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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[tiedyeddog]

Pretty good picture. I photoshopped it a bit for clarity.

haha, I finally understand this pathway today. One quesiton: Where exactly are the D1 and D2 receptors? Dopamine is made in the SNc and the receptors are in the striatum, right?

So, the signals OUT of D2 receptor positive neurons in the striatum are negative right?

Signals OUT of D1 positive receptor neurons in the striatum are positive?

Ok, so related to this:

Parkinson's disease results in atrophy of the striatum and the subthalamic nucleus, this basically inhibits the indirect pathway causing disinhibitied movement. Why does this cause Parkin's symptoms too, if the striatum is affected?

Similarly, why doesn't Parkin's disease, which is death of the dopamine producing sunstantia niagra pars compacta, effect both the indirect and direct pathway??

I swear to God, I knew this stuff so well at the end of M1.... ugh.

 

[bangarang]

haha, I finally understand this pathway today. One quesiton: Where exactly are the D1 and D2 receptors? Dopamine is made in the SNc and the receptors are in the striatum, right?

So, the signals OUT of D2 receptor positive neurons in the striatum are negative right?

Signals OUT of D1 positive receptor neurons in the striatum are positive?

Ok, so related to this:

Parkinson's disease results in atrophy of the striatum and the subthalamic nucleus, this basically inhibits the indirect pathway causing disinhibitied movement. Why does this cause Parkin's symptoms too, if the striatum is affected?

Similarly, why doesn't Parkin's disease, which is death of the dopamine producing sunstantia niagra pars compacta, effect both the indirect and direct pathway??

I swear to God, I knew this stuff so well at the end of M1.... ugh.

Sh**. I just realized something. I think the output pathway from the striatum to the GPi is actually inhibitory, so even though DA to striatum in the direct pathway is via D1, the output from the striatum to the GPi is actually inhibitory (arrow should be black).

Edit: I might be confusing myself. IDK. Gotta think this through again, dang it.

 

[SLC]

Anyone have any tips for what antibiotics are used for what infections? This still seems like a mystery to me....

Same here. It's all jumbled up in my head somewhere.

Ask and ye shall receive, these are Pholston's lectures, and the antibiotics one is really good. It's not complete by any means, but it's extremely good and an excellent start...

http://forums.studentdoctor.net/showthread.php?t=994504

The other two were helpful for me as well!

 

[tiedyeddog]

Sh**. I just realized something. I think the output pathway from the striatum to the GPi is actually inhibitory, so even though DA to striatum in the direct pathway is via D1, the output from the striatum to the GPi is actually inhibitory (arrow should be black).

Edit: I might be confusing myself. IDK. Gotta think this through again, dang it.

yeah, I just figured this out. That diagram is wrong. I have been staring at it and viewing youtube videos for the past ten minutes trying to figure this out.

This one is right:

Edit: different picture simplifying it

Basically: GPi/SNr is always INHIBITORY of the Thalamus. Direct path inhibits it, indirect lets it work.

 

[tiedyeddog]

Ask and ye shall receive, these are Pholston's lectures, and the antibiotics one is really good. It's not complete by any means, but it's extremely good and an excellent start...

http://forums.studentdoctor.net/showthread.php?t=994504

The other two were helpful for me as well!

you're a boss, thanks for this

 

[bangarang]

Ask and ye shall receive, these are Pholston's lectures, and the antibiotics one is really good. It's not complete by any means, but it's extremely good and an excellent start...

http://forums.studentdoctor.net/showthread.php?t=994504

The other two were helpful for me as well!

Thanks a lot, man.

yeah, I just figured this out. That diagram is wrong. I have been staring at it and viewing youtube videos for the past ten minutes trying to figure this out.

This one is right:

Edit: different picture simplifying it

Basically: GPi/SNr is always INHIBITORY of the Thalamus. Direct path inhibits it, indirect lets it work.

haha, I finally understand this pathway today. One quesiton: Where exactly are the D1 and D2 receptors? Dopamine is made in the SNc and the receptors are in the striatum, right?

So, the signals OUT of D2 receptor positive neurons in the striatum are negative right?

Signals OUT of D1 positive receptor neurons in the striatum are positive?

Ok, so related to this:

Parkinson's disease results in atrophy of the striatum and the subthalamic nucleus, this basically inhibits the indirect pathway causing disinhibitied movement. Why does this cause Parkin's symptoms too, if the striatum is affected?

Similarly, why doesn't Parkin's disease, which is death of the dopamine producing sunstantia niagra pars compacta, effect both the indirect and direct pathway??

I swear to God, I knew this stuff so well at the end of M1.... ugh.

Nice. I think I get it now. So going back to your questions, I think Parkinson's only involves the degeneration of the SNpc. I don't think the striatum or the STN is involved, so that might be the source of your confusion.

Going from that, if you get the loss of dopaminergic neurons in the SNpc, you get loss of the modulatory effects of dopamine on D1/D2 receptors in the putamen; SNpc to putamen serves to increase movement in both pathways, so if you lose that, then there is less movement or bradykinesia. I think the tremor or rigidity is due to a different pathway.

SNpc dopamine to D1 on putamen: excites the putamen in the direct pathway > increases movement. D1 = Gs (increased AC activity).
SNpc dopamine to D2 on putamen: inhibits the putamen in the indirect pathway > increases movement. D2 = Gi (decreased AC activity).

 

[tiedyeddog]

Thanks a lot, man.





Nice. I think I get it now. So going back to your questions, I think Parkinson's only involves the degeneration of the SNpc. I don't think the striatum or the STN is involved, so that might be the source of your confusion.

Going from that, if you get the loss of dopaminergic neurons in the SNpc, you get loss of the modulatory effects of dopamine on D1/D2 receptors in the putamen; SNpc to putamen serves to increase movement in both pathways, so if you lose that, then there is less movement or bradykinesia. I think the tremor or rigidity is due to a different pathway.

SNpc dopamine to D1 on putamen: excites the putamen in the direct pathway > increases movement. D1 = Gs (increased AC activity).
SNpc dopamine to D2 on putamen: inhibits the putamen in the indirect pathway > increases movement. D2 = Gi (decreased AC activity).

Wait, I think the purpose of the D2-indirect pathway is to inhibit motion.

I think I figured it out, if you lose dopamine the direct pathway is inhibited (no movement) and the indirect pathway is active. That would cause the rigidity found in parkinsons.

for huntington's, this explains it. it also explains why levodopa yields dyskinesia when treating parkinsons:

 

[dbeast]

Has anybody gotten any questions on streptogramins/pristins? First aid only mentions them tangentially but in lecture (as if that means anything) we were told they're going to be a big deal in the near future. I feel like the boards likes to throw in "newer" drugs like that.

 

[bangarang]

Wait, I think the purpose of the D2-indirect pathway is to inhibit motion.

I think I figured it out, if you lose dopamine the direct pathway is inhibited (no movement) and the indirect pathway is active. That would cause the rigidity found in parkinsons.

for huntington's, this explains it. it also explains why levodopa yields dyskinesia when treating parkinsons:

Haha. All right, I dusted off my Blumenfeld book to look into it. My explanation is for sure correct. I think you're making the same mistake I did in thinking that the direct/indirect pathways include the SNpc, but they don't. Think of the SNpc as something outside of the pathways that modulates those two pathways.

- The direct pathway refers to the cortex > striatum (putamen) > GPi/SNr > thalamus > cortical neurons.
- The indirect pathway refers to the cortex > striatum (putamen) > GPe > STN > GPi/SNr > thalamus > cortical neurons.
- The SNpc modulates the direct/indirect pathways via D1 and D2 receptors, exciting and inhibiting those pathways respectively, with the net result being increased movement. This is straight from Blumenfeld. For example, dopamine from the SNpc binds the D2 receptors in the putamen in the indirect pathway, which prevents the putamen from inhibiting the GPe, so the GPe inhibits the STN, which results in less activation of the GPi/SNr, which results in disinhibition of the thalamus and thus increased movement. The same end result is true for the direct pathway if you follow the SNpc's influence on it.
- The loss of the dopaminergic neurons in the SNpc results in the loss of the modulatory effects on the striatum/putamen, with the net result being loss of movement (bradykinesia). The rigidity that you're referring to is involved in a different pathway I think. Blumenfeld doesn't cover it in this chapter, but I think it has something to do with the reticular formation.

In Huntington's, you lose the indirect pathway (from the striatum being damaged), so you get less inhibition of the GPe, meaning the GPe will inhibit the STN, which results in less activation of the GPi/SNr, which results in disinhibition of the thalamus, and thus there is more movement.

 

[dbeast]

Those diagrams always confuse the crap out of me. I just remember a couple facts, and I haven't seen a single question that is more advanced than the following few sentences:

The direct pathway stimulates movement. It is tonically inactive until it gets a stimulatory signal for the cortex telling you to move. D1 (which is G-stimulatory) strengthens this signal. In Huntington's, you lose this tonic inhibition/GABA-ergic neurons. Dopamine is "upstream" from the degeneration so it has nothing to do with it. Also, B6 deficiency = no GABA synthesis, which leads to seizures via a similar pathway.

The indirect pathway strengthens the tonic inhibition of the direct pathway via glutamate coming from the subthalamic nucleus (it's the only glutamatergic part of the pathway). This is clinically important because you can lesion the STN to treat parkinsons. D2 (which is G-inhibitory) as you may guess inhibits this pathway, to also facilitate movement.

Parkinson's = you lose 2 pathways that facilitate movement.

 

[bangarang]

Those diagrams always confuse the crap out of me. I just remember a couple facts, and I haven't seen a single question that is more advanced than the following few sentences:

The direct pathway stimulates movement. It is tonically inactive until it gets a stimulatory signal for the cortex telling you to move. D1 (which is G-stimulatory) strengthens this signal. In Huntington's, you lose this tonic inhibition/GABA-ergic neurons. Dopamine is "upstream" from the degeneration so it has nothing to do with it. Also, B6 deficiency = no GABA synthesis, which leads to seizures via a similar pathway.

The indirect pathway strengthens the tonic inhibition of the direct pathway via glutamate coming from the subthalamic nucleus (it's the only glutamatergic part of the pathway). This is clinically important because you can lesion the STN to treat parkinsons. D2 (which is G-inhibitory) as you may guess inhibits this pathway, to also facilitate movement.

Parkinson's = you lose 2 pathways that facilitate movement.

Dude, yeah. You just completed the picture for me. Thanks!

 

[tiedyeddog]

Haha. All right, I dusted off my Blumenfeld book to look into it. My explanation is for sure correct. I think you're making the same mistake I did in thinking that the direct/indirect pathways include the SNpc, but they don't. Think of the SNpc as something outside of the pathways that modulates those two pathways.

- The direct pathway refers to the cortex > striatum (putamen) > GPi/SNr > thalamus > cortical neurons.
- The indirect pathway refers to the cortex > striatum (putamen) > GPe > STN > GPi/SNr > thalamus > cortical neurons.
- The SNpc modulates the direct/indirect pathways via D1 and D2 receptors, exciting and inhibiting those pathways respectively, with the net result being increased movement. This is straight from Blumenfeld. For example, dopamine from the SNpc binds the D2 receptors in the putamen in the indirect pathway, which prevents the putamen from inhibiting the GPe, so the GPe inhibits the STN, which results in less activation of the GPi/SNr, which results in disinhibition of the thalamus and thus increased movement. The same end result is true for the direct pathway if you follow the SNpc's influence on it.
- The loss of the dopaminergic neurons in the SNpc results in the loss of the modulatory effects on the striatum/putamen, with the net result being loss of movement (bradykinesia). The rigidity that you're referring to is involved in a different pathway I think. Blumenfeld doesn't cover it in this chapter, but I think it has something to do with the reticular formation.

In Huntington's, you lose the indirect pathway (from the striatum being damaged), so you get less inhibition of the GPe, meaning the GPe will inhibit the STN, which results in less activation of the GPi/SNr, which results in disinhibition of the thalamus, and thus there is more movement.

yup, you're right, I was thinking about the SPc being within the pathway so everytime I read the indirect pathway inhibited movement I thought D2 played a part in that.

Those diagrams always confuse the crap out of me. I just remember a couple facts, and I haven't seen a single question that is more advanced than the following few sentences:

The direct pathway stimulates movement. It is tonically inactive until it gets a stimulatory signal for the cortex telling you to move. D1 (which is G-stimulatory) strengthens this signal. In Huntington's, you lose this tonic inhibition/GABA-ergic neurons. Dopamine is "upstream" from the degeneration so it has nothing to do with it. Also, B6 deficiency = no GABA synthesis, which leads to seizures via a similar pathway.

The indirect pathway strengthens the tonic inhibition of the direct pathway via glutamate coming from the subthalamic nucleus (it's the only glutamatergic part of the pathway). This is clinically important because you can lesion the STN to treat parkinsons. D2 (which is G-inhibitory) as you may guess inhibits this pathway, to also facilitate movement.

Parkinson's = you lose 2 pathways that facilitate movement.

makes sense, thanks for the explanation guys, I really appreciate it! you guys are awesome, if we had bitcoins or the equivalent of reddit gold I would be giving them out like candies.

 

[Zzmed]

Guys, the thing about spermatogenesis (also in the scores thread, but I would like it to be here).

FA says: Spermatogonia 2N,2C 1o spermatocytes 2N,4C 2o spermatocytes 1N,2C Spermatids 1N,1C

Here is what I say and I don't know why we can't get along with FA in a so simple thing (actually I remember it from undergrad)

Spermatogonia 46,2N 1o spermatocytes 46,4N 2o spermatocytes 23,2N Spermatid 23,N

Is it a matter of nomenclature (C, N etc)?

 

[bangarang]

Has anybody gotten any questions on streptogramins/pristins? First aid only mentions them tangentially but in lecture (as if that means anything) we were told they're going to be a big deal in the near future. I feel like the boards likes to throw in "newer" drugs like that.

I have run into one or two questions, but I forgot from where. I just remember that they both inhibit the 50S ribosome, and that they are bacteriostatic individually and bactericidal when combined (quinupristin/dalfopristin). I've run into questions where they expected you to know that macrolides inhibit translocation and AGs inhibit the formation of the initiation complex, so I'm assuming those details are fair game for the streptogramins too.

 

[Zzmed]

EDIT: This thread is awesome, but it gets hard to follow.

 

[SLC]

Guys, the thing about spermatogenesis (also in the scores thread, but I would like it to be here).

FA says: Spermatogonia 2N,2C 1o spermatocytes 2N,4C 2o spermatocytes 1N,2C Spermatids 1N,1C

Here is what I say and I don't know why we can't get along with FA in a so simple thing (actually I remember it from undergrad)

Spermatogonia 46,2N 1o spermatocytes 46,4N 2o spermatocytes 23,2N Spermatid 23,N

Is it a matter of nomenclature (C, N etc)?

FA is wrong on this (2013 has it right, but previous versions had it wrong).

primary spermatocytes are 2N 4C, which means two sets of chromosomes (or 46 chromosomes) which all have sister chromatids. There are 2 sister chromatids for each of the two chromosomes making 4C (2 chromatids x 2 chromosomes).

To be 4N there would have to be 92 chromosomes in there, which never happens. N refers to the number of copies of each chromosome present in the cell.

The correct values:

Spermatogonia (germ cells): 2N 2C, they have two copies of each chromosome, each consisting of a single chromatid of just like every other cell in your body. They divide through mitosis just like every other cell too.

Primary spermatocyte: Generates sister chromatids to become 2N 4C, these cells undergo Meiosis 1 where the chromosomes are separated (but not the sister chromatids), so you end up with two cells (secondary spermatocytes)

Secondary spermatocyes, as mentioned above have had their chromosomes separated, but not their sister chromatids. So they are 1N (23 chromosomes) and 2C (each chromosome has two sister chromatids). These cells enter meiosis 2 where the sister chromatids are separated and become spermatids.

Spermatids, as mentioned above have had their sister chromatids separated so they are now 1N (23 chromosomes) and 1C (1 chromatid each). Spermatids then lose their cytoplasmic contents, gain an acrosome (which is made of modified Golgi complex) and middle piece (where the mitochondria are, and which doesn't enter the egg leading to the strictly maternal inheritence of mitochondrial disease), and a tail that is a modified centriole used as a flagella. Completion of these modifications make a spermatid into a mature spermatozoon.

Mature spermatazoon are 1N1C just like spermatids.

FA really bungled this one for a long time apparently. I have no idea why the whole 4N thing got by...there is never a time (that I'm aware of) where a human cell is ever 4N. That would be tetraploidy for every single chromosome in the entire cell.

Hope that helps.

 

[tiedyeddog]

FA is wrong on this (2013 has it right, but previous versions had it wrong).

primary spermatocytes are 2N 4C, which means two sets of chromosomes (or 46 chromosomes) which all have sister chromatids. There are 2 sister chromatids for each of the two chromosomes making 4C (2 chromatids x 2 chromosomes).

To be 4N there would have to be 92 chromosomes in there, which never happens. N refers to the number of copies of each chromosome present in the cell.

The correct values:

Spermatogonia (germ cells): 2N 2C, they have two copies of each chromosome, each consisting of a single chromatid of just like every other cell in your body. They divide through mitosis just like every other cell too.

Primary spermatocyte: Generates sister chromatids to become 2N 4C, these cells undergo Meiosis 1 where the chromosomes are separated (but not the sister chromatids), so you end up with two cells (secondary spermatocytes)

Secondary spermatocyes, as mentioned above have had their chromosomes separated, but not their sister chromatids. So they are 1N (23 chromosomes) and 2C (each chromosome has two sister chromatids). These cells enter meiosis 2 where the sister chromatids are separated and become spermatids.

Spermatids, as mentioned above have had their sister chromatids separated so they are now 1N (23 chromosomes) and 1C (1 chromatid each). Spermatids then lose their cytoplasmic contents, gain an acrosome (which is made of modified Golgi complex) and middle piece (where the mitochondria are, and which doesn't enter the egg leading to the strictly maternal inheritence of mitochondrial disease), and a tail that is a modified centriole used as a flagella. Completion of these modifications make a spermatid into a mature spermatozoon.

Mature spermatazoon are 1N1C just like spermatids.

FA really bungled this one for a long time apparently. I have no idea why the whole 4N thing got by...there is never a time (that I'm aware of) where a human cell is ever 4N. That would be tetraploidy for every single chromosome in the entire cell.

Hope that helps.

Great explanation here, I hope Jp sees it, he asked about this earlier.

 

[tiedyeddog]

I am going to make a spreadsheet with genetic disease with their chromosome mutations. Anyone interested in that?

 

[loveoforganic2]

The way I understood it was that a hormone with permissive effects only sensitizes the body to a response from a certain drug (via increased transcription of genes, upregulation of receptors, etc.), meaning it increases the body's response to a drug without having any effects itself, like thyroid hormone increasing the body's response to epinephrine by increasing the number of receptors. Thyroid hormone in and of itself doesn't act or bind the adrenergic receptors.

I think according to the definition of potentiation, two different drugs act on different aspects but produce the same response, so those two drugs would have an effect greater than the summation of each of those drugs alone. This is different than the permissive effect because the two different drugs can individually produce a response. I hope this makes sense. Someone correct me if I'm wrong.



Thanks, man. I haven't been able to find a good diagram for the pathway, and that's probably why I haven't learned it. I might try to look in Costanzo in a bit.

I was under the impression

potentiation = 2 + 0 = 4 (drug w/effect + drug w/no effect => increased drug effect)
synergism = 2 + 2 = 8 (drug w/effect + drug w/effect => greater than expected drug effect)
addition = 2 + 2 = 4 (drug w/effect + drug w/effect => expected combined drug efficacy)

Unless I'm mixing up definitions?

 

[223556]

EDIT: This thread is awesome, but it gets hard to follow.

Maybe a well controlled google doc would be better? Like if something of this thread is asked and answered (correctly), it could be incorporated into the doc.

 

[tiedyeddog]

Maybe a well controlled google doc would be better? Like if something of this thread is asked and answered (correctly), it could be incorporated into the doc.

This is a good idea

 

[bangarang]

I was under the impression

potentiation = 2 + 0 = 4 (drug w/effect + drug w/no effect => increased drug effect)
synergism = 2 + 2 = 8 (drug w/effect + drug w/effect => greater than expected drug effect)
addition = 2 + 2 = 4 (drug w/effect + drug w/effect => expected combined drug efficacy)

Unless I'm mixing up definitions?

No, I think you're right now that I looked it up. I think my confusion stems from the lack of clear definitions for each thing, with some people using potentiation to mean the same thing as synergism. This along with the whole 2N/4N ploidy thing (which I finally understand) really grinds my gears.

 

[tiedyeddog]

No, I think you're right now that I looked it up. I think my confusion stems from the lack of clear definitions for each thing, with some people using potentiation to mean the same thing as synergism. This along with the whole 2N/4N ploidy thing (which I finally understand) really grinds my gears.

 

[loveoforganic2]

No, I think you're right now that I looked it up. I think my confusion stems from the lack of clear definitions for each thing, with some people using potentiation to mean the same thing as synergism. This along with the whole 2N/4N ploidy thing (which I finally understand) really grinds my gears.

I'm saving reading that for a break... I have NEVER understood the 2n/4c etc. stuff - hoping that post clears it up

 

[Zzmed]

Maybe a well controlled google doc would be better? Like if something of this thread is asked and answered (correctly), it could be incorporated into the doc.

Totally

 

[Zzmed]

FA is wrong on this (2013 has it right, but previous versions had it wrong).

primary spermatocytes are 2N 4C, which means two sets of chromosomes (or 46 chromosomes) which all have sister chromatids. There are 2 sister chromatids for each of the two chromosomes making 4C (2 chromatids x 2 chromosomes).

To be 4N there would have to be 92 chromosomes in there, which never happens. N refers to the number of copies of each chromosome present in the cell.

The correct values:

Spermatogonia (germ cells): 2N 2C, they have two copies of each chromosome, each consisting of a single chromatid of just like every other cell in your body. They divide through mitosis just like every other cell too.

Primary spermatocyte: Generates sister chromatids to become 2N 4C, these cells undergo Meiosis 1 where the chromosomes are separated (but not the sister chromatids), so you end up with two cells (secondary spermatocytes)

Secondary spermatocyes, as mentioned above have had their chromosomes separated, but not their sister chromatids. So they are 1N (23 chromosomes) and 2C (each chromosome has two sister chromatids). These cells enter meiosis 2 where the sister chromatids are separated and become spermatids.

Spermatids, as mentioned above have had their sister chromatids separated so they are now 1N (23 chromosomes) and 1C (1 chromatid each). Spermatids then lose their cytoplasmic contents, gain an acrosome (which is made of modified Golgi complex) and middle piece (where the mitochondria are, and which doesn't enter the egg leading to the strictly maternal inheritence of mitochondrial disease), and a tail that is a modified centriole used as a flagella. Completion of these modifications make a spermatid into a mature spermatozoon.

Mature spermatazoon are 1N1C just like spermatids.

FA really bungled this one for a long time apparently. I have no idea why the whole 4N thing got by...there is never a time (that I'm aware of) where a human cell is ever 4N. That would be tetraploidy for every single chromosome in the entire cell.

Hope that helps.

Thanks man!

 

[bangarang]

I'm saving reading that for a break... I have NEVER understood the 2n/4c etc. stuff - hoping that post clears it up

If you don't understand after reading that post, then go here: http://www.auburn.edu/academic/classes/zy/vert_embryo/html/PloidyandMeiosis.html

That link really solidified my understanding of the whole thing (basically boils down to proper nomenclature). The picture that they have at the end is cash too. Ignore the weird background and horrible font color.

 

[SLC]

If you don't understand after reading that post, then go here: http://www.auburn.edu/academic/classes/zy/vert_embryo/html/PloidyandMeiosis.html

That link really solidified my understanding of the whole thing (basically boils down to proper nomenclature). The picture that they have at the end is cash too. Ignore the weird background and horrible font color.

Yeah, that site is pretty good. And it helped me realize that something I wrote in my post was technically incorrect. The term ploidy can be used to describe both the N and the C term.

When I said "4N can't exist because the cell would be tetraploid for all the chromosomes, which never happens" that was technically incorrect. Because when primary spermatocytes replicate their chromosomes and become 2N 4C they're technically tetraploid with respect to the C value.

It's a technicality, and doesn't matter with respect to the topic at hand. I simply wanted to point out that there is never a time where a cell is 4N.

In humans each "N" refers to the complete complement of each of the 23 chromosomes in the human genome. 2N=46 chromosomes (a maternal and paternal copy of each), while 4N would be 92 chromosomes.

________________________________________________________________________

So pop quiz then.

Can anyone tell me an example where a human cell that is not a gamete would be 1N and/or 1C in any way shape or form?

 

[tiedyeddog]

Yeah, that site is pretty good. And it helped me realize that something I wrote in my post was technically incorrect. The term ploidy can be used to describe both the N and the C term.

When I said "4N can't exist because the cell would be tetraploid for all the chromosomes, which never happens" that was technically incorrect. Because when primary spermatocytes replicate their chromosomes and become 2N 4C they're technically tetraploid with respect to the C value.

It's a technicality, and doesn't matter with respect to the topic at hand. I simply wanted to point out that there is never a time where a cell is 4N.

In humans each "N" refers to the complete complement of each of the 23 chromosomes in the human genome. 2N=46 chromosomes (a maternal and paternal copy of each), while 4N would be 92 chromosomes.

________________________________________________________________________

So pop quiz then.

Can anyone tell me an example where a human cell that is not a gamete would be 1N and/or 1C in any way shape or form?

Turner syndrome has a unisomy? I dunno. I don't think any live can be sustained from a uniplody and there are no other unisomies that I can think of.

 

[tiedyeddog]

Very stupid question, I know, but can children get shingles?

I myself have never had chicken pox, and neither has any of my brothers, so I am not familiar with it occuring in kids....

matter of fact, I have somehow never seen chickenpox in real life.

 

[dbeast]

I'm gonna take a wild guess that the regulars in this thread are gonna have really kick ass step scores when all is said and done.

 

[dbeast]

Very stupid question, I know, but can children get shingles?

I myself have never had chicken pox, and neither has any of my brothers, so I am not familiar with it occuring in kids....

matter of fact, I have somehow never seen chickenpox in real life.

I'd imagine yes, as long as they got chickenpox beforehand and then became immunocompromised, allowing the latent virus to get back out. This is why every shingles patient under a certain age gets an HIV test with it. If you're old, then your immunity is just weak and allows the virus to shingle you. Anybody know if you can get shingles after the chicken pox vaccine?

Buuuut this led me to another question, more out of curiosity. So they say 1/4 people is infected with HSV-1 or 2 but nearly all of them are asymptomatic. So... are there a bunch of elderly people, once their immune systems decline, with outbreaks of latent genital herpes? It makes sense scientifically, but I so want to believe it's not true.

 

[SLC]

Turner syndrome has a unisomy? I dunno. I don't think any live can be sustained from a uniplody and there are no other unisomies that I can think of.

Turners is exactly what I was thinking.

1N 1C with respect to the X chromosome. (1N2C from some point in interphase to metaphase [chromosome replication till separation at anaphase]).

You got it!

 

[SLC]

Very stupid question, I know, but can children get shingles?

I myself have never had chicken pox, and neither has any of my brothers, so I am not familiar with it occuring in kids....

matter of fact, I have somehow never seen chickenpox in real life.

I've actually had a question where a kid had shingles. Yes, they can.

What was tough was that it wasn't in the stereotypical intercostal nerve distribution, it was running down the C5 distribution on the lateral antebrachium. I was tempted not to pick it, but that's what it was.



All it takes to get shingles is a reactivation of latent VZV. If they've had chickenpox, then they've got a latent VZV infection and are technically susceptible to shingles.

Moral of the story, if it looks like shingles, it is shingles.

 

[tiedyeddog]

Buuuut this led me to another question, more out of curiosity. So they say 1/4 people is infected with HSV-1 or 2 but nearly all of them are asymptomatic. So... are there a bunch of elderly people, once their immune systems decline, with outbreaks of latent genital herpes? It makes sense scientifically, but I so want to believe it's not true.

haha, I don't even want to think about the answer to that.

 

[SLC]

Buuuut this led me to another question, more out of curiosity. So they say 1/4 people is infected with HSV-1 or 2 but nearly all of them are asymptomatic. So... are there a bunch of elderly people, once their immune systems decline, with outbreaks of latent genital herpes? It makes sense scientifically, but I so want to believe it's not true.

I actually once had a FM doc point out that STI's are on the rise in the elderly population since the advent of PDE-5 inhibitors.

It's been a while but he might have even said that they have the fastest increasing rate of all age groups...

 

[JP2740]

neermind

 

[MLT2MT2DO]

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

I'm having a hard time getting these to stick

 

[loveoforganic2]

In UW qid 1701, they mention portal v. thrombosis as a potential etiology of portal HTN. With this etiology, they say that ascites is typically NOT present due to a lack of hepatic sinusoidal HTN. My question is, what does sinusoidal HTN have to do with the development of ascites? My understanding of pathogenesis is portal HTN => Increased venous pressure in splanchnic vessels => Increased pressure gradient between peritoneal space and splanchnic vessels => Transudate

 

[dbeast]

In UW qid 1701, they mention portal v. thrombosis as a potential etiology of portal HTN. With this etiology, they say that ascites is typically NOT present due to a lack of hepatic sinusoidal HTN. My question is, what does sinusoidal HTN have to do with the development of ascites? My understanding of pathogenesis is portal HTN => Increased venous pressure in splanchnic vessels => Increased pressure gradient between peritoneal space and splanchnic vessels => Transudate

Good question... I'd imagine that the increased pressure is only half the problem. Sinusoidal HTN would cause hepatocyte damage and subsequent loss of albumin production = unfavorable oncotic gradient in addition to pressure gradient.

Source: My imagination. So I could be wrong.

 

[loveoforganic2]

Good question... I'd imagine that the increased pressure is only half the problem. Sinusoidal HTN would cause hepatocyte damage and subsequent loss of albumin production = unfavorable oncotic gradient in addition to pressure gradient.

Source: My imagination. So I could be wrong.

It's a logical explanation. Building on that use of imagination, if you have hepatic v. thrombosis, you're going to have all that crap I drew arrows for, but you're also selectively going to building up albumin within the circulatory system more quickly than in the peritoneal space (assuming there isn't vessel damage and you've got transudate). This would serve to retain the fluid within the vessels rather than becoming ascitic fluid.

BS explanations work great, thanks!

 

[Jonari]

Any good tips/suggestions for A-a gradient, and how to be able to differentiate spontaneous pneumothorax vs tension pneumothorax?

 

[bangarang]

In UW qid 1701, they mention portal v. thrombosis as a potential etiology of portal HTN. With this etiology, they say that ascites is typically NOT present due to a lack of hepatic sinusoidal HTN. My question is, what does sinusoidal HTN have to do with the development of ascites? My understanding of pathogenesis is portal HTN => Increased venous pressure in splanchnic vessels => Increased pressure gradient between peritoneal space and splanchnic vessels => Transudate

Good question... I'd imagine that the increased pressure is only half the problem. Sinusoidal HTN would cause hepatocyte damage and subsequent loss of albumin production = unfavorable oncotic gradient in addition to pressure gradient.

Source: My imagination. So I could be wrong.

It's a logical explanation. Building on that use of imagination, if you have hepatic v. thrombosis, you're going to have all that crap I drew arrows for, but you're also selectively going to building up albumin within the circulatory system more quickly than in the peritoneal space (assuming there isn't vessel damage and you've got transudate). This would serve to retain the fluid within the vessels rather than becoming ascitic fluid.

BS explanations work great, thanks!

http://books.google.com/books?id=KiFuMyJl0CUC&pg=PA66&lpg=PA66&dq=presinusoidal+ascites&source=bl&ots=YoGv6DJCzS&sig=YhhIPdJ02Dfi_ATGW3vOeJYh7DU&hl=en&sa=X&ei=H6WVUaajAZOK9gSGh4CYDg&ved=0CGcQ6AEwCQ#v=onepage&q=presinusoidal%20ascites&f=false

According to that link, the hepatic sinusoids don't have a basement membrane and are more permeable to proteins, so any increase in the sinusoidal hydrostatic pressure will easily increase lymph formation to the point of ascites. The splanchnic vessels are less permeable to protein, so they only produce lymph with low concentrations of protein. The link also offer counterpoints to that mechanism, so it's probably not well-defined.

 

[Pinkleton]

Any good tips/suggestions for A-a gradient, and how to be able to differentiate spontaneous pneumothorax vs tension pneumothorax?

Just think of tension pneumothorax as a stab wound that creates a flap that allows air to get in but not back out. So you'll have the trachea being pushed away from that side

And spontaneous pneumothorax happens when you have a rupture of a subpleural bleb. I like to think of this process as creating an air vacuum inside a closed cavity, "sucking" the trachea towards it

Now I have a question as well:

In regards to regulation of glycogenolysis, is the following basically how it works?

In order to turn on glycogenolysis, glucagon and epi have to first activate glycogen phosphorylase KINASE which then turns on glycogen phosphorylase. Whereas insulin shuts down this pathway by both inactivating glycogen phosphorylase directly and by inactivating glycogen phosphorylase kinase?

Just something to memorize?

 

[SLC]

Any good tips/suggestions for A-a gradient, and how to be able to differentiate spontaneous pneumothorax vs tension pneumothorax?

A-a gradient: You need to calculate the PAO2 and the formula for that is:

150-(PaCO2/0.8) MEMORIZE THIS

You should get a PaO2 from the stem.

From there it's just a matter of subtraction. Normally the gradient is 10-15 mmHg

 

[bangarang]

Any good tips/suggestions for A-a gradient, and how to be able to differentiate spontaneous pneumothorax vs tension pneumothorax?

Spontaneous pneumothorax: tracheal deviation towards the side of the lesion. Think: the lung is collapsed, so there is more space for the trachea to move towards.

Tension pneumothorax: tracheal deviation away from the lesion. Think: air gets trapped in the pleural space > increased pressure on the side of the lesion which pushes the trachea away.

Not sure about the A-a gradient. I gotta brush up on that. Good luck tomorrow, man.

 

[loveoforganic2]

http://books.google.com/books?id=KiFuMyJl0CUC&pg=PA66&lpg=PA66&dq=presinusoidal+ascites&source=bl&ots=YoGv6DJCzS&sig=YhhIPdJ02Dfi_ATGW3vOeJYh7DU&hl=en&sa=X&ei=H6WVUaajAZOK9gSGh4CYDg&ved=0CGcQ6AEwCQ#v=onepage&q=presinusoidal%20ascites&f=false

According to that link, the hepatic sinusoids don't have a basement membrane and are more permeable to proteins, so any increase in the sinusoidal hydrostatic pressure will easily increase lymph formation to the point of ascites. The splanchnic vessels are less permeable to protein, so they only produce lymph with low concentrations of protein. The link also offer counterpoints to that mechanism, so it's probably not well-defined.

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?

 

[loveoforganic2]

Now I have a question as well:

In regards to regulation of glycogenolysis, is the following basically how it works?

In order to turn on glycogenolysis, glucagon and epi have to first activate glycogen phosphorylase KINASE which then turns on glycogen phosphorylase. Whereas insulin shuts down this pathway by both inactivating glycogen phosphorylase directly and by inactivating glycogen phosphorylase kinase?

Just something to memorize?

I'm not sure about insulin directly shutting down glycogen phosphorylase, but the rest sounds like what I remember. In general, insulin => phosphatase activity, glucagon and stress hormones => kinase activity

 

[dbeast]

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.

 

[SLC]

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)