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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[loveoforganic2]

I got one for you geniuses- anybody have a good way of remembering the differences between neurofibromatosis and tuberous sclerosis? It's like they're totally similar but completely different and it's irritating.

Ash leaf spots vs. cafe-au lait spots is a big one.

Ash leaf are hypopigmented (Tuberous sclerosis)
Cafe-au-lait are pigmented (NF-1)

Axillary/Inguinal freckling is also pathognomonic for NF-1, and adenoma sebaceum is classically TS (and I'd know that adenoma sebaceum are actually angiofibromas)

 

[Jonari]

Axillary/Inguinal freckling is also pathognomonic for NF-1, and adenoma sebaceum is classically TS (and I'd know that adenoma sebaceum are actually angiofibromas)

this.

one of the questions i encountered gave basically the text book description of TS everything from the angiofibromas, rhabdomyosarcomas (100% predictive of TS), angiomyolipomas of the liver. however, the biggest clue i think about TS is seeing a kid with the angiofibromas + mental ******ation + presence of seizures. there's a picture in the earlier NBMEs which shows the angiofibromas, and ask what else is associated with this condition...ill find it for you, shortly.

also remember that the ash-leaf spots are hypopigmented, but you also see them in mccune-albright's.

 

[Jonari]

Here you go. I didn't directly link them in case somebody here plans on doing the early NBMEs.

***SPOILER - EARLY NBME QUESTIONS***

http://i.imgur.com/HClv7uh.png
http://i.imgur.com/EBwjGDb.png
http://i.imgur.com/Gs5VoUw.png

 

[tiedyeddog]

Anyone have a good resource for the familial hypercholesterimia/dyslipidemia etc.?

I'm having a hard time getting these to stick

quizlet quiz: http://quizlet.com/19424252/types-of-hyperlipidemia-pharmacology-flash-cards/
maybe this helps a bit?

also, a picture of Corneal Arcus I thought was cool:

 

[MLT2MT2DO]

quizlet quiz: http://quizlet.com/19424252/types-of-hyperlipidemia-pharmacology-flash-cards/
maybe this helps a bit?

also, a picture of Corneal Arcus I thought was cool:

This is actually quite awesome, thank you.

 

[Jonari]

Make sure you remember with Type 1 you see acute pancreatitis, there was a question about this. Q said when you looked at the blood sample of the patient it was a turbid/milky color indicating elevated chylomicrons in the blood.

Don't forget that Type 2 has the pathognomonic Achilles' tendon involvement.
- Can be heterozyous for the gene and LDL levels are around 350
- Can be homozygous for the gene and LDL levels are around 700 --> one of the few differentials for having a MI before the age of 20 years old.

Don't forget apoE (4) = Alzheimer's

 

[bangarang]

Those couple pages were an interesting read, thanks for digging it up. This is the gist, if I'm understanding right. Both splanchnic HTN and sinusoidal HTN are causative agents in ascites. Sinusoidal HTN tends to cause exudative ascites, while splanchnic HTN tends to cause transudative ascites. The combination of the two accounts for the normal finding in ascitic fluid of "somewhat less protein concentration than serum". Extrapolating here - With regard to portal v. thrombosis, you are LESS likely to ascites (though it isn't impossible.

Due to the fenestration of hepatic sinusoids, a tiny increase in pressure (relative to what it would require for splanchnic transudation) is able to cause ascites.

So presinusoidal portal HTN (hepatic v. thrombosis) => low probability of ascites.

Sinusoidal HTN (cirrhosis, HCC) and postsinusoidal HTN (Budd Chiari) => high probability of ascites.

Sound good?

Good summary. That's basically what I got out of it.

Make sure you remember with Type 1 you see acute pancreatitis, there was a question about this. Q said when you looked at the blood sample of the patient it was a turbid/milky color indicating elevated chylomicrons in the blood.

Don't forget that Type 2 has the pathognomonic Achilles' tendon involvement.
- Can be heterozyous for the gene and LDL levels are around 350
- Can be homozygous for the gene and LDL levels are around 700 --> one of the few differentials for having a MI before the age of 20 years old.

Don't forget apoE (4) = Alzheimer's

Nice. Don't forget apoE2 is protective vs. Alzheimer's.

 

[MLT2MT2DO]

Make sure you remember with Type 1 you see acute pancreatitis, there was a question about this. Q said when you looked at the blood sample of the patient it was a turbid/milky color indicating elevated chylomicrons in the blood.

Don't forget that Type 2 has the pathognomonic Achilles' tendon involvement.
- Can be heterozyous for the gene and LDL levels are around 350
- Can be homozygous for the gene and LDL levels are around 700 --> one of the few differentials for having a MI before the age of 20 years old.

Don't forget apoE (4) = Alzheimer's

Please for the love of god tell me you aren't on here an hour before your test trying to answer questions

 

[Jonari]

Please for the love of god tell me you aren't on here an hour before your test trying to answer questions

Thanks for the concern, but I pushed it back. Too much on the line for the next 40-50 years, couldn't settle with the scores I was getting.

 

[Jonari]

Good summary. That's basically what I got out of it.



Nice. Don't forget apoE2 is protective vs. Alzheimer's.

yup...nice work!

 

[MLT2MT2DO]

Thanks for the concern, but I pushed it back. Too much on the line for the next 40-50 years, couldn't settle with the scores I was getting.

Good call, truthfully what's a couple hundred dollars in the long run

 

[Jamiu22]

Thanks for the concern, but I pushed it back. Too much on the line for the next 40-50 years, couldn't settle with the scores I was getting.

Smart choice Jonari! Good luck with your studies

 

[JP2740]

Anyone know why ischemia is an example of intrinsic renal failure when that seems to be the definition of prerenal azotemia (first aid pg.496)

 

[doctoritis]

Anyone know why ischemia is an example of intrinsic renal failure when that seems to be the definition of prerenal azotemia (first aid pg.496)

My guess would be that it can cause an acute tubular necrosis = intrarenal.

And I'm also curious about pelvic anatomy ... what to do about it?!

 

[JP2740]

My guess would be that it can cause an acute tubular necrosis = intrarenal.

And I'm also curious about pelvic anatomy ... what to do about it?!

f.uck it

 

[SLC]

Anyone know why ischemia is an example of intrinsic renal failure when that seems to be the definition of prerenal azotemia (first aid pg.496)

Ischemia will initially cause Pre-renal azotemia (as urea is re-absorbed in an attempt to retain volume. Remember it is osmotically active)

If left untreated, ischemia leading to ATN is inevitable. Once that happens, you've got intrinsic renal failure (aka renal azotemia).

 

[JP2740]

Why is NH3 toxicity associated w/ CCB?

 

[dbeast]

Here you go. I didn't directly link them in case somebody here plans on doing the early NBMEs.

***SPOILER - EARLY NBME QUESTIONS***

http://i.imgur.com/HClv7uh.png
http://i.imgur.com/EBwjGDb.png
http://i.imgur.com/Gs5VoUw.png

These are very good... what was the right answer about special education?

 

[MLT2MT2DO]

Ischemia will initially cause Pre-renal azotemia (as urea is re-absorbed in an attempt to retain volume. Remember it is osmotically active)

If left untreated, ischemia leading to ATN is inevitable. Once that happens, you've got intrinsic renal failure (aka renal azotemia).

To piggy back. You get the ATN because the epithelial cells of the tubules die without O2 and will slough off and block the tubule

 

[Jonari]

These are very good... what was the right answer about special education?

highlight the text below
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[Jonari]

To piggy back. You get the ATN because the epithelial cells of the tubules die without O2 and will slough off and block the tubule

this.

The ATN questions I've been doing from various sources [ie UWorld, Kaplan, WebPath, UWSA, NBME - so don't worry about me giving away any particular spoilers ] many of the questions in the stem will have the phrase "muddy brown casts" which is pathognomonic for ATN, in add'n they'll describe the stem and ask what will you see under microscopy.

- Keep in mind, that MI is a good example of a situation that is initially pre-renal then becomes intra-renal. In add'n anything that causes hypovolemic conditions, imo, I've seen associated with eventual ATN.
- Don't forget that areas that most affected by ATN are the PCT and the thick ascending LOH, whereas with heavy metal toxicity (ie lead) and aminoglycosides cause damage to the PCT, only.
- Most importantly, I've seen this question getting asked a lot - what happens post ATN? Are the kidneys permanently damanged - no. Patients will be placed on dialysis, and since the cells of the kidneys are stable cells you'll see regeneration of the tubules, but with time. Only way this won't occur is when the basement membranes have been destroyed completely, inhibiting regeneration.

 

[Jonari]

Why is NH3 toxicity associated w/ CCB?

ammonia toxicity with calcium channel blockers?

 

[addo]

Why is NH3 toxicity associated w/ CCB?

Ive never heard of this but through a quick pub med search i found

The data suggest that hyperammonemia exerts a calcium channel blocking action which enhances the effects of central nervous system depressants and certain opioid analgesics.

http://www.ncbi.nlm.nih.gov/pubmed/6323692

Not going to dig any further since i doubt this is at all relevant to step

 

[Charlie Hustle]

Ischemia will initially cause Pre-renal azotemia (as urea is re-absorbed in an attempt to retain volume. Remember it is osmotically active)

If left untreated, ischemia leading to ATN is inevitable. Once that happens, you've got intrinsic renal failure (aka renal azotemia).

If the relationship is temporal, how would one differentiate early ischemia (prerenal azotemia) from late ischemia (ATN)? How would this be presented in the vignette? Would they simply present a patient with "longstanding renal ischemia" or something similar?

By the way, I've just started reading through this thread, and there are some great discussions going on here.

 

[Jonari]

If the relationship is temporal, how would one differentiate early ischemia (prerenal azotemia) from late ischemia (ATN)? How would this be presented in the vignette? Would they simply present a patient with "longstanding renal ischemia" or something similar?

By the way, I've just started reading through this thread, and there are some great discussions going on here.

Looking at the BUN: Cr levels would be allow one to differentiate between the two, in addition to the microscopic findings of "muddy brown casts" for ATN, and the overall setting of the picture (ie patient had a MI a couple of days ago, and now this happens; patient has massive blood loss and a couple of days later you see this...)

Pre-Renal
- BUN: Cr ratio is x > 15
- the kidneys are working fine, in the current setting, so if you look at the urine sample, you'll notice that there isn't much sodium excreted out. it's less than 1%, which gives rise to another value ka Fe[Na] ka...lol, i forgot what the F stands for, but "something excretion rate of sodium". If it's less than 1%, kidneys are working fine.


IntraRenal
- BUN: Cr x < 15
- Fe[Na] will be over 2% - meaning that it's damaged and not reabsorbing sodium, and you're losing it.

Concept is hard to explain in words, but when you see the question - it's really easy to decipher what's happening and making the diagnosis.

 

[bangarang]

Looking at the BUN: Cr levels would be allow one to differentiate between the two, in addition to the microscopic findings of "muddy brown casts" for ATN, and the overall setting of the picture (ie patient had a MI a couple of days ago, and now this happens; patient has massive blood loss and a couple of days later you see this...)

Pre-Renal
- BUN: Cr ratio is x > 15
- the kidneys are working fine, in the current setting, so if you look at the urine sample, you'll notice that there isn't much sodium excreted out. it's less than 1%, which gives rise to another value ka Fe[Na] ka...lol, i forgot what the F stands for, but "something excretion rate of sodium". If it's less than 1%, kidneys are working fine.


IntraRenal
- BUN: Cr x < 15
- Fe[Na] will be over 2% - meaning that it's damaged and not reabsorbing sodium, and you're losing it.

Concept is hard to explain in words, but when you see the question - it's really easy to decipher what's happening and making the diagnosis.

This is correct. Goljan also goes over this and explains it pretty well. Fe = Fractional excretion.

 

[Charlie Hustle]

Looking at the BUN: Cr levels would be allow one to differentiate between the two, in addition to the microscopic findings of "muddy brown casts" for ATN, and the overall setting of the picture (ie patient had a MI a couple of days ago, and now this happens; patient has massive blood loss and a couple of days later you see this...)

Pre-Renal
- BUN: Cr ratio is x > 15
- the kidneys are working fine, in the current setting, so if you look at the urine sample, you'll notice that there isn't much sodium excreted out. it's less than 1%, which gives rise to another value ka Fe[Na] ka...lol, i forgot what the F stands for, but "something excretion rate of sodium". If it's less than 1%, kidneys are working fine.


IntraRenal
- BUN: Cr x < 15
- Fe[Na] will be over 2% - meaning that it's damaged and not reabsorbing sodium, and you're losing it.

Concept is hard to explain in words, but when you see the question - it's really easy to decipher what's happening and making the diagnosis.

Got it! Thanks for putting all the pieces together for me.

BTW it's fractional excretion of sodium that you're thinking of.

 

[223556]

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Why that one instead of the other option that is similar?

 

[Jonari]

Why that one instead of the other option that is similar?

honestly, i thought it was the other, because it's autosomal dominant, correct? AD disorders usually have manifestations later in life, however the offline answers say differently. However, it's possible that it could be wrong. As we know, autosomal recessive disorders manifest with s/s earlier in stages of life (ie Pompe's, CFibrosis, Infantile PCKD), so a bit iffy about the answer. Your thoughts?

 

[loveoforganic2]

honestly, i thought it was the other, because it's autosomal dominant, correct? AD disorders usually have manifestations later in life, however the offline answers say differently. However, it's possible that it could be wrong. As we know, autosomal recessive disorders manifest with s/s earlier in stages of life (ie Pompe's, CFibrosis, Infantile PCKD), so a bit iffy about the answer. Your thoughts?

These are just trends. In addition to variable expressivity and penetrance, you're only going to be selecting away from defects when they affect reproduction. Plenty of people with learning disabilities / mild MR go on to have families. Additionally, unless there's an abnormal accumulation that's going to slowly cause brain damage over time, I would intuitively expect most MR to manifest early in life

 

[MLT2MT2DO]

Anyone know why there's a decreased platelet count in Bernard-Soulier's?

 

[Jonari]

Anyone know why there's a decreased platelet count in Bernard-Soulier's?

source for where you found this?

- BSoulier's
- Glanzmann's
- Uremia

These are causes of qualitative dysfunction of the platelets, meaning something is wrong with them, but blood work shows a normal count of these. Different from the quantitative disorders involving numbers of platelets (ie ITP, TTP, DIC, HUS, HIT)

Edit: Here's a NBME question basically asking you to differentiate between various platelet pathologies. I got this wrong, which I shouldn't have, but as you can see the platelet count is low, indicative of a quantitative disorder.

***NBME 12 SPOILER***

http://i.imgur.com/BCEJWek.png

 

[loveoforganic2]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046265/

BS has thrombocytopenia. You can also get erroneously low thrombocytopenia on automated CBC d/t the platelet size causing instrument error. No idea on pathogenesis

 

[MLT2MT2DO]

source for where you found this?

- BSoulier's
- Glanzmann's
- Uremia

These are causes of qualitative dysfunction of the platelets, meaning something is wrong with them, but blood work shows a normal count of these. Different from the quantitative disorders involving numbers of platelets (ie ITP, TTP, DIC, HUS, HIT)

Edit: Here's a NBME question basically asking you to differentiate between various platelet pathologies. I got this wrong, which I shouldn't have, but as you can see the platelet count is low, indicative of a quantitative disorder.

***NBME 12 SPOILER***

http://i.imgur.com/BCEJWek.png

FA 2013 is my source

 

[bangarang]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046265/

BS has thrombocytopenia. You can also get erroneously low thrombocytopenia on automated CBC d/t the platelet size causing instrument error. No idea on pathogenesis

http://emedicine.medscape.com/article/954877-overview#a0104

"The cause of the thrombocytopenia is not definitely known, but it is probably related to a decreased platelet life span."

 

[MLT2MT2DO]

Ok good stuff, just wanted to make sure there wasn't a basic science concept I was missing

 

[blaqmamba]

@Jonari
I know pathoma made a point about quality/vs quantity, but I wouldn't think about it like that. I think he just said that to make it easier to remember what function of the platelets are lost

 

[sharklasers]

I was hoping someone would be able to explain SNS activation/blockade and its effect on pulse pressure.

For some reason I have it written down that alpha-1 incresaes systolic BP and beta-2 decreases diastolic BP.

i know that alpha-1 increases PVR and beta-2 decreases PVR, but i'm having a hard time understanding how this ties back into pulse pressure.

Thanks!

 

[Jonari]

I was hoping someone would be able to explain SNS activation/blockade and its effect on pulse pressure.

For some reason I have it written down that alpha-1 incresaes systolic BP and beta-2 decreases diastolic BP.

i know that alpha-1 increases PVR and beta-2 decreases PVR, but i'm having a hard time understanding how this ties back into pulse pressure.

Thanks!

what's the equation for pulse pressure? that should help you out...

 

[sharklasers]

what's the equation for pulse pressure? that should help you out...

haha systolic - diastolic right?

but i guess i don't know how the SNS effects systolic blood pressure versus diastolic blood pressure

I just know that alpha-1 increases BP and beta-2 decreases BP

 

[Jonari]

read post 247

 

[tiedyeddog]

that's really all there is to the concept...but as you mentioned SNS affects TPR because NE will bind to a1 receptors causing vasoconstriction on the vessels...increasing TPR. increasing TPR will obviously increase the systolic BP. NE doesn't bind to b2-receptors because these are "non-innervated", so it has no affect on diastolic BP.

weak explanation, but not really sure how else to explain it...

dude, I never knew that, thanks for the explanation.

So the B-receptors do more systolic (increasing heart contraction and rate) while the A receptors increased diastolic by increasing TPR?

 

[tiedyeddog]

I was hoping someone would be able to explain SNS activation/blockade and its effect on pulse pressure.

For some reason I have it written down that alpha-1 incresaes systolic BP and beta-2 decreases diastolic BP.

i know that alpha-1 increases PVR and beta-2 decreases PVR, but i'm having a hard time understanding how this ties back into pulse pressure.

Thanks!

Building on what Jonari said, things that effect diastolic are going to be like the elasticity + size of the systemic vessels. If you contract arteriolar smooth muscle or you make arteries less elastic, diastolic pressure is going to go up. This is why old people can have a huge pulse pressure gap, due to loss of elasticity.

Systolic is more of a function of the heart contracting itself. B-agonists directly cause the heart to have stronger contractions.

This is my logic, anyway.

 

[Jonari]

dude, I never knew that, thanks for the explanation.

So the B-receptors do more systolic (increasing heart contraction and rate) while the A receptors increased diastolic by increasing TPR?

correct.

Systolic = Cardiac Output
Diastolic = Total peripheral resistance

learned this from Kaplan, and the questions that Kaplan asks about this are kinda hard to wrap my mind around.

 

[sharklasers]

that's really all there is to the concept...but as you mentioned SNS affects TPR because NE will bind to a1 receptors causing vasoconstriction on the vessels...increasing TPR. increasing TPR will obviously increase the diastolic BP. NE doesn't bind to b2-receptors because these are "non-innervated", so it has no affect on diastolic BP.

weak explanation, but not really sure how else to explain it...

edit: well said below...easier explanation

hmm i just want to address a contradiction here, just to make sure i am understanding this right.

You say that NE both increases diastolic BP via a1 and has no effect on diastolic BP bc it doesn't innervate b2.

So NE really increases diastolic BP, but something like isoproterenol would decrease diastolic BP due to its effects on b2 and increase systolic BP due to its effects on b1?

I guess my confusion and need for clarification came for questions like "which of the following would increase pulse pressure"

but it seems like all SNS drugs would increase pulse pressure? except maybe NE, because it would increase both diastolic BP and systolic BP, and does not have the effect of b2 to decrease diastolic BP a little bit more.

wow this is confusing and im sure i am overthinking it to the point where this is becoming very low yield lol

 

[sharklasers]

EDIT: Another question

On FA2013 page 255, it shows a cardiac and vascular function curve.

I don't understand number 3 of that curve, the one with an increase in TPR.

I understand why the venous return curve would shift to the left, because the increase in TPR would limit blood flow back to the heart.

What I don't understand is why the CO curve shows a (-) inotropy change. I don't understand how an increase in TPR would cause inotropy to go down.

I would think the following would happen:

1) Increase in TPR
2) Decrease in blood return back to heart
3) Decrease in preload, so decrease in CO
4) Compensatory INCREASE in inotropy

Now number 3 is labeled as "before compensation can occur" but that would make me think that inotropy would remain unchanged, definitely not decrease. Thanks!

 

[Jonari]

I'm going to split up what you wrote in sections to make everything easier.

hmm i just want to address a contradiction here, just to make sure i am understanding this right.

You say that NE both increases diastolic BP via a1 and has no effect on diastolic BP bc it doesn't innervate b2.

To start this, the blood pressure 120/80 represents systolic/diastolic, as we all know. What determines systolic/diastolic, well that's CO/TPR. So we can say:

120 = systolic = cardiac output
80 diastolic TPR

So NE would increase diastolic pressure, because what determines DP -> TPR. I believe you made a typo in the 2nd part of your sentence. If you mean it wouldn't lower DP, because it doesn't bind to beta2, then yes that is correct. Similarly, NE can also bind to b1 and cause an increase in systolic, which would thus lead to increase in CO, from the equation above.

So NE really increases diastolic BP, but something like isoproterenol would decrease diastolic BP due to its effects on b2 and increase systolic BP due to its effects on b1?

IsoP is a non-selective beta-agonist, correct? So when it binds to beta1 it'll increase the systolic pressure, meaning increase cardiac output. However, it'll also bind to beta2 receptors causing vasodilation of the vessels. So, now look at the equation I posted above of where S/D, correct? We know that pulse pressure (PP) equals systolic - diastolic. If you had to increase pulse pressure, how would you do it?

a. increase systolic aka increase co
b. decrease diastolic aka decrease tpr
c. using a drug that does both a + b aka just like our drug IsoP

I guess my confusion and need for clarification came for questions like "which of the following would increase pulse pressure"

actually yeah, my original comment was improperly worded/structured, so i take full blame for that. i apologize

but it seems like all SNS drugs would increase pulse pressure? except maybe NE, because it would increase both diastolic BP and systolic BP, and does not have the effect of b2 to decrease diastolic BP a little bit more.

is this a question from Kaplan qbank? watch the kaplan pharm video on this topic...it does a good job clearing it up. if i typed it up, would end up being another good 20 minutes on the topic.

wow this is confusing and im sure i am overthinking it to the point where this is becoming very low yield lol

if it makes you feel better...i haven't received a question on the topic from UWorld, UWSA, or NBME 1, 2, 3, 4, 5, 6, 7, 11, 12, 13, 15 - but doesn't mean you shouldn't learn it.

 

[sharklasers]

Haha thanks!

And to refer back to the most recent question I posted about the cardiac and vascular function curve...

Does an increase in afterload and decrease in contractility shift the frank starling curve the same way??

 

[tiedyeddog]

EDIT: Another question

On FA2013 page 255, it shows a cardiac and vascular function curve.

I don't understand number 3 of that curve, the one with an increase in TPR.

I understand why the venous return curve would shift to the left, because the increase in TPR would limit blood flow back to the heart.

What I don't understand is why the CO curve shows a (-) inotropy change. I don't understand how an increase in TPR would cause inotropy to go down.

I would think the following would happen:

1) Increase in TPR
2) Decrease in blood return back to heart
3) Decrease in preload, so decrease in CO
4) Compensatory INCREASE in inotropy

Now number 3 is labeled as "before compensation can occur" but that would make me think that inotropy would remain unchanged, definitely not decrease. Thanks!

Doesn't inotropy go down with decreased preload and thus less stretching of heart muscle?

edit: deeper explanation of the cardiac and vascular function curve
http://scribe-notes.com/wp-content/uploads/2013/02/Lecture-181.pdf

basically, it says an increased TPR shifts both the cardiac and the vascular curve down, but it doesn't say why....

 

[Jonari]

EDIT: Another question

On FA2013 page 255, it shows a cardiac and vascular function curve.

I don't understand number 3 of that curve, the one with an increase in TPR.

I understand why the venous return curve would shift to the left, because the increase in TPR would limit blood flow back to the heart.

What I don't understand is why the CO curve shows a (-) inotropy change. I don't understand how an increase in TPR would cause inotropy to go down.

I would think the following would happen:

1) Increase in TPR
2) Decrease in blood return back to heart
3) Decrease in preload, so decrease in CO
4) Compensatory INCREASE in inotropy

Now number 3 is labeled as "before compensation can occur" but that would make me think that inotropy would remain unchanged, definitely not decrease. Thanks!

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

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

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

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

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