Histotoxic hypoxia (also called histoxic hypoxia) is the inability of cells to take up or use oxygen from the bloodstream, despite physiologically normal delivery of oxygen to such cells and tissues.
[ ] Histotoxic hypoxia results from tissue poisoning, such as that caused by
cyanide
Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms.
In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...
(which acts by inhibiting
cytochrome oxidase
The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes.
It is the last enzyme in the respiratory elect ...
) and certain other
poisons like
hydrogen sulfide (byproduct of sewage and used in leather tanning).
Causes
Histotoxic hypoxia refers to a reduction in
ATP production by the
mitochondria due to a defect in the cellular usage of oxygen.
Cyanide
An example of histotoxic hypoxia is
cyanide poisoning
Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, sl ...
. There is a profound drop in tissue oxygen consumption since the reaction of oxygen with cytochrome oxidase is blocked by the presence of cyanide. Cyanide binds to the ferric ion on cytochrome oxidase a
3 and prevents the fourth and final reaction in the electron transport chain. This completely stops oxidative phosphorylation and prevents the mitochondria from producing ATP.
There are other chemicals that interrupt the mitochondrial electron transport chain (e.g.,
rotenone
Rotenone is an odorless, colorless, crystalline isoflavone used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the seeds and stems of several plants, such as the jicama vine plant, and the roots of several mem ...
,
antimycin A
Antimycin A (more exactly Antimycin A1b) is a secondary metabolite produced by ''Streptomyces'' bacteria and a member of a group of related compounds called antimycins. Antimycin A is classified as an extremely hazardous substance in the United ...
) and produce effects on tissue oxygenation similar to that of cyanide. Oxygen extraction decreases in parallel with the lower oxygen consumption, with a resulting increase in venous oxygen content and PvO2. Although cyanide stimulates the peripheral respiratory chemoreceptors, increasing the inspired oxygen fraction is not helpful, since there is already an adequate amount of oxygen which the poisoned cells cannot use.
Treatments
Cyanide antidote kit is a widely used method in treating cyanide induced histotoxic hypoxia. It consists of three different parts that are administered one after the other. The three parts are
amyl nitrite
Amyl nitrite is a chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrite functional group. The alkyl group is unreactive and the chemical and biological properties ...
,
sodium nitrite
Sodium nitrite is an inorganic compound with the chemical formula NaNO2. It is a white to slightly yellowish crystalline powder that is very soluble in water and is hygroscopic. From an industrial perspective, it is the most important nitrite ...
, and
sodium thiosulfate
Sodium thiosulfate (sodium thiosulphate) is an inorganic compound with the formula . Typically it is available as the white or colorless pentahydrate, . The solid is an efflorescent (loses water readily) crystalline substance that dissolves well in ...
.
The nitrites act with
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
to form
methemoglobin
Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Sometimes, it i ...
which binds cyanide. Cyanide has a preference to the ferric ion on methemoglobin over the ferric ion on cytochrome oxidase a
3 and causes cyanide to be drawn out of the mitochondria. This causes the mitochondria to produce ATP again and stop histotoxic hypoxia.
Ischemia
Histotoxic hypoxia can be a consequence of ischemia in the case of
stroke or inflammation. In the case of inflammation, neuro-inflammatory diseases like
Alzheimer's disease,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and
Multiple Sclerosis can all lead to histotoxic hypoxia. During a stroke, there is an interruption in the blood supply followed by reperfusion which leads to histotoxic hypoxia because of an accumulation of
reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
(ROS).
In the case of inflammatory diseases, histotoxic hypoxia can also be triggered by ROS from mitochondrial damage in the active lesions of chronic multiple sclerosis. Inflammatory mediators such as
heme oxygynase-1(HO-1) can result in histotoxic hypoxia when they are released in excess and cause the sequestration of iron as in the cases of Alzheimer's disease, Parkinson's disease and Multiple Sclerosis.
See also
*
Hypoxia
References
{{DEFAULTSORT:Histotoxic Hypoxia
Poisoning by drugs, medicaments and biological substances
Respiration