The fundamental purpose of the cardiorespiratory system is to deliver O2 and nutrients to cells and to remove CO2 and other metabolic products from them. Proper maintenance of this function depends not only on intact cardiovascular and respiratory systems, but also on an adequate number of red blood cells and hemoglobin and a supply of inspired gas containing adequate O2.
Decreased O2 availability to cells results in an inhibition of oxidative phosphorylation and increased anaerobic glycolysis. This switch from aerobic to anaerobic metabolism, the Pasteur effect, maintains some, albeit reduced, adenosine 5´-triphosphate (ATP) production. In severe hypoxia, when ATP production is inadequate to meet the energy requirements of ionic and osmotic equilibrium, cell membrane depolarization leads to uncontrolled Ca2+ influx and activation of Ca2+-dependent phospholipases and proteases. These events, in turn, cause cell swelling, activation of apoptotic pathways, and, ultimately, cell death.
The adaptations to hypoxia are mediated, in part, by the upregulation of genes encoding a variety of proteins, including glycolytic enzymes, such as phosphoglycerate kinase and phosphofructokinase, as well as the glucose transporters Glut-1 and Glut-2; and by growth factors, such as vascular endothelial growth factor (VEGF) and erythropoietin, which enhance erythrocyte production. The hypoxia-induced increase in expression of these key proteins is governed by the hypoxia-sensitive transcription factor, hypoxia-inducible factor-1 (HIF-1).
During hypoxia, systemic arterioles dilate, at least in part, by opening of KATP channels in vascular smooth-muscle cells due to the hypoxia-induced reduction in ATP concentration. By contrast, in pulmonary vascular smooth-muscle cells, inhibition of K+ channels causes depolarization which, in turn, activates voltage-gated Ca2+ channels raising the cytosolic [Ca2+] and causing smooth-muscle cell contraction. Hypoxia-induced pulmonary arterial constriction shunts blood away from poorly ventilated portions toward better ventilated portions of the lung; however, it also increases pulmonary vascular resistance and right ventricular afterload.
Effects on the central nervous system
Changes in the central nervous system (CNS), particularly the higher centers, are especially important consequences of hypoxia. Acute hypoxia causes impaired judgment, motor incoordination, and a clinical picture resembling acute alcohol intoxication. High-altitude illness is characterized by headache secondary to cerebral vasodilation, gastrointestinal symptoms, dizziness, insomnia, fatigue, or somnolence. Pulmonary arterial and sometimes venous constriction causes capillary leakage and high-altitude pulmonary edema (HAPE) (Chap. 5), which intensifies hypoxia, further promoting vasoconstriction. Rarely, high-altitude cerebral edema (HACE) develops, which is manifest by severe headache and papilledema and can cause coma. As hypoxia becomes more severe, the regulatory centers of the brainstem are affected, and death usually results from respiratory failure.
Effects on the cardiovascular system
Acute hypoxia stimulates the chemoreceptor reflex arc to induce venoconstriction and systemic arterial vasodilation. These acute changes are accompanied by transiently increased myocardial contractility, which is followed by ...