General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)
- Richard H Sterns, MD
Richard H Sterns, MD
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
Disorders of water balance and sodium balance are common, but the pathophysiology is frequently misunderstood. As an example, the plasma sodium concentration is regulated by changes in water intake and excretion, not by changes in sodium balance. As will be described in the following sections, hyponatremia is primarily due to the intake of water that cannot be excreted, hypernatremia is primarily due to the loss of water that has not been replaced, hypovolemia represents the loss of sodium and water, and edema is primarily due to sodium and water retention. Understanding these basic principles is essential for appropriate diagnosis and treatment.
The general principles and disorders of water balance and sodium balance will be reviewed here. The causes and evaluation of hyponatremia, hypernatremia, hypovolemia, and edema are presented separately. (See "Causes of hyponatremia in adults" and "Evaluation of adults with hyponatremia" and "Etiology and evaluation of hypernatremia" and "Etiology, clinical manifestations, and diagnosis of volume depletion in adults" and "Clinical manifestations and diagnosis of edema in adults".)
The following terms are commonly used when discussing disorders of water and sodium balance. Understanding what these terms represent is essential for appropriate diagnosis and treatment.
Total body water — The total body water (TBW) as a percentage of lean body weight varies with age. Approximate normal values are 80 percent in premature infants, 70 to 75 percent in term infants, 65 to 70 percent in toddlers, and 60 percent after puberty (figure 1) . These values vary with the amount of fat since fat has a much lower water content than muscle. Thus, the TBW as a percentage of total body weight is lower in individuals with more fat. As examples, the TBW as a percentage of total body weight is lower in young adult females than in young adult males (50 versus 60 percent) and becomes progressively lower with increasing obesity or with loss of muscle mass.
The TBW has two main compartments: the extracellular fluid and the intracellular fluid, which are separated by the cell membrane. The relative size of the two main compartments varies with age. The extracellular fluid component is increased in infants and young children compared with older patients, which also contributes to the younger patients' greater TBW percentage of lean body weight (figure 1). The cell membranes are freely permeable to water but not electrolytes and therefore help to maintain the different solute composition of the two compartments: sodium salts in the extracellular fluid, with chloride and bicarbonate being the major anions; and potassium salts in the intracellular fluid, with large macromolecular organic phosphates being the main anions.
- FRIIS-HANSEN B. Body water compartments in children: changes during growth and related changes in body composition. Pediatrics 1961; 28:169.
- EDELMAN IS, LEIBMAN J. Anatomy of body water and electrolytes. Am J Med 1959; 27:256.
- Verbalis JG. Disorders of body water homeostasis. Best Pract Res Clin Endocrinol Metab 2003; 17:471.
- Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol 2011; 22:2166.
- Silver SM, Sterns RH, Halperin ML. Brain swelling after dialysis: old urea or new osmoles? Am J Kidney Dis 1996; 28:1.
- Otvos B, Kshettry VR, Benzel EC. The history of urea as a hyperosmolar agent to decrease brain swelling. Neurosurg Focus 2014; 36:E3.
- Sterns RH, Silver SM. Urea for hyponatremia? Kidney Int 2014.
- Nielsen S, DiGiovanni SR, Christensen EI, et al. Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci U S A 1993; 90:11663.
- Sasaki S, Fushimi K, Saito H, et al. Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct. J Clin Invest 1994; 93:1250.
- Hayashi M, Sasaki S, Tsuganezawa H, et al. Expression and distribution of aquaporin of collecting duct are regulated by vasopressin V2 receptor in rat kidney. J Clin Invest 1994; 94:1778.
- Deen PM, Verdijk MA, Knoers NV, et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994; 264:92.
- Deen PM, Croes H, van Aubel RA, et al. Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing. J Clin Invest 1995; 95:2291.
- Harris HW Jr, Strange K, Zeidel ML. Current understanding of the cellular biology and molecular structure of the antidiuretic hormone-stimulated water transport pathway. J Clin Invest 1991; 88:1.
- Yamamoto T, Sasaki S. Aquaporins in the kidney: emerging new aspects. Kidney Int 1998; 54:1041.
- Nielsen S, Kwon TH, Christensen BM, et al. Physiology and pathophysiology of renal aquaporins. J Am Soc Nephrol 1999; 10:647.
- Brown D. Membrane recycling and epithelial cell function. Am J Physiol 1989; 256:F1.
- Strange K, Spring KR. Absence of significant cellular dilution during ADH-stimulated water reabsorption. Science 1987; 235:1068.
- Baylis PH. Osmoregulation and control of vasopressin secretion in healthy humans. Am J Physiol 1987; 253:R671.
- Robertson GL. Physiology of ADH secretion. Kidney Int Suppl 1987; 21:S20.
- LEAF A, MAMBY AR. The normal antidiuretic mechanism in man and dog; its regulation by extracellular fluid tonicity. J Clin Invest 1952; 31:54.
- Zimmerman EA, Ma LY, Nilaver G. Anatomical basis of thirst and vasopressin secretion. Kidney Int Suppl 1987; 21:S14.
- Mann JF, Johnson AK, Ganten D, Ritz E. Thirst and the renin-angiotensin system. Kidney Int Suppl 1987; 21:S27.
- Seckl JR, Williams TD, Lightman SL. Oral hypertonic saline causes transient fall of vasopressin in humans. Am J Physiol 1986; 251:R214.
- Thompson CJ, Burd JM, Baylis PH. Acute suppression of plasma vasopressin and thirst after drinking in hypernatremic humans. Am J Physiol 1987; 252:R1138.
- Appelgren BH, Thrasher TN, Keil LC, Ramsay DJ. Mechanism of drinking-induced inhibition of vasopressin secretion in dehydrated dogs. Am J Physiol 1991; 261:R1226.
- Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev 2010; 90:513.
- Lahiri S, Nishino T, Mokashi A, Mulligan E. Relative responses of aortic body and carotid body chemoreceptors to hypotension. J Appl Physiol Respir Environ Exerc Physiol 1980; 48:781.
- Ghosh N, Haddad H. Atrial natriuretic peptides in heart failure: pathophysiological significance, diagnostic and prognostic value. Can J Physiol Pharmacol 2011; 89:587.
- Johnston CI, Hodsman PG, Kohzuki M, et al. Interaction between atrial natriuretic peptide and the renin angiotensin aldosterone system. Endogenous antagonists. Am J Med 1989; 87:24S.
- Dunn FL, Brennan TJ, Nelson AE, Robertson GL. The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J Clin Invest 1973; 52:3212.
- Bie P, Secher NH, Astrup A, Warberg J. Cardiovascular and endocrine responses to head-up tilt and vasopressin infusion in humans. Am J Physiol 1986; 251:R735.
- Goldsmith SR, Francis GS, Cowley AW, Cohn JN. Response of vasopressin and norepinephrine to lower body negative pressure in humans. Am J Physiol 1982; 243:H970.
- Goldsmith SR. Vasopressin as vasopressor. Am J Med 1987; 82:1213.
- Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 2008; 359:1018.
- Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation 1986; 73:257.
- Hantman D, Rossier B, Zohlman R, Schrier R. Rapid correction of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. An alternative treatment to hypertonic saline. Ann Intern Med 1973; 78:870.
- Sagnella GA, Markandu ND, Buckley MG, et al. Hormonal responses to gradual changes in dietary sodium intake in humans. Am J Physiol 1989; 256:R1171.
- Hall JE, Granger JP, Smith MJ Jr, Premen AJ. Role of renal hemodynamics and arterial pressure in aldosterone "escape". Hypertension 1984; 6:I183.
- Maronde RF, Milgrom M, Vlachakis ND, Chan L. Response of thiazide-induced hypokalemia to amiloride. JAMA 1983; 249:237.
- Rudy DW, Voelker JR, Greene PK, et al. Loop diuretics for chronic renal insufficiency: a continuous infusion is more efficacious than bolus therapy. Ann Intern Med 1991; 115:360.
- Mange K, Matsuura D, Cizman B, et al. Language guiding therapy: the case of dehydration versus volume depletion. Ann Intern Med 1997; 127:848.
- Total body water
- - Extracellular fluid volume
- Effective arterial blood volume
- - Intracellular fluid volume
- Plasma osmolality
- Plasma tonicity
- REGULATION OF WATER AND SODIUM BALANCE
- Regulation of plasma tonicity
- Regulation of effective arterial blood volume
- - Later role of ADH
- Combined regulation of plasma tonicity and effective arterial blood volume
- - Isotonic saline in SIADH
- - Hypertonic saline in SIADH
- THE STEADY STATE
- OVERVIEW OF DISORDERS OF WATER AND SODIUM BALANCE
- Disorders of water balance
- - Determinants of the plasma sodium concentration
- - Hyponatremia
- - Hypernatremia
- Disorders of sodium balance
- - Hypovolemia
- Concurrent changes in plasma sodium concentration
- - Edema
- Effect on plasma sodium concentration