Extracellular volume: its structure and measurement and the influence of age and disease

Abstract

Summary 1. Extracellular volume is an importantparameter of the body. Extracellular fluid surrounds the tissue cells and has a high chloride and low potassium concentration. Extracellular fluid is comprised of interstitial fluid (36 per cent), connective tissue water (35 per cent), and plasma, bone, and gastrointestinal water (29 per cent). Extracellular volume closely approximates, biochemically and morphologically, under physiologic conditions the volume of the corrected chloride space. The chloride space is defined as the volume of distribution of chloride in the body having a net concentration of chloride equal to that of a plasma ultrafiltrate (120 mEq. per liter). When this chloride space is corrected for chloride outside the extracellular fluid (red blood cell and visceral cell chloride), the resulting volume approximates true extracellular volume. Evidence is presented that 10 to 13 per cent of chloride is intracellular, and 10 per cent is taken as the correction factor. The chloride space can be conveniently measured with stable bromide since the distribution of these anions in the body is almost identical. 2. Data are presented on extracellular volume from the first day of life up through childhood. During the first year of life the volume comprises 47 per cent of total body water and during the second year 41 per cent. Chemical maturity is then reached and this relationship alters less noticeably with further maturation. 3. At various age levels the relation betweenextracellular volume and the volume of glomerular filtration per day is almost linear. The turnover of extracellular fluid through the glomerular membrane is greater in the infant than in the adult (maximum at 18 months). 4. Basal metabolic rate is linearly relatedto the volume in the older child and adult, but in the infant there is less fluid for each basal calorie. Since metabolic functions are accelerated in early life, the reserves of extracellular fluid at this time may be inadequate, particularly if “stress” supervenes and metabolism is raised further. 5. From a consideration of the differentialgrowth equation, evidence is presented that during growth a change in the mathematical relationship between body weight and extracellular volume occurs at about 5 kilograms in weight (6 weeks of age). It was known that the growth equation for total chloride and body weight in the fetus and newborn infant changed to a new equation at about that period. 6. Mention is made of pathologic changes in extracellular volume during early life, including some aspects of adrenal, renal, and gastrointestinal disease. Changes in volume due to malnutrition are discussed, and attention is drawn to fibrocystic disease of the pancreas, where evidence is presented that the volume is reduced in terms of total body water. Muscle data indicate that the sodium and chloride content is decreased in the disease. 7. Change in extracellular volume and sodium concentration in central nervous system disease are reviewed and the suggestion is made that the biochemical lesion seen in patients with tubercular meningitis is related to allergy. A brief note concerning “volume receptors” is included.