Because PNa is normally kept constant by the vaso-pressin and thirst mechanisms, the extracellular fluid volume is proportional to the total extracellular fluid Na+ content. Thus, in order to maintain a constant ECF volume the total amount of Na+ in the body must be regulated. This regulation revolves around the usual considerations of body mass balance in order to maintain homeostasis of the extracellular fluid. As a fixed cation, Na+ is not produced by metabolism. Therefore, the maintenance of a constant amount of Na+ in the body involves matching its daily output to daily intake primarily by adjustments in its urinary excretion.


On a typical American diet, the average adult human ingests on the order of 8-15 g (0.3-0.5 oz., or 2 to more than 3 cooking teaspoons) of NaCl per day. This represents 150-250 mmol of Na+ per day, which would result in a dramatic expansion of the ECF volume if it were not matched by an equivalent daily output of Na+. For example, if one were to retain just 1 day's intake of Na+ (let's say, 150 mmol), this would obligate the retention of 1 L of water in order to maintain an isotonic extracellular fluid. (A solution of 150 mmol Na+ with accompanying monovalent anions in 1 L of water is approximately isosmotic to plasma.) This extra water comes from increased intake of water in response to thirst and the retention of water by the kidneys. The retention of just 1 day's Na+ and an accompanying 1 L of water would increase the body weight by 1 kg (2.2 lb). The body weight of most individuals is relatively constant as long as their daily caloric intake is relatively constant. Therefore, weight gain or loss over a short period on a constant diet is an important indicator of the status of Na+ balance. Patients with chronic renal failure and patients on dialysis are requested to follow their daily weight as an indicator of the extent to which they are retaining fluid and, thus, how much hemodia-lysis may be required to return them to a state of Na+ balance.

The kidneys are typically the primary route of Na+ output, but there are also losses from the gastrointestinal tract and from the skin. Normally the feces contain little Na+, but gastroenteritis with diarrhea can produce dramatic losses of NaHCO3. Vomiting also results in the loss of an isotonic NaCl solution plus a further Cl" loss as HC1. Sweat is approximately one-half isosmotic, and the usual daily insensible loss of perspiration by the skin is less than 50 mmol/day. However, with exercise or work, or in a hot environment, Na+ losses in the sweat can be considerable.

The body normally has no difficulty matching Na+ output to Na+ input. However, with severe gastrointestinal losses, especially when these are not replaced by adequate salt and water intake, or with excessive sweating, net daily Na+ losses may compromise the maintenance of ECF volume. The normal balance of Na+ input and output is also disturbed when the ability of the kidney to retain Na+ is compromised, for example, with the use of diuretics.

As noted earlier, the plasma Na+ concentration is not a good indicator of a deficit or excess in ECF volume. Therefore, the clinician must rely on other signs of extracellular volume excess or deficit. Extracellular volume contraction is often indicated by a decrease in systemic blood pressure (hypotension). Although this may not be marked when the patient is lying in a hospital bed, it often occurs when the patient stands up. Because of cardiovascular regulatory mechanisms, which operate effectively in a well-hydrated individual, little change is typically seen in blood pressure upon standing. However, when plasma volume is significantly reduced, these reflex mechanisms cannot restore blood pressure upon standing, and both systolic and diastolic blood pressure fall and the pulse rate rises. This sign is referred to as orthostatic hypotension and is generally an indicator of an extracellular volume deficit.

Extracellular volume expansion, when moderate to severe, is usually indicated by the presence of edema. Edema is evidenced as a swelling of the lower extremities in the ambulatory patient, but it may be seen more frequently in the tissues of the back in the bedridden patient, because excess interstitial fluid pools in those parts of the body that are the lowest in relation to the heart. Although localized edema may be observed in several settings not associated with significant volume expansion, generalized edema is evident clinically only if the ECF volume is increased by 2.5-3 L. The presence of generalized edema is often the presenting symptom in patients with chronic renal failure or heart failure due to excessive salt and water retention.

As ECF volume expansion progresses, pulmonary edema may also develop. This is diagnosed by a chest X ray or by hearing fine rales upon auscultation of the lungs. These rales are due to the presence of fluid in the alveoli. Excess ECF volume is also indicated in the heart sounds by the presence of an S3 gallop, which occurs as venous return and venous congestion progressively increase.

The extent of distension of the large veins is also an indicator of ECF volume. With volume expansion, one expects to find an elevated central venous pressure. This rise in central venous pressure can also be inferred without direct measurement by the degree of distension of the neck veins. In the normal patient, as the upper body is raised from the recumbent to the sitting position, it is found that the neck veins (the internal jugular is the best indicator) collapse at a body angle of about 25° to 45° from the horizontal. However, in the severely volume-expanded patient, neck vein distension may occur even in the full upright position.


Chapters 26 and 27 discussed the mechanisms of Na+ reabsorption in the proximal tubule, the loop of Henle,

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