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. )
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.
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).
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.
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.
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