Chapter 035. Hypoxia and Cyanosis (Part 1)

Harrisons Internal Medicine Chapter 35. Hypoxia and CyanosisHYPOXIAThe fundamental task of the cardiorespiratory system is to deliver O 2 (and substrates) to the cells and to remove CO2 (and other metabolic products) from them. Proper maintenance of this function depends on intact cardiovascular and respiratory systems, an adequate number of red blood cells and hemoglobin, and a supply of inspired gas containing adequate O2. Effects Decreased O2 availability to cells results in an inhibition of the respiratory chain and increased anaerobic glycolysis. This switch from aerobic to anaerobic metabolism, Pasteurs effect, maintains some, albeit markedly reduced, adenosine triphosphate...
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Chapter 035. Hypoxia and Cyanosis (Part 1) Chapter 035. Hypoxia and Cyanosis (Part 1) Harrisons Internal Medicine > Chapter 35. Hypoxia and Cyanosis HYPOXIA The fundamental task of the cardiorespiratory system is to deliver O 2 (andsubstrates) to the cells and to remove CO2 (and other metabolic products) fromthem. Proper maintenance of this function depends on intact cardiovascular andrespiratory systems, an adequate number of red blood cells and hemoglobin, and asupply of inspired gas containing adequate O2. Effects Decreased O2 availability to cells results in an inhibition of the respiratorychain and increased anaerobic glycolysis. This switch from aerobic to anaerobicmetabolism, Pasteurs effect, maintains some, albeit markedly reduced, adenosinetriphosphate (ATP) production. In severe hypoxia, when ATP production isinadequate to meet the energy requirements of ionic and osmotic equilibrium, cellmembrane depolarization leads to uncontrolled Ca2+ influx and activation of Ca2+-dependent phospholipases and proteases. These events, in turn, cause cell swellingand ultimately cell necrosis. The adaptations to hypoxia are mediated, in part, by the upregulation ofgenes encoding a variety of proteins, including glycolytic enzymes such asphosphoglycerate kinase and phosphofructokinase, as well as the glucosetransporters Glut-1 and Glut-2; and by growth factors, such as vascular endothelialgrowth factor (VEGF) and erythropoietin, which enhance erythrocyte production. During hypoxia systemic arterioles dilate, at least in part, by opening ofKATP channels in vascular smooth-muscle cells due to the hypoxia-inducedreduction 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 causingsmooth-muscle cell contraction. Hypoxia-induced pulmonary arterial constrictionshunts blood away from poorly ventilated toward better-ventilated portions of thelung; however, it also increases pulmonary vascular resistance and rightventricular afterload. EFFECTS ON THE CENTRAL NERVOUS SYSTEM Changes in the central nervous system, particularly the higher centers, areespecially important consequences of hypoxia. Acute hypoxia causes impairedjudgment, motor incoordination, and a clinical picture resembling acutealcoholism. High-altitude illness is characterized by headache secondary to cerebralvasodilatation, and by gastrointestinal symptoms, dizziness, insomnia, and fatigue,or somnolence. Pulmonary arterial and sometimes venous constriction causecapillary leakage and high-altitude pulmonary edema (HAPE) (Chap. 33), whichintensifies hypoxia and can initiate a vicious circle. Rarely, high-altitude cerebraledema (HACE) develops. This is manifest by severe headache and papilledema and can cause coma.As hypoxia becomes more severe, the centers of the brainstem are affected, anddeath usually results from respiratory failure. Causes of Hypoxia RESPIRATORY HYPOXIA When hypoxia occurs consequent to respiratory failure, PaO2 declines, andwhen respiratory failure is persistent, the hemoglobin-oxygen (Hb-O2)dissociation curve (see Fig. 99-2) is displaced to the right, with greater quantitiesof O2 released at any level of tissue PO2. Arterial hypoxemia, i.e., a reduction of O2 saturation of arterial blood(SaO2), and consequent cyanosis are likely to be more marked when suchdepression of PaO2 results from pulmonary disease than when the depressionoccurs as the result of a decline in the fraction of oxygen in inspired air (FIO2). Inthis latter situation, PaCO2 falls secondary to anoxia-induced hyperventilation andthe Hb-O2 dissociation curve is displaced to the left, limiting the decline in Sa O2 atany level of PaO2. The most common cause of respiratory hypoxia is ventilation-perfusionmismatch resulting from perfusion of poorly ventilated alveoli. Respiratoryhypoxemia may also be caused by hypoventilation, and it is then associated withan elevation of PaCO2 (Chap. 246). These two forms of respiratory hypoxia are usually correctable by inspiring100% O2 for several minutes. A third cause is shunting of blood across the lungfrom the pulmonary arterial to the venous bed (intrapulmonary right-to-leftshunting) by perfusion of nonventilated portions of the lung, as in pulmonaryatelectasis or through pulmonary arteriovenous connections. The low Pa O2 in thissituation is correctable only in part by an FIO2 of 100%.