Zatrucie tlenkiem węgla – Patofizjologia i mechanizm

Zatrucie tlenkiem węgla
Patofizjologia i mechanizm

Zatrucie tlenkiem węgla (CO) jest poważnym problemem zdrowotnym, charakteryzującym się wysoką śmiertelnością i szerokim spektrum objawów klinicznych zależnych od stężenia karboksyhemoglobiny (COHb). CO wykazuje 200-300-krotnie większe powinowactwo do hemoglobiny niż tlen, co prowadzi do tworzenia COHb i znaczącego upośledzenia transportu tlenu oraz przesunięcia krzywej dysocjacji oksyhemoglobiny w lewo, ograniczając uwalnianie tlenu do tkanek. Toksyczność CO obejmuje również hamowanie cytochromu c oksydazy, wiązanie z mioglobiną sercową oraz indukcję stresu oksydacyjnego i reaktywnych form tlenu (ROS), co skutkuje uszkodzeniem mitochondrialnym, apoptozą komórek oraz stanem zapalnym. Objawy kliniczne zaczynają się od bólów głowy przy poziomach COHb około 10%, a stężenia powyżej 50-60% mogą prowadzić do drgawek, śpiączki i zgonu. Ponadto, zatrucie CO wiąże się z powikłaniami neurologicznymi, takimi jak opóźniona encefalopatia (DEACMP), oraz kardiologicznymi, w tym ostrym uszkodzeniem mięśnia sercowego i dysfunkcją lewej komory.

Zatrucie tlenkiem węgla: Patogeneza, mechanizm

Zatrucie tlenkiem węgla (CO) stanowi istotny problem zdrowotny, dotykający rocznie około 50 000 osób w Stanach Zjednoczonych i jest jedną z głównych przyczyn śmierci w wyniku zatruć na całym świecie.¹² Znany jako „cichy zabójca”, CO jest gazem bezbarwnym, bezwonnym i pozbawionym właściwości drażniących, co sprawia, że jest szczególnie niebezpieczny, ponieważ osoby narażone mogą być nieświadome ekspozycji.³⁴

Wiązanie CO z hemoglobiną

Główny mechanizm toksycznego działania tlenku węgla opiera się na jego zdolności do wiązania się z żelazem protohemowym hemoglobiny (Hb), tworząc karboksyhemoglobinę (COHb).¹⁵ CO wykazuje 200-300 razy większe powinowactwo do hemoglobiny niż tlen, co powoduje, że hemoglobina preferencyjnie wiąże CO zamiast tlenu.⁶⁷ To prowadzi do:

Zmniejszenia zdolności krwi do transportu tlenu poprzez wypieranie tlenu z miejsc wiążących hemoglobiny⁸⁹
Stabilizacji hemoglobiny w stanie rozluźnionym (stan R) o wysokim powinowactwie, co zwiększa powinowactwo do tlenu pozostałych miejsc wiążących w tetramerze hemoglobiny¹¹⁰
Przesunięcia krzywej dysocjacji oksyhemoglobiny w lewo, co dodatkowo ogranicza uwalnianie tlenu do tkanek, pogłębiając niedotlenienie⁶¹¹

Wiązanie CO z hemoglobiną powoduje zmniejszenie zdolności przenoszenia tlenu oraz utrudnia tworzenie karbaminohemoglobiny, która odpowiada za około 30% eksportu dwutlenku węgla, co może prowadzić do ciężkiego niedotlenienia i kwasicy (zarówno oddechowej, jak i metabolicznej).¹²

Wpływ na mitochondria i oddychanie komórkowe

Toksyczność CO wykracza poza zaburzenia transportu tlenu przez hemoglobinę. Około 10-15% tlenku węgla znajduje się poza układem naczyniowym i wiąże się z innymi białkami zawierającymi hem, zakłócając funkcje komórkowe:⁹¹³

Cytochrom c oksydaza: CO hamuje oksydazę cytochromu w sposób podobny do cyjanku, blokując łańcuch oddechowy i upośledzając fosforylację oksydacyjną, co prowadzi do zmniejszenia produkcji ATP i nasilenia beztlenowego metabolizmu¹⁴¹⁵
Mioglobina: CO wiąże się z mioglobiną sercową i mięśni szkieletowych z jeszcze większym powinowactwem niż do hemoglobiny, powodując zaburzenia funkcji mięśnia sercowego, obniżenie kurczliwości i relaksację mięśni gładkich naczyń¹⁶⁷
NADPH reduktaza i inne enzymy zawierające hem: CO upośledza fosforylację oksydacyjną na poziomie mitochondrialnym⁹

Czas połowicznego rozpadu CO związanego z tymi cząsteczkami jest dłuższy niż w przypadku COHb, co może przyczyniać się do przedłużonego działania toksycznego.⁹ Znaczenie tych efektów niezwiązanych z hemoglobiną najlepiej udokumentowano w sercu, gdzie dysfunkcja mitochondrialna wywołana przez CO może powodować ogłuszenie mięśnia sercowego pomimo odpowiedniego dostarczania tlenu.¹¹

Generowanie reaktywnych form tlenu i stres oksydacyjny

CO powoduje powstawanie reaktywnych form tlenu (ROS) i stres oksydacyjny, co przyczynia się do uszkodzenia komórek i tkanek:¹⁷¹³

Indukuje tworzenie nadtlenku, co powoduje peroksydację lipidów, szczególnie w tkance nerwowej¹⁵¹⁸
Zamiast tworzyć wodę i ATP, mitochondria produkują destrukcyjne wolne rodniki tlenowe¹⁵
CO powoduje uwalnianie wolnych rodników tlenku azotu z płytek krwi i śródbłonka naczyniowego¹⁹
Prowadzi do stresu oksydacyjnego mitochondriów i apoptozy¹⁵

Badania wykazały uwalnianie wolnych rodników tlenku azotu (zaangażowanych w patofizjologię miażdżycy) z płytek krwi i śródbłonka naczyniowego po ekspozycji na stężenia CO wynoszące 100 ppm.¹⁹

Reakcje zapalne i immunologiczne

CO uruchamia kaskadę zapalną, która może prowadzić do oksydacyjnej degradacji lipidów układu nerwowego i opóźnionych następstw neurologicznych:²⁰

Aktywacja płytek krwi i neutrofili¹¹
Peroksydacja lipidów przez neutrofile¹⁵
Sekwestracja i aktywacja leukocytów, co prowadzi do uszkodzeń okołonaczyniowych²¹
Uszkodzenia immunologiczne¹⁵
Opóźniony stan zapalny¹⁵

CO powoduje stres oksydacyjny (z powodu zwiększonych poziomów hemu cytoplazmatycznego) i przerywa oddychanie komórkowe (przez wiązanie się z białkami płytek krwi i oksydazą cytochromu c) z wytwarzaniem reaktywnych form tlenu, które powodują apoptozę i martwicę neuronów.²²

Uszkodzenia narządowe

Toksyczność CO dotyka głównie organy o wysokim zapotrzebowaniu na tlen, przede wszystkim mózg i serce:¹⁶²²

Uszkodzenia mózgu

Mózg jest jednym z głównych celów toksycznego działania CO, ze względu na wysokie zapotrzebowanie na tlen:²²

Po ciężkim zatruciu pacjenci wykazują patologię ośrodkowego układu nerwowego, w tym demielinizację istoty białej¹⁹
Prowadzi to do obrzęku i ogniskowych obszarów martwicy, typowo w obustronnej gałce bladej¹⁹
Badania obrazowe ujawniają hiperintensywność istoty białej mózgu, z opóźnioną leukoencefalopatią posthipoksyczną lub rozlanym zanikiem mózgu²
CO wpływa na układ dopaminergiczny, powodując wzrost zewnątrzkomórkowego poziomu dopaminy poprzez zwiększenie uwalniania przy jednoczesnym hamowaniu metabolizmu i wychwytu zwrotnego²³²⁴

Nadmiar dopaminy utrzymuje się przez tygodnie i jest powiązany z uszkodzeniem oksydacyjnym, apoptozą i śmiercią synaps i jąder w układzie mezolimbicznym, szczególnie w gałce bladej.²³

Uszkodzenia serca

Zatrucie CO jest ściśle związane z szerokim zakresem powikłań sercowych:²⁵

Ostre uszkodzenie mięśnia sercowego, ciężka martwica i dysfunkcja kurczliwości²⁵
CO wiąże się z grupą hemową w mioglobinie z 60-krotnie większym powinowactwem niż tlen, ograniczając dostarczanie tlenu do mitochondriów i fosforylację oksydacyjną²³
To zaburzenie zmusza kardiomiocyty do wykorzystania metabolizmu beztlenowego, prowadząc do niedotlenienia, kwasicy mleczanowej i śmierci²³
CO ma znaczne działanie protrombotyczne, związane z zakrzepicą tętniczą i żylną²³
Powoduje również zmiany anatomiczne, takie jak włóknienie mięśnia sercowego i słabą funkcję lewej komory²³

Około jednej trzeciej umiarkowanie do ciężko zatrutych pacjentów wykazuje dysfunkcję sercową, w tym arytmię, dysfunkcję skurczową lewej komory i zawał mięśnia sercowego.²

Uszkodzenia nadnerczy

Zatrucie CO prowadzi również do zmian w nadnerczach, odpowiedzialnych za produkcję trzech podstawowych klas hormonów (glikokortykoidów, mineralokortykoidów i androgenów).²⁶ Ryzyko rozwoju niewydolności nadnerczy wzrasta po zatruciu CO, szczególnie u kobiet i młodszych pacjentów, a pacjenci z ostrą niewydolnością oddechową mają jeszcze wyższe ryzyko niewydolności nadnerczy.²⁷

Opóźnione następstwa neurologiczne

U około 10-30% pacjentów po ostrym zatruciu CO rozwija się opóźniona encefalopatia (DEACMP – Delayed Encephalopathy After CO Poisoning).²⁸ Objawy mogą pojawić się po okresie utajenia wynoszącym od 2 dni do 6 tygodni:²⁹

Patofizjologia DEACMP jest niejasna, ale większość badaczy uważa, że związana jest z demielinizacją, destrukcją i apoptozą neuronów w istocie białej mózgu i gałce bladej²⁹
Stan zapalny wywołany zatruciem CO odgrywa rolę w rozwoju DEACMP, obejmując uwalnianie cytokin, peroksydację lipidów, stres oksydacyjny mitochondriów, hamowanie funkcji mitochondriów i adaptacyjne odpowiedzi immunologiczne²⁹
Mechanizm DEACMP jest niekompletnie rozumiany, ale prawdopodobnie obejmuje peroksydację lipidów przez reaktywne formy tlenu generowane przez oksydazę ksantynową¹³

Deficyty neurologiczne niekoniecznie korelują z poziomem CO we krwi, ale prawdopodobnie wynikają z plejotropowych efektów CO na komórkowe oddychanie mitochondrialne, wykorzystanie energii komórkowej, zapalenie i generowanie wolnych rodników, szczególnie w mózgu i sercu.¹³⁰

Czynniki wpływające na nasilenie zatrucia

Nasilenie i objawy zatrucia CO są zależne od wielu czynników:³¹

Stężenie CO i czas ekspozycji³¹
Istniejące wcześniej schorzenia, które mogą wpływać na zdolność przenoszenia tlenu (np. przewlekła choroba płuc)³¹
Wiek³¹
Palenie tytoniu³¹
Ciąża – CO wiąże się z hemoglobiną płodową i przesuwa już przesunięta w lewo krzywą dysocjacji oksyhemoglobiny płodowej jeszcze bardziej w lewo³²³³

Czas połowicznego rozpadu CO u zdrowych osób oddychających powietrzem atmosferycznym wynosi od 3 do 4 godzin. Istnieje korelacja między poziomami COHb a obrazem klinicznym, jednak korelacja ta nie jest dokładna, ponieważ zależy od czynników takich jak wielkość i czas ekspozycji, częstość i głębokość oddychania, objętość minutowa serca oraz aktywność metaboliczna.³⁴

Nowe spojrzenie na mechanizm zatrucia CO

Tradycyjny pogląd, że CO działa głównie poprzez wiązanie się z hemoglobiną i zaburzenie transportu tlenu, nie wyjaśnia w pełni mechanizmów zatrucia CO. Badacze z University of Pennsylvania Medical Center odkryli alternatywny mechanizm toksyczności CO:³⁵³⁶

CO wiąże się do tych samych miejsc w białkach hemowych co tlenek azotu (NO)³⁶
Ilość tlenku azotu we wnętrzu komórki wzrasta, ponieważ CO zajmuje miejsce NO na białkach hemowych³⁶
Ta nierównowaga sprawia, że NO jest dostępny dla reakcji biochemicznych, które normalnie nie występowałyby w komórce, a mianowicie tych, które wytwarzają utleniacze i wolne rodniki uszkadzające tkanki³⁶

Ten mechanizm wyjaśnia, w jaki sposób CO może uszkadzać komórki przy poziomach odpowiadających sytuacjom z rzeczywistego świata, a mechanizm ten nie ma nic wspólnego z klasycznym niedotlenieniem.³⁶

Tabela 1: Objawy kliniczne w zależności od stężenia karboksyhemoglobiny (COHb)
Poziom COHb (%)	Objawy kliniczne
0-10%	Brak objawów lub łagodne objawy (ból głowy, zawroty głowy)
10-20%	Ból głowy, duszność podczas wysiłku, rozszerzenie naczyń skórnych
20-30%	Silny ból głowy, osłabienie, nudności, wymioty, zaburzenia koordynacji
30-40%	Nasilony ból głowy, wymioty, zawroty głowy, dezorientacja, zaburzenia widzenia
40-50%	Tachykardia, tachypnoe, omdlenia, zaburzenia świadomości
50-60%	Drgawki, śpiączka, niewydolność krążeniowo-oddechowa
>60%	Śpiączka, zgon

Warto zauważyć, że poziomy COHb często nie odzwierciedlają obrazu klinicznego, jednak objawy zazwyczaj zaczynają się od bólów głowy przy poziomach około 10%. Poziomy 50-70% mogą prowadzić do drgawek, śpiączki i śmierci.¹⁹

Podsumowanie mechanizmów patogenetycznych

Mechanizm toksycznego działania CO jest złożony i obejmuje kombinację niedotlenienia i niedokrwienia spowodowanych produkcją COHb oraz bezpośrednią toksyczność, która występuje na poziomie komórkowym:²²

Zmniejszenie zdolności przenoszenia tlenu przez krew i przesunięcie krzywej dysocjacji hemoglobiny¹
Zahamowanie oddychania mitochondrialnego i produkcji ATP¹⁴
Indukcja dysfunkcji mitochondrialnej, stresu oksydacyjnego, nadprodukcji wolnych rodników⁵
Peroksydacja lipidów i uszkodzenie komórek¹⁵
Wywołanie stanu zapalnego i apoptozy⁵

Zrozumienie tych złożonych mechanizmów jest kluczowe dla opracowania skutecznych strategii leczenia zatrucia CO, w tym tych ukierunkowanych na przeciwdziałanie skutkom zapalnym i oksydacyjnym zatrucia CO oraz nowych metod bezpośredniego przeciwdziałania toksycznemu efektowi CO, takich jak środki wychwytujące CO, które są obecnie w fazie rozwoju.³⁰³⁷

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC5363978/
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. […] The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. […] CO binds to hemoglobin (Hb) in the blood with high affinity, forming COHb. […] CO binds with high affinity to many ferrous heme-containing proteins. […] CO competes with oxygen for binding to Hb and, by displacement of oxygen, reduces oxygen carrying capacity. […] CO binding to Hb also stabilizes the relaxed, high-affinity quaternary state of Hb (known as R-state), increasing the affinity for oxygen of other sites within the Hb tetramer, and further reducing oxygen release and delivery.
#2
https://step1.medbullets.com/evidence/27753502
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. […] Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.
#3 Carbon Monoxide Poisoning: From Occupational Health to Emergency Medicine
https://www.mdpi.com/2077-0383/13/9/2466
Carbon monoxide poisoning remains a leading cause of accidental poisoning worldwide (both at home and at work), and it is also a cause of suicidal poisoning. […] Despite the widespread nature of this form of poisoning, known about for centuries and whose damage mechanisms have been recognized (or rather hypothesized about) since the 1800s, early recognition, especially of late complications, and treatment remain a medical challenge. […] The ultimate aim of our work is to bring together the pathogenesis, mechanisms of damage, and symptoms related to CO intoxication with a view to its treatment in emergency department settings, providing ideas that can lead to the early recognition of intoxication and its treatment. […] The main biochemical effects and mechanisms of CO toxicity have been studied and have been known since the 1800s.
#4 Carbon Monoxide Poisoning: Diagnosis, Prognostic Factors, Treatment Strategies, and Future Perspectives
https://www.mdpi.com/2075-4418/15/5/581
Carbon monoxide (CO) poisoning is a critical public health concern due to its high morbidity and mortality rates. CO is a colourless, odourless, and tasteless gas, making it extremely insidious as individuals may be unaware of exposure until symptoms emerge. Once breathed, CO bonds with haemoglobin to produce carboxyhaemoglobin, limiting oxygen delivery and leading to tissue hypoxia. This can result in serious health implications, including brain impairment and death. […] Carbon monoxide (CO) is hazardous chiefly due to its interaction with haemoglobin and disruption of cellular functions. CO binds to haemoglobin with around 200â250 times the affinity of oxygen, resulting in carboxyhaemoglobin (COHb). This binding lowers the bloodâs oxygen-carrying capacity and decreases oxygen delivery to tissues. Furthermore, COHb modifies the conformation of the haemoglobin molecule, enhancing its affinity for oxygen at the remaining binding sites. This change in the oxygen dissociation curve impedes oxygen delivery to peripheral tissues, exacerbating the symptoms of hypoxia.
#5 Carbon monoxide: mechanism of toxic action, pathogenesis and clinical manifestations of acute intoxication – Grebenyuk – Toxicological Review
https://jdigitaldiagnostics.com/0869-7922/article/view/641280
Carbon monoxide (CO) remains one of the most common causes of acute poisoning and death, both in everyday life and in emergency situations, especially in fires. […] The paper summarizes information about the regulatory effects, mechanisms of toxic action, pathogenesis and clinical picture of intoxication, as well as predictors of the severity of CO poisoning. […] The main mechanism of the toxic effect of CO is due to its ability to bind to the protohemal iron of hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The toxicity of CO may also be enhanced by impaired functions of the myoglobin of the myocardium and skeletal muscles, mitochondrial cytochrome oxidase, and iron-containing enzymes of the antioxidant system. The leading link in the pathogenesis of acute CO intoxication is a violation of the oxygen transport function of hemoglobin and the associated development of hemic and tissue hypoxia. CO-induced cell and tissue damage due to the induction of mitochondrial dysfunction, oxidative stress, free radical hyperproduction, lipid peroxidation, inflammation, and apoptosis also play a role in the pathogenesis of intoxication.
#6 What is the pathophysiology of CO poisoning? | The Faculty of Intensive Care Medicine
https://www.ficm.ac.uk/documents/what-is-the-pathophysiology-of-co-poisoning
CO is absorbed via the lungs and binds with haemoglobin; it binds 200-300 times more than oxygen. […] The presence of COHb leads to a left shift in the oxygen dissociation curve, resulting in tissue hypoxia and therefore increasing serum lactate levels. […] It is also hypothesised that CO has some direct negative effects on cells within the body; impairing the respiratory function of cells due to the binding of CO to hemeproteins. This leads to permanent mitochondrial damage, especially in cells of the heart and central nervous system. […] CO also binds to cardiac myoglobin causes depression of the cardiovascular system. […] Regarding the clinical significance of CO within the blood, it becomes difficult to use this marker to predict clinical picture as this is often dependent of the length of exposure and the amount of CO which has permeated into the tissues. Physiological reserve, amount of Hb and length of exposure are likely to contribute to severity of presentation. However, general consensus is that COHb of over 25% and/or features such as altered consciousness dictate severe poisoning.
#7 Carbon monoxide toxicity – Knowledge @ AMBOSS
https://www.amboss.com/us/knowledge/carbon-monoxide-toxicity/
Carbon monoxide (CO) toxicity causes tissue hypoxia via multiple mechanisms and is most commonly due to exposure to house fires, wood-burning stoves, or motor vehicle exhaust fumes. […] COHb causes tissue hypoxia via the following mechanisms: […] Decreased oxygen-carrying capacity of hemoglobin […] Shift in the O2 dissociation curve to the left affinity for O2 release of O2 in tissue […] Binding of CO to myoglobin cardiac ischemia decreased cardiac output. […] CO inhibits mitochondrial cytochrome c oxidase defective oxidative phosphorylation anaerobic metabolism with ATP production and hypoxia. […] CO inhibits cytochrome p450 in the brain lipid peroxidation and leukocyte-mediated inflammatory damage cerebral edema. […] pH , exposure to fire, loss of consciousness, higher COHb level, and need for endotracheal intubation are all associated with higher short-term mortality. […] Chronic mild hypoxia erythropoietin erythrocytosis, polycythemia, hemoglobin. […] Chronic CNS effects: unclear mechanism (probably anoxia and ischemia).
#8 Carbon monoxide poisoning – Wikipedia
https://en.wikipedia.org/wiki/Carbon_monoxide_poisoning
Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as „flu-like” and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. […] Large exposures can result in loss of consciousness, arrhythmias, seizures, or death. […] Carbon monoxide primarily causes adverse effects by combining with hemoglobin to form carboxyhemoglobin (symbol COHb or HbCO) preventing the blood from carrying oxygen and expelling carbon dioxide as carbaminohemoglobin. […] The harmful effects of carbon monoxide are generally considered to be due to tightly binding with the prosthetic heme moiety of hemoproteins that results in interference with cellular operations, for example: carbon monoxide binds with hemoglobin to form carboxyhemoglobin which affects gas exchange and cellular respiration. Inhaling excessive concentrations of the gas can lead to hypoxic injury, nervous system damage, and even death.
#9 Carbon monoxide poisoning – UpToDate
https://www.uptodate.com/contents/carbon-monoxide-poisoning
Carbon monoxide poisoning causes impaired oxygen delivery and utilization as well as generation of reactive oxygen species. CO diffuses rapidly across the pulmonary capillary membrane. Elimination is dependent upon the degree of oxygenation and, to a lesser extent, minute ventilation. […] Impaired oxygen delivery â CO binds to the iron moiety of heme (and other porphyrins) with approximately 240 times the affinity of oxygen forming carboxyhemoglobin (COHb). This induces an allosteric change that greatly diminishes the ability of the other three oxygen binding sites in hemoglobin to off-load oxygen to peripheral tissues. This results in a deformation and leftward shift of the oxyhemoglobin dissociation curve, and compounds the impairment in tissue oxygen delivery. […] Impaired oxygen utilization â Approximately 10 to 15 percent of CO is extravascular and bound to molecules such as myoglobin, cytochromes, and NADPH reductase, resulting in impairment of oxidative phosphorylation at the mitochondrial level. The half-life of CO bound to these molecules is longer than that of COHb. The importance of these nonhemoglobin-mediated effects has been best documented in the heart, where mitochondrial dysfunction due to CO can produce myocardial stunning despite adequate oxygen delivery.
#10 Carbon Monoxide Poisoning | 5-Minute Clinical Consult
https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816786/all/Carbon_Monoxide_Poisoning?q=Metabolic+acidosis%2C+anion+gap+increased
Carbon monoxide (CO) is an odorless, tasteless, colorless gas produced during the incomplete combustion of carbon-based compounds. If inhaled, CO may cause nonspecific symptoms and is potentially fatal. […] CO inhalation leads to displacement of oxygen (O2) from binding sites on hemoglobin to form carboxyhemoglobin (COHb). The formation of COHb leads to tissue hypoxia from decreased O2 carrying capacity and a left shift of the oxyhemoglobin dissociation curve (resulting in less O2 delivery to a tissue at a given arterial O2 pressure). CO binds to mitochondrial cytochrome oxidase, impairing adenosine triphosphate (ATP) production. It also binds to myoglobin, resulting in decreased contractility and vascular smooth muscle relaxation. […] CO is rapidly absorbed through the lungs, binding hemoglobin with 210 to 240 times the affinity of O2. This stabilizes hemoglobin in the relaxed high affinity state (R state), reducing O2-carrying capacity and delivery, leading to left shift of the oxyhemoglobin dissociation curve. CO inactivates cytochrome oxidase. This leads to decreased ATP production, especially in tissues with high metabolic demands (brain, heart). The electron transport chain continues, generating superoxide radicals, leading to further damage.
#11 Carbon Monoxide Poisoning – RCEMLearning
https://www.rcemlearning.co.uk/reference/carbon-monoxide-poisoning/
Carbon monoxide (CO) is a colourless, odourless, tasteless, non irritating gas that is produced by incomplete combustion of organic material due to insufficient oxygen. […] The mechanism of CO poisoning is not completely understood. CO binds to haemoglobin (Hb) with an affinity of approximately 220 times that of oxygen. CO shifts the oxygen dissociation curve to the left. It also binds to myoglobin and mitochondrial cytochrome oxidase, impairing adenosine triphosphate production. […] CO poisoning causes platelet and neutrophil activation, free radical formation and lipid peroxidation in brain and other tissues through an immunological mechanism. The importance of these non-hemoglobin-mediated effects has been best documented in the heart, where mitochondrial dysfunction due to CO can produce myocardial stunning despite adequate oxygen delivery.
#12 Carbon monoxide poisoning – Wikipedia
https://en.wikipedia.org/wiki/Carbon_monoxide_poisoning
The precise mechanisms by which the effects of carbon monoxide are induced upon bodily systems are complex and not yet fully understood. Known mechanisms include carbon monoxide binding to hemoglobin, myoglobin and mitochondrial cytochrome c oxidase and restricting oxygen supply, and carbon monoxide causing brain lipid peroxidation. […] 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.
#13 Carbon monoxide poisoning – UpToDate
https://www.uptodate.com/contents/carbon-monoxide-poisoning/print
Impaired oxygen utilization â Approximately 10 to 15 percent of CO is extravascular and bound to molecules such as myoglobin, cytochromes, and NADPH reductase, resulting in impairment of oxidative phosphorylation at the mitochondrial level. […] CO also inactivates cytochrome oxidase in a manner similar to cyanide. CO and cyanide poisoning can occur simultaneously in patients following smoke inhalation, and their combined effects on oxygen transport and utilization appear to be synergistic. […] Reactive oxygen species â CO results in superoxide generation and oxidative stress, which likely contributes to lipid peroxidation and neurologic injury. […] The mechanism of DNS is incompletely understood, but it probably involves lipid peroxidation by reactive oxygen species generated by xanthine oxidase.
#14 Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC5363978/
CO inhibits mitochondrial respiration by binding the ferrous heme a3 in the active site of COX, effectively shutting down oxidative phosphorylation, similar to the effects of cyanide and nitric oxide (NO). […] CO-mediated reductions in oxygen delivery and mitochondrial oxidative phosphorylation produce ischemic and anoxic brain injury, leading to cognitive deficits in survivors. […] The pathophysiology of CO poisoning involves the reduction of global oxygen delivery and the inhibition of mitochondrial respiration.
#15 Carbon Monoxide Toxicity: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/819987-overview
CO can produce direct cellular changes involving immunologic or inflammatory damage by a variety of mechanisms, including the following: Binding to intracellular proteins (myoglobin, cytochrome a,a3), Nitric oxide generation leading to peroxynitrite production, Lipid peroxidation by neutrophils, Mitochondrial oxidative stress, Apoptosis, Immune-mediated injury, Delayed inflammation. […] CO directly impairs aerobic metabolism in tissues by poisoning the mitochondrial electron-transport chain. It does so by binding mitochondrial cytochromes, preventing the binding and subsequent reduction of oxygen at the end of the cycle. The process of oxidative phosphorylation cannot be completed, and the mitochondria, instead of making water and adenosine triphosphate (ATP), make destructive oxygen free radicals.
#16 Carbon Monoxide Toxicity: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/819987-overview
CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO affects several different sites within the body but has its most profound impact on the organs (eg, brain, heart) with the highest oxygen requirement. […] Cellular hypoxia from CO toxicity is caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative functional anemia. Because it binds hemoglobin 230-270 times more avidly than oxygen, even small concentrations can result in significant levels of carboxyhemoglobin (HbCO). […] CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Decrease in oxygen delivery is insufficient, however, to explain the extent of the CO toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.
#17 Carbon monoxide poisoning – UpToDate
https://www.uptodate.com/contents/carbon-monoxide-poisoning
CO also inactivates cytochrome oxidase in a manner similar to cyanide. CO and cyanide poisoning can occur simultaneously in patients following smoke inhalation, and their combined effects on oxygen transport and utilization appear to be synergistic. […] Reactive oxygen species â CO results in superoxide generation and oxidative stress, which likely contributes to lipid peroxidation and neurologic injury.
#18
https://step2.medbullets.com/pulmonary/121734/carbon-monoxide-poisoning
carbon monoxide (CO) poisoning results from exposure to CO resulting in hypoxia […] Pathogenesis […] mechanism […] displaces oxygen from hemoglobin […] causes left-shift of oxygen-hemoglobin curve, leading to decreased delivery of oxygen to tissues […] binds to cytochrome oxidase […] disrupts electron transport chain […] increases lipid peroxidation in the central nervous system
#19 Carbon Monoxide Toxicity: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/819987-overview
Studies have indicated that CO may cause lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by hyperbaric oxygen (HBO) therapy. […] Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination. This leads to edema and focal areas of necrosis, typically of the bilateral globus pallidus. […] Studies have demonstrated release of nitric oxide free radicals (implicated in the pathophysiology of atherosclerosis) from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm. One study suggests a direct toxicity of CO on myocardium that is separate from the effect of hypoxia. […] HbCO levels often do not reflect the clinical picture, yet symptoms typically begin with headaches at levels around 10%. Levels of 50-70% may result in seizure, coma, and fatality.
#20 Carbon Monoxide Poisoning | 5-Minute Clinical Consult
https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816786/all/Carbon_Monoxide_Poisoning?q=Metabolic+acidosis%2C+anion+gap+increased
CO displaces nitric oxide (NO) from platelets, leading to platelet activation and aggregation. Oxidative stress, lipid peroxidation, and apoptosis are additional effects. NO also causes vasodilation and profound hypotension. […] Mitochondrial dysfunction and hypoxia leads to myocardial stunning and injury. Proteases released from neutrophil degranulation interact with xanthine hydrogenase forming xanthine oxidase. This inhibits endogenous defense against oxidative stress. […] CO also initiates an inflammatory cascade that can lead to oxidative degradation of nervous system lipids and delayed neurologic damage.
#21 Mechanisms of Action of Hyperbaric Oxygen Therapy in Carbon Monoxide Poisoning – Rx Pad – Wound Care Education Partners
https://www.woundeducationpartners.com/resources/rx-pad-blog/entry/mechanisms-of-action-of-hyperbaric-oxygen-therapy-in-carbon-monoxide-poisoning.html
Current knowledge indicates that there are multiple mechanisms of action of hyperbaric oxygen therapy in CO poisoning. […] HBO2 also promotes normalization of tissue hypoxia. […] Brown and Piantadosi demonstrated that hyperbaric oxygen at 3 ATA markedly accelerates the dissociation of CO from cytochrome oxidase. […] Hyperbaric oxygen was found to be effective for preventing brain oxidative injury through increased heme oxygenase and upregulation of antioxidants. […] Given that vascular changes are prominent in clinical CO poisoning, it is feasible that neurological sequelae in patients may involve a perivascular injury mediated by leukocyte sequestration and activation. […] Moreover, HBO2 reduces neuronal apoptosis and necrosis, and it also mobilizes stem cells via a nitric oxide-dependent mechanism. […] Hence, timely administration of hyperbaric oxygen may ameliorate the cascade leading to brain injury via multiple mechanisms.
#22 Carbon Monoxide Poisoning: From Occupational Health to Emergency Medicine
https://www.mdpi.com/2077-0383/13/9/2466
There is now common agreement that this is its least influential toxic mechanism because tissue toxicity is by far the most influential. […] Carbon monoxide causes oxidative stress (due to increased levels of cytosolic heme) and interrupts cellular respiration (through binding to platelet proteins and cytochrome c oxidase) with the production of reactive oxygen species, which cause apoptosis and neuronal necrosis. […] The toxic mechanism of CO is determined by a combination of hypoxia and ischemia due to the production of COHb and the direct toxicity that occurs at the cellular level. […] The brain is one of the main targets of the toxic action of CO, representing, together with the myocardium, one of the tissues with the highest oxygen demand. […] The effects of CO on the heart and neurological sequelae are among the main causes of mortality following CO intoxication.
#23 Carbon Monoxide Poisoning: Diagnosis, Prognostic Factors, Treatment Strategies, and Future Perspectives
https://www.mdpi.com/2075-4418/15/5/581
CO binds to the heme group in myoglobin with 60 times more affinity than oxygen, limiting oxygen delivery to mitochondria and oxidative phosphorylation. This disturbance compels cardiomyocytes to use anaerobic metabolism, resulting in hypoxia, lactic acidosis, and death. […] CO poisoning has considerable prothrombotic effects, as evidenced by multiple research and case reports linking it to arterial and venous thrombosis, including stent thrombosis. It also causes anatomical alterations such as myocardial fibrosis and poor left ventricular function. […] CO poisoning affects the dopaminergic system, causing an increase in extracellular dopamine levels by increasing release while inhibiting metabolism and reuptake. This dopamine excess lasts for weeks and is linked to oxidative damage, apoptosis, and the death of synapses and nuclei in the mesolimbic system, notably in the globus pallidus.
#24 Carbon Monoxide Poisoning: Diagnosis, Prognostic Factors, Treatment Strategies, and Future Perspectives
https://www.mdpi.com/2075-4418/15/5/581
The clinical manifestations of CO poisoning range from mild symptoms like headache, dizziness, and nausea to severe effects such as confusion and delayed neuropsychiatric issues. They underscore the importance of early recognition and intervention to prevent long-term complications. […] Acute carbon monoxide (CO) poisoning has a profound impact on the central nervous system (CNS), with symptoms ranging in severity according to the intensity and duration of CO exposure. During the acute phase, patients may have headaches, dizziness, syncope, seizures, brain infarction, and loss of consciousness. Following recovery, some individuals suffer delayed neurological sequelae (DNS), including cognitive impairments, Parkinsonism, motor abnormalities, and peripheral neuropathy. […] CO poisoning affects the dopaminergic system, causing an increase in extracellular dopamine levels by increasing release while inhibiting metabolism and reuptake. This dopamine excess lasts for weeks and is linked to oxidative damage, apoptosis, and the death of synapses and nuclei in the mesolimbic system, notably in the globus pallidus.
#25 Carbon Monoxide Poisoning: Diagnosis, Prognostic Factors, Treatment Strategies, and Future Perspectives
https://www.mdpi.com/2075-4418/15/5/581
CO poisoning causes oxidative stress by releasing reactive oxygen species (ROS) and activating inflammatory pathways. These effects can induce lipid peroxidation, protein degradation, and apoptosis, especially in highly oxygen-demanding organs like the brain and heart. The combination of hypoxia and oxidative damage causes the neurological and cardiovascular symptoms that are hallmarks of CO poisoning. […] Carbon monoxide (CO) poisoning is closely linked to a wide range of cardiac complications, including acute myocardial damage, severe necrosis, and contractile dysfunction. Myocardial tissue, which is extremely vulnerable to oxygen deprivation, experiences hypoxic damage that is aggravated by increased oxygen demand due to increased contractility, decreased coronary reserve, and hindered cellular respiration.
#26 Carbon Monoxide Poisoning: From Occupational Health to Emergency Medicine
https://www.mdpi.com/2077-0383/13/9/2466
CO intoxication also leads to alterations in the adrenal glands, responsible for the production of three classes of hormones fundamental to the correct functioning of important functions in our organism (glucocorticoids, mineralocorticoids, and androgens). […] CO intoxication can lead to an increased risk of developing autoimmune connective tissue diseases.
#27 Association between carbon monoxide poisoning and adrenal insufficiency: a nationwide cohort study | Scientific Reports
https://www.nature.com/articles/s41598-022-20584-y
Carbon monoxide poisoning may damage the brain and adrenal glands, but it is unclear whether it is associated with adrenal insufficiency. […] The risk for developing adrenal insufficiency elevated after COP, especially in female and younger patients. […] The COP patients who had acute respiratory failure had an even higher risk for adrenal insufficiency than those without acute respiratory failure, which may indicate a doseresponse relationship. […] Hypoxic injury in the brain and adrenal glands may be the major cause of adrenal insufficiency observed in this study. […] This association might be attributable to the hypoxic injury, inflammation, and immunological reaction in the brain and adrenal glands following COP. […] More study is needed to clarify the mechanism between COP and adrenal insufficiency. […] The increased risk may be attributable to COP-related hypoxic injury, inflammatory, and immunological reaction on the brain and adrenal gland; however, the underlying mechanism needs further study.
#28
https://journals.lww.com/md-journal/fulltext/2019/12060/management_of_delayed_encephalopathy_after_co.40.aspx
Approximately 10% to 30% patients develop delayed encephalopathy after acute CO poisoning (DEACMP). […] Previous studies have demonstrated that CO-mediated delayed neuropathology were associated with the enhancement of lipid peroxidation, increased reactive oxygen species (ROS), depletion of antioxidant defense systems, cytochrome aa3 binding, and disruption of intracellular oxygen utilization of brain. […] The exact mechanism of DEACMP remains unclear. […] No specific treatment is available for DEACMP, and poor prognosis is one of the characteristics of this disease. […] It seemed to be that MSC transplantation was superior to HBO, and combined-therapy of MSC and butylphthalide was superior to MSC transplantation alone, in improving cognitive function, activities of daily living, and neurological recovery rate assessed by neuroimages for DEACMP patients.
#29 Real-world effectiveness of hyperbaric oxygen therapy for delayed neuropsychiatric sequelae after carbon monoxide poisoning | Scientific Reports
https://www.nature.com/articles/s41598-021-98539-y
Carbon monoxide (CO) is one of the main environmental causes of acute poisoning worldwide, and is associated with a high mortality rate and specific complications. Long periods or high atmospheric concentrations of CO exposure however can cause damage to vital organs, which have high oxygen demand and consumption, such as the heart and the brain. In addition to causing acute morbidity and mortality, CO poisoning can cause delayed neuropsychiatric sequelae (DNS), with the lag time ranging from 2 days to 6 weeks. The pathophysiology of DNS after CO poisoning is unclear, but most researchers consider it to be related to demyelination, destruction and apoptosis of neurons in cerebral white matter and the globus pallidus. Inflammation caused by CO poisoning also plays a role in DNS development, including cytokine release, lipid peroxidation, mitochondrial oxidative stress, inhibition of mitochondrial function, and adaptive immunological responses, all of which influence the pathogenesis of neuron damage. The mechanism of recovery through HBOT after the development of DNS may be related to the transfer of functional mitochondria to the injury site, re-myelination of damaged neurons, angiogenesis and neurogenesis, production of anti-inflammatory cytokines and balancing inflammatory and anti-inflammatory cytokines to protect the integrity of the blood-brain barrier. The proposed mechanism of HBOT in treating DNS is that HBOT could improve post-ischemic or inflammatory tissue survival by increasing reactive species to temporarily inhibit 2-integrin function of neutrophils, as well as inducing antioxidant enzymes and anti-inflammatory proteins in many tissues.
#30 SafetyLit: Carbon monoxide poisoning: pathogenesis, management and future directions of therapy
https://www.safetylit.org/citations/index.php?fuseaction=citations.viewdetails&citationIds[]=citjournalarticle_534479_28
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. […] The neurologic deficits do not necessarily correlate with blood CO levels, but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation and free radical generation, especially in the brain and heart. […] Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. […] While hyperbaric oxygen significantly reduces the permanent neurological and affective effects CO poisoning, a portion of survivors still remain with substantial morbidity. […] There is some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. […] New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.
#31 Carbon monoxide poisoning: a clinical case report | International Journal of Emergency Medicine | Full Text
https://intjem.biomedcentral.com/articles/10.1186/s12245-024-00777-0
Carbon monoxide (CO) poisoning is a serious yet frequently overlooked condition with diverse and nonspecific clinical presentations. […] CO binds to hemoglobin, causing tissue hypoxia and symptoms such as confusion, tachypnea, syncope, and chest pain. […] The diagnostic challenge in CO poisoning is underscored in these cases. The triad of symptoms consistent with CO poisoning, a history of exposure, and elevated carboxyhemoglobin (COHb) levels is crucial for diagnosis. […] Factors influencing severity and symptoms of CO poisoning include CO concentration and duration of exposure; pre-existing conditions that might impact oxygen carrying capacity (e.g., chronic lung disease); age; smoking; and pregnancy. […] Given that no single symptom is pathognomonic for CO poisoning, arterial blood gas analysis and measurement of COHb levels are indispensable for diagnosis.
#32 Carbon Monoxide Poisoning – RCEMLearning
https://www.rcemlearning.co.uk/reference/carbon-monoxide-poisoning/
CO binds to fetal haemoglobin and shifts the already left-shifted fetal oxyhaemoglobin dissociation curve further to the left. The half-life of CO in the fetus is longer than that in the mother and is of particular concern when considering treatment options. […] Administration of oxygen speeds the elimination of CO from the body. Without therapy, the elimination half life of CO is 4-6 hours. Administration of high flow oxygen by a tightfitting mask at normal atmospheric pressure reduces half life to approximately 76 mins. In hyperbaric oxygen chamber at 2.5 atmosphere absolute pressure, the elimination half life is further decreased to 20 mins. […] CO remains a difficult diagnosis to make due to its insidious and non-specific symptoms.
#33 Basic Science and Pathophysiology – RCEMLearning
https://www.rcemlearning.co.uk/modules/carbon-monoxide-poisoning/lessons/basic-science-and-pathophysiology-21/
The mechanism of CO poisoning is not completely understood. CO binds to haemoglobin (Hb) with an affinity of approximately 220 times that of oxygen. CO shifts the oxygen dissociation curve to the left. It also binds to myoglobin and mitochondrial cytochrome oxidase, impairing adenosine triphosphate production. […] CO poisoning causes platelet and neutrophil activation, free radical formation and lipid peroxidation in brain and other tissues through an immunological mechanism. The importance of these non-hemoglobin-mediated effects has been best documented in the heart, where mitochondrial dysfunction due to CO can produce myocardial stunning despite adequate oxygen delivery. […] CO binds to fetal haemoglobin and shifts the already left-shifted fetal oxyhaemoglobin dissociation curve further to the left. The half-life of CO in the fetus is longer than that in the mother and is of particular concern when considering treatment options.
#34 Asfixiantes bioquÃmicos: MonÃ³xido de Carbono y Cianuro
http://www.scielo.org.pe/scielo.php?pid=S2308-05312022000300614&script=sci_arttext&tlng=en
CO is also capable of binding to other hemoproteins located at the tissue level, such as myoglobin, cytochrome oxidase, cytochrome P450, and hydroperoxidase. Between 15-20% of the CO binds to these proteins, thus interrupting cellular respiration and causing the production of reactive oxygen species, which lead to neuronal necrosis and apoptosis. […] Exposure to CO also causes inflammation, through multiple pathways independent of those of hypoxia, resulting in further neurological and cardiac damage. […] The half-life of CO in healthy people who breathe ambient air ranges between 3 and 4 hours. There is a correlation between the levels of COHb and the clinic, however, this correlation is not as exact, since it depends on factors such as the magnitude and time of exposure, the frequency and depth of respiration, and the minute cardiac volume and the metabolic activity.
#35 New Mechanism To Explain Carbon Monoxide Poisoning Identified | ScienceDaily
https://www.sciencedaily.com/releases/1997/09/970927111303.htm
Researchers at the University of Pennsylvania Medical Center have discovered a novel biochemical mechanism for carbon monoxide (CO) poisoning that may someday lead to new clinical approaches for dealing with exposure to this deadly gas. […] The classic explanation for CO’s poisonous action is that it binds to hemoglobin molecules in the blood, impairing oxygen delivery to the body’s cells. Eventually cells essentially suffocate and die. „This traditional view explains the mechanism of carbon-monoxide toxicity in only a small fraction of all people exposed to it,” says senior author Stephen R. Thom, MD, PhD, Associate Professor of Emergency Medicine, and chief of hyperbaric medicine at Penn’s Institute for Environmental Medicine. „The vast number of patients we see clearly don’t fit this traditional explanation. Science falls down in terms of what we see in day-to-day practice.”
#36 New Mechanism To Explain Carbon Monoxide Poisoning Identified | ScienceDaily
https://www.sciencedaily.com/releases/1997/09/970927111303.htm
Now, Thom and Penn colleagues Harry Ischiropoulos, PhD, Research Assistant Professor of Biochemistry and Biophysics, and Y. Anne Xu, Research Specialist in Environmental Medicine, have identified a mechanism that provides an alternate explanation for CO toxicity. „We found that carbon dioxide binds to the same sites on heme proteins as nitric oxide,” notes Thom. […] „The amount of nitric oxide in the cell interior rises because carbon monoxide usurps the spot of nitric oxide on the heme proteins,” says Thom. This imbalance makes NO available for biochemical reactions that would not normally occur within the cell, namely ones that produce tissue-damaging oxidants and free radicals. […] „This is the first time this mechanism of carbon-monoxide toxicity has been demonstrated,” states Thom. […] „The big picture is that we have identified a mechanism of how carbon monoxide can damage cells at levels that are relevant to real-world situations, and a mechanism that has nothing to do with classic hypoxia,” Thom concludes.
#37 Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy – University of Iowa
https://iro.uiowa.edu/esploro/outputs/journalArticle/Carbon-Monoxide-Poisoning-Pathogenesis-Management-and/9984304682602771
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. […] Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.