Antidiuretic Hormone. Antidiuretic hormone (ADH) is a stress hormone that increases thirst and reduces free water clearance. Both osmolality and volume status modulate its level. Changes in ADH response would be an attractive explanation for the alterations in fluid metabolism seen at high altitudes. Thirteen studies were examined where the effect of hypoxia on ADH was investigated (Ashack et al., 1985; Bärtsch et al., 1991a; Brahmachari et al., 1973; Claybaugh et al., 1982, 1987b; Forsling and Milledge, 1977; Hackett et al., 1978; Harber et al., 1981; Heyes et al., 1982; Okazaki et al., 1984; Porchet et al., 1984; Ramirez et al., 1992; Subramanian et al., 1975). The results are controversial, and there is both evidence for an increase in ADH with hypoxia (Hackett et al., 1978; Singh et al., 1974), no change (Ashack et al., 1985; Forsling and Milledge, 1977; Heyes et al., 1982; Porchet et al., 1984), or a decrease (Brahmachari et al., 1973; Porchet et al., 1984; Subramanian et al., 1975). Part of the explanation for this disagreement may lie in the variety of methods used in these studies and the differences in the nature and degree of hypoxia used (Subramanian et al., 1975). Mild hypoxia causes a reduction in ADH and may be important in the diuresis seen in the early stages of high-altitude ascent (Brahmachari et al., 1973; Porchet et al., 1984). Although ADH is important in mediating thirst, reduced thirst at high altitudes cannot be explained by a change in ADH since a similar response is seen in diabetes insipidus (Jones et al., 1981a, b). Severe hypoxia, extreme altitudes, exercise, and any form of stress, including nausea and vomiting, increase ADH (Ashack et al., 1985; Heyes et al., 1982). ADH is increased in AMS, and subjects prone to develop this condition show an exaggerated increase in ADH during exercise at high altitudes ().
FIGURE 18-10 Neurohormones and renal function in normal subjects living at extreme altitudes (> 6,000 m [19,865 ft]) for a prolonged period (> 10 weeks). ns, not significant; Epi, epinephrine; Norepi, norepinephrine; PRA, plasma renin activity; Aldo, aldosterone; ANP, atrial natriuretic peptide. SOURCE: Adapted from Anand et al. (1993).
Extreme altitude pulmonary oedema (EAPO) in …
Changes in urine output are also common at high altitudes, but the data are controversial. This laboratory reviewed 57 studies where urine output was measured at high altitudes. The data suggest that there is usually a transient diuresis at high altitudes lasting, on an average, 3 to 4 days. Diuresis is common at moderate altitudes, in subjects who do not exercise soon after transfer to high altitudes, in subjects who do not develop AMS, and in subjects for whom fluid intake is strictly enforced. Diuresis is also seen in acute experiments at sea level when subjects breathe hypoxic gas mixtures (Ashack et al., 1985). In contrast, anti-diuresis commonly accompanies severe hypoxia, at extreme altitudes, in subjects who exercise soon after arriving at high altitudes, and in those who are prone to and later develop AMS.
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Probably the most comprehensive human data on body fluid compartments at high altitudes come from studies on Indian soldiers (Jain et al., 1980, 1981; Singh et al., 1986, 1988, 1990). These investigators had the unique advantage of a captive population that they could study at sea level and then again, under strict conditions of complete rest, for a period of up to 12 days after being flown to 3,500 m (11,483 ft). The soldiers lost about 3 percent of body weight during the first 3 days, with a further decrease in weight of about 1 percent during the next 10 days. Total body water (TBW) decreased by about 3.5 percent during the first 3 days but showed no further significant decrease until day 12. Extracellular volume (ECV) fell by a much smaller amount. The most significant change was seen in the plasma volume (PV), which was reduced by about 8 percent on day 3 with a further decrease over the next 10 days. When these changes in body fluid compartment are expressed as percent of body weight, no change in the calculated TBW is noted (), suggesting that the decrease in TBW is in proportion to the decrease in weight.
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Phillips et al. (1969) carried out one of the few studies that tested the effect of prolonged stay at simulated extreme altitudes. They found that sheep kept at 6,200 m (20,341 ft) for up to 32 days had an initial weight loss that later stabilized (). At 10 days, sheep were hypohydrated with a significant decrease in TBW, but by 32 days, the animals had regained all the lost water. PV, unlike results in most other studies, did not change and BV increased. Therefore, the initial response of the body even at extreme altitudes is hypohydration lasting a few days. Thereafter the body fluids normalize. Whether further stay at that altitude would have caused fluid retention was not tested.