Neuro path ?

[usmleprep88]

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Hope you guys can help me out with this...

How exactly does diabetes cause CN3 palsy (diabetic third nerve palsy)? p.441 of first aid 2013 makes mention of it, but don't quite understand it. Details on the pathyphysio would be appreciated. Thanks!

 

[EazyE1907]

Hey. Cranial nerves are lined by schwaan cells. Schwaan cells are one of the the few cell types in the body (other examples include kidney, retina, lens) that lack the enzyme sorbitol dehydrogenase. This enzyme helps with the metabolism of sorbitol into fructose. Without the action of sorbitol dehydrogenase, sorbitol accumulates within peripheral nervous tissue causing an osmotic draw of water into the nerves. This damages the nerve conduction pathway and leads to peripheral neuropathy and cranial nerve dysfunction.

Hope that cleared things up.

 

[usmleprep88]

brilliant. thanks for the explanation! =]

not sure why First aid refers to a vascular etiology though..

"affected primarily by vascular disease (e.g., diabetes: glucose-->sorbitol) due to decreased diffusion of oxygen and nutrients to the interior fibers from compromised vasculature that resides on outside of nerve."

 

[EazyE1907]

No prob. Good luck with your studies!

 

[usmleprep88]

not sure why First aid refers to a vascular etiology though..

"affected primarily by vascular disease (e.g., diabetes: glucose-->sorbitol) due to decreased diffusion of oxygen and nutrients to the interior fibers from compromised vasculature that resides on outside of nerve."

 

[EazyE1907]

not sure why First aid refers to a vascular etiology though..

"affected primarily by vascular disease (e.g., diabetes: glucose-->sorbitol) due to decreased diffusion of oxygen and nutrients to the interior fibers from compromised vasculature that resides on outside of nerve."

Yup, i totally forgot about that.

So CN3 has both a motor and parasympathetic component and there are two ways in which you could have damage. The Motor component involves damage due to vessel ischemia from Diabetes. So same concept as above, sorbitol accumulation causes an osmotic draw of water into the vessel. The increase pressure in the vessel destroy's the endothelial lining creating a thrombus formation within the vessel. This impedes blood flow to the vessels causing ischemia to vessels supplying CN 3 nerve fibers.


The parasympathetic component is due to compression by a mass such as un uncal herniation from a pre-existing brain truama or tumor. So Something compressing the CN 3 parasympathetic fibers and causing dysfunction.

the important thing thing to take note here is that damage to the MOTOR component of cranial nerve 3 via diabetes causes ptosis and the down and out gaze, however pupil size and reactivity ARE NORMAL so you're pupillary light reflex will be intact.

However, damage to the parasympathetic component via herniation will give you BOTH a down and out gaze, ptosis AND a DIMINSHED pupillary light reflex.

this is somewhere in uworld.

hope that helped.

 

[usmleprep88]

thanks EasyE1907, that really cleared things up. there was another question I had regarding Wilsons dsz if you dont mind.
why is there a decrease in serum copper? i suppose its because there is a lack of copper incoporation into ceruloplasmin..so thus copper cant enter serum...but if this is true, how then does copper get deposited into other tissues (brain, eyes, etc)?

 

[EazyE1907]

No problem im glad i can help.

So with Wilson disease, the main problem is a mutation in the gene ATP7B. This gene codes for a protein (an ATPase: which would be an example of secondary active transport) that allows copper to be excreted into bile. ATP7B also allows copper to enter the serum bound to ceruloplasmin. So these two things 1)inability to excrete copper in bile and 2) inablity of copper to enter serum bound to ceruloplasmin, INCREASES copper serum levels. (Copper like iron and other transitional metals must be bound to protein when they are in serum) The copper then gets deposited into various organs leading to organ dysfunction.

important note, anytime you have accumulation of transitional metals(copper, iron. etc) in the serum that are not bound to protein, can cause hydroxyl free radical damage to the tissue via a process called fenton rxn. So besides the mechanism of copper deposition within tissues, copper unbound to protein also causes tissue damage via conversion to free radicals by the fenton rxn.

 

[usmleprep88]

if ATP7B gene is mutated, then copper can enter serum. so shouldn't there be a decrease in copper serum levels?

 

[EazyE1907]

No. the NORMAL gene codes for a protein that EXCRETES copper in bile, so it gets rid of copper. If that gene is mutated, copper CANNOT be excreted in bile, so it accumulates in blood.

Also, i would really really not recommend using FA 2013. It is known to have a gazilllion mistakes. I think 2015 version comes out pretty soon so i would def invest in a new FA, ASAP.

 

[usmleprep88]

sorry i meant to say that if the gene is mutated-->then copper CANNOT enter serum nor can it be excreted in bile-->thus accumulates in liver-->spill out of liver into blood?...but i thought copper couldn't enter serum unless its bound to ceruloplasmin.

i'll definitely be sure to get the 2015 edition when it comes out. thanks for the reminder

 

[EazyE1907]

sorry i meant to say that if the gene is mutated-->then copper CANNOT enter serum nor can it be excreted in bile-->thus accumulates in liver-->spill out of liver?...but i thought copper couldn't enter serum unless its bound to ceruloplasmin.

i'll definitely be sure to get the 2015 edition when it comes out. thanks for the reminder

i think you are missing the point here. the gene product has nothing to do with copper going into serum.It's with the excretion of copper. the thing is that copper CANNOT LEAVE. so if it can't leave where else does it go? serum!

 

[usmleprep88]

you mentioned earlier that: "ATP7B also allows copper to enter the serum bound to ceruloplasmin". so if this gene is mutated, then how does copper enter serum?

 

[EazyE1907]

Dude. copper still enters the blood.... ***just not bound to ceruloplasmin***.

 

[usmleprep88]

oh right, so we're talking about free serum copper here. makes sense. thanks again for the help

 

[usmleprep88]

Hey EazyE1907, can you help me out wit this one:

I'm very much confused about the pathophysiology behind parkinsons. Is it due to a loss in the balance b/w striatonigral (ACh) & nigrostriatal? From my understanding... striatum release ACh on substantia nigra, whereas substantia nigra releases dopamine on striatum. P.152 of kaplan pharm lecture notes shows a pic which shows a Dopaminergic neuron & a Cholinergic neuron both acting on a GABA-nergic neuron in striatum...but should not the cholinergic neuron be acting on substantia nigra..?

Thanks.

 

[EazyE1907]

Listen man. you are getting a little carried away, I can't even understand what you are saying. Keep the pathophysiology and pathology a little simple. And seriously DO NOT USE KAPLAN for pathology. HUGE MISTAKE. use pathoma and FA and read the uworld explanations for things you have trouble with in path. The Path in uworld is what makes uworld so popular for step 1 review. With that said.

Parkinsons is just a degeneration of the substania nigra pars compacta. This area of the brain produces Dopamine. Destruction to this area causes a decrease in dopamine. Dopamine is a neurotransmitter that functions in allowing movement. So decrease dopamine = decrease movement = all the symptoms of TRAPS. that is really it.

as for the dopaminergic pathways. Keep it simple. there are two pathways. the excitatory pathway and the inhibitory pathway. Dopamine binds to d1 receptors stimulating the the excitatory pathway = increase movement and dopamine also binds d2 receptors INHIBITING the inhibitory pathway = increase movement. all of this is straight out of first aid. so do yourself a favor and chunk kaplan ASAP.

Hey EazyE1907, can you help me out wit this one:

I'm very much confused about the pathophysiology behind parkinsons. Is it due to a loss in the balance b/w striatonigral (ACh) & nigrostriatal? From my understanding... striatum release ACh on substantia nigra, whereas substantia nigra releases dopamine on striatum. P.152 of kaplan pharm lecture notes shows a pic which shows a Dopaminergic neuron & a Cholinergic neuron both acting on a GABA-nergic neuron in striatum...but should not the cholinergic neuron be acting on substantia nigra..?

Thanks.

 

[usmleprep88]

Hey EasyE,

Do you mind helping me out with the following question:

Suppose that certain patients with breast cancer are found to have high serum concentrations of a particular compound that is at very low levels in normal individuals. A new blood test is developed for breast cancer screening based on this finding, and a study is performed to determine the correct upper limit of normal for the compound, with a test sensitivity of 80% (the test compared with mammography).
What can be done to reduce the probability of making a type II error in a similar study?

• A.
  Decrease the disease prevalence in the population studied
• B.
  Decrease the sensitivity of the test
• C.
  Increase the size of the population studied
• D.
  Increase the specificity of the test
• E.
  Increase the upper limit of the normal concentration range

Answer: c

Answer explanation: Type II error (B) is when no effect or difference is found when one exists. Increasing sample size, sensitivity, or P value threshold decreases B.

Why isn't the answer D? I don't quite understand how sensitivity, specificity, & p value relate to B.....