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Regulation of Electrolyte Homeostasis
Regulation of Electrolyte Homeostasis Abdel A. Abdel-Rahman East Carolina University, Greenville, USA Robert G. Carroll East Carolina University, Greenville, USA ã 2007 Elsevier Inc. All rights reserved.
The regulation of electrolyte homeostasis involves balancing the intake of fluid and electrolytes against their loss from the body. While fluid and electrolyte intake is primarily from diet, loss can occur by a variety of mechanisms. Thus, there are hormonally regulated losses of water and electrolytes in the urine (Na+ and K+) and feces (primarily K+), and there is an unregulated loss of water and electrolytes during respiration and through the skin through various mechanisms, including sweating. Clinically, plasma electrolytes are reported as a concentration (amount/volume) that can be affected by the amount of electrolytes, and the volume of water in the plasma. The normal range for serum electrolytes below are: Na+ 136–145 mEq/L; K+ 3.5–5.0 mEq/L; Ca++ 2.4–2.8 mEq/L; Pi (inorganic phosphate) 3.0–4.5 mg/dl; and Mg++ 1.5–2.0 mEq/ L. Na+ Balance: Sodium intake is under a weak behavioral control that is reinforced by the preference for foods with a salty taste, and its conservation is regulated by a variety of redundant endocrine agents. Acute renal Na+ conservation is mediated by angiotensin II, norepinephrine, and aldosterone. Aldosterone also promotes a minor Na+ conservation in the sweat and feces. The acute renal excretion of Na+ is increased by atrial natriuretic peptide, although this mechanism is of minor physiological importance. Chronic regulation of plasma Na+ is more closely associated with the amount of water in the body and is regulated by antidiuretic hormone (ADH). Acute Na+ imbalance can occur after abnormal water intake. Whereas excessive water intake leads to a dilutional hyponatremia, dehydration causes hypernatremia. Sodium retention may result from treatment with peripheral vasodilators (e.g., hydralazine and minoxidil). Disease states often involve chronic disturbances in fluid or electrolyte balance. Among the hypernatremic Na+ disorders are central diabetes insipidus, which is characterized by insufficient ADH, nephrogenic diabetes insipidus, which is associated with a defective ADH receptor (receptor subtype V2), and hyperaldosteronism. Hyponatremic Na+ disorders include SIADH (Syndrome of Inappropriate ADH), which is characterized by excessive ADH secretion, and impaired aldosterone secretion (Addison’s disease). K+ Balance: While potassium is the major intracellular cation, its homeostasis is poorly regulated. However, K+ is a significant component of food, which accounts for the majority of its intake. Ninety percent of K+ excretion occurs in the urine, with 10 percent in feces. Urinary loss is regulated in the short-term by the filtered K+ load and by the action of aldosterone on the distal tubule in the nephron. The filtered K+ load depends on the glomerular filtration rate and the plasma concentration of K+. When the filtrate reaches the end of the thick ascending limb of the loop of Henle, usually 100 percent of the filtered load of K+ has been reabsorbed. This reabsorption, however, is an active transport process, with a transport maximum close to the normal filtered load. Consequently, any increase in filtered load, from an increase in plasma K+, or a marked increase in glomerular filtration rate, results in K+ delivery exceeding the transport maximum, increasing the excretion of this cation. Normally, K+ appearing in the urine results from its secretion in the later tubular segments. This aldosterone sensitive secretion depends on the development of a lumen negative transepithelial electrical gradient, generated by the reabsorption Na+ on the apical surface. Agents that increase the distal tubule delivery of Na+ enhance K+ secretion and, are therefore, termed potassium wasting diuretics. High lumanal H+ concentrations can also disrupt the electrical gradient and, consequently, decrease K+ excretion. 1
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Regulation of Electrolyte Homeostasis
In the body, the majority of K+ is located within cells. Consequently, changes in plasma K most likely reflect a shift between plasma and the intracellular storage pool. Cellular uptake of K+ is stimulated by insulin, by the beta adrenoceptor–mediated action of catecholamines, and by an increase in the concentration of extracellular H+. Chronic plasma K+ disorders occur from aldosterone imbalances, excessive K+ excretion, and inappropriate exchange with cellular storage pools. Hyperkalemia disorders include insufficient aldosterone (Addison’s disease), or excessive cell injury, causing K+ to enter plasma. Hypokalemia disorders include hyperaldosteronism, or depletion of K+ stores from prolonged use of some diuretics. Calcium balance: The Ca++ concentration in plasma reflects the combined effects of diet, excretion, and movement between body storage pools, with over 99% of Ca++ stored in bones. Of the plasma Ca++, 40% is bound to plasma proteins and, therefore, not filtered by the kidney. The remaining 60% is either free or complexed to small anions and filtered at the glomerulus. Renal reabsorption of filtered Ca++ occurs in the proximal tubules (60%) and loop of Henle (30%). Renal excretion of Ca++ is controlled by parathyroid hormone stimulation of Ca++ reabsorption in the loop of Henle and the distal tubule. Calcitonin causes entry of Ca++ into cellular storage pools and serves to acutely buffer plasma Ca++ concentrations. +
Regulation of Electrolyte Homeostasis
Phosphate Balance: Plasma phosphate (2 mEq/L) reflects the combined effects of dietary intake, excretion, and the movement between body storage pools. Nearly 80% of the body load of phosphate is complexed as HPO-4, and 20% as H2PO4. Most of plasma inorganic phosphate (Pi) is filterable at the glomerulus, with reabsorption occuring in the proximal tubules (70%) and collecting duct (20%). The balance between the amount of Pi filtered at the glomerulus (tubular load) and the maximal tubular reabsorption capacity for phosphate (Tmax) determine renal Pi excretion. Because the normal plasma Pi filtered load exceeds Tmax, Pi is normally excreted. A drop in plasma Pi decreases the filtered load, which, in turn, decreases Pi excretion. Parathyroid hormone increases renal Pi excretion by decreasing proximal tubule absorption. Magnesium Balance: Plasma Mg++ (2 mEq/ L) is regulated by a combination of dietary intake, excretion, and movement between tissue storage pools. In the kidney, 60% is ionized (free) and filterable, with an additional 20% complexed to nonprotein anions, and is also filtered. Because approximately 20% of plasma Mg is bound to plasma proteins, it is not filtered by the kidney. Renal reabsorption of filtered Mg++ occurs in the loop of Henle (65%) and the proximal tubules (25%), and is not under hormonal control. While a decrease in plasma Mg++ is rarely a clinical problem, it occurs with malabsorption syndromes, chronic alcoholism, and during prolonged use of loop diuretics.
Other Information – Web Sites http://www.nephron.com/. This site describes the function of the kidney and provides an interactive medium for obtaining information on the physiology and pathophysiology of the kidney. http://www.kidney.ca/index-eng.html. This site provides updated information on research, patient services, and education and contains several links to other sites that deal with the kidney. http://www.kidneydirections.com/us/eng.htm. This site provides a comprehensive set of links to diabetes and hypertension websites, kidney associations, and information to patients and health professionals.
Further Reading Guyton, A. C. and Hall, J.E., Urine formation by the kidneys: I. Glomerular filtration, Renal blood flow, and their control. In A. C. Guyton and J. E. Hall (Eds.), Medical Physiology, Ed. 10, W. B. Saunders, Philadelphia, PA, 2000, pp. 279–312. Carroll, R., Anatomy and physiology review: The elimination systems. In J.M.Black, J. H. Hawks and A. M. Keene (Eds.), Medical-Surgical Nursing, Ed. 6, W. B. Saunders Company,Philadelphia, PA 2001, pp.732–738.
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The regulation of electrolyte homeostasis involves balancing the intake of fluid and electrolytes against their loss from the body. While fluid and electrolyte intake is primarily from diet, loss can occur by a variety of mechanisms. Thus, there are hormonally regulated losses of water and electrolytes in the urine (Na+ and K+) and feces (primarily K+), and there is an unregulated loss of water and electrolytes during respiration and through the skin through various mechanisms, including sweating. Clinically, plasma electrolytes are reported as a concentration (amount/volume) that can be affected by the amount of electrolytes, and the volume of water in the plasma. The normal range for serum electrolytes below are: Na+ 136–145 mEq/L; K+ 3.5–5.0 mEq/L; Ca++ 2.4–2.8 mEq/L; Pi (inorganic phosphate) 3.0–4.5 mg/dl; and Mg++ 1.5–2.0 mEq/ L. Na+ Balance: Sodium intake is under a weak behavioral control that is reinforced by the preference for foods with a salty taste, and its conservation is regulated by a variety of redundant endocrine agents. Acute renal Na+ conservation is mediated by angiotensin II, norepinephrine, and aldosterone. Aldosterone also promotes a minor Na+ conservation in the sweat and feces. The acute renal excretion of Na+ is increased by atrial natriuretic peptide, although this mechanism is of minor physiological importance. Chronic regulation of plasma Na+ is more closely associated with the amount of water in the body and is regulated by antidiuretic hormone (ADH). Acute Na+ imbalance can occur after abnormal water intake. Whereas excessive water intake leads to a dilutional hyponatremia, dehydration causes hypernatremia. Sodium retention may result from treatment with peripheral vasodilators (e.g., hydralazine and minoxidil). Disease states often involve chronic disturbances in fluid or electrolyte balance. Among the hypernatremic Na+ disorders are central diabetes insipidus, which is characterized by insufficient ADH, nephrogenic diabetes insipidus, which is associated with a defective ADH receptor (receptor subtype V2), and hyperaldosteronism. Hyponatremic Na+ disorders include SIADH (Syndrome of Inappropriate ADH), which is characterized by excessive ADH secretion, and impaired aldosterone secretion (Addison’s disease). K+ Balance: While potassium is the major intracellular cation, its homeostasis is poorly regulated. However, K+ is a significant component of food, which accounts for the majority of its intake. Ninety percent of K+ excretion occurs in the urine, with 10 percent in feces. Urinary loss is regulated in the short-term by the filtered K+ load and by the action of aldosterone on the distal tubule in the nephron. The filtered K+ load depends on the glomerular filtration rate and the plasma concentration of K+. When the filtrate reaches the end of the thick ascending limb of the loop of Henle, usually 100 percent of the filtered load of K+ has been reabsorbed. This reabsorption, however, is an active transport process, with a transport maximum close to the normal filtered load. Consequently, any increase in filtered load, from an increase in plasma K+, or a marked increase in glomerular filtration rate, results in K+ delivery exceeding the transport maximum, increasing the excretion of this cation. Normally, K+ appearing in the urine results from its secretion in the later tubular segments. This aldosterone sensitive secretion depends on the development of a lumen negative transepithelial electrical gradient, generated by the reabsorption Na+ on the apical surface. Agents that increase the distal tubule delivery of Na+ enhance K+ secretion and, are therefore, termed potassium wasting diuretics. High lumanal H+ concentrations can also disrupt the electrical gradient and, consequently, decrease K+ excretion. 1
2
Regulation of Electrolyte Homeostasis
In the body, the majority of K+ is located within cells. Consequently, changes in plasma K most likely reflect a shift between plasma and the intracellular storage pool. Cellular uptake of K+ is stimulated by insulin, by the beta adrenoceptor–mediated action of catecholamines, and by an increase in the concentration of extracellular H+. Chronic plasma K+ disorders occur from aldosterone imbalances, excessive K+ excretion, and inappropriate exchange with cellular storage pools. Hyperkalemia disorders include insufficient aldosterone (Addison’s disease), or excessive cell injury, causing K+ to enter plasma. Hypokalemia disorders include hyperaldosteronism, or depletion of K+ stores from prolonged use of some diuretics. Calcium balance: The Ca++ concentration in plasma reflects the combined effects of diet, excretion, and movement between body storage pools, with over 99% of Ca++ stored in bones. Of the plasma Ca++, 40% is bound to plasma proteins and, therefore, not filtered by the kidney. The remaining 60% is either free or complexed to small anions and filtered at the glomerulus. Renal reabsorption of filtered Ca++ occurs in the proximal tubules (60%) and loop of Henle (30%). Renal excretion of Ca++ is controlled by parathyroid hormone stimulation of Ca++ reabsorption in the loop of Henle and the distal tubule. Calcitonin causes entry of Ca++ into cellular storage pools and serves to acutely buffer plasma Ca++ concentrations. +
Regulation of Electrolyte Homeostasis
Phosphate Balance: Plasma phosphate (2 mEq/L) reflects the combined effects of dietary intake, excretion, and the movement between body storage pools. Nearly 80% of the body load of phosphate is complexed as HPO-4, and 20% as H2PO4. Most of plasma inorganic phosphate (Pi) is filterable at the glomerulus, with reabsorption occuring in the proximal tubules (70%) and collecting duct (20%). The balance between the amount of Pi filtered at the glomerulus (tubular load) and the maximal tubular reabsorption capacity for phosphate (Tmax) determine renal Pi excretion. Because the normal plasma Pi filtered load exceeds Tmax, Pi is normally excreted. A drop in plasma Pi decreases the filtered load, which, in turn, decreases Pi excretion. Parathyroid hormone increases renal Pi excretion by decreasing proximal tubule absorption. Magnesium Balance: Plasma Mg++ (2 mEq/ L) is regulated by a combination of dietary intake, excretion, and movement between tissue storage pools. In the kidney, 60% is ionized (free) and filterable, with an additional 20% complexed to nonprotein anions, and is also filtered. Because approximately 20% of plasma Mg is bound to plasma proteins, it is not filtered by the kidney. Renal reabsorption of filtered Mg++ occurs in the loop of Henle (65%) and the proximal tubules (25%), and is not under hormonal control. While a decrease in plasma Mg++ is rarely a clinical problem, it occurs with malabsorption syndromes, chronic alcoholism, and during prolonged use of loop diuretics.
Other Information – Web Sites http://www.nephron.com/. This site describes the function of the kidney and provides an interactive medium for obtaining information on the physiology and pathophysiology of the kidney. http://www.kidney.ca/index-eng.html. This site provides updated information on research, patient services, and education and contains several links to other sites that deal with the kidney. http://www.kidneydirections.com/us/eng.htm. This site provides a comprehensive set of links to diabetes and hypertension websites, kidney associations, and information to patients and health professionals.
Further Reading Guyton, A. C. and Hall, J.E., Urine formation by the kidneys: I. Glomerular filtration, Renal blood flow, and their control. In A. C. Guyton and J. E. Hall (Eds.), Medical Physiology, Ed. 10, W. B. Saunders, Philadelphia, PA, 2000, pp. 279–312. Carroll, R., Anatomy and physiology review: The elimination systems. In J.M.Black, J. H. Hawks and A. M. Keene (Eds.), Medical-Surgical Nursing, Ed. 6, W. B. Saunders Company,Philadelphia, PA 2001, pp.732–738.
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