Hypoxia (medical)

Hypoxia (medical)

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Hypoxia, or hypoxiation, is a pathological
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is deprived of adequate oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 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.

Hypoxia differs from hypoxemia
Hypoxemia
Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...

 in that, in the latter, the oxygen concentration within the arterial blood is abnormally low. It is possible to experience hypoxia and have a low oxygen content (e.g., due to anemia) but maintain high oxygen partial pressure (pO2). Incorrect use of these terms can lead to confusion, especially as hypoxemia is among the causes of hypoxia (in hypoxemic hypoxia).

Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness
Altitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...

 leading to potentially fatal complications: high altitude pulmonary edema
High Altitude Pulmonary Edema
High altitude pulmonary edema is a life-threatening form of non-cardiogenic pulmonary edema that occurs in otherwise healthy mountaineers at altitudes typically above ....

 (HAPE) and high altitude cerebral edema
High altitude cerebral edema
High altitude cerebral edema is a severe form of altitude sickness. HACE is the result of swelling of brain tissue from fluid leakage and almost always begins as acute mountain sickness...

 (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
Rebreather
A rebreather is a type of breathing set that provides a breathing gas containing oxygen and recycled exhaled gas. This recycling reduces the volume of breathing gas used, making a rebreather lighter and more compact than an open-circuit breathing set for the same duration in environments where...

 systems that control the amount of oxygen in the supplied air. A mild and non-damaging intermittent hypoxia is used intentionally during altitude training
Altitude training
Altitude training is the practice by some endurance athletes of training for several weeks at high altitude, preferably over above sea level, though more commonly at intermediate altitudes due to the shortage of suitable high-altitude locations...

s 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 foetus 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
Continuous positive airway pressure
Positive airway pressure is a mode of respiratory ventilation used primarily in the treatment of sleep apnea, for which it was first developed. PAP ventilation is also commonly used for those who are critically ill in hospital with respiratory failure, and in newborn infants...

 (also known as a humidicrib).

In humans, hypoxia is detected by chemoreceptors in the carotid body
Carotid body
The carotid body is a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery ....

. 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
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, increasing pO2 despite a falling pCO2

Classification

  • Hypoxemic hypoxia is a generalized hypoxia, an inadequate supply of oxygen to the body as a whole. The term "hypoxemic hypoxia" specifies hypoxia caused by low partial pressure
    Partial pressure
    In a mixture of ideal gases, each gas has a partial pressure which is the pressure which the gas would have if it alone occupied the volume. The total pressure of a gas mixture is the sum of the partial pressures of each individual gas in the mixture....

     of oxygen in arterial blood. In the other causes of hypoxia that follow, the partial pressure of oxygen in arterial blood is normal. Hypoxemic hypoxia may be due to:
    • Hypoventilation
      Hypoventilation
      In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...

      . Inadequate pulmonary minute ventilation (e.g., respiratory arrest
      Respiratory failure
      The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...

       or by drugs such as opiates)
    • Shunts
      Shunt (medical)
      In medicine, a shunt is a hole or a small passage which moves, or allows movement of fluid from one part of the body to another. The term may describe either congenital or acquired shunts; and acquired shunts may be either biological or mechanical.* Cardiac shunts may be described as...

       in the pulmonary circulation or a right-to-left shunt in the heart. Shunts can be caused by collapsed alveoli that are still perfused or a block in ventilation to an area of the lung. Whatever the mechanism, blood meant for the pulmonary system is not ventilated and so no gas exchange occurs (the ventilation/perfusion ratio is decreased).
      • Normal anatomical shunt occur due to Thebesian veins which empty into the left ventricle
        Ventricle (heart)
        In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...

         and the bronchial circulation which supplies the bronchi with oxygen.
      • Normal physiological shunts occur due to the effect of gravity. The highest concentration of blood in the pulmonary circulation occurs in the bases of the pulmonary tree compared to the highest pressure of gas in the apices of the lungs.
    • V/Q mismatch
      Ventilation/perfusion ratio
      In respiratory physiology, the ventilation/perfusion ratio is a measurement used to assess the efficiency and adequacy of the matching of two variables: It is defined as: the ratio of the amount of air reaching the alveoli to the amount of blood reaching the alveoli.* "V" – ventilation – the air...

      . When the ventilation does not match the perfusion through the paranchyema of the lung. This can occur for a variety of reasons, the commonest being a Pulmonary embolism
      Pulmonary embolism
      Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...

    • Diffusing defects such as pulmonary fibrosis where the Aa gradient has increased.
    • Decreased concentration of oxygen in inspired air. Low partial pressure
      Partial pressure
      In a mixture of ideal gases, each gas has a partial pressure which is the pressure which the gas would have if it alone occupied the volume. The total pressure of a gas mixture is the sum of the partial pressures of each individual gas in the mixture....

       of atmospheric
      Atmosphere
      An atmosphere is a layer of gases that may surround a material body of sufficient mass, and that is held in place by the gravity of the body. An atmosphere may be retained for a longer duration, if the gravity is high and the atmosphere's temperature is low...

       oxygen such as found at high altitude or by reduced replacement of oxygen in the breathing mix.
      • Low partial pressure of oxygen in the lungs when switching from inhaled anaesthesia to atmospheric air, due to the Fink effect
        Fink Effect
        The Fink effect, also known as "diffusion anoxia", "diffusion hypoxia",or the "third gas effect",is a factor that influences the Po2 within the alveolus. When soluble gases are breathed in large quantities can be dissolved in body fluids rapidly...

        , or diffusion hypoxia.
  • Anaemia in which arterial oxygen pressure is normal, but total oxygen content of the blood is reduced. This is due to a decreased total carrying capacity.
  • Hypoxia when the blood fails to deliver oxygen to target tissues.
    • Carbon monoxide poisoning
      Carbon monoxide poisoning
      Carbon monoxide poisoning occurs after enough inhalation of carbon monoxide . Carbon monoxide is a toxic gas, but, being colorless, odorless, tasteless, and initially non-irritating, it is very difficult for people to detect...

       which inhibits the ability of hemoglobin
      Hemoglobin
      Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

       to release the oxygen bound to it.
    • Methaemoglobinaemia in which an abnormal version of hemoglobin accumulates in the blood
      Blood
      Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

  • Histotoxic hypoxia in which quantity of oxygen reaching the cells is normal, but the cells are unable to use the oxygen effectively, due to disabled oxidative phosphorylation enzymes. Cyanide toxicity
    Cyanide poisoning
    Cyanide poisoning occurs when a living organism is exposed to a compound that produces cyanide ions when dissolved in water. Common poisonous cyanide compounds include hydrogen cyanide gas and the crystalline solids potassium cyanide and sodium cyanide...

     is one example.

Signs and symptoms


The symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of altitude sickness
Altitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...

, where hypoxia develops gradually, the symptoms include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

s, fatigue, shortness of breath, a feeling of euphoria and nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

. In severe hypoxia, or hypoxia of very rapid onset, changes in levels of consciousness, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

, priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...

, and death occur. Severe hypoxia induces a blue discolouration of the skin, called cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...

. Because hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

 is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red colour that it has when bound to oxygen (oxyhemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye. In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic.

Pathophysiology


After mixing with water vapour and expired CO2
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 in the lungs, oxygen diffuses down a pressure gradient to enter arterial
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....

 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 cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

ic structures strip hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

 from fuels (glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...

s and some amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s) to burn with oxygen to form water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

. 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
Pyruvic acid
Pyruvic acid is an organic acid, a ketone, as well as the simplest of the alpha-keto acids. The carboxylate ion of pyruvic acid, CH3COCOO−, is known as pyruvate, and is a key intersection in several metabolic pathways....

 converting it to lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

. 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
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

. By widening the blood vessels, the tissue allows greater perfusion.

By contrast, in the lungs, the response to hypoxia is vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

. This is known as "Hypoxic pulmonary vasoconstriction
Hypoxic Pulmonary Vasoconstriction
Hypoxic pulmonary vasoconstriction is a paradoxical, physiological phenomenon in which pulmonary arteries constrict in the presence of hypoxia without hypercapnia , redirecting blood flow to alveoli with a higher oxygen content.The process might at first seem illogical, as low oxygen levels should...

", or "HPV".

Treatment


To counter the effects of high-altitude diseases, the body must return arterial pO2 toward normal. Acclimatization
Acclimatization
Acclimatisation or acclimation is the process of an individual organism adjusting to a gradual change in its environment, allowing it to maintain performance across a range of environmental conditions...

, the means by which the body adapts to higher altitudes, only partially restores pO2 to standard levels. Hyperventilation
Hyperventilation
Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, causing excessive expulsion of circulating carbon dioxide. It can result from a psychological state such as a panic attack, from a physiological condition such as metabolic acidosis, can be brought about by...

, the body’s most common response to high-altitude conditions, increases alveolar pO2 by raising the depth and rate of breathing. However, while pO2 does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar pO2 with full acclimatization, yet the pO2 level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

 (COPD). In addition, there are complications involved with acclimatization. Polycythemia
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...

, in which the body increases the number of red blood cells in circulation, thickens the blood, raising the danger that the heart can’t pump it.

In high-altitude conditions, only oxygen enrichment can counteract the effects of hypoxia. By increasing the concentration of oxygen in the air, the effects of lower barometric pressure are countered and the level of arterial pO2 is restored toward normal capacity. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 4000 m, raising the oxygen concentration level by 5 percent via an oxygen concentrator and an existing ventilation system provides an altitude equivalent of 3000 m, which is much more tolerable for the increasing number of low-landers who work in high altitude. In a study of astronomers working in Chile at 5050 m, oxygen concentrators increased the level of oxygen concentration by almost 30 percent (that is, from 21 percent to 27 percent). This resulted in increased worker productivity, less fatigue, and improved sleep.

Oxygen concentrator
Oxygen concentrator
An oxygen concentrator is a device providing oxygen therapy to a patient at minimally to substantially higher concentrations than available in ambient air. They are used as a safer, less expensive, and more convenient alternative to tanks of compressed oxygen. Common models retail at around US$800...

s are uniquely suited for this purpose. They require little maintenance and electricity, provide a constant source of oxygen, and eliminate the expensive, and often dangerous, task of transporting oxygen cylinders to remote areas. Offices and housing already have climate-controlled rooms, in which temperature and humidity are kept at a constant level. Oxygen can be added to this system easily and relatively cheaply.

See also

  • Altitude training
    Altitude training
    Altitude training is the practice by some endurance athletes of training for several weeks at high altitude, preferably over above sea level, though more commonly at intermediate altitudes due to the shortage of suitable high-altitude locations...

     for beneficial use of mild hypoxia
  • Asphyxia
    Asphyxia
    Asphyxia or asphyxiation is a condition of severely deficient supply of oxygen to the body that arises from being unable to breathe normally. An example of asphyxia is choking. Asphyxia causes generalized hypoxia, which primarily affects the tissues and organs...

  • Cerebral hypoxia
    Cerebral hypoxia
    Cerebral hypoxia refers to a reduced supply of oxygen to the brain. Cerebral anoxia refers to a complete lack of oxygen to the brain. There are four separate categories of cerebral hypoxia; in order of severity they are; diffuse cerebral hypoxia , focal cerebral ischemia, cerebral infarction, and...

  • Deep water blackout
    Deep water blackout
    A deep water blackout is a loss of consciousness caused by cerebral hypoxia on ascending from a deep freedive or breath-hold dive, typically of ten metres or more when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have...

     for special case of latent hypoxia
  • Drowning
    Drowning
    Drowning is death from asphyxia due to suffocation caused by water entering the lungs and preventing the absorption of oxygen leading to cerebral hypoxia....

  • g-LOC
    G-LOC
    G-LOC, pronounced 'GEE-lock', is the abbreviation of G-force induced Loss Of Consciousness, a term generally used in aerospace physiology to describe a loss of consciousness occurring from excessive and sustained g-forces draining blood away from the brain causing cerebral hypoxia...

     cerebral hypoxia induced by excessive g-forces
  • Hypoxic tumor
  • Hypoxicator
    Hypoxicator
    A hypoxicator is a medical device intended to provide a stimulus for the adaptation of an individual's cardiovascular system by means of breathing reduced oxygen hypoxic air and triggering mechanisms of compensation...

     a device intended for hypoxia acclimatisation in a controlled manner
  • Ischemia
    Ischemia
    In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

  • Hyperoxia
    Hyperoxia
    Hyperoxia is excess oxygen or higher than normal partial pressure of oxygen.In medicine, it refers to excess oxygen in the lungs or other body tissues, which can be caused by breathing air or oxygen at pressures greater than normal atmospheric pressure...

  • Sleep apnea
    Sleep apnea
    Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...

  • Intermittent hypoxic training
    Intermittent hypoxic training
    Intermittent hypoxic training , also known as intermittent hypoxic therapy, is a non-invasive, drug-free technique aimed at improving human performance and well-being by way of adaptation to reduced oxygen.-Procedure:...

  • Shallow water blackout
    Shallow water blackout
    A shallow water blackout is a loss of consciousness caused by cerebral hypoxia towards the end of a breath-hold dive in water typically shallower than five metres , when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have...

     for special case of hypoxia via self-induced hypocapnia
  • Time of useful consciousness
    Time of Useful Consciousness
    Time of useful consciousness is defined as the amount of time an individual is able to perform flying duties efficiently in an environment of inadequate oxygen supply...



For aircraft decompression incidents at altitude see:
  • 1999 South Dakota Learjet crash
    1999 South Dakota Learjet crash
    On October 25, 1999, a chartered Learjet 35 was scheduled to fly from Orlando, Florida to Dallas, Texas. Early in the flight the aircraft, which was cruising at altitude on autopilot, gradually lost cabin pressure. As a result, all on board were incapacitated due to hypoxia— a lack of oxygen...

     (the crash which claimed the life of golfer Payne Stewart
    Payne Stewart
    William Payne Stewart was an American professional golfer who won three majors in his career, the last of which occurred only months before he died in an airplane accident at the age of 42....

    )
  • 2000 Australia Beechcraft King Air crash
    2000 Australia Beechcraft King Air crash
    Sierra Kilo Charlie was the call sign for chartered Beechcraft 200 Super King Air which, on 4 September 2000, crashed near Mount Isa, Queensland, Australia. The flight plan of the aircraft called for the pilot to fly between Perth, Western Australia, and the mining town of Leonora, Western...

  • Helios Flight 522
  • Soyuz 11
    Soyuz 11
    Soyuz 11 was the first manned mission to arrive at the world's first space station, Salyut 1. The mission arrived at the space station on June 7, 1971 and departed on June 30, 1971. The mission ended in disaster when the crew capsule depressurized during preparations for re-entry, killing the...

    fatal spacecraft decompression on re-entry