Cyanide poisoning

[MarylandGal]

Hey, all, I have a question that a friend and I are stumped on about cyanide poisoning.

CN-, a non-competitive inhibitor, binds to a regulatory site on Hb, thereby changing its conformation so that O2 can no longer bind. Saturation will be low, but why is PO2 normal? (My friend and I did a flow chart comparing this to carbon monoxide, where sats are normal and Po2 is low, and every explanation for CN- can easily be refuted).

We're probably overlooking something really simple, but can someone please explain to me WHY, with CN- poisoning, you would have NORMAL PO2 levels?

[Sree Cheruku]

The short answer to your question is that CN- disrupts the binding of O2 with heme, which lowers SaO2. But CN- does not interfere with the oxygen in the blood, thereby leaving PaO2 intact.

PaO2 depends on environmental conditions like the percent of oxygen in the atmosphere and the ability of this oxygen to get into your lungs, pass through the alveoli and enter the blood without any problems. Examples of problems that lower PaO2 are ventilation problems like ARDS, perfusion problems like a pulmonary embolus and diffusion problems like pulmonary fibrosis. CN- poisoning doesn't interfere with any of these processes, and therefore it has no impact on PaO2.

SaO2 is affected by anything that prevents O2 from binding heme. This includes low PaO2 (because if O2 is not getting through to the blood, it's not available to bind heme), but also includes problems that mess with hemoglobin directly like methemoglobenemia, CO poisoning and CN poisoning.

I don't believe that CO poisoning under normal circumstances would lower PaO2. Maybe in an acute poisoning situation, when a patient is breathing both O2 and CO, CO probably diffuses faster and lowers PaO2 or something like that.

[opnr2k2]

The short answer to your question is that CN- disrupts the binding of O2 with heme, which lowers SaO2. But CN- does not interfere with the oxygen in the blood, thereby leaving PaO2 intact.

PaO2 depends on environmental conditions like the percent of oxygen in the atmosphere and the ability of this oxygen to get into your lungs, pass through the alveoli and enter the blood without any problems. Examples of problems that lower PaO2 are ventilation problems like ARDS, perfusion problems like a pulmonary embolus and diffusion problems like pulmonary fibrosis. CN- poisoning doesn't interfere with any of these processes, and therefore it has no impact on PaO2.

SaO2 is affected by anything that prevents O2 from binding heme. This includes low PaO2 (because if O2 is not getting through to the blood, it's not available to bind heme), but also includes problems that mess with hemoglobin directly like methemoglobenemia, CO poisoning and CN poisoning.

I don't believe that CO poisoning under normal circumstances would lower PaO2. Maybe in an acute poisoning situation, when a patient is breathing both O2 and CO, CO probably diffuses faster and lowers PaO2 or something like that.

If you have CN- poisoning then Hb cannot bind any oxygen. Then how does the oxygen make it out of the alveoli and into the blood?

[Sree Cheruku]

I don't think that being bound to hemoglobin is a requirement for diffusion. Oxygen should be able to dissolve in the blood and achieve its equilibrium regardless. One of us should probably look it up.

[Hatim]

O2 is perfusion limited, and it diffuses across into the arteries, where it is picked up by Hb thats why i belive its not affected.

As for in CO poisoining PaO2 is normal same with cyanide as explained above

[MarylandGal]

thanks, all.

[jameslynton]

Hey, all, I have a question that a friend and I are stumped on about cyanide poisoning.

CN-, a non-competitive inhibitor, binds to a regulatory site on Hb, thereby changing its conformation so that O2 can no longer bind. Saturation will be low, but why is PO2 normal? (My friend and I did a flow chart comparing this to carbon monoxide, where sats are normal and Po2 is low, and every explanation for CN- can easily be refuted).

We're probably overlooking something really simple, but can someone please explain to me WHY, with CN- poisoning, you would have NORMAL PO2 levels?You'll are missing the main mechanism with Cyanide - It stop the cytochrome p450 system. As it circulates in the blood. It dissolved in the blood as an ion. It is not really attached to heme as much as it likes to clog up the cytochrome p450 system very quickly because CN- likes/loves Cr ions more than Fe ions. Thus heme gets free quickly and it does not effect the PO2. It does effect the cellular respiration systems ability to process O2 at the cellular level - it just stops it cold! It does not bind at the allosteric regulatory site on Heme - Heme is just carries the CN- to where it is attracted off by Cr ions at the best. Also consider the way cyanide is used normally KCN = K+ CN- via digestion or injection. As a gas CN-CN while bad news is hard to weaponise due resonance bonds in the molecule and high reactivity. Normally, a strong acid has KCL thrown it to create the shortly lived gas.

[MarylandGal]

You'll are missing the main mechanism with Cyanide - It stop the cytochrome p450 system. As it circulates in the blood. It dissolved in the blood as an ion. It is not really attached to heme as much as it likes to clog up the cytochrome p450 system very quickly because CN- likes/loves Cr ions more than Fe ions. Thus heme gets free quickly and it does not effect the PO2. It does effect the cellular respiration systems ability to process O2 at the cellular level - it just stops it cold! It does not bind at the allosteric regulatory site on Heme - Heme is just carries the CN- to where it is attracted off by Cr ions at the best. Also consider the way cyanide is used normally KCN = K+ CN- via digestion or injection. As a gas CN-CN while bad news is hard to weaponise due resonance bonds in the molecule and high reactivity. Normally, a strong acid has KCL thrown it to create the shortly lived gas.

I understand the effects of CN- on complex IV. HOwever, CN- binds irrversibly to the regulatory site on Hb (it is considered a noncompetitive inhibitor). That is why it's important to treat quickly...no amount of O2 will displace it. you must treat it with sodium thiosulfate (to form methemoglobin which also helps to grab the rest of the dissolved CN- in the body) followed by methylene blue (to treat the methemoglobin that you just formed).

[Sree Cheruku]

O2 is perfusion limited,

yep, that was it. thanks