Hypoxia arterial

During experiments on dogs, we studied the influence of arterial hypoxia on cerebral blood flow, cerebral oxygen supply, and cerebral metabolism under normal acid-base conditions as well as under conditions of respiratory and nonrespiratory acidosis. During investigations on patients, we studied the influence of local brain edema (in the periphery of brain tumors or brain lesions) on the cerebral blood flow, the oxygen supply, and the metabolite concentrations of the edematous tissue. 

The same calculations of this type have also been performed for a set of parameters corresponding to arterial hypoxia (pa02 = 46 mm Hg). Analysis of these results demonstrates that there exist only minute differences in the histogram patterns of the various capillary models. 

Weitzberg, E., Rudehill, A., Alving, K., and Lundberg, J. M. (1991). Nitric oxide inhalation selectively attenuates pulmonary hypertension and arterial hypoxia in procine endotoxin shock. Acta Physiol. Scand. 143, 451-452. 

In primary cell cultures from the tunica media of human pulmonary arteries, hypoxia inhibited platelet-derived growth factor-induced [ Hjgluco-samine incorporation in secreted glycosaminogly-cans, especially hyaluronic acid, in vascular smooth muscle cells (Papakonstantinou et al. 2000). In contrast, it stimulated glycosaminoglycan secretion, specially heparan sulphate, by fibroblasts. 

Initial animal studies quickly confirmed the efficacy orf equipment and the physiologic information obtained encouraged us to proceed with clinical trials (3). Typical muscle pH responses in the experimental animal are shown in Figures 1, 2 and 3. In these studies, the oxygen supply to the muscle being monitored was decreased by vascular occlusion, hemorrhagic shock or arterial hypoxia. 

Carlsson C, Hagerdal M, Siesjo BK. Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia. Anesthesiology 1976 44(l) 27-35. 

A much-studied respiratory depressant effect of hypoxia that is either directly or indirectly mediated by the CNS has been termed hypoxic ventilatory decline. That the ventilatory deeline with arterial hypoxia in carotid sinus nerve (CSN) denervated anesthetized eats with maintained arterial Pco2 could be reversed by electrical stimulation of the eut CSN suggests that the CSN input maintained ventilation with eoneomitant central nervous system (CNS) hypoxic depression (19a). This evidenee also suggests that hypoxic CNS inhibition is an active process (see later. Refs. 2,4,11). In adult humans and some animals, when isocapnic hypoxia is produced in a square-wave fashion, the initial enhancement of respiratory output is followed, in about 5-7 min, by a decline to approximately 50% of the peak level (20-22). The phenomenon is best observed in the imanaesthetized state, but may be seen in anesthetized animals as well. It is far more prominent in the early neonate (1-5 days in humans) where the decline in respiratory output may be to baseline or below the initial level of respiratory output. Recent studies in the neonate have demonstrated a significant genetic variation to expression of this phenomenon (23). 

Retinal Hemorrhages Although usually asymptomatic, retinal hemorrhages caused by arterial hypoxia are common at high altitudes. Spontaneous resolution can occm within 2 weeks. 

Anoxia Anoxia is the absence of oxygen in inspired gases or in arterial blood and/or in the tissues. This is closely related to hypoxia, which is a severe oxygen deficiency in the tissues. One can think of anoxia as the most extreme case of hypoxia. 

A classification of the causes of hypoxia is presented in Table II. Only anoxic anoxia (due to decreased ambient oxygen or to respiratory disease) has arterial P02 values decreased (with accompanying decreased venous P02 values). However, hemic, ischemic, and histoxic hypoxia may be present (termed non-ventilatory hypoxia) with normal arterial P02 values. Thus the best evaluation of hypoxia is an analysis of both arterial and venous... 

Hypoxia Arterial blood gases, Ventilation, oxygen... 

The principal function of the circulatory system is to supply oxygen and vital metabolic substrates to cells throughout the body, as well as removal of metabolic waste products. Circulatory shock is a life-threatening condition whereby this principal function is compromised. When circulatory shock is caused by a severe loss of blood volume or body water it is called hypovolemic shock, the focus of this chapter. Regardless of etiology, the most distinctive manifestations of hypovolemic shock are arterial hypotension and metabolic acidosis. Metabolic acidosis is a consequence of an accumulation of lactic acid resulting from tissue hypoxia and anaerobic... 

The goal of oxygen therapy is to maintain Pao2 above 60 mm Hg (8 kPa) or Sao2 above 90% in order to prevent tissue hypoxia and preserve cellular oxygenation.1 Increasing the Pao2 much further confers little added benefit and may increase the risk of C02 retention, which may lead to respiratory acidosis. An arterial blood gas should be obtained after 1 to 2 hours to assess for hypercapnia. 

Abnormal arterial blood gases (ABCs) due to hypoxia and respiratory or metabolic acidosis... 

Hypoxia A pathologic condition in which the body (generalized hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply (partial arterial oxygen pressure less than 80 mm Hg). Hypoxia in which there is complete deprivation of the oxygen supply is referred to as anoxia. 

Chemoreceptors. The peripheral chemoreceptors include the carotid bodies, located at the bifurcation of the common carotid arteries, and the aortic bodies, located in the aortic arch. These receptors are stimulated by a decrease in arterial oxygen (hypoxia), an increase in arterial carbon dioxide (hypercapnia),... 

Chemoreceptor response to decreased arterial P02. Hypoxia has a direct depressant effect on central chemoreceptors as well as on the medullary respiratory center. In fact, hypoxia tends to inhibit activity in all regions of the brain. Therefore, the ventilatory response to hypoxemia is elicited only by the peripheral chemoreceptors. 

Holland et al. [125] have shown that the potent vascular smooth muscle cell mitogen and phospholipase A2 activator thrombin stimulated superoxide production in human endothelial cells, which was inhibited by the NADPH oxidase inhibitors. Similarly, thrombin enhanced the production of oxygen species and the expression of )Alphos and Rac2 subunits of NADPH oxidase in VSMCs [126,127]. Greene et al. [128] demonstrated that the activator of NO synthase neuropeptide bradykinin is also able to stimulate NADPH oxidase in VSMCs. Similar to XO, NADPH oxidase enhanced superoxide production in pulmonary artery smooth muscle cells upon exposure to hypoxia [129]. 

It is important that mitochondrial oxygen radical production depends on the type of mitochondria. Recently, Michelakis et al. [78] demonstrated that hypoxia and the proximal inhibitors of electron transport chain (rotenone and antimycin) decreased mitochondrial oxygen radical production by pulmonary arteries and enhanced it in renal arteries. This difference is probably explained by a lower expression of the proximal components of electron transport chain and a greater expression of mitochondrial MnSOD in pulmonary arteries compared to renal arteries. 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Characteristic symptoms include fever and dyspnea clinical signs are tachypnea, with or without rales or rhonchi, and a nonproductive or mildly productive cough. Chest radiographs may show florid or subtle infiltrates or may occasionally be normal, although infiltrates are usually interstitial and bilateral. Arterial blood gases may show minimal hypoxia (Pao2 80 to 95 mm Hg) but in more advanced disease may be markedly abnormal. 

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