Overview High altitude → ↓ atmospheric pressure (Patm) and ↓ alveolar PO2 Ventilation ↓ alveolar PO2 → ↑ respiratory rate (hyperventilation) ↓ alveolar PO2 stimulates peripheral chemoreceptors in aortic bodies and carotid bodies to instruct medullary inspiration center to increase respiratory rate Arterial blood ↑ ventilation rate → ↑ PaO2 and ↓ PaCO2 → respiratory alkalosis CO2 + H2O → H2CO3 → H+ + HCO3- ↓ CO2 shifts equilibrium left ↓ H+→ ↑ pH respiratory alkalosis → ↑ renal HCO3- excretion carbonic anhydrase inhibitors (e.g., acetazolamide) → ↑ renal HCO3- excretion and create a metabolic acidosis, which can be used to "acclimate" someone going to a higher altitude because they will naturally increase ventilation to compensate for metabolic acidosis Pulmonary blood flow ↓ alveolar PO2 → hypoxic vasoconstriction of pulmonary vasculature → ↑ pulmonary vasculature resistance → ↑ pulmonary arterial pressure pulmonary arterial pressure increases to maintain a constant blood flow right ventricle pumps against ↑ pulmonary arterial pressure (↑ afterload) chronic hypoxic vasoconstriction of pulmonary vasculature causes cor pulmunale (right ventricular hypertrophy (RVH)) Cerebral blood flow primarily controlled by PCO2 ↓ PCO2 → vasoconstriction therapeutic hyperventilation (↓ PCO2) → ↓ intracranial pressure by decreasing cerebral perfusion used in cases of cerebral edema effect is usually only temporary PO2 can have effects during severe hypoxic events ↓ PO2 → vasodilation and ↑ cerebral perfusion pressure Cellular changes chronic hypoxia → ↑ erythropoietin → ↑ hemoglobin concentration and ↑ hematocrit synthesis of erythropoietin in kidneys erythropoietin acts on bone marrow to stimulate RBC synthesis ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content synthesis of erythropoietin in kidneys erythropoietin acts on bone marrow to stimulate RBC synthesis ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content synthesis of erythropoietin in kidneys erythropoietin acts on bone marrow to stimulate RBC synthesis ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content ↑ mitochondria synthesis of erythropoietin in kidneys erythropoietin acts on bone marrow to stimulate RBC synthesis ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content Oxygen-hemoglobin dissocation curve ↑ 2,3-BPG → shifts to right ↓ hemoglobin affinity for O2 → ↑ O2 unloading