Step 1 Complicated Concepts Thread

[TheSeanieB]

ASK AND ANSWER TOUGH QUESTIONS RELATED TO STEP 1.

Starting with me:
physiologic chloride shift - When CO2 diffuses into a RBC, it quickly converts with H2O to H+ and HCO3- so that CO2 will continue to passively diffuse into the RBC. The HCO3- is then excreted into the plasma by a Cl-/HCO3- exchanger. When the RBC enters the pulmonary capillaries, the process reverses. HCO3- is taken up by exchange for a Cl-. It combines with H+ to creates CO2 +H2O. The CO2 then diffuses out of the RBC and ultimately into the alveoli. This process allows for maximal CO2 excretion by a RBC.

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[tiedyeddog]

You have points 1-3 down, which is good, because that's the hardest part of the concept.

Think of this concept from the opposite manner, and this scenario will make better sense.

Lets say you're losing blood, right...you're becoming hypotensive...aortic/carotid bodies sense this and send a message to solitary nucleus of medulla to increase SNS and decrease PSNS. vessels constrict and heart pumps harder...as the initial response to loss of blood, cool?

Now, lets do the reverse. you're hypertensive, you're aortic/carotid bodies sense this. send a message to same area of medulla, to decrease SNS drive, and increase PSNS by working on the muscarinic receptors &...these two mechanisms are ka "reflex tachycardia" and "reflex bradycardia" respectively.

ok, in add'n think for a minute. you're blood pressure is high. the drugs we use to treat hypertensive are trying to decrease TPR, as their main mechanism of action (ie CCBs, hydralazine, minoxidil, nitroprusside, etc etc). so you said you would think inotropy would increase. basically, you want the heart to push blood against high resistance. well, this doesn't work, because we know from Pathology 101 increase systemic blood pressure, causes remodeling of the heart and leads to concentric hypertrophy --> this leads to angina ---> and the rest of the spiraling downward problems. hence, why we give ACE-I to prevent remodeling of the vents.

http://www.usmle-forums.com/usmle-s...iac-output-venous-return-curves-question.html

this also has a good explanation, see post 10.

Increased TPR shifts both curves down:

Vascular: leads to decreased venous return because blood is slower getting through the arterioles.

cardiac: higher pressure in the arterial side means a higher afterload, afterload decreases cardiac output.

 

[Jonari]

http://www.usmle-forums.com/usmle-s...iac-output-venous-return-curves-question.html

this also has a good explanation, see post 10.

Increased TPR shifts both curves down:

Vascular: leads to decreased venous return because blood is slower getting through the arterioles.

cardiac: higher pressure in the arterial side means a higher afterload, afterload decreases cardiac output.

this is honestly the one concept i hate the most in cardio phys...and pressure volume loops...

 

[tiedyeddog]

this is honestly the one concept i hate the most in cardio phys...and pressure volume loops...

me too, me too

I hate looking at those cardiac - venous curves. they just hurt my brain

 

[loveoforganic2]

As far as adrenergics

NE binds alpha 1/2 and beta 1; ZERO affinity for beta 2.
EPI binds ALL adrenergic receptors.

The AFFINITY for receptors is beta 2 > alpha 1
The EFFICACY for receptors is alpha 1 > beta 2

The sequelae of this is that NE will ALWAYS vasoconstrict. EPI may vasodilate OR vasoconstrict dependent on its concentration. Low concentration EPI => vasodilation while high concentration EPI => vasoconstriction. This is because at low concentration, the higher affinity of beta 2 receptors leads to selective binding by EPI. At high concentration, there's enough EPI to go around, and the higher EFFICACY of alpha 1 receptors overpowers the effect of beta 2 binding.

I think all of that prior stuff is step relevant. Additional explanation that isn't so step relevant is beta 2 to alpha 1 ratio in tissue (there's a variable distribution). In vessels of the leg and other areas with lots of skeletal muscle, beta 2 to alpha 1 ratio is high, so SNS activation => vasodilation in this regions. In the GI tract and kidney (splanchnic vessels), beta 2 to alpha 1 ratio is low, so SNS activation => vasoconstriction in these regions.

Finally, dopamine has differential adrenergic activity. With increasing dose, you get D1 => beta 1 => alpha 1 activity

I think this has been more or less explained, but thought it might be helpful to have condensed into one post

 

[tiedyeddog]

As far as adrenergics

NE binds alpha 1/2 and beta 1; ZERO affinity for beta 2.
EPI binds ALL adrenergic receptors.

The AFFINITY for receptors is beta 2 > alpha 1
The EFFICACY for receptors is alpha 1 > beta 2

The sequelae of this is that NE will ALWAYS vasoconstrict. EPI may vasodilate OR vasoconstrict dependent on its concentration. Low concentration EPI => vasodilation while high concentration EPI => vasoconstriction. This is because at low concentration, the higher affinity of beta 2 receptors leads to selective binding by EPI. At high concentration, there's enough EPI to go around, and the higher EFFICACY of alpha 1 receptors overpowers the effect of beta 2 binding.

I think all of that prior stuff is step relevant. Additional explanation that isn't so step relevant is beta 2 to alpha 1 ratio in tissue (there's a variable distribution). In vessels of the leg and other areas with lots of skeletal muscle, beta 2 to alpha 1 ratio is high, so SNS activation => vasodilation in this regions. In the GI tract and kidney (splanchnic vessels), beta 2 to alpha 1 ratio is low, so SNS activation => vasoconstriction in these regions.

Finally, dopamine has differential adrenergic activity. With increasing dose, you get D1 => beta 1 => alpha 1 activity

I think this has been more or less explained, but thought it might be helpful to have condensed into one post

very helpful, thanks

 

[dbeast]

Don't you just love when you find something you wrote down a while ago and have no idea what you're talking about? Here's a good one from my notes:

Uremia causes platelet dysfunction (bleeding risk) and neutrophil dysfunction (infection risk)... anybody know why this happens? Is it just that urea is toxic to the cells?

 

[dbeast]

very helpful, thanks

Agreed

 

[loveoforganic2]

Don't you just love when you find something you wrote down a while ago and have no idea what you're talking about? Here's a good one from my notes:

Uremia causes platelet dysfunction (bleeding risk) and neutrophil dysfunction (infection risk)... anybody know why this happens? Is it just that urea is toxic to the cells?

Dunno how it happens, but uremia definitely at least causes platelet dysfxn. Don't think I'd previously heard of PMN dysfxn

 

[SLC]

Don't you just love when you find something you wrote down a while ago and have no idea what you're talking about? Here's a good one from my notes:

Uremia causes platelet dysfunction (bleeding risk) and neutrophil dysfunction (infection risk)... anybody know why this happens? Is it just that urea is toxic to the cells?

It's thought that uremia leads to platelet dysfunction through increased NO production by both platelets and endothelial cells.

At least that's what we were taught in Heme.

I've also never heard of neutrophil dysfunction due to Uremia.

 

[Jamiu22]

It's thought that uremia leads to platelet dysfunction through increased NO production by both platelets and endothelial cells.

At least that's what we were taught in Heme.

I've also never heard of neutrophil dysfunction due to Uremia.

So if you are have HUS or TTP, you are doubly screwed!

 

[loveoforganic2]

Something I completely forgot about, but a good concept that just came up indirectly in UW -

Pop quiz - What's a differentiating symptom between cholinomimetic toxicity and AChEi toxicity?

 

[MLT2MT2DO]

So if you are have HUS or TTP, you are doubly screwed!

Uremic platelet dysfunction and HUS, though I'm sure have overlapping similarities, are two different things. Uremic platelet dysfunction happens usually due to chronic renal failure whereas HUS is normally seen in Shiga toxin as with Sonnei (kids) or E.Coli H (raw meat).

 

[tiedyeddog]

Something I completely forgot about, but a good concept that just came up indirectly in UW -

Pop quiz - how do you differentiate cholinomimetic toxicity and AChEi toxicity?

CNS signs? I dunno.

 

[loveoforganic2]

CNS signs? I dunno.

Going to give it a little bit to see if someone comes up with it. It's something I wouldn't think would be HY (and probably isn't overall), but it came up as part of a patient presentation in UW, and the oddball side effect was throwing me off

 

[tiedyeddog]

Brings up a similar point, however.

Anticholinergic and sympathomimetic toxidromes are also very similar.

Difference only being that in sympathomimetic toxidrome you have sweating and hyperactive bowel sounds (no parasympathetic innervation of those).

 

[dbeast]

Going to give it a little bit to see if someone comes up with it. It's something I wouldn't think would be HY (and probably isn't overall), but it came up as part of a patient presentation in UW, and the oddball side effect was throwing me off

There's a drug that "regenerates" AChE I'm just blanking on the name...

Edit: I cheated and looked it up, highlight below to see the name

Pralidoxime

 

[coolforschool]

There's a drug that "regenerates" AChE I'm just blanking on the name...

Pralidoxime (2-PAM).

 

[Pons Asinorum]

There's a drug that "regenerates" AChE I'm just blanking on the name...

Edit: I cheated and looked it up, highlight below to see the name

Pralidoxime

Pralidoxime. Get off here and study! Are you June 7 too? We need to catch up after this hell is over.

 

[loveoforganic2]

Brings up a similar point, however.

Anticholinergic and sympathomimetic toxidromes are also very similar.

Difference only being that in sympathomimetic toxidrome you have sweating and hyperactive bowel sounds (no parasympathetic innervation of those).

That ones definitely HY. Another would be between sympathomimetics and ganglionic stimulators (get muscle sx, e.g. fasciculations w/ganglionic stimulators)

There's a drug that "regenerates" AChE I'm just blanking on the name...

Edit: I cheated and looked it up, highlight below to see the name

Pralidoxime

That's completely right, but not what I had in mind - revised the question to be more clear

 

[loveoforganic2]

Something I completely forgot about, but a good concept that just came up indirectly in UW -

Pop quiz - What's a differentiating symptom between cholinomimetic toxicity and AChEi toxicity?

Answer and explanation in white below

Hypotension can occur with cholinomimetics due to binding extrajunctional M3 receptors on vascular endothelium (stimulates release of NO). This doesn't occur with AChEi's because ACh is only increased where it is being released from nerve terminals. Extrajunctional receptors do not synapse with a nerve terminal. One of the few situations you get bradycardia and hypotension

 

[MLT2MT2DO]

In that case wouldn't you have an increase in stomach acid/pain as well with cholinomimetic toxicity?

 

[loveoforganic2]

In that case wouldn't you have an increase in stomach acid/pain as well with cholinomimetic toxicity?

If you mean by parietal cell stimulation, I was under the impression those ACh receptors were junctional (so it would be a possible side effect of both, though I've never heard of it as a symptom). I might be wrong on that though. I added a sentence at the end of the explanation btw, after you posted - an odd combination of things that should clue you into the cholinomimetic toxidrome as a possibility

 

[dbeast]

Pralidoxime. Get off here and study! Are you June 7 too? We need to catch up after this hell is over.

10th. I miss you so much it hurts.

 

[MLT2MT2DO]

If you mean by parietal cell stimulation, I was under the impression those ACh receptors were junctional (so it would be a possible side effect of both, though I've never heard of it as a symptom). I might be wrong on that though. I added a sentence at the end of the explanation btw, after you posted - an odd combination of things that should clue you into the cholinomimetic toxidrome as a possibility

Ok, that last sentence you added helped out. Was trying to tie my limited knowledge of M3 receptors into it. You're correct only junctional on parietal cells.

 

[SLC]

Brings up a similar point, however.

Anticholinergic and sympathomimetic toxidromes are also very similar.

Difference only being that in sympathomimetic toxidrome you have sweating and hyperactive bowel sounds (no parasympathetic innervation of those).

Ok, on that note, what's unique about the adrenergic stimulation at the sweat glands?

 

[loveoforganic2]

Are patients with fulminant hepatitis or acute vitamin K deficiency at risk of skin necrosis?

 

[SLC]

Are patients with fulminant hepatitis or acute vitamin K deficiency at risk of skin necrosis?

I don't think they are.

Skin necrosis (Warfarin induced I assume your thinking about) is usually associated with Protein C deficiency, which is gamma-carboxylated and has the shortest half life of the gamma-carboxylated factors.

People who have a deficiency are at an increased risk of short term hyper coagulable state when placed on Warfarin because what little ProteinC they had doesn't last long enough to protect them till they have a therapeutic INR.

In fulminant hepatitis I'd expect an equal effect on all factors.

In VitK deficiency, initially and with comorbid ProteinC deficiency, maybe.

 

[loveoforganic2]

Protein C is the 1st to go, so regardless of the etiology of the factor deficiencies, it seems like you'd end up with a relative deficiency of Protein C and become hypercoagulable prior to developing bleeding diathesis (that is, for any etiology that involves defective production and not factor consumption). I haven't ever heard of thrombotic susceptibility in either vitamin K deficiency or fulminant hepatitis, but physiologically it seems like something that should happen and has always had me curious. Maybe it's just a factor of frequency, where there are so many opportunities for lapses in compliance with warfarin?

 

[Jonari]

Protein C is the 1st to go, so regardless of the etiology of the factor deficiencies, it seems like you'd end up with a relative deficiency of Protein C and become hypercoagulable prior to developing bleeding diathesis (that is, for any etiology that involves defective production and not factor consumption). I haven't ever heard of thrombotic susceptibility in either vitamin K deficiency or fulminant hepatitis, but physiologically it seems like something that should happen and has always had me curious. Maybe it's just a factor of frequency, where there are so many opportunities for lapses in compliance with warfarin?

Just wanted to clarify, but Protein C isn't the first factor to go. It's actually factor 7. It has even a shorter half life compared to PC, approximately half the t.5 of PC. So when you take warfarin the extrinsic pathway is immediately wiped out, and the next factor it acts on is PC, and wiping out PC is what makes the patient hyper coagulable.

 

[SLC]

Just wanted to clarify, but Protein C isn't the first factor to go. It's actually factor 7. It has even a shorter half life compared to PC, approximately half the t.5 of PC. So when you take warfarin the extrinsic pathway is immediately wiped out, and the next factor it acts on is PC, and wiping out PC is what makes the patient hyper coagulable.

The entire basis of Warfarin Induced Skin necrosis is hypercoagulability due to ProteinC being affected before factor7.

But that's mainly a concern in patients with a ProC deficiency, so maybe there's something else at play here?

 

[loveoforganic2]

Just wanted to clarify, but Protein C isn't the first factor to go. It's actually factor 7. It has even a shorter half life compared to PC, approximately half the t.5 of PC. So when you take warfarin the extrinsic pathway is immediately wiped out, and the next factor it acts on is PC, and wiping out PC is what makes the patient hyper coagulable.

I was initially going to say you're right, but then I was thinking maybe fVII is just the 1st clotting factor to go, so I looked it up, but it turns out you're right

The entire basis of Warfarin Induced Skin necrosis is hypercoagulability due to ProteinC being affected before factor7.

But that's mainly a concern in patients with a ProC deficiency, so maybe there's something else at play here?

That may be. I think I can answer the test questions fine for this, but as far as knowing what's actually going on, I'm pretty confused

 

[JP2740]

I don't think it's been fully figured out why skin necrosis occurs, but the theory right now is that cholesterol emboli to arterioles in the extremities is caused by that temporary procoagulant state (protein C deficiency)

 

[223556]

This might sound stupid, but:

IL-4 stimulates IgE
IL-5 stimulates IgA

Which one of the two creates eosinophilia? For whatever reason, I have written down from a previous question that IL-5 stimulates them...yet IgE is more of a "worm-attack" Ig.

 

[Jamiu22]

This might sound stupid, but:

IL-4 stimulates IgE
IL-5 stimulates IgA

Which one of the two creates eosinophilia? For whatever reason, I have written down from a previous question that IL-5 stimulates them...yet IgE is more of a "worm-attack" Ig.

Wikipedia

IgE mediated eosinophil production is induced by compounds released by basophils and mast cells, including eosinophil chemotactic factor of anaphylaxis, leukotriene B4, complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration).[3]

 

[JP2740]

Anterior spinal artery. wtf is up with this in 1st aid pg.422. It throws out contralateral/ipsi, etc, but I thought there was only one anterior spinal artery? How could there be an opposite body defect?

 

[Jamiu22]

Anterior spinal artery. wtf is up with this in 1st aid pg.422. It throws out contralateral/ipsi, etc, but I thought there was only one anterior spinal artery? How could there be an opposite body defect?

The ASA also supplies the caudal medulla.. so if the lesion is prior to the pyramid of decussation then you would get contralateral hemiplegia and loss of sensation... but further down along the ASA, then it'd be ipsilateral...

Since FA also mentioned ipsilateral loss of hypoglossal nerve function, then we know that they are referring to a lesion that high up.... which could cause those symptoms.

 

[Jonari]

this was posted on the allopathic portion of the forum. might come in handy...

http://www.winona.edu/biology/adam_ip/home/

 

[sharklasers]

I don't remember this being a "Complicated Concept" while doing renal stuff, but I don't get ACE inhibitors

"Inhibit angiotensin-converting enzyme (ACE) - decrease angiotensin II - decrease GFR by preventing constriction of efferent arterioles. "

From first aid.

I would think that ACE inhibitors decrease blood pressure by reducing the amount of aldosterone. First aid lists the mechanism of ACE inhibitors as the above. I know it actually does decrease angiotensin II, but is this the actual mechanism of ACE inhibitors decreasing BP?

It seems as though decreasing angiotensin II could actually lead to an INCREASE in BP by decreasing the amount of filtration in the glomerulus.

Thanks!

 

[Jamiu22]

I don't remember this being a "Complicated Concept" while doing renal stuff, but I don't get ACE inhibitors

"Inhibit angiotensin-converting enzyme (ACE) - decrease angiotensin II - decrease GFR by preventing constriction of efferent arterioles. "

From first aid.

I would think that ACE inhibitors decrease blood pressure by reducing the amount of aldosterone. First aid lists the mechanism of ACE inhibitors as the above. I know it actually does decrease angiotensin II, but is this the actual mechanism of ACE inhibitors decreasing BP?

It seems as though decreasing angiotensin II could actually lead to an INCREASE in BP by decreasing the amount of filtration in the glomerulus.

Thanks!

ACE inhibitor does a lot of things, but with regards to BP, the main concepts to keep in mind is that the name comes from "Angio-tension"... so if you inhibit tension on peripheral blood vessels - it makes sense that the BP would decrease, right? another aspect is that you don't get ATII - this normally stimulates aldosterone.. if you don't get aldosterone, you can't reabsorb salt and water at the collecting duct....so with less plasma/water in the blood... you would also get a lower BP. Those are the two main mechanism you need to know in terms of BP...

Why do they use it for diabetic patients? because they get constriction of the blood vessels through enzymatic glycosylation...by blocking the "angio-tension" portion, then the blood vessels in the kidney are vasodilated .. and the kidney can be perfused.

Also in terms of filtration... you have to also know that although ATII works on both afferent and efferent arterioles, its effects is mainly on the efferent arteriole.. so when you block ATII.. you get vasodilation of the efferent arteriole, thereby increasing RPF (don't talk about FF w/o also looking at what's going on with the GFR - also depends on knowing what's going on in the afferent arteriole)

 

[JP2740]

How to tell a lacunar ischemia from lacunar hemorrhage?

 

[dbeast]

This is probably minutae, but does anybody have a good way to differentiate lymphogranuloma venerium (chlamydia) vs. granuloma inguinale (klebsiella/donovonosis)?

Here's why it's annoying: Transmission and symptoms are identical, both are a non-painful genital ulcer, both have intra-cytoplasmic inclusions on histology. Besides that, what else is left to tell the difference? Giemsa stain? Why are all my questions about STD's? Ugh.

 

[tiedyeddog]

How to tell a lacunar ischemia from lacunar hemorrhage?

like based on symptoms or imaging?

 

[Jamiu22]

like based on symptoms or imaging?

I agree, I don't think you can tell through physical diagnosis... on the other hand, with imaging.. you could discern the difference between the two... and various imaging modalities would elucidate varying abnormalities.

 

[Jamiu22]

This is probably minutae, but does anybody have a good way to differentiate lymphogranuloma venerium (chlamydia) vs. granuloma inguinale (klebsiella/donovonosis)?

Here's why it's annoying: Transmission and symptoms are identical, both are a non-painful genital ulcer, both have intra-cytoplasmic inclusions on histology. Besides that, what else is left to tell the difference? Giemsa stain? Why are all my questions about STD's? Ugh.

lol.. couldn't tell ya!

 

[tiedyeddog]

This is probably minutae, but does anybody have a good way to differentiate lymphogranuloma venerium (chlamydia) vs. granuloma inguinale (klebsiella/donovonosis)?

Here's why it's annoying: Transmission and symptoms are identical, both are a non-painful genital ulcer, both have intra-cytoplasmic inclusions on histology. Besides that, what else is left to tell the difference? Giemsa stain? Why are all my questions about STD's? Ugh.

Seems like in general lymphogranuloma venerium is more likely to have adenopathy and also it seems they unlikely form chronically infected sinus tracts.

Granuloma inguinale less often has associated adenopathy but can form "pseduobuboes" which are large nodules they do not ulcerate.

http://www.ncbi.nlm.nih.gov/pubmed/8304262

 

[JP2740]

I agree, I don't think you can tell through physical diagnosis... on the other hand, with imaging.. you could discern the difference between the two... and various imaging modalities would elucidate varying abnormalities.

Could you explain

 

[sharklasers]

This is probably minutae, but does anybody have a good way to differentiate lymphogranuloma venerium (chlamydia) vs. granuloma inguinale (klebsiella/donovonosis)?

Here's why it's annoying: Transmission and symptoms are identical, both are a non-painful genital ulcer, both have intra-cytoplasmic inclusions on histology. Besides that, what else is left to tell the difference? Giemsa stain? Why are all my questions about STD's? Ugh.

i have in my notes that granuloma inguinale can cause elephantiasis, maybe that would be a distinguishing characteristic if they were to ask about it?

but i feel like an easier way to distinguish would be gram stain, right? i don't think chlamyidia would show on a gram stain.

or i guess you can use macconkey agar for klebsiella

 

[JP2740]

The ASA also supplies the caudal medulla.. so if the lesion is prior to the pyramid of decussation then you would get contralateral hemiplegia and loss of sensation... but further down along the ASA, then it'd be ipsilateral...

Since FA also mentioned ipsilateral loss of hypoglossal nerve function, then we know that they are referring to a lesion that high up.... which could cause those symptoms.

But if you knock out the asa which is central, aren't you hitting both sides?

 

[Jamiu22]

Could you explain

Small Vessel Disease/Lacunar Infarction
Small vessel disease, or lacunar infarction, occurs when blood flow is blocked to a very small arterial vessel. The term's origin is from the Latin word lacuna which means hole, and describes the small cavity remaining after the products of deep infarct have been removed by other cells in the body.

The way I look at Lacunar hemorrhage on the other hand is that is mostly arises from Charcot Bouchard Aneuryms probably hypertensive induced.. whenever the aneurysms rupture, you then get the Lacunar hemorrhage, so with this you would see blood pooling in the lenticulo-striate area on CT. While on the other hand with the Lacunar infarct.. it would mainly be from occlusion of the artery i.e. less likely to see blood in a the area of interest (lol, unless the infarct is caused by hemorrhage in another area - then you would still see blood, but not resulting in the pathology of interest)

At least that's what I think. lol

 

[Jamiu22]

But if you knock out the asa which is central, aren't you hitting both sides?

You are absolutely right...I read FA as simply highlighting what is actually happening to each side of the spinal chord...but since ASA is happens to be in the middle, the pathology would most likely affect both sides of the spinal chord... but there would always be that patient that get's affected on one side more than the other....

...so it's all in how FA was trying to interpret that. But for most cases, I believe that you are absolutely correct that it'd affect the spinal chord bilaterally. And of course, I could be wrong.