The location of micronuclei or where bubbles initially form is not known.

[60] 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.[60] 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.[60]
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.[60]

Pathophysiology[edit]
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.[61]
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.[62] If the diver
has a patent foramen ovale (or a 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."[63] Bubbles form within other tissues as
well as the blood vessels.[62] Inert gas can diffuse into bubble nuclei between tissues. In this case, the
bubbles can distort and permanently damage the tissue.[64] As they grow, the bubbles may also
compress nerves as they grow causing pain.[65][66]Extravascular or autochthonous[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.[65][62][67]
Bubble size and growth may be affected by several factors - gas exchange with adjacent tissues, the
presence of surfactants, coalescence and disintegration by collision.[61] Vascular bubbles may cause
direct blockage, aggregate platelets and red blood cells, and trigger the coagulation process,
causing local and downstream clotting.[64]
Arteries my be blocked by intravascular fat aggregation. Platelets accumulate in the vicinity of
bubbles. 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.[61] 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.[61]
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.[68]
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.[68] 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. Microthrombi are found in the blood vessels associated with the infarcts.[68]
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 collagenised.[68] 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.[68]
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.[69]

Diagnosis