Any condition that increases vascular capacity will also cause the blood volume to increase to fill this extra capacity. An increase in vascular capacity initially reduces mean circulatory filling pressure (see Figure 29-12), which leads to decreased cardiac output and decreased arterial pressure. The fall in pressure causes salt and water retention by the kidneys until the blood volume increases sufficiently to fill the extra capacity. For example, in pregnancy the increased vascular capacity of the uterus, placenta, and other enlarged organs of the woman's body regularly increases the blood volume 15 to 25 per cent. Similarly, in patients who have large varicose veins of the legs, which in rare instances may hold up to an extra liter of blood, the blood volume simply increases to fill the extra vascular capacity. In these cases, salt and water are retained by the kidneys until the total vascular bed is filled enough to raise blood pressure to the level required to balance renal output of fluid with daily intake of fluid.
Conditions That Cause Large Increases in Extracellular Fluid Volume but with Normal Blood Volume
There are several conditions in which extracellular fluid volume becomes markedly increased but blood volume remains normal or even slightly reduced. These conditions are usually initiated by leakage of fluid and protein into the interstitium, which tends to decrease the blood volume. The kidneys' response to these conditions is similar to the response after hemorrhage. That is, the kidneys retain salt and water in an attempt to restore blood volume toward normal. Much of the extra fluid, however, leaks into the interstitium, causing further edema.
Liver Cirrhosis—Decreased Synthesis of Plasma Proteins by the Liver and Sodium Retention by the Kidneys
A similar sequence of events occurs in cirrhosis of the liver as in nephrotic syndrome, except that in liver cirrhosis, the reduction in plasma protein concentration results from destruction of the liver cells, thus reducing the ability of the liver to synthesize enough plasma proteins. Cirrhosis is also associated with large amounts of fibrous tissue in the liver structure, which greatly impedes the flow of portal blood through the liver. This in turn raises capillary pressure throughout the portal vascular bed, which also contributes to the leakage of fluid and proteins into the peritoneal cavity, a condition called ascites. Once fluid and protein are lost from the circulation, the renal responses are similar to those observed in other conditions associated with decreased plasma volume. That is, the kidneys continue to retain salt and water until plasma volume and arterial pressure are restored to normal. In some cases, plasma volume may actually increase above normal because of increased vascular capacity in cirrhosis; the high pressures in the portal circulation can greatly distend veins and therefore increase vascular capacity.
Nephrotic Syndrome—Loss of Plasma Proteins in Urine and Sodium Retention by the Kidneys
The general mechanisms that lead to extracellular edema are reviewed in Chapter 25. One of the most important clinical causes of edema is the so-called nephrotic syndrome. In nephrotic syndrome, the glomerular capillaries leak large amounts of protein into the filtrate and the urine because of an increased permeability of the glomerulus. Thirty to 50 grams of plasma protein can be lost in the urine each day, sometimes causing the plasma protein concentration to fall to less than one-third normal. As a consequence of the decreased plasma protein concentration, the plasma colloid osmotic pressure falls to low levels. This causes the capillaries all over the body to filter large amounts of fluid into the various tissues, which in turn causes edema and decreases the plasma volume.
Renal sodium retention in nephrotic syndrome occurs through multiple mechanisms activated by leakage of protein and fluid from the plasma into the interstitial fluid, including activation of various sodium-retaining systems such as the renin-angiotensin system, aldosterone, and possibly the sympathetic nervous system. The kidneys continue to retain sodium and water until plasma volume is restored nearly to normal. However, because of the large amount of sodium and water retention, the plasma protein concentration becomes further diluted, causing still more fluid to leak
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