Upon return of venous blood into the lung and subsequent exhalation of carbon dioxide, the blood is "de-acidified" (see also: hyperventilation) allowing for the deprotonation/unionization of hemoglobin to then re-enable oxygen-binding as part of the transition to arterial blood (note this process is complex due to involvement of chemoreceptors and other physiological functionalities). Carbon monoxide is not ejected due to acid, therefore carbon monoxide poisoning disturbs this physiological process hence the venous blood of poisoning patients is bright red akin to arterial blood since the carbonyl/carbon monoxide is retained. Hemoglobin is dark in deoxygenated venous blood, but it has a bright red color when carrying blood in oxygenated arterial blood and when converted into carboxyhemoglobin in both arterial and venous blood, so poisoned cadavers and even commercial meats treated with carbon monoxide acquire an unnatural lively reddish hue.At toxic concentrations, carbon monoxide as carboxyhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells and preventing formation of carbaminohemoglobin which accounts for approximately 30% of carbon dioxide exportation. Therefore, a patient with carbon monoxide poisoning may experience severe hypoxia and acidosis (potentially both respiratory acidosis and metabolic acidosis) in addition to the toxicities of excess carbon monoxide inhibiting numerous hemoproteins, metallic and non-metallic targets which affect cellular machinery. Myoglobin
Carbon monoxide also binds to the hemeprotein myoglobin. It has a high affinity for myoglobin, about 60 times greater than that of oxygen. Carbon monoxide bound to myoglobin may impair its ability to utilize oxygen.
Different mutations are associated with differential severity of symptoms, such as mild to severe gynecomastia. For example, duplications result in relatively mild gynecomastia, while deletions, resulting in chimeric genes, cause moderate or severe gynecomastia. Diagnosis
Genetic tests are now available to identify the variants in CYP19A1 associated with AEXS. The National Institutes of Health maintains a list. Treatment
Several treatments have been found to be effective in managing AEXS, including aromatase inhibitors and gonadotropin-releasing hormone analogues in both sexes, androgen replacement therapy with non-aromatizable androgens such as DHT in males, and progestogens (which, by virtue of their antigonadotropic properties at high doses, suppress estrogen levels) in females. In addition, male patients often seek bilateral mastectomy, whereas females may opt for breast reduction if warranted.Medical treatment of AEXS is not absolutely necessary, but it is recommended as the condition, if left untreated, may lead to excessively large breasts (which may necessitate surgical reduction), problems with fertility, and an increased risk of endometriosis and estrogen-dependent cancers such as breast and endometrial cancers later in life. At least one case of male breast cancer has been reported. Society and culture
Names
AEXS has also been referred to as familial hyperestrogenism, familial gynecomastia, and familial adrenal feminization. Notable cases
It has been hypothesized that the Pharaoh Akhenaten (husband of Queen Nefertiti) and other members of the 18th Dynasty of ancient Egypt may have had AEXS.