values to about 10g/L by 30 weeks of gestation, and then decreases more slowly toward term. The reduced plasma albumin concentration (resulting in a fall in plasma oncotic pressure) would be expected to result in a loss of fluid from the intravascular to the interstitial compartment. Such a change would be expected to result in a fall in plasma volume, a rise in interstitial fluid volume and a reduction in the interstitial oncotic pressure. In fact, plasma volume increases during normal pregnancy and interstitial fluid volume remains fairly constant until late pregnancy, when edema usually becomes clinically evident. Examination of transcapillary fluid balance during normal pregnancy has shown evidence of a fall in plasma colloid osmotic pressure from 23.2mmHg during the first trimester to 21.2 mmHg in the third trimester (a gradient of 2 mmHg). In these studies however, the interstitial oncotic pressure has been shown to fall even more (4 to 5 mmHg). The trans-capillary colloid osmotic pressure difference was therefore increased in spite of reduced plasma oncotic pressure. Thus, it would seem that the reduced interstitial oncotic pressure maintains the normal transcapillary oncotic pressure gradient, thus preserving the circulating blood volume and protecting against edema. Although the mechanism(s) for the fall in interstitial oncotic pressure during normal pregnancy remain unexplained, it could be due to upregulation of lymphatic flow stimulated by increased capillary pressure or increased rate of transcapillary fluid flux. Increased lymph flow removes filtered proteins from the interstitium, thereby restoring a normal plasma/interstitial fluid protein concentration gradient.

Plasma oncotic pressure has been shown to fall from 22 mmHg at the onset of labor to a nadir of 16mmHg at 6 hours after delivery. This is irrespective of the mode of delivery or method of analgesia, although it does appear to be exacerbated by use of excessive amounts of intravenous crystalloids during labor and delivery. The value of plasma oncotic pressure at the time of delivery is close to values at which noncardiogenic pulmonary edema occurs, which is 13 to 16 mm Hg.

Hydrostatic Pressure Gradient in Normal Pregnancy

Capillary hydrostatic pressure, calculated from Starling's equation using values of plasma oncotic pressure, interstitial oncotic pressure (wick method), and interstitial fluid hydrostatic pressure (wick-in needle technique), increases by about 30 percent between the first and third trimesters. However, in these studies, no significant difference in interstitial hydrostatic pressure was observed. According to Starling's equation, the combined effects of increased hydrostatic and oncotic pressure gradients would increase net fluid filtration into the interstitial compartment, thereby reducing intravas-cular volume. In fact, plasma volume actually increases during pregnancy, while the interstitial fluid volume remains constant, until late pregnancy when edema is usually observed.

The pulmonary vascular resistance, as well as the systemic vascular resistance, also falls during normal pregnancy. Pulmonary wedge pressure is slightly reduced from nonpregnant values, in spite of an increased cardiac output. Pulsed Doppler pulmonary blood velocities have been used to calculate pulmonary artery pressure. The results indicated that pulmonary pressure falls from 2.8 resistance units before pregnancy to 2.7 resistance units at 8 weeks of gesta tion. It then remains unchanged for the rest of the pregnancy, returning to nonpregnant values by 6 months after delivery.

Given the fact that plasma oncotic pressure at the time of delivery falls close to values at which noncardiogenic pulmonary edema occurs (i.e., 13 to 16mmHg), it is perhaps surprising that the modern management of labor, with liberal use of crystalloid intravenous fluids, does not result in pulmonary edema more frequently.

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Essentials of Human Physiology

Essentials of Human Physiology

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