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Hypoxia is a condition in which the body or a region of the body is deprived of adequate
oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...

oxygen
supply at the
tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubitata'', a species of geometer mot ...
level. Hypoxia may be classified as either ''generalized'', affecting the whole body, or ''local'', affecting a region of the body. Although hypoxia is often a
pathological Pathology is the study of the causesCauses, or causality, is the relationship between one event and another. It may also refer to: * Causes (band), an indie band based in the Netherlands * Causes (company), an online company See also * Cau ...
condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during
hypoventilation training Hypoventilation training is a physical training method in which periods of exercise with reduced breathing frequency are interspersed with periods with normal breathing. The hypoventilation technique consists of short breath holdings and can be per ...
or strenuous physical exercise. Hypoxia differs from
hypoxemia Hypoxemia is an abnormally low level of oxygen Oxygen is the chemical element with the chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen Group (periodic table), group in the periodic table, a highly Chemic ...
and anoxemia in that hypoxia refers to a state in which oxygen supply is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or zero arterial oxygen supply. 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 Altitude or height (also sometimes known as depth) is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context ...

high altitude
, where it causes
altitude sickness Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptom ...
leading to potentially fatal complications:
high altitude pulmonary edema High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema (fluid accumulation in the lungs) that occurs in otherwise healthy people at altitudes typically above . However, cases have also been reported betwe ...
(
HAPE High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema Pulmonary edema is fluid accumulation in the tissue and air spaces of the lungs. It leads to impaired gas exchange and may cause respiratory ...
) and
high altitude cerebral edema High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves diso ...
(
HACE High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness Altitude sickn ...
). 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 A rebreather is a breathing apparatus that absorbs the carbon dioxide Carbon dioxide (chemical formula ) is a colorless gas with a density about 53% higher than that of dry air. Carbon dioxide molecules consist of a carbon atom covalent bon ...
systems that control the amount of oxygen in the supplied air. Mild, non-damaging intermittent hypoxia is used intentionally during
altitude trainingImage:Swiss Olympic training base.jpg, Altitude training in the Swiss Olympic Training Base in the Alps (elevation ) in St. Moritz. Altitude training is the practice by some endurance Sportsperson, athletes of training for several weeks at high altit ...
to develop an athletic performance adaptation at both the systemic and cellular level. In acute or
silent hypoxia Silent hypoxia (also happy hypoxia) is hypoxia that does not coincide with shortness of breath Shortness of breath (SOB), also known as dyspnea (BrE: dyspnoea) is a feeling of not being able to breathe well enough. The American Thoracic Societ ...
, a person's oxygen level in blood cells and tissue can drop without any initial warning, even though the individual's chest x-ray shows diffuse pneumonia with an oxygen level below normal. Doctors report cases of silent hypoxia with
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease A contagious disease is a disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization o ...
patients who did not experience shortness of breath or coughing until their oxygen levels had plummeted to such a degree that the patients risked acute respiratory distress (ARDS) and organ failure. In a ''
New York Times ''The New York Times'' is an American daily newspaper A newspaper is a periodical Periodical literature (also called a periodical publication or simply a periodical) is a category of Serial (publishing), serial published, publicatio ...

New York Times
'' opinion piece (April 20, 2020), emergency room doctor
Richard Levitan Richard Mark Levitan is an American emergency medicine physician and businessperson. He is a clinical professor of medicine at Dartmouth College and a practicing physician at the Littleton Regional Hospital. He also runs a company that creates m ...
reports "a vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage—seemingly incompatible with life—but they were using their cellphones as we put them on monitors." Hypoxia is a common complication of
preterm birth Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Very early preterm birth is before 32 weeks, early preterm birth ...
in newborn infants. Because the lungs develop late in pregnancy, premature infants frequently possess underdeveloped lungs. To improve lung function, doctors frequently place infants at risk of hypoxia inside incubators (also known as humidicribs) that provide warmth, humidity, and oxygen. More serious cases are treated with . The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza in recognition of their discovery of cellular mechanisms to sense and adapt to different oxygen concentrations, establishing a basis for how oxygen levels affect physiological function.


Generalized hypoxia

The symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of
altitude sickness Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptom ...
, where hypoxia develops gradually, the symptoms include
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
numbness Hypoesthesia or numbness is a common side effect of various medical conditions which manifests as a reduced sense of touch The somatosensory system is a part of the sensory nervous system. The somatosensory system is a complex system of sensory ...
/ tingling of extremities,
nausea Nausea is a diffuse sensation of unease and discomfort, often perceived as an urge to vomiting, vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, upper abdomen, or ...

nausea
, and
cerebral anoxia Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen Oxygen is the chemical element with the chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen Group (periodic table), group in the periodic tab ...
. These symptoms are often difficult to identify, but early detection of symptoms can be critical. In severe hypoxia, or hypoxia of very rapid onset,
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality Gait abnormality is a deviation from normal walking ( gait). Watching a patient walk is the most important part ...

ataxia
, confusion, disorientation,
hallucination A hallucination is a perception Perception (from the Latin ''perceptio'', meaning gathering or receiving) is the organization, identification, and interpretation of Sense, sensory information in order to represent and understand the pr ...

hallucination
s, behavioral change, severe
headache Headache is the symptom of pain Pain is a distressing feeling often caused by intense or damaging stimuli. The defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or ...

headache
s, reduced level of consciousness, papilloedema,
breathlessness Shortness of breath (SOB), also known as dyspnea (BrE: dyspnoea) is a feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that consists of qualita ...
,
pallor Pallor is a pale color of the skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic ...
,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate Heart rate is the speed of the heartbeat Heartbeat or heartbeats may refer to: Physiology *Cardiac cycle, of the heart *Contraction of the cardiac muscle, muscles of the heart, or a per ...
, and
pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure within the arteries of the lungs. Symptoms include shortness of breath, syncope, tiredness, chest pain, pedal edema, swelling of the legs, and a fast heartbeat. The ...
eventually leading to the late signs
cyanosis Cyanosis is the change of body Tissue (biology), tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the Red blood cell, red blood cells of the capillary bed. Body tissues that reflect ...
,
slow heart rate Bradycardia is a condition typically defined wherein an individual has a resting heart rateHeart rate is the speed of the heartbeat measured by the number of contractions (beats) of the heart The heart is a muscle, muscular Organ (anatomy ...
,
cor pulmonale Pulmonary heart disease, also known as cor pulmonale, is the enlargement and failure Image:Train wreck at Montparnasse 1895.jpg, The 1895 Montparnasse derailment in Paris, alt= Failure is the state or condition of not meeting a desirable or i ...
, and
low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
followed by
heart failure Heart failure (HF), also known as congestive heart failure (CHF) and (congestive) cardiac failure (CCF), is a set of manifestations caused by the failure of the heart The heart is a cardiac muscle, muscular Organ (biology), organ in mo ...
eventually leading to shock and
death Death is the permanent, irreversible cessation of all biological functions that sustain a living Living or The Living may refer to: Common meanings *Life, a condition that distinguishes organisms from inorganic objects and dead organi ...

death
. Because
hemoglobin Hemoglobin or haemoglobin (spelling differences Despite the various English dialects Dialect The term dialect (from Latin , , from the Ancient Greek word , , "discourse", from , , "through" and , , "I speak") is used in two distinct wa ...

hemoglobin
is a darker red when it is not bound to oxygen ( deoxyhemoglobin), as opposed to the rich red color that it has when bound to oxygen (
oxyhemoglobin Hemoglobin, or haemoglobin ( spelling differences) (Greek αἷμα (haîma, “blood”) + -in) + -o- + globulin (from Latin globus (“ball, sphere”) + -in) (), abbreviated Hb or Hgb, is the iron-containing oxygen Oxygen is the chemica ...

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. Hypoxia can cause
premature birth Preterm birth, also known as premature birth, is the birth Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause ...
, and injure the liver, among other deleterious effects.


Local hypoxia

If tissue is not being perfused properly, it may feel cold and appear pale; if severe, hypoxia can result in
cyanosis Cyanosis is the change of body Tissue (biology), tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the Red blood cell, red blood cells of the capillary bed. Body tissues that reflect ...
, a blue discoloration of the skin. If hypoxia is very severe, a tissue may eventually become gangrenous. Extreme pain may also be felt at or around the site. Tissue hypoxia from low oxygen delivery may be due to low haemoglobin concentration (anaemic hypoxia), low cardiac output (stagnant hypoxia) or low haemoglobin saturation (hypoxic hypoxia). The consequence of oxygen deprivation in tissues is a switch to anaerobic metabolism at the cellular level. As such, reduced systemic blood flow may result in increased serum lactate. Serum lactate levels have been correlated with illness severity and mortality in critically ill adults and in ventilated neonates with respiratory distress.


Cause

Oxygen passively diffuses in the lung
alveoli Alveolus (pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Alveolus may refer to: In anatomy and zoology in general * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ...
according to a pressure gradient. Oxygen diffuses from the breathed air, mixed with water vapour, to
arterial An artery (plural arteries) () is a blood vessel that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pulmonary arteries, pulmonary ...

arterial
blood, where its partial pressure is around 100 mmHg (13.3 kPa). – Online interactive oxygen delivery calculator. In the blood, oxygen is bound to hemoglobin, a protein in
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

red blood cell
s. The binding capacity of hemoglobin is influenced by the
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas mix ...
of oxygen in the environment, as described in the
oxygen–hemoglobin dissociation curve The oxygen–hemoglobin dissociation curve, also called the oxyhemoglobin dissociation curve or oxygen dissociation curve (ODC), is a graph of a function, curve that plots the proportion of hemoglobin in its saturated (oxygen-laden) form on the ve ...
. A smaller amount of oxygen is transported in solution in the blood. In peripheral tissues, oxygen again diffuses down a pressure gradient into cells and their
mitochondria A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

mitochondria
, where it is in conjunction with the breakdown of
glucose Glucose is a simple with the . Glucose is the most abundant , a subcategory of s. Glucose is mainly made by and most during from water and carbon dioxide, using energy from sunlight, where it is used to make in s, the most abundant carbohydr ...

glucose
,
fat In nutrition Nutrition is the biochemical Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided ...

fat
s, and some
amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properties, reactions, a ...

amino acid
s. Hypoxia can result from a failure at any stage in the delivery of oxygen to cells. This can include decreased partial pressures of oxygen, problems with diffusion of oxygen in the lungs, insufficient available hemoglobin, problems with blood flow to the end tissue, and problems with breathing rhythm. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 60 mmHg (5.3 kPa) or below. Almost all the oxygen in the blood is bound to hemoglobin, so interfering with this carrier molecule limits oxygen delivery to the periphery. Hemoglobin increases the oxygen-carrying capacity of blood by about 40-fold, with the ability of hemoglobin to carry oxygen influenced by the partial pressure of oxygen in the environment, a relationship described in the
oxygen–hemoglobin dissociation curve The oxygen–hemoglobin dissociation curve, also called the oxyhemoglobin dissociation curve or oxygen dissociation curve (ODC), is a graph of a function, curve that plots the proportion of hemoglobin in its saturated (oxygen-laden) form on the ve ...
. When the ability of hemoglobin to carry oxygen is interfered with, a hypoxic state can result.


Ischemia

Ischemia Ischemia or ischaemia is a restriction in blood Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells and transports metabolic waste products away fr ...
, meaning insufficient blood flow to a tissue, can also result in hypoxia. This is called 'ischemic hypoxia'. This can include an embolic event, a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory sy ...

heart attack
that decreases overall blood flow, or trauma to a tissue that results in damage. An example of insufficient blood flow causing local hypoxia is
gangrene Gangrene is a type of tissue death Necrosis (from Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often rou ...
that occurs in
diabetes Diabetes mellitus, commonly known as just diabetes, is a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and carbohydrate ...

diabetes
. Diseases such as
peripheral vascular disease Peripheral artery disease (PAD) is an abnormal narrowing of artery, arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular ...
can also result in local hypoxia. For this reason, symptoms are worse when a limb is used. Pain may also be felt as a result of increased hydrogen ions leading to a decrease in blood pH (acidity) created as a result of
anaerobic metabolism Anaerobic respiration is respiration using electron acceptors other than molecular oxygen (O2). Although oxygen is not the final electron acceptor, the process still uses a respiratory electron transport chain. In aerobic organisms 300px, Aero ...
.


Hypoxemic hypoxia

This refers specifically to hypoxic states where the arterial content of oxygen is insufficient. This can be caused by alterations in respiratory drive, such as in
respiratory alkalosis Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH beyond the normal range (7.35–7.45) with a concurrent reduction in arterial levels of carbon dioxide Carbon dioxide (chemical formula A ch ...
, physiological or pathological shunting of blood, diseases interfering in lung function resulting in a
ventilation-perfusion mismatchIn respiratory physiology, the ventilation/perfusion ratio (V̇/Q̇ ratio or V/Q ratio) is a ratio used to assess the efficiency and adequacy of the matching of two variables: * V̇ or V – Ventilation (physiology), ventilation – the air that re ...
, such as a
pulmonary embolus Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain pa ...
, or alterations in the
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas mix ...
of oxygen in the environment or lung alveoli, such as may occur at altitude or when diving.


Carbon monoxide poisoning

Carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom. It is the simplest molecule of the oxocarbon family. In ...

Carbon monoxide
competes with oxygen for binding sites on hemoglobin molecules. As carbon monoxide binds with hemoglobin hundreds of times tighter than oxygen, it can prevent the carriage of oxygen.
Carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom. It is the simplest molecule of the oxocarbon family. In ...

Carbon monoxide
poisoning can occur acutely, as with smoke intoxication, or over a period of time, as with cigarette smoking. Due to physiological processes, carbon monoxide is maintained at a resting level of 4–6 ppm. This is increased in urban areas (7–13 ppm) and in smokers (20–40 ppm). A carbon monoxide level of 40 ppm is equivalent to a reduction in hemoglobin levels of 10 g/L. CO has a second toxic effect, namely removing the allosteric shift of the oxygen dissociation curve and shifting the foot of the curve to the left. In so doing, the hemoglobin is less likely to release its oxygens at the peripheral tissues. Certain abnormal hemoglobin variants also have higher than normal affinity for oxygen, and so are also poor at delivering oxygen to the periphery.


Altitude

Atmospheric pressure reduces with altitude and with it, the amount of oxygen. The reduction in the partial pressure of inspired oxygen at higher altitudes lowers the oxygen saturation of the blood, ultimately leading to hypoxia. The clinical features of altitude sickness include: sleep problems, dizziness, headache and oedema.


Hypoxic breathing gases

The
breathing gas A breathing gas is a mixture of gaseous chemical elements and compounds used for breathing, respiration. Air is the most common, and only natural, breathing gas. But other mixtures of gases, or pure oxygen, are also used in breathing equipment ...
in
underwater diving Underwater diving, as a human activity, is the practice of descending below the water's surface to interact with the environment. Immersion in water and exposure to high ambient pressure have physiological effects that limit the depths and d ...
may contain an insufficient partial pressure of oxygen, particularly in malfunction of rebreathers. Such situations may lead to unconsciousness without symptoms since carbon dioxide levels are normal and the human body senses pure hypoxia poorly. Hypoxic breathing gases can be defined as mixtures with a lower oxygen fraction than air, though gases containing sufficient oxygen to reliably maintain consciousness at normal sea level atmospheric pressure may be described as normoxic even when slightly hypoxic. Hypoxic mixtures in this context are those which will not reliably maintain consciousness at sea level pressure. Gases with as little as 2% oxygen by volume in a helium diluent are used for deep diving operations. The ambient pressure at 190 msw is sufficient to provide a partial pressure of about 0.4 bar, which is suitable for
saturation diving Saturation diving is diving for periods long enough to bring all tissues into equilibrium List of types of equilibrium, the condition of a system in which all competing influences are balanced, in a wide variety of contexts. Equilibrium may al ...
. As the divers are decompressed, the breathing gas must be oxygenated to maintain a breathable atmosphere. Inert gas asphyxiation may be deliberate with use of a
suicide bag A suicide bag, also known as an exit bag or hood, is part of a euthanasia device consisting of a large plastic bag A plastic bag, poly bag, or pouch is a type of container made of thin, flexible, plastic film, nonwoven fabric, or plastic t ...

suicide bag
. Accidental death has occurred in cases where concentrations of nitrogen in controlled atmospheres, or methane in mines, has not been detected or appreciated.


Other

Hemoglobin's function can also be lost by chemically oxidizing its iron atom to its ferric form. This form of inactive hemoglobin is called
methemoglobinMethemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Methemoglobin ...
and can be made by ingesting sodium nitrite as well as certain drugs and other chemicals.


Anemia

Hemoglobin plays a substantial role in carrying oxygen throughout the body, and when it is deficient,
anemia Anemia (American and British English spelling differences#ae and oe, also spelled anaemia) is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood, or a lowered ability of the blood to carry oxygen. When anemia c ...

anemia
can result, causing 'anaemic hypoxia' if tissue
perfusion Perfusion is the passage of fluid through the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a biological system A biological system is a c ...
is decreased.
Iron deficiency Iron deficiency, or sideropenia, is the state in which a body lacks enough iron Iron () is a with Fe (from la, ) and 26. It is a that belongs to the and of the . It is, on , right in front of (32.1% and 30.1%, respectively), formi ...
is the most common cause of anemia. As iron is used in the synthesis of hemoglobin, less hemoglobin will be synthesised when there is less iron, due to insufficient intake, or poor absorption. Anemia is typically a chronic process that is compensated over time by increased levels of
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

red blood cell
s via upregulated erythropoetin. A chronic hypoxic state can result from a poorly compensated anaemia.


Histotoxic hypoxia


Cyanide poisoning

Histotoxic hypoxia results when the quantity of oxygen reaching the cells is normal, but the cells are unable to use the oxygen effectively as a result of disabled oxidative phosphorylation enzymes. This may occur in
cyanide poisoning Cyanide poisoning is poisoning A poison In biology, poisons are Chemical substance, substances that can cause death, injury or harm to organs, Tissue (biology), tissues, Cell (biology), cells, and DNA usually by chemical reactions or oth ...
.


Physiological compensation


Acute

If oxygen delivery to cells is insufficient for the demand (hypoxia), electrons will be shifted to
pyruvic acid Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is R ...

pyruvic acid
in the process of
lactic acid fermentation Lactic acid fermentation is a metabolic process by which glucose or other hexose, six-carbon sugars (also, disaccharides of six-carbon sugars, e.g. sucrose or lactose) are converted into cellular energy and the metabolite lactic acid, lactate, wh ...

lactic acid fermentation
. 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. In humans, hypoxia is detected by the peripheral chemoreceptors in the
carotid body The carotid body is a small cluster of chemoreceptor cells, and supporting sustentacular cells. The carotid body is located in the adventitia, in the bifurcation (fork) of the common carotid artery In anatomy, the left and right common carotid ...
and
aortic body The aortic bodies are one of several small clusters of peripheral chemoreceptors located along the aorta, aortic arch. They are important in measuring Partial pressure, partial pressures of oxygen and carbon dioxide in the blood, and Acid–base hom ...

aortic body
, with the carotid body chemoreceptors being the major mediators of reflex responses to hypoxia. This response does not control ventilation rate at normal p, 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 The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
, increasing p despite a falling p In most tissues of the body, the response to hypoxia is
vasodilation Vasodilation is the widening of blood vessel The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is ...

vasodilation
. By widening the blood vessels, the tissue allows greater perfusion. By contrast, in the
lung The lungs are the primary organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma ...

lung
s, the response to hypoxia is
vasoconstriction Vasoconstriction is the narrowing of the blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of th ...

vasoconstriction
. This is known as hypoxic pulmonary vasoconstriction, or "HPV".


Chronic

When the pulmonary capillary pressure remains elevated chronically (for at least 2 weeks), the lungs become even more resistant to pulmonary edema because the lymph vessels expand greatly, increasing their capability of carrying fluid away from the interstitial spaces perhaps as much as 10-fold. Therefore, in patients with chronic
mitral stenosis Mitral stenosis is a valvular heart disease Valvular heart disease is any cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart The heart is a muscle, muscular Organ (anatomy), organ in mo ...

mitral stenosis
, pulmonary capillary pressures of 40 to 45 mm Hg have been measured without the development of lethal pulmonary edema. uytun and Hall physiology Hypoxia exists when there is a reduced amount of oxygen in the tissues of the body. Hypoxemia refers to a reduction in PO2 below the normal range, regardless of whether gas exchange is impaired in the lung, CaO2 is adequate, or tissue hypoxia exists. There are several potential physiologic mechanisms for hypoxemia, but in patients with
COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease The lungs are the primary Organ (anatomy), organs of the respiratory system in humans and many other animals including a few fish and some snails. In mammal ...

COPD
the predominant one is V/Q mismatching, with or without alveolar hypoventilation, as indicated by PaCO2. Hypoxemia caused by V/Q mismatching as seen in COPD is relatively easy to correct, so that only comparatively small amounts of supplemental oxygen (less than 3 L/min for the majority of patients) are required for LTOT. Although hypoxemia normally stimulates ventilation and produces dyspnea, these phenomena and the other symptoms and signs of hypoxia are sufficiently variable in patients with COPD as to be of limited value in patient assessment. Chronic alveolar hypoxia is the main factor leading to development of cor pulmonale—right ventricular hypertrophy with or without overt right ventricular failure—in patients with COPD. Pulmonary hypertension adversely affects survival in COPD, to an extent that parallels the degree to which resting mean pulmonary artery pressure is elevated. Although the severity of airflow obstruction as measured by
FEV1 Spirometry (meaning ''the measuring of breath'') is the most common of the pulmonary function test Pulmonary function testing (PFT) is a complete evaluation of the respiratory system The respiratory system (also respiratory apparatus, ven ...
is the best correlate with overall prognosis in patients with COPD, chronic hypoxemia increases mortality and morbidity for any severity of disease. Large-scale studies of LTOT in patients with COPD have demonstrated a
dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual co ...
between daily hours of oxygen use and survival. There is reason to believe that continuous, 24-hours-per-day oxygen use in appropriately selected patients would produce a survival benefit even greater than that shown in the NOTT and MRC studies.


Treatment

To counter the effects of high-altitude diseases, the body must return arterial p toward normal.
Acclimatization Acclimatization or acclimatisation ( also called acclimation or acclimatation) is the process in which an individual organism In biology Biology is the natural science that studies life and living organisms, including their a ...
, the means by which the body adapts to higher altitudes, only partially restores p to standard levels.
Hyperventilation Hyperventilation occurs when the rate or tidal volume Tidal volume (symbol VT or TV) is the volume of air moved into or out of the lungs during a normal breath. In a healthy, young human adult, tidal volume is approximately 500 ml per i ...
, the body's most common response to high-altitude conditions, increases alveolar p by raising the depth and rate of breathing. However, while p does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar p with full acclimatization, yet the p level remains equal to or even below the threshold for continuous oxygen therapy for patients with
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease The lungs are the primary Organ (anatomy), organs of the respiratory system in humans and many other animals including a few fish and some snails. In mammal ...
(COPD). In addition, there are complications involved with acclimatization.
Polycythemia Polycythemia (also known as polycythaemia or polyglobulia) is a disease state in which the hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cell Red blood cells (RBCs), a ...
, 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 p 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 An oxygen concentrator is a device that concentrates the oxygen Oxygen is the chemical element with the chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen Group (periodic table), group in the periodic table ...
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. A prescription renewal for home oxygen following hospitalization requires an assessment of the patient for ongoing hypoxemia.


See also

* * or cerebral anoxia, a reduced supply of oxygen to the brain * or autoerotic hypoxia, intentional restriction of oxygen to the brain for sexual arousal * , or diffusion hypoxia, a factor that influences the partial pressure of oxygen within the pulmonary alveolus * cerebral hypoxia induced by excessive g-forces * , the inability of cells to take up or utilize oxygen from the bloodstream * * * or hypoxemic hypoxia, a deficiency of oxygen in arterial blood * , responses of fish to hypoxia * * , a result of insufficient oxygen available to the lungs * * a device intended for hypoxia acclimatisation in a controlled manner * * , when a fetus is deprived of an adequate supply of oxygen * or deep water blackout, loss of consciousness on ascending from a deep freedive * , increased cytosolic ratio of free NADH to NAD+ in cells * * * * , the situation where tumor cells have been deprived of oxygen


Notes


References

{{DEFAULTSORT:Hypoxia (Medical) Aviation medicine Diving medicine Mountaineering and health Oxygen Pulmonology