The High Altitude Physiology Physical Education Essay

The term high altitude has no precise scientific definition (see section on epidemiology for working definitions). Physiologically, high altitudes are generally accepted as altitudes above 2700 m. At this altitudes the arterial partial pressure of oxygen (PaO2) is around 66 mm Hg giving an arterial oxygen saturation of hemoglobin (SaO2) of 92%. During sleep the resultant hypoventilation produces a further drop of PaO2, and the SaO2 drops significantly due to the sigmoid shape of the hemoglobin oxygen dissociation curve, leading to significant tissue hypoxia. Cardio-respiratory changes are normally seen only above these altitudes. The term extreme altitude (altitudes above 5800M) also has a physiological significance. Long term human survival above these heights is not possible, as the physiological changes of acclimatization cannot compensate for the severity of the hypoxia.

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High altitudes, compared to sea level environments have higher levels of ionizing and non ionizing radiation and lower levels of temperature and barometric pressures. Of these factors, lowered barometric pressure is unique to high altitude, and is the main factor involved in acclimatization and pathogenesis of high altitude disorders. The percentage of oxygen remains the same at all altitudes. However, the drop in ambient barometric pressure results in progressive lowered partial pressures of oxygen with increase in altitude. Figure 1.1 gives the relationship of altitude, barometric pressure and partial pressure of oxygen.

A major environmental hazard at high altitude associated with hypoxia is cold. There is approximately 10 C drop in temperature for every 150 m of altitude. Though low temperatures are not unique to high altitude, the combined effects of hypoxia and cold alters the course of cold related injuries of frostbite and chilblains in terms of severity and incidence. High wind velocities further aggravate the cold due to the wind chill factor.

Mountain air is generally drier than sea level air. This drop in humidity is directly proportional to the drop in temperature. Dry air has important physiological effects. Insensible water loss due to evaporation is increased. The hyperventilation seen at high altitudes further increases the water loss, and the resultant dehydration predisposes to thrombosis. The combination of low temperature and low humidity is subjectively unpleasant.

Solar and ionizing radiation is significantly higher at high altitudes. Radio sensitivity of tissues increases with higher oxygen tension. The potentially harmful effects of the increased ionizing radiation are partly offset due to the hypoxia seen at high altitude. Characteristic changes occur on exposed skin which has been termed as ‘High altitude Dermatopathy’. These changes are similar to histological changes seen in skin on prolonged exposure to solar radiation.

Acclimatization and Adaptation

Native Highlanders are adapted and not merely acclimatized

Indian Army observed that very few Ladakhi soldiers (native highlanders: NHL) were hospitalized for high altitude pulmonary oedema. Some Ladakhi soldiers who were taken to lower altitudes and reinducted to high altitude were studied. Mean pulmonary arterial pressures in NHL on day 1 of induction was significantly lower at 25.8 +/- 6.5 mmHg as compared to 31.9 +/- 9.5 mmHg in Low Landers (P = 0.0002). NHL also had very low Lake Louise acute mountain sickness score (0.278 +/- 0.461 on day 2). This appears to be further evidence that the natives of Ladakh are adapted to hypoxia and not merely acclimatized

Recent studies on sherpas have supported the view that NHL from the Himalayas are adapted to HA.

1. Gupta ML, Rao KS, Anand IS, Banerjee AK, Boparai MS. Lack of smooth muscle in the small pulmonary arteries of the native Ladakhi. Is the Himalayan highlander adapted? Am Rev Respir Dis 1992;145:1201-1204

2. Apte CV. Pulmonary artery pressure in Ladakhi men on exposure to acute hypoxia after a stay at sea level. Indian J Physiol Pharmacol 2004;48(3):321-328.

3. Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A, Sharma D, Ito M, Miwa N, Katsuyama Y, Ota M, Kubo K. Adaptation to high altitude in Sherpas: association with the insertion/deletion polymorphism in the Angiotensin-converting enzyme gene. Wilderness Environ Med. 2008 Spring;19(1):22-9

4. Masayuki Hanaoka, Yunden Droma, Buddha Basnyat, Michiko Ito, Nobumitsu Kobayashi,Yoshihiko Katsuyama, Keishi Kubo, and Masao Ota. Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas. PLoS One. 2012; 7(12)Ascent to high altitude is accompanied by physiological adjustments to cope with the environment stress which constitutes acclimatization. Acclimatization is defined as a reversible, non-inheritable change in the anatomy or physiology of an organism that enable it to survive in stressful environments. Complete acclimatization depends on the altitude and duration of exposure. Adaptation on the other hand involves biochemical, physiological and anatomical changes in the organism which have a genetic basis and is inheritable. Highlanders who have lived for generations at high altitudes show features of adaptation. Acquired acclimatization has qualitatively similar features to adaptation. Failure to acclimatize or loss of acclimatization is the basis of commonly occurring high altitude disorders. Fig. 1.2 illustrates the relationships with some of the high altitude disorders and acclimatization. The main features of acclimatization are related to changes in respiratory, cardiovascular and oxygen transport and delivery systems.


Respiration involves ventilation, diffusion, gas transport and tissue diffusion. All these components are involved in the carriage of oxygen from the ambient air to the respiratory enzymes in the intracellular mitochondria. Oxygen moves along a diffusion gradient from the inspired air to the tissues. The oxygen cascade refers to the gradients at these stages. Acclimatization alters these gradients to improve oxygen availability to the tissues. Fig. 1.3 illustrates these gradients at sea level and at an altitude of 4550 m [1]. As evident from the figure the drop in partial pressure of oxygen at high altitude, and the resultant drops in the gradients for oxygen diffusion is the key problem at high altitude.


At sea level the ambient air has an oxygen partial pressure of 159 mm Hg which drops to 100 mm in the alveoli. This drop is on account of humidification, oxygen uptake and carbon dioxide in the alveoli. Hyperventilation would reduce this oxygen gradient present from the inspired air to the alveoli. At high altitude, ventilation increases as a direct response to hypobaric hypoxia, thereby reducing this oxygen gradient from the inspired to alveolar air. Hyperventilatory response is seen within few hours of ascent to high altitude and increases rapidly over the next few days. There is an increase in both respiratory rate and tidal volume. Increase tidal volume is more predominant. Hyperventilation usually begins when alveolar oxygen tension drops to around 55 mm Hg. The initial hyperventilation is mediated by the peripheral chemoreceptors in the aortic and carotid bodies. On complete acclimatization chemoreceptor induced hyperventilation can occur with partial pressures of oxygen as high as 90 mm Hg. [2]

The hypoxia induced hyperventilation leads to drop in arterial carbon dioxide tension and arterial pH rises. The resultant respiratory alkalosis is compensated by renal excretion of bicarbonate. This metabolic compensation is slow. The drop in arterial carbon dioxide would lead to alkalosis in the cerebrospinal fluid (CSF), thereby inhibiting the central medullary chemoreceptors. However other studies have shown a rise in CSF pH on ascent to high altitude. The strong peripheral chemoreceptor drive is offset by lowered activity of the medullary chemoreceptors. However, the activity of the respiratory centres is restored as the sensitivity to carbon dioxide increases within by eight to ten days of ascent.

A blunted hypoxic chemoreceptor ventilatory response obstructs the process of acclimatization and is a predisposing factor for high altitude related disorders.

Pulmonary Diffusion

Arterial oxygen tension is lower than the alveolar oxygen tension. This Alveolar to arterial difference (A-a difference) is normally around 6 mm Hg at sea level below the age of 40 yrs and can increase to 17 mm Hg in people above 40 yrs. The anatomical diffusion barrier contributes partly to this difference. A second factor is the physiological shunts due to admixture of venous blood from the bronchial and Thebesian veins, and another shunting due to the uneven ventilation-perfusion ratios in the lung. The A-a difference found at sea level is not of much significance, as the oxygen carriage in blood is not affected due to this difference. At high altitude, the prevalent partial pressure of oxygen lies on the steep portion of the hemoglobin oxygen dissociation curve, and a small drop in oxygen tension would cause significant drop in SaO2 . A-a difference is reduced at high altitude. Increase in lung diffusion capacity is a significant factor. [3]. One of the factors for this reduction is the decrease in alveolar capillary wall thickness, effectively increasing the diffusion capacity. This is strikingly seen in highlanders. Native highlanders at 4270 m were found to have an A-a difference of only 2 mm Hg . Thinning of the alveolar-capillary wall is not evident in acclimatized lowlanders.

A second factor that operates in reducing the A-a difference is improvement in the ventilation perfusion ratio of the lung. Elevation of pulmonary artery pressures due to the hypoxic pulmonary vasoconstriction, leads to more uniform perfusion especially in the upper zones that were less perfused at sea level. Rise in pulmonary artery pressure is uniformly seen in all acclimatized lowlanders and contributes to a reduction in A-a difference and better arterial oxygen tensions.

Oxygen Transport

The tissues normally require about 250 ml per minute of O2 at rest. The amount of oxygen transported and released to the tissues is a function of the cardiac output, SaO2 , and affinity of hemoglobin with oxygen. Despite the hyperventilation and reduction in A-a difference arterial oxygen tension at high altitude remains lower than at sea level. To ensure adequate oxygen availability to the tissues there is increase in hemoglobin, increased cardiac output, and a reduced affinity of hemoglobin with oxygen. Increase in hemoglobin concentration is generally seen in all lowlanders on ascent to high altitude. The extent of the increase depends on the magnitude of the elevation and duration of the exposure. Highlanders, on the other hand may have a minimal increase especially in Himalayan highlanders. Hemoglobin increases within few days of ascent, and returns to sea level values within 20 days of descent. Hemoglobin levels of 17.8 to 20.6 g/dL have been seen at extreme altitudes between 5350m and 6300m [4]. The initial increase immediately on ascent may be due to haemoconcentration, as there is an immediate diuresis on ascent to high altitude in the majority of lowlanders leading to decrease in plasma volumes by 15 to 20%. (Absence of this diuresis leads to fluid retention and has been implicated in the pathogenesis of acute mountain sickness.) Subsequent increase is due to increased erythropoiesis resulting in increase in total blood volume.

The rise in hemoglobin and hematocrit is mediated through release of erythropoietin. Erythropoietin levels rise within hours of ascent to high altitude, and fall subsequently over the next few days, although the levels remain higher than the sea level values. This secondary fall is due to the improvement in arterial oxygen tension following the hyperventilation and drop in A-a difference. The levels of erythropoietin relate to the hypoxia and the altitude. However, in severe hypoxia seen at altitudes above 6000m erythropoietin levels start to decline on further ascent.

The increase in hemoglobin levels compensate for the drop in SaO2 . This compensation brings the oxygen content of blood to values similar to sea level values up to altitudes of 5300 m. Increased hematocrit though beneficial, increases the viscosity of blood. Hematocrits above 50% significantly lower tissue blood flow due to the higher viscosity, and offset the beneficial value of increased hematocrit. Brief ascents to extreme altitude may show changes in red cell morphology, including echinocytes. The altered morphology further contributes to the increase in viscosity.

Oxygen Release

Hyperventilation, reduction in A-a difference and increased hemoglobin and hematocrit ensure that oxygen content in blood is brought closer to sea level values on ascent to high altitude. Adequate release of the oxygen from the blood depends on the affinity of hemoglobin with oxygen. The partial pressure of oxygen at which hemoglobin is 50% saturated at a pH of 7.4 and temperature of 370 C is termed as P50. P50 of adult whole blood at a carbon dioxide tension of 40 mmHg, pH of 7.4 and a temperature of 370 C is 26-27 mm Hg. Lowered P50 increases the affinity of hemoglobin to oxygen, and an increased P50 decreases the affinity of hemoglobin to oxygen. At high altitude P50 increases and shifts the hemoglobin oxygen dissociation curve to the right. This rightward shift reduces the affinity of hemoglobin to oxygen and favors offloading the oxygen from hemoglobin. The shift is due to stabilization of the de-oxygenated form of hemoglobin, and is seen with increase in carbon dioxide tension, drop in pH (Bohr’s effect) and increase in levels of 2,3 Diphosphoglycerate (2,3 DPG). 2,3 DPG is generated by the anaerobic glycolytic pathway in the RBCs. One mole of 2,3 DPG increases the P50 of hemoglobin by 0.5 mm Hg. 2,3 DPG levels rise occurs within hours of ascent [5]. Alkalosis favors the formation of 2,3 DPG. The respiratory alkalosis occurring at high altitude due to hyperventilation increases 2,3 DPG levels. The increase in 2,3 DPG levels are higher in active people compared to sedentary ones. The rightward shift of the hemoglobin dissociation curve though beneficial at high altitude, would aggravate the hypoxia at extreme altitude, as the reduced affinity would interfere with hemoglobin oxygenation at the alveoli.

In native highlanders (Quechuas) the rightward shift with lowering of pH is increased. This increased ‘Bohr’s effect’ further helps in offloading the available oxygen to the tissues.

Tissue Diffusion/ Utilization

The factors discussed above enhance oxygen availability from the blood to the tissues at high altitude. Additional changes in muscle further improve oxygen availability and usage. Increase in capillary density and a decrease in the muscle fibre size would reduce the distance oxygen has to traverse from the capillary to the mitochondria. Himalayan native highlanders (Sherpas ) have an average muscle fibre cross sectional area of 3186 m2 compared to sedentary sea level inhabitants who have average cross sectional area of 3640 m2. The capillary density in Sherpa is 467 / m m2 compared to 387 / m m2 found in sedentary sea level inhabitants [6]. Sustained stay at extreme altitudes is associated with progressive loss of muscle mass due to muscle protein catabolism, and this could account for some of the observed decrease in muscle fibre diameter seen in sojourners to extreme altitude. Increased capillary density reported may be due to capillary recruitment rather than angiogenesis.

Myoglobin levels increase in muscle in man on ascent to high altitude. Myoglobin is an iron containing protein which combines loosely and reversibly with oxygen. The myoglobin oxygen dissociation curve is parabolic. The shape of the curve causes myoglobin to be 70% saturated at oxygen partial pressures of 10 mm Hg, compared to a 10% saturation of hemoglobin at the same oxygen tension. The presence of myoglobin facilitates diffusion of oxygen to the cell .

Mitochondrial enzymatic activity is altered at high altitude. Enzymes of electron transport chain are significantly higher in native highlanders. Ascent to extreme altitudes decreases levels of succinate dehydrogenase an enzyme involved in Krebs cycle.

Systemic Circulation

Ascent to high altitude induces tachycardia. The tachycardia is due to increased sympathetic activity as evidenced by the rise in urinary and plasma catecholamines. Despite the tachycardia there is a drop in cardiac output indicating a drop in stroke volume. One factor leading to decreased stroke volume is the diminished venous return. Hypoxia also has a direct depressing action on myocardium and leads to reduction in stroke volume. Stroke volumes may drop by 20 to 25% of sea level values. The maximum decline occurs by the tenth day, descent to sea level restores stroke volume to normal levels. The reduction in cardiac output is more prominent in lowlanders on ascent to high altitude compared to highlanders.

The reduced systemic blood flow is redistributed. Renal blood flow is decreased in lowlanders on ascent to high altitude and in highlanders. Renal function is not impaired as there is an increased filtration fraction.

Plasma volume normally decreases on ascent to high altitude. There is usually an alkaline diuresis. Lack of diuresis is a feature seen in patients suffering from acute mountain sickness. The reduction in plasma volume is sustained on continued stay at high altitude. Though the plasma volume is reduced, the total blood volume increases after two to three weeks of residence at high altitude. The increase in blood volume is a result of the higher hematocrit. Patients of chronic mountain sickness show higher blood volumes due to raised hematocrit. Vigorous exercise at high altitude expands the plasma volume. Peripheral vasoconstriction shifts the blood from the periphery causing higher right atrial pressures. This leads to release of atrial natriuretic peptide, causing sodium and water loss, thereby reducing the plasma volume. Hypoxia directly stimulates ANP (Atrial Natriuretic Polypetide) gene expression and ANP release in cardiac myocytes in vitro [7, 8].

Western studies show a slightly reduced systemic blood pressure in sojourners to high altitude and in native highlanders of the Andes. In the Indian context raised blood pressures have been reported in lowlanders on ascent to high altitude and also in native highlanders of Ladakh. High intake of salt and butter in the local tea consumed by native ladakhis contributes to the hypertension. Hypertension seen in sojourners to high altitude in the Indian context is probably related to increased norepinephrine secretions[9]. Rise in blood pressure on ascent to HA has also been reported in the Andes [10].

Pulmonary Circulation

Native highlanders in the Andes have a mild degree of pulmonary hypertension with remodeling of the pulmonary vasculature which shows a characteristic muscularisation. Native highlanders in Ladakh on the contrary show lower pulmonary artery pressures with a lack of smooth muscle in the pulmonary vasculature (see text box) [11].

Pulmonary hypertension on exposure to hypoxia results from sustained vasoconstriction. Compared with an average of 22/6 mm Hg ( mean 12 mm Hg) of pulmonary artery pressures seen in sea level residents adults at high altitude show pulmonary artery pressures of 41/15 mm Hg (mean 28 mm Hg). Pulmonary wedge pressures are not elevated. Pulmonary vascular resistance increases from 159 dynes/ cm-5 seen at sea level to 401 dynes/ cm-5 at high altitude. Young children between ages 1 to 5 show higher pulmonary artery pressures at high altitude. Exercise increases pulmonary artery pressures and wedge pressures. Mean pulmonary artery pressures at high altitude have been reported to increase to 60 mm Hg during exercise. Thus, exercise may be a predisposing factor for the development of high altitude pulmonary edema. Hypoxic pulmonary vasoconstriction is a homeostatic, vasomotor response of pulmonary arterioles to alveolar hypoxia. The hypoxic pulmonary vasoconstriction ensures better ventilation-perfusion matching. Improved ventilation perfusion ratios, reduce the shunt fraction and enhances the arterial oxygen tension. Hypoxic pulmonary vasoconstriction is modulated by the endothelium. The core mechanisms for vasoconstriction are in the smooth muscle. The vasoconstriction is mediated by voltage gated potassium (K(v)) and calcium channels. Inhibition of O(2)-sensitive K(v) channels, particularly K(v)1.5 and K(v)2.1, depolarizes pulmonary artery smooth muscle cells, activating voltage-gated Calcium channels and causing Ca(2+) influx and vasoconstriction [12]. Low endogenous Nitric Oxide levels in pulmonary vessels contribute to the enhanced hypoxic pulmonary vascular response in individuals susceptible to high altitude pulmonary edema.

The hypoxic vasoconstriction is central to the development of high altitude pulmonary edema. The vasoconstriction is non uniform and patchy. Patchy vasoconstriction exposes parts of the capillary bed to high pressure resulting in stress failure. Raised hypoxic vasoconstrictive responses are seen in subjects susceptible to high altitude pulmonary edema.

On exposure to hypoxia, the initial rise in pulmonary vascular resistance is largely due to vasoconstriction. Sustained exposure to hypoxia, leads to structural changes in the pulmonary vascular bed and may become the major determinant of elevated vascular resistance. Due to the remodeling of the vasculature, on return to sea levels there is an immediate drop in pulmonary artery pressures (due to vasodilatation), however the pulmonary arterial pressure remains elevated above normal values for a longer duration. This persistence of the elevated pressures has a role in the observed increased susceptibility of reinductees to high altitude pulmonary edema.

Remodeling results in thickening of the arterial wall. This wall remodeling is due to muscularisation of previously non-muscular arterioles, medial thickening of muscular arterioles, adventitial hypertrophy and deposition of additional matrix components, including collagen and elastin, in the vascular walls. The sustained pulmonary hypertension is an invariable feature seen in sojourners and residents of high altitude. However, native highlanders of Ladakh have significantly lower pulmonary artery pressures and there is no muscularisation of the pulmonary vasculature. It is also observed that these natives compared to highlanders of the Andes are not susceptible to high altitude pulmonary edema, and chronic mountain sickness. It has been argued that Himalayan highlanders show features of adaptation to high altitude, whereas, the Andes highlanders are essentially lowlanders fully acclimatized to high altitude.

High altitude related pulmonary hypertension has a key role in the pathogenesis of right ventricular failure, sub acute adult mountain sickness, and in the commonly seen ECG changes at high altitude.

Chronic hypoxia and pulmonary hypertension seen at high altitude leads to high incidence of patent ductus arteriosus in infants born at high altitude. In a study done at Peruvian Andes the prevalence was 18 times more than at sea levels.

Endocrines [13]

High altitude environments have a profound effect on most of the endocrine glands. Hypoxia is no doubt the major factor affecting endocrine function. Associated low temperatures and exercise are also factors affecting endocrine function.

Antidiuretic hormone (ADH) levels generally show a fall on ascent to high altitude. Diuresis, commonly seen on ascent is associated with reduction in antidiuretic hormone levels. The drop in ADH levels is probably related to inhibitory impulses arising from the right atrium. The right atrium is distended due to increased blood volume and pulmonary hypertension seen at high altitude.

Thyroid hormones are the main hormones regulating oxygen consumption. Most human studies suggest increased thyroid activity at high altitude. High altitude environments are relatively iodine deficient, and secondly the natural high altitude environment is associated with low temperatures, which is known to affect thyroid function. Studies on 24 hour I131 uptake at 4300 m have shown a rise from 34% seen at sea level to 51.4%. There was no change in the basal metabolic rate. T3 and T4 are elevated at high altitude, however, TSH levels are unchanged, indicating that the increased activity is not mediated through the pituitary. The raised levels return towards control values by the third week and again rise. These findings are consistent with the reports on basal metabolic rate , which is seen to increase on ascent to high altitude and reduces by third week and then rises again. At altitudes above 5500 m rise in basal metabolic rate may persist.

Adrenocortical activity increases on exposure to hypoxia. The increase in activity is related to raised adrenocorticotrophic hormones released by the pituitary. Histological changes seen in the pituitary and adrenals are consistent with the view that both the structures are stimulated at high altitude. Abnormally high levels of urinary 17 hydroxy corticosteroids are seen on exposure to extreme altitudes exceeding 8000m.

Aldosterone levels are depressed on ascent to high altitude. Low aldosterone levels contribute to the diuresis seen on ascent to high altitude. The fall in aldosterone levels is probably mediated by the stretch of the right atrium, which is known to depress aldosterone release. The fall in aldosterone levels is more prominent in older subjects.

ANP is released mainly from the right atrium. Right atrial stretch increases levels of the hormone at high altitude. Hypoxia may have an additional direct stimulatory effect on the release of atrial natriuretic hormone. Atrial natriuretic peptide may have a role in the pathophysiology of high altitude pulmonary edema as it increases vascular permeability.

Ascent to high altitude raises blood glucose levels. The rise may persist for months and subsequently fall. The rise in glucose levels immediately on ascent may be the result of increased sympathetic activity and raised cortisol levels. Native highlanders show reduction in glucose levels compared to lowlanders at sea level.[14]

Other Changes

Renal Function

Renal function is essentially normal at moderate altitudes. At extreme altitudes beyond 5800 m, the renal compensation for respiratory alkalosis is slow and is incomplete. At these altitudes bicarbonate excretion is inadequate and leads to increasing alkalosis. The alkalosis may have a beneficial effect at extreme altitude as it shifts the hemoglobin oxygen dissociation curve to the left, increasing affinity of hemoglobin to oxygen. This increased affinity benefits oxygen transfer at the alveolar level. Proteinuria is present in native highlanders and lowlanders on ascent to high altitude. The protein concentration in early morning samples correlates with altitude. High levels of proteinuria is often seen in patients with acute mountain sickness. Proteinuria is probably caused due to decreased protein reabsorption from the tubules as a direct effect of hypoxia. Increased capillary permeability secondary to hypoxia contributes to a greater filtered load which may exceed reabsorptive capabilities of the tubule. As described earlier, diuresis commonly occurs on ascent to high altitude due to decreased antidiuretic hormone and aldosterone. Natriuresis is often seen after one to two days of ascent to high altitude and correlates with decreased aldosterone levels. A Hurtado and others have suggested a new clinical syndrome termed high altitude renal syndrome (HARS) in view of their patient series at HA presenting with systemic hypertension, microalbuminuria and relatively preserved GFR coupled with polycythemia and hyperuricemia. ACE inhibitors was effective at reducing proteinuria and lowering hemoglobin levels in these patients.[15]

Coagulation Disorders

High altitude environment induces a hypercoagulability state. The increased hematocrit predisposes the individual to thrombotic episodes. At extreme altitudes thrombotic episodes is a hazard and often presents as pulmonary thromboembolism, commonly following thrombophlebitis in the lower limbs. Increased platelet counts, higher levels of factors X and XII have been reported. Prothrombin time and clotting time shortens, with impaired clot retraction. The hypercoagulability is partly offset by an increase in fibrinolytic activity. The hypercoagulability state is more prominent on ascent and decreases with prolonged stay at altitude.Hemostatic parameters of D Dimer, PT, aPTT has shown an increase on ascent to HA, along with decrease in von Willebrand Factor activity. [16]. The hypercoagulability has been implicated in the pathogenesis of high altitude pulmonary edema and cerebral edema. Thrombosis in pulmonary arteries and dural venous sinuses is a common necropsy finding in high altitude pulmonary edema and cerebral edema. However pulmonary thrombosis in high altitude pulmonary edema is more likely to follow edema formation rather than be a causative factor in the development of pulmonary edema. The hypercoagulability state at high altitude coexist with increased incidence of hemorrhage. The mechanism for the increase in hemorrhagic events is due to increased capillary friability. The increased capillary friability often presents as epistaxis. Systemic hypertension seen on ascent aggravates the epistaxis. Gastric hemorrhages are also commonly seen at high altitude due to the increased capillary fragility.

Body Weight and Nutrition

Weight loss is seen in most sojourners to high altitude. The weight lost is related to the altitude and duration of stay. Prolonged stay at extreme altitude often leads to emaciation. The initial weight loss of one to two kg seen on ascent to high altitude is probably due to the dehydration following the diuresis. Low humidity aggravates the dehydration due to evaporative loss of water coupled with the hyperventilation due to hypoxia. Increase in basal metabolic rate combined with anorexia and hypophagia seen in the initial couple of weeks of ascent contributes further to the weight loss. Increased metabolic rate is associated with the increased sympathetic activity which occurs on ascent. Acute mountain sickness is a common disorder seen on ascent to high altitude. Headache and nausea which are common features of acute mountain sickness may be the basis for hypophagia. Loss of body fat accounts for the weight loss in moderate altitudes. At extreme altitudes catabolism of muscle protein is more prominent. Weight loss at extreme altitude occurs despite increased supplementary protein intake. There is a preference for carbohydrate over fat in food intake. A craving for sweets is often reported by sojourners to high altitude. Fat absorption is significantly decreased in high altitude. The malabsorption is more prominent at extreme altitudes and contributes to the weight loss. Raised levels of leptin have been implicated as a causative mechanism for hypophagia. Members of a Himalayan expedition lost weight ranging from 6.5 to 9 kg. Native highlanders of the Himalayan region (Sherpas) maintain body weight on ascent to extreme altitude, as protein catabolism is not seen these highlanders.


Sleep disturbances are common in lowlanders on ascent to high altitude. The quality of sleep deteriorates. Stages I and II of non rapid eye movement sleep (NREM) is increased, deeper NREM stage III and stage IV sleep is decreased. Rapid eye movement sleep shows a decrease on ascent to high latitude. Sleep at high altitude is associated with periodic breathing with apnea. This periodic breathing (Cheyne Stoke pattern) is associated with hypoxia. The ventilatory drive is