Step 1 Complicated Concepts Thread

[TheSeanieB]

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ASK AND ANSWER TOUGH QUESTIONS RELATED TO STEP 1.

Starting with me:
physiologic chloride shift - When CO2 diffuses into a RBC, it quickly converts with H2O to H+ and HCO3- so that CO2 will continue to passively diffuse into the RBC. The HCO3- is then excreted into the plasma by a Cl-/HCO3- exchanger. When the RBC enters the pulmonary capillaries, the process reverses. HCO3- is taken up by exchange for a Cl-. It combines with H+ to creates CO2 +H2O. The CO2 then diffuses out of the RBC and ultimately into the alveoli. This process allows for maximal CO2 excretion by a RBC.

 

[tiedyeddog]

i have in my notes that granuloma inguinale can cause elephantiasis, maybe that would be a distinguishing characteristic if they were to ask about it?

but i feel like an easier way to distinguish would be gram stain, right? i don't think chlamyidia would show on a gram stain.

or i guess you can use macconkey agar for klebsiella

yeah, lab tests would be the best way to go

 

[Jonari]

yeah, lab tests would be the best way to go

i wish there was a pdf of best screening test/confirmatory test choice list...to go with different pathologies...

you know...whats the gold standard treatment for epidural hematoma - CT scan
whats the screening test for TB - auromine rhodamine test..
etc
etc
etc

 

[dbeast]

i have in my notes that granuloma inguinale can cause elephantiasis, maybe that would be a distinguishing characteristic if they were to ask about it?

but i feel like an easier way to distinguish would be gram stain, right? i don't think chlamyidia would show on a gram stain.

or i guess you can use macconkey agar for klebsiella

Duh. Thank you!

 

[tiedyeddog]

i wish there was a pdf of best screening test/confirmatory test choice list...to go with different pathologies...

you know...whats the gold standard treatment for epidural hematoma - CT scan
whats the screening test for TB - auromine rhodamine test..
etc
etc
etc

Hmmm that would be useful, I'll make a google doc for it if I get bored here in the next week for so

 

[Pinkleton]

FA says that you have hyperpigmentation in Addison's disease because of increased ACTH. But what about for Cushing's disease or paraneoplastic syndrome, wouldn't you have skin darkening because of the increased ACTH? FA doesn't have it listed

 

[sharklasers]

I have it written in that you can get hyperpigmentation with all forms of cushing that increase ACTH!

 

[MLT2MT2DO]

I have it written in that you can get hyperpigmentation with all forms of cushing that increase ACTH!

Does this mean that the ectopic ACTH production is actually ectopic POMC production?

 

[Pinkleton]

Does this mean that the ectopic ACTH production is actually ectopic POMC production?

Good question. I was under the impression that POMC --> ACTH occurs only in pituitary cells. So I could see cushing's DISEASE having hyperpigmentation. But is ectopic ACTH cleaved from POMC as well? I guess that is asking if the paraneoplastic cells are actually corticotrophs

 

[sharklasers]

Good question. I was under the impression that POMC --> ACTH occurs only in pituitary cells. So I could see cushing's DISEASE having hyperpigmentation. But is ectopic ACTH cleaved from POMC as well? I guess that is asking if the paraneoplastic cells are actually corticotrophs

hmm never thought about it like that. just figured that even something like small cell lung cancer would need to make ACTH somehow, and figured the mechanism it would is the same.

i guess i don't know haha

 

[Jamiu22]

hmm never thought about it like that. just figured that even something like small cell lung cancer would need to make ACTH somehow, and figured the mechanism it would is the same.

i guess i don't know haha

• Cushing syndrome: You get hyperpigmentation
• Addison's Disease: You get hyperpigmentation
• Cushing's disease: No hyperpigmentation
• Small Cell Cancer: No hyperpigmentation
• Adrenocortical Cortisol releasing tumor: No hyperpigmentation...

For you to get the hyperpigmentation associated with cortisol production, the ACTH has to be produced from POMC...it's what's first produced, and then split into 3 products

• ACTH
• alpha-MSH
• beta-endorphins

The alpha-MSH would be what would cause the hyperpigmentation; if the higher concerntration of ACTH is not coming from the pituitary or POMC... you wouldn't get associated hyperpigmentation.

 

[MLT2MT2DO]

Couldn't find anything worthwhile through google except this previous SDN post, which explains it well enough. I think sometimes this site is > uptodate

http://forums.studentdoctor.net/showthread.php?t=715408

 

[tiedyeddog]

nvm, I got it

 

[MLT2MT2DO]

Can someone walk me through, "what exactly causes S3/S4". I've read confounding things on the internet. Additionally I'm finding conflicting things about what causes what, FA says Dilated cardiomyopathy is S3, I now find a reputable source that says it causes and S4.

I think I really just need to understand what's going on so I can figure out these types of questions instead of memorizing. Such as if S3 is due to increased atrial pressure, why is it seen in Dilated cardiomyopathy and not Hypertrophic cardiomyopathy...this seems counter intuitive to me

 

[loveoforganic2]

Can someone walk me through, "what exactly causes S3/S4". I've read confounding things on the internet. Additionally I'm finding conflicting things about what causes what, FA says Dilated cardiomyopathy is S3, I now find a reputable source that says it causes and S4.

I think I really just need to understand what's going on so I can figure out these types of questions instead of memorizing. Such as if S3 is due to increased atrial pressure, why is it seen in Dilated cardiomyopathy and not Hypertrophic cardiomyopathy...this seems counter intuitive to me

S3 = ventricular fluid overload (heard on early diastolic filling), S4 = ventricular noncompliance (heard on atrial kick)

That hasn't steered me wrong yet

 

[coolforschool]

S3 = ventricular fluid overload (heard on early diastolic filling), S4 = ventricular noncompliance (heard on atrial kick)

That hasn't steered me wrong yet

Also, S3 can be normal in patients under a certain age (I think 40 or 50), whereas S4 is always pathological.

This might not be entirely correct, but I imagine S3 to be caused by the AV cusps opening and blood rushing into the ventricles where there is still a lot of fluid (e.g., CHF, dilated cardiomyopathy, etc.), so it causes turbulence that makes a rushing sound in early diastole, kind of like a fish tank with the filter or something.

Like loveoforganic said: for S4, I think of the atrial kick in late diastole pushing against the ventricular walls, which, due to pressure overload, have hypertrophied and stiffened.

 

[MLT2MT2DO]

S3 = ventricular fluid overload (heard on early diastolic filling), S4 = ventricular noncompliance (heard on atrial kick)

That hasn't steered me wrong yet

Ok ty. If it hasn't steered you wrong I think I'll just keep it simple and stick to this.

 

[tiedyeddog]

Also, S3 can be normal in patients under a certain age (I think 40 or 50), whereas S4 is always pathological.

This might not be entirely correct, but I imagine S3 to be caused by the AV cusps opening and blood rushing into the ventricles where there is still a lot of fluid (e.g., CHF, dilated cardiomyopathy, etc.), so it causes turbulence that makes a rushing sound in early diastole, kind of like a fish tank with the filter or something.

Like loveoforganic said: for S4, I think of the atrial kick in late diastole pushing against the ventricular walls, which, due to pressure overload, have hypertrophied and stiffened.

yeah, S3 can be normal in teenagers who are athletic, kids(something to do with small heart compared to volume load, can't remember...), and in pregnancy (high volume load).

S4 is always pathologic as far as I know.

 

[Jamiu22]

S3 = ventricular fluid overload (heard on early diastolic filling), S4 = ventricular noncompliance (heard on atrial kick)

That hasn't steered me wrong yet

Great explanation.. Goljan explains this pretty well in his audio....and there's just one more thing I want to add...

• S3 as guys have said is seen in both the young (<32yrs) and those with dilated cardiomyopathy. Murmur occurs because one's trying to add fluid to a chamber that already has a lot of fluid in it - so you hear the murmur, especially during the rapid filling phase.
  .
  
• S4 on the other hand is heard because of an atrial kick through a thickened wall or septum....in this case, we just have to think of any pathology with a thickened wall
  .
  
• The extra caveat I wanted to point to was that in some instances of dilated heart, you do hear an S4 heart sound... depending on the etiology of the dilation, the heart can either be just dilated and the only murmur you hear would be S3, but when dilated & hypertrophied, then you get both S3 and S4 heart sounds...

.......

 

[Jamiu22]

One that has really baffled me is the urine osmolality in pre-renal azotemia.

Urinary excretion of Na is low, but yet the urine osmolality is high (>500).

How is that possible? other stuff besides sodium is being excreted? if so what is it, and is there a physiological reason for the excretion? thanks for the help... renal phys seems to be a weak area for me. 🙁

 

[addo]

One that has really baffled me is the urine osmolality in pre-renal azotemia.

Urinary excretion of Na is low, but yet the urine osmolality is high (>500).

How is that possible? other stuff besides sodium is being excreted? if so what is it, and is there a physiological reason for the excretion? thanks for the help... renal phys seems to be a weak area for me. 🙁

Urine is highly concentrated in pre renal azotemia as the kidney attempts to conserve as much water as possible. Reabsorb sodium and water will follow, and there is also ADH which will reabsorb free water. Theres all sort of waste excreted in urine and when it is all packed in a very small volume youll get a high osmolarity.

 

[Jamiu22]

Urine is highly concentrated in pre renal azotemia as the kidney attempts to conserve as much water as possible. Reabsorb sodium and water will follow, and there is also ADH which will reabsorb free water. Theres all sort of waste excreted in urine and when it is all packed in a very small volume youll get a high osmolarity.

haaa! that makes so much sense... it was so simple and I thought about it for weeks now and didn't see it, lol

...thanks man!!

 

[Pinkleton]

Squamous cell carcinoma can be associated with "chronic draining sinuses"

This may be stupid, but:
A) WTH is a a chronic draining sinus
B) How does that cause SCC

Google is definitely not helping on this one 😕

 

[Jamiu22]

Squamous cell carcinoma can be associated with "chronic draining sinuses"

This may be stupid, but:
A) WTH is a a chronic draining sinus
B) How does that cause SCC

Google is definitely not helping on this one 😕

A) WTH is a a chronic draining sinus
- typically I look at it as a non-healing ulcer. See link below for additional info.
- http://ezinearticles.com/?What-is-a-Sinus-Tract?---An-Insight-of-the-Sinus-Tract&id=1477052


B) How does that cause SCC
Since it's "chronic"... there's constant regeneration of cells around the sinus.... or chronic irritation... and anything that causes chronic irritation pretty much predisposes one to hyperplasia.... and "most" hyperplasia predisposes you to neoplasia... in this case SCC.. (note that one place hyperplasia doesn't predispose to cancer is BPH.. but most do.)

 

[tiedyeddog]

Got this statement from a UW explanation I don't understand:

how does repeated gonnococal infections lead to complement deficiencies, leading to an inability of the MAC to form?

 

[Pinkleton]

A) WTH is a a chronic draining sinus
- typically I look at it as a non-healing ulcer. See link below for additional info.
- http://ezinearticles.com/?What-is-a-Sinus-Tract?---An-Insight-of-the-Sinus-Tract&id=1477052


B) How does that cause SCC
Since it's "chronic"... there's constant regeneration of cells around the sinus.... or chronic irritation... and anything that causes chronic irritation pretty much predisposes one to hyperplasia.... and "most" hyperplasia predisposes you to neoplasia... in this case SCC.. (note that one place hyperplasia doesn't predispose to cancer is BPH.. but most do.)

Thanks a bunch, that is a great explanation. I'm baffled how I have not heard of this before!

Got this statement from a UW explanation I don't understand:

how does repeated gonnococal infections lead to complement deficiencies, leading to an inability of the MAC to form?

Hmm that is a good question. I know that complement deficiencies can cause repeated gonococcal infection, but haven't read it happening the other way around


One more question from my end guys...in 17-a-hydroxylase deficiency, I understand that you get a drop in adrenal steroids. But why does that cause pseudohermpahdroditism in boys? I thought that the source of steroids for males in the testes beginning in utero..

 

[coolforschool]

Got this statement from a UW explanation I don't understand:

how does repeated gonnococal infections lead to complement deficiencies, leading to an inability of the MAC to form?

Maybe you read that wrong. Complement deficiencies --> no MAC --> susceptibility to Neisseria because you can't punch holes in them. I've never heard of it being the other way around.

 

[Jamiu22]

👍

Maybe you read that wrong. Complement deficiencies --> no MAC --> susceptibility to Neisseria because you can't punch holes in them. I've never heard of it being the other way around.

 

[Jamiu22]

Thanks a bunch, that is a great explanation. I'm baffled how I have not heard of this before!



Hmm that is a good question. I know that complement deficiencies can cause repeated gonococcal infection, but haven't read it happening the other way around


One more question from my end guys...in 17-a-hydroxylase deficiency, I understand that you get a drop in adrenal steroids. But why does that cause pseudohermpahdroditism in boys? I thought that the source of steroids for males in the testes beginning in utero..

Both males and females get some of their androgens from the renal cortex (zona reticularis)... so a deficiency in 17-a-hydroxylase would get result in some sort of pathology... that's the way I look at it... it might not be 100% accurate though.

 

[tiedyeddog]

Thanks a bunch, that is a great explanation. I'm baffled how I have not heard of this before!



Hmm that is a good question. I know that complement deficiencies can cause repeated gonococcal infection, but haven't read it happening the other way around


One more question from my end guys...in 17-a-hydroxylase deficiency, I understand that you get a drop in adrenal steroids. But why does that cause pseudohermpahdroditism in boys? I thought that the source of steroids for males in the testes beginning in utero..

Maybe you read that wrong. Complement deficiencies --> no MAC --> susceptibility to Neisseria because you can't punch holes in them. I've never heard of it being the other way around.

you guys are right, I read it wrong.

ok, another possibly dumb question. what is the difference between the perianal fistulas seens in crohns and the "rectal involvement" ALWAYS seen with ulcerative colitis?

 

[coolforschool]

One more question from my end guys...in 17-a-hydroxylase deficiency, I understand that you get a drop in adrenal steroids. But why does that cause pseudohermpahdroditism in boys? I thought that the source of steroids for males in the testes beginning in utero..

Both males and females get some of their androgens from the renal cortex (zona reticularis)... so a deficiency in 17-a-hydroxylase would get result in some sort of pathology... that's the way I look at it... it might not be 100% accurate though.

I looked into it. Apparently, the same 17-alpha-hydroxylase enzyme is present in both the adrenal cortex and the gonads, or at least the same gene codes for both of them; mutations in that gene will produce varying levels of deficiency in the enzyme. I think something like 10-15% of testosterone is made from the adrenals, but still, if you get a mutation that also affects the enzyme in the gonads, then you might get pseudohermaphroditism.

Under the paragraph about the P450c17 mutations: http://emedicine.medscape.com/article/920532-overview#a0104

It's one line in the third paragraph under "Pathophysiology," but it's there: http://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_17_alpha-hydroxylase_deficiency

 

[Pinkleton]

I looked into it. Apparently, the same 17-alpha-hydroxylase enzyme is present in both the adrenal cortex and the gonads, or at least the same gene codes for both of them; mutations in that gene will produce varying levels of deficiency in the enzyme. I think something like 10-15% of testosterone is made from the adrenals, but still, if you get a mutation that also affects the enzyme in the gonads, then you might get pseudohermaphroditism.

Under the paragraph about the P450c17 mutations: http://emedicine.medscape.com/article/920532-overview#a0104

It's one line in the third paragraph under "Pathophysiology," but it's there: http://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_17_alpha-hydroxylase_deficiency

Dang, good call. Totally missed that connection. Costanzo doesnt' even mention that

 

[Jamiu22]

I looked into it. Apparently, the same 17-alpha-hydroxylase enzyme is present in both the adrenal cortex and the gonads, or at least the same gene codes for both of them; mutations in that gene will produce varying levels of deficiency in the enzyme. I think something like 10-15% of testosterone is made from the adrenals, but still, if you get a mutation that also affects the enzyme in the gonads, then you might get pseudohermaphroditism.

Under the paragraph about the P450c17 mutations: http://emedicine.medscape.com/article/920532-overview#a0104

It's one line in the third paragraph under "Pathophysiology," but it's there: http://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_17_alpha-hydroxylase_deficiency

cool thanks... I didn't think about that!

 

[Akarat]

One more question from my end guys...in 17-a-hydroxylase deficiency, I understand that you get a drop in adrenal steroids. But why does that cause pseudohermpahdroditism in boys? I thought that the source of steroids for males in the testes beginning in utero..

Lack of 17-a-hydroxylase causes pseudohermaphroditism in boys due to the lack of dihydrotestosterone which is derived from testosterone, and which is itself deficient with the lack of 17-a-hydroxylase.

No link, but this is from Greenspan's Basic and Clinical Endocrinology, 9e
Note: T = Testosterone

Differentiation of the external genitalia along male lines depends on the action of DHT, the 5-reduced metabolite of T. In the male fetus, T is secreted by the Leydig cells, autonomously at first and later under the influence of human chorionic gonadotropin (hCG), and later fetal pituitary luteinizing hormone (LH). Masculinization of the external genitalia and urogenital sinus of the fetus results from the action of DHT, which is synthesized from T in the target cells by the enzyme 5[a]-reductase-2 as well as possibly secreted by the testes via the backdoor pathway (Figure 14–10). This pathway was first found in marsipials and then implicated in patients with P450 oxidoreductase (POR) deficiency. This backdoor pathway synthesizes DHT, a nonaromatized androgen, without utilizing T as a precursor. This pathway may play a signifcant role in male differentiation; however, further studies are necessary to define this.

Incomplete masculinization of the male fetus results from (1) impairment in the synthesis or secretion of fetal T and/or DHT (3-HSD-3 deficiency) or the conversion of T to DHT (5[a]-reductase-2 deficiency, (2) deficient or defective androgen receptor activity, or (3) defective production and local action of AMH.

 

[step1april2013]

Someone please explain to me the pathogenesis of chronic transplant rejection

 

[coolforschool]

Lack of 17-a-hydroxylase causes pseudohermaphroditism in boys due to the lack of dihydrotestosterone which is derived from testosterone, and which is itself deficient with the lack of 17-a-hydroxylase.

No link, but this is from Greenspan's Basic and Clinical Endocrinology, 9e
Note: T = Testosterone

Yep, this is pretty important to know and I failed to mention it. DHT --> differentiation of external genitalia. Lack of 5-alpha reductase can also cause pseudohermaphroditism (has lots of causes, actually).

 

[MLT2MT2DO]

Why do you not have an increased bleeding time with an OD of Warfarin?

Additionally, how is it you have bleeding issues with a normal bleeding time? I feel there's some sort of clotting physiology that I'm missing.

 

[coolforschool]

Why do you not have an increased bleeding time with an OD of Warfarin?

Additionally, how is it you have bleeding issues with a normal bleeding time? I feel there's some sort of clotting physiology that I'm missing.

Bleeding time = platelet disorder (independent of coagulation factors).
PT/PTT elevation = coagulation factor disorder (independent of platelets).

Think of platelets as the early response, and coagulation as the delayed response to bleeding. Pretty important concept!

To clarify, it's kind of like platelets are the EMTs, and they can show up to stop the bleeding, but the coagulation factors are the doctors who eventually fix the problem. The platelets can form a clot, but if it's a more serious bleed then they're going to need the coagulation cascade to maintain the clot and stop the bleeding.

 

[Jonari]

Why do you not have an increased bleeding time with an OD of Warfarin?

Additionally, how is it you have bleeding issues with a normal bleeding time? I feel there's some sort of clotting physiology that I'm missing.

Bleeding time = platelet disorder (independent of coagulation factors).
PT/PTT elevation = coagulation factor disorder (independent of platelets).

Think of platelets as the early response, and coagulation as the delayed response to bleeding. Pretty important concept!

To clarify, it's kind of like platelets are the EMTs, and they can show up to stop the bleeding, but the coagulation factors are the doctors who eventually fix the problem. The platelets can form a clot, but if it's a more serious bleed then they're going to need the coagulation cascade to maintain the clot and stop the bleeding.

Yeah, but that doesn't answer his question, warfarin, an epoxide reductase inhibitor shouldn't affect bleeding time, since it has no effect on the platelets. It would only affect PT and PTT values.

Examples where bleeding times are normal, and you're still having bleeding issues can occur with Heparin od, warfarin od, aspirin intake, bernard-soulier, glanzmann's, uremia, hemophilia a, hemophilia b

 

[coolforschool]

Yeah, but that doesn't answer his question, warfarin, an epoxide reductase inhibitor shouldn't affect bleeding time, since it has no effect on the platelets. It would only affect PT and PTT values.

Examples where bleeding times are normal, and you're still having bleeding issues can occur with Heparin od, warfarin od, aspirin intake, bernard-soulier, glanzmann's, uremia, hemophilia a, hemophilia b

It was answered indirectly. I assumed he knew that Warfarin affected the vitK-dependent coagulation factors, which has nothing to do with platelets and bleeding time as explained further down in my comment.

 

[Pinkleton]

***NBME 3 spoiler***

This question really annoyed me....



Which of the following is the rationale for advising a decrease in dietary intake of NaCl in patients with hepatic disease who develop edema?
a. Edema fluid has a high concentration of Cl
b.Glomerular filtration rate is increased
c. Injured hepatocytes are more permeable to Na
d. Secondary hyperaldosteronism is present
e. serum globulin concentration is increased


Why is the answer D? I figured that with liver disease you have impaired production of angiotensinogen. So how could you have hyperaldosteronism? I put B, thinking that a loss of albumin would cause an increase GFR would affect the macula densa somehow and related that to NaCl

 

[Jonari]

It was answered indirectly. I assumed he knew that Warfarin affected the vitK-dependent coagulation factors, which has nothing to do with platelets and bleeding time as explained further down in my comment.

Pathoma does an awesome job with that chapter. One of the few topics of the questions I always get right. Have friends that still confuse Hemo-A vs vWDisease...

 

[MLT2MT2DO]

It was answered indirectly. I assumed he knew that Warfarin affected the vitK-dependent coagulation factors, which has nothing to do with platelets and bleeding time as explained further down in my comment.

Ok your original explanation was way too simplified and I know all of that, but thank you for the effort. (seriously, not being sarcastic)

So why is there excessive bleeding when someone ODs on anticoagulant yet there is no difference in "bleeding time".

The reason I ask this is I had a vignette on a question where the lady had Warfarin + a 450 inhibitor. She gets a papercut and can't stop bleeding, yet her bleeding time is normal. Now having done bleeding times on patients I know if you bleed excessively from a paper cut you're going to bleed more from the lancet with a bleeding time but clearly that's not what the USMLE wants

 

[Jonari]

***NBME 3 spoiler***

This question really annoyed me....



Which of the following is the rationale for advising a decrease in dietary intake of NaCl in patients with hepatic disease who develop edema?
a. Edema fluid has a high concentration of Cl
b.Glomerular filtration rate is increased
c. Injured hepatocytes are more permeable to Na
d. Secondary hyperaldosteronism is present
e. serum globulin concentration is increased


Why is the answer D? I figured that with liver disease you have impaired production of angiotensinogen. So how could you have hyperaldosteronism? I put B, thinking that a loss of albumin would cause an increase GFR would affect the macula densa somehow and related that to NaCl

You're really close on tying the pieces together....hepatic disease causes a decrease in albumin synthesis, the main protein in our body that maintains our oncotic pressure in our vessels. John Doe here has some liver disease, and he's not making enough albumin to keep the fluid in the vessels, and is leaking out - hence his edema.

Now fill out the rest of the scenario as to why you think NaCl would cause a problem...

 

[Jonari]

Ok your original explanation was way too simplified and I know all of that, but thank you for the effort. (seriously, not being sarcastic)

So why is there excessive bleeding when someone ODs on anticoagulant yet there is no difference in "bleeding time"

warfarin inhibits epoxide reductase...an enzyme needed to gamma-carboxylate factors 2, 7, 9, 10, protein c, and protein S.

these factors are completely independent and not needed for a platelet clot to form, hence why bleeding time is normal.

compare this to aspirin, which irreversible inhibits platelet cyclo-oxygenase (cox). this inhibits txa2 and inhibits platelet aggregation. this inhibition is completely independent and not needed for the clotting factors to form a fibrin clot.

make sense?

 

[Pinkleton]

You're really close on tying the pieces together....hepatic disease causes a decrease in albumin synthesis, the main protein in our body that maintains our oncotic pressure in our vessels. John Doe here has some liver disease, and he's not making enough albumin to keep the fluid in the vessels, and is leaking out - hence his edema.

Now fill out the rest of the scenario as to why you think NaCl would cause a problem...

I get that the loss of albumin and body water is causing renin release, but figured that liver dz would lower angiotensinogen and not result in a rise in aldosterone...I guess that is not the case

P.S...dude you need to change your avatar lol. It is distracting the hell out of me

 

[MLT2MT2DO]

warfarin inhibits epoxide reductase...an enzyme needed to gamma-carboxylate factors 2, 7, 9, 10, protein c, and protein S.

these factors are completely independent and not needed for a platelet clot to form, hence why bleeding time is normal.

compare this to aspirin, which irreversible inhibits platelet cyclo-oxygenase (cox). this inhibits txa2 and inhibits protein aggregation. this inhibition is completely independent and not needed for the clotting factors to form a fibrin clot.

make sense?

Again, know all this. So why the excessive bleeding then? But not increased bleeding time.

 

[Jonari]

Again, know all this. So why the excessive bleeding then?

😕 there's nothing really else to explain. that's basically why you see excessive bleeding....with normal bleeding time

 

[Pinkleton]

Again, know all this. So why the excessive bleeding then? But not increased bleeding time.

My understanding is that you bleed more frequently, but each bleeding occurrence lasts a normal amount of time

 

[MLT2MT2DO]

My understanding is that you bleed more frequently, but each bleeding occurrence lasts a normal amount of time

Ok that makes sense. I'm pretty sure the question using a paper cut was a horrible example, but it got me thinking. Thank you.

 

[Jamiu22]

Ok your original explanation was way too simplified and I know all of that, but thank you for the effort. (seriously, not being sarcastic)

So why is there excessive bleeding when someone ODs on anticoagulant yet there is no difference in "bleeding time".

The reason I ask this is I had a vignette on a question where the lady had Warfarin + a 450 inhibitor. She gets a papercut and can't stop bleeding, yet her bleeding time is normal. Now having done bleeding times on patients I know if you bleed excessively from a paper cut you're going to bleed more from the lancet with a bleeding time but clearly that's not what the USMLE wants

I had the same confusion earlier... and everything Jonari said is accurate, let me at least take a stab at it from another perspective....

Whenever you bleed, the process to stop the wound bleed and healing occurs in two different steps...

the first step is a temporary hemostatic plug...which is strictly done by platelet aggregation. All this does is to put something on that wound to stop the bleeding - this is the bleeding time and note that we haven't talked about the coagulation cascade in this process. this temporary plug is not strong so a light touch on the wound would cause it to rebleed.

the second step in healing the wound is coagulation.... and in this step all the coagulation cascade is activated to eventually deposit more fibrin on temporary plug to make them stronger... this usually occurs much later and since the bleeding was already controlled, you can't measure this with bleeding time (that part was taking care off by platelets) - tis why the only way you can test for coagulation factor deficiency is PT or PTT (depending on which factor you think is deficient)...

Now, when you think of bleeding time... the would is usually small and the temp plug could do the job... but if the wound is a lot bigger, it makes it really hard for the platelets to stop bleeding.. folks with factor VIII deficiency (hemophilia) have bleeding issues mainly because once they get a cut, depending on how large the wound is - the temp plug may not be sufficient especially for this folks... this is same thing with warfarin overdose... they will bleed a lot more than regular folks with an injury... reason why surgery on hemophiliac's a lot more complicated.

Another perl
1. Platelet issue - superficial bleeds
2. Coagulation factor issue - Rebleeding issue; or bleeding into joints (hemarthrosis) from mechanical wear and tear and lack of factors..


I know that was verbose...and you may already know that, lol....but just in case it helps.