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A comprehensive review on water balance
Biomedicine & Preventive Nutrition 3 (2013) 193–195
Available online at
www.sciencedirect.com
Review
A comprehensive review on water balance Muhammad Akram a,∗ , Abdul Hamid b a b
Department of Eastern Medicine and Surgery, Faculty of Medical and Health Sciences, The University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan Department of Horticulture, Faculty of Agriculture, The University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan
a r t i c l e
i n f o
Article history: Received 28 September 2012 Accepted 23 October 2012 Keywords: Water balance Regulation of water ICF ECF
a b s t r a c t Water is more important than any other single compound to life. It is involved in several body functions. Water acts as a vehicle for transport of solutes. Water is the major body constituent. An adult human contains about 60% water (men 55–70%, women 45–60%). A 70 kg man contains 42 L of water. This is distributed in intracellular (inside the cells 28 L) and extracellular (outside the cells 14 L) compartments, respectively known as intracellular fluid and extracellular fluid. The body has tremendous capacity to regulate its water content. In a healthy individual, this is achieved by balancing the daily water intake and water output. © 2012 Elsevier Masson SAS. All rights reserved.
1. Introduction Water intake is normally by mouth and absorption is from all parts of gastrointestinal tract. Water is the solvent of life. Undoubtedly, water is more important than any other single compound to life. It is involved in several body functions. Water provides the aqueous medium to the organism which is essential for the various biochemical reactions to occur. Water directly participates as a reactant in several metabolic reactions. It acts as a vehicle for transport of solutes. Water is closely associated with the regulation of body temperature. Water is the major body constituent. An adult human contains about 60% water (men 55–70%, women 45–60%). The women and obese individuals have relatively less water which is due to the higher content of stored fat in an anhydrous form. A 70 kg man contains 42 L of water. This is distributed in intracellular (inside the cells 28 L) and extracellular (outside the cells 14 L) compartments, respectively known as intracellular fluid and extracellular fluid. The ECF is further divided into interstitial fluid and plasma. 2. Physiological functions of water It acts as solvent for transportation of substances inside and outside the cells. It is an essential constituent of cell structures. It provides media for biochemical reactions. It regulates body temperature by losing heat through water lost from the body. It provides a lubricating action to prevent friction in joints, pleura and
∗ Corresponding author. E-mail addresses: makram [email protected], makram [email protected] (M. Akram). 2210-5239/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.bionut.2012.10.003
conjuctiva, etc. The fluidity of blood is due to water. Makino et al. [1] have studied the physiological functions of the water-water cycle (Mehler reaction) and the cyclic electron flow around PSI in rice leaves. 3. Total body water It is the amount of water content present in the body. It is 75% of total body weight in a newborn. It is 55% of total body weight in adult males. It is 50% of total body weight in adult females. The difference in the percentage of body water is due to excess amount of fat depot in the females. The amount of total body water content (60% of total body weight or 42 L in 70 kg patient) is an accepted average in adults for clinical calculations [2]. 4. Intracellular fluid Two third (66%) of total body weight (40% of total body weight) is present in the intracellular compartments. Largest proportion of this water is present in female; the percentage of intracellular water is lower than in males. The principle cations of intracellular compartments are potassium and magnesium and principle anion are phosphates and proteins. 5. Extracellular fluid One third (33%) of the total body water (20% of body water) is present in the extracellular compartment. It is further subdivided into intravascular and interstitial fluid compartments. In the ECF, sodium is the principle cation and chloride and bicarbonate are the principle anions.
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M. Akram, A. Hamid / Biomedicine & Preventive Nutrition 3 (2013) 193–195
6. Intravascular fluid
13. Urine
It is the part of extracellular fluid present in intravascular compartment. It is 5% of body weight or ¼ of ECF (2.8 L in 70 kg adult). Intravascular fluid is present in the blood which is composed of cells (red cells, white cells, platelets and plasma [fluids into dissolved protein]).
This is the major route for water loss from the body. In a healthy individual, the urine output is about 1–2 L/day. Water loss through kidneys although highly variable, is well regulated to meet the body demands–to get rid of water or to retain, it should, however, be remembered that man cannot completely shut down urine production, despite there being no water intake. This is due to the fact that some amounts of water (about 500 mL/day) are essential as the medium to eliminate the waste products from the body.
7. Interstitial fluids It is the part of the extracellular fluid present in the interstitial space (15% of body weight or ¾ of ECF). The interstitial fluid is further complicated by having a rapidly equilibrating or functional compartment as well as several more slowly equilibrating or relatively non-functioning components. These non-functioning components comprise connective tissue water as well as transcellular water including: • • • • •
cerebrospinal fluid; peritoneal fluid; joint fluids; secretions of the gastrointestinal tract; fluid in renal tubules.
This non-functioning component normally represents only 10% of the interstitial fluid volume (1–3% of body weight).
14. Hormonal regulation of urine production It is indeed surprising to know that about 180 L of water is filtered by the glomeruli into the renal tubules every day. However, most of this is reabsorbed and only 1–2 L are excreted as urine. Water excretion by the kidney is tightly controlled by vasopressin also known as antidiuretic hormone of the posterior pituitary gland. The secretion of ADH is regulated by the osmotic pressure of plasma. An increase in osmolality promotes ADH secretion that leads to increased water reabsorption from the renal tubules (less urine formation). On the other hand, a decrease in osmolality suppresses ADH secretion that results in reduced water reabsorption from the renal tubules (more urine output). Plasma osmolality is largely dependent on the sodium concentration, hence sodium indirectly controls the amount of water in the body [3]. 15. Diabetes insipidus
8. Water turns over and balance The body has tremendous capacity to regulate its water content. In a healthy individual, this is achieved by balancing the daily water intake and water output.
Diabetes insipidus is a disorder characterized by the deficiency of ADH which results in an increased loss of water from the body [4]. 16. Skin
9. Water intake Water is supplied to the body by exogenous and endogenous sources. 10. Exogenous water Ingested water and beverages, water content of solid foods constitute the exogenous source of water. Water intake is highly variable which may range from 0.5–5 L. It largely depends on the social habits and climate. In general, people living in hot climate drink more water. Ingestion of water is mainly controlled by a thirst center located in the hypothalamus. Increase in the osmolality of plasma causes increased water intake by stimulating thirst centre. 11. Endogenous water The metabolic water produced within the body is the endogenous water. This water is derived from the oxidation of foods stuffs. It is estimated that 1 g each of carbohydrate, protein and fat, respectively, yield 0.6 mL, 0.4 mL and 0.1 mL of water. On an average, about 125 mL of water is generated for 1000 Cal consumed by the body.
Loss of water (450 mL/day) occurs through the body surface by perspiration. This is an unregulated process by the body which mostly depends on the atmospheric temperature and humidity. The loss is more in hot climate. Fever causes increased water loss through the skin. It is estimated that for every 1 centigrade rise in body temperature, about 15% increase is observed in the loss of water (through skin). 17. Lungs During perspiration, some amount of water (about 400 mL/day) is lost through the expired air. The latter is saturated with water and expelled from the body. In hot climates and/or when the person is suffering from fever, the water loss through lungs is increased. The loss of water by perspiration (via skin) and respiration (via lungs) is collectively referred to as insensible loss. 18. Feces Most of the water entering the gastrointestinal tract is reabsorbed by the intestine. About 150 mL/day is lost through feces in a healthy individual. Fecal loss of water is tremendously increased in diarrhea.
12. Water output
19. Water intoxication
Water losses from the body are variable. There are different routes for the elimination of water from the body, urine, skin, lungs, feces, tears, milk and vomiting. Amount of water intake or loss depends upon temperature and other environmental conditions.
This occurs in the following conditions: hypersecretion of ADH: this occurs after anesthesia for surgery, administration of narcotic drugs such as morphia and stress due to any cause including surgery. There is usually a period of water retention for 12–36 hours
M. Akram, A. Hamid / Biomedicine & Preventive Nutrition 3 (2013) 193–195
following a surgical operation; renal failure due to any cause can lead to water retention; excessive administration of fluids by mouth or parenterally. Gardner has reported death by water intoxication [5]. 20. Symptoms of intoxication The subject becomes mentally confused, develops aphasia, in co-ordination, delirium, muscular weakness, nausea and vomiting. He may finally develop convulsions and coma [6].
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hypothalamus anterior to the supraoptic nuclei. Thirst center is stimulated by hypertonicity of ECF, hypovolemia, decrease cardiac output, drying of mouth. ADH is secreted in supraoptic nuclei of hypothalamus. When hypertonicity occurs then ADH is increased. Pure water deprivation occurs when water loss is not completely replaced by water intake. If subject fails to receive water, cellular proteins undergoes breakdown liberating K into body fluid which ultimately excreted in exchange of NA. All these effects result in depressed cell function, if these processes continue, death ensues. Water intoxication occurs when water content of body increases without proportional increase in electrolytes [9,10].
21. Clinical changes 24. Conclusion The PCV, hemoglobin and plasma protein concentrations are all decreased. Urine volume is usually increased and is of low specific gravity. Okura et al. [7] have reported the electroencephalographic changes during and after water intoxication. 22. Role of Withania somnifera in dehydration Dehydration or water deprivation in the body decreases urine output and urea and other waste products are accumulated in the blood. A study was conducted to evaluate the association of uremia and oxidative stress by applying the herbal plant Withania somnifera (W. somnifera) (Aswagandha). The study was performed on dehydrated male rats. Eighteen rats were selected for study and were randomly divided into three groups: Group-1, control, Group2, only dehydration and Group-3, dehydration + administration of aqueous root extract of W. somnifera, orally. After 25 days of treatment, it was observed that the body weight of Group-3 animals had increased significantly, while that in Group-2 had decreased significantly. In Group-2 animals, the serum urea and creatinine levels increased significantly when compared with animals in Groups-1 and 3. The low levels of serum urea and creatinine in Group-3 animals indicate the protective effect of the plant extract against renal injury caused by dehydration. Dehydration-induced oxidative stress was established in our study by noting the low activities of super-oxide dismutase and catalase, both important antioxidant enzymes, in Group-2 animals; both enzymes were stabilized in animals of Groups-3 and 1. As a conclusion, it was hypothesized that W. somnifera has antioxidant activity that is responsible in reducing the extent of renal injury as a result of oxidative stress [8]. 23. Discussion Water balance is maintained mainly by two mechanisms that are thirst mechanism and ADH mechanism. Thirst sensation often referred to the mouth and throat, interpreted as a conscious desire for water. Thirst center is located in lateral preoptic area of the
Water is involved in several body functions. Water is closely associated with the regulation of body temperature. Water is the major body constituent. Water is supplied to the body by exogenous and endogenous sources. Ingested water and beverages, water content of solid foods constitute the exogenous source of water. The metabolic water produced within the body is the endogenous water. There are different routes for the elimination of water from the body, urine, skin, lungs, feces, tears, milk and vomiting. Amount of water intake or loss depends upon temperature and other environmental conditions. Disclosure of interest None of the individuals compiling this information has any affiliations or financial involvement that conflicts with the material presented in this article. References [1] Makino A, Miyake C, Yokota A. Physiological functions of the water-water cycle (Mehler reaction) and the cyclic electron flow around PSI in rice leaves. Plant Cell Physiol 2001;43(9):1017–26. [2] Bedogni G, Borghi A, Battistini N. Body water distribution and disease. Acta Diabetol 2003;40(1):200–2. [3] Mukhtiar B. Urinanalysis, pract. 1st ed. Biochem, Fair fan printer Karachi; 1998. p. 19–20. [4] Crowley RK, Sherlock M, Agha A, Smith D, Thompson CJ. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf) 2007;66(4):475–82. [5] Gardner J. Death by water intoxication. Mil Med 2002;167(5):432–4. [6] Farrell D, Bower L. Fatal water intoxication. J Clin Pathol 2003;56(10):803–4. [7] Okura M, Okada K, Nagamine I, Yamaguchi H, Karisha K, Ishimoto Y, et al. Electroencephalographic changes during and after water intoxication. Jpn J Psychiatry Neurol 1990;44(4):729–34. [8] Koushik D, Tanushree T. Effect of extract of Withania somnifera on dehydrationinduced oxidative stress-related uremia in male rats. Saudi J Kidney Dis Transpl 2010;21(1):75–80. [9] Robert K. Water metabolism. 26th ed. Harper biochem, Appletion and Lange; 2000. p. 15. [10] Kumar C. Endocrine system. 6th ed. Bas. Path. W.B. Saunder Company; 2003. p. 643.
Available online at
www.sciencedirect.com
Review
A comprehensive review on water balance Muhammad Akram a,∗ , Abdul Hamid b a b
Department of Eastern Medicine and Surgery, Faculty of Medical and Health Sciences, The University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan Department of Horticulture, Faculty of Agriculture, The University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan
a r t i c l e
i n f o
Article history: Received 28 September 2012 Accepted 23 October 2012 Keywords: Water balance Regulation of water ICF ECF
a b s t r a c t Water is more important than any other single compound to life. It is involved in several body functions. Water acts as a vehicle for transport of solutes. Water is the major body constituent. An adult human contains about 60% water (men 55–70%, women 45–60%). A 70 kg man contains 42 L of water. This is distributed in intracellular (inside the cells 28 L) and extracellular (outside the cells 14 L) compartments, respectively known as intracellular fluid and extracellular fluid. The body has tremendous capacity to regulate its water content. In a healthy individual, this is achieved by balancing the daily water intake and water output. © 2012 Elsevier Masson SAS. All rights reserved.
1. Introduction Water intake is normally by mouth and absorption is from all parts of gastrointestinal tract. Water is the solvent of life. Undoubtedly, water is more important than any other single compound to life. It is involved in several body functions. Water provides the aqueous medium to the organism which is essential for the various biochemical reactions to occur. Water directly participates as a reactant in several metabolic reactions. It acts as a vehicle for transport of solutes. Water is closely associated with the regulation of body temperature. Water is the major body constituent. An adult human contains about 60% water (men 55–70%, women 45–60%). The women and obese individuals have relatively less water which is due to the higher content of stored fat in an anhydrous form. A 70 kg man contains 42 L of water. This is distributed in intracellular (inside the cells 28 L) and extracellular (outside the cells 14 L) compartments, respectively known as intracellular fluid and extracellular fluid. The ECF is further divided into interstitial fluid and plasma. 2. Physiological functions of water It acts as solvent for transportation of substances inside and outside the cells. It is an essential constituent of cell structures. It provides media for biochemical reactions. It regulates body temperature by losing heat through water lost from the body. It provides a lubricating action to prevent friction in joints, pleura and
∗ Corresponding author. E-mail addresses: makram [email protected], makram [email protected] (M. Akram). 2210-5239/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.bionut.2012.10.003
conjuctiva, etc. The fluidity of blood is due to water. Makino et al. [1] have studied the physiological functions of the water-water cycle (Mehler reaction) and the cyclic electron flow around PSI in rice leaves. 3. Total body water It is the amount of water content present in the body. It is 75% of total body weight in a newborn. It is 55% of total body weight in adult males. It is 50% of total body weight in adult females. The difference in the percentage of body water is due to excess amount of fat depot in the females. The amount of total body water content (60% of total body weight or 42 L in 70 kg patient) is an accepted average in adults for clinical calculations [2]. 4. Intracellular fluid Two third (66%) of total body weight (40% of total body weight) is present in the intracellular compartments. Largest proportion of this water is present in female; the percentage of intracellular water is lower than in males. The principle cations of intracellular compartments are potassium and magnesium and principle anion are phosphates and proteins. 5. Extracellular fluid One third (33%) of the total body water (20% of body water) is present in the extracellular compartment. It is further subdivided into intravascular and interstitial fluid compartments. In the ECF, sodium is the principle cation and chloride and bicarbonate are the principle anions.
194
M. Akram, A. Hamid / Biomedicine & Preventive Nutrition 3 (2013) 193–195
6. Intravascular fluid
13. Urine
It is the part of extracellular fluid present in intravascular compartment. It is 5% of body weight or ¼ of ECF (2.8 L in 70 kg adult). Intravascular fluid is present in the blood which is composed of cells (red cells, white cells, platelets and plasma [fluids into dissolved protein]).
This is the major route for water loss from the body. In a healthy individual, the urine output is about 1–2 L/day. Water loss through kidneys although highly variable, is well regulated to meet the body demands–to get rid of water or to retain, it should, however, be remembered that man cannot completely shut down urine production, despite there being no water intake. This is due to the fact that some amounts of water (about 500 mL/day) are essential as the medium to eliminate the waste products from the body.
7. Interstitial fluids It is the part of the extracellular fluid present in the interstitial space (15% of body weight or ¾ of ECF). The interstitial fluid is further complicated by having a rapidly equilibrating or functional compartment as well as several more slowly equilibrating or relatively non-functioning components. These non-functioning components comprise connective tissue water as well as transcellular water including: • • • • •
cerebrospinal fluid; peritoneal fluid; joint fluids; secretions of the gastrointestinal tract; fluid in renal tubules.
This non-functioning component normally represents only 10% of the interstitial fluid volume (1–3% of body weight).
14. Hormonal regulation of urine production It is indeed surprising to know that about 180 L of water is filtered by the glomeruli into the renal tubules every day. However, most of this is reabsorbed and only 1–2 L are excreted as urine. Water excretion by the kidney is tightly controlled by vasopressin also known as antidiuretic hormone of the posterior pituitary gland. The secretion of ADH is regulated by the osmotic pressure of plasma. An increase in osmolality promotes ADH secretion that leads to increased water reabsorption from the renal tubules (less urine formation). On the other hand, a decrease in osmolality suppresses ADH secretion that results in reduced water reabsorption from the renal tubules (more urine output). Plasma osmolality is largely dependent on the sodium concentration, hence sodium indirectly controls the amount of water in the body [3]. 15. Diabetes insipidus
8. Water turns over and balance The body has tremendous capacity to regulate its water content. In a healthy individual, this is achieved by balancing the daily water intake and water output.
Diabetes insipidus is a disorder characterized by the deficiency of ADH which results in an increased loss of water from the body [4]. 16. Skin
9. Water intake Water is supplied to the body by exogenous and endogenous sources. 10. Exogenous water Ingested water and beverages, water content of solid foods constitute the exogenous source of water. Water intake is highly variable which may range from 0.5–5 L. It largely depends on the social habits and climate. In general, people living in hot climate drink more water. Ingestion of water is mainly controlled by a thirst center located in the hypothalamus. Increase in the osmolality of plasma causes increased water intake by stimulating thirst centre. 11. Endogenous water The metabolic water produced within the body is the endogenous water. This water is derived from the oxidation of foods stuffs. It is estimated that 1 g each of carbohydrate, protein and fat, respectively, yield 0.6 mL, 0.4 mL and 0.1 mL of water. On an average, about 125 mL of water is generated for 1000 Cal consumed by the body.
Loss of water (450 mL/day) occurs through the body surface by perspiration. This is an unregulated process by the body which mostly depends on the atmospheric temperature and humidity. The loss is more in hot climate. Fever causes increased water loss through the skin. It is estimated that for every 1 centigrade rise in body temperature, about 15% increase is observed in the loss of water (through skin). 17. Lungs During perspiration, some amount of water (about 400 mL/day) is lost through the expired air. The latter is saturated with water and expelled from the body. In hot climates and/or when the person is suffering from fever, the water loss through lungs is increased. The loss of water by perspiration (via skin) and respiration (via lungs) is collectively referred to as insensible loss. 18. Feces Most of the water entering the gastrointestinal tract is reabsorbed by the intestine. About 150 mL/day is lost through feces in a healthy individual. Fecal loss of water is tremendously increased in diarrhea.
12. Water output
19. Water intoxication
Water losses from the body are variable. There are different routes for the elimination of water from the body, urine, skin, lungs, feces, tears, milk and vomiting. Amount of water intake or loss depends upon temperature and other environmental conditions.
This occurs in the following conditions: hypersecretion of ADH: this occurs after anesthesia for surgery, administration of narcotic drugs such as morphia and stress due to any cause including surgery. There is usually a period of water retention for 12–36 hours
M. Akram, A. Hamid / Biomedicine & Preventive Nutrition 3 (2013) 193–195
following a surgical operation; renal failure due to any cause can lead to water retention; excessive administration of fluids by mouth or parenterally. Gardner has reported death by water intoxication [5]. 20. Symptoms of intoxication The subject becomes mentally confused, develops aphasia, in co-ordination, delirium, muscular weakness, nausea and vomiting. He may finally develop convulsions and coma [6].
195
hypothalamus anterior to the supraoptic nuclei. Thirst center is stimulated by hypertonicity of ECF, hypovolemia, decrease cardiac output, drying of mouth. ADH is secreted in supraoptic nuclei of hypothalamus. When hypertonicity occurs then ADH is increased. Pure water deprivation occurs when water loss is not completely replaced by water intake. If subject fails to receive water, cellular proteins undergoes breakdown liberating K into body fluid which ultimately excreted in exchange of NA. All these effects result in depressed cell function, if these processes continue, death ensues. Water intoxication occurs when water content of body increases without proportional increase in electrolytes [9,10].
21. Clinical changes 24. Conclusion The PCV, hemoglobin and plasma protein concentrations are all decreased. Urine volume is usually increased and is of low specific gravity. Okura et al. [7] have reported the electroencephalographic changes during and after water intoxication. 22. Role of Withania somnifera in dehydration Dehydration or water deprivation in the body decreases urine output and urea and other waste products are accumulated in the blood. A study was conducted to evaluate the association of uremia and oxidative stress by applying the herbal plant Withania somnifera (W. somnifera) (Aswagandha). The study was performed on dehydrated male rats. Eighteen rats were selected for study and were randomly divided into three groups: Group-1, control, Group2, only dehydration and Group-3, dehydration + administration of aqueous root extract of W. somnifera, orally. After 25 days of treatment, it was observed that the body weight of Group-3 animals had increased significantly, while that in Group-2 had decreased significantly. In Group-2 animals, the serum urea and creatinine levels increased significantly when compared with animals in Groups-1 and 3. The low levels of serum urea and creatinine in Group-3 animals indicate the protective effect of the plant extract against renal injury caused by dehydration. Dehydration-induced oxidative stress was established in our study by noting the low activities of super-oxide dismutase and catalase, both important antioxidant enzymes, in Group-2 animals; both enzymes were stabilized in animals of Groups-3 and 1. As a conclusion, it was hypothesized that W. somnifera has antioxidant activity that is responsible in reducing the extent of renal injury as a result of oxidative stress [8]. 23. Discussion Water balance is maintained mainly by two mechanisms that are thirst mechanism and ADH mechanism. Thirst sensation often referred to the mouth and throat, interpreted as a conscious desire for water. Thirst center is located in lateral preoptic area of the
Water is involved in several body functions. Water is closely associated with the regulation of body temperature. Water is the major body constituent. Water is supplied to the body by exogenous and endogenous sources. Ingested water and beverages, water content of solid foods constitute the exogenous source of water. The metabolic water produced within the body is the endogenous water. There are different routes for the elimination of water from the body, urine, skin, lungs, feces, tears, milk and vomiting. Amount of water intake or loss depends upon temperature and other environmental conditions. Disclosure of interest None of the individuals compiling this information has any affiliations or financial involvement that conflicts with the material presented in this article. References [1] Makino A, Miyake C, Yokota A. Physiological functions of the water-water cycle (Mehler reaction) and the cyclic electron flow around PSI in rice leaves. Plant Cell Physiol 2001;43(9):1017–26. [2] Bedogni G, Borghi A, Battistini N. Body water distribution and disease. Acta Diabetol 2003;40(1):200–2. [3] Mukhtiar B. Urinanalysis, pract. 1st ed. Biochem, Fair fan printer Karachi; 1998. p. 19–20. [4] Crowley RK, Sherlock M, Agha A, Smith D, Thompson CJ. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf) 2007;66(4):475–82. [5] Gardner J. Death by water intoxication. Mil Med 2002;167(5):432–4. [6] Farrell D, Bower L. Fatal water intoxication. J Clin Pathol 2003;56(10):803–4. [7] Okura M, Okada K, Nagamine I, Yamaguchi H, Karisha K, Ishimoto Y, et al. Electroencephalographic changes during and after water intoxication. Jpn J Psychiatry Neurol 1990;44(4):729–34. [8] Koushik D, Tanushree T. Effect of extract of Withania somnifera on dehydrationinduced oxidative stress-related uremia in male rats. Saudi J Kidney Dis Transpl 2010;21(1):75–80. [9] Robert K. Water metabolism. 26th ed. Harper biochem, Appletion and Lange; 2000. p. 15. [10] Kumar C. Endocrine system. 6th ed. Bas. Path. W.B. Saunder Company; 2003. p. 643.