Hypoxia , or oxygen deprivation (also Hypoxidose ) refers to a the body of a living organism or parts thereof concerned lack supply of oxygen . The arterial hypoxia is reduced as the oxygen partial pressure in arterial defines blood; it can most easily be measured indirectly via a reduced oxygen saturation and shows itself clinically as central cyanosis . The product of oxygen saturation, hemoglobin concentration and a constant (the Hüfner number ) gives the oxygen content of the blood ; a reduced oxygen content is called hypoxemia . Despite this distinction, the two terms are often used synonymously. The complete lack of oxygen is known as anoxia .
The physiological response to hypoxic conditions in the tissue is coordinated by the activation of hypoxia-induced factors (HIF). The transcription factor HIF-1 is stabilized by hypoxic conditions and, as a result, several genes are upregulated in order to promote survival under low-oxygen conditions. These include glycolysis enzymes, which enable ATP synthesis to be independent of oxygen, and the Vascular Endothelial Growth Factor (VEGF), which promotes angiogenesis . HIF-1 acts by binding to hypoxia-responsive elements (HREs) in promoters . The researchers William G. Kaelin , Peter J. Ratcliffe and Gregg L. Semenza received the 2019 Nobel Prize in Physiology or Medicine for their discovery of how oxygen deficiency influences physiological and cellular processes .
Affected people show u. a. a gray or bluish ( cyanotic ) skin color, livid lips , clouding of consciousness up to fainting , shortness of breath and muscle weakness occur . In chronic hypoxia, drumstick fingers and watch glass nails can develop.
The normal value of the arterial oxygen partial pressure p a O 2 is age-dependent and is calculated using the formula:
p a O 2 = 102 - (age in years 0.33) mmHg
A healthy 20-year-old therefore has a p a O 2 of 95 mmHg , while this value should be around 82 mmHg for a healthy 60-year-old.
The oxygen partial pressure in the blood decreases significantly from the arteries via the capillary blood vessels to the target cells in the tissue. If a p a O 2 of 80–100 mmHg is found in the pulmonary veins and the arteries of the body's circulation ( see above), it is already reduced to approx. 40–60 mmHg in the arterioles and lies in the consumption organelles of the cells, the mitochondria , only between 4 and 20 mmHg.
Possible causes are in particular vascular constrictions, respiratory or pulmonary diseases (lung diseases), partially or completely cut off supply of organs due to heart failure , thrombosis (s), embolism (s), sleep apnea , or other factors or diseases that hinder the oxygen supply - such as reaction to mountain air, oxygen utilization disorders in cells, asphyxia (exogenous oxygen deficiency), anemia, in particular due to insufficient oxygen binding to red blood cells , etc.
Depending on the cause, one differentiates:
- Arterial hypoxia
- Diseases of the lung ventilation , e.g. B. COPD , bronchial asthma and respiratory failure .
- Diseases of gas exchange in the lungs , e.g. B. pulmonary edema , pulmonary embolism .
- reduced oxygen partial pressure in the breath
- Hypobaric hypoxia: exposure to high altitudes is accompanied by a decrease in the ambient air pressure while the oxygen content remains the same (around 20%), and the oxygen partial pressure drops.
- Normobaric hypoxia: The proportion of oxygen is reduced while the air pressure is unchanged, e.g. B. by supplying nitrogen, nitrous oxide (see. Diffusion hypoxia ) or carbon dioxide, the oxygen partial pressure drops.
- Tissue hypoxia due to increased exhaustion of the oxygen content
- Anemia : A deficiency of the oxygen carrier hemoglobin in the blood results in a reduced oxygen content regardless of the arterial oxygen partial pressure.
- insufficient blood supply
- Circulatory failure, see shock .
- Ischemia : Vascular restriction of the organ blood flow; the oxygen does not reach its destination. Causes can be ( atherosclerotic ) narrowing or ( thrombotic ) obstruction (e.g. heart attack , stroke ) of larger supplying vessels ( macroangiopathy ) or damage to the small arterioles, venules or capillaries ( microangiopathy ). If the body reduces the blood flow to the acra through regulated vasoconstriction to minimize heat loss , tissue hypoxia (for example, blue lips) can also be observed in healthy people.
- Histotoxic hypoxia, also cytotoxic hypoxia: The cells cannot utilize the oxygen and a non- asphyxial (without asphyxia associated) oxygen deficiency caused by disturbances of the gas exchange inside the body (for example by blocking cellular enzymes as in potassium cyanide poisoning, by overconsumption) alcohol, sleeping pills or anti-emetics).
- Causes of Hypoxia in the Infant
In infants , external influences can trigger hypoxia. Health influences are mostly due to an underdevelopment of the organ apparatus. Are at risk newborns with heart problems, circulatory problems , lack of red blood cells , abnormal cross-links of the blood vessels in the lungs or an immature respiratory system . In preterm these causes occur due to the lower maturity more frequently than in mature born baby.
In the brain specific hypoxia areas are particularly affected, the nerve cell damage occurs in these regions first. These include the Purkinje cells of the cerebellum and the CA1 area of the Ammon's horn . The cells react to external influences by activating so-called heat shock proteins . These and other products from the c-Fos and c-Jun protein family change certain cell functions that are supposed to regulate the survival or controlled death of cells.
Morphologically, necroses , shrinkage of the cerebral mantle and, above all, a selective destruction of neurons can be observed in damaged areas of the brain . The latter shrink to a characteristic triangle with a homogeneous appearance and can be diagnosed by pathologists under a microscope.
According to a study, if infants and toddlers are ventilated with pure oxygen after cerebral hypoxia, this could increase brain damage even further. Cerebral hypoxia can occur during childbirth or through near- drowning . Experiments with mice provided evidence for the assumption that pure oxygen only aggravates brain damage: After hypoxia, they received 100 percent oxygen for 30 minutes. Compared to animals that breathed normal air, myelin formation was more disturbed and they had more motor deficits, similar to those of cerebral palsy . The animals also accumulated highly reactive oxygen compounds such as nitrotyrosine , and a population of immature glial cells in the cortex perished. This could be avoided by adding an antioxidant . According to the study hypothesis, the myelin damage in the white matter of the brain could be caused by oxidative stress .
Hypoxia lasting 3 minutes can lead to irreversible damage to the brain cells. From a p a O 2 of 70 mmHg, the body concentrates on supplying vital organs with oxygen, primarily the brain. This state of compensation collapses from a p a O 2 of 50 mmHg: the heart rate drops ( bradycardia ) and the blood pressure drops ( hypotension ). A p a O 2 of 30 mmHg or more is regarded as the lethal threshold.
Hypoxia in the lower extremities (feet and lower legs)
Because diabetes mellitus damages the blood vessels, it often results in a circulatory disorder in the lower extremities. A frequent clinical picture is therefore the diabetic foot syndrome with chronic wounds due to the low oxygen supply to the legs. Poorly healing lower leg ulcers ( ulcus cruris , "open leg", estimated at around 1.5 million people affected in Germany) due to venous stasis or (more rarely) arterial circulatory disorders are also extremely common .
The transcutaneous oxygen partial pressure (tcPO2) is often determined to estimate the oxygen content of skin with chronic wounds . It is determined from the amount of oxygen that diffuses through the skin to the outside and can be determined non-invasively. At every point on the skin, tcPO2 is a function of locally and systemically effective factors. The general supply of oxygen plays just as much a role as the local metabolic conditions of the skin and the underlying tissues as well as the diffusibility of oxygen through the skin. In healthy skin one usually finds a transcutaneous oxygen partial pressure that is above 40 mmHg. In the case of chronic wounds that have arisen due to an oxygen deficiency in chronic venous insufficiency (CVI) or in the context of diabetes mellitus, the periulcerally measured transcutaneous oxygen partial pressures are well below 40 mmHg and, depending on the degree of the disease, can drop to 0 mmHg. However, partial pressures of over 35 mmHg are described as necessary for the reparative processes of wound healing. For the synthesis of collagens in particular , an oxygen partial pressure of around 50-100 mmHg is necessary due to the high oxygen demand of the enzymes involved.
Therapeutic approaches in wound treatment
As described in the relevant clinical guidelines, the basis of every treatment of a chronic wound is the respective causal treatment of the underlying disease (e.g. diabetes or blood vessel obstruction) or at least the compensation of the causal factors (e.g. decongestion of the Tissue with venous insufficiency), as well as a moist, phase-adapted local wound treatment. On the other hand, approaches that aim directly at improving the oxygen content in the wound are not well established. Systemic hyperbaric oxygen supply ( hyperbaric oxygenation : HBO), the effectiveness of which has been shown in diabetic foot syndrome, has not yet been able to establish itself in a broad clinical application. In addition, therapies using topical emulsions or sprays for topical use have been developed that either contain oxygen, release it directly or, as an oxygen carrier, bring atmospheric oxygen to the wound bed, which can contribute to improved wound regeneration. Various studies and therapeutic attempts have shown that the local provision of additional oxygen, e.g. B. via a spray with hemoglobin as an oxygen carrier, which promotes wound regeneration and can lead to the healing of long-standing wounds. Topical peroxide formulations can release oxygen through spontaneous or enzymatic reactions. However, due to their antibacterial effect with local cytotoxicity, they are primarily used in wound cleaning. Oxygen-saturated topical emulsions in combination with synthetic oxygen carriers such as perfluorocarbon have so far only shown limited possibilities for use in acute treatments.
Therapy for hypoxic respiratory failure
- Cerebral infarction , penumbra
- Altitude sickness
- Hypoxia-induced factor
- Oxygen content of the blood
- Oxygen saturation
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