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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[MLT2MT2DO]

thanks bud!

another question for discussion...it's a NBME spoiler question so highlight the text below to see it...easy concept, but why am i being a potato about it?
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last warning - **NBME 6 SPOILERS** - highlight text to see the question


kaplan says omeprazole is a cyp450 inhibitor but it's not in FA...was the drug recently removed from the list[/COLOR]

You're correct, unfortunately your answer isn't "more correct". I've never really cared for the term "more correct" and think it's a nice way to cover up a b.s. question

 

[Pinkleton]

I have written in my FA that osteoporosis is causing by IL-1 aka osteoclast activating factor. Does that mean osteoporosis is an inflammatory condition? Never thought so, but if cytokines are involved...

 

[MLT2MT2DO]

I have written in my FA that osteoporosis is causing by IL-1 aka osteoclast activating factor. Does that mean osteoporosis is an inflammatory condition? Never thought so, but if cytokines are involved...

I thought RANK was osteoclast acivating factor

 

[Jonari]

You're correct, unfortunately your answer isn't "more correct". I've never really cared for the term "more correct" and think it's a nice way to cover up a b.s. question

damn it...banking on getting most if not all of the pharm questions right...

I thought RANK was osteoclast acivating factor

 

[Pinkleton]

I believe IL1 causes up regulation of rankL. But does that imply inflammation?

 

[Jamiu22]

I believe IL1 causes up regulation of rankL. But does that imply inflammation?

Another name for IL-1 is osteoclast activating factor... which is part of the reason why IL-1 is associated with osteoporosis.. now I wouldn't go as far as saying that osteoporosis is an inflammatory rxn... cos I have never seen it mentioned that way. but who knows.. you may very well be right

EDIT: I just saw that Jonari already had this info... you can tell how much I've listened to Goljan - straight verbatim, lol

 

[dbeast]

Another name for IL-1 is osteoclast activating factor... which is part of the reason why IL-1 is associated with osteoporosis.. now I wouldn't go as far as saying that osteoporosis is an inflammatory rxn... cos I have never seen it mentioned that way. but who knows.. you may very well be right

EDIT: I just saw that Jonari already had this info... you can tell how much I've listened to Goljan - straight verbatim, lol

I read your post in Goljan's voice in my head.

 

[Jonari]

I read your post in Goljan's voice in my head.

his voice is really annoying...used it for prep during my CBSE, which was a while back. need to get one more run in of the audio before the exam, but can't get myself to do it...

sounds like the joker from the dark knight

 

[Jonari]

Another name for IL-1 is osteoclast activating factor... which is part of the reason why IL-1 is associated with osteoporosis.. now I wouldn't go as far as saying that osteoporosis is an inflammatory rxn... cos I have never seen it mentioned that way. but who knows.. you may very well be right

EDIT: I just saw that Jonari already had this info... you can tell how much I've listened to Goljan - straight verbatim, lol

don't forget...IL-1 is also associated with multiple myeloma, in addition to IL-6.

 

[coolforschool]

his voice is really annoying...used it for prep during my CBSE, which was a while back. need to get one more run in of the audio before the exam, but can't get myself to do it...

sounds like the joker from the dark knight

Haha. Dude, I love Goljan's voice. He's like a no-BS tough guy who beats information into your brain. DUH-UH!

 

[Jonari]

Haha. Dude, I love Goljan's voice. He's like a no-BS tough guy who beats information into your brain. DUH-UH!

most i've able to listen to in one sitting is 2 lectures...wish iTunes had a way to edit the audio when he goes off tangent about farting in the lab, eating meat off the floor and his wife complaining, etc

 

[223556]

Two questions:

I can't tell the difference between two images from FA and Pathoma (see attached).

1) What is the difference between Cobblestone mucosa in Crohns and pseudopolyps in Ulcerative colitis?

2) In a biliary tract obstruction (obstructive jaundice), why the crap would you get hypercholesterolemia with xanthomas? (pathoma pg 119)

 

[coolforschool]

most i've able to listen to in one sitting is 2 lectures...wish iTunes had a way to edit the audio when he goes off tangent about farting in the lab, eating meat off the floor and his wife complaining, etc

Those are what makes his lectures memorable though. I love those stories. I got through his transcript and audio in ~2.5 days (2x speed) and liked it a lot. There were a lot of times where I remembered the exact question that I missed on the NBMEs because Goljan said something like, "This is how they're going to do it." Same with Dr. Sattar.

 

[Jonari]

Those are what makes his lectures memorable though. I love those stories. I got through his transcript and audio in ~2.5 days (2x speed) and liked it a lot. There were a lot of times where I remembered the exact question that I missed on the NBMEs because Goljan said something like, "This is how they're going to do it." Same with Dr. Sattar.

lol wow...2.5x...i cant listen to it higher than 1.5x...feel like i miss out on too much

 

[Pinkleton]

Pemphigus vulgaris and staph SSS both attack desmoglein. But for pemphigus this is in the spinosum layer and SSSS is in granulosum? It's all jumbled in my head

 

[sharklasers]

Contraction Alkalosis: am i missing anything?

Due to diuretics
Loss of volume increases renin-angiotensin system activation
Angiotensin II stimulates Na/H exchange in PCT, which indirectly stimulates HCO3 absorption
Aldosterone upregulates prinicpal cell K+ channels and intercalated cell H+ channels, promoting the excretion of both.

I don't really understand the significance of Cl- in all of this. Also, is the "contraction" only referring to the initial factor that stimulates the RAAS system (diuretics --> contraction)?

Thanks!

 

[Pinkleton]

Contraction Alkalosis: am i missing anything?

Due to diuretics
Loss of volume increases renin-angiotensin system activation
Angiotensin II stimulates Na/H exchange in PCT, which indirectly stimulates HCO3 absorption
Aldosterone upregulates prinicpal cell K+ channels and intercalated cell H+ channels, promoting the excretion of both.

I don't really understand the significance of Cl- in all of this. Also, is the "contraction" only referring to the initial factor that stimulates the RAAS system (diuretics --> contraction)?

Thanks!

If you are reabsorbing bicarbonate in the pct, you are using the chloride antiport so your serum chloride drops. And yes, contraction refers to the initial stimulus

 

[sharklasers]

If you are reabsorbing bicarbonate in the pct, you are using the chloride antiport so your serum chloride drops. And yes, contraction refers to the initial stimulus

Is this the correct mechanism for HCO3 changes?

Increased H+/Na+ exchange on luminal side --- more H+ in lumen.

This combined with HCO3 in the lumen, to uses carbonic anhydrase to form CO2 and H2O in the lumen.

CO2 diffuses inside the cell, combines with H2O, forms H+ and HCO3.

H+ is sent back across the lumen due to increased H+/Na+ activity, and the HCO3 concentration is increasing in the cell and needs to go somewhere so you can form more H+ for the exchange, so it leaves the cell via an HCO3/Cl antiporter.

 

[MLT2MT2DO]

Pemphigus vulgaris and staph SSS both attack desmoglein. But for pemphigus this is in the spinosum layer and SSSS is in granulosum? It's all jumbled in my head

Yeah that sounds right, additionally SSS is desmoglein 1 and Pemphigus vulgaris is 3 (wtf ever that random factoid means)

 

[Pinkleton]

Is this the correct mechanism for HCO3 changes?

Increased H+/Na+ exchange on luminal side --- more H+ in lumen.

This combined with HCO3 in the lumen, to uses carbonic anhydrase to form CO2 and H2O in the lumen.

CO2 diffuses inside the cell, combines with H2O, forms H+ and HCO3.

H+ is sent back across the lumen due to increased H+/Na+ activity, and the HCO3 concentration is increasing in the cell and needs to go somewhere so you can form more H+ for the exchange, so it leaves the cell via an HCO3/Cl antiporter.

Spot on

 

[coolforschool]

Two questions:

I can't tell the difference between two images from FA and Pathoma (see attached).

1) What is the difference between Cobblestone mucosa in Crohns and pseudopolyps in Ulcerative colitis?

2) In a biliary tract obstruction (obstructive jaundice), why the crap would you get hypercholesterolemia with xanthomas? (pathoma pg 119)

1. I have trouble telling between the two also. I think of the cobblestone in Crohn's as fissures that form crevices between the walls of tissue (so they're diving down into the wall). Pseudopolyps from UC are more like outpouchings from scar tissue. I can't really tell one from the other though.

2. I'm not sure of the pathophysiology. I think it has something to do with the bile not being able to be recirculated, so there is impaired cholesterol elimination. Eventually the elevated cholesterol levels cause it to be redistributed into the skin and other organs, which may cause xanthomas to form. That's how I think of it, but I haven't run into a lot of things that explain this well.

 

[223556]

1. I have trouble telling between the two also. I think of the cobblestone in Crohn's as fissures that form crevices between the walls of tissue (so they're diving down into the wall). Pseudopolyps from UC are more like outpouchings from scar tissue. I can't really tell one from the other though.

2. I'm not sure of the pathophysiology. I think it has something to do with the bile not being able to be recirculated, so there is impaired cholesterol elimination. Eventually the elevated cholesterol levels cause it to be redistributed into the skin and other organs, which may cause xanthomas to form. That's how I think of it, but I haven't run into a lot of things that explain this well.

Thank you. That works for me!

 

[issey]

Friends,

Can anyone please explain to me the difference between Coagulation vs Platelet Disorders, perhaps with pictures & theoretical lab values(ie. PT, platelet count up down, etc)?

From my understanding the most specific findings in Coagulation disorders would be deep tissue bleeds? While platelet disorders are cutaneous or mucosal bleeds, especially after injury or trauma?

btw-Would that make menorrhagia a platelet disorder?

many thanks!

 

[Jonari]

Friends,

Can anyone please explain to me the difference between Coagulation vs Platelet Disorders, perhaps with pictures & theoretical lab values(ie. PT, platelet count up down, etc)?

From my understanding the most specific findings in Coagulation disorders would be deep tissue bleeds? While platelet disorders are cutaneous or mucosal bleeds, especially after injury or trauma?

btw-Would that make menorrhagia a platelet disorder?

many thanks!

click here:

http://forums.studentdoctor.net/showthread.php?t=1002331&page=7

go to post #336 and start to read from there

 

[issey]

click here:

http://forums.studentdoctor.net/showthread.php?t=1002331&page=7

go to post #336 and start to read from there

thanks!

 

[TheSeanieB]

Can someone explain why thiazide diuretics are used to treat nephrogenic diabetes insipidus? Seems like more water would be lost.

 

[skyblue2000]

Anyone have a good site or source for understanding lab techniques??

 

[addo]

Can someone explain why thiazide diuretics are used to treat nephrogenic diabetes insipidus? Seems like more water would be lost.

As far as I know, it is not completely understood why thiazides help in nephrogenic DI. I was going to attempt to explain in my own words but i figure ill quote

It is possible that the natriuretic action of thiazides and resulting extracellular fluid volume depletion play an important role in thiazide-induced antidiuresis. In this regard, whenever extracellular fluid volume is reduced, compensatory mechanisms increase NaCl reabsorption in proximal tubule, reducing the volume delivered to the distal tubule. Consequently, less free water can be formed, which should diminish polyuria.

This is from Goodman's and Gilman's pharmacologic basis of theraupeutics

Not a completely satisfactory answer to be honest... but what I gather from that is that since Lithium exerts its DI effects due to interference with vassporessin, you would want to reabsorb as much NaCl/water as possible from the early segments of the nephron which are vassopressin independent. This is apparently what thiazides are able to accomplish- induce mechanisms to increase early nephron NaCl and water reabsorption, so that not as much water is able to reach the collecting duct and therefore be dependent on the concentrating effect of vassopressin.

 

[Greenbayslacker]

Can someone explain why thiazide diuretics are used to treat nephrogenic diabetes insipidus? Seems like more water would be lost.

Since you're not responding to ADH in the collecting tubule, you won't be able to reabsorb water there. Instead, you use a thiazide to increase diuresis, causing a loss of plasma volume and therefore GFR. In turn the kidney will increase reabsorption at the PCT, where reabsorption still works since it's not ADH-dependent.

 

[sharklasers]

What about the mechanism behind ACE inhibitors being used for diabetic renal disease?

 

[sharklasers]

Also, regarding maternal diabetes, when do you get symptoms like caudal regression syndrome (anal atresia, sirenomelia) versus something like macrosomia or postnatal hypoglycemia?

 

[Jonari]

for apoptosis...it talks about nuclear shrinkage as a finding. however in,

FA'12 it says we see basophilia (nothing in errata)
Pathoma it says we see eosinophilia (has a picture attached with it)

any ideas?

 

[sharklasers]

for apoptosis...it talks about nuclear shrinkage as a finding. however in,

FA'12 it says we see basophilia (nothing in errata)
Pathoma it says we see eosinophilia (has a picture attached with it)

any ideas?

Pathoma refers to cytoplasm eosinophilia, while maybe FA is referring to nuclear basophilia? That would make sense because as the nucleus is shrinking, it becomes more dense, and appears more basophilic?

I think the cytoplasm vs. nucleus distinction should clear this up for you though!

 

[CrouchingLiger]

Pathoma refers to cytoplasm eosinophilia, while maybe FA is referring to nuclear basophilia? That would make sense because as the nucleus is shrinking, it becomes more dense, and appears more basophilic?

I think the cytoplasm vs. nucleus distinction should clear this up for you though!

Yeah, first aid definitely indicates that its nuclear basophilia (although they don't make that very clear with how its worded), while pathoma is talking about cytoplasm. So yeah, nuclear basophilia and cytoplasmic eosinophilia for apoptosis.

 

[Pinkleton]

I understand that with homocystinuria you don't convert homocysteine to cystathionine, and elevated homocysteine damage blood vessels and cause Marfanoid features.

But let's relate this to folate/B12 deficiency. I know you would start accumulating homocysteine, BUT is that shunted toward cystathione synthesis since that pathway is intact? And is this why you don't read about atherosclerosis/Marfanoid symptoms in folate/B12 deficient patients?

 

[Greenbayslacker]

What about the mechanism behind ACE inhibitors being used for diabetic renal disease?

A lot of the damage in diabetic renal disease comes from hyperfiltration, as the efferent arteriole is affected before the afferent arteriole (via non-enzymatic glycosylation). This increases GFR too much and causes glomerular damage (specifically to the mesangium). ACE inhibitors are able to block Ang II from causing efferent arteriole constriction. This lowers GFR, thereby slowing the damage to the glomeruli and preventing progression to diabetic glomerulonephropathy (nephrotic syndrome).

 

[Jamiu22]

A lot of the damage in diabetic renal disease comes from hyperfiltration, as the efferent arteriole is affected before the afferent arteriole (via non-enzymatic glycosylation). This increases GFR too much and causes glomerular damage (specifically to the mesangium). ACE inhibitors are able to block Ang II from causing efferent arteriole constriction. This lowers GFR, thereby slowing the damage to the glomeruli and preventing progression to diabetic glomerulonephropathy (nephrotic syndrome).

More information http://www.ncbi.nlm.nih.gov/pubmed/12882873

Blockade of the renin-angiotensin system in type 2 diabetic patients with diabetic nephropathy reduces uMCP-1 levels and improves renal function. Because MCP-1 induces monocyte immigration and differentiation to macrophages, which augment extracellular matrix production and tubulointerstitial fibrosis, pharmacological reduction of angiotensin II may also exert its beneficial effects in diabetic nephropathy by downregulation of renal MCP-1.

Even more info... http://www.uptodate.com/contents/diabetic-kidney-disease-diabetic-nephropathy-beyond-the-basics

ACE inhibitors and ARBs are particularly useful for people with diabetic nephropathy because they decrease the amount of protein in the urine and can prevent or slow the progression of diabetes-related kidney disease. In fact, the kidney benefits of ACE inhibitors and ARBs are so robust that healthcare providers sometimes prescribe them for people with diabetic nephropathy who have normal blood pressure.

 

[JP2740]

Cretinism, can this be caused by iron excess? I believe iron excess messes with thyroid hormone synthesis too.

Also, does the baby mainly synthesize it's own thyroid hormone from maternal iodine, or does it receive from mom i.e. if she's hypothyroid, will the baby be a cretin? (untreated hypothyroid, as I assume levothyroxine is transported across placenta?)

 

[JP2740]

A lot of the damage in diabetic renal disease comes from hyperfiltration, as the efferent arteriole is affected before the afferent arteriole (via non-enzymatic glycosylation). This increases GFR too much and causes glomerular damage (specifically to the mesangium). ACE inhibitors are able to block Ang II from causing efferent arteriole constriction. This lowers GFR, thereby slowing the damage to the glomeruli and preventing progression to diabetic glomerulonephropathy (nephrotic syndrome).

edit: Jamiu22, didn't know your post was referring to this same thing lol. You covered all this stuff in your post before me

To add to this, one of the first signs of diabetic renal damage is microalbuminuria because of efferent arteriole constriction (non-enzymatic glycosylation)>afferent arteriole constriction (same mechanism). This causes a hyperfiltration injury, you can just picture the blood getting jam packed into the glomeruli and can't get out through the efferent arteriole because its a smaller lumen due to the basement membrane enlargement. Angiotensin II constricts the efferent arteriole, so if you use an ACEI, you're opening up the efferent arteriole a little bit more and relieving that hyperfiltration injury.

But note, once you put a diabetic on an ACEI, there will be a transient increase in creatinine and BUN because you're decreasing the GFR. However, in the long-run, this increases the lifespan of the kidney. Idk if step 1 will go that far, but you might envision a question: diabetic comes in with microalbuminuria, receives the proper treatment, on follow up the BUN and creatinine seem to rise, what happened? It's the meds.

 

[JP2740]

I understand that with homocystinuria you don't convert homocysteine to cystathionine, and elevated homocysteine damage blood vessels and cause Marfanoid features.

But let's relate this to folate/B12 deficiency. I know you would start accumulating homocysteine, BUT is that shunted toward cystathione synthesis since that pathway is intact? And is this why you don't read about atherosclerosis/Marfanoid symptoms in folate/B12 deficient patients?

I think in a deficiency, the pathway is still active, and the homocysteine levels don't even begin to approach that of homocysteinuria. I don't know if this is a fact, but remember reading/hearing it somewhere.

 

[John Lannister]

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

 

[JP2740]

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

lol you cannot teach boss. jamiu just is one

 

[Leonidis I]

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

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.

 

[JP2740]

I read all of pubmed over the past 2 years. Having trouble getting through all of pubmed in my dedicated study. Discouraging

 

[Pinkleton]

I think in a deficiency, the pathway is still active, and the homocysteine levels don't even begin to approach that of homocysteinuria. I don't know if this is a fact, but remember reading/hearing it somewhere.

Yeah sounds about right. I looked into it, and apparently the homocysteine levels in B12/folate def are somewhere between a control patient and a heterozygote w/ cystathione synthase deficiency. There may be a "theoretical risk" for vascular disease

Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency.
Brattström L, Israelsson B, Lindgärde F, Hultberg B.
Source
Department of Internal Medicine, Malmö General Hospital, University of Lund, Sweden.
Abstract
Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12-deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease

 

[Jamiu22]

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.

I read all of pubmed over the past 2 years. Having trouble getting through all of pubmed in my dedicated study. Discouraging

you guys are cracking me up!

 

[Jamiu22]

edit: Jamiu22, didn't know your post was referring to this same thing lol. You covered all this stuff in your post before me

To add to this, one of the first signs of diabetic renal damage is microalbuminuria because of efferent arteriole constriction (non-enzymatic glycosylation)>afferent arteriole constriction (same mechanism). This causes a hyperfiltration injury, you can just picture the blood getting jam packed into the glomeruli and can't get out through the efferent arteriole because its a smaller lumen due to the basement membrane enlargement. Angiotensin II constricts the efferent arteriole, so if you use an ACEI, you're opening up the efferent arteriole a little bit more and relieving that hyperfiltration injury.

But note, once you put a diabetic on an ACEI, there will be a transient increase in creatinine and BUN because you're decreasing the GFR. However, in the long-run, this increases the lifespan of the kidney. Idk if step 1 will go that far, but you might envision a question: diabetic comes in with microalbuminuria, receives the proper treatment, on follow up the BUN and creatinine seem to rise, what happened? It's the meds.

Nice post! also, with ACEi, they can get a first dose hypotension.. mimicking pre-renal azotemia....(this one always gets me...)

 

[Pinkleton]

Nice post! also, with ACEi, they can get a first dose hypotension.. mimicking pre-renal azotemia....(this one always gets me...)

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

 

[dbeast]

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.

I read all of pubmed over the past 2 years. Having trouble getting through all of pubmed in my dedicated study. Discouraging

In all seriousness, wikipedia's gonna score me at least 20 points on this test.

 

[JP2740]

pg. 510, congenital pharyngo-cutaneous fistula. It says a fistula between tonsilar area, where does the fistula lead to?
Is the cleft in the lateral neck the same idea as the branchial cleft cyst from persistent cervical sinus?