Health Worlds

First, the poisoning mechanism
Cyanide ions on the respiratory chain of mitochondria cytochrome oxidase (EC1.9.3.1) with high affinity, and cytochrome oxidase so that the loss of binding activity, thereby blocking cell respiration and oxidative phosphorylation.
Cytochrome oxidase is supplemented based porphyrin protein, contains two heme A groups and two copper atoms, respectively, of cytochrome a and a3. a and a3 has failed to separate the two components, it is cytochrome a and a3 will be collectively known as cytochrome oxidase. Hydrocyanic acid on the inhibition of cytochrome oxidase, mainly CN-and cytochrome a3 in the iron (Fe3) caused by ligand binding.
Oxidized cytochrome oxidase with CN-binding capacity after loss of electron transfer. And even oxygen can not be used, blocked oxidative phosphorylation, ATP synthesis decreased cellular uptake of energy a serious shortage of suffocation.
In vitro experiments show that, KCN1.5 10-6M inhibited liver cytochrome oxidase activity of 50%; concentration of 4.2 10-2M, the enzyme activity was completely inhibited.
Animal experiments show, poisoning symptoms and activity of cytochrome oxidase inhibition is equal, the enzyme activity is restored, the symptoms disappear. Cyanide inhibition of cytochrome oxidase on the speed and toxic dose and animal categories. Figure 14-3, mice were injected intraperitoneally KCN3mg/kg and 5mg/kg 5 to 15 minutes after the inhibition reached a maximum 70%, recovery time is 20


to 30 minutes.Cyanide ion can inhibit other enzymes with high heme iron, such as catalase and peroxidase cytochrome C peroxidase complex formation, but the concentration of inhibition of cytochrome oxidase than 1 ~ 2 to orders of magnitude. Some non-heme enzyme metal element, such as tyrosinase, ascorbic acid oxidase, xanthine oxidase, amino acid oxidase, can also form complexes with cyanide ions. But its high concentration of 10-2 ~ 10-3M to present different degrees of inhibition only. In addition, the cyanide containing Schiff base intermediate with the ribose -2- enzyme carboxyl phosphate and 2 - keto -4- hydroxy-glutaric acid salt to form cyanate aldolase inhibit the activity of intermediates.
Second, the toxicological effects
(A) of the central nervous system
Central nervous system on the cyanide ion sensitive, acute cyanide poisoning can cause certain brain regions and spinal cord degeneration of phosphate ester. At the same time in a variety of cyanide inhibition of enzyme systems, metabolic changes in the medium, Ca concentration significantly increased and membrane peroxidation ester enhanced antioxidant defense system damage, oxidative phosphorylation can not use the blocks and tissue of oxygen and so on. The changes in the toxicity of oxygen present. First, the central function of the cortex affected. Small dose of hydrogen cyanide can cause cortical inhibition, conditioned reflex disappeared. Severe poisoning, central nervous system inhibition showed from top to bottom. Changes in brain electrical activity consistent with the central activities, such as a monkey, cat, intravenous injection of NaCN, the first motor cortex regional activities reduced or lost, followed by the nucleus of the hypothalamus, midbrain, reticular formation and extension of brain electrical activity have been suppressed. EEG activity is restored, then start with the lower part of the start, bottom-up retrograde recovery.
(B) of the respiratory system
Small doses cause respiratory excited; large doses, respiratory inhibition after the first excitement. First accelerated in the deep breathing, then apnea, irregular breathing, and then again a second respiratory arrest. Paralysis of the respiratory center is the main reason for hydrogen cyanide poisoning. Changes in respiratory function caused by cyanide factors: the direct effect on the respiratory center; excited carotid body and aortic body chemoreceptor reflex respiratory center excitability. Cut off the neural pathway excitability was significantly reduced breathing; hypoxia, energy metabolism disorders, changes in blood pH; respiratory muscle spasm and paralysis.
(C) of the circulatory system
Small dose of cyanide on the cardiovascular excitatory effects, the performance of heart rate, cardiac output increases, blood pressure, then gradually returned to normal. If the toxic dose larger, after following the excitement, there may be suppression, bradycardia, decreased cardiac output, blood pressure, until the heart stops. Heart rate can be maintained in a few minutes after breathing stops. Circulatory failure also contributed to the cyanide poisoning death of one of the reasons. The factors causing these changes are: the cyanide ion on cardiovascular exercise and the direct effect of the central; aortic body and carotid body chemoreceptor reflex function; direct effect on the heart. Experiments show that injection of small doses of human intravenous NaCN (0.11 ~ 0.2mg/kg), ECG sinus arrest, sinus arrhythmia, heart rate to gradually speed up, 3 minutes back to normal. Lethal dose of inhaled hydrogen cyanide, there slow heart rate, sinus arrhythmia, P wave disappeared, atrioventricular block, ventricular fibrillation; QRS wave voltage and morphological changes may have, T wave amplitude increases, ST segment shortening and even disappear. ECG after poisoning is a complex mechanism, the early changes may be neurogenic, is the central toxic effects of reflection or result of the change late cyanide ions on the heart may be the direct damage and hypoxia. direct expansion of peripheral vascular function and tissue toxicity of oxygen and so on.
(D) changes in metabolism
Cyanide toxicity caused by tissue hypoxia and cellular metabolism changes include: aerobic oxidative metabolism blocked, anaerobic metabolism increased, decreased oxidative phosphorylation, ATP / ADP ratio of reduced or even reversed; glucose, lactate and inorganic phosphorus machine salt, hexose diphosphate, glycerol phosphate, phosphoric acid and other significant increase in pyruvate. Product due to an increase in blood acidity, acid-base balance, pH decreased, the occurrence of metabolic acidosis. Because oxygen can not be fully utilized, venous oxygen content increased, significantly reduced venous oxygen difference, arterial blood was bright red like blood.
Experiments show that rats injected KCN spasm, the -aminobutyric acid in brain tissue significantly reduced glutaredoxin acid content increased significantly, the concentration of intracellular Ca2 increase and neurotransmitter release; blood oxidized glutathione levels decreased rapidly , has increased the total glutathione; the prothrombin and coagulation factor deficiency, reducing the blood coagulation; thiocyanate in blood and urine were significantly increased. Temperature drops with the toxic dose, the dose the greater the reduction was even worse.



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