Hypoxia caused local

Damaging mechanisms. Due to their physical and chemical properties, toluol molecules cause local irritative hyperemic lesions on the contact mucosa of the respiratory tract, dystrophic damage of the cerebrum and liver cells mainly by inhibition of enzyme groups and intracellular hypoxia. 

Some of the vasoconstrictor may be absorbed systemically, occasionally to an extent sufficient to cause untoward reactions (see below). There also may be delayed wound healing, tissue edema, or necrosis after local anesthesia. These effects seem to occur partly because sympathomimetic amines can cause hypoxia and local tissue damage. The use of vasoconstrictors in local-anesthetic preparations for anatomical regions with Umited collateral circulation could produce irreversible hypoxic damage, tissue necrosis, and gangrene, and therefore is contraindicated. 

State of deviation of plasma pH (systemic acidosis) or tissue extracellular pH (tissue or local acidosis) from normal (ca. pH 7.4) towards lower values. Deviation of 0.1 pH units is significant. Systemic acidosis can be caused by lung or kidney failure. Local acidosis can be the consequence of injury, inflammation, or tumor growth, due to disruption of blood supply. Local acidosis is normally associated with hypoxia. 

The other major toxic effect of methanol is the ocular toxicity. Although formaldehyde might be formed locally in the retina, this seems unlikely, whereas formate is known to cause experimental ocular toxicity. The mechanism suggested involves inhibition by formate of cytochrome oxidase in the optic nerve. As the optic nerve cells have few mitochondria, they are very susceptible to this "histotoxic hypoxia,"... 

As described above, early in wound healing, there is an increase in HA. This transient increase correlates with hypoxia and the production of lactate that follows the compromised local blood supply. A cause and effect was documented in this laboratory between enhanced levels of HA and lactate production.251,252 Lactic acid is an alpha-hydroxy acid, the latter being a frequent additive to skin preparations. Enhanced HA deposition and the attendant water-of-hydration may be a common mechanism for the enhanced appearance of skin when such lotions are used. 

Depolarization Local depolarization caused by focal hypoxia decompensates already threatened metabolism in penumbra and propagates ischemic damage... 

Excessive absorption results in paraesthesiae (face and tongue), anxiety, tremors and even convulsions. The latter are very dangerous, are followed by respiratory depression and may require diazepam or thiopental for control. Cardiovascular collapse and respiratory failure occur with higher plasma concentrations of the local anaesthetic and is caused by direct myocardial depression compounded by hypoxia associated with convulsions. Cardiopulmonary resuscitation must be started immediately. 

It has also been established that the RBC itself could act as a mobile sensor for hypoxia [61]. The mechanism works as follows Under conditions of low oxygen and pH, the RBC releases ATP, which binds to purinergic receptors on the endothelial cells. This leads to the production in the endothelial cells of the vasodilator NO. Since the most likely location for hypoxia would be in or near the venular network, the local vasodilatory response to NO is propagated to upstream vessels causing arteriolar vasodilation (see the following section on Coordination of Vasomotor Responses). 

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