Editing Decompression sickness (section)

== Mechanism ==
{{See also|Physiology of decompression}}
[[File:Preparing for recompression.jpg|thumb|upright|alt=A diver being helped out of his bulky diving gear|This surfacing diver must enter a [[decompression chamber]] for [[Decompression practice#Surface decompression|surface decompression]], a standard operating procedure to avoid decompression sickness after long or deep {{Diving term|bounce dives.}}]]

Depressurisation causes [[inert gas]]es, which were dissolved under higher [[pressure]], to come out of physical [[Solution (chemistry)|solution]] and form gas [[liquid bubble|bubble]]s within the body. These bubbles produce the symptoms of decompression sickness.{{r|38uhms | Ackles}} Bubbles may form whenever the body experiences a reduction in pressure, but not all bubbles result in DCS.{{sfn|Nishi Brubakk & Eftedal|p=501}} The amount of gas dissolved in a liquid is described by [[Henry's Law]], which indicates that when the pressure of a gas in contact with a liquid is decreased, the amount of that gas dissolved in the liquid will also decrease proportionately.

On ascent from a dive, inert gas comes out of solution in a process called "[[outgassing]]" or "offgassing". Under normal conditions, most offgassing occurs by [[gas exchange]] in the [[lung]]s.{{r|Kindwall1 | Kindwall2}} If inert gas comes out of solution too quickly to allow outgassing in the lungs then bubbles may form in the blood or within the solid tissues of the body. The formation of bubbles in the skin or joints results in milder symptoms, while large numbers of bubbles in the venous blood can cause lung damage.{{sfn|Francis & Mitchell, ''Manifestations''|pp=583–584}} The most severe types of DCS interrupt{{snd}}and ultimately damage{{snd}}spinal cord function, leading to [[paralysis]], [[Sensory system|sensory]] dysfunction, or death. In the presence of a [[right-to-left shunt]] of the heart, such as a [[patent foramen ovale]], venous bubbles may enter the arterial system, resulting in an [[arterial gas embolism]].{{r|Francis}}{{sfn|Francis & Mitchell, ''Pathophysiology''|pp=530–541}} A similar effect, known as [[ebullism]], may occur during [[explosive decompression]], when water vapour forms bubbles in body fluids due to a dramatic reduction in environmental pressure.{{r|Landis}}

=== Inert gases ===
The main inert gas in air is [[nitrogen]], but nitrogen is not the only gas that can cause DCS. [[Breathing gas]] mixtures such as [[Trimix (breathing gas)|trimix]] and [[heliox]] include [[helium]], which can also cause decompression sickness. Helium both enters and leaves the body faster than nitrogen, so different decompression schedules are required, but, since helium does not cause [[Nitrogen narcosis|narcosis]], it is preferred over nitrogen in gas mixtures for deep diving.{{sfn|Hamilton & Thalmann|p=475}}
There is some debate as to the decompression requirements for helium during short-duration dives. Most divers do longer decompressions; however, some groups like the [[WKPP]] have been experimenting with the use of shorter decompression times by including [[Decompression practice#Deep stops|deep stops]].{{r|Wienke2002}} The balance of evidence as of 2020 does not indicate that deep stops increase decompression efficiency.<!-- Several sources, Mitchell? Doolette and Mitchell? -->

Any inert gas that is breathed under pressure can form bubbles when the ambient pressure decreases. Very deep dives have been made using [[hydrogen]]–oxygen mixtures ([[Hydrox (breathing gas)|hydrox]]),{{r|fife}} but controlled decompression is still required to avoid DCS.{{r|uhms33}}

=== Isobaric counterdiffusion ===
{{Further|Isobaric counterdiffusion}}

DCS can also be caused at a constant ambient pressure when switching between gas mixtures containing different proportions of inert gas. This is known as [[isobaric counterdiffusion]], and presents a problem for very deep dives.{{sfn|Hamilton & Thalmann|p=477}} For example, after using a very helium-rich [[trimix (breathing gas)|trimix]] at the deepest part of the dive, a diver will switch to mixtures containing progressively less helium and more oxygen and nitrogen during the ascent. Nitrogen diffuses into tissues 2.65 times slower than helium but is about 4.5 times more soluble. Switching between gas mixtures that have very different fractions of nitrogen and helium can result in "fast" tissues (those tissues that have a good blood supply) actually increasing their total inert gas loading. This is often found to provoke inner ear decompression sickness, as the ear seems particularly sensitive to this effect.{{r|burton2004}}

=== Bubble formation ===
The location of micronuclei or where bubbles initially form is not known.{{r|Papadopoulou 2013}} The most likely mechanisms for bubble formation are [[tribonucleation]], when two surfaces make and break contact (such as in joints), and heterogeneous [[nucleation]], where bubbles are created at a site based on a surface in contact with the liquid. Homogeneous nucleation, where bubbles form within the liquid itself is less likely because it requires much greater pressure differences than experienced in decompression.{{r|Papadopoulou 2013}} The spontaneous formation of nanobubbles on [[hydrophobic]] surfaces is a possible source of micronuclei, but it is not yet clear if these can grow large enough to cause symptoms as they are very stable.{{r|Papadopoulou 2013}}

Once microbubbles have formed, they can grow by either a reduction in pressure or by diffusion of gas into the gas from its surroundings. In the body, bubbles may be located within tissues or carried along with the bloodstream. The speed of blood flow within a blood vessel and the rate of delivery of blood to capillaries ([[perfusion]]) are the main factors that determine whether dissolved gas is taken up by tissue bubbles or circulation bubbles for bubble growth.{{r|Papadopoulou 2013}}

=== Pathophysiology ===
The primary provoking agent in decompression sickness is bubble formation from excess dissolved gases. Various hypotheses have been put forward for the nucleation and growth of bubbles in tissues, and for the level of supersaturation which will support bubble growth. The earliest bubble formation detected is subclinical intravascular bubbles detectable by doppler ultrasound in the venous systemic circulation. The presence of these "silent" bubbles is no guarantee that they will persist and grow to be symptomatic.{{sfn|Calder 1986 |pp=241-245 }}

Vascular bubbles formed in the systemic capillaries may be trapped in the lung capillaries, temporarily blocking them. If this is severe, the symptom called "chokes" may occur.{{r|Vann 1989}} If the diver has a [[patent foramen ovale]] (or a [[shunt (medical)|shunt]] in the pulmonary circulation), bubbles may pass through it and bypass the pulmonary circulation to enter the arterial blood. If these bubbles are not absorbed in the arterial plasma and lodge in systemic capillaries they will block the flow of oxygenated blood to the tissues supplied by those capillaries, and those tissues will be starved of oxygen. Moon and Kisslo (1988) concluded that "the evidence suggests that the risk of serious neurological DCI or early onset DCI is increased in divers with a resting right–to-left shunt through a PFO. There is, at present, no evidence that PFO is related to mild or late onset bends.{{r|Moon1998}} Bubbles form within other tissues as well as the blood vessels.{{r|Vann 1989}} Inert gas can diffuse into bubble nuclei between tissues. In this case, the bubbles can distort and permanently damage the tissue.{{r|Spira 1999}} As they grow, the bubbles may also compress nerves, causing pain.{{r|Stephenson |Medscape}} [[Extravascular]] or autochthonous{{ref label|a|a}} bubbles usually form in slow tissues such as joints, tendons and muscle sheaths. Direct expansion causes tissue damage, with the release of [[histamines]] and their associated affects. Biochemical damage may be as important as, or more important than mechanical effects.{{r|Vann 1989 |Stephenson |Kitano}}

Bubble size and growth may be affected by several factors – gas exchange with adjacent tissues, the presence of [[surfactants]], coalescence and disintegration by collision.{{sfn|Calder 1986 |pp=241–245 }} Vascular bubbles may cause direct blockage, aggregate platelets and red blood cells, and trigger the coagulation process, causing local and downstream clotting.{{r|Spira 1999}}

Arteries may be blocked by intravascular fat aggregation. [[Platelet]]s accumulate in the vicinity of bubbles. [[Endothelium|Endothelial]] damage may be a mechanical effect of bubble pressure on the vessel walls, a toxic effect of stabilised platelet aggregates and possibly toxic effects due to the association of lipids with the air bubbles.{{sfn|Calder 1986 |pp=241–245 }} Protein molecules may be denatured by reorientation of the secondary and tertiary structure when non-polar groups protrude into the bubble gas and hydrophilic groups remain in the surrounding blood, which may generate a cascade of pathophysiological events with consequent production of clinical signs of decompression sickness.{{sfn|Calder 1986 |pp=241–245 }}

The physiological effects of a reduction in environmental pressure depend on the rate of bubble growth, the site, and surface activity. A sudden release of sufficient pressure in saturated tissue results in a complete disruption of cellular organelles, while a more gradual reduction in pressure may allow accumulation of a smaller number of larger bubbles, some of which may not produce clinical signs, but still cause physiological effects typical of a blood/gas interface and mechanical effects. Gas is dissolved in all tissues, but decompression sickness is only clinically recognised in the central nervous system, bone, ears, teeth, skin and lungs.{{sfn|Calder 1986 |pp=246–254 }}

Necrosis has frequently been reported in the lower cervical, thoracic, and upper lumbar regions of the spinal cord. A catastrophic pressure reduction from saturation produces explosive mechanical disruption of cells by local effervescence, while a more gradual pressure loss tends to produce discrete bubbles accumulated in the white matter, surrounded by a protein layer.{{sfn|Calder 1986 |pp=246–254 }} Typical acute spinal decompression injury occurs in the columns of white matter. Infarcts are characterised by a region of [[oedema]], haemorrhage and early [[myelin]] degeneration, and are typically centred on small blood vessels. The lesions are generally discrete. Oedema usually extends to the adjacent grey matter. [[Thrombus|Microthrombi]] are found in the blood vessels associated with the infarcts.{{sfn|Calder 1986 |pp=246–254 }}

Following the acute changes there is an invasion of lipid [[phagocytes]] and degeneration of adjacent neural fibres with vascular [[hyperplasia]] at the edges of the infarcts. The lipid phagocytes are later replaced by a cellular reaction of [[astrocytes]]. Vessels in surrounding areas remain patent but are [[collagen]]ised.{{sfn|Calder 1986 |pp=246–254 }} Distribution of spinal cord lesions may be related to vascular supply. There is still uncertainty regarding the [[aetiology]] of decompression sickness damage to the spinal cord.{{sfn|Calder 1986 |pp=246–254 }}

[[Dysbaric osteonecrosis]] lesions are typically bilateral and usually occur at both ends of the [[femur]] and at the proximal end of the [[humerus]]. Symptoms are usually only present when a joint surface is involved, which typically does not occur until a long time after the causative exposure to a hyperbaric environment. The initial damage is attributed to the formation of bubbles, and one episode can be sufficient, however incidence is sporadic and generally associated with relatively long periods of hyperbaric exposure and aetiology is uncertain. Early identification of lesions by [[radiography]] is not possible, but over time areas of radiographic opacity develop in association with the damaged bone.{{sfn|Calder 1986 |pp=254–258 }}