Most susceptible hepatic zone to TOXIC injury - zone I or zone III ?

[Phloston]

P.342 of FA2012, under the "Liver anatomy" heading in the middle of the page, all the way on the right, says zone III as most sensitive to toxic injury.

However, look at the below PrntScr image from Kaplan QBank (which I've just started). This is the first question I've done and there's ALREADY a discrepancy.

Press Ctrl+ to make the image bigger.

Anyone's thoughts?

I'm aware that phosphorus poisoning affects zone I before zone III, so I'm actually wondering if FA is incorrect...

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[Boardz]

P.342 of FA2012, under the "Liver anatomy" heading in the middle of the page, all the way on the right, says zone III as most sensitive to toxic injury.

However, look at the below PrntScr image from Kaplan QBank (which I've just started). This is the first question I've done and there's ALREADY a discrepancy.

Press Ctrl+ to make the image bigger.

Anyone's thoughts?

I'm aware that phosphorus poisoning affects zone I before zone III, so I'm actually wondering if FA is incorrect...

Ha! I JUST did that question! I bet it depends on the toxin. Like, if the toxin messes with mitochondria then it owns zone III more, but if the toxin just in general owns, then it owns where it's concentration is highest, which would be zone I.

 

[Charles_Carmichael]

In histology/cell biology, what was taught to us was that zone III was susceptible to cytotoxic damage from toxic metabolites that are produced during detoxification reactions (since it's the main site of alcohol/drug detox) -- maybe that's what FA is referring to?

 

[normtheniner]

P.342 of FA2012, under the "Liver anatomy" heading in the middle of the page, all the way on the right, says zone III as most sensitive to toxic injury.

However, look at the below PrntScr image from Kaplan QBank (which I've just started). This is the first question I've done and there's ALREADY a discrepancy.

Press Ctrl+ to make the image bigger.

Anyone's thoughts?

I'm aware that phosphorus poisoning affects zone I before zone III, so I'm actually wondering if FA is incorrect...

My Netter's Essential Histology says:

Zone 1, most central, is closest to the terminal distributing branches of the portal venule and hepatic arteriole. This zone first receives oxygen, hormones, and nutrients from the bloodstream, and most glycogen and plasma protein synthesis by hepatocytes occurs here. Zone 3 is furthest from the distributing vessels; between zones 1 and 3 is the intermediate zone 2. A gradient of metabolic activity exists for many hepatic enzymes in the three zones. Zone 3 is poorly oxygenated, is the first to show ischemic necrosis and fat accumulation if metabolism is altered, and is the site of most drug and alcohol detoxification

Not sure if that helps at all though...

 

[Phloston]

My guess would be that since P-450 is at zone III, drugs/toxins that become deleterious having undergone P-450 metabolism will lead to damage here. In contrast, drugs that are P-450 independent, or are on their own detrimental, will instead cause zone I damage.

As far as which drugs/toxins affect the particular zones, that's probably beyond the scope of Step1, but I'd just stick to knowing that viral hepatitis and phosphorus poisoning hurt zone I, but alcohol, ischaemia and paracetamol knock out zone III.

And of course yellow fever (with Councilman bodies) is zone II...

 

[Belleza156]

P.342 of FA2012, under the "Liver anatomy" heading in the middle of the page, all the way on the right, says zone III as most sensitive to toxic injury.

However, look at the below PrntScr image from Kaplan QBank (which I've just started). This is the first question I've done and there's ALREADY a discrepancy./COLOR]

Press Ctrl+ to make the image bigger.

Anyone's thoughts?

I'm aware that phosphorus poisoning affects zone I before zone III, so I'm actually wondering if FA is incorrect...

First Aid sucks IMO. It's replete with errors, which doesn't even make sense that 20+ edition of a book be so full of errors year to year. I've seen errors that were in last years errata list repeated this year. I stopped reading FA for info after the 1st two weeks. If you haven't done so, sit down with the errata list its like over 14 pages long. Annotate all errata, and from now on if what Kaplan or Uworld (especially Uworld) differs from FA, by default FA is WRONG!!! Seriously, 9,89999 times out of 10.

 

[Belleza156]

My guess would be that since P-450 is at zone III, drugs/toxins that become deleterious having undergone P-450 metabolism will lead to damage here. In contrast, drugs that are P-450 independent, or are on their own detrimental, will instead cause zone I damage.

As far as which drugs/toxins affect the particular zones, that's probably beyond the scope of Step1, but I'd just stick to knowing that viral hepatitis and phosphorus poisoning hurt zone I, but alcohol, ischaemia and paracetamol knock out zone III.

And of course yellow fever (with Councilman bodies) is zone II...

Paracetomol? You are definiteley not in the states! I think you will only see Acetaminophen here.

Straight from Medscape:

Acute hepatocellular injury: Manifestations of acute liver injury may range from spotty necrosis to fulminant liver failure. Spotty necrosis resembles classic viral hepatitis and involves all acinar zones. Hepatocellular injury consists of ballooning degeneration or apoptosis with eosinophils, especially in cases of peripheral eosinophilia. Drugs that can cause this type of injury are INH, halothane, phenylbutazone, indomethacin, and disulfiram. Submassive necrosis, as the name suggests, may affect zone 1 (periportal) or zone 3 (central necrosis). Periportal changes occur with ferrous sulfate poisoning, phosphorus poisoning, and cocaine toxicity. Central necrosis occurs with acetaminophen, halothane, methoxyflurane, trovafloxacin, ketoconazole, dihydralazine, tacrine, and mushroom poisoning. Massive necrosis is an extension of submassive necrosis and manifests as fulminant failure.

 

[Phloston]

First Aid sucks IMO. It's replete with errors, which doesn't even make sense that 20+ edition of a book be so full of errors year to year. I've seen errors that were in last years errata list repeated this year. I stopped reading FA for info after the 1st two weeks. If you haven't done so, sit down with the errata list its like over 14 pages long. Annotate all errata, and from now on if what Kaplan or Uworld (especially Uworld) differs from FA, by default FA is WRONG!!! Seriously, 9,89999 times out of 10.

LOL. I spent ~2 hours going through the errata back in late-April, I believe. I'll have to do so again soon.

 

[Abby_Normal]

Zone I is the first to get hit with toxins but it's also the most able to handle them due to the blood flow. Zone III is located at a "safer" distance, but its susceptibility to ischemia makes it harder for damage there to be repaired. That's what I remember from histo lectures, at least.

 

[Phloston]

Zone I is the first to get hit with toxins but it's also the most able to handle them due to the blood flow. Zone III is located at a "safer" distance, but its susceptibility to ischemia makes it harder for damage there to be repaired. That's what I remember from histo lectures, at least.

Good point. I think the idea for the USMLE would be to know which specific toxins damage where as opposed to the generality (e.g. knowing paracetamol/EtOH hit zone III or yellow fever at zone II, vs just "toxins at zone III or I").

 

[Brucelaa67]

What about cocaine toxicity?

Paracetomol? You are definiteley not in the states! I think you will only see Acetaminophen here.

Straight from Medscape:

Acute hepatocellular injury: Manifestations of acute liver injury may range from spotty necrosis to fulminant liver failure. Spotty necrosis resembles classic viral hepatitis and involves all acinar zones. Hepatocellular injury consists of ballooning degeneration or apoptosis with eosinophils, especially in cases of peripheral eosinophilia. Drugs that can cause this type of injury are INH, halothane, phenylbutazone, indomethacin, and disulfiram. Submassive necrosis, as the name suggests, may affect zone 1 (periportal) or zone 3 (central necrosis). Periportal changes occur with ferrous sulfate poisoning, phosphorus poisoning, and cocaine toxicity. Central necrosis occurs with acetaminophen, halothane, methoxyflurane, trovafloxacin, ketoconazole, dihydralazine, tacrine, and mushroom poisoning. Massive necrosis is an extension of submassive necrosis and manifests as fulminant failure.

I know its an old post, but I hope I can get a solution to my confusion.
What about Cocaine toxicty?
FA 2017 mentions it in Zone 1, as does your reference from medscape.
Bu following expalanations, links present a slightly different picture, as they say P450 metabolism is mechanism behind coacaine toxicty, so should affect Zone 3.
Cocaine
The role of CYP enzymes in cocaine-induced liver damage

 

[Jabbed]

What about cocaine toxicity?

I know its an old post, but I hope I can get a solution to my confusion.
What about Cocaine toxicty?
FA 2017 mentions it in Zone 1, as does your reference from medscape.
Bu following expalanations, links present a slightly different picture, as they say P450 metabolism is mechanism behind coacaine toxicty, so should affect Zone 3.
Cocaine
The role of CYP enzymes in cocaine-induced liver damage

Forest and trees.

Just know the generalities and any vignette that's not a super classic situation (tylenol ingestion, shock liver, yellow fever, viral hepatitis) will give you some clue as to whether it's a metabolic toxin (affecting zone III) or a direct toxin (affecting zone I).

For absolute ****s and giggles.. a quick literature search shows that there is evidence of both zone I and zone III necrosis in cocaine toxicity, suggesting that there's a combination of direct toxicity (zone I) as well as metabolic (zone III) and ischemic (zone III).