Official Step 1 High Yield Concepts Thread

[Transposony]

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Let's discuss our doubts/offer clarifications about mechanisms/concepts for Step 1

ASK ANY QUESTIONS here.

To kick start the thread here is something I didn't know:

1. Penicillin-binding proteins (PBPs) are actually enzymes (transpeptidases & carboxypeptidases) which cross-link peptidoglycan. Penicillins binds to these enzymes and inactivating them thereby preventing cross-linkiing of peptidoglycan.

2. Periplasmic space (Gram -ve) contain proteins which functions in cellular processes (transport, degradation, and motility). One of the enzyme is β-lactamase which degrades penicillins before they get into the cell cytoplasm.
It is also the place where toxins harmful to bacteria e.g. antibiotics are processed, before being pumped out of cells by efflux transporters (mechanism of resistance).

There are three excellent threads which you may find useful:

List of Stereotypes

Complicated Concepts Thread

USMLE images

 

[pathologyDO]

Can someone explain to me why Vitamin A excess is an etiology of pseudotumor cerebri?

 

[Radiolucent]

Can someone explain to me why Vitamin A excess is an etiology of pseudotumor cerebri?

From what I remember Vitamin A/all-trans retinoic acid somehow interacts with the arachnoid granulations and inhibits reabsorbtion of the CSF and therefore increasing the ICP.

 

[aspiringmd1015]

^if so, thank god. thats been killing me for the longest time.

 

[aspiringmd1015]

is chronic bronchitis also associated with increases in RV and TLC? I always thought it was, but UW says in addition to COPD, emphysema increases RV and TLC

 

[faisal 2000]

is chronic bronchitis also associated with increases in RV and TLC? I always thought it was, but UW says in addition to COPD, emphysema increases RV and TLC

COPDs (bronchitis\emphysema) will increase RV and TLC due to trapping air in the lung. also asthma increases RV and TLC.

 

[Radiolucent]

Donovanosis
Lymphygranuloma venereum
Chancroid
Chancre

Which of these are painful/painless?
Which of these have intracytoplasmic inclusions?
Causative organisms?

 

[seminoma]

Just noticed that FA says HSV-2 causes meningitis in adults, but as a TORCH it causes encephalitis in neonates. Anyone know if there's any significance to that?

Pages 173 and 175 FA 15

whats the mechanism of hyaline membrane formatoin in neonatal RDS, adult ards is obvious.

Hypoxemia and CO2 retention --> acidosis, pulmonary vasoconstriction --> hypoperfusion --> endothelial/epithelial cell damage --> necrosis + fibrin deposition --> hyaline membranes --> reduced DLCO --> further hypoxemia --> as above.

COPDs (bronchitis\emphysema) will increase RV and TLC due to trapping air in the lung. also asthma increases RV and TLC.

I don't think bronchitis necessarily increases TLC. Compliance is normal in CB so TLC should be normal. FRC is up because of air trapping like you said, but TLC won't necessarily change.

Donovanosis
Lymphygranuloma inguinale
Chancroid
Chancre

Which of these are painful/painless?
Which of these have intracytoplasmic inclusions?
Causative organisms?

Donovanosis and chancre are painless; chancroid/LGV painful.
Donovanosis and LGV have inclusions.

Donovanosis - Kleb
Lymphygranuloma inguinale - chlamydia L1-L3
Chancroid - H.ducreyi
Chancre - treponema pallidum

 

[Radiolucent]

Donovanosis and chancre are painless; chancroid/LGV painful.
Donovanosis and LGV have inclusions.

Donovanosis - Kleb
Lymphygranuloma inguinale - chlamydia L1-L3
Chancroid - H.ducreyi
Chancre - treponema pallidum

Excellent. Though according to FA, LGV is painless.

 

[seminoma]

Excellent. Though according to FA, LGV is painless.

Nice, thanks for that. I wasn't sure, though I thought I created a paradigm in my head that syphillis and kleb were the only painless lesions. I guess I did that wrong!

Edit: Actually just found the UW note I made. Initial lesions in syph, LGV, and kleb inguinale are painless, but the lesions in LGV progress to painful adenopathy and ulcers/ulceration. Now I remember why I got that UW question wrong. Also worth noting that adenopathy is much more common when it's LGV than when it's kleb inguinale. QID 1154 if anyone is interested.

Really sad to think that I went through all of MS1 micro and all of MS2 thinking that painless genital lesion = syphilis 100%.

 

[seminoma]

Anyone know about tertiary syphilis testing? I was watching a Conrad Fischer video and he says CSF FTA is more sensitive than CSF VDRL, while CSF VDRL is more specific (which is accurate per uptodate), but FA says "For neurosyphilis: test spinal fluid with VDRL and PCR" (page 141). Is clinical suspicion of tertiary syphilis simply enough to bypass the sensitive test and go straight for the specific test (despite commonplace practice of screen before going for the confirmatory test)?

 

[QualityProcess]

With what level of detail are we expect to know the most recent indications for antibiotics and infections? For example, DIT 2015 says that macrolides are indicated for pneumococcus URI, but up to date says in 2011, 25-45% of pneumococcal strains were resistant to macrolides. This topic is highly dependent on geography as well. My area in particular is notorious for overprescription of Azithromycin.

My grasp of this subject is precarious enough without incorporating the most recent developments...

 

[seminoma]

With what level of detail are we expect to know the most recent indications for antibiotics and infections? For example, DIT 2015 says that macrolides are indicated for pneumococcus URI, but up to date says in 2011, 25-45% of pneumococcal strains were resistant to macrolides. This topic is highly dependent on geography as well. My area in particular is notorious for overprescription of Azithromycin.

My grasp of this subject is precarious enough without incorporating the most recent developments...

Can't really offer a general guideline, but I think it's worth knowing that macrolides > penicillin for s.pneumo because of the increasing penicillin-resistance. I think uptodate is getting at the fact that s.pneumo resistance to macrolides is starting to rise as well and a new DOC will need to be found soon. I think the whole point is that penicillin used to be, but is no longer, the best choice. At least that's the message I got from one of our ID lectures in respiratory this year.

Also I don't think the USMLE would make you choose between Penicillin, Azithromycin, or any other drug that technically covers s.pneumo without giving you information to rule one or the other out. I don't think we are expected to know the latest trends in resistance. A realistic scenario (imo) would be describing s.pneumo infection, then giving you the mic results to see if you can interpret them to pick the pcn or macrolide, though.

 

[QualityProcess]

Thanks. I think another possible way to present it would be to describe the trend in ineffectiveness and ask for the mechanism of resistance

 

[Transposony]

From what I remember Vitamin A/all-trans retinoic acid somehow interacts with the arachnoid granulations and inhibits reabsorbtion of the CSF and therefore increasing the ICP.

The reason pseudotumor cerebri is also known as idiopathic intracranial hypertension is because the cause is not known.
It's a diagnosis of exclusion and diplopia due to a sixth-nerve palsy suggests pseudotumor cerebri.

 

[Transposony]

Anyone know about tertiary syphilis testing? I was watching a Conrad Fischer video and he says CSF FTA is more sensitive than CSF VDRL, while CSF VDRL is more specific (which is accurate per uptodate), but FA says "For neurosyphilis: test spinal fluid with VDRL and PCR" (page 141). Is clinical suspicion of tertiary syphilis simply enough to bypass the sensitive test and go straight for the specific test (despite commonplace practice of screen before going for the confirmatory test)?

That's because a treponemal test like FTA detects antibodies and in syphilis there can be a passive transfer of serum antibody into the CSF.
Also, treponemal test like FTA-ABS cannot differentiate past from current infection as compared to nontreponemal tests like VDRL & RPR.

 

[Radiolucent]

The reason pseudotumor cerebri is also known as idiopathic intracranial hypertension is because the cause is not known.
It's a diagnosis of exclusion and diplopia due to a sixth-nerve palsy suggests pseudotumor cerebri.

I dont remember where I read it and I dont have access to uptodate from home but I did google it and found:

" The pathogenesis of pseudotumor cerebri in patients with APML being treated with ATRA is thought to be similar to the mechanism in vitamin A overdose: overdosage of vitamin A is postulated to impair cerebrospinal fluid absorption at the level of the arachnoid villi or granulations."
(ATRA= all-trans retinoic acid)

http://archopht.jamanetwork.com/article.aspx?articleid=415469

 

[aspiringmd1015]

for spironolactone, the general activity of steroid anatagonism leads to gynecomastia in men bc it blocks the testosterone receptors, but how does that produce gynecomastia(must be increased estrogen related?) so in women are there going to be signs of estrogen excess?

 

[seminoma]

FA says pseudotumor cerebri is a consequence of chronic Vit A toxicity. Robbins says pseudotumor is an acute vit A toxicity. FA 14 didn't have "chronic" and "acute" differentiation, so I'm guessing this is an errata that nobody caught? I was going to submit it a few weeks back when I noticed it, but since the official errata was already out I figured it would've been pointless.

Just thinking about it again today so I figured I'd post.

@Phloston

FA15 page 89
Robbins 9e page 438

 

[Phloston]

FA says pseudotumor cerebri is a consequence of chronic Vit A toxicity. Robbins says pseudotumor is an acute vit A toxicity. FA 14 didn't have "chronic" and "acute" differentiation, so I'm guessing this is an errata that nobody caught? I was going to submit it a few weeks back when I noticed it, but since the official errata was already out I figured it would've been pointless.

Just thinking about it again today so I figured I'd post.

@Phloston

FA15 page 89
Robbins 9e page 438

Just because Robbin's says acute doesn't mean chronic is wrong (can you find anything in the literature saying chronic is wrong?) I'd say ~90% of the FA errata submissions are regarding omissions in the text, but these often are purposeful and are not errata. For instance, if a disease is caused by three mechanisms and we list one, it's not wrong because we don't list the other two since if everything was elaborated on then it goes beyond the scope of Step 1. I can't comment on the hypervitaminosis A entry specifically, but you can submit that entry and the current staff will evaluate it. If chronic and acute are both correct then it could be flagged as a clarification to simply remove the acute. Btw, I resigned as editor earlier this year so do not have a role in the 2016 book.

 

[Transposony]

FA says pseudotumor cerebri is a consequence of chronic Vit A toxicity. Robbins says pseudotumor is an acute vit A toxicity. FA 14 didn't have "chronic" and "acute" differentiation, so I'm guessing this is an errata that nobody caught? I was going to submit it a few weeks back when I noticed it, but since the official errata was already out I figured it would've been pointless.

They are currently having a Crowdproofing event for Basic sciences which ends tonight.
So, you can still submit the errata and earn a Gift card.

 

[seminoma]

Just because Robbin's says acute doesn't mean chronic is wrong (can you find anything in the literature saying chronic is wrong?) I'd say ~90% of the FA errata submissions are regarding omissions in the text, but these often are purposeful and are not errata. For instance, if a disease is caused by three mechanisms and we list one, it's not wrong because we don't list the other two since if everything was elaborated on then it goes beyond the scope of Step 1. I can't comment on the hypervitaminosis A entry specifically, but you can submit that entry and the current staff will evaluate it. If chronic and acute are both correct then it could be flagged as a clarification to simply remove the acute. Btw, I resigned as editor earlier this year so do not have a role in the 2016 book.

I understand omissions aren't errata. Could be mistaken but I think I looked it up on uptodate when I first found it and uptodate said associated with acute presumptively because of some compensation or equilibration of factors in chronic excess. It's probably a non issue though. I'm 3.5 weeks into dedicated and I think I'm getting anxious about details that I shouldn't be worried about.

 

[seminoma]

They are currently having a Crowdproofing event for Basic sciences which ends tonight.
So, you can still submit the errata and earn a Gift card.

Cool. I submitted bunch when they started it a month or so ago but at the time the biochem book wasn't open for crowd proofing. Too lazy to navigate there now.

 

[Transposony]

Btw, I resigned as editor earlier this year so do not have a role in the 2016 book.

@Phloston
I thought you were proofing the USMLERx Qbank ?

 

[pathologyDO]

Who can explain the reasoning behind the 3 parts of the treatment regimen for Guillain-Barre Syndrome (e.g. Respiratory Support, Plasmapheresis, IVIG)

 

[stepone2015]

Who can explain the reasoning behind the 3 parts of the treatment regimen for Guillain-Barre Syndrome (e.g. Respiratory Support, Plasmapheresis, IVIG)

Respiratory support = so the ascending paralysis doesn't mean they stop breathing when it gets to the diaphragm.
Plasmapheresis = antibodies from flu/campylobacter cross react with endoneural tissue. Plasmapheresis removes those antibodies to prevent progression of the paralysis.
IV Ig = as Sattar would say, 'throw the stick to distract the dog.' IV Ig dilutes the autoreactive antibodies and high levels of antibodies can actually cause negative feedback inhibition on B cells to cause them to produce less antibodies (similar effect seen in multiple myeloma, the cancer's Ig is so dominant partially because the regular B cells stop making antibodies).

 

[Phloston]

@Phloston
I thought you were proofing the USMLERx Qbank ?

I've been involved in numerous FA projects (author FA14, editor FA15, author Express, editor Rx; was editor FA16 but resigned cuz I don't have time). Also just want to point out I'm not here to self-aggrandize (and I really don't see working with FA as a huge deal), but from a professional standpoint have briefly clarified my involvement per your question.

 

[Transposony]

What is Root cause analysis and it's significance ?

 

[aspiringmd1015]

theres a question in UW that asks pretty much about a HF patient and what is the difference between their pulmonary artery and vein, and by process of elimination i chose AT2, even though Goljans audio talked about this, i thought it coudlnt be the answer bc the patient is taking carvedlilol, so shouldnt that block renin secretion(B1) and if theres no renin there should be no AT2 floating around?

 

[pathologyDO]

theres a question in UW that asks pretty much about a HF patient and what is the difference between their pulmonary artery and vein, and by process of elimination i chose AT2, even though Goljans audio talked about this, i thought it coudlnt be the answer bc the patient is taking carvedlilol, so shouldnt that block renin secretion(B1) and if theres no renin there should be no AT2 floating around?

The beta-blocker would decrease renin secretion but not completely destroy it.. make sense? So there is still AT I -> AT II conversion happening at the lungs

 

[aspiringmd1015]

ah i see, okay cool. Is there any difference between regular nephrotoxicty and crystalline nephrotoxicty?

 

[Radiolucent]

ah i see, okay cool. Is there any difference between regular nephrotoxicty and crystalline nephrotoxicty?

Nephrotoxicity is the broader term and has many causes where crystalline induced nephrotoxicity is one of them.

Basically the MAO of the latter is precipitation of crystals in the renal tubules --> obstruction --> renal damage (similar to hydronephrosis). This can be caused for example by ethylene glycol, uric acid and certain antivirals.

 

[aspiringmd1015]

is the prolacintoma mechanism causing osteoperosis due to decreasing gnrh, decrease fsh/lh, decrease estrogen?

 

[cwwm]

is the prolacintoma mechanism causing osteoperosis due to decreasing gnrh, decrease fsh/lh, decrease estrogen?

Yes - same reason why anorexics are predisposed to osteoporosis -> all b/c decreased GnRH

 

[seminoma]

What is Root cause analysis and it's significance ?

Interviewing people potentially related to the problem and figuring out why the problem exists. Significance is that it allows you to formulate a solution that assesses the cause of the problem.

theres a question in UW that asks pretty much about a HF patient and what is the difference between their pulmonary artery and vein, and by process of elimination i chose AT2, even though Goljans audio talked about this, i thought it coudlnt be the answer bc the patient is taking carvedlilol, so shouldnt that block renin secretion(B1) and if theres no renin there should be no AT2 floating around?

The question just tests your understanding of the location of ACE. There is always a basal level of all hormones. The only thing that can be higher in the PV than the PA are things made in the lung or absorbed by the lung (e.g. ATII, O2).

is the prolacintoma mechanism causing osteoperosis due to decreasing gnrh, decrease fsh/lh, decrease estrogen?

yes

 

[aspiringmd1015]

seminoma you seem like youre going to beast the exam(if you havent already taken it that is) another ? for you is, does calcitonin have an effect on the kidney?

 

[seminoma]

seminoma you seem like youre going to beast the exam(if you havent already taken it that is) another ? for you is, does calcitonin have an effect on the kidney?

Many people in this thread have a way better handle on everything than I do!

It probably does, but the main effect (i.e. the testable point) is on bone. I would guess it just opposes PTH in the kidney.

 

[aspiringmd1015]

sattar mentioned it in his lecture on medullary carcinoma of the thyroid, thats why i brought it up

 

[aspiringmd1015]

tried googling and finding the answer on diff forums couldnt find it, but why does hyperoxaluria specifically cause calcium stones to precipitate? ie with crohns and such

 

[pathologyDO]

tried googling and finding the answer on diff forums couldnt find it, but why does hyperoxaluria specifically cause calcium stones to precipitate? ie with crohns and such

Calcium stones are made of either Ca2+ and phosphate, or of Ca2+ and oxalate. By increasing the concentration of oxalate in the urine, you are increasing one of the reactants -> leading to increased product, aka calcium oxalate stones.

 

[aspiringmd1015]

i see, thought it maybe had to do with the fact that oxalate effecting calciums solubility or something. In general, hypercalemia increases your chances for calcium p04 or calcium oxalate more? or is there no particular preference?

 

[pathologyDO]

Calcium oxalate is more common

 

[stepone2015]

i see, thought it maybe had to do with the fact that oxalate effecting calciums solubility or something. In general, hypercalemia increases your chances for calcium p04 or calcium oxalate more? or is there no particular preference?

Low pH -> phosphoric acid is less acidic than oxalic acid and hence gets protonated and becomes uncharged more easily -> oxalate is free to bind calcium (prefer it at low urine pH)

High pH -> both phosphate and oxalate are available, but phosphate is usually far more available than oxalate -> phosphate binds calcium

There are exceptions to this rule, but it's a good starting point if you don't have an obvious answer choice.

 

[aspiringmd1015]

for osmolar gap, which is measured serum osmolarity - calculated osmolarity. They have to provide you with serum osmolarity if they want you to calculate it correct?

 

[seminoma]

tried googling and finding the answer on diff forums couldnt find it, but why does hyperoxaluria specifically cause calcium stones to precipitate? ie with crohns and such

You're mixing concepts.

Crohns --> Ca-oxalate stones because high fat intestinal fat content (2/2 malabsorption)results in fat binding to calcium --> oxalate is absorbed (now that it isn't bound to calcium) --> lots of oxalate in blood --> lots of oxalate in urine --> oxalate-related stones. The key here is why crohn's predisposes to hyperoxaluria, not why hyperoxaluria in crohns causes renal stones.

Hyperoxaluria from any cause will increase risk of stone formation because the oxalate-calcium complexes precipitate and form crystals.

for osmolar gap, which is measured serum osmolarity - calculated osmolarity. They have to provide you with serum osmolarity if they want you to calculate it correct?

Yes.

sattar mentioned it in his lecture on medullary carcinoma of the thyroid, thats why i brought it up

I think he was talking about the excessive calcitonin seen with MTC. Normal caltionin physiology has negligible effects everywhere except the bone (and even there it doesn't do much).

 

[aspiringmd1015]

yeah hats what i was talking about, so in pathological amounts besides acting on your osteoclasts, it can act on your kidneys

 

[Transposony]

Type of Gallstones in Crohn's disease and mechanism?

 

[stepone2015]

Type of Gallstones in Crohn's disease and mechanism?

I don't know, but I'm going to guess. Illeal damage and scarring from Crohn's means you can't absorb bile salts. Decreased levels of bile salts due to loss via lack of enterohepatic recirculation leads to cholesterol stones.

That paragraph is the sum of like 5 minutes of intense thinking. My head hurts now. I hope you're proud of yourself.

 

[seminoma]

I don't know, but I'm going to guess. Illeal damage and scarring from Crohn's means you can't absorb bile salts. Decreased levels of bile salts due to loss via lack of enterohepatic recirculation leads to cholesterol stones.

That paragraph is the sum of like 5 minutes of intense thinking. My head hurts now. I hope you're proud of yourself.

More commonly radiolucent or opaque?

 

[stepone2015]

More commonly radiolucent or opaque?

Lucent but I feel like I just get tricked.

 

[seminoma]

Lucent but I feel like I just get tricked.

Yeah mostly lucent. FA says 10-20% (or maybe it's 20-30%) are opaque. Black pigment (the hemolysis ones) are opaque, brown pigment (the infection ones) are lucent.