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salicylate toxicity

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doopdidoop

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does anyone know what the timeline is for salicylate poisoning? i know it initially starts out as respiratory alkalosis because of the direct stimulation of the respiratory center and later becomes AG metabolic acidosis as salicylate levels rise, but what is the timeline of all this? just asking since i do recall seeing some questions about salicylate poisoning blood gas levels coming in at different times...but it was a while ago so i don't know which test in UWorld has the explanation. thanks!! :D
 

AndyRSC

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Stage 1 occurs in first 12 hours. Respiratory alkalosis from direct stimulation of respiratory drive predominates. Bicarb is lost in the urine.
Stage 2 occurs from 12-24 hours. Paradoxical aciduria occurs, which may lead to hypokalemia.
Stage 3 occurs after 24 hours (earlier in infant). Metabolic acidosis (due to lactic acidosis, dehydration, and hypokalemia) sets in. Hyperpnea is now due to acidosis.
 

Phloston

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Stage 1 occurs in first 12 hours. Respiratory alkalosis from direct stimulation of respiratory drive predominates. Bicarb is lost in the urine.
Stage 2 occurs from 12-24 hours. Paradoxical aciduria occurs, which may lead to hypokalemia.
Stage 3 occurs after 24 hours (earlier in infant). Metabolic acidosis (due to lactic acidosis, dehydration, and hypokalemia) sets in. Hyperpnea is now due to acidosis.

Could you elaborate on the mechanisms here?
 

AndyRSC

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Sure. The medullary respiratory center is directly stimulated, causing primary respiratory alkalosis and leading to compensatory renal bicarbonate excretion. Increased renal secretion of sodium, potassium, and water accompanies loss of bicarbonate in the urine. When enough potassium has been depleted and enough dehydration has occurred, paradoxical aciduria takes place.

Salicylates are an uncoupling agent at high doses, and allow protons to go through the inner mitochondrial membrane instead of ATP synthase, which causes a shutdown of ATP production, and all the energy created in the process of electron flow and proton gradient formation is given off as heat, leading to fever. Furthermore, salicylates inhibit the Krebs cycle, specifically the succinate dehydrogenase and alpha-ketogluterate dehydrogenase enzymes, which causes lactic acidosis to predominate. The metabolism of fatty acids likewise becomes increased, generating ketosis. Finally, salicylate toxicity may cause renal insufficiency and retention of phosphoric and sulfuric acids. Cumulatively, this creates an anion-gap metabolic acidosis.

The end-result is a hypermetabolic state, with increased O2 consumption, increased CO2 production, accelerated glycolytic and lipolytic pathways, and hyperpyrexia. The hyperpyrexia, hyperventilation, renal losses, and possibly vomiting, result in severe dehydration.

This is all just a curiosity, in the context of Step 1 studying, and you'll have to know none of the above. The questions you will probably be asked are what the disturbances are early vs late (possibly including an up/down arrow set of choices), and about alkalinization of urine to help facilitate excretion.
 

zeevee

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There is a UW question that specifically mentions MIXED resp alkalosis with metabolic acidosis at 4-5 hrs and another question from the usmle free practice material on their website says 3 hrs for mixed.So I think a combined picture starts as soon as 3 hrs.Does it stay mixed or totally transform to metabolic acidosis ?
 

worldbeater

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So, this is really nice concept that you can get some points on because it makes sense once you go through it a couple times. As the poster mentioned above, there are three stages to aspirin poisoning. He explained it well with the biochem involved, I'll try simplify a little bit more. They are (with time frame):

1) Less than 15 minutes -> respiratory alkalosis
2) 30 - 60 minutes -> combined respiratory alkalosis and metabolic acidosis. This will be 90% of questions, since this the time frame for the patient to come to the ER*(see below)
3) mixed acidosis

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Stage 1 - you have ingested aspirin. This stimulates your respiratory rate (increased respiratory drive as I was taught earlier this week by a poster), so you have respiratory alkalosis -> blowing off CO2 (an acid) -> high pH

Stage 2 - the acid(aspirin) dissociates. So you still have respiratory alkalosis and now you have a metabolic acidosis with it. The term for two items in opposite directions is called combined, so this is combined respiratory alkalosis and metabolic acidosis. The two pH's will cancel each other out -> so you will have a normal pH (again this is your 90%, so know this point well)

Stage 3 - GABA increases. This slows everything down. You now have a decrease respiratory rate -> so your retaining CO2 -> respiratory acidosis and metabolic acidosis from the aspirin. The term for pH in the same direction is called mixed, so this is a mixed acidosis.

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*One thing that doesn't fit in terms of timeframe, as a poster mentioned above. So there is UWorld question where the patient has combined metabolic alkalosis with metabolic acidosis(which is stage 2, 90% of questions), which makes sense, but the OD was 4-5 hours ago. So I don't know how hard and fast the rules are for time, but that's the best way to keep it organized is above.
 
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