Official Step 1 High Yield Concepts Thread

[Transposony]

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

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[Dr.serotonin]

A mother takes her 17 year old son to a doctor and complains he is home all the time and plays all the time on computer and has very few friends if any.
The doctor then talks to the son. If the son says I am ok, Mom is crazy I like being alone.


What personality disorder the guy has?

A. Schizoid
B. Histrionic
C. Avoident
D. Schizotypal
E. Paranoid
F. Narcissistic
G. Borderline
F. Anti-social

 

[psylocke]

A mother takes her 17 year old son to a doctor and complains he is home all the time and plays all the time on computer and has very few friends if any.
The doctor then talks to the son. If the son says I am ok, Mom is crazy I like being alone.


What personality disorder the guy has?

Schizoid personality disorder

 

[aspiringmd1015]

pathoma mentions that calcitonin lowers serum calcium by increasing renal calcium excretion? is that true?

 

[aspiringmd1015]

Il-1 and RANKL promote differentiation of osteoclasts. Anyway to differentiate this?

 

[Pisiform]

This thread says High Yield. None of the **** is high yield

 

[aspiringmd1015]

^take your dumb **** elsewhere

 

[aspiringmd1015]

In pseudohypoparathyroidism, is the defect only in the kidney, but the bone receptors are functioning? Hence the receptors on 4th and 5th digits

 

[seminoma]

Il-1 and RANKL promote differentiation of osteoclasts. Anyway to differentiate this?

Pretty sure one promotes maturation into osteoclasts, while the other promotes increased production of progenitor cells, but don't ask me which one is which. Definitely a differentiation you could be expected to make for a school exam, but unlikely to show up on step 1.

 

[faisal 2000]

\
2) Which are known to cause gout? --> pyrazinamide, ethambutol
\

what is the mechanism of ethambutol to cause gout?

 

[Phloston]

Exact mechanism remains undefined but gout is due to either under-excretion or over-production of uric acid. Drugs typically compete with excretion and I'd believe this is the primary mechanism. Alcohol is the one that stands out as causing over-production in addition to under-excretion.

 

[faisal 2000]

what is most common organism that causes pneumonia in Cystic Fibrosis ??
gram - bacteria causes endocarditis ??

 

[Dr.serotonin]

what is most common organism that causes pneumonia in Cystic Fibrosis ??
gram - bacteria causes endocarditis ??

pseudomonas aeruginosa for pneumonia in CF.
yes gram - bacteria can cause IE. pseudomonas aeruginosa and H. influenza is famous for that

 

[Transposony]

gram - bacteria causes endocarditis ??

Infective endocarditis due to Gram-ve bacteria is classified into two main categories:

1. HACEK (Haemophilus species, Actinobacillusactinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella species) bacteria and

2. Non-HACEK (mostly due to Pseudomonas & E coli but also Klebsiella, Serratia, Salmonella, Enterobacter, Proteus, Providencia and Citrobacter).

 

[Macaroon_Berry]

Infective endocarditis due to Gram-ve bacteria is classified into two main categories:

1. HACEK (Haemophilus species, Actinobacillusactinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella species) bacteria and

2. Non-HACEK (mostly due to Pseudomonas & E coli but also Klebsiella, Serratia, Salmonella, Enterobacter, Proteus, Providencia and Citrobacter).

It's crazy that I didn't even know all those bugs in your 2nd category could cause endocarditis! I knew HACEK group could cause Gram -ve endocarditis without showing up on blood cultures, but wow didn't know about Pseudomonas and E. Coli, etc!! Thanks for that

 

[dfib slim]

It's crazy that I didn't even know all those bugs in your 2nd category could cause endocarditis! I knew HACEK group could cause Gram -ve endocarditis without showing up on blood cultures, but wow didn't know about Pseudomonas and E. Coli, etc!! Thanks for that

HACEKs will show up on cultures, you just need to grow them for a bit longer. Common culture negatives are Coxiella, Bartonella, T. whipplei, and fungi.

 

[sepsis 3050]

Aspergillus species, Brucellaspecies, Coxiella burnetii, Chlamydia, and HACEK bacteria. All have delay in growth, which means they grow but takes so long to grow on culture. So they are classified as "culture-negative" endocarditis.

 

[faisal 2000]

hypo or hyper thyroidism can cause jaundice and why ??

 

[faisal 2000]

which anemia will occur in hypothyroidsm ? and why (be specific) ?

 

[Keto]

which anemia will occur in hypothyroidsm ? and why (be specific) ?

Hi faisal
UpToDate describes 3 forms

1. Generally → Normocytic hypoproliferative anemia
2. Pernicious anemia occurs in 10 percent of patients with hypothyroidism caused by chronic autoimmune thyroiditis → macrocytic megaloblastic anemia
3. Iron deficiency anemia, if menorrhagia is present (women with hypothyroidism may have either oligo- or amenorrhea or hypermenorrhea-menorrhagia) → microcytic

Good luck with the prep!


Question break time

A 25-year-old man is diagnosed with hyperthyroidism and treatment is begun with a drug that inhibits thyroid peroxidase but has no effect on 5-deiodinase. This patient is at an increased risk for developing which of the following?

1) Blood clots
2) Hypoglycemia
3) Infection
4) Yellow skin
5) Pancreatitis



PS where have you read that thing with thyroid problems + jaundice? Have you found out anything so far?

 

[faisal 2000]

Question break time

A 25-year-old man is diagnosed with hyperthyroidism and treatment is begun with a drug that inhibits thyroid peroxidase but has no effect on 5-deiodinase. This patient is at an increased risk for developing which of the following?

1) Blood clots
2) Hypoglycemia
3) Infection
4) Yellow skin
5) Pancreatitis

methimazole causes agranulocytosis and leukopenia so that will increase risk for infection. also methimazole causes papular rash and it is contraindicated in pregnancy bec it can cross placenta causing fetal goiter.

 

[faisal 2000]

how petechiae develop in fat embolism ?






@Phloston @Transposony

 

[Transposony]

how petechiae develop in fat embolism ?
@Phloston @Transposony

It's due to occlusion of dermal capillaries by fat globules leading to extravasation of RBCs.
There is no platelet dysfunction.

 

[Phloston]

I thought the thrombocytopenia that's often present in fat embolism is permissive of petechiae formation. I wouldn't think the fat alone causes the petechiae.

 

[Transposony]

I thought the thrombocytopenia that's often present in fat embolism is permissive of petechiae formation. I wouldn't think the fat alone causes the petechiae.

That's what I used to believe as Goljan mentions it but a review of literature points towards increased capillary fragility due to occlusion of dermal capillaries by microglobules.
Thrombocytopenia maybe contributes secondarily.

 

[Transposony]

Here is a good picture showing petechiae

 

[Phloston]

That's what I used to believe as Goljan mentions it but a review of literature points towards increased capillary fragility due to occlusion of dermal capillaries by microglobules.
Thrombocytopenia maybe contributes secondarily.

Perhaps the petechiae are similar to splinter haemorrhages seen in endocarditis, in terms of mechanism of formation.

 

[Phloston]

Btw (changing the subject), there's a Step 2CK clinical mastery series (NBME) question on mitral valve prolapse syndrome. When I saw the question I thought it was a bit odd because at the time I had never before heard of mitral valve prolapse "syndrome." Well anyway, I just came off an ED term and we had a young patient who fit the vignette to that question to a T and I was able to make a diagnosis.

- Young patient
- Hx of recurrent fleeting severe pain on the left side of the chest (i.e., visited the hospital/GP many times before about this)
- Palpitations, dizziness
- Confirmed MVP
- Often Hx of relative(s) with similar Sx, or MVP, MR or prior MI.
- Tx is observation first-line, not beta-blockers

 

[Phloston]

I've also seen quite a few patients with Meniere disease.

- Adult-onset usually; typically family member with similar Sx
- Caused by abnormal/deficient endolymphatic drainage in the inner ear (aka endolymphatic hydrops)
- Hx of vertigo, tinnitus and/or hearing loss (usually all three); tends to wax and wane, starting with one ear, then alternating between ears, then eventually becoming bilateral and permanent; it's good to say "does it seem like sometimes it might be in one ear, then in the other, or sometimes in both; in other words, it doesn't seem like there's any fixed pattern per se in terms of where and how you experience the Sx?" And they say yes to this. Patients tends to get accustomed to the tinnitus and forget it's there (but if you ask they're like "yeah it's there now"). A good question to ask is if they hear it while going to bed, which is typical.
- Loss of low-frequency sounds (unlike high-frequency loss in presbycusis). It's good to say something along the lines of "do you feel like it's hard sometimes to hear people in conversation, especially if there are a lot of other people around/in a busy area/restaurant?" And then telling them "for example, older people tend to lose ability to hear high-pitched sounds, but is that what it seems like here?" They say yes to the former and no to the latter.
- Tx is trial of antihistamine; if that doesn't work, a diuretic may be trialed, especially if they're hypertensive; in general though, there's no cure and it can sometimes progress to total hearing loss.

----

- The most recent patient I saw with this had a Hx of viral infection that appeared to present as a secondary labrynthitis. So while vestibular neuritis and labrythitis were top DDx, the ten-year Hx of symptoms (despite being exacerbated here) pointed to an underlying Meniere. So diagnosis was viral-induced labrynthitis on background of Meniere.

 

[Phloston]

methimazole causes agranulocytosis and leukopenia so that will increase risk for infection. also methimazole causes papular rash and it is contraindicated in pregnancy bec it can cross placenta causing fetal goiter.

Methimazole can also cause aplasia cutis congenita. That question is floating around on the Step 1.

 

[aspiringmd1015]

A/c to a UW explanation, fat embolism syndrome causes anemia and thrombocytopenia with petechia due to the emboli themselves consuming the platelets and rbc's as they aggregate to the emboli, also something about how they get activated when they adhere, thus releasing mediators to call in more platelets.

 

[faisal 2000]

(colchicine, probenecid, allopurinol)
1- moa
2- side effects
3- which drug used for acute\chronic gout ?




@Phloston
@Transposony
@aspiringmd1015
@Keto

 

[Phloston]

(colchicine, probenecid, allopurinol)
1- moa
2- side effects
3- which drug used for acute\chronic gout ?




@Phloston
@Transposony
@aspiringmd1015
@Keto

I'll let other people answer #1 + 2.
But for 3 probenecid/sulfinpyrazone and allopurinol/febuxostat are only used in chronic gout and never in acute gout (as they can exacerbate the attack; acutely increased OR decreased concentrations of uric acid make acute attacks worse). Allopurinol is always the go-to drug for chronic gout. But it's a sulfa drug. If one can't tolerate it then fubuxostat is used. Allopurinol is also never given if someone is taking 6-MP because 6-MP requires xanthine oxidase for catabolism. Probenecid or sulfinpyrazone aren't first-line Txs in chronic gout. Their uricosuric effects are good for gout caused by under-excretion (90%), but one must be aware these are contraindicated with any Hx of uric acid stones (cuz they're increasing tubular concentration). Probenecid can also be used in conjunction with beta-lactams to increase renal retention of the latter. I've seen this done occasionally. And I've read that one of its uses is in neurosyphilis, where doses of penicillin are extraordinarily high. Colchicine has shown utility in preventing recurrent gout attacks and as far as I'm aware can be given after indomethacin (or another NSAID) and steroids acutely.

And btw rasburicase/pegloticase are also good to know for self-entertainment. But LY for Step 1.

 

[psylocke]

What's the toughest way they can present a Charcot-Bouchard aneurysm on step 1?

 

[Keto]

Hi

thanks Phloston for the great input! Especially the pearl with Probenecid + Penicillin - didn't know that!

Your gout treatment approach in simple terms would be:

Acute Gout Strategy:
Reduce pain and inflammation.
Use NSAIDs, Colchicine.

Chronic gout Strategy:
Reduce uric acid pool.
Use Allopurinol, Probenecid. Consider Pegloticase and Rasburicase (for tumor lysis syndrome).

Also don't forget about dietary modifications: Less red meat, beer, seafood. Gout reducing food and drinks are cherries, whole grains and coffee (so more of those! 4-5 cups coffee apparently reduced gout attacks by up to 40%.. I remember there was a huge study done in Canada some years ago...)

Colchicine
is an old, anti-inflammatory drug that was historically used for decades for a lot of conditions such as for RA (before methotrexate, NSAIDs, steroids,... came along).
Nowadays it is used for gout (esp in acute attacks in combination with NSAIDs or alone for patients with NSAIDs allergy, or in a case where indomethacin is contraindicated such as in patients with renal failure. Also I've heard, that colchicine works "faster" than steroids.)
Colchicine is a boards-favourite for the use in pericarditis (idiopathic or acute viral).
It can also be considered for OA that is refractory to NSAIDs and intra-articular steroids.
Colchicine works by inhibiting neutrophil activity. Binds to tubulin and ↓ microtubule polymerization (colchicine is a M-phase specific type of drug; compare it to Vincristine, Vinblastine, Paclitaxel, Griseofulvin).
Colchicine has a narrow therapeutic index.
Side effects include gastrointestinal "mucositis", neutropenia (BM suppression), and peripheral neuropathy.

Colchicine can be extracted from a beautiful but very toxic plant, which is common here in Europe (it has also a beautiful name in german Herbstzeitlose, which means "autumn, timeless"). Management of intoxication includes consideration of GI decontamination with activated charcoal (if intoxication is <60 min, and a lot of colchicine) and supportive treatments including administration of granulocyte colony-stimulating factor.

Allopurinol and Febuxostat (Xanthine Oxidase inhibitors)
inhibits xanthine oxidase, which catalyzes the last step in the conversion of purines → uric acid (allopurinol is a suicide inhibitor, as it is a substrate). Both can initially precipitate an acute gout attack. Allopurinol causes hypersensitivity (Stevens-Johnson syndrome). Febuxostat (never drug) does not cause hypersensitivity reactions.
Drug interactions with other purine analogs: Inhibition of the metabolism of 6-mercaptopurine and its prodrug azathioprine (can be used as a benefit allopurinol + 6-MU).


Probenecid (Uricosuric drug)
↑ rate of excretion of uric acid (inhibits tubular reabsorption of filtered urate, need good kidney function - don't use it if GFR < 50 mL/min - also don't use it in patients with history of urate renal stones and get an U/A before starting probenecid), ↓ risk of gout attacks. Probenecid is also a sulfa drug.

Rasburicase and Pegloticase (Uricases)
are more for tumor lysis syndrome (or chronic gout refractory to other therapies). They are enzymes (a.k.a. expensive drugs) that break down uric acid into allantoin, which is more water-soluble than uric acid. Rasburicase for tumor lysis syndrome. Pegloticase for chronic, refractory gout. Pegloticase has a FDA black box warning for hypersensitivity. Prophylactic steroids might be needed.

Have a great day

 

[Phloston]

Hi

thanks Phloston for the great input! Especially the pearl with Probenecid + Penicillin - didn't know that!

Your gout treatment approach in simple terms would be:

Acute Gout Strategy:
Reduce pain and inflammation.
Use NSAIDs, Colchicine.

Chronic gout Strategy:
Reduce uric acid pool.
Use Allopurinol, Probenecid. Consider Pegloticase and Rasburicase (for tumor lysis syndrome).

Also don't forget about dietary modifications: Less red meat, beer, seafood. Gout reducing food and drinks are cherries, whole grains and coffee (so more of those! 4-5 cups coffee apparently reduced gout attacks by up to 40%.. I remember there was a huge study done in Canada some years ago...)

Colchicine
is an old, anti-inflammatory drug that was historically used for decades for a lot of conditions such as for RA (before methotrexate, NSAIDs, steroids,... came along).
Nowadays it is used for gout (esp in acute attacks in combination with NSAIDs or alone for patients with NSAIDs allergy, or in a case where indomethacin is contraindicated such as in patients with renal failure. Also I've heard, that colchicine works "faster" than steroids.)
Colchicine is a boards-favourite for the use in pericarditis (idiopathic or acute viral).
It can also be considered for OA that is refractory to NSAIDs and intra-articular steroids.
Colchicine works by inhibiting neutrophil activity. Binds to tubulin and ↓ microtubule polymerization (colchicine is a M-phase specific type of drug; compare it to Vincristine, Vinblastine, Paclitaxel, Griseofulvin).
Colchicine has a narrow therapeutic index.
Side effects include gastrointestinal "mucositis", neutropenia (BM suppression), and peripheral neuropathy.

Colchicine can be extracted from a beautiful but very toxic plant, which is common here in Europe (it has also a beautiful name in german Herbstzeitlose, which means "autumn, timeless"). Management of intoxication includes consideration of GI decontamination with activated charcoal (if intoxication is <60 min, and a lot of colchicine) and supportive treatments including administration of granulocyte colony-stimulating factor.

Allopurinol and Febuxostat (Xanthine Oxidase inhibitors)
inhibits xanthine oxidase, which catalyzes the last step in the conversion of purines → uric acid (allopurinol is a suicide inhibitor, as it is a substrate). Both can initially precipitate an acute gout attack. Allopurinol causes hypersensitivity (Stevens-Johnson syndrome). Febuxostat (never drug) does not cause hypersensitivity reactions.
Drug interactions with other purine analogs: Inhibition of the metabolism of 6-mercaptopurine and its prodrug azathioprine (can be used as a benefit allopurinol + 6-MU).


Probenecid (Uricosuric drug)
↑ rate of excretion of uric acid (inhibits tubular reabsorption of filtered urate, need good kidney function - don't use it if GFR < 50 mL/min - also don't use it in patients with history of urate renal stones and get an U/A before starting probenecid), ↓ risk of gout attacks. Probenecid is also a sulfa drug.

Rasburicase and Pegloticase (Uricases)
are more for tumor lysis syndrome (or chronic gout refractory to other therapies). They are enzymes (a.k.a. expensive drugs) that break down uric acid into allantoin, which is more water-soluble than uric acid. Rasburicase for tumor lysis syndrome. Pegloticase for chronic, refractory gout. Pegloticase has a FDA black box warning for hypersensitivity. Prophylactic steroids might be needed.

Have a great day

Good post you've made.

Yeah, according to UpToDate, NSAIDs are first-line for most cases of pericarditis, followed by steroids and colchicine.

For acute gout, indomethacin is always the answer on the Step, even if the patient is already on aspirin.

The Johns Hopkins IM boards review book also made a point that uric acid levels are increased by fructose and decreased by dairy.

 

[faisal 2000]

what is the mechanism beyond increase cardiac output in paget disease of bone and wet beriberi ?











@Phloston
@Transposony
@aspiringmd1015
@Keto
@seminoma

 

[seminoma]

Pagets is AV fistula formation in the bones. Don't know about beriberi

 

[psylocke]

In wet beriberi it's vasodilation and the consequent activation of RAAS

 

[Transposony]

what is the mechanism beyond increase cardiac output in paget disease of bone and wet beriberi ?

In wet beriberi it's due to dysautonomia and since the predominant automatic outflow to blood vessels (arterioles) is sympathetic there is vasodilation leading to decreased TPR. Decreased perfusion pressure leads to activation of RAAS which stimulates salt and water retention (edema) as well as heart to increase CO leading to a high cardiac output state. This is quite similar to septic shock.
Reminds me of Goljan audio -- heart (surprised) asks blood "you are back already? I just pumped you out !" Blood (in embarrassed voice) to heart "arterioles are dilated!"

In later stages the heart can't cope as impaired myocardial energy metabolism (due to lack of thiamine itself) leads to dilated cardiomyopathy followed by low output state.

Two interesting pearls about thiamine:

1. Thiamine phosphorylation takes place in small intestine.
2. Prolonged diuretic therapy can lead to thiamine deficiency.

 

[Dr.serotonin]

a 22 year old male presents to a psychiatrist with the complaint of having depressed mood most of the time which he explains is secondary to his belief of having small penis. for which he is using various penis enlargement medicines purchased over internet. but no improvement at all. because of this fear he is still single despite having strong desire to be in a relationship. when asked to be examined he refuses to do so because of the embracement.
your diagnosis?

A. body dismorphic disorder
B. somatization disorder
C. avoident PD
D. genrealized anxiety disorder
E. social anxiety
F. persistent depressive disorder

 

[psylocke]

a 22 year old male presents to a psychiatrist with the complaint of having depressed mood most of the time which he explains is secondary to his belief of having small penis. for which he is using various penis enlargement medicines purchased over internet. but no improvement at all. because of this fear he is still single despite having strong desire to be in a relationship. when asked to be examined he refuses to do so because of the embracement.
your diagnosis?

Body dismorphic disorder..

 

[Dr.serotonin]

I was reviewing Ethics and came across with the fact that if a Trauma surgeon is diagnosed with HIV by you then you should treat him with out notifying this to the chair of his department or his patients or any other health related official at his hospital. aren't we putting his patients at risk of acquiring HIV ?? plus if a doctor is bound to report substance abuse of his colleagues then why not such serious condition?

 

[Keto]

Hi Dr. serotonin

MKSAP 16 (general medicine review) talks about this in detail and there are good articles you can find online for both topics.

The risk of HIV transmission depends on a lot of things. Bottom line: If the surgeon is treated, and takes the right precautions (2 glows, etc...) the risk of transmission is like 5/1 000 000 (which is thought to be negligible compared to other risk factors).

Also, there is no black and white in ethics... Maybe in a few years, surgeons have to disclose more things... f.e. number of cases for procedure X, or percentage of complications for procedure X, ...

Have a great day


BTW here is the passage from MKSAP
(they also specifically talked about HIV but this was in the audio files)

PS Great Article on Surgeon with HIV (JAMA Ethics)
VM -- A Surgeon with HIV, Dec 09... Virtual Mentor

 

[Dr.serotonin]

Hi Dr. serotonin

MKSAP 16 (general medicine review) talks about this in detail and there are good articles you can find online for both topics.

The risk of HIV transmission depends on a lot of things. Bottom line: If the surgeon is treated, and takes the right precautions (2 glows, etc...) the risk of transmission is like 5/1 000 000 (which is thought to be negligible compared to other risk factors).

Also, there is no black and white in ethics... Maybe in a few years, surgeons have to disclose more things... f.e. number of cases for procedure X, or percentage of complications for procedure X, ...

Have a great day


BTW here is the passage from MKSAP
(they also specifically talked about HIV but this was in the audio files)

PS Great Article on Surgeon with HIV (JAMA Ethics)
VM -- A Surgeon with HIV, Dec 09... Virtual Mentor

thankyou v much. I always wait for your explanations.

 

[Dr.serotonin]

strange ethics rule . .
prescribe syringes to your IV drug abuser patient so that he can safely practice his drugs with out acquiring HIV/HCV/HBV

 

[Dr.serotonin]

you must accept the beliefs of your patient and act accordingly in order to develop good doc-pt relationship, eg if he asks for a homeopathic drug for his condition then you should give that drug provided there are no side effects of it and there is no possibility of harming the pt.
thats very strange :/

 

[aspiringmd1015]

why does diabetes cause renal papillary necrosis? is it due to ischemia? and if so, how is ischemia occuring in nephropathy bc isnt the efferent arteriole effected? unless the afferent is affected too, then that would make sense.

 

[aspiringmd1015]

also, in diabetic Neprhopathy, the EM should be negative bc of no immune complex deposits correct? and IF findings?

 

[Dr.serotonin]

a 10 year old girl presents to you with the pallor, failure to thrive and motor abnormalities. her Hb is 8g/dL. peripheral blood smear shows target cells and acanthocytes. bone marrow cells are isolated to know the possible cause of genetic defect leading to the abnormality.
which of the following lab techniques will be used to find out the defect?

A. Dot blot
B. Southern blot
C. Northern blot
D. western blot
E. PCR

 

[faisal 2000]

how hypothyroidsm causing non pitting edema (be specific) ?













@Phloston
@Transposony
@aspiringmd1015
@Keto
@seminoma