June 1996, Volume 46, Issue 6

Original Article

Changes in Plasma Electrolytes During Acclimatisation at High Altitude

Dilshad Ahmad Khan  ( Department of Chemical Pathology, Armed Forces, Army Medical College, Rawalpindi. )
Muhammad Aslam  ( Institute of Pathology and High Altitude Medical Research Council, Army Medical College, Rawalpindi. )
Zia UIlah Khan  ( Institute of Pathology and High Altitude Medical Research Council, Army Medical College, Rawalpindi. )


The effects on plasma electrolytes and related honnones were determined in non-acclimatized low lander males, exposed for 96 hours to an altitude of 4424 meters. Twenty healthy soldiers aged 18-34 years travelled by road from an altitude of 2303 meters to 4424 meters over a period of 10 hours. Plasma sodium levels (142..09±1.14 mmol/l) and aldosterone (16.61±5.70 ng/ml) decreased to 139.69 mmolIl and 11.6±4.60 ug/ml respectively after 96 hours of acute expoure to high altitude (p<0.05). The plasma potassium and chloride levels did not show significant change, while, plasma HCO3 decreased gradually from 21.06±1.38 mmol/l to 18.55±0.82 mmol/l after 96 hours exposure to this altitude (p<0.01). The plasma ionized calcium and plasma phosphate concentration decreased from 1.32±0.11 mmol/l and 1.58±1.3 mmoLfl to 1.20±0.05 mmol/l and 1.47±0.99 mmolIl respectively (p


Acute mountain sickness (AMS), high altitude pulmo­nary edema (HAPE) and cerebral edema (HACE) are associ­ated with fluid retention and weight gain in non-acclimatized men who rapidly ascend to high altitude1-4. It has been suggested that increased capillaey permeability and fluid retention are important factors in the causation of these high altitude disorders5-6. Acclimatization changes occumng in human body include changes in water, electrolytes and related hormones such as serum aldosterone, antidiuretic hormone (ADH) and parathyroid hormone (P11-I). The urinaiy excre­tion of solutes such as sodium, potassiumand bicarbonate may induce paitial compensation of respiratory alkalosis in unac­climatizedmen at high altitude7,8.
The experience shows that AMS, HAPE and HACE cany considerable importance for troops who ascend rapidly to high altitude9,10. This study was planned to investigate the acute effects of exposure to high altitude on plasma sodium, potassium, HCO3, calcium, phosphate and the related hor­mones (aldosterone and PTH) in unacclimatized low landers.

Subjects and Methods

The study was carried out in the Karakomm Range of Pakistan by the High Altitude Medical Research Cell (HAL-MARC) under auspices of Armed Forces Medical Research and Development Council (AFMRandDC), Pakistan Army in 1993.
Twenty non-acclimatized healthy male volunteers of 18-34 years of age were selected after proper medical examination for the study. They had never been exposed to high altitude before.
Study Protocol: At 2303 meter: The baseline arterial blood samples were collected from the volunteers in heparinized tubes and they travelled by road to a height of 4424 meters the same day.
At 4424 meter: The volunteers stayed at this altitude for 5 days, taking normal diet. The arterial blood samples were collected in basal conditions after 48 and 96 hours . Plasma was separated by centrifugation immediately after blood collection, samples were stored in liquid nitrogen for sub­sequent measurement of hormones.
Electrolyte analysis
Plasma sodium, potassium, ionized calcium and bicar­bonate were determined from hepannised arterial blood samples immediately after their collection by Gem-stat blood gas analyzer (Mallinckmdt, USA) at mountainous area. Plasma chloride and phosphate were analysed at AFIP using commercially available kits. (Merck, Germany).
Hormonal analysis
Plasma aldostemne and PTH were assayed by standard radioimmunoassay technique11,12 at AFIP, Rawalpindi using commercially available kits (DPC; USA). The RIA hormonal controls were run at the same time and intra assay CV’s for aldosterone and PTH were 5% and 6.2% respectively.


The plasma sodium, potassium, chloride and bicaibon­ate showed individual variation inbase line and at highaltitude (Table).

The results are presented as mean±SD. Plasma sodium decreased from 142.09±1.14 to 139.69±0.96 mmol/L after 96 hours of acute exposure to high altitude (p<0.01).
Plasma bicarbonate also decreased from 21.06±1.38 to 19.50±1.24 and 18.55±0.82 mmoLfL after 48 and 96 hours exposure (P
Plasma ionized calcium and plasma phosphate concentra­tion decreased from 1.32±0.11 and 1.58±1.3 to 1.20±0.05 and 1.47±0.94 mmol/l (p<0.01) respectively at high altitude after 96 hours exposure (Figure 2).


Homeostatic mechanism for sodium and water are interlinked and distribution of fluid between intra and ex­tracellular fluid compartments depends on changes in ex­tracellular sodium concentration. Plasma sodium level signifi­cantly decreased after acute exposure to high altitude in this study. This could be due to decreased serum aldosterone. Decreased level of serum aldostemne and arterial chemore­ceptor stimulation by hypoxic hypoxia is counteracted by excretion of sodium, water and bicarbonate from the body13 - Many studies have demonstrated the excretionof sodium from the body for initial several days at high altitude14,15.
Potassium and hydrogen compete for exchange with sodium in renal tubules and other body cells membranes. 96 hours exposure (Figure 3).

Hypoxia causes impairment of the pump in all cells, with a net gain of potassium within the extracellular fluid. Such impair­ment in the distal tubules causes potassium retention and hyperkalaemia16. But, in this study no significant change was observed in plasma potassium level after acute exposure to high altitude. The possible explanation could be that respira­tory alkalosis at high altitude leads to decreased plasma potassium in extracellular fluid. Sutton and his colleagues17 found no change in plasma potassium concentration in men exposed to simulated altitude of 4700 m for 2 days but like other observers, they found a decrease in urinary potassium excretion. There is a tendency of the body to consume potassium on acute exposure to high altitude especially during the first three days18. Hypoxia at high altitude stimulates respiratory centres and causes hyperventilation in normal subjects. This hyperventilation lowers plasma Pco2 and bicarbonate concentrations primarily by inhibiting the excre­tion of net acid19. Aldosterone appears to regulate sodium and water balance by its action exerted mainly on the distal renal tubule stimulating sodium reabsorption and potassium excre­tion. The aldosterone levels decreased after 48 and 96 hours exposure to high altitude as compared with the baseline level (p<0.01) in this study. The fall in aldosterone is related to the increased blood volume that occurs in acclimatization process to altitude. This leads to stimulation of the stretch receptors in the right atrium which is known to depress aldostemne secretion20. Jung and his colleagues21 found that the fall in blood aldosterone at high altitude occurs in older subjects rather than in the young. The reduction in aldosterone secrction has been confirmed in climbers. The exact mecha­nisms of this decrease in aldosterone have notbeen elucidated. Aldosterone concentrations at high altitude appear to depend on the duration of exposure. Okazaki et al21 reported significant increase in aldosterone on arrival at a simulated altitude of 6000 m. This increased level appeared to be due to increased adrenocorticotrophic hormone (ACTH)because the concentrations of serum cortisol were also elevated signifi­cantly22. After longer periods of exposure to hypobaric hypoxia, there occur significant decrease in both blood and urinary aldosterone23,24. Plasma ionized calcium and phos­phate depression at high altitude after 48 hours of exposure, could be due to respiratory alkalosis. Krapt et al25 reported sustained decrease in ionized calcium in four normal male subjects at 3450 m altitude but the plasma phosphate level increased. Hypoxic pulmonary vasoconstriction and respira­tory alkalosis at high altitude also enhances penetration of ionized calcium across sarcolemma of smooth muscle cells. This causes increased cytosol free ionized calcium concentra­tion due to alteration in sodium handling and in the sodium -ionized calcium exchange system26. Hypophosphataemia is associated with disturbances of ionized calcium metabolism and phosphate is lost from the body in urine. Phosphate may be reduced because like potassium, it enters the cells from extracellular fluid because of increased rate of glucose metabolism at high altitude27. Low plasma free ionized calcium concentration with normal total calcium due to respiratory alkalosis leads to increased plasma PTH after 48 hours of exposure but subsequent decrease in PTH level after 96 hours cannotbe explained at the moment.
It may be concluded that the human body tends to acclimatize to high altitude by decreasing plasma aldosterone, with associated fall in sodium and bicarbonate levels, There occurs a significant decrease in plasma ionized calcium and phosphate levels while PTH concentration fluctuates accord­ing to the dumtion of exposure to high altitude.


1. Bartsch, P.S., Shaw, M. and Franciolli, M. Atrial natriuretic peptide in acute mountain sickness. J. AppI. Physiol, 1988;65:1929.37.
2. Bartsch, PP. Vock, M, Maggiorini, Metal. Respiratory symptoms, X-ray and physiological correlations at high altitude. In: Hypoxia. The adaptions, Sutton, J.R. Castes, 0., and Remmers, LE.(eds). Toronto, Decka 1990, pp. 241-5.
3. Hackett, P.H.,Rennie,D.,Rales,J.E. Peripheral edema, retinal haemorrhage and acute mountain sickness. Am. J. Med., 1979;67:214-8.
4. Hackett, PH., Rennie, D., Hoflucister, SE. at al. Fluid retention and relative hypoventilation in acute mountain sickness, Respiration, 1982;43:321-9.
S. Hackett, RH.,Rennie. D.,Grove,R.F.et aL Acute mountain sidmeas and the edana of high altitude: A common pathogenesis. Respir Physiol., 1981,46:383-90.
6. Sutton, J.R. and Lassan, N. Pathophysiology of acute mountain sickness and high altitude pulmonary oedema: An hypothesis. Bull. Eut Physiopathol. Respir, 1979;15:1045-52.
7. Ullmann, E. Acute anoxia and the excretion of water and electrolyte. J. Physiol., 1961;155:417-37.
8. Van-Liere, E.J and Stickney, J.C. Hypoxia, Chicago, University of Chicago Press, 1963, pp. 236-55.
9. Chaudhry, M.A., Khan, Z.U. and Malik, IA. Incidence of medical problems at high terrestrial altitudes: A retrospective study. Pak. Armed Forces Med. J., 1994;44:128-33,
10. Oelz, 0., Maggiorini, M., Ritter, M. et al. Pathophysiology, prevention and therapy of altitude pulmonary edema. Schweiz Med Wochenschr., 1992;122: 1151-8.
11. Chard, T. An introduction to radioimmunoassay and related techniques, ed 3, New york, 1987, Elsevier Science Publishing Co., Inc. Theorell, J.I. Editor: Radioimmunoassay design and quality control. World Federation of Nuclear Medicine and Biology, Oxford, Pergamon Press, Inc., 1983.
12. Ekins, R.P. The physiological significance and measurement of free hormones in blood. In radioimmunoassays and related procedures in medicine. ed: Sonski ER: 1st edition: Vienna, International Atomic Energy Agency, 1982, pp. 191-218.
13. Koller, E.A., Buhrer, A. Felder, L. et al. Altitude diuresis: Endocrine and renal responses to acute hypoxia of acclimatized and non-acclimatized subjects. Eur. J. Appi. PhysioL, 1991 ;62:228-34.
14. Janoski, A.H., Whitten, B.K., Shields, J.L. et at. Electrolyte patterns and regulation in man during acute exposure to high altitude. Federation Proc., 1969;28:1183-9.
15. Slater, J.D.H.,Williams,E.S.,Edwards,R.H.T. at al.Potassium retention during the respiratory alkalosis of mild hypoxia in man: Its relationship to aldosterone secretion and other metabolic changes. Chin. Sci., 1969,37:311-26.
16. Philip, D. Mayne. Sodium and Water balance. In: Clinical Chemistry in Diagnosis and Treatment (6th ed) London, ELBS, 1994, pp.25-57.
17. Sutton,J.R., Viol, G.W., Gray, OW. etal. Renin, aldosterone, electrolyte and cortisot respiratory in hypoxic decompression. J. AppI. Physiol,, 1977;43:421-4.
18. Hannson, J.R Chinn, K.S.K. and Shields, J.L. Alterations in serum and extracellular electrolytes during high altitude exposure. J. Appi Physiol., 1972;31:266-70.
19. Krapf, R., Becler I., Healner, D. et al. Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid base equilibrium. N. EngI. J.Med., 1991;324:1394-401.
20. Halhuber, M.J. and Gabl, F. 17-OHCS excretion and blood eosinophils at an altitude of 2000 m. In: The physiological effects of high altitude (W.H. Weihe, Ed) Oxford, Pregamon Press, 1964, p. 131.
21. Okazaki, S., Tamura, Y., Hatano, T. at al. Hormonal disturbance of fluid electrolyte metabolism under altitude exposure in man. Aviat. Space Environ. Med., 1984;55:200-5.
22. Khan, D.A., Khan,Z.S. and Aslam, M Hormonal changes in non- acclimatized men at high altitude. Pak. Armed Forces Med. J., 1994;44:51-56.
23. Milledge, J.S., Catley, D.M., Blume, F.D. at al. Renin angiotensin-conveiting enzyme and aldosterone in humans on Mount Everest. J. AppL PhysioL, 1983;55:1599-1604.
24. Maresh, C.M., Noble, B.J., Robertson, K.L. at al Adrenocostical responses to maximal exercise in moderate altitude natives at 447 Torr, J. AppI. PhysioL, 1984;56:482-6.
25. Krapf, R.,Jaeger, P. and Hulter, H.N. Chronic respiratory alkalosis induces renal PTH-resistance,hyperphosphatemia and hypocalcamia in human Kidney Int., 1992;42:727-34.
26. Guazzi, M.D., Alimarto, M., Barti, M. at al. Enhanced hypoxic pulmonary vasoconstriction in hypertension. Circulation, 1989;79:337-43.
27. Philip, D. Mayne. Calcium, phosphate and magnesium metabolism. In: Clinical Chemistry inDiagnosis and treatment (6th ed)London, ELBS, 1994, pp. 171-91.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: