Development of hypoxia Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole (generalized hypoxia) or a region of the body

(tissue hypoxia) is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise. A mismatch between oxygen supply and its demand at the cellular level may result in a hypoxic condition. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia. Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness leading to potentially fatal complications: high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, e.g. while diving underwater especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. A mild and non-damaging intermittent hypoxia is used intentionally during altitude trainings to develop an athletic performance adaptation at both the systemic and cellular level. Hypoxia is also a serious consequence of preterm birth in the neonate. The main cause for this is that the lungs of the human fetus are among the last organs to develop during pregnancy. To assist the lungs to distribute oxygenated blood throughout the body, infants at risk of hypoxia are often placed inside an incubator capable of providing continuous positive airway pressure (also known as a humidicrib). In humans, hypoxia is detected by chemoreceptors in the carotid body. This response does not control ventilation rate at normal pO2, but below normal the activity of neurons innervating these receptors increases dramatically, so much so to override the signals from central chemoreceptors in the hypothalamus, increasing pO2 despite a falling pCO2. Subtypes of hypoxia: 1. Anemic hypoxia: hypoxia due to a decreased concentration of functional hemoglobin or a reduced number of red blood cells, as seen in anemia and hemorrhage; 2. Hypoxic hypoxia: hypoxia resulting from a defective mechanism of oxygenation in the lungs, as caused by a low tension of oxygen, abnormal pulmonary function, airway obstruction, or a right-to-left shunt in the heart 3. Ischemic hypoxia: tissue hypoxia characterized by tissue oligemia and caused by arteriolar obstruction or vasoconstriction 4. Oxygen affinity hypoxia: hypoxia due to reduced ability of hemoglobin to release oxygen; 5. Stagnant hypoxia: tissue hypoxia characterized by intravascular stasis due to impairment of venous outflow or decreased arterial inflow. Mechanisms of Tissue Hypoxia Oxygen enters the body via the lungs, is transported to the tissues via the blood, and is consumed by the intracellular respiratory engine to provide the energy for metabolism. A defect at any point in the system-lungs, heart, blood, or tissues-can disrupt normal oxygenation and cause tissue damage or death of the organism. In clinical practice a deficiency of oxygen in the arterial blood is commonly defined in relation to the oxyhemoglobin dissociation curve .

Pathophysiology After mixing with water vapor and expired CO2 in the lungs, oxygen diffuses down a pressure gradient to enter arterial blood where its partial pressure is around 100 mmHg (13.3 kPa). Arterial blood flow delivers oxygen to the peripheral tissues, where it again diffuses down a pressure gradient into the cells and into their mitochondria. These bacteria-like cytoplasmic structures striphydrogen from fuels (glucose, fats and some amino acids) to burn with oxygen to form water. The fuel's carbon is oxidized to CO2, which diffuses down its partial pressure gradient out of the cells into venous blood to be exhaled finally by the lungs. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 40 mmHg (5.3 kPa) or below. If oxygen delivery to cells is insufficient for the demand (hypoxia), hydrogen will be shifted to pyruvic acid converting it to lactic acid. This temporary measure (anaerobic metabolism) allows small amounts of energy to be released. Lactic acid build up (in tissues and blood) is a sign of inadequate mitochondrial oxygenation, which may be due to hypoxemia, poor blood flow (e.g., shock) or a combination of both. If severe or prolonged it could lead to cell death.

Vasoconstriction and vasodilation In most tissues of the body, the response to hypoxia is vasodilation. By widening the blood vessels, the tissue allows greater perfusion. By contrast, in the lungs, the response to hypoxia is vasoconstriction. This is known as "Hypoxic pulmonary vasoconstriction", or "HPV".