Clarification on the mechanism of acetaminophen toxicity on the kidneys?

[Old Style Nanny]

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I was trying to recall this and I got confused. I remember something about the medulla being most susceptible to the free radical injury by acetaminophen while at the same time acetaminophen being able to release angiotensin via its effect on PGE2 and thereby causing constriction of renal blood vessels, further reducing the amount of blood the medulla gets.

Could someone throw more light on the exact mechanism?

Thanks.

 

[ZGX]

I was trying to recall this and I got confused. I remember something about the medulla being most susceptible to the free radical injury by acetaminophen while at the same time acetaminophen being able to release angiotensin via its effect on PGE2 and thereby causing constriction of renal blood vessels, further reducing the amount of blood the medulla gets.

Could someone throw more light on the exact mechanism?

Thanks.

What you are referring to is Analgesic Nephropathy. This is seen when people combine acetaminophen with aspirin. Remember Acetaminophen is not considered an NSAID therefore it wont inhibit PGE2. It is the Aspirin that inhibits PGE2, thus leaving AT2 unopposed, hence decreased renal blood flow in renal medulla.

 

[Old Style Nanny]

What you are referring to is Analgesic Nephropathy. This is seen when people combine acetaminophen with aspirin. Remember Acetaminophen is not considered an NSAID therefore it wont inhibit PGE2. It is the Aspirin that inhibits PGE2, thus leaving AT2 unopposed, hence decreased renal blood flow in renal medulla.

Oh that is it. Thanks!

I think I was confused because I had annotated from Goljan when he talked about this mechanism in CCl4 + Acetaminophen toxicity on the kidneys saying PGE2 is inhibited. Is there a relation between CCl4 and PGE2 by the way?

 

[ZGX]

Oh that is it. Thanks!

I think I was confused because I had annotated from Goljan when he talked about this mechanism in CCl4 + Acetaminophen toxicity on the kidneys saying PGE2 is inhibited. Is there a relation between CCl4 and PGE2 by the way?

You are confusing the bullet points in his audio lecture (if that is what you are listening to) in the cell injury chapter

He mentions Carbon tetrachloride CCL4 is converted by the liver to CCL3 (active form) which is a free radical. Consider the dry cleaning industry.

the other cause of cell injury he mentions is

Acetaminophen + Aspirin to the Renal Medulla

However
Remember our body has Glutathione that neutralize free radicals.

Let's say you work in dry cleaning and all your Glutathione is used to neutralize the CCL3.

After work you go home and decide to pop some Aspirin + Acetaminophen.

Then your body cannot reduce free radicals anymore. Then I guess there is some relation to them exacerbating the damage to the Renal Medulla. He also states the main mediator of renal medullary nephropathy is the free radicals from Acetaminophen.

Sounds like a bit of a stretch but I can't ponder any other possibility of how CCL4 is related to Renal Medullary Injury with Acetaminophen Toxicity.

 

[Old Style Nanny]

You are confusing the bullet points in his audio lecture (if that is what you are listening to) in the cell injury chapter

He mentions Carbon tetrachloride CCL4 is converted by the liver to CCL3 (active form) which is a free radical. Consider the dry cleaning industry.

the other cause of cell injury he mentions is

Acetaminophen + Aspirin to the Renal Medulla

However
Remember our body has Glutathione that neutralize free radicals.

Let's say you work in dry cleaning and all your Glutathione is used to neutralize the CCL3.

After work you go home and decide to pop some Aspirin + Acetaminophen.

Then your body cannot reduce free radicals anymore. Then I guess there is some relation to them exacerbating the damage to the Renal Medulla. He also states the main mediator of renal medullary nephropathy is the free radicals from Acetaminophen.

Sounds like a bit of a stretch but I can't ponder any other possibility of how CCL4 is related to Renal Medullary Injury with Acetaminophen Toxicity.

Crystal. Thanks again. I definitely did not hear the aspirin mentioned in the lecture. I should really learn to listen more carefully!

 

[Mirron]

just curious, who are you listening to? which audio lectures?