High-Altitude Acclimatization PDF

1. Increased Pulmonary Ventilation— Role of Arterial Chemoreceptors Immediate response to low Po2: Arterial chemoreceptors stimulate ventilation (~1.65x normal). Allows ascent to higher altitudes. Prolonged high-altitude exposure (days): Ventilation increases up to 5x normal....

1. Increased Pulmonary Ventilation— Role of Arterial Chemoreceptors Immediate response to low Po2: Arterial chemoreceptors stimulate ventilation (~1.65x normal). Allows ascent to higher altitudes. Prolonged high-altitude exposure (days): Ventilation increases up to 5x normal. Initial CO2 loss reduces Pco2 and increases body fluid pH, temporarily inhibiting respiratory drive. However, this inhibition fades after 2-5 days due to: Mechanism of adjustment over days: Reduced bicarbonate in cerebrospinal fluid and brain tissues restores respiratory center sensitivity. Kidney compensation: Decreases hydrogen ion secretion. Increases bicarbonate excretion. Restores plasma and cerebrospinal fluid pH toward normal. 2. Increase in Red Blood Cells and Hemoglobin During Acclimatization Hypoxia triggers red blood cell production: Hematocrit increases from 40%-45% to about 60%. Hemoglobin concentration rises from 15 g/dl to approximately 20 g/dl. Blood volume also increases: Expands by 20%-30%. Total body hemoglobin increases by 50% or more: Combines effects of increased hematocrit, hemoglobin, and blood volume. 3. Increased Diffusing Capacity During Acclimatization Normal O₂ diffusing capacity: 21 ml/mm Hg/min, increases 3- fold during exercise and high altitude. Contributing factors: Increased pulmonary capillary blood volume expands capillaries, increasing diffusion surface area. Increased lung air volume enlarges the alveolar-capillary interface. Higher pulmonary arterial pressure improves capillary recruitment, particularly in poorly perfused upper lung regions. 4. Peripheral Circulatory Changes During Acclimatization Initial increase in cardiac output: Rises by up to 30%, normalizing as hematocrit increases. Angiogenesis: Growth of systemic capillaries, most prominent in: Animals bred at high altitudes. Active tissues under chronic hypoxia. Right ventricular adaptation: Increased capillary density due to hypoxia and pulmonary hypertension. 5. Cellular Acclimatization to High Altitude Enhanced mitochondrial function: Animals at 13,000–17,000 feet have increased mitochondria and oxidative enzymes. Presumed adaptation in humans: High-altitude-acclimatized individuals likely utilize oxygen more efficiently than sea-level residents. Hypoxia-Inducible Factors (HIFs): The Master Switch for Hypoxia Response Function: DNA-binding transcription factors activated by low oxygen levels. Activated Genes: Vascular Endothelial Growth Factor (VEGF): Promotes angiogenesis. Erythropoietin genes: Stimulate red blood cell production. Mitochondrial genes: Enhance energy utilization. Glycolytic enzymes: Support anaerobic metabolism. Nitric oxide genes: Induce pulmonary vasodilation. Mechanism: HIFs are downregulated in normoxia by HIF hydroxylases. Hypoxia inactivates HIF hydroxylases, enabling HIF complex formation and gene activation. Natural Acclimatization of High-Altitude Natives Population Characteristics: Native populations in the Andes and Himalayas live above 13,000 feet, some even at 19,000 feet. Natives exhibit superior acclimatization compared to lowlanders, even after decades at high altitudes. Key Adaptations: Increased chest size relative to body size: Enhances ventilatory capacity. Larger hearts: Pump extra cardiac output from infancy. Enhanced oxygen delivery: Higher hemoglobin levels. Greater O₂ content in arterial blood despite low Po₂. Efficient oxygen utilization with minimal reduction in venous Po₂. Reduced Work Capacity at High Altitudes and Benefits of Acclimatization Work Capacity Decline: Hypoxia significantly reduces muscle work capacity (cardiac and skeletal). Work capacity decreases proportionally with the reduction in maximum O₂ uptake. Impact of Acclimatization: Acclimatization significantly improves work capacity at high altitudes. At 17,000 feet: Naturally acclimatized natives maintain work output similar to lowlanders at sea level. Acclimatized lowlanders show improvement but cannot match natives' performance. Acute Mountain Sickness and High-Altitude Pulmonary Edema Acute Mountain Sickness: Affects individuals who ascend rapidly to high altitudes. Symptoms appear within hours to 2 days. Two Major Complications: Acute Cerebral Edema: Caused by local vasodilation due to hypoxia. Increases capillary pressure, leading to fluid leakage and cerebral swelling. May involve vascular endothelial growth factor and inflammatory cytokines, causing disorientation. Acute Pulmonary Edema: Caused by uneven pulmonary arteriole constriction due to severe hypoxia. Increases capillary pressure in some lung areas, causing local and spreading edema. Breathing oxygen can reverse symptoms rapidly. Chronic Mountain Sickness Key Effects: Excessively high red blood cell mass and hematocrit. Elevated pulmonary arterial pressure beyond normal acclimatization. Enlargement of the right side of the heart. Decreased peripheral arterial pressure. Congestive heart failure and possible death without descent to lower altitude. Causes: Increased Blood Viscosity: High red cell mass reduces tissue blood flow and oxygen delivery. Pulmonary Vasoconstriction: Lung hypoxia causes widespread arteriole constriction, raising pulmonary pressure and straining the right heart. Increased Pulmonary Shunt: Alveolar arteriolar spasms divert blood to poorly oxygenated nonalveolar vessels, worsening hypoxia. Effects of Acceleratory Forces on the Body Acceleratory Forces in Aviation and Space: Linear acceleration: Felt during takeoff or launch. Deceleration: Experienced at the end of flight or landing. Centrifugal acceleration: Occurs during sharp turns or maneuvers. Body adapts to changes in velocity and direction.. Centrifugal Acceleratory Forces Centrifugal Force During Turns: Formula: f=mv2/r Centrifugal acceleratory force (f): Mass (m): Higher mass increases force. Velocity (v): Force increases with the square of velocity. Radius (r): Force increases with sharper turns (smaller radius). f increases in proportion to the square of the velocity. f is directly proportional to the sharpness of the turn (the less the radius). Measurement in G-Forces: +1 G: Normal gravitational pull. +5 G: Experienced during pull-out from a dive; force is five times body weight. -1 G: Negative G when inverted; body weight counteracts seat belt restraint. Effects of Centrifugal Acceleratory Force on the Body (Positive G) - Circulatory System Blood Pooling: Positive G forces push blood toward the lower body. Venous pressure increases: Standing: ≈450 mm Hg. Sitting: ≈300 mm Hg. Impact on Cardiac Output: Blood pooling reduces the volume returning to the heart. Cardiac output decreases as blood vessels in the lower body dilate. Effects of Centrifugal Acceleratory Force on the Body (Positive G) - Blood Pressure Changes Blood Pressure Response: Initial drop in systolic and diastolic pressures: Falls below 22 mm Hg in the upper body. Baroreceptor reflex recovery: Systolic: ~55 mm Hg. Diastolic: ~20 mm Hg. Critical Thresholds: +4 to +6 G: Causes blackout and unconsciousness. Prolonged exposure can result in death. Effects of Centrifugal Acceleratory Force on the Body - Effects on the Vertebrae Vertebral Risk: High acceleratory forces can cause vertebral fractures. Threshold: About +20 G in a sitting position. Effects of Centrifugal Acceleratory Force on the Body - Negative G Impact of Negative G: Negative G forces centrifuge blood into the head. Head Hyperemia: Up to −4 to −5 G causes intense head hyperemia. Extreme negative G (e.g., −20 G) increases cerebral blood pressure to 300–400 mm Hg. Risks: Brain Protection: Cerebrospinal fluid cushions brain vessels, reducing rupture risk. Redout: Eyes often experience hyperemia, leading to temporary blindness. Protection Against Centrifugal Forces Protective Measures: Abdominal Compression: Tightening abdominal muscles and leaning forward delays blood pooling. Anti-G Suits: Apply positive pressure to legs and abdomen. Water Immersion: Theoretically balances G forces, but lung displacement limits safety to