Oxygen Toxicity

In a broad sense, if the oxygen partial pressure is higher than the oxygen partial pressure at atmospheric pressure (21kPa), they can be called high partial pressure oxygen or hyperoxia. Hyperoxia is often used in diving operations, underwater special operations and clinic treatment. When in diving operations. Hyperoxia can shorten the decompression time after diving and avoid decompression sickness. In underwater special operations, a fully closed breathing apparatus is used to breathe high partial pressure. Oxygen can also improve its concealment. Hyperoxia can also improve the function of ischemic and hypoxic tissues in clinic treatment. However, if the oxygen pressure exceeds a certain threshold, or the breathing oxygen exceeds a certain time, it will cause adverse effects on the body, that is, oxygen toxicity. Currently, oxygen toxicity is a major factor that limited oxygen use in diving operations, underwater special operations, and clinical treatment. Oxygen toxicity is divided into lung type, brain type and eye type. When the oxygen partial pressure is between at 60 ~ 200 kPa, the damage to the body is mainly manifested in the lungs. It is called pulmonary oxygen toxicity. When the oxygen partial pressure exceeds 300 kpa, the damage caused by oxygen toxicity is mainly manifested in the central nervous system, which is called central nervous system oxygen toxicity or brain-type oxygen toxicity.

History of oxygen toxicity

In 1878, Paul Bert published his pioneer work La pression barometrique, in which he presented the results of years of study of the physiological effects of exposure to high and low pressures. He showed that although oxygen is essential to sustain life, it is lethal at high pressures. Larks exposed to air at 15 to 20 ATA developed convulsions. The same effect could be produced by oxygen at 5 ATA. Bert recorded similar convulsions in other species and clearly established the toxicity of oxygen on the CNS (Central nervous system), also known as the Paul Bert effect [1]. He did not report respiratory damage [2,3]. In 1899, the pathologist J. Lorrain Smith noted fatal pneumonia in a rat after exposure to 73 per cent oxygen at atmospheric pressure. He conducted further experiments on mice and gave the first detailed description of pulmonary changes resulting from moderately high oxygen tensions (approximately 1 ATA) for prolonged periods of time. Smith was aware of the limitations that this toxicity could place on the clinical use of oxygen. He also noted that early changes are reversible and that higher pressures shortened the time of onset. Pulmonary changes are also called the Lorrain Smith effect [1].

Clinical consequences of oxygen toxicity

The main systems or organs involved in oxygen toxicity are different with different oxygen partial pressure. Of all the presenting types of oxygen toxicity, pulmonary and central nervous system oxygen toxicity is the most important.

Pulmonary

When the partial pressure of oxygen is between 60 kpa and 200 kpa, the damage caused by oxygen toxicity is mainly manifested in the lungs, which is called pulmonary oxygen toxicity. Because the partial pressure of oxygen is relatively low, it takes a long time for oxygen toxicity to occur and is therefore also called chronic oxygen toxicity. The earliest symptom is usually a mild tracheal irritation similar to the tracheitis of an upper respiratory infection. This irritation is aggravated by deep inspiration, which may produce a cough. Smoking has a similar result. Chest tightness is often noted; then a substernal pain develops that is also aggravated by deep breathing and coughing. The cough becomes progressively worse until it is uncontrollable. Dyspnoea at rest develops and, if the exposure is prolonged, is rapidly progressive. The higher the inspired oxygen pressure, the more rapidly symptoms develop and the greater is the intensity. Physical signs, such as rales, nasal mucous membrane hyperaemia and fever, have been produced only after prolonged exposure in normal subjects [4,5].

CNS

When the partial pressure of oxygen exceeds 300 kpa, the damage caused by oxygen poisoning to the body is mainly manifested in the central nervous system, which is called Central Nervous System oxygen toxicity (CNS). It is also called acute oxygen toxicity for the partial pressure of oxygen is relatively high and the time required for oxygen poisoning to occur is short. Clinical signs of CNS toxicity start with visual changes such as tunnel vision, tinnitus, nausea, facial twitching, dizziness and confusion. The time for the appearance of symptoms is inversely related to the oxygen pressure and may be as short as 10 minutes at pressures of 4-5 atmospheres absolute [6]. This may be followed by tonic clonic seizures and subsequent unconsciousness. However, there appears to be no consistent pattern in the appearance of minor signs before the development of seizures. Seizures are the most dramatic and dangerous sign of oxygen toxicity but are reversible without residual neurological damage if the inspired oxygen partial pressure is reduced. The onset of seizures is dependent on the partial pressure of oxygen and the exposure duration. However, exposure time before onset is unpredictable amongst individuals and even in the same individual day-to-day [6,8,9]. Many external factors such as underwater action, exposure to cold and exercise will decrease the time to CNS symptoms [7,9]. Decreased performance is also closely related to the retention of carbon dioxide [7,10] Oxygen toxicity is particularly hazardous during diving because of the risks of drowning following a seizure.

Mechanisms of oxygen toxicity

The exact mechanism of oxygen toxicity is not fully understood. Oxygen is a very active element and an essential substance for the basic activities of life. It has a direct regulatory effect on a variety of physiological functions, including blood flow, tissue oxidation and energy metabolism, and this regulatory effect is directly related to its tension in the body.

The most biologically significant of these reactive oxidant species are the hydroxyl ion and peroxynitrite. Peroxynitrite, the product of the reaction between superoxide and nitric oxide, in particular, interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms [7,11]. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. The understanding of the molecular mechanisms underpinning both hyperoxia and hypoxic is still emerging [7,11-14] Although the body has many antioxidant systems these are eventually overwhelmed at very high concentrations of free oxygen when the rate of oxidative damage overwhelms the capacity of the systems that prevent or repair it. Cell damage and death result. Baik et al. systematically investigate the major cellular pathways affected by excess molecular oxygen in vitro and in vivo. They find that hyperoxia impairs diphthamide synthesis, de novo purine biosynthesis, nucleotide excision repair, and ETC bioenergetics due to the degradation of specific labile Fe-S cluster-containing proteins. Additionally, they prove a new model of cyclic oxygen Toxicity [15].

Oxygen is both essential and toxic for life. Although responses to hypoxic have been extensively studied, the specific molecular effects of hyperoxia are less understood. Though prior oxygen toxicity research has focused on tissue-level phenomena such as inflammation and non-specific oxidative injury, the molecular mechanisms involved have not been determined [16,17].

Other manifestations of oxygen toxicity shows on haematopoietic system, eye, ear, Vasoconstriction. Repeated or long-term exposure to high levels of oxygen free radicals could be expected to enhance tumour development. It is likely that, as more sensitive methods of detection are used, evidence of oxygen toxicity in many other cells and organs will be observed. However, it is urgent to understand the exact mechanism of oxygen toxicity in order to prevent and treat it.

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