Interesting Medical Tidbits

[Sela]

If you block alpha first, you'll get vasodilation and reduced heart rate, which will lead to reflex tach. . . except with pheo you've already got that reflex tach effect. . . okay, nevermind; that cna't be the mechanism, nm. I'll just wait to see what they tell us next week ! We've started ICM/Path Renal.

[Sela]

Okay - what about this. Say you give the beta blocker first to your pheo patient. This will cause decreased heart rate, and decreased force of contraction right? But the body is still making all that Epinephrine and Adrenaline thanks to the pheochromocytoma. So we'll still have all the alpha1 action and vasoconstriction. In other words: massively increased systemic vascular resistance to blood flow, but way decreased ability for the heart to pump against it - risking cardiogenic shock.

Though that doesn't explain why you can't give them together.

[Broomstick]

I don't really have anything to add here that's factual, but I find this thread compelling reading. Please do continue it.

[mr friendly guy]

Okay - what about this. Say you give the beta blocker first to your pheo patient. This will cause decreased heart rate, and decreased force of contraction right? But the body is still making all that Epinephrine and Adrenaline thanks to the pheochromocytoma. So we'll still have all the alpha1 action and vasoconstriction. In other words: massively increased systemic vascular resistance to blood flow, but way decreased ability for the heart to pump against it - risking cardiogenic shock.

Though that doesn't explain why you can't give them together.

We do give them together.. eventually. I guess to be on the safe side we start with alpha blockers then later add beta blockers.

[Sela]

@mr friendly guy: Neat stuff .
@Broomstick: Thanks! Always great to know someone's enjoying it.

Here's one for today that I found kinda nifty - it's actually two separate paths for the disorder, so I'm throwing them both in:

Diabetes Insipidus: Central & Nephrogenic
Short 'n Sweet: Disruption in proper function of the body's water-regulatory pathway resulting in excessive urination.

Background Anat&Physio:
Sodium ion (Na+) is an extraordinarily important ion for human beings. Many cell functions rely on an electro-chemical gradient (like an osmotic gradient, but based on ion-charges [Na+,K+,Ca2+, etc.]across the membrane). The concentration of sodium outside the cell in the water part of the bloodstream (or 'plasma') is the major ion for maintaining the gradient and as such the plasma concentration of Na (P[Na]) must be strictly maintained.

In the brain, there are sensors that detect changes in P[Na] and then try to regulate it. As you all know, concentration = solute/solvent. So for the body to change its P[Na], it must change the amount of water (solvent) in the bloodstream! If P[Na] is too high (like after eating potato chips), then we need to take in more water to go back to normal. At this point the brain reacts by making you thirsty, and also by cutting secretion of a critical hormone: Anti-Diuretic Hormone (ADH). "Diuretic" literally just means something that makes you urinate more, so ADH makes you urinate less. The ADH gets secreted from the brain, then circulates through the blood all the way to the kidneys. Here it binds at its receptor (the ADH-receptor) and causes Aquaporins (literally: 'water holes') to appear in the kidney tubules. When our kidneys filter out water to pee, these aquaporins at the end will reabsorb that water back into the blood stream so that your body retains it. This keeps P[Na] from growing any higher - remember: solute/solvent, so water-up, means P[Na] down, until eventually it gets back to normal.

ADH is very good at what it does. At normal P[Na], when there's no need to conserve water, or to get rid of it, the body still needs to urinate out sodium and other ions for other reasons. The concentration of our urine is determined by how much water we end up excreting to dilute those ions. With very high ADH, we can have up to 1200 mOsm of solute per Liter of water, conversely, with minimal to no ADH, our urine can be so dilute that we have 50mOsm/L (300 is normal). And thus, in general, the body's control of water balance is *very* effective.


What goes wrong?:

So now let's break our happy little system . Diabetes is a term that means "increase in urination" - this includes Diabetes Mellitus (glucose issues, the one we all know). In Diabetes Insipidus, there's a problem with the ADH-pathway. If the problem is that the hormone cannot be secreted from the brain (central nervous system) it is termed "Central Diabetes Insipidus". On the other hand, if the ADH-receptors no longer function properly - either due to toxic damage or genetic problems - it is termed Nephrogenic Diabetes Insipidus (or 'kidney-generated' DI).

So now let's see what happens. Our patient is happy with a normal P[Na] of 140. In central DI, the brain senses this and says "all's well in the neighborhood" and tries to put out a normal level of ADH to maintain it; but it can't excrete the ADH. In nephrogenic DI, the brain does secrete this basal-level of ADH, but when it gets to the kidney, it can't bind the ADH-receptor to do its job. The kidney, of course, can only interpret this lack of ADH action as the body purposefully withholding ADH, as it would do if the P[Na] was too low and needed to be increased. So at once the kidney obliges by secreting *MAXIMALLY DILUTED*, quickly concentrating the sodium in the bloodstream, and bringing the P[Na] up!

Now our P[Na] is high - say 150! The brain sees this and freaks out - quick, make more ADH! Bind that receptor, let out the aquaporins! But the body doesn't respond, and P[Na] goes higher and higher. . . .


Why it's cool:
Remember how I said there were *two* things the body did to respond to an increase in P[Na]? The automatic one is to make sure it doesn't get much worse with ADH. . . but eventually we'll need more water to dilute the extra sodium. So the brain makes you feel thirsty. It's an interesting fact about thirst actually, the impulse of thirst is so strong, that -given a functioning impulse and access to water- no healthy mammal will ever accidentally suffer from P[Na] elevation due to poor diet. It can even wake you from your sleep .
Well our diabetes mellitus patient doesn't have the ability to stop losing water, thus increasing his P[Na], but he *does* have intact thirst, and the ability to decrease his P[Na] by water intake. Thus patients with this condition will frequently be exceedingly thirsty and find themselves forced to keep drinking water all the time! An average person excretes about 600mOsm/day, and this maximally-diluted urine is, say, 50mOsm/L; so our patient is peeing out 12Liters of water a day. Twelve liters that she intensely needs - and is mentally compelled- to replace by drinking that much back. She's got to drink 12L of water a day.

Then there's the other factor - the volume. Sure, she's unable to concentrate her urine and so thorughout the day she's gonna drink and pee 12L. But think about it - we can't exactly pee 3 liters at a time here - a bladder can only hold so much ! Though there's a lot of variation between men and women and individual to individual, the urge to urinate typically starts at around 200mL. . . and is impossible to mentally override /control at 600mL. BTW, these numbers are generous. So say she holds it till about 400mL every time, this means 12000/400=30 trips to the bathroom every day!

Treatment:
The first step is kinda cool - you've got to figure out whether the problem is in her head or in her kidneys. The simplest way (and one commonly done) is to give an artificial version of ADH (called DDAVP). If the receptors are healthy and functioning, we should see a more concentrated urine instead of the abnormally dilute kind. If not, then we can conclude that ADH is present, but not working.
If it's central, then the patient continues taking synthetic ADH; though it's important not to take too much, as unlike the brain's sensors, our patient has no way to instantly tell their P[Na] and regulate it with more or less water. As a rule, less is better than more. If it's nephrogenic, then quite honestly I'm not sure what the treatment is even if it's there at all.
Its important to realize that. No matter how infuriating or frustrating it doubtlessly is to the patient, there are much worse things in life and in kidney-disease than having to go to the bathroom every hour and drink a ton of water.


That's probably the coolest thing about this disease: in terms of ion-balance, heart function, toxin removal, blood pressure, and all the other super-important body-physiology things, your just fine. But if you find yourself without water for an hour, and suddenly get a large increase in salt/potassium/chloride/electrolytes, then god help you.

[mr friendly guy]

Since we are going with the electrolyte inbalance & endocrine diseases, I will suggest Addison's disease.

JFK had it, and its rumoured Osama Bin Laden has it (how he supposedly survived for so long without medical treatment is another matter entirely). This can become rapidly fatal. In my state of Western Australia (in the rural area) a few years ago there was a death related to Addison's disease where a patient had been investigated incessantly but the doctors didn't think of Addison's. Its easy in hindsight to say it.

Last year I saw an Addison's and I learnt something from it. If you suspect it, treat the disease first and ask questions later, rather than treat the electrolyte disturbance and wait for the test to come back. Those few hours could make a difference. Needless to say I did the latter and waited for my test to come back (the next day), but fortunately no adverse outcome occurred. Considering what happen in the rural area and the Emergency consultant didn't think Addison's likely when I suggested it, it just goes to show how hard it is to pick up without hindsight.

What is it?

A lack of steroid hormones produced by the adrenals. Of particular note are the two classes of steroids, the glucocorticoids and the mineralocorticoids. Various things can cause the adrenals to malfunction, eg autoimmune, infection etc. Fun fact. Your body registers these lack of steroid hormones and tries secreting more "messenger" hormones to the adrenals to produce more. In particular the hormone ACTH (which is actually used in some new tanning products). Basically ACTH has a similar structure to the hormone which stimulates melanin production. What's melanin? Why ask Michael Jackson. Its what gives the pigmentation in skin colour.

So in people who have struggled with Addison's for a few weeks without diagnosis, there skin gradually darkens. No a white man won't suddenly become a black man, and the level of pigmentation isn't unexpected in a sunny country like Australia. However, say put them next to a photograph of themselves a year ago, the difference is there. The other thing with this is, that the pigmentation can occur in areas where it normally doesn't, for example in the mouth you will see black patches and also in the creases of your palm.

Why is it serious?

Low blood pressure from the lack of water retention because you have a lack of aldosterone (one of the mineralocorticoids), and glucocorticoids. Low sodium isn't good either. High potassium leads to cardiac arrthymias and death. Renal failure to boot as you become dehydrated because you don't retain salt (and by extension water) due to lack of aldosterone.

Treatment?
Initially just give glucocorticoid. For those who actually have read this, you might wonder why we don't give mineralocorticoid initially as well. Well we do eventually give them. Its just that glucocorticoids can have similar function to mineralocorticoids because the receptors are similar shape.

In fact IIRC glucocorticoids have more activity on the mineralocorticoid receptor than mineralocorticoids. Its just that the body produces an enzyme which inactives glucocorticoids. So much for an intelligent designer. A smart designer will simply have the hormones serving the glucocorticoid and mineralocorticoid be so different structurally that they can't set off each others receptors, without having to resort to an enzyme to correct the "design flaw."

Anyway, the treatment doses of glucocorticoid can overwhelm this enzyme so it activates both the glucocorticoid and mineralocorticoid receptors. Eventually once they are stabilise we switch them over to lower dose glucocorticoids and mineralocorticoid. Now you might be asking, why we don't just continue the glucocorticoid, after all less tablets to take right? Well prolong use of steroids (especially high doses ones) can have nasty side effects. Among them osteoporosis, thin skin, fatty deposition (buffalo hump anyone?), easy bruising and a whole host of others.

[Broomstick]

You didn't mention increased risk of cataracts with high and/or prolonged steroid use. Fortunately, it's relatively easy to treat those these days, but going blind as a side effect is something patients take rather seriously, even when it's reversible.

Cataracts are funny in that the older you are the easier they are to remove. In someone 70 it's become very routine these days and the patient goes home the same day. That's because in old folks the clouded lens is stiff and sort of pops right out, in the young it's more flexible and more difficult to remove. This is the opposite of how things normally work, where it's easier to do surgery on the young than the old. For people with poor eyesight due to refraction errors modern artificial lenses that can be inserted in place of the cataract means that post-surgery they might need a lower eyeglass/contact prescription than before the surgery. There has been speculation that this could one day replace LASIK type surgical correction, except for the part about the surgery being more difficult in the young - who wants to wait until 70 to get your eyesight corrected? Yet another thing - artificial lenses block less UV light than natural ones, so post-cataract surgery people can actually seen somewhat into the ultraviolet. No, it's not some dramatic superpower. However, between that and the fact that cataracts block more light at the upper end of the spectrum than the red end, people do report an alteration in color perception, basically everything is blue-shifted a little.

[Sela]

Hypertension due to Renal Artery Stenosis

Short 'n Sweet:
A whiny self-centered kid(ney) in the car insists on cranking the A/C BP (blood pressure) when it's already too high.

Anatomy & Physiology:
The kidneys really are a wonderful pair of organs. They self-regulate to make sure they keep working, have at least a 75% reserve capacity at baseline performance, and purge toxins with incredible selectivity. You can think of the kidneys as a filter for the bloodstream - they sample the bloodstream, filter out toxins, and retain useful levels of useful nutrients. The rest goes to the ureter, then the bladder, and finally to our lovely friends in the plumbing department .

In order to do this job, it should be obvious that the kidneys need to sample the blood, right? Roughly 30% of the heart's output is sent towards the kidneys through a blood vessel (artery) known as the Renal Artery. After passing through the renal artery, blood flows into a million tiny vessels and then glomeruli. The glomerulous is where the blood is "squeezed" and little particles filtered out into the urine along with fluid. Not 100% of it, mind, but certainly most of it. The kidney then reabsorbs teh stuff it doesn't want to get rid of (>90% of filtrate) and sends the rest on to the bladder. Special sensors through the tubules sense the flow-speed of filtrate. If it goes down, the sensors triggers the release of hormones (chemical signals) including eventually Aldosterone and Angiotensin II (Ald and AngII).
Ald makes the body retain extra sodium (and thus water). This causes the fluid-volume in the blood space to go up, which causes blood *pressure* to go up, which means: more blood gets to the kidney - so flow goes to normal! (self-regulating)
AngII does lots of things - but one thing it does is to constrict (tighten) arteries throughout the body. Imagine squeezing down on a small volume of fluid in a tube - doing this leads to increased *pressure*, which again means more kidney blood flow - which helps filtrate-flow go to normal.

The last thing you need to know to appreciate Renal Artery Stenosis is hypertension. Hypertension means that your blood is at too high of a pressure, that either the blood vessels are "squeezing" the blood too tightly, or the blood is pushing out against the blood vessels too much (since there's too much blood). It's almost always the latter, as blood vessels don't have the muscle strength to tighten that much to the point of hurting you. Hypertension isn't painful - but it is dangerous. Left unmanaged, it can steadily cause damage to the smaller more vulnerable sized arteries throughout your body. It also accelerates the process of artery narrowing (stenosis) (described later) The #1 organ for blood-pressure maintenance, though, is the kidney - since the #1 way to drop or increase blood pressure is to hold more fluid or get rid of it, respectively.



How it goes wrong!:

As good as this system is - there *is* an underlying issue - it's reliant on the idea that low *kidney* blood pressure means low *body* blood pressure! Now remember what I said earlier - the heart sends 30% of its output to the kidney almost directly: (Aorta -> Abdominal Aorta -> Renal Artery). 99% of the time, if the kidney sees low blood pressure that means there really is low blood pressure. But most the time isn't the same as always .

In greek, stenosis means "narrowing". For whatever reason (usually plaque buildup) our patient gets a buildup of plaque in the renal artery . . . blocking the kidney. This blockage starts off small - <10%, and so blood flow is only marginally lower and the kidney doesn't have to compensate. But then it gets more and more blocked as the stenosis gets bigger - 20%, 30%, 50%. Now stenosis like this isn't exactly a rare thing, and the normal result is that the end-organ just suffers from lack of blood and oxygen. Like, say the end blood vessel in my left toe got blocked; it won't get any blood, will cry for a while, then just die. Tragic, sure, but you can survive without a left toe.

But the kidney is very different from other organs! Firstly, it doesn't need much of that blood supply to survive - 30% of heart output is a TON of blood, it only takes so much to filter it, it could survive with a lot less. Secondly, even if the kidney dies, there's a second one to keep you alive. The problem is that the kidney doesn't KNOW this! And it's not able to tell the difference between low blood delivery from - say - someone getting dehydrated and losing blood pressure and from it *personally* not getting any blood. So the kidney does what it knows best: increase blood pressure to increase its blood supply.

So picture this: you've got the whole body sitting at a nice, healthy blood pressure (120). Your renal artery is blocked though, and so the kidney gets much less blood = less pressure = (80).


The kidney freaks out and starts shouting at the rest of the body - "Emergency, Blood
pressure collapsing! Raise the blood pressure! All hands to water-retention stations
and blood vessel constriction! This is NOT a drill people, this is NOT a drill!!!"


The body responds. . . and body's blood pressure flies up to 150!. But this only increases the kidney blood pressure to 82, since the blockage is still in place!!! What's worse, one of the major factors that helps a stenosis get bigger is - get this - high blood pressure ! The block gets worse, the kidney shouts even louder, and the hypertension gets even WORSE.


It's like having a thermostat switch outdoors (in winter) with a building full of people indoors. The guy outside keeps cranking the heat up higher and higher since he's still freezing. He's oblivious to the fact that he's making everyone inside melt with the heat! And what was supposed to regulate blood pressure now becomes responsible for ruining it.




Treatment:

Treatment is actually really straightforward: just remove the block. We've got an awesome procedure called 'stenting' where we literally just pass a wire through the bloodstream with a balloon attached to the end. when the ballon gets "stuck" in the blocked artery, we blow it up - which smushes the plaque out of the way and opens the artery! Then we add a metal sheath to hold the artery open. That's a bit of an oversimplification, but it's the basic outline of a stenting procedure.

How bad is it really?:

So there's two major factors affecting outcome. First is whether it's one renal artery or both that are blocked. If just one is blocked, sure it's bad. But it's a tug-of-war situation. One kidney is trying to increase blood pressure as hard as it can, the other ends up growing extra big (since it needs to handle 2x the filtered amount of toxins) and tries to stabilize blood pressure. If it's both blocked, then nobody is keeping the blood pressure down and treatment is URGENT.
Second factor is how long it's lasted. Remember how hypertension increases the risk of damage and stenosis? Well the longer you leave this type of condition untreated the less likely it is you've got a healthy patient when all is said and done. He'll be at greater risk (due to damage of the hypertension) of getting fresh problems and stenoses.



And that's Renal Artery Stenosis

[Sela]

[quote=RectoVaginal Fistula (Symptom)]
Rectovaginal Fistula [Symptom]

This isn't a disease - just a symptom. But it's so distinctive that it deserves its own entry. Recall the purpose of this blog to recount the "cool, weird, fascinating, or just plain bizarre"? Well today's entry *DEFINITELY* qualifies as bizarre and weird. Perhaps most bizarre is just how emotionlessly the teacher mentioned it in class. Also, this merits a disclaimer:

*IF YOU ARE EASILY GROSSED OUT, DO NOT READ THIS ENTRY*
You've been warned

Short 'n Sweet: Full-thickness colonic ulceration leads to an anastamosis between it and the vaginal tract.

Background Anatomy&Physiology:

Our body's digestive tract can be thought of as a series of tubes (quite like the internet, per a certain Ted Stevens ). Food starts in the mouth, then esophagus (hollow tube for swallowing), the stomach itself, then the small intestine (where most nutrients are absorbed), the large intestine or "colon"(which handles the remaining water) the rectum, which empties out into the anus (back-end). Each of these structures has an empty space in the middle through which food - or what's left of it - passes. A space like this is referred to as a lumen.

Now the walls of each of these structures are made of multiple different parts (not discussed fully here). Each layer having its own function. Needless to say, they all fit together quite nicely, and there's (for the most part) no branches, T-junctions, or other alternate paths for food to take as it gets squeezed down through the tube!

Next is the term "fistula". A fistula is an abnormal connection between two eptihelial-lined organs or tissue areas. If an artery - for example - had an abnormal direct connection to a vein, that would be a fistula. . .more specifically an arterio-venous fistula.

Lastly, as most men and women eighteen and up know (actually most twelve and up, but who's counting?) the vagina opens up into a tube-like structure of its own - the vaginal tract.


What goes wrong:

So, we've got this normally-healthy wall of the colon or rectum right? But there are disease processes that can cause it to weaken and even form an ulcer - a hole through one or more layers. Sometimes the ulceration is so bad that it can go all the way through and form a fissure - a cut through *ALL* the layers, leading to a small hole in the colon-wall (or rectal wall, depending where it occurs along the path).

Now the body doesn't like open wounds like this, so naturally it tries to heal itself. However, sometimes, the healing leads it to "attach" to an adjacent structure. Sometimes this adjacent structure is a different part of the colon - entero-enteric fistula. Sometimes it's the skin - entero-cutaneous fistula. And sometimes, if you're unlucky, it's the vaginal tract - or an enterovaginal fistula (or Rectovaginal, if rectum affected).

What does this mean? It means that instead of the lumen of the colon/rectum just moving on towards the anus, part of the lumen branches off. . . leading to the vaginal tract, and the vagina.


An affected patient will pass some part of her
stools and possibly even fart out of her vagina!


Treatment:

As scary/disconcerting as the symptoms are, in the grand scheme of things this isn't a very dangerous symptom/complication by itself. Obviously it's bad if left untreated, but a woman's not likely to "not notice" this for very long . Once it's diagnosed, surgery can correct the fistula, and detach or - if necessary - simply remove the affected portion of the colon.

But unlike all previous entries -as indicated by the title- this is a symptom, not the disease itself. It's something a disease *causes* that's a hint as to what's *REALLY* wrong. The real issue is to figure out what causd it in the first place. As we mentioned earlier, healthy colons don't spontaneously get deep-fissures through the side of their walls! One typical reason is a chronic illness known as Crohn's disease (one of the inflammatory bowel diseases), which in and of itself is something to be worried about. [/quote]