Smoke inhalation injuries in fire victims
The clinical manifestations of acute and chronic smoke inhalation injuries are due to two processes; one, the direct effects the inhaled substances have on the respiratory system that is, pulmonary injuries and the systemic effects induced by the toxic gases such as cyanide and carbon monoxide absorbed. Pulmonary injuries can further be categorized into those affecting the upper airway and those below the level of the glottis. Smoke inhalation triggers a systemic inflammatory response. Diagnosis of smoke inhalation injuries is based on the presenting symptoms and a battery of diagnostic tests majorly blood gas analysis.
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Injuries of the upper airway occur due to direct heat and they manifest with erythema of the pharnynx and/or oral mucosa and edema which causes mechanical obstruction of either or both the larynx and pharynx. For pulmonary injuries below the level of the glottis, toxic chemicals contained in smoke stimulate the release of mediators of inflammation such as histamine and certain neuropeptides like the calcitonin-gene neuropeptide in the respiratory system. These neuropeptides in turn activate nitric oxide synthase (NOS) resulting in the release of nitric oxide which combines with superoxide radicals/ reactive oxygen species (ROS) forming reactive nitrogen species (RNS) peroxynitrite. RNS damages DNA activating PARP (poly ADP ribose polymerase) and in the process nitrates a number of other molecules and causes the production of other reactive species such as hydroxyl radicals. Activation of PARP results in the depletion of high-energy phosphates NAD and ATP which in turn leads to cell dysfunction and apoptosis (Hamahata et al., 2008). The pathological changes in the respiratory system mediated by NO and superoxide radicals therefore include airway blockage, an increase in pulmonary transvascular fluid flux resulting in massive pulmonary edema and the loss of hypoxic pulmonary vasoconstriction. This manifests clinically with one or more of the following, a fall in arterial oxygenation/hypoxemia, laryngeal stridor, sore throat, larngospasms, bronchospasms, cough, dyspnea, bradypnea, respiratory arrest, carbonaceous sputum and cyanosis (Traber et al., 2007).
Both carbon monoxide and cyanide bind to iron ions of erythrocytes and in specific, the mitochondrial enzyme cytochrome-c oxidase a. As such, they compete with oxygen for the available hemoglobin biding sites. CO affinity for hemoglobin is 200 times higher than that of oxygen while cyanide is a small lipid soluble molecule whose distribution and penetration into cells is quite rapid. The binding site of the cytochrome-c oxidase a enzyme is binuclear consisting of heme a3 and CuB. Carbon monoxide binds to the reduced heme forming carboxyhemoglobin while cyanide binds to either the oxidized heme or the reduced heme. Carbon monoxide impairs the ability of red blood cells to transfer oxygen while cyanide prevents the formation of ATP through blockage of the mitochondrial respiration chain. The net effect of both gases is cytotoxic hypoxia especially to the brain and heart which are very sensitive to tissue hypoxia. The initial symptoms of cyanide poisoning include a short interval of hyperpnea due to direct stimulation of aortic and carotid chemoreceptors by cyanide and sensations of dryness or burning in the nose and/or throat due to the stimulative effects cyanide has on nociceptors. Symptoms of mild cyanide poisoning include headaches, vertigo, nausea, hypertension, tachypnea and altered mental status. A patient with moderate cyanide poisoning presents with bradycardia, dyspnoea, arrhythmias and hypotension. Signs and symptoms of severe cyanide poisoning include unconsciousness, convulsions, pulmonary edema, cardiovascular collapse and death due to respiratory failure. Chronic signs of mild cyanide poisoning develop over a long time and encompass neurological impairments ranging from extrapyramidal syndromes to vegetative states, parkinson-like symptoms amongst others (Lawson-Smith, Jansen & Hyldegaard, 2011).
The symptoms of CO poisoning are due to tissue hypoxia and include headache, nausea, confusion, visual disturbances, unconsciousness, convulsions, malaise, fatigue and shortness of breath. The three cardinal signs of CO poisoning that is retinal hemorrhages, cherry red lips and peripheral cyanosis are however rare. Similar to cyanide, CO and nitric oxide also cause delayed neurological sequelea. Experiments on animal models show that CO poisioning leads to the activation of N-methyle-D-asparatate neurons whilst overactivity of NOS causes perivascular changes that lead to the sequestration and activation of of neutrophils. Activated neutrophils, xanthine oxidase and mitochondria on the other hand produce reactive oxygen species that cause brain lipid peroxidation. The exact mechanism via which these events cause neurological injuries is poorly understood. Inflammatory and immunologic responses in the brain to the products of brain lipid peroxidation are however thought to play a role in the development of neurological sequelea (Thom et al., 2004). NO and CO delayed neurological sequelea may present between 2 and 240 days after the fire injury incident. They include encephalopathy, memory loss, parkinsonism, personality changes, cognitive deficits, affective disorders (Olson & Smollin, 2008).
Inhalation injuries should be suspected in any patient who manifests with the following a history of the fire accident occurring within an enclosed area, burns affecting the face and neck, singled nasal hairs, bloody or sooty sputum, dyspnoea, tachypnea, sings of hypoxemia, hoarseness of the voice, dry cough, stridor and inflammation of the oral and/or pharyngeal mucosa. Since the symptoms of CO poisoning are non-specific, it is diagnosed via measurements of carboxyhemoglobin levels, arterial oxygenation and the partial pressures of oxygen. Cyanide poisoning should be suspected if two or more of the following diagnostic criteria are present, signs of neurological involvement such as alterations in the patient’s mental status, convulsions and unconsciousness, presence of soot in the mouth or nose or sooty sputum, lactate levels in arterial blood exceeding 8mmol/l which is indicative of metabolic acidosis. Blood analysis methods for cyanide are normally unavailable in most emergency settings or take too long whilst the patient requires immediate management. The two methods for whole blood cyanide analysis used currently include Conway/microdiffusion method and isotope-dilution gas chromatography-mass spectrometry (Lawson-Smith, Jansen & Hyldegaard, 2011). ROS can be detected via the measurement of their reaction products like 3-nitrotyrosine from the airway (Traber et al, 2007).
Conclusion
In conclusion thus, the clinical manifestations of acute and chronic smoke inhalation injuries are due to two processes; one, the direct effects the inhaled substances have on the respiratory system that is, pulmonary injuries and the systemic effects induced by the toxic gases. Direct heat is responsible for smoke inhalation injuries that affect the upper airway. Reactive oxygen and nitrogen species are on the other hand responsible for the pathophysiological processes below the level of the glottis and present with symptoms such as bronchospams, pulmonary edema amongst others. Absorbed toxic gases such as CO, NO and cyanide elicit systemic symptoms by causing tissue hypoxia with the brain and the heart being the most affected organs. Signs of tissue hypoxia include headache, nausea, dizziness amongst others. Chronic manifestations of smoke inhalation injuries are thought to be caused by immunologic and inflammatory processes prompted by pathological processes in the brain. CO, NO and cyanide have all been shown to cause neurological deficits such as parkinsonism in the long-term. The diagnosis of smoke inhalation injuries is based on clinical manifestations and blood analysis.
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