How Does Hypoxia REALLY Kill?

[funkytomtom]

Hey all-I'm wondering how hypoxia actually physically kills you on the cellular level. I know that your cells use O2 in the final stages of cellular respiration as your "terminal electron acceptor." But...with hypoxia, CO poisoning, or cyanide poisoning, this final step in energy production is inhibited. Does the cell even attempt the electron transport chain without the presence of O2? Or does it go through electron transport only to end up with free floating electrons? And...how long can anaerobic respiration sustain life...and (lastly) is it the accumulation of acids or the lack of energy that kills?

Thanks for the help! I've been having a difficult time trying to tease out the answer using my EMTI textbook, bio textbook, a&p textbook, and yes...the internet.

Edited April 6, 2010 by funkytomtom

[funkytomtom]

wow...not even any views yet...

[Eydawn]

You DO realize that it's 3am EST, 1am MST? Of course there haven't been many views yet!

Hang tight, let me find you some references. I'm kind of busy studying but I'll see what I can pull out for you. I think you're on the right track with the ETC shutting down and byproducts building up resulting in death on the cellular level... but I'm not entirely sure myself.

Wendy

CO EMT-B

[funkytomtom]

Yeah I guess it is rather late...I'm curious and impatient and figured we all had to be creatures of the night like me.

[NRPinNEPA]

The first stage of cellular metobolism is anaerobic, meaning it occurs without the use of oxygen. Glucose enters the cells and through a process called glycolysis creates lactic acid and pyruvian acid. The second stage is aerobic. Oxygen enters the cells and through a process called the Krebs acid cycle creates ATP and carbon dioxide. ATP is the energy source, carbon dioxide is a waste. Now, when you're hypoxic, oxygen isn't being delivered to the cells. The Krebs acid cycle can't take place without oxygen, so the lactic acid and pyruvian acid continues to build up inside the cell. Eventually, the cell becomes acidotic, resulting in cellular death.

In other words, acids build in the cell and cause the cell to die.

[Lone Star]

http://www.answers.com/topic/citric-acid-cycle

[chbare]

Glycolysis does not require oxygen; however, ATP production is rather modest via glycolysis. As stated, the ETC requires the electronegativity of oxygen to act as an electron receptor. This is an aerobic process and by proxy the TCA cycle is as reduced NAD & FAD needs to dump off protons and electrons. Why not take a microbiology course or study up on what happens to pyruvic acid in an anerobic environment. In addition, you should appreciate what happens when ion channels are no longer to move ions and various other cellular activities that require ATP.

Take care,

chbare.

[chbare]

The first stage of cellular metobolism is anaerobic, meaning it occurs without the use of oxygen. Glucose enters the cells and through a process called glycolysis creates lactic acid and pyruvian acid. The second stage is aerobic. Oxygen enters the cells and through a process called the Krebs acid cycle creates ATP and carbon dioxide. ATP is the energy source, carbon dioxide is a waste. Now, when you're hypoxic, oxygen isn't being delivered to the cells. The Krebs acid cycle can't take place without oxygen, so the lactic acid and pyruvian acid continues to build up inside the cell. Eventually, the cell becomes acidotic, resulting in cellular death.

In other words, acids build in the cell and cause the cell to die.

Just to clarify a few points:

1) Pyruvate is a product of glycolysis along with a net of 2 ATP via substrate level phosphorylation. In addition, two NADH are produced per glucose molecule. However, the pyruvate is turned into acetyl-CoA after entering the mitochondria. Lactate is produced in the TCA cycle.

2) The Krebs Cycle (TCA) is not the major ATP producing pathway. I believe only about two ATP are produced via substrate level phosphorylation in the TCA cycle. The major site of energy production is the ETC. Hydrogen ions and electrons help run ATP production in two ways. 1) The electrons give up energy as they cascade through the cycle. 2) Hydronium ions are utilised to make a gradient and by use of proton motive force (PMF) powers ADP to ATP conversion through a protein known as ATP synthase. The oxygen "scavenges" the hydronium ions and electrons at the cytochrome c oxidase protein complex.

3) Several things actually occur beyond cell death by acidosis. We have failure of multiple mechanisms including ion channels. Then, as cells die, inflammatory mediators are released opening a systemic bag of worms. This is part of why people with say a femur fracture can develop ARDS and MODS. Clearly, hypoperfusion related to hypovolemia can be another part of the puzzle. However, it is not uncommon for somebody to sustain a hypoxic insult or an episode of hypovolemia and end up developing MODS and so on.

I am sure the Docs and JPINFV can go deeper, but I just wanted to clear a few thing up.

Take care,

chbare.

[funkytomtom]

Just to clarify a few points:

1) Pyruvate is a product of glycolysis along with a net of 2 ATP via substrate level phosphorylation. In addition, two NADH are produced per glucose molecule. However, the pyruvate is turned into acetyl-CoA after entering the mitochondria. Lactate is produced in the TCA cycle.

2) The Krebs Cycle (TCA) is not the major ATP producing pathway. I believe only about two ATP are produced via substrate level phosphorylation in the TCA cycle. The major site of energy production is the ETC. Hydrogen ions and electrons help run ATP production in two ways. 1) The electrons give up energy as they cascade through the cycle. 2) Hydronium ions are utilised to make a gradient and by use of proton motive force (PMF) powers ADP to ATP conversion through a protein known as ATP synthase. The oxygen "scavenges" the hydronium ions and electrons at the cytochrome c oxidase protein complex.

3) Several things actually occur beyond cell death by acidosis. We have failure of multiple mechanisms including ion channels. Then, as cells die, inflammatory mediators are released opening a systemic bag of worms. This is part of why people with say a femur fracture can develop ARDS and MODS. Clearly, hypoperfusion related to hypovolemia can be another part of the puzzle. However, it is not uncommon for somebody to sustain a hypoxic insult or an episode of hypovolemia and end up developing MODS and so on.

I am sure the Docs and JPINFV can go deeper, but I just wanted to clear a few thing up.

Take care,

chbare.

You are correct that only two ATP are produced in the TCA Cycle. I will have to investigate further on A) the ion channels, and the inflammatory mediators. Thanks for the help!