Physiological Changes at High Altitude

Introduction

High altitude presents a unique physiological challenge because reduced atmospheric oxygen availability produces hypoxia. The body activates multiple adaptive mechanisms to preserve tissue oxygenation; however, rapid ascent to extreme altitudes may overwhelm these compensatory responses and can result in life-threatening complications.

• The physiological effects of high altitude result primarily from reduced inspired oxygen tension rather than a decrease in the percentage of oxygen in air.
• At high altitude, atmospheric oxygen concentration remains approximately 21 percent, but barometric pressure progressively decreases.
• The fall in barometric pressure lowers the partial pressure of inspired oxygen, producing hypoxemia.
• Symptoms of altitude-related hypoxia commonly appear above 10,000 feet (3,000 meters) and become more severe between 15,000 and 18,000 feet.
• At altitudes exceeding 20,000 feet (6,000 meters), barometric pressure is nearly half of sea-level values.
• Slow, staged ascent permits acclimatization, thereby reducing the severity of hypoxic manifestations.

Compensatory Mechnisms

• High altitude reduces inspired oxygen tension, decreasing oxygen delivery to tissues.
• To maintain tissue oxygenation, several compensatory mechanisms are activated, the most important being hyperventilation.
• Hypoxia-induced hyperventilation becomes prominent when alveolar oxygen tension falls below approximately 60 millimeters of mercury, which usually occurs at an altitude of about 4,500 meters (14,000 feet).

Stages of Compensation

In First Stage

• The initial response occurs immediately after exposure to high altitude.
• Ventilation increases rapidly, primarily because of stimulation of peripheral chemoreceptors in the carotid bodies.
• However, the increase in ventilation is relatively modest.
• Hyperventilation lowers arterial carbon dioxide tension by increasing carbon dioxide elimination.
• The resulting hypocapnia produces respiratory alkalosis.
• Reduced carbon dioxide tension and increased blood pH suppress respiratory center activity and partially oppose the hypoxic ventilatory drive.

In Second Stage

• A more sustained increase in ventilation develops gradually over the next 8 to 10 hours.
• This prolonged response is termed ventilatory acclimatization and occurs during continued exposure to hypoxia.
• Hyperventilation progressively increases and generally reaches a stable plateau after approximately two weeks.
• One mechanism involves changes in chemoreceptor sensitivity.
• During the acute phase, cerebrospinal fluid becomes alkaline because of hypocapnia.
• With continued exposure, bicarbonate ions are removed from cerebrospinal fluid, restoring its pH toward normal and permitting greater respiratory stimulation.
• Prolonged hypoxia also enhances the sensitivity of carotid body chemoreceptors to reduced arterial oxygen tension.
• A second mechanism involves renal compensation.
• The kidneys respond to respiratory alkalosis by increasing bicarbonate excretion.
• This renal adjustment gradually lowers blood pH toward normal, usually within about three days.
• Correction of alkalosis reduces inhibition of the respiratory centers, allowing the hypoxic drive to increase minute ventilation and maintain a new steady state.

Acclimatization at High Altitude

• Acclimatization refers to the gradual physiological adaptation that occurs during prolonged exposure to high altitude.
• The process begins within approximately 12 hours of ascent and may require several days to weeks for completion.
• The principal aim of acclimatization is to improve oxygen delivery to tissues despite reduced ambient oxygen availability.
• Adaptive changes involve the respiratory system, cardiovascular system, blood, and peripheral tissues.
• Effective acclimatization generally occurs up to altitudes of about 18,000 feet (5,500 meters).
• At greater altitudes, supplemental oxygen therapy is often required for prolonged survival.

Respiratory Changes

• High-altitude hypoxemia stimulates peripheral chemoreceptors, particularly the carotid bodies.
• This increases both the rate and depth of breathing, resulting in sustained hyperventilation.
• Hyperventilation lowers arterial carbon dioxide tension, producing respiratory alkalosis.
• Respiratory alkalosis initially opposes the stimulatory effect of hypoxia on ventilation.
• The kidneys compensate by increasing bicarbonate excretion, causing alkaline urine and gradually restoring blood pH toward normal.
• Renal compensation allows the hypoxic ventilatory drive to persist and maintain elevated ventilation.
• Adjustment of cerebrospinal fluid acid-base balance further enhances ventilatory acclimatization during prolonged exposure.·  Although ventilatory responses may partially decline after several days, ventilation remains higher than sea-level values.
• The magnitude of hyperventilation increases with increasing altitude.
• The ventilatory equivalent, defined as the ratio of minute ventilation to oxygen consumption, rises progressively with altitude and is a useful indicator of ventilatory adaptation.
• Permanent high-altitude residents exhibit increased pulmonary oxygen diffusion capacity and greater maximal voluntary ventilation.

Hematological Changes

• High-altitude hypoxia stimulates renal production of erythropoietin, which enhances erythrocyte formation.
• Erythropoiesis usually begins within approximately three days of exposure and continues as long as hypoxia persists.
• Increased red cell mass and hemoglobin concentration improve oxygen transport to tissues.
• Hypoxia also increases the concentration of 2,3-bisphosphoglycerate in erythrocytes.
• Elevated 2,3-bisphosphoglycerate shifts the oxyhemoglobin dissociation curve to the right, facilitating oxygen unloading at the tissue level.
• Although acute respiratory alkalosis initially shifts the curve to the left, increased 2,3-bisphosphoglycerate eventually predominates and enhances tissue oxygen delivery.

Cardiovascular Changes

• During the early phase of high-altitude exposure, heart rate, cardiac output, and arterial blood pressure increase.
• These responses result primarily from activation of the sympathetic nervous system by hypoxemia.
• With acclimatization, heart rate gradually returns toward normal, although some individuals may continue to exhibit elevated arterial pressure.
• Increased cardiac output enhances tissue perfusion and improves oxygen delivery.
• Hypoxemia also produces systemic vasodilation, further increasing blood flow to peripheral tissues.
• Marked polycythemia improves oxygen-carrying capacity but also increases blood viscosity.
• Increased blood viscosity raises cardiac workload and may lead to ventricular hypertrophy during prolonged exposure.

Tissue Changes

• Long-term adaptation to high altitude produces several changes, particularly in skeletal muscle.
• Capillary density increases, improving oxygen diffusion to tissues.
• The number of mitochondria within cells increases.
• Activities of oxidative enzymes, such as cytochrome oxidase, are enhanced.
• Myoglobin concentration increases, facilitating intracellular oxygen storage and transport.
• Hypoxia also stimulates angiogenesis, resulting in the formation of new blood vessels.

Other Changes

• Described in “Environmental Physiology”

High Altitude Illness

Types of Illness

High-altitude illness includes acute mountain sickness, chronic mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema.

Acute Mountain Sickness

• Acute mountain sickness develops after rapid ascent to high altitude without adequate acclimatization.
• Symptoms usually appear within 4 to 8 hours of arrival and may persist for several days.
• Common manifestations include fatigue, dyspnea, headache, nausea, vomiting, insomnia, palpitations, and gastrointestinal disturbances.
• Neurological symptoms such as impaired coordination, reduced judgment, memory disturbances, and emotional changes may also occur.
• Severe hypoxemia can progress to high-altitude pulmonary edema or high-altitude cerebral edema.

Chronic Mountain Sickness (Monge’s Disease)

• Chronic mountain sickness develops after prolonged residence at high altitude.
• Affected individuals may experience malaise, fatigue, exercise intolerance, and excessive erythrocytosis.
• Persistent hypoxemia may lead to hypervolemia, pulmonary hypertension, right ventricular hypertrophy, and eventually right-sided heart failure.

Pulmonary Hypertension and Edema

• Chronic alveolar hypoxemia causes persistent pulmonary vasoconstriction, increasing pulmonary arterial pressure.
• Prolonged hypoxia induces hypertrophy and hyperplasia of pulmonary vascular smooth muscle, resulting in narrowing of pulmonary vessels.
• Elevated pulmonary capillary pressure promotes fluid leakage into alveoli, producing high-altitude pulmonary edema.
• Pulmonary hypertension increases the workload on the right ventricle and may eventually cause right ventricular failure.

Cerebral Edema

• Increased cerebral capillary permeability leads to cerebral edema.
• Clinical manifestations include severe headache, confusion, disorientation, and ataxia.
• Untreated cases may progress to coma and can be fatal because of brain herniation.

Treatment of High Altitude Illness

• Immediate descent to a lower altitude is the most effective treatment for severe altitude illness.
• Supplemental oxygen therapy rapidly improves hypoxemia and is essential in severe cases.
• Acetazolamide is commonly used because it promotes bicarbonate excretion, corrects alkalosis, and facilitates acclimatization.
• Glucocorticoids, particularly dexamethasone, are effective in reducing cerebral edema.
• Nifedipine lowers pulmonary arterial pressure and is useful in high-altitude pulmonary edema.
• Additional supportive treatment should be provided according to clinical severity.