Q&A #7 | Pitting oedema, intracranial pressure, Alport disease, and more!
01:09:52 Share

What if I told you that right now, millions of people are living with a debilitating condition that's so misunderstood, many of them don't even know that they have it. That condition is obsessive compulsive disorder, or OCD. I'm Dr. Patrick McGrath, the Chief Clinical Officer of NoCD. And in the 25 years I've been treating OCD, I've met so many people who are suffering from the condition in silence, unaware of just what it was. OCD can create overwhelming anxiety and fear around what you value most, make you question your identity,

beliefs, and morals, and drive you to perform mentally and physically draining compulsions or rituals. Over my career, I've seen just how devastating OCD can be when it's left untreated. But help is available. That's where NoCD comes in. NoCD is the world's largest virtual therapy provider for obsessive compulsive disorder.

Our licensed therapists are trained in exposure and response prevention therapy, a specialized treatment proven to be incredibly effective for OCD. So visit nocd.com to schedule a free 15-minute call with our team. That's nocd.com.

Long gone are the days of waiting to be seen in a doctor's office only to have that awkward conversation with your healthcare provider. WISP gives you access to sexual and reproductive healthcare from the comfort of your home. Get treatment for BV, yeast infections, UTIs, and much more delivered directly to your home or ready for pickup at your local pharmacy in less than three hours. The best part? WISP is discreet, convenient, and you don't need medical insurance to receive care or prescription medication.

Visit us today at HelloWisp.com. Hey, guys.

Have you heard of Goldbelly? It's this amazing site where they ship the most iconic, famous foods from restaurants across the country, anywhere, nationwide. I've never found a more perfect gift than food. They ship Chicago deep dish pizza, New York bagels, Maine lobster rolls, and even Ina Garten's famous cakes. So if you're looking for a gift for the food lover in your life, head to goldbelly.com and get 20% off your first order with promo code GIFT.

Welcome everybody to another episode of Dr. Matt and Dr. Mike's medical podcast Q&A special episode. I'm your host Dr. Mike Todorovic. Yeah, it is. We haven't done one in a while, Matthew. I'm your host Dr. Mike Todorovic, joined by my co-host Dr. Matthew Barton. How are you, Matty?

I'm well. Thanks for having me again, Mike. Well, on your own podcast, you're welcome. You should thank me for more things that I don't deserve thanks for. We are doing a Q&A. We've accumulated so many different questions and thanks and even some hate mail, which I've forwarded on to you because they're all directed to you anyway. So we're going to do just some of them today. Obviously can't do a lot. Should we just jump straight into it, Matthew? What do you reckon?

Yeah, let's do it. I think we should. All right. So first is a thank you from Dana. Dana says, hello! I'm a physician assistant student in Winchester, Virginia at Sheffield.

Shenandoah University. Actually, I've heard of Shenandoah University, but I'm from Indiana. I've been listening to your podcast the last couple of years, even before beginning PA school. Awesome. Your YouTube videos are also a lifesaver. I've recommended your YouTube channel to a few of my classmates.

Thank you for your easy to understand education. I'm also curious about what PAs do in Australia versus the US. Is the position similar and is it becoming more autonomous like it is here? Thank you, Dana. So thank you, Dana. First thing I'd like to say is I'm recording from home today and my office is

is right next to a whole bunch of bushes and trees. So you're going to hear a lot of birds, and for some reason it's crows this morning. Hopefully that's not ominous for any reason. Stephen King, Stephen King.

Yes, that's right. It's pet cemetery in my backyard at the moment. Now, this is a really interesting question because the question is about PA, so physician assistants in Australia versus in the US. And the thing is, we don't really have physician assistants in Australia, right, Maddy?

Yeah, when I did my undergraduate in medical science, I had a close friend who is now went into medicine, but he worked for a short period as a PA in Liverpool Hospital. And so his role was, I don't know how you describe it, probably doing like in terms of in the emergency department, probably putting cannulas in and taking brief histories before the physicians came in.

or the clinicians. But yeah, I think as you said, it's been somewhat phased out and maybe in Australia context, it's been probably not taken over, but maybe some of the work is more commonly done by nurse practitioners within the ED department. Well, that's right.

I think you're right. I think more of the responsibilities aren't going to separate trained fields. I know that you could argue that it's all medicine, but I think it's more so giving more of the medical responsibility to nurses and upskilling nursing staff and providing them with more options and so forth. But I mean, it's not that the concept of physician assistants

don't exist in Australia or specifically in Queensland, which is where Matthew and I are, but there's just no uni programs for PAs. And it's not a profession that's registered through our governing medical organisation, which we call APRA. So it basically is non-existent in Australia. So hopefully that answers your question, Dana. But there might be opportunities for it to exist.

be a bigger thing. Now, we've got another email here from Chakra and the subject is advice on pursuing a postgraduate in human anatomy. All right. So the message says, "Hey there, Dr. Matt and Dr. Mike, big fan of your work. Thank you for the work that you guys do. The reason I am writing to you is to ask for some advice.

Now, just very quickly here, we're the worst people to ask advice to, I believe. I don't even give advice to my own kids. So for context, I studied nursing for my undergraduate program, but I've since left nursing. To pay the bills, I tutor high school and pre-university level biology, and I've been doing this for more than a decade.

There is a part of me that is interested in continuing my postgraduate in biology, but I'm not sure if my nursing undergraduate degree is sufficient to enrol in any postgraduate programs associated with any biological fields. I'm interested in pursuing something in the realm of evolutionary biology or human anatomy and physiology and hopefully specialise in an overlap between these two fields. My question to you is, and I know this is a difficult one, where do I even start in terms of courses?

Would I need to go back and do a completely new undergraduate program? Would my nursing degree be sufficient to pursue a postgraduate program? I look forward to your reply, but even if you may not have the answer to my question, please accept this as a rather odd fan mail. Regards, Chakra from Malaysia. Thank you, Chakra. Matt, do you want to field this one? Oh, yeah.

What's the process? If you've got a nursing undergraduate degree, what is... We can only talk within the context of Australia, right? So what would be the options for somebody who's got an undergraduate nursing degree to pursue something within the postgraduate realm that sort of sits a little bit outside of nursing? Yeah, well, I reckon evolutionary biology might be a little bit more challenging, but I

But I think human anatomy physiology has a broad degree, which possibly in Australia that might fit within something like medical science. Generally speaking, if you were to go and do that degree, they introduce you pretty well in the first year to the subjects that you're likely to need to scaffold you into the more challenging subjects in the latter years. So I think in that regard you should be fine. When it comes to a bit more technical things that may require more science prerequisites,

Could be a bit more challenging, but that's not to say you won't have the capabilities of doing so. Like there's no reason for why you can't catch up or your professors provide you with material to be able to kind of do it in your own time. So to answer broadly and quickly, I'd say yes, but no.

just chat with the educators and ask them. They're probably better placed in the context of Malaysia to know, do you have the prerequisite science knowledge to be able to go into these avenues? Yeah. And then I guess with both of those pursuits, whether it's evolutionary biology or more broadly human anatomy physiology, you probably just need to ask yourself, what avenues would this take me into a career? Is there viable careers in Malaysia? Yeah.

that these two degrees or one of these degrees will provide me. I mean, maybe it's in science teaching, maybe it's more in the scientific side of research, but these are probably good conversations you can have with some of the universities in your areas and the professors that, I don't know, I guess you'd say oversee the programs. Well, the way I'd look at it is, like you said, what's...

do you have an end goal inside or is it because you're simply interested in those particular fields? Both are, both are fine. If you want to specifically study evolutionary biology, I would say you should do an undergraduate degree in evolutionary biology. Uh, if you want to teach human anatomy and physiology within the context of nursing students, then you are already within that space. So you could potentially go back to university and do a master's or honors in, uh,

the field of education,

anatomy and physiology. So teaching anatomy and physiology, you can do an education degree, right? In addition to that. And that would be, that would allow for you to seamlessly transition into a PhD where it could be anatomy and physiology focused, but within the education space. But if you more so are looking at becoming a physiologist or an anatomist, it's very likely you'll have to do a new undergraduate degree. That's what I would think.

All right. Thank you, Chakra. Appreciate the email. Maddy, we're going to go into some questions now because we've got people asking us questions. Let me again preface this like I always do with the fact that we cannot offer medical advice.

We cannot do that at all. We don't want to do that and that's not our job here. We are educators. We teach anatomy and physiology. So all these questions, some people might frame it within the context of themselves and wanting advice or information about conditions that they may have or think they have. All we can do is talk about the anatomy and physiology or pathophysiology of diseases broadly. Nothing in regards to the specifics of an individual. So please...

This is education purposes only, not specific medical advice. Now, what's the first question, Matty? Yeah, so this question comes from Jennifer and the subject of this question is idiopathic intracranial hypertension. And Jennifer says, hello, I was wondering if you can explain this condition to me. I have some of the classic symptoms of it waiting for a diagnosis, but it hasn't been well explained to me. So essentially, can you do so for me? All right. So, Mike...

Idiopathic. Well, that describes you to some degree. Idiopathic intracranial hypertension. Yeah. What is it? All right, so let's break the terms up. Idiopathic means...

Unknown cause. We don't know what's causing it. It's basically our get out of jail free card. When we don't know what's causing a disease, we'll put idiopathic in front of it. So it sounds like it's really fancy. So that means don't know what's going on. Intracranial means inside of that cranial vault, which is your skull and hypertension simply means that the pressure is elevated. So there's an elevated pressure inside the cranial vault and we have no idea what's causing it.

Right. Other name for this. Did you come across the other name? Yeah. Pseudotumor cerebri. Okay. Right. And so, which means false tumor in the brain, because generally speaking, when people have, and you're probably going to talk about this in a sec, cause I've got a question for you, Matt. Uh, when people tend to have, uh, increased intracranial pressure, which is, uh, you know, ICP increased intracranial, uh, pressure, um, uh,

often it can be due to a tumor, right? So that's why it's called false brain tumor or pseudotumor cerebri. So Matt, I want to ask you a question. When it comes to the pressure...

Well, my turn. When it comes to the pressure inside of your cranial vault, your skull, there is something that I've heard before called the Munro-Kelly hypothesis. Would you be able to define that and its relevance within the context of intracranial pressure?

Well, that works out well because that was pretty much going to be my question to you. So there you go. Yeah, so basically if you look at the skull as a closed box, okay, so it is a hard outer casing. In your case, an empty box. Empty box. Well, then this hypothesis won't work so well if that's the case. But anyway, inside a typical cranium, which is a hard outer case, you have basically three main things. You have...

the brain and the associated tissue. You have the blood and you have the CSF, which stands for cerebral spinal fluid. And those three components...

collectively together make up the substances in your cranium, but also the potential for increasing the pressure within the cranium. Because if you increase any one of those three or more than three, or more than one of these three, it will increase the pressure inside your cranium, which we call intracranial pressure.

So basically, it's incompressible in there. There's no room for movement effectively, or at least very little room for movement. So you increase the blood, you impede the other two. You increase the cerebral spinal fluid, you impede the other two. You increase the matter of the brain, you impede the other two. And at the end of the day, if you're increasing that pressure, one of the issues here is

is going to be the blood that's entering into the cranial vault that needs to feed the brain tissue itself. That's a term we use, which is perfusion, and that is of a particular pressure itself. So in the vessel, in the blood vessel, you've got the blood moving through, which is pushing out and against the vessel, right? Now, once it hits capillaries, that outward push leaks the blood out, which has oxygen and nutrients to feed the tissues.

But if you've got an opposing inward pressure, which is the intracranial pressure, as soon as that intracranial pressure equals or exceeds that outward blood pressure, the perfusion pressure, the brain doesn't get fed. And that's one of the big issues with it. And the intracranial pressure can increase very quickly because there's not much room for movement there. So it doesn't take much of an increase in either blood, cerebral spinal fluid or brain mass to

in order to significantly increase that pressure to stop the feeding of the brain. Now, when it comes to this situation, idiopathic intracranial hypertension,

We don't know what's causing it. So then the question is, what can cause increased intracranial pressure in other instances? So, I mean, you could work off first principles really here, but let's talk about what could cause an increase in intracranial pressure. Okay. So let's work off those three broad areas again. So just remind me again, Mike, what were the three that make up the... Blood? Blood.

Cerebral spinal fluid and tissue mass, so the brain. Okay. So let's start with tissue mass. This is probably the most common causes of increased intracranial pressure and that would be where you increase the amount of tissue in your brain or your brain tissue. So that would be commonly done through or you might commonly see it in clinical practice with tumours, whether it is primary brain tumours or secondary brain tumours, which is metastatic. Okay.

On top of that, we could have additional tissue, I guess you'd kind of say, which is hematomas where bleeding comes out of the blood vessel and goes into the tissue mass. And so that would add, I know it's blood, but it's not really so much blood volume. It's more just going into the tissue space. So that would also increase the mass of hematomas.

within the cranium as would an abscess like an infection and like an encapsulated infection. So those three could be good examples of adding a mass effect within the cranium. And so if these were the causes, you could ascertain a diagnosis fairly simply with an imaging scan.

Because if you did a scan, you would actually see a density with tumors or a bleed or an abscess. So you could rule that out fairly quickly. Now the other, then we go into more the blood side of things. So you could actually increase the amount of blood going into the brain tissue. So it's almost like a hyperemia, if that makes sense. You're just increasing the amount of blood going in there or you would increase the amount of blood

plasma, I guess you could say, going out of the blood vessels. So this would be kind of like a form of edema. So if edema starts to go out into the brain tissue extracellularly, then this would also add in, I guess you would say, it's kind of part of the blood side of things. Does that make sense? Yeah.

Any one of those things can increase it. And then we go to the last one, which is the cerebral spinal fluid. So this is just looking at the amount of cerebral spinal fluid and that's fairly straightforward. It comes down to are you making too much or are you not removing it quick enough? And so this would kind of come down to...

The term here would be... So in excess amount of CSF, you would call it a hydrocephalus or kephalus. It just means water on the brain essentially and that can come through a communicating or a non-communicating cause. So you're kind of producing too much or not reabsorbing or there's a blockage and it's not getting pushed through its circulation channels which we can talk to shortly if you wish. Now...

The idiopathic, it doesn't fit into any of these. It's kind of like... Or at least not that we can see. Yes, not that we can manage or measure, should I say. That's right. In a way, it sort of has to be one of those things, though, because you're limited... I shouldn't say has to be, but...

because it's, you've only got three things to deal with, right? So the production of cerebral spinal fluid, the accumulation of cerebral spinal fluid and the removal of cerebral spinal fluid, or the increase in blood in the area and removal of blood in the area and, or the production of, uh, brain mass, meaning, um, the, uh,

Just so you know, we're on teams at the moment and we just realized that if you put a thumb up,

it makes it a thumb up emoji on your image. And because as I was counting, I was counting with my thumb as being number one and it gave Matt a thumb up and he gave it back. Sorry. And then the last one is the brain mass. So obviously brain tissue accumulation. So effectively idiopathic simply means we can't see that it's any one of these particular things. But I mean, in a way, doesn't it sort of have to be one of these things? Because you've only got three things

types of tissues present in there. Yes, in principle, you're correct. But I guess coming down to trying to ascertain a diagnosis, if like, for instance, if you're wanting to explore an increased CSF volume,

you would look for the main contenders that would lead to that, whether it is a clot or whether there's some kind of issue with the choroid plexus or whether you feel it's not being reabsorbed, so the granulations or something like that. Now, with idiopathic, there's no real diagnosable. Identifiable. Yeah, that's right. I mean, like the same outcome is, you know, for instance, you do a lumbar puncture, which is you put a...

a needle into the space in your spinal cord and you measure the CSF and it would tell you that there is increased pressure there. But in terms of when you do the scan and look at what could be going wrong in the brain, you don't find anything. Yeah, yeah. Now, issues with this can be, you know, headaches, pain,

blurred vision or alterations in vision and so forth. And one of the long-term issues can be damage to your vision, permanent vision loss. So generally it would be good to be able to identify what's going on and be able to help fix the issue. The way that it tends to be managed can be things like weight loss,

if appropriate. Acetazolamide, which is often used as a diuretic to reduce the amount of fluid within the body. Therapeutic lumbar punctures could potentially relieve pressure. Surgery may be in regards to helping the optic nerve, but it could also be by putting something called a shunt in, which is not something that I call Matt when he annoys me, but a shunt is something that

basically replaces the normal movement of something from one area to another. So you could have a shunt placed that can sort of take the fluid from the ventricles of the brain to the peritoneal space within the abdominal cavity, things like that. Have I missed anything, Matt? No, that's pretty good. So just to look at CSF for a second, we have within the brain tissue, we have these things called ventricles, which are...

Different to the ones in the heart, but these are kind of cisterns, I guess you would say, that helped produce CSF. And there's a particular structure called the cholera plexus, and there's a few of those in the different...

ventricles. So we have the lateral ventricles, which is more around the cerebri, the third ventricle, which is around the diencephalon, fourth ventricles, which is the back of the brainstem. And now in those areas, we also have choroid plexuses or plexi. What would you say? They're blood vessels that almost look like glomeruli. So they're real bunched up in

of yarn-ish like appearances, but they have huge amounts of microvilli which gives them a massive amount of surface area. So just as an example that I came across which I thought was interesting. Let me see if I can find where I...

So, you might only have two grams of Chloroplexis within the floor of the lateral ventricle, which is in the cerebri, but when you add the microvilli to it, so in terms of the Chloroplexis size, it's no bigger than four millimeters in size, so it's not huge, but then when you add an outer microvilli appearance to it, it can increase the surface area up to

70 meters squared. So it is huge in terms of the way it then can produce its CSF, which is kind of like a blood brain barrier of such. So it determines what can go from the blood into the CSF because remember the CSF is what's bathed in the brain. It not only provides buoyancy, so it takes the weight off,

of the brain away from the skull, I guess you'd say, but it also provides its microenvironment, buoyancy, but it also provides a dynamic. So if you do those maneuvers like you spoke about that causes the headache or the changes in pain, which is a Valsalva maneuver, that's changing the pressure transiently in your CSF system. So it increases it.

for that period quickly. And so a function of the CSF is almost like to dampen that pressure. But if it's pressurized, so in this case, because you've got intracranial pressure increase, then when you do those maneuvers, it becomes painful because you are stretching the lining of where a lot of the CSF is, which is your meninges, right? And that's what...

That's where you feel pain in your brain, right? You don't actually feel pain in the brain tissue per se, but you do in the lining. So this CSF and its production is important because if it's not moving through the system well and it has to get reabsorbed back into the venous sinuses, back into the venous blood, then it's going to encounter the issues as you spoke about. And that's kind of where the issue lies. So one of the treatment is to get a...

I don't know, is it a cannula or a needle of such and put it into the ventricles and then put a big long tube all the way down to your peritoneum so it can just drain off into your abdominal cavity. And that's a way of relieving the pressure. Yeah. It's not getting rid of the cause of it, but it's getting rid of the symptoms. Well, hopefully anyway, because when you have a very high pressurized cranium,

certain things will get pressed on and in this case two things that are going to get pressed on is the optic nerve and the abducin nerve and as a result because that's

taking sensory information from the eye but also helping move the eye so you're going to see symptoms associated with it like blurred vision, double vision, vision loss. And that's also how it may be diagnosed is a fundoscope where the doctor looks in your eye and they can see the bulging optic disc which is an indication that you've got high intracranial pressure and that's just adding to the diagnosis I guess you'd say.

Yeah. Cool. But everything else you said is, you know, management, not necessarily getting rid of the cause because we don't know what the cause is, but hopefully dealing with the symptoms which can be debilitating. Yes. Thank you so much, Jen, for the email. We have some more thank yous. So we've got a thank you here from Ayasa and the subject is MCAT video contents. It says...

Hi, Dr. Matt and Dr. Mike. My name's Ayasa. I'm a 40-year-old person trying to prepare for the MCAT with the aspiration of entering medical school. While the journey is challenging, your incredible videos have been a tremendous source of support and motivation for me. I wanted to extend my heartfelt thanks for the wonderful content you create. Your videos have significantly enhanced my understanding of complex subjects, and I truly appreciate the effort you put into making them accessible.

If I may have a small suggestion that could further benefit students like myself, please remove Matt from all content. Oh, wow. Interesting. No problem. I'm happy to assist. No, it says, I'm using the Kaplan MCAT books for my studies and I've noticed that organizing video content to closely follow the structure of these books could be exceptionally helpful.

For example, integrating the discussion of organs and their functions together as outlined in the Kaplan materials would make it easier to follow along and reinforce my learning. I absolutely love Dr. Matt's video on the immune system. Okay. It brilliantly summarizes everything I need to know for the MCAT.

It would be fantastic if similar approaches could be applied to other topics, ensuring they align seamlessly with the Kaplan curriculum. Thank you again for the dedication and the invaluable resources you provide. Your work is making a significant difference in the lives of many aspiring medical professionals. I look forward to your future videos and wish you continued success.

Warmest regards, Claire. That's pretty nice. Oh, sorry, Ayasa. So warmest regards, Ayasa. Thank you so much, Ayasa. That's such a very kind email and a great idea to take a particular approach. At the moment, the approach that we take is, you know, we teach on a daily basis. We know what we're teaching and we know that pretty much

Pretty much every medical school, nursing program, biology degree will cover certain organ systems and structures in particular orders. And that's generally how we record it. Sometimes we tackle it as whole organ systems. Sometimes we tackle it as individual structures or disease states. So that's a great idea to tackle it in a similar way that Kaplan does. So we will look into that. Thank you so much, Ayasa.

We've got another question or another point here from Claire and the subject is, G'day. So do you think Claire's from Australia? Let's have a look. Hello, Drs. Eminem. I'm a pre-nursing student in Colorado. Okay, the US of A. You've been to Colorado, haven't you? Have you skied there? Yeah, I drove through it. But no skiing? It's outside ski season. Oh, okay. Beautiful place though, right?

Lovely. I'm a pre-nursing student. I went through it on a moped. Really? On a moped? It would have taken you forever. You know, Aspen. Wow. Okay. That's a link to Dumb and Dumber. Okay. I forgot. Yes. Were you wearing an orange suit or was it a baby blue suit? Yeah. Actually, I think me being Harry would be the orange one.

If you need inspiration to prepare food, go to Fry's, where you'll find delicious food and delicious ingredients. Choose what you like, and with our low prices, you'll save money. Also, take advantage of more than $600 in digital coupons every week, and up to $1 discount per gallon of fuel with your points. At Fry's, you'll find rich flavors and great savings. Fry's. Fry's.

Fresh for everyone. Hi there. It's your vagina speaking. I know sometimes I have a hard time getting there when we get down, but OMG Cream from Wisp is here to help. The instant arousal makes it easier to, you know...

It takes two minutes to order online, so let's give it a try. O-M-G. I literally just went to heaven. I'm going to try that again. Go tell your friends, though. Get on Wisp. Order OMG cream online at HelloWisp.com. That's HelloWisp.com and have it delivered for free. Use code OMG for 15% off your first order. Yeah, and I was on the back. I was on the back holding on to you. All right.

I'm a pre-nursing student in Colorado and found you through your podcast on Apple. At first, I was like, who are these two Aussie idiots and what I put idiots in there and what the heck are they talking about? Many of the concepts went over my head until I took AMP1 and currently AMP2. I find your podcast delightful because of the balance of banter, jokes, mostly Mike being mean to Matt, lol,

Thank you so much, firstly, Claire. Thank you so much for recognizing that when I'm mean to Matt, it's out of love and it's all in the name of fun and joy. Matt loves it. At the end of every podcast, Matt always slaps me on the back and says, ha ha, that was great how you called me an idiot 12 times. So,

Matt appreciates it. You appreciate it. Everyone appreciates it. I'll keep being mean to Matt. It's not bullying. And the dialogue between you guys to help explain difficult concepts is great. So thank you. I find all of the podcasts to be incredibly helpful, even if I'm not learning that particular topic in class because I will have to one day learn it in nursing school, but mostly because it's helping me to connect the dots when it comes to understanding the human body as a whole. That's what we aim to do. Connect the dots. And one last thing.

I find your knowledge or lack thereof of American geography and culture to be especially endearing.

A few things. We don't use the term granny flat. Oh, yeah. Remember that episode we were talking about the granny flat? Because we had to record a couple of episodes in your granny flat. In my parents. Yeah. I've never heard of that until you talked about it on the podcast. They're called ADUs, accessory dwelling units. That is very specific. It's like saying a waste paper bin.

You know, instead of just a bin. It's a waste paper bin. That's where the waste paper goes. This is an accessory dwelling unit. Wow, ADUs. So anyway, a granny flat because it's where the grands live. Now, our lack thereof when it comes to American geography is

It's probably mostly on my end. I've been to the US twice, have loved every trip there. You've been there far more times, right? How many times do you reckon you've been there? Half a dozen times? Yeah, I think so. But you stayed there for a long time, right? Each time you were there for months. I've only been to Colorado once and that was because Colorado is obviously neighbor's Alaska.

And so that's a joke, Michael. That was a joke. Okay, okay. I know we're colourist. I didn't know. But, you know, I will say this. I will say this, that when one evening shift we were, when I was working in America, we had not a great deal of things to do and I had a competition with all the Americans who could name most American states and I beat them all. Really? You could name more American states than the Americans? Yeah.

Yes. And how many states are they? 52? 51? I mean, if you count Canada now, it'll be 51. And soon to be Greenland. But I think I named it at 30 at that point. Nice. Now, I haven't finished –

Claire's email. Claire's also said that you're also right about many States, I Ohio and Nebraska being somewhere in the middle. So we're not wrong there. So thank you for clarifying that Claire. I know another listener wrote in about this, but I too would love an episode on menopause and what happens to the female body. Did we record that? You just did a video on it. You just did a video on it. So I have done a video on that, but we will do a podcast on it. So, uh,

Thank you for everything you guys do. Love the podcast. Your biggest fangirl, Claire. Thank you, Claire. We love emails like this. And we are so glad that you appreciate our stupidity and sometimes the content that we produce. Yes, thank you, Claire. And if you want to fly us out to Aspen, we'll do some lectures for you. Live podcast episodes in Aspen when they film the new White Lotus there.

All right. Now, Matt, we have another question. Is that correct? Yeah. So this one's from Nicole and the subject is Alport disease or Alport syndrome. Spell that for me. Alport. A-L-P-O-R-T. Okay. Alport disease. All right. What's Nicole asking? All right. So, hello. I've recently been listening to your podcast. Thank you. It's very entertaining and educational. My brother has been diagnosed with Alport disease, so it's X-linked.

And basically, Nicole just wants to know a bit more about the condition and specifically, she's aware that it has inflammation associated with it at the chlamyrile. Is there anything that can be done to decrease this inflammation or damage naturally or from a medication standpoint? Okay. So let's dig into Alport syndrome. Now, Mike, I'm going to start off with the first question. Yeah. To you. Are you ready? I'm ready. All right. All right.

Okay, so my question to you, Mike, is what would you say is the top three most common proteins in the body? I would say... First, second, third. Okay. Number one would be albumin. Number two would probably be the globins. So L from beta globins maybe, right, which are other carrier proteins. And then the third would probably be globulins, which are... Okay. Antibody... Am I right or wrong?

Wrong. Okay. So you'd be right in, so you've listed all transport proteins. Yes. As a collective group, these would come in as number three. All right. Okay. So, and I think the order that you gave would be correct in terms of plasma proteins. So albumin, what was your second one? Globins, alpha beta globins. Cool. Yeah. I guess the only one you potentially missed was hemoglobin, but that's inside a cell. Exactly. But that would be probably more abundant than albumin.

in terms of being in the blood, if you consider that to be the case. But by far the most common protein in the body is collagen. About 30% of all protein is collagen. There's different types which I'll get to in a second. So you're not talking plasma. You're talking about just proteins in the entire body. No, no, whole body. Okay, yes. I would have said collagen is number one. Okay, number two being the –

The proteins in your muscle, so actin and myosin, they would be number two. And then you have the transport proteins, which, as you said, hemoglobin and albumin would be the big ones.

So that's a starting point. Collagen is going to be where we're focusing on this condition, Alport syndrome. Why is that? The next one, because this is where the dysfunction lies in the collagen within the canal. Probably good to state that, don't you think? Okay. I haven't linked us in yet. Okay. Now let's go focus on collagen. Yeah. Okay.

Yeah. Now collagen has four types, four types of collagen type and you can do it in Roman numerals. Yeah. One, two, three, four. Now...

This is, I don't know, you're going to hate me for this, but this is me trying to come up with memorable ways of trying to remember where these types of collagen are in the body. Here we go. Yes, yes, yes. Okay. So collagen type one. If you wrote out the number one, so O-N-E. Oh, and let me guess, put a B in front of it. Put a B in front of it. There we go. So bone, bone.

Collagen in bone is most commonly type 1. Okay. So this is the most abundant type of collagen in the body. This is strong things in the body, so tendons, bone, some parts of the skin. Yeah.

Then we go to collagen two. Yeah. So you write out two and then you put, this doesn't work so well, but you put CR in front of it and end it with Lidge, Car-2-Lidge. Car-2-Lidge. Car-2-Lidge. Car-2-Lidge. Okay. So if you've got speech impairment, then this one works. So Car-2-Lidge is type two collagen. Okay. Then we go to, no, I'm going to get to the kicker here because you're going to be going, why are we going through this? Yeah. Then we go to collagen three. Yeah. Um,

Free and flexi. I can only come up with a rhyme with it. So free and flexi. So this is flexible tissue. You could say three elastic. Three, think of the E in three is elastic.

Okay. Whatever works. These are blood vessels and skin. So these are stretchy things. Yep. Now, this is the important for today's output syndrome. We have four. Now, this one makes sense. Four is on the floor. So all basement membrane is type four collagen. What's basement membrane? Basement membrane is connective tissue that usually anchors the bottom of epithelial tissue. So wherever you find epithelial tissue, it usually has a basement membrane underneath it. Yep.

So in terms of today, now this is where we're getting at, Alport syndrome is... So that's fine. And no one knows what Alport syndrome is. So keep going. Alport syndrome is basically where there's a dysfunction in the collagen, in the base membrane of glomeruli. So now I'm going to throw it to you and ask you, Michael, what is a glomeruli? Why is it important? Why do we have them? All right. So you said that

Alport syndrome is a genetic disease that results in type 4 collagen not working. Is that right? Yeah. Basically, the structure of the collagen gets disrupted. So normally it's a, what do you call it, a trihelix. Okay.

It's kind of three protein fibers wound together which gives it its strength. And so in that protein, because we know proteins are just made up of amino acids, normally what the collagen for should be is a lot of glycine, which if I am correct, this is the smallest amino acid. That means you can jam-pack...

a lot of amino acids together and make it a really tight collagen fiber. But with this genetic abnormality, the coding for the amino acids changes. And so instead of glycines, you make bigger amino acids and they don't fit together as nicely. So the way that the collagen packs in into base membranes, they become smaller.

arranged differently and makes it not work as it should. Yes. And you could hypothesise from this that since basement membranes are the membranes that all the epithelia sit upon, that then this should affect heaps of different multiple areas within the body. And it does, but

Like with many disorders and diseases, you're going to get the most pronounced effects on regions of the body that depend heavily on basement membranes, right? And so this includes, like you said before, the glomerulus within the kidney, but also in the cochlea as well, which is in the ear, and also the eye.

itself. So these are three areas that tend to be affected mostly within Alport disease. But let's talk about the glomerulus because that's what the question was mostly referring to. So

Within the kidneys, the kidneys filter our blood. We all know this. We've got two kidneys. Each kidney has one million filtration units each, which are called the nephron. And the nephron has very small blood vessels that enter it and leave it. And the blood that enters gets filtered through three filtration layers. And those filtration layers are referred to as the glomerular filtration barrier, right? Or membrane. And it's made up of

three layers or three distinct regions of filtration, right? So this is so that ultimately we want to filter everything that's small enough and appropriate to be filtered and keep large things like proteins and cells in the blood and not lose them into a potentially urine. So

Three layers. First layer is something called fenestrated epithelia. So lining the inside of this glomerulus is going to be epithelial cells like most hollow tubes have. And these epithelial cells have big, what we call fenestrations or pores, basically holes in them. They're pretty big in regards to their size, but that's a relative thing. They're big enough to let through fluid and

and ions and small solutes like glucose and nutrients, but they are too small to let cells through. So they don't let red blood cells, white blood cells through. Then underneath that membrane, you've got the glomerular basement membrane. Now, this is the one that's made up of the type four collagen. And what we know is that collagen is quite negatively charged.

And it acts not only as a size barrier like the previous one, but also as a charge barrier. So it will repel negatively charged things and proteins are negatively charged because of their phosphate backbone, right? So they're negatively charged. So it sort of repels. So importantly in this instance, this glomerular basement membrane,

which the type 4 collagen is required repels proteins specifically. Then the next layer is what we call the podocyte layer and this is where you've got cells that have these big extensions or feet

And between the feet, you've got these slits called slit diaphragms. They're very small, right? So they're like a tenth of the pores that we were talking about earlier in the epithelia. And they, again, offer another size barrier to not let through any further proteins and cells as well. Now, all three of these layers together are really important to provide what we call an ultra-filtrate. Basically, no cells, no proteins. Let's filter everything else through.

This is very important. Now, if you have damage to any one of these three or multiple, you can let things through that shouldn't, like proteins and cells. Therefore, it's probably easy to recognize that in Alport syndrome, when you don't have the type 4 collagen, that with this layer gone, it's not uncommon for these individuals to have, and sorry about all the birds that you can possibly hear in the

that can be present within the filtrate, within the urine. But it can also lead to cells moving through because over time, that tissue becomes more and more damaged, leading through larger things. So you can get hematuria, which is blood in the urine, but also proteinuria, which is proteins in the urine as well. And this can lead to damage, further damage happening at that tissue, which can also lead to scarring and so forth. Now,

Nicole said that in the question that, and we may not have read this part, but said her understanding is it's inflammation of the glomerulus.

but it's not really inflammation. It can lead to inflammation of the glomerulus, but the problem isn't the inflammation necessarily. The problem is the type four collagen not forming appropriately. And because it's genetic, it's not necessarily something that an intervention can be very easily managed for in regards to trying to remedy that situation. What do you have to add in regards to this, Maddy? What have I missed out? What would you like to add?

Now, you've covered it pretty well. So as you said, the root cause here is a collagen for structural abnormality. Now, most individuals won't have these problems at birth. They will start to develop them over time. And that, as you spoke about, can affect the basement membrane in the cochlea and the front of the lens. So you may...

On top of, and the most common genetic abnormality is an X-linked chromosomal defect, which codes for just one of the strands of the collagen for, as I spoke about, the trihelix. So one of those strands get impacted by a gene on the X chromosome. But it can also come from autosomes, which can be both recessive and dominant autosomes.

But usually what will happen is over time as we age, we need to replace the collagen in these basement membranes and when they're getting replaced, they get replaced by faulty collagen. So this is why it's not usually present at birth. You start to develop as we get older and as it gets laid down with a different collagen process,

it becomes dysfunctional. And like you mentioned, the thickness of the basement membrane starts to change. That means we start to let things through. From my understanding, the first things that generally go through would be actually microscopically blood. So you get hematuria microscopically. So if you were to do a urinalysis, you would find that. Because blood cells are very small.

Yeah, as it progresses and gets worse, so as it gets thinner and becomes more porous, you'll start to let through more gross amount of blood. So you may actually see it in your urine. And then as we start to get scarring, so we get sclerosis now of that basement membrane and we start to see proteins go through. And the distinction there is sometimes what we call proteins going through interurine nephrotic syndrome, which just means...

Yeah, basically it's just high amounts of protein whereas if you get blood with the protein, it's generally nephritic syndrome. Now when this is all happening, you may get changes with the podocyte and also the connected tissues around the nephron which is sometimes termed menangeal. What would you call it? Tissue, I guess. That can be inflamed to some degree.

But unlike some other causes of nephrotic or nephrotic syndrome which can be inflammatory based which can cause what we call glomerulonephritis, using steroids or anti-inflammatories won't be overly helpful because the crux of the problem is not inflammation. It's actually a collagen deficiency or a defect. And so using anti-inflammatories won't overly be helpful. So what the...

will be trying to work with is decreasing the pressure on the kidney. So you're trying to take stress off the kidney so that they usually use blood pressure medication like ACE inhibitors or ARBs, which is angio-receptor inhibitors. We have done, even though we can't pronounce them, we have done episodes on them. So it takes the pressure off the kidney so it decreases it to worsening. Literally.

And because essentially you don't want to progress into, even though it's likely it will, progress into a renal insufficiency and then ultimately a renal failure of such, which then requires dialysis. But if you are able to take the stress off the kidney, particularly from a blood pressure point of view. Yeah. And early diagnosis is really important to help this.

Now in terms of the other areas, they probably have a little bit more, or at least the eye, they can actually put artificial lenses in and that can overcome the weaknesses at the front of the lens which can happen also from the collagen full defect. And in terms of hearing, hearing aids and so forth may be useful in that regard. But in terms of anti-inflammatories, from my understanding, because it's not really an immune-driven device,

inflammatory driven process, the use of anti-inflammatories is in a mainstay approach. Yeah, yeah.

So, look, hopefully that helps Nicole in regards to understanding a bit more about that disease and what's happening anatomically and physiologically. Now, we have... Just a... Can I just say one... Yeah, keep going. We'll add another 20 minutes to this part. I'll add one minute to it. I'm just playing. The only contrasting... Go on. Another contrasting example is...

There's another condition called Goodpasture Syndrome, which is also an issue with the base membrane. But instead of a collagen 4 defect, what happens in this regard is we actually get an immune-driven process, which actually, I think from my understanding, I think it's a type 3 hypersensitivity disorder where we have immune complexes that's happening in the body and they get stuck in the base membrane. Okay.

That can also happen in the lung because the lung also has basement membranes and that causes inflammation of the basement membrane which then can cause all those symptoms we spoke about. But the difference here between good pasture and Alport is good pasture has an inflammatory immune component and that can be treated with those type of drugs where Alport is a collagen 4 defect. So...

anti-inflammatory or immune mediated won't be as useful. Yes. Now that's a great distinction and I'm glad you added that.

So thank you. We now have some feedback from Julia. The subject is feedback with three exclamation marks. So I'll be interested to see what happens here. Hello! With two exclamation marks. My name is Julia and I'm a Brazilian med student still in year one and I reached out to you guys to say that I've been learning so much from your classes and that they are actually helping me to adapt to my college's active learning method. Smiley face.

You two are excellent professors. Keep it up. Well, thank you so much, Julia. We appreciate it. If you have any suggestions for videos, let us know. And it's great to hear that our content is reaching Brasilia. So it's very cool. I've never been to Brazil. You've been to Brazil? I have. Yeah, Rio? Been to Rio?

Rio, I love Rio. Lovely. I always say this to my mum when she gets angry. DiCaprio? No, no. I always say this to mum. I said, Rio, I think, is the most beautiful city in the world. And mum says, that is a lie. Sydney is. Sydney's up there. But Rio's stunning. I'm sure. I've never been. I'd love to go. I'm waiting for a conference in Rio so that I can attend. This is an email from Ben. Ben?

And it says, biology and human anatomy, thank you. And I'm already going to say no, thank you, Ben. Hey, Dr. Matt and Dr. Mike, I'm 29 years old from Canada. I've never been to Canada either. There's all these places. You know, if you're listening and you're, I don't know, you work at a university and you would like me or you're a student there, feel free to advocate for me and suppose Matt as well to come over and do a presentation, guest lecture series, whatever

maybe present on using YouTube or podcasting within education. Just advocate for us to come and we will come over and we will present to you guys. We would love to do that, any opportunity. And it will be tariff-free? Well, no, I'll charge 10% extra. So 29 years, no, actually it's Canada. So no, it's going to be tariff-free.

I recently elected to upgrade my high school biology and your channel has been a huge help. Covering complex topics like endocrinology and in-depth nervous system functions were initially daunting until I found your channel and podcast. I love this type of feedback because this is exactly why we made these platforms, right? For people to not find these relatively complex topics daunting. Okay.

I walked into my final exam today with a 93% class average. That's very good. That's better than you and I ever got. And I'm confident I maintained that standard. That is bloody awesome. Your channel, both YouTube and Spotify, were critical in my development as an advanced age student. Because of you, I've gained academic confidence in myself, which I did not previously believe was possible.

My current aspiration is to become a paramedic and I know that the tools and teachings you've given me will assist in my academic journey. Thank you both so much for your time and patience. Sincerely, Ben from Canada. How good is it to read these emails? Lovely. Thank you, Ben. I mean, not many people get emails like this to say thank you for what you're doing. It's awesome. It is. That's why we do it. We should be humbled. I've never seen you humbled before, but we should be humbled. What's the opposite of humble? All right, last question.

Arrogant. That's you. All right, last question.

If you need inspiration to prepare food, go to Fry's, where you'll find delicious food and delicious ingredients. Choose what you like, and with our low prices, you'll save money. Also, take advantage of more than $600 in digital coupons every week, and up to $1 discount per gallon of fuel with your points. At Fry's, you'll find rich flavors and great savings. Fry's. Fry's.

Fresh for everyone. Does it ever feel like you're a marketing professional just speaking into the void? Well, with LinkedIn ads, you can know you're reaching the right decision makers. You can even target buyers by job title, industry, company, seniority, skills...

Wait, did I say job title yet? Get started today and see how you can avoid the void and reach the right buyers with LinkedIn ads. We'll even give you a $100 credit on your next campaign. Get started at linkedin.com slash results. Terms and conditions apply. Okay, this one is from Grant and subject is I've got a challenge for you. Oh my gosh, here we go. Is it a three-legged race?

Okay. I have pitting edema in my legs, mid-shins, so bracket mid-shins and ankles. I'm a healthy person. I don't have too much body fat. So basically what Grant's saying here, very active. He works as a firefighter, been in the military, healthy diet, no known comorbidities, but he has noticed that he has been seeing some pitting edema in his legs.

Lower extremities. He's also in the medical field now as an EMT. So that's awesome, Grant. Nice.

So basically he's not sure what is the cause of his pitting edema and he would like us to present some thoughts around this. So again, all we can present is, you know, what is the pathophysiology of pitting edema versus other types of edema? We can talk about the anatomy and the changes that can happen. Obviously we can't talk about your specific case, Greg, because obviously we know... And he has said that. He said...

I'm going to the doctor to find out, but I just want to see what you guys think physiologically is going on. Cool. Well, where should we begin? There's a concept that I always talk about called capillary exchange, which I think is always a good place to start. But what do you think? Yeah, I think that's where we begin. The only distinction I'll just say here is pitting versus non-pitting. Well, let's address that next.

Okay, all right. Well, you take over and look at the dynamics of capillary exchange. Well, all I really want to say is that, you know, as we were talking about before with intracranial pressure, we've got blood vessels that feed all the tissues of our body and they feed at the capillaries. So as the blood moves through all of our arteries and moves through into smaller and smaller what we call arterioles and then ultimately into capillaries, there is that blood pressure which is the outward push.

Now, that outward push, once we get to the capillaries where there's holes or pores, that's where blood can actually leak out under that pressure, that blood pressure, which we call hydrostatic pressure, but we don't really need to talk about that too much. And what is that pressure approximately? Oh, gosh. From a numerical standpoint. I don't know. What is it like? Off the top of my head, I don't know. I always have to revisit it. 55? Is it 55? 55.

The number in my head was around about 50-ish. So yeah, 50 millimeters mercury-ish. But anyway, let's not worry about the numbers. Let's just say as the blood enters into the capillary, there's an outward push and that pushes fluids, nutrients, gases out of the capillaries, right? The problem is...

Because we've got capillaries at every tissue, if we are pushing all the fluid out of our capillaries, we would lose our blood fluid and therefore blood pressure very quickly if we didn't reclaim that fluid. So while on, as the blood enters the capillary, fluid gets pushed out, on the other end of the capillary, the fluid gets dragged back in. And that dragging back in is due to mostly proteins within the blood vessel that are too large to leave.

So you've got the outward push by the blood pressure called hydrostatic pressure and the inward pull, which we call... Okay. And let's not worry about the numbers because it gets confusing. And the inward pull from the proteins, which we call the oncotic pressure. Okay.

And then that allows for us to reclaim the lost fluid so we don't lose our blood pressure. Now, it's not perfect. Sometimes that fluid can also be reclaimed by the lymphatic system and then the lymphatic system will dump that excess fluid that we couldn't reclaim back into the bloodstream. But the point I'm trying to get across here is that there's a couple of really important things that happen to maintain fluid in the blood vessel and not outside of the blood vessel, which we call edema.

And that is the outward push from the blood pressure has to be a particular value and the inward pull has to be a particular value. The outward push is due to the blood pressure and the inward pull is due to proteins. So I love this concept because it allows students to understand edema perfectly, right? Because if I said to you, Matt, what if your blood pressure increased...

Your answer would be, well, then the outward push would be greater and more fluid would leave the blood vessel and accumulate in the tissue, which we call edema. Okay, that makes sense. What if we were to remove the proteins from inside the blood vessel? We would have less of an inward pull and the fluid would remain outside. So two big contributors to edema is increased blood pressure, but also a reduction in the plasma proteins.

that are inside. I just put my thumbs up again and I've just got fireworks behind my head on the team's meeting. That's two thumbs up. Two thumbs up. So, you know, these are just some of the basic, and then you can think about all the things that can increase. But now there's obviously other things such as the venous return. So if you're blocking the end of the capillary, if you're blocking venous return to the heart, that blood pressure can back up as well. So it's not just blood pressure from upstream where the heart is, but blood pressure downstream.

of the capillary bed as well. And, you know, many, it could be a blockage in the lymphatic system where that fluid reclaims. So there's just a whole bunch of, now, this then leads us to, I've just sort of indicated very quickly what leads to an accumulation of fluid in the interstitium or the tissue, which we call edema. But you were going to talk about

pitting edema versus non-pitting edema. And I think this now gives us a nice understanding as to what can contribute. So firstly, Grant has said he's getting that pitting edema. So what's that? That's basically where you have fluid accumulated, let's just say, in your ankles. And if you were to stick your finger into your ankle skin...

and kind of try to push it in as far as you can do without causing too much pain and then remove your finger, it stays pitted. So there's an indentation that remains in your ankle. Whereas if you were to non-pitting, you push it in and it bounces back straight away. So usually the most common is pitting edema. Now what would likely cause non-pitting edema is that there are certain –

molecules that's remaining in the extracellular or interstitial space. Are you saying for non-pitting? Non-pitting. So it's kind of... So if the... Let's just say the fluid that left the blood vessel had not only fluid with it but also other molecules... Including proteins. ...that are osmonically active, including proteins, that would...

cause a different dynamics or a different fluid dynamic within the extracellular space or the interstitial space, which kind of allows it to remain...

Yeah, the way I think about it is that the water's going to be more greatly associated with those substances like the proteins in the interstitium. So when you push your thumb down in pitting edema, when the proteins and those osmotically active substances aren't there, the water has places to displace and move, right? Hence the pitting. Yeah.

But if you've got proteins and osmotically active substances in the interstitium, the water is going to be associated with it so that when you push your thumb down, it doesn't really move the water out the way very well. It's more like a gel-like substance in which it just bounces back, right? Yeah.

Yep, and a good example of that would be edema associated with inflammation. So we've all had inflammation. Let's say you've – we'll stay in the ankle. You've rolled your ankle. You've sprained your ankle. You caused injury to your ankle tissue. There's inflammation that happens there. So what's actually going on microscopically is –

are released from injured cells. They go to the near blood vessels. Blood vessels dilate but they also become leaky and not only fluid goes out which is plasma but also plasma proteins and some white blood cells. Yeah. Now, in doing so, they cause the tissue to remain Swollen. How did you describe it? So,

So when you put your finger into it, it will just bounce straight back. Yeah. So if you've ever had an inflammatory injury like muscle – so I tore my calf, remember? Yeah.

and that led to a lot of inflammation and a lot of swelling. But it was a non-pitting edema because that inflammation led to proteins and also osmotically active substances being in the interstitium. So the whole thing was just tight and swollen without the pitting. But in this instance, we're talking about pitting edema, which is...

potentially an indication that proteins are remaining inside of the blood vessel, but also osmotically active substances are remaining inside of the blood vessel.

Yep. And so now going to you, Grant, because you don't typically, from what you've said, you don't typically fall into the main candidates of where those categories could break down. So as Mike said, you may have a situation where you have increased hydrostatic pressure, particularly at the venous end. A good example there would be heart failure.

specifically right-sided heart failure, or you may have a deep vein thrombosis or portal hypertension. So going to what could be situations with a healthy person, quote unquote, that could lead to a pit endema in the leg could be things as simple as prolonged standing because when you stand in

Vertically, for long periods of time, gravity is working against us and so it's just harder for us to reclaim that fluid back into the venous system. So again, people who don't have comorbidities or diseases, they can still experience edema associated with gravity or even high amounts of exercise. So if you were to do a lot of exercise that still required you to be in a vertical position,

you can experience edema just because of working against gravity. And you can see that profoundly when we go on aeroplanes. It's very common for individuals to experience edema after aeroplane.

hours of inactivity on an aeroplane. Does that make sense, Mike? And generally, so generally speaking, pitting edema, you know, in most instances is due to a hydrostatic issue. So an increase in the pressure that's entering the blood vessel or an increase in the pressure of the blood leaving the vessel. And there could be multiple causes for that

So again, that's not anything referring specifically to Grant or your situation, but it's just identifying the fact that generally with pitting edema, it tends to be a hydrostatic issue upstream or downstream of the capillary network.

Yep, that's right. And remember also in the context of exercise and a lot of exercise, you've also got changes with thermodynamics. So by temperature, temperature changes the way that fluid moves in and out of tissue because of the way it's trying to regulate things. So it is quite common for, again, healthy individuals to be when they're in hot, humid climates to develop some of the early stages of heat stress, which is known as

heat-related edema and that's because the body, again, is just trying to regulate temperature and one of the methods is to get fluid out into the periphery to help dissipate temperature and as a result you may experience more degrees of edema. And even just by vigorous exercise you're going to get degrees of muscle injury, right? Microscopic muscle injury which can...

induce small amounts of inflammation, which again can lead to edema and even just profound increased blood flow to those regions, which again will change the dynamics. These things are always happening in our bodies and it's only when we are looking at some of those exams that we gave earlier where you have actual structural abnormalities elsewhere, like heart failure or liver issues or kidney issues where

you know, you'd want to explore some of the reasons behind why this is happening. And it's important to say that it's great that you're going to go see a doctor and find out exactly what the cause is. So hopefully us talking about the anatomy and physiology helps in regards to the understanding of this particular process. So

Maddy, we have gone through, we've done the episode. We have many questions and thanks in the backlog that we need to go through, but we're going to do more Q&A episodes. But Maddy, thank you so much for joining me and thank you, dear listener, for the email and for the thanks. We want more of them. My ego needs to continually grow.

be stroked. That's the only thing keeping me going, to be honest, is my ego. And if there's anything that you'd like from us in regards to episodes, podcasts or YouTube, just let us know and we will be happy to review and hopefully record some more stuff for you very soon in the future. So, thank you, Maddy. ... ...

♪

Fries.

Fresh for everyone. Aplican restricciones en combustible.

I can't tell you how often I hear, oh, I'm a little OCD. I like things neat. That's not OCD. I'm Howie Mandel and I know this because I have OCD. Actual OCD causes relentless unwanted thoughts. What if I did something terrible and forgot? What if I'm a bad person? Why am I thinking this terrible thing? It makes you question absolutely everything and you'll do anything to feel better. OCD is debilitating, but it's also highly treatable with the right kind of therapies.

Regular talk therapy doesn't cut it. OCD needs specialized therapy. That's why I want to tell you about NoCD. NoCD is the world's largest virtual therapy provider for OCD. Their licensed therapists provide specialized therapy virtually, and it's covered by insurance for over 155 million Americans.

If you think you might be struggling with OCD, visit nocd.com to schedule a free 15-minute call and learn more. That's nocd.com. Hey, guys.

Have you heard of Goldbelly? It's this amazing site where they ship the most iconic, famous foods from restaurants across the country, anywhere, nationwide. I've never found a more perfect gift than food. They ship Chicago deep dish pizza, New York bagels, Maine lobster rolls, and even Ina Garten's famous cakes. So if you're looking for a gift for the food lover in your life, head to goldbelly.com and get 20% off your first order with promo code GIFT.