Oxygen toxicity

# Overview
Oxygen toxicity or oxygen toxicity syndrome (also known as the "Paul Bert effect") is severe hyperoxia caused by breathing oxygen at elevated partial pressures. The high concentration of oxygen damages cells. The precise mechanism(s) of the damage are not known, but oxygen gas has a propensity to react with certain metals to form superoxide which may attack double bonds in many organic systems, including the unsaturated fatty acid residues in cells. High concentrations of oxygen are known to increase the formation of cascades of such free-radicals in biological systems, at which in many then go on to directly harm DNA and other structures (see nitric oxide, peroxynitrite, and trioxidane). Normally, the body has many defense systems against such damage (see glutathione, catalase, and superoxide dismutase) but at higher concentrations of free oxygen, these systems are eventually overwhelmed with time, and the rate of damage to cell membranes exceeds the capacity of systems which control or repair it. Cell damage and cell death then results.

# Classification
In humans, there are several types of oxygen toxicity:
- Central nervous system (CNS) oxygen toxicity.
The onset depends upon partial pressure of oxygen (ppO2) in the breathing gas and exposure duration and manifests as dizziness, nausea and twitching, especially on the face.  As partial pressure or duration increases, it leads to more severe symptoms, such as convulsions, which although not lethal themselves, when it occurs in divers, can cause drowning or lethal pressure damage during a rapid ascent to the surface. The maximum single exposure limits recommended in the NOAA Diving Manual are 45 minutes at 1.6 bar, 120 minutes at 1.5 bar, 150 minutes at 1.4 bar, 180 minutes at 1.3 bar and 210 minutes at 1.2 bar, but is impossible to predict with any reliability whether or when CNS symptoms will occur.
- Pulmonary oxygen toxicity
The risk of bronchopulmonary dysplasia ("BPD") in infants, or adult respiratory distress syndrome in adults, begins to increase with exposure for over 16 hours to partial pressures of 0.5 bar or more. Experimentally, early symptoms of breathing 100% oxygen are breathing difficulty and substernal pain, but in a healthy adult these are rarely seen before 24 hours of exposure. The lungs show inflammation and pulmonary edema. Partial pressures between 0.2 bar (normal at sea level) and 0.5 bar usually are considered non-toxic. BPD is reversible in the early stages during "break" periods on lower oxygen pressures, but it may eventually result in irreversible lung damage, if allowed to progress to severe damage. Usually several days of exposure without "oxygen breaks" are needed to cause severe lung damage. The time-factor and the naturally intermittent nature of most diving makes this a relatively rare (and even then, reversible) complication for divers. However, it is of concern in intensive care patients needing continuous high inspired oxygen concentrations.
At sea-level, 0.5 bar is exceeded by gas mixtures having oxygen fractions greater than 50%. Lung oxygen toxicity damage-rates at sea-level pressure rise non-linearly between the 50% threshold of toxicity, and the rate of damage on 100% oxygen. For this reason, intensive care patients requiring more than 60% oxygen, and especially patients at fractions near 100% oxygen, are considered to be at especially high risk, since if the situation is not corrected, the treatment may begin to cause lung damage which contributes to need for the high-oxygen mixture.
Care must be used in distinguishing oxygen mole fraction from oxygen partial pressure.  As noted earlier in this article, the toxicity is from high partial pressure.  This is illustrated by oxygen use in spacesuits and other low-pressure applications (historically, for example, the Gemini spacecraft and Apollo spacecraft).  High fraction oxygen is non-toxic even at breathing mixture oxygen fractions approaching 100%, because the oxygen partial pressure is not allowed to chronically exceed 0.35 bar in these applications.
- Retinopathic oxygen toxicity causes damage to the retina. Oxygen may be a contributing factor for the disorder called retinopathy of prematurity.

# Hyperoxia
Hyperoxia is excess oxygen in body tissues or higher than normal partial pressure of oxygen.  Hyperoxia is caused by breathing gas at pressures greater than normal atmospheric pressure or by breathing oxygen-rich gases at normal atmospheric pressure for a prolonged period of time.

# Common causes
The oxygen toxicity syndrome may occur
- as a diving disorder, when divers breathe any breathing gas deeper than its maximum operating depth,
- as a potential complication of mechanical ventilation with pure oxygen, where it is called the respiratory lung syndrome.
Oxygen toxicity is not a major factor in hyperventilating, as some people believe. The problems caused by hyperventilating are due to decreased carbon dioxide within the blood.  With or without hyperventilating, it is impossible to develop oxygen toxicity breathing air at typical surface atmospheric pressure.

# Avoiding oxygen toxicity while diving
CNS oxygen toxicity is a deadly but entirely avoidable event while diving. The diver generally experiences no warning signs because the brain primarily monitors carbon dioxide levels. The symptoms are sudden convulsions and unconsciousness, during which the victim will lose his regulator and drown. There is an increased risk of CNS oxygen toxicity on deep dives, long dives or dives where oxygen-rich breathing gases are used.
In some diver training courses for these types of diving, divers are taught to plan and monitor what is called the "oxygen clock" of their dives. This clock is a notional alarm clock, which "ticks" more quickly at increased ppO2 and is set to activate at the maximum single exposure limits recommended in the NOAA Diving Manual stated in the Types of Oxygen Toxicity section of this article. Many Nitrox-capable dive computers also calculate this "Oxygen Loading".
The aim is to avoid activating the alarm by reducing the ppO2 of the breathing gas or the length of time breathing gas of higher ppO2. As the ppO2 depends on the fraction of oxygen in the breathing gas and the depth of the dive, the diver can obtain more time on the oxygen clock by diving at a shallower depth, by breathing a less oxygen-rich gas or by shortening the exposure to oxygen-rich gases.

# Related chapters
- Maximum operating depth
- Breathing gas
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