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13.3.2 Binding of carbon monoxide to myoglobin

Myoglobin is the oxygen-binding protein in muscle and is similar to haemoglobin in the blood. It too has an increased affinity for CO when compared to oxygen, forming carboxymyoglobin, but the difference is only 60-fold. However, the lack of adequate oxygen supplies to the muscle results in fatigue or decreased exercise tolerance and early onset of tiredness. About 15 % of the CO that enters the body binds to myoglobin (Coburn 1970 ).

13.3.3 Other toxic effects of carbon monoxide

During CO exposure, cells are deprived of their normal oxygen supply due to reduced oxyhaemoglobin levels, but cells are also unable to utilize the oxygen that they do receive due to CO interfering with the activity of enzymes such as cytochrome oxidase, and other mechanisms that are involved in the utilization of oxygen by the cells.

CO is also directly toxic and several other symptoms, signs, and biochemical changes following acute CO exposures have been reported, although they have not been substan-tiated by studies in humans. Some studies suggest that the re-oxygenation process may affect the central nervous system and that the production of oxygen radicals may damage cells (Ernst and Zibrak 1998 ).

13.4

Health effects of acute and chronic carbon monoxide poisoning

Adverse health effects associated with CO are related to the concentration of COHb in the blood ( Tables 13.2 and 13.3 ) and the duration of exposure. There are two well-defined forms of CO poisoning. Acute poisonings are usually due to exposure to high Table 13.2 Human health effects following exposure to carbon monoxide

Blood

carboxyhaemoglobin levels ( %)

Observed health effects

<2 No significant health effects

2.5–4.0 Decreased short-term maximal exercise duration in young healthy men 2.7–5.1 Decreased exercise duration due to increased chest pain (angina) in

patients with ischaemic heart disease

2.0–20.0 Equivocal effects on visual perception, audition, motor, and sensorimotor performance, vigilance, and other measures of neurobehavioural performance

4.0–33.0 Decreased maximal oxygen consumption with short-term strenuous exercise in young healthy men

20–30 Throbbing headache

30–50 Dizziness, nausea, weakness, collapse > 50 Unconsciousness and death

Adapted from the Department of the Environment, Transport and the Regions ( 1998 ) and the Department of Health ( 2004 ).

concentrations of CO for short durations (minutes or hours). Chronic poisonings occur when exposure takes place at lower but nevertheless toxic concentrations of CO over more prolonged periods, such as days, weeks, or even years. Both types have non-specific symptoms that mimic other common diseases, such as influenza or food poisoning, which may lead to mis-diagnosis (Department of Health 2010 ).

13.4.1 Acute carbon monoxide poisoning

13.4.1.1 Immediate effects

With acute, high-level exposure to CO, headache, nausea, and vomiting are early symptoms and there may be rapid progression to dizziness, confusion, shortness of breath, blurred vision, loss of consciousness, fits, and death.

Following acute exposures, patients are likely to seek immediate medical assistance.

However, disease progression may be so rapid that confusion and un-coordination may be severe enough to prevent the patient from dialling 999 or asking for help. Death is likely if the person is not immediately evacuated or removed from the source of exposure and treated with high concentrations of oxygen.

Acute poisoning may be severe enough to cause brain damage and damage to the heart muscle. Irregular heart rhythms (arrhythmias) are commonly seen, as are signs and symptoms of heart attacks. In 2005, Satran et al. reported that permanent damage to heart muscle (myocardial injury) is common in patients hospitalized following moderate to severe CO poisoning (Satran et al. 2005 ). The group showed that enzymes that con-firmed injury to heart muscle were raised and that there were abnormal changes in the electrocardiogram. They also showed that those who sustained damage to heart muscle died earlier than those who did not.

Many CO poisoned patients have symptoms and signs of abnormal brain function such as impaired memory, tendency to abnormal involuntary movements, gait abnormalities, and some disturbances of vision. Twenty-four hours after acute severe exposure to CO, where there has been loss of consciousness, CT scanning may show changes indicative of brain damage. Damage to the basal ganglia is a characteristic of CO-induced brain damage.

Table 13.3 Threshold toxicity values for exposure to carbon monoxide by inhalation Concentration of

400–600 460–690 4–5 hours Severe headache, weakness, dizziness, nausea, vomiting

1100–1500 1265–1840 4–5 hours Increased pulse and breathing rate, syncope, coma, intermittent seizures 5000–10,000 5750–11,500 1–2 minutes Weak pulse, depressed respiration/

respiratory failure, death

Reproduced from Carbon Monoxide Incident Management, HPA 2010, http://www.hpa.org.uk/web/HPAwebFile/

HPAweb_C/1194947341118, with data from IPCS 1996 Poisons Information Monograph http://www.inchem.org/

documents/pims/chemical/pim947.htm

Neurological symptoms such as headache, lethargy, irritability, and Parkinsonism may be delayed for 2–240 days post exposure, although the mechanisms for this are not well understood (Ernst and Zabrik 1998 ).

13.4.1.2 Long-term effects

Following recovery from acute exposure, many patients suffer from a wide range of residual ill-health.

a. The exposure itself may have been so emotionally traumatic that symptoms of post-traumatic stress disorder may occur.

b. The patient may suffer from the effects of brain damage due to the lack of adequate oxygen to the brain cells during the period of severe poisoning. These symptoms may range from personality changes to memory loss to deterioration of mental acuity or mental sharpness.

c. The patient may suffer damage to heart muscle, which may result in changes in the electrocardiogram associated with an elevation of enzymes, indicative of injury to heart muscle (Sartran et al. 2005 ). For example, plasma levels of a structural protein found in the myocardium, troponin, may increase. This damage to the heart muscle would make an individual more vulnerable to subsequent ischaemic episodes and also pre-disposed to clinical states such as heart failure.

d. Damage to muscle cells due to a lack of oxygen during exposure may lead to a break-down of muscle fibres and release of myoglobin, which can damage the kidneys and cause renal failure.

13.4.2 Chronic carbon monoxide poisoning

13.4.2.1 Immediate effects

Chronic CO toxicity occurs when there has been long-term exposure (months or even years) to low but toxic doses of CO. This usually occurs in homes and more rarely at workplaces or in cars. It is therefore usual for more than one person to have been exposed to the toxic environment and for other household members, including pets, to present with similar symptoms. Symptoms often improve once the patient is away from their home for a period of time and may worsen over weekends and during the winter months when more time is spent indoors, resulting in prolonged exposures.

With such exposures, death is most unlikely and patients usually seek assistance from GPs, often on a very regular basis. It is very difficult to make a diagnosis without a high index of awareness of the nature of ill-health associated with such exposures as the signs and symptoms are very non-specific.

Patients tend to attend the surgeries of GPs with recurrent flu-like illnesses, sore throats, coughs, impaired memory, and confusion. It is unfortunate that most of these patients are diagnosed as suffering from minor ailments or from depression, anxiety, or another psychiatric illness. In the vast majority of cases, the identification of the cause of ill-health as exposure to CO is only made or confirmed following the detection of a faulty appliance at the home or another source of exposure. As discussed in section 13.3.1, the short half-life

of COHb makes biological confirmation difficult if exposure was to low levels and time has passed since exposure ceased.

13.4.2.2 Long-term effects

The main problem with exposure to low but toxic concentrations of CO is that diagnosis is often delayed and as a result patients have suffered considerable emotional, mental and physical disability. Patients may have suffered from months or years of poor memory, impaired concentration, poor effort tolerance, apathy, and lethargy. They may have a sense of frustration as they have not been diagnosed for a long period despite repeated medical consultations and treatment schedules.

Following cessation of exposure, these patients require considerable encouragement to resume their normal lives. A substantial degree of recovery can be expected within about three years of cessation of exposure provided no further exposure takes place. Patients may benefit from cognitive behavioural therapy to overcome their deficits. However, some may not show significant recovery and may fail to lead the lives they led prior to toxic exposure. This can be especially important for children, who may have performed poorly at school due to impaired concentration and mental ability.

In recognition of the importance of chronic CO poisoning and its toxicological differ-ences to acute poisoning, the World Health Organization in 2010 published a guideline value for chronic (24-hour mean) exposure to CO in the indoor environment (WHO 2010 ; Table 13.1 ).