DIP Episode 425 - Pulmonary Pathophysiology Series 13

Okay, welcome. My name is Divine. This is episode 425 of the Divine Intervention Podcasts. It's into this podcast now be continued on the Pomonari Pathophysiology series. And this is going to be series 13. So let's just jump right into it. So the next thing I want to talk about here is just how Kabondalk side really moves around in the body. How does Kabondalk side really move around in the body? We know that obviously Kabondalk side is produced in the tissues. You know after tissues go through metabolism, they produce a lot of CO2. Now that CO2 can travel in certain ways. Contrave it in a few ways. One, it can travel as dissolved Kabondalk side in the blood, about 5% of the Kabondalk side that's produced are the tissues, travels as dissolved Kabondalk side in the blood. Now the remaining CO2 gets into red blood cells. So the remaining 95% gets into red blood cells. Now that's CO2 that dwells in red blood cells. Generally has two feats, right? So one feat is the Kabondalk side can bind up with water and then there's an enzyme called carbonic and hydrates that will produce carbonic acid. Carbonic and hydrates produces carbonic acid and then that carbonic acid is split because it's an equilibrium reaction. It's split into hydrogen ions and bicarb. And some of that bicarb, there's a bicarb chloride antiporter that exists on the surfaces of red blood cells. As bicarb leaves the cell, then chloride will come into the cell. In fact that's something known as a chloride shift.

That's a pretty high-youtu note. That's something known as a chloride shift. And if you really want to think about it, this Kabondalk and hydrates system is what largely transports CO2 in the blood, right? That bicarb that's made inside that red blood cell is then put into the blood stream. That bicarb is actually really helpful as a very excellent buffer in the blood stream. So just don't forget this chloride shift that happens with CO2 metabolism. Now, another feat of Kabondalk's side when it gets into a red blood cell is that it can bind with hemoglobin to form something called carbaminol, hemoglobin, carbaminol, hemoglobin. That's a more minor pathway. And since we're talking about carbonic and hydrates, remember, carbonic and hydrates is not just something you find in red blood cells. It's something you find in many cells of the body. And the friends at the end being is they love to go after carbonic and hydrates for many different things, right? So like for example, they love to go after it for many of the cells in the kidneys, right? So like for example, like your beta intercalated cells that deal with bicarb absorption in the nephron and stuff, it has this Kabondalk and hydrates system. Carbonic and hydrates is also necessary for CSF production. If you want to produce herbospein or fluid, use a lot of Kabondalk and hydrates.

In fact, this is one of the reasons why if you have a problem with too much CSF, like pseudo-tumor cerebride, for example, which we did this called idiopathic intracranial hypertension, then we use Kabondalk and hydrates inhibitors, like I said, azolamide or azolamide, to inhibit CSF, to inhibit Kabondalk and hydrates, you'll make less CSF. It's also necessary to know that Kabondalk and hydrates is used to make ekeosumer, so it's also used to make ekeosumer. Well, we know that there is an ekeosumer problem that can arise in the eye, eke glaucoma. And that glaucoma, again, you can try to temper the production of CSF by inhibiting carbonic and hydrates. When you inhibit carbonic and hydrates, you would make less ekeosumer and that will lower the drug pressure in the eye. Now, another reason why you also want to know about Kabondalk and hydrates is the fact that Kabondalk and hydrates, again, is inhibited by drugs like acidosolamide. The thing is, those drugs actually can actually serve as diuretics. So if you take acidosolamide and inhibit Kabondalk and hydrates, they'll prevent you from absorbing bicarb in the proximal convoluted tubule. Now, when that happens, that bicarb will stay in your urine, it will attract more water, or it's more particularly on your pee more. So it's a diuretic. So being a diuretic, it literally makes you volume depleted. And if you volume depleted, what's gonna happen?

Well, your body is gonna be like, wow, I'm volume down, so I'm gonna have to increase the activity of the reneal and jutensin aldosterone system. When that happens, you will make a lot of our duster and one of the jobs of our duster needs to make you urine-it potassium. When that happens, you're gonna have hypochylemia. So you're gonna get hypochylemia as a consequence of taking acidosolamide. But what kind of acid bays are normally what you get? Well, the thing is, normally reneal and jutensin aldosterone system is working in high gear to develop a metabolic alkalosis and hypochylemia. But in the case of acidosolamide, you'll actually develop a metabolic acidosis, because you're literally preventing bicarb reabsorption by virtue of your mechanism of action. By inhibiting the reabsorption of bicarb, you're literally losing bicarb at the level of your proximal tubule. That's essentially a type 2 RTA that's in operation. So it's pretty high to know that acidosolamide can cause a type 2 RTA, a type 2 reneal tubular acidosis. So on like most diuretics that cause the combination of metabolic alkalosis and hypochylemia, acidosolamide and diologribonic anhydrous inhibitors are unique in the sense that it causes a combination of a normal anion gap, metabolic acidosis and hypochylemia. It's a factor you want to make sure you're able to integrate properly in your head.

Now, one other thing I want to talk about with CO2 movement, before I go to another topic, is talking about the halden and the bor effect. The thing is, many people they kind of press a very over this. This stuff is pretty loyal, really tested on the exam, but I'm going to cover it for completeness sake. But basically the halden effect, think of it as having to do with CO2 loading and unloading. So if for example you're living in an area that has a high CO2 partial pressure, like in the tissues, for example in your periphery, then CO2 loading on hemoglobin is favored. It just makes sense. You want that CO2 to get away from the tissues, right? You want that CO2 to get away from the tissues so you can go to take it to the lungs where they can then be excreted. But CO2 unloading from hemoglobin is favored where you have low CO2 partial pressures, which is what happens in the lungs. So your flow that CO2, right? So that unloading is favored in a low partial pressure of CO2 situation like you have in the lungs. For CO2 loading on hemoglobin is favored when you're in a high CO2 partial pressure environment, like your tissues like the periphery. Just basically think of things again moving down their pressure gradients. Now what's the bore effect? Well the bore effect, the BOHR effect, right? It has to do more with oxygen loading and unloading, right?

So the thing is if you have an area of the body where you have a high CO2, a high CO2 partial pressure, then oxygen on loading is favored. Again that makes sense because you're essentially going down your gradient to resolve the hypoxia. Now the reverse is the case in the lungs. The reverse is the case in the lungs. The reverse is the case in the lungs. So the bore effect again deals with oxygen loading and unloading. The whole DNA effect deals with CO2 loading and unloading. Very high you to make sure that you understand that. Now the thing is our friends at the MBM is again remember they're not, they're smart. So what is one way they can try to make this a little hotter than it needs to be instead of talking about or a high CO2 environment, they can use a surrogate for a high CO2 environment. They can see like in an acidic environment or in an environment with a high concentration of hydrogen ions because again remember CO2 when you have high levels of CO2 that makes a place acidic in general because that CO2 can combine with the water in blood and foam by carb and then that by carb can be split into hydrogen ions. That's very important to keep in mind. And then another thing I also want to talk about is that with this bore hole DNA effect business whenever hydrogen ions bind to the globin chain of hemoglobin it actually converts it to from a relaxed to a taught confirmation. So the thing is maybe let me backtrack a little bit here.

So hemoglobin can have two conformations. You can have a relaxed confirmation we're going to call that R. We can have a taught TAUT confirmation we're going to call that a T. Now the thing is the T confirmation does not like to hang onto oxygen it likes to unload oxygen. That R confirmation likes to hold onto oxygen it does not like to release oxygen. So again think about what I just say with a bore effect when you're in a situation where there's a lot of CO2 there's a lot of hydrogen ions around it favors oxygen unloading from hemoglobin well how does that happen that happens because those hydrogen ions that you generate from that CO2 right it binds to hemoglobin when it binds to hemoglobin it's going to convert it from the R form to the T form. Hemoglobin the T form is going to unload oxygen it's going to unload oxygen and again just FYI as I said already all these CO2 by carb interconversions they're pretty much all carried out by carbonych and hydrates. So again just try to make sure you are not memorizing these things try to make sure that you actually understand what in the world is going on again I'm telling you understanding bits memorization most of the time.

The thing is for these USML exams you're taking if you have the understanding it's really going to help you but you also need to memorize unfortunately but that understanding makes your memorization a lot cleaner and the thing is many of the questions they write on the USML is these days are problem solving questions there are questions where yes you may know the concept you may have memorized it through a card or something but if you don't have an understanding you're going to struggle with answering the questions properly or even knowing okay this is exactly where this question is going this is exactly what they're trying to get me to answer and if you like the way explained things you may be interested in some of the classes I have this month I have an MBA me testing strategy scores sticking place on the 18th of this month that's next week Friday from 5 to 7 30 p.m. mountain again many people have taken this course and they found it to be supremely helpful in being good at dealing with MBA me questions because sometimes you may have all the knowledge we may be a bad test sticker and that's the thing that keeps your scores down also if you want content knowledge then you'll be interested in my 20 hour review course it's going to be taking place on the 21st 22nd 25th and 26th of November so that's a Monday Tuesday Friday and Saturday from noon to 5 p.m.

Mountain standard type on all 4 days so it's going to be 5 hours each day we're a few more than a thousand concepts from internal medicine, PEED surgery, OB-GYN, neuropsych, FX, communications and healthcare systems and also multi-systems processes and disorders and then if you're interested in learning about bio stats because again most of the bio stats questions these days on exams they are not questions where I know the formula will help you answer them correctly no most of them are reasoning these questions so I said I create a separate course just for bio statistics that one is going to be taking place on the 28th of this month from noon to 4 p.m. Mountain standard type that's from 2 to 6 p.m.

Eastern standard type okay so let's go ahead and continue so if you're interested in any of these courses just should be an email through the website and I'll give you some more information yeah held over zoom and these courses are almost exclusively based on scenarios they're not courses where I'm going to be giving you lectures if you're interested in lectures that's not the course for you because again your MBA exam is not going to be a series of lectures it's going to be a series of clinical scenarios they're supposed to navigate through to picking out an answer to the question okay so let's go ahead and continue with obstructive are long diseases so let's go into the purview of obstructive long disease and the thing is as I'm discussing obstructive long disease I'll try to kind of tie in obstructive long disease I feel like that's probably one of the better ways to understand it's when you can do this compare and contrast this this versus that situation so the thing is I've mentioned this in an earlier podcast and the big problem with obstructive long disease is that you have trouble getting air out of the locks you have trouble getting air out of the locks right the trouble is with you getting air out the trouble is with you getting air out if you understand this one concept you'll help your rationalize a lot of the other things I'm going to be saying about obstructive long disease so you're going to have trouble getting air out of the locks and that trouble you have is going to decrease the FVV1 and it's also going to decrease the FVC but the thing is your FVV1 is the thing that goes down the most so you know obstructive long disease your FVV1 and your FVC both go down but FVV1 goes down way more so overall your FVV1 to FVC ratio decreases again look at this ratio at the top of the ratio is FVV1 at the bottom of the ratio is FVC if both are decreasing well ask

yourself which one is decreasing more the one that's decreasing more is the one at the top the FVV1 so overall the ratio should go down but your restrictive disease on the other hand the problems with getting air in your lungs are not very distensible they're not very compliant so they have trouble expanding you don't have trouble blowing out air you have trouble bringing in air so what happens in restrictive long disease where you're restrictive long disease your FVV1 and your FVC both decrease your FVV1 and your FVC both decrease but the thing is your FVC just goes down more I may ask yourself why is the FVC going down a lot there isn't the FVC going down is you're not bringing in enough oxygen to start into the lungs so when you're blowing stuff out the stuff you're going to be blowing out is smaller it's just simple as that I think that's something you really want to make sure you understand the reason that the FVC goes down in restrictive long disease is because the impute right you are bringing in smaller amounts of oxygen because your lungs are not very compliant to start so when you're blowing out air it'll be blowing out as much oxygen but your FVV1 also goes down it just doesn't go down as quickly as your FVC so overall the ratio is going to be normal or increased that's something that's very important very high yield to actually understand some that's very important very high yield to actually understand so do not forget that understand the reason why the FVC goes down the FVV1 doesn't go it goes down but not as much because again your blowing out mechanism of air is completely fine in general when you have restrictive long disease now what is another thing that's important to know about obstructive long disease the thing is when you have obstructive long disease you are conducting a respiration of higher long volumes you are conducting respiration at highe

r long volumes I'll explain the pathophys behind this you think this podcast or in the next podcast but you're conducting respiration at high long volumes why because again you have a lot of air trapping and I'll explain why that air trapping happens we have a lot of air trapping so your lungs are working is almost like think of a balloon normally your lungs are supposed to like inflate and then deflate inflate and then deflate but if your lungs are working at like high inflation all the time then that's not a good that's not a good situation just kind of think of an economy working on that high inflation as you know we're seeing right now in the US it's kind of a tough situation to be on there right everything is very expensive it's just hard to do things because things are so costly money has lost so much value that's the same thing with obstructive long disease your lungs are working at such high volumes that they are not able to respirate efficiently because again they've not completely deflated so it's almost like oh let's say wow your lungs are supposed to inflate to full capacity and then deflate to like 20% capacity well if you deflate to 20% capacity you have that extra 80% to fill up with oxygen again which is a good thing but if because you have air trapping the lungs are like inflated at 80% capacity then you have only have 20% to work with in terms of bringing in oxygen that can really help you understand why people that have obstructive long diseases tend to have significant hypoxia tend to have significant hypoxia right so again because of your prison at these high long volumes because of air trapping long volumes in general are increased in obstructive long disease so like your residual volume your functional residual capacity your total long capacity all those things are going to be increased in obstructive long disease but when you're dealing with re

strictive disease the problem is with getting air in you're not bringing in enough air that's why you're hypoxic so and why do you have that because again your lungs are not very compliant your lungs are fibroasts so they cannot expand so because you cannot bring in enough oxygen in the first place your long volumes in general are going to be low so long volumes in restrictive disease in general are pretty low now the key obstructive diseases you kind of need to know for your exam you need to know about chronic bronchitis you need to know about infezima into know about asthma and I guess to a lesser degree bronchi ectasis I believe we've kind of talked about asthma already now the first three you know chronic bronchitis and phezima asthma most times they are kind of placed under the umbrella of COPD so let's talk about chronic bronchitis look at the name the name is very descriptive chronic bronchitis the problem is largely with the airway it's largely an airway problem I'll say that again chronic bronchitis is largely an airway problem your vial eye are generally not affected in a person that has chronic bronchitis the affected but that's not the general rule the primary thing that's messed up in chronic bronchitis is your airway is your airway so let me explain a few things here so the thing is how do we diagnose chronic bronchitis well basically we say that if you have a chronic productive cough that goes on for at least three months in a two-year span that's chronic bronchitis okay you see a person they have a chronic productive cough very juicy cough those that work in hospitals you know what I mean by a juicy cough they have a juicy cough a lot of sputum right so you go in for at least three months in over two-year span that's chronic bronchitis now what's the biggest risk factor for chronic bronchitis the biggest risk factor is smoking people that smoke are the

people that get chronic bronchitis right they put a get chronic bronchitis because again if you think about it when you smoke you're depositing a lot of harmful particles in your airway so your body is like man I got a get rid of all this garbage right so in doing this your body makes a lot of mucus and a lot of things and those things go on top of your airway that's really the pathophys ultimately behind chronic bronchitis right so all that sputum right in our eyes is because again you have hypertrophy of your mucus secreting glands that's very high you to understand when there's a lot of junk in your airway your body is going to try to secret mucus so that you can I'm just going to think of it as like little bags that used to suck up the bad stuff like the smoke particles and everything and then you cough up that mucus contain the smoke particles to expel them from your body now everyone in here smoke particles if you live in any major city you have a car or anything you're going to be hitting some smoke particles you're going to be making some mucus to get rid of it but you see people you know they get rid of those things every now and they're not a big deal but if your body is just chronically exposed to smoke particles because you're a smoker smoker smoker then your body chronically has to keep making mucus making mucus making mucus again too much of most things is almost always never good so the thing that's going to happen is your mucus secreting glands are going to hypertrophy they're going to produce a sputum a lot of mucus right and so with that mucus right plugs up your earway it plugs up your earway it plugs up your earway as it plugs up your earway it's going to cause a lot of trouble with you being able to get air out of the lungs right so chronic bronchitis is not a it's not a good thing and also if you think about it those mucus secreting glands as th

e hypertrophy they also take it up more space within your earway right real estate is limited in your earway but if you have hypertrophy of some glands that are just taking up space taking up space taking up space that's going to make it hard for you to respirate adequate now one thing you may occasionally see is this thing called the read index R E I D the read index is something that we use occasionally with chronic bronchitis it's really not used clinically but it's something we see on exams but basically it measures the ratio of your earway taking up let's say you're looking at your earways like an ear like a defined ear what ratio is taken up by these mucus secreting glands compared to like the total length of the earway the reading index in general is increased in a person that has chronic bronchitis right chronic bronchitis and again the thing is these these mucus particles decrease little these little pockets in your earway as well right all those little pockets that create again they can be taken over by bugs by microbes especially sudomones in causing the person to have just chronic infection right chronic infection now again all that mucus plug-in from all the mucus you're producing again it's going to plug up your earway it's going to cause an earway obstruction it's going to make it hard for air to get out of your lungs if it's hard for air to get out of your lungs then your viola oxygen is going to go down because oxygen is not going to coming through easily and your viola CO2 is also going to build up because again through the halden effect you're dumping a lot of CO2 in the lungs but it has nowhere to go because the earway is closed up now the thing is the chronic hypoxia that these people have from not being able to get air out the chronic hypoxia they have where what does hypoxia do to the pulmonary vessels is going to cause hypoxic pulmonary viso-co

nstruction they're going to get pulmonary viso-construction that's going to cause pulmonary hypertension right it's going to cause pulmonary hypertension right it's going to cause pulmonary hypertension and your body is going to try to be like okay wow let me try to get blood to better ventilated regions of the lungs right because again you're constructing those vessels especially the vessels around the really really bad airways so you don't send blood to those areas that don't have enough oxygen to properly ventilate I mean to properly oxygenate that blood that's coming through right but the thing is all that viso-construction is going to increase the resistance that our right heart has to pump against and ultimately that can cause right heart failure and again what is this right heart failure called it's called corpumunali that's just a term I want you to be very familiar with I don't know for whatever reason you know from my 101 tutoring from just working with people like say a lot of people get stuff like this wrong whenever you have right heart failure because your lungs are messed up that's what's called corpumunali but remember the most common cause of right heart failure is left heart failure when your left heart fails for any reason or because you have mitrosenosis or you have live ventricular failure whatever and then your right heart fails as a result of that that's not corpumunali but if you have something bad going on with your lungs like cystic fibrosis or you have infecima we have chronic bronchitis and that leads to right heart failure that's what's called corpumunali heart failure from a pulmonary cause pulmonali pulmonali pulmonali pulmonali pulmonali again that's pretty high up to kind of keep in mind as you're as you're as you're studying for for your for your exams now one thing I want to say is so if you're pressing out chronic bronchitis what ha

ppens to their lungs what's the like the primary cause of the hypoxemia if you want to use more professional pulmonary terms well the thing that causes the hypoxemia is that you have an increase in shunt physiology you have an increase in shunt physiology right so again remember shunt is where blood doesn't get an opportunity to get properly oxygenated blood flow is happening what prop oxygenation is not happening the easiest kind of shunt to remember and think about is like a VSD for example let's say a person has isomengar syndrome where blood is going from the right ventricle to the left ventricle it completely speaks skips the skips the lungs it doesn't get oxygenated in chronic bronchitis blood is going to be flowing through the lungs but it's not going to get properly oxygenated why is it not getting properly oxygenated because again air is just not coming through those gunked up airways right so but again the thing is is obviously it's not a 100% shunt so if you give supplemental oxygen it's going to improve the presence hypoxia okay it's going to improve the presence hypoxia it's going to improve the presence hypoxia so I think I'm going to go ahead and pause here because I do want to talk about infezima but again I want to have enough time I don't I don't want these things to go too long so they can just look at it as little packets of information that you're learning but in the next podcast on pulmonary pathophysiology I'm going to infezima because there are a lot of derivatives I want to mention with regards to infezima although I will say for chronic bronchitis I think there's actually one more thing I want to say so people that have chronic bronchitis they have hypoxia granted I agree with that but what's going to be true of their EE gradient what's going to be true of their EE gradient what's going to be true of the EE gradient what's going to be true of

the DLC when a person that has chronic bronchitis well here's the thing in general a person that has chronic bronchitis has a normal DLC they have a normal DLC remember DLC relates to how well oxygen traverses barrier remember in chronic bronchitis is the bronchitis that are affected not the ovula so because the ovula are not affected there is adequate diffusion of oxygen across that of your barrier so in general your DLC is normal in a person that has chronic bronchitis and the EE gradient should be roughly normal in a person that has chronic bronchitis although in general it's decreased but I'm not going to go there in terms of talking about it in in great detail they almost never ask about EE gradient same chronic bronchitis because it's very variable but the DLC of for sure you need to understand the DLC is normal the DLC is normal the DLC is normal the DLC is normal the DLC is normal but the EE gradient is roughly or normal or increased you can kind of put it that way again they almost never test that on exempt so I wouldn't worry about that because it's very variable there's a lot of technical factors you need to consider which is just not something that I think is appropriate for a podcast that's going over US Emily material even boards material this is more like you're going for like poem fellowship and whatnot so we're not going to going to going to that now another thing I want to say is so what happens in infosima let's just do a compare contrast and wrap up in infosima you've literally true it up your viali your viali member it's so because you don't have enough surface area your diffusibility goes down so your DLC actually goes down in infosima so what happens to your EE gradient so EE gradient actually is increased in infosima your EE gradient is increased in infosima because your viali member is affected so because you don't have enough surface area th

e PBG-02 is not going to equilibrate your p little to so you're going to have hypoxia as a result of that right so again remember if you see obstructive disease with a reduced DLC think of infosima you see obstructive long disease with a normal DLC you think of chronic bronchitis and in infosima as well the EE gradient in general is increased okay for chronic bronchitis the EE gradient in general is normal or increased it could go either way right again so that's not something that's classically tested on exams as I wrap up I do offer one or one to learn for many exams step one to step three complex one to three pre-clean cometscal exams 30-ish-elf exams I also help with ear-ass applications and mocking reviews there's something I'm doing a lot of right now so again I've been on an admissions committee before I've worked with lots of people that have much that virus residences all over the country so if you're interested in any of those things shoot me an email through the website I have these podcasts on the major apps Apple Podcast Google Podcast Spotify at least the most recent 150 if you want everything from a episode one to episode 425 which is this episode if you want to go ahead and check out the website deraininterventionpodcasts.com if you actually subscribe to your Word Press account you get an email notification whenever I make a new podcast and then finally I have a You Tube channel derainintervention USM Ly podcast and videos that's where I post the videos that I make and then I also have another website called deraininterventionlifelessons.com that's where I post I post life lessons that are Bible based in fact we have I think almost 130 or more episodes right now it post about two a week they're about 10 minutes long where I use a Bible verse to just talk about a classic problem that's faced by a lot of people again a lot of people have found those podcast

s to be really helpful so thank you for listening to me today I will see in the next podcast have a wonderful rest of your day God bless you bye for now

The majority ($\sim 95\%$) enters red blood cells and reacts with water via carbonic anhydrase to form bicarbonate ($\text{HCO}_3^-$) and hydrogen ions ($\text{H}^+$).

Chloride shift. This maintains electrical neutrality as $\text{HCO}_3^-$ enters the plasma.

Carbonic anhydrase (CA).

Type 2 Renal Tubular Acidosis (RTA), caused by impaired bicarbonate reabsorption.

Obstructive disease decreases this ratio significantly; restrictive disease maintains a normal or increased ratio.

The Haldane effect relates $\text{CO}_2$ loading/unloading on hemoglobin, while the Bohr effect relates $\text{O}_2$ loading/unloading to changes in $\text{H}^+$ concentration.

Smoking; it leads to hypertrophy of mucus-secreting glands, resulting in excessive sputum production that plugs airways.

Chronic hypoxemia triggers hypoxic pulmonary vasoconstriction, increasing pulmonary vascular resistance and straining the right ventricle.

A productive cough lasting at least three months in two successive years.

The diffusing capacity of the lung ($\text{DL}_{\text{CO}}$).

Chronic bronchitis (because the alveoli are patent, but airways are narrowed).

Metabolic acidosis and hypokalemia (Type 2 RTA).

The hemoglobin shifts from the relaxed (R) state to the taut (T) state.

Chronic hypoxemia triggers hypoxic pulmonary vasoconstriction, increasing pulmonary vascular resistance and straining the right ventricle.

A productive cough lasting at least three months in two successive years.

The diffusing capacity of the lung ($\text{DL}_{\text{CO}}$).

Chronic bronchitis (because the alveoli are patent, but airways are narrowed).

Metabolic acidosis and hypokalemia (Type 2 RTA).

The hemoglobin shifts from the relaxed (R) state to the taut (T) state.