correlate well with the dietary history of salt intake in these individuals. The sodium chloride intake of the malnourished subject is extremely variable, and when easily available, salt is taken in large quantities. Sodium balance studies performed in four nonedematous malnourished patients before and after protein repletion [36] demonstrated that on a 10 mEq salt diet, these subjects were able to decrease their urinary sodium excretion to 10 mEq or less in 24 hours. By contrast, when receiving a diet containing 170 mEq of sodium chloride, these same four patients in the malnourished state demonstrated a mean positive sodium balance of 400 mEq and weight gain of 2800 g after five days. After protein repletion the U/P Inulin I I 800 1000 Chronic protein-calorie malnutrition 133 same patients on an identical diet demonstrated a mean positive sodium balance of 150 mEq and a weight gain of 1 200 g. The results of these balance studies indicate that subjects with protein malnutrition have an impaired ability to handle sodium loads when malnourished as compared to their capacity to handle the same loads after protein repletion. We have also studied the effects of acute expansion of the extracellular fluid volume with hypotonic saline in three subjects with chronic protein malnutrition before and after protein repletion. These data are summarized in Table 2. During the malnourished state, the rapid intravenous administration of saline resulted in an almost negligible increase in fractional sodium excretion. When the same studies were repeated after protein repletion, a marked increase in fractional sodium excretion was observed. We have also demonstrated that of the saline infused during the determination of inulin or PAH clearances, a smaller percentage was excreted in malnourished than in recovered children: in the former group, approximately 20% was excreted, there being no difference between edematous and nonedematous cases; this increased to nearly 50% in repleted children [37]. In three children with malnutrition and clinical dehydration, Gordillo et al [8] infused hypertonic saline. In only one of the children did glomerular filtration rate and effective renal plasma flow increase during the administration of hypertonic saline. Sodiumdiuresis did not ensue in any of the patients. A calculation of sodium balance of these three children showed that virtually all the infused sodium, and a large part of the infused water, was retained; the fact that extracellular fluid osmolality did not rise to the extent expected indicates that water moved from the intracellular compartment to the extracellular compartment and that the latter compartment presumably was expanded. Despite this, glomerular function was not restored towards normal. The possible mechanisms responsible for the inability to handle sodium loads and the occurrence of sodium retention and edema during protein-calorie malnutrition are depicted in Fig. 2. As a consequence of a markedly decreased protein intake, there is a progressive fall in plasma albumin leading to the development of hypoalbuminemia. It is known that cardiac output is decreased in patients with chronic protein malnutrition [20]. This in turn may Table 2. Effects of ECE volume expansion on sodium excretion in three malnourished patients before and after protein repletion Patient V mi/mm C1 mt/mm Na mEq/ liter UNaV pEq/min FLNa pEq/min UNaV/FL Before repletion Control 0 Before repletion Control 41.1 26.3 5034 0.50 Expansion 45.3 46.1 5296 0.82 Mean After repletion Control 77.0 112.8 9686 1.23 Expansion 86.6 1169.3 10603 11.07 V, urine flow; C1, inulin clearance; DNa' plasma sodium; UNaV, sodium excretion; FLNa, filtered load of sodium; UNaV/FL, fractional sodium excretion. 134 Klahr/Alleyne Decreased Protein Intake Hypoalbuminemia Decreased Plasma Volume? Decreased Cardiac Output Decreased /NArterial Decreased RBF Blood Pressure and GFR Decreased / Peritubular Increased Renin / Hydrostatic Pressure Angiotensin / \ Increased Decreased Filtered Aldosterone Load of Salt and Water Increased Tubular/ Fig. 2. Possible mechanisms responsible for the development of edema in malnourished subjects. be the result of decreased plasma volume, but other factors presumably play a role [38]. Most studies suggest that both renal blood flow and GFR are decreased in chronic protein malnutrition. This is presumably the consequence of a decrease in absolute plasma volume and decreased cardiac output. A fall in GFR will markedly decrease the filtered load of salt and water. At the same time, other stimuli acting at the tubular level will tend to increase sodium reabsorption. These stimuli include: 1) elevated levels of aldosterone, presumably the result of decreased plasma volume and increased