Step 1 Complicated Concepts Thread

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TheSeanieB

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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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:thumbup: yessirr!!!!
Ind33d. This occurs mostly in volume depleted patients put on an ACEi. It's due to decreased venous return, which activates the Bezold-Jarisch reflex which causes a paradoxical reflex hypotension/bradycardia. So you need a few day clearing period if you are switching a patient from a thiazide for instance to a ACEi
 
Pg. 511 Another embryo question... for cleft palate. Lateral palatine processes- are these analogous to the palatine shelves? Are these different from the maxillary process?

Median palatine process, is this term analogous to something else?
 
yeah ever since that one poster said that first aid and uworld are becoming obsolete we've had to move on to other sources. currently on my 2nd pass of big robbins (annotating extensively from pubmed of course) and about 1% of the way through harrison's.

Awesome, I'm going to take this advice.

Do you just search "cleft palate" or whatever on pubmed? How do you go about organizing this. Very exciting times.
 
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Gout. Why is prpp excess a cause? I thought prpp was a substrate for hgprt which goes the opposite direction of uric acid synthesis
 
Gout. Why is prpp excess a cause? I thought prpp was a substrate for hgprt which goes the opposite direction of uric acid synthesis

PRPP makes nucleotides yo. There are no ways in biochemistry, only building blocks to makes crap.

That figure is probably the most confusing and least helpful one (purine salvage). Uworld had a better figure that was more linear instead of chaotic circular. That and the B12/homocystein/methionine figures are the worst.
 
Dudes... I just spent an hour trying to get this.

What the hell is the difference between attributable risk and attributable risk percent? Uworld asked a question that sounds just like attributable risk in first aid, but apparently they wanted attributable risk percent, which is different... but the attributable risk in first aid is a percentage too. How the hell to know when to provide one or the other?
 
PRPP makes nucleotides yo. There are no ways in biochemistry, only building blocks to makes crap.

That figure is probably the most confusing and least helpful one (purine salvage). Uworld had a better figure that was more linear instead of chaotic circular. That and the B12/homocystein/methionine figures are the worst.

Thanks, I never really learned the stuff the first time and FA figures are horrible. I need to look for some good diagrams. So prpp is involved in both de novo an salvage purine synth? And too much results in excess AMP etc?
 
Dudes... I just spent an hour trying to get this.

What the hell is the difference between attributable risk and attributable risk percent? Uworld asked a question that sounds just like attributable risk in first aid, but apparently they wanted attributable risk percent, which is different... but the attributable risk in first aid is a percentage too. How the hell to know when to provide one or the other?

Sounds like over complicating things. Post the question or something.
 
Thanks, I never really learned the stuff the first time and FA figures are horrible. I need to look for some good diagrams. So prpp is involved in both de novo an salvage purine synth? And too much results in excess AMP etc?

Yup.

Purines? PRPP + base
Pyrimidine? PRPP + orotic + base

Salavage? PRPP + base

Same process. Your original thought was right, just the diagram is kind of funky. So yeah, it can be used for either. And yes, excess results in more purines in general and more purines means more uric acid. Just like cancer cells = more DNA, PRPP = more purines.

Honestly, I didn't learn this stuff well from class either. I just used RR biochem + lippincott for anything that didn't make sense.
 
Does anyone have an easy method or know of a resource when trying to figure out breath sounds and forming this into a differential? I tend to get confused between Rhonchi, Rales, Wheezes, stridor, bilateral vs. unilateral, what you'd hear in asthma vs. pneumonia, etc. Combine this with the fact that the heart and lungs are so intimately related, and I sometimes get overwhelmed in figuring out the origin of the pathology. I feel like First Aid doesn't cover this that well, but maybe that's just me.

Also, any advice for XR? Not sure how people study for this, but X-rays of the lungs/heart/abdomen are the bane of my Step 1 existence.
 
Sounds like over complicating things. Post the question or something.

Relative risk of cancer in smokers v.s. non-smokers is 5.

What percentage of cancer in smokers can be attributed to smoking?

I couldn't answer the Q but I thought they were asking for attributable risk (pg.52 first aid), but they said they were asking for the attributable risk percent. When would you go for one or the other?
 
Relative risk of cancer in smokers v.s. non-smokers is 5.

What percentage of cancer in smokers can be attributed to smoking?

I couldn't answer the Q but I thought they were asking for attributable risk (pg.52 first aid), but they said they were asking for the attributable risk percent. When would you go for one or the other?

Attributable risk is a percentage. It's always a percentage.

The whole concept of attributable risk is to see what the differences are in event rates when comparing two different groups with the same risk factors. The "event rates" are essentially percentages of the group that had an event when exposed to that risk. The difference b/t the two groups event rates is the attributable risk of that one group.

Anyway, these questions can be quite confusing unless you give a Uworld QID or write out an example with actual #'s / data.
 
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Relative risk of cancer in smokers v.s. non-smokers is 5.

What percentage of cancer in smokers can be attributed to smoking?

I couldn't answer the Q but I thought they were asking for attributable risk (pg.52 first aid), but they said they were asking for the attributable risk percent. When would you go for one or the other?

So was the whole number AND the percentage number both available for answers?
 
Relative risk of cancer in smokers v.s. non-smokers is 5.

What percentage of cancer in smokers can be attributed to smoking?

I couldn't answer the Q but I thought they were asking for attributable risk (pg.52 first aid), but they said they were asking for the attributable risk percent. When would you go for one or the other?
I remember that Uworld question, it was weird. The attributable risk percent is actually a percent of a percent, and its not actually described in first aid. The attributable risk percent is the (attributable risk to smoking in %)/(total risk with smoking in %). Going with the example in first aid for attributable risk, smoking and non-smoking have a 21% and 1% risk of cancer, so the attributable risk is the difference (21%-1% = 20%). Attributable Risk Percent would then be (20%)/(21%) = about 95%.
 
Relative risk of cancer in smokers v.s. non-smokers is 5.

What percentage of cancer in smokers can be attributed to smoking?

I couldn't answer the Q but I thought they were asking for attributable risk (pg.52 first aid), but they said they were asking for the attributable risk percent. When would you go for one or the other?

I hope I'm remembering this right... but when I came across that question, I just thought it through like someone who had never seen biostats before (because I keep forgetting what I read in First Aid) and surprisingly got it right (I'm pretty sure anyway!).

Basically, if they say that a smoker is 5x more likely to get cancer than a nonsmoker, I figure there's 5x more cancerous smokers than cancerous nonsmokers. So for every 100 smokers with cancer, 20 nonsmokers have cancer. 100-20 = 80, and wasn't the answer 80%? I.e. 80% of the time, you can blame the cancer on smoking; 20% of the time it would have happened anyway.

Anyway, that could be a totally wrong way to approach it, but I didn't dwell on it too much after I saw that I got it right. I kind of hate all the different biostats definitions with their various formulas and would rather reason my way through those...
 
I remember that Uworld question, it was weird. The attributable risk percent is actually a percent of a percent, and its not actually described in first aid. The attributable risk percent is the (attributable risk to smoking in %)/(total risk with smoking in %). Going with the example in first aid for attributable risk, smoking and non-smoking have a 21% and 1% risk of cancer, so the attributable risk is the difference (21%-1% = 20%). Attributable Risk Percent would then be (20%)/(21%) = about 95%.
:thumbup:
 
Does anyone have an easy method or know of a resource when trying to figure out breath sounds and forming this into a differential? I tend to get confused between Rhonchi, Rales, Wheezes, stridor, bilateral vs. unilateral, what you'd hear in asthma vs. pneumonia, etc. Combine this with the fact that the heart and lungs are so intimately related, and I sometimes get overwhelmed in figuring out the origin of the pathology. I feel like First Aid doesn't cover this that well, but maybe that's just me.

Also, any advice for XR? Not sure how people study for this, but X-rays of the lungs/heart/abdomen are the bane of my Step 1 existence.

It would be useful to define what is the cause of each breath sound and also know what each is associated with.

Wheezing happens mostly during the expiratory phase, is associated with airway obstruction and asthma is the most common cause.

Rhonchi is a manifestation of obstruction of medium sized airways-- the bronchi and most often associated with secretions. For rhonchi think bronchiectasis (CF) or COPD (smoker).

Crackles or rales are a sign or alveolar disease. Whatever disease process that fills the alveoi with fluid can cause crackles. Could be pneumonia or pulmonary edema (cardiogenic or non cardiogenic). Interstitial fibrosis can also cause crackles.

Stridor is a high pitched sound that usually occurs during inspiration (as opposed to wheezes) and this is associated with upper airway obstruction, at the level of the larynx. Stridor needs to be evaluated immediately as it may signal impending complete airway obstruction and resp failure. I think as far as step goes the most likely cause of stridor would probably be parainfluenza croup.

Egophony; hearing AH instead of EEE when patient phonates EEE, is suggestive of lung consolidation, such as what occurs with lobar pneumonia. This is useful to differentiate between alveoli fluid and interstitial fibrosis crackles. Egophony is present in alveloi fluid crackles but not in interstitial fibrosis crackles.

Tactile fremitus is increased in consolidation (pneumonia), and decreased in pleural effusion.

Lack of breath sounds might suggest a pleural effusion or a pneumothorax.

Dullness on percussion- Pleural effusion, which on CXR looks like opacification, with a fluid level (meniscus sign).

Hyperresonance on percussion- Pneumothorax with hyperlucency on CXR and contralateral deviation of mediastinal structures (if tension pneumothorax).

Anyways, I know this isnt complete but its a start. For more on chest and abdomen X-rays, I would make sure to learn the most common signs of things like pneumothorax, CHF, atelectasis, pleural effusion, small bowel obstruction, large bowel obstruction, volvulus, colorectal cancer, kidney stones and other common things. Might sound like a lot, but I think xrays/CTs on step should be pretty straight forward and knowing the very basics should be sufficient.
 
I remember that Uworld question, it was weird. The attributable risk percent is actually a percent of a percent, and its not actually described in first aid. The attributable risk percent is the (attributable risk to smoking in %)/(total risk with smoking in %). Going with the example in first aid for attributable risk, smoking and non-smoking have a 21% and 1% risk of cancer, so the attributable risk is the difference (21%-1% = 20%). Attributable Risk Percent would then be (20%)/(21%) = about 95%.

When would you look for one over the other?
 
I hope I'm remembering this right... but when I came across that question, I just thought it through like someone who had never seen biostats before (because I keep forgetting what I read in First Aid) and surprisingly got it right (I'm pretty sure anyway!).

Basically, if they say that a smoker is 5x more likely to get cancer than a nonsmoker, I figure there's 5x more cancerous smokers than cancerous nonsmokers. So for every 100 smokers with cancer, 20 nonsmokers have cancer. 100-20 = 80, and wasn't the answer 80%? I.e. 80% of the time, you can blame the cancer on smoking; 20% of the time it would have happened anyway.

Anyway, that could be a totally wrong way to approach it, but I didn't dwell on it too much after I saw that I got it right. I kind of hate all the different biostats definitions with their various formulas and would rather reason my way through those...

Ok brilliant. I'm usually able to make something up and get it right but for the reason of thinking about the first aid equation I **** myself.
 
lol, this is why you need a real question. Two answers have said 80% and 95%. I'm not paying attention to this to save myself from confusion!
 
lol, this is why you need a real question. Two answers have said 80% and 95%. I'm not paying attention to this to save myself from confusion!
lol, i remember this... It was asking for attributable risk, which would be 80%.

The question was- large cohort to study association between smoking and esophageal scc. After follow up it was found relative risk for smokers to develop scc compared to non smokers was 5... which means that for every 5 cases, 4 are smokers and 1 is a non smoker... therefore attributable risk is 4/5 or 80%.

the formula they gave for attributable risk percentage was (RR-1)/RR
 
Ok brilliant. I'm usually able to make something up and get it right but for the reason of thinking about the first aid equation I **** myself.
The question would either specify, or it would depend on how it was asked. For example, the Attributable Risk would answer the question of "what is the additional percent risk for getting disease x as a result of having risk factor y," whereas the attributable risk Percent would answer the question "Of all people who have disease x, what percent can be attributed to risk factor y." (There's probably a more direct way to ask about attributable risk, I just can't get my brain to figure it out right now).

Edit: also we were using different numbers when we both answered, I was going with the example in first aid about Attributable risk and extending that to attributable risk percent, other people were answering the Uworld question directly. Sorry for the confusion
 
lol, i remember this... It was asking for attributable risk, which would be 80%.

The question was- large cohort to study association between smoking and esophageal scc. After follow up it was found relative risk for smokers to develop scc compared to non smokers was 5... which means that for every 5 cases, 4 are smokers and 1 is a non smoker... therefore attributable risk is 4/5 or 80%.

the formula they gave for attributable risk percentage was (RR-1)/RR

:thumbup:
 
Wow, are you guys really using pubmed and uptodate to study for Step 1?

Uptodate is actually pretty nice for when there's a discrepancy between FA and UW or when you're looking for a pathophys explanation for something in FA. That said, I probably actually go to uptodate rather than just looking at wiki maybe once a week
 
Uptodate is actually pretty nice for when there's a discrepancy between FA and UW or when you're looking for a pathophys explanation for something in FA. That said, I probably actually go to uptodate rather than just looking at wiki maybe once a week

Oh, it's great. I'll be in it everyday for M3.

Just right now, I've yet to find a topic I can't figure out with a review book, wiki, or Uworld explanation. I guess I have a lot of searchable review books though.:thumbup:
 
I don't understand lead time bias.

If increased survival is due to earlier detection by a test, how is this bias? If the study is to determine which test is better, wouldn't that be the result you would want to achieve, not some sort of "bias"?
 
I don't understand lead time bias.

If increased survival is due to earlier detection by a test, how is this bias? If the study is to determine which test is better, wouldn't that be the result you would want to achieve, not some sort of "bias"?

Increased survival from earlier detection isn't bias; the perception of increased survival from earlier detection is lead-time bias.

If you are able to detect a malignancy earlier, but this detection doesn't change the outcome of the disease (you still die at around the same time) --> lead-time bias. You're detecting the disease earlier, so you think you're surviving longer but you really aren't (e.g., you still die at age 75 whether you detected the disease at age 20 or age 35).
 
Definitely... lead time bias doesnt increase survival, it just increases the time you live knowing you have a disease.
 
I want to know the Adverse effects of Filgrastim & Sargramostim and difference between both of them and which is recommended for treatment of bone marrow suppression?
 
Marian's. FA says its locus heterogeneity, but I thought it was pleiotropic. Or can it be both?

I assume you mean Marfan's? Bc I've never heard of Marian's. If I'm wrong about that then please ignore...

Marfan's syndrome is an example of pleiotropy, because its one gene that has multiple different effects. MarfanOID HABITUS is an example of locus heterogeneity, because it can be caused by Marfan's syndrome or by different mutations like MEN2B and homocystinuria. Hope that helps?
 
I assume you mean Marfan's? Bc I've never heard of Marian's. If I'm wrong about that then please ignore...

Marfan's syndrome is an example of pleiotropy, because its one gene that has multiple different effects. MarfanOID HABITUS is an example of locus heterogeneity, because it can be caused by Marfan's syndrome or by different mutations like MEN2B and homocystinuria. Hope that helps?

Dang autocorrect :laugh:

Thank you, I understand now. For locus heterogeneity it says the mutations are at different loci. Does that mean that all the diseases you mentioned are caused by mutations in the same chromosome?
 
Dang autocorrect :laugh:

Thank you, I understand now. For locus heterogeneity it says the mutations are at different loci. Does that mean that all the diseases you mentioned are caused by mutations in the same chromosome?

Nope, just the opposite! The genes involved in those diseases are on different chromosomes, have practically nothing to do with each other, but somehow end up all causing a similar phenotype (the Marfanoid habitus in this case). In my understanding, that's what locus heterogeneity means :)
 
Anyone know why there is macula sparing in PCA infarct of occipital lobe

that particular area gets bilateral blood supply

hopefully someone can chime in and give more details, thats all i know (even though i think that would be enough for step 1, it always helps to understand these things better!)
 
that particular area gets bilateral blood supply

hopefully someone can chime in and give more details, thats all i know (even though i think that would be enough for step 1, it always helps to understand these things better!)

Wikipedia
In the case of Occipitoparital ischemia owing to occlusion of elements of either posterior cerebral artery, patients may display cortical blindness(which, rarely, can involve blindness that the patient denies having, as seen in Anton's Syndrome), yet display sparing of the macula. This selective sparing is due to the collateral circulation offered to macular tracts by the middle cerebral artery.[1] Neurological examination that confirms macular sparing can go far in representing the type of damage mediated by an infarct, in this case, indicating that the caudal visual cortex (which is the principal recipient of macular projections of the optic nerve) has been spared. Further, it indicates that cortical damage rostral to, and including, lateral geniculate nucleus is an unlikely outcome of the infarction, as too much of the lateral geniculate nucleus is, proportionally, devoted to macular-stream processing.[2]
 
Wikipedia

oh true, so its not bilateral supply, just collateral from the MCA


another question.

airway resistance is minimal in the bronchioles where the cross sectional area is the highest. Why is resistance in arterioles the greatest when they have a higher cross sectional area than arteries/aorta then?

thanks!
 
So pain and temperature fibers are large unmyelinated fibers.
Local anesthetics block small myelinated fibers first and large unmyelinated last.

Why is pain and temperature the first thing to go with localized anesthetics?
 
This is basically the month that I started studying. You irate brah?

no i'm not irate lol, just amused :p

So pain and temperature fibers are large unmyelinated fibers.
Local anesthetics block small myelinated fibers first and large unmyelinated last.

Why is pain and temperature the first thing to go with localized anesthetics?


i thought pain and temp fibers were small? and a-delta fibers are myelinated while c fibers aren't, but both transmit pain and temperature.

and local anesthetics care more about size then myelin, so thats why they go for the smaller ones first
 
Can someone explain to me this statement: "If the prevalence is low, then the odds ratio approaches the relative risk." What does that even mean, or what is the significance of that? Is that a good thing or a bad thing? Never understood this.
 
Can someone give me a little explanation of the cre-lox system on pg.81 first aid? How exactly is this pulled off? How do you think you can relevantly have a Q on this?
 
I have a good one for you guys, from NBME 3
que ****NBME 3 spoiler alert****









A previously healthy 30 yr old man comes to the emergency department because of the sudden onset of right shoulder pain and shortness of breath. Breath sounds are absent over the right lung . His cervical trachea at the superior sternal border is shifted to the left. The most likely cause of his condition is rupture of which of the following?

a. Anterior hernia
b, Apical pulmonary bleb
c, Bronchial diverticulum
d, Cystic adenomatoid malformation
e, Posterolateral hernia

The answer is apparently B. I thought that with spontaneous pneumothorax the trachea shifts TOWARD that side? And wtf is an anterior/posterolateral hernia>
 
Can someone give me a little explanation of the cre-lox system on pg.81 first aid? How exactly is this pulled off? How do you think you can relevantly have a Q on this?

I used this for my research last summer.. it was amazing.. mainly for transgenic mice... kinda like having a on and off switch for DNA in mice experiment.

Anyways, what it is a system of turning on and off gene in mice model.. what you do is flank a DNA sequence with tag (or on and off switch)... so when the mice is born an bred... it doesn't display the phenotype of the flanked gene. But what we did was turn it on when the mice was about 10wks old by injecting special virus into it... and then the flanked portion will become phenotypically expressed. I doubt this would be asked though.

https://upload.wikimedia.org/wikipedia/commons/5/58/CreLoxP_experiment.png
 
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