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Hank takes us on the fascinating journey through our excretory system to learn how our kidneys make pee.

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References
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookexcret.html
http://www.khanacademy.org/science/biology/v/the-kidney-and-nephron
Campbell Biology, 9th ed.

Table of Contents
1) Homeostasis & Osmoregulation 00:00
2) Urea & Uric Acid 01:30
3) Kidneys 02:49
4) Nephron 03:40
5) Glomerulus 4:15
6) Bowman's Capsule 04:25
7) Proximal Convoluted Tubule 04:49
8) Biolography 06:16
9) Loop of Henle 07:36
10) Distal Convoluted Tubule 09:23
11) Collecting Ducts 09:57
12) Ureters, Bladder & Urethra 10:45

crashcourse, crash course, biology, science, human, anatomy, physiology, homeostasis, organ, urine, urinary, kidney, ureter, bladder, urethra, osmoregulation, balance, metabolism, ammonia, urea, uric acid, toxicity, blood, nephron, renal artery, glomerulus, bowman's capsule, filtrate, loop of henle, renal cortex, renal medulla, freidrich henle, diuretic, anti-diuretic hormone, kangaroo rat, beaver, pee, osmosis Support CrashCourse on Subbable: http://subbable.com/crashcourse

 Homeostasis and Osmoregulation


One of the coolest and most important things that our bodies do is maintain this thing called homeostasis, the regulation of a stable internal environment, no matter where we are, or what we're doing.

After all, we put our bodies through a lot every single day. We're always adding food and liquid and chemicals and we're constantly changing temperature and our levels of activity but our bodies can roll with it. It's like no big deal for them.

All of our organ systems have some hand in maintaining homeostasis, I mean its basically the thing that makes us not dead, but the excretory system, aka the urinary system, which includes the kidneys, the ureters, the bladder, and the urethra, is the star quarterback of the homeostasis team.

That's because your excretory system is responsible for maintaining the right levels of water and dissolved substances in your body. This is called osmoregulation and its how our bodies get rid of the stuff we don't need like the byproducts of metabolizing food, while also making sure that we don't get dehydrated. It's the body's greatest balancing act, and your body is doing it right now, and all of the time, as long as you're not dead.

As with other organ systems we've talked about, not all excretory systems in the animal kingdom are created equal.  Different animals excrete wastes in different ways based on their evolutionary histories, what environments they live in, and what their hobbies and interests are. These factors all influence how an animal regulates water and most metabolic waste needs to be dissolved in water in order to be excreted. 

 Urea and Uric Acid


(01:30)

A problem is a main byproduct of metabolizing food is ammonia, which comes from breaking down proteins, and it's pretty toxic, so depending on how much water is available to an animal and how easy it is for the animal to lug a bunch of water around inside it, animals convert this ammonia into either urea or uric acid.

Mammals like us as well as amphibians and some marine animals like sharks and sea turtles convert ammonia into urea, a compound made from combining ammonia and carbon dioxide in their livers. The advantage of urea is its very low toxicity- it can hang out in your circulatory systems for a while with no ill effects, but you have to have some extra water available to dissolve it and get rid of it.

This isn't such a tall order really, I mean peeing isn't a huge inconvenience, I mean is it? Its not for me , anyways. Well, it would be, though, if you were a bird, or an insect, or a lizard living in the desert.

Animals that have to be light enough to fly or don't have a bunch of spare water hanging around convert ammonia into uric acid, which can be excreted as a kind of paste, so not a lot of water is needed.

Using bird poop- if you haven't taken a good look, next time do that, just look, the white stuff in the bird droppings is actually the uric acid-y pee, and the brown stuff is the poop.

So now that we've established what is and what is not bird poop, lets get down to the brass tacks of how humans get all of this urea out of our blood and into our toilets.

 Kidneys


(2:49)

The excretory system starts with the kidneys, the organs that do all the heavy lifting from maintaining those levels of water and dissolved materials in our bodies to controlling our blood pressure.

And even though they do an amazing job - I'm not badmouthing your kidneys here - the way that they do it is frankly a little bit janky and inefficient.

They start out by filtering a bunch of fluid and the stuff dissolved in the fluid out of your blood, and then, uh, they basically absorb 99% of it back before sending that 1% on its way in the form of urine. Seriously, 99% gets reabsorbed. On an average day your kidneys filter out about 180 liters of fluid from your blood, but only 1.5 liters of that ends up getting peed out.

So most of you excretory system isn't dedicated to excreting, its dedicated to reabsorbing. But the system works, obviously, I'm still alive, so we can't argue with that.

 Nephron


(03:40)
And now it is time to get into the nitty gritty details of how your kidneys do all this and it's pretty cool, but there's lots of weird words, so get ready.

Your kidneys do all this work by using a tiny network of filtering structures called nephrons. Each one of your mango sized kidneys has about a million of them.

If you were - don't do this - but if you were to unravel all of your nephrons and put them end to end, they would stretch over 80 kilometers. This is where all the crazy action happens, so to understand how they work, we're just going to follow the flow from your heart to the toilet. 

Blood from the heart enters the kidneys through renal arteries, and just so you know, whenever you hear the word renal,  it means we're dealing with kidney stuff.

 Glomerulus


(04:15)

As the blood enters, it's forced into a system of tiny capillaries until it enters a tiny tangle of porous capillaries called the glomerulus. This is the starting point for a single nephron. 

 Bowman's Capsule


(04:25)

The pressure in the glomerulus is high enough that it squeezes some of the fluid out of the blood, about 20% of it, and into a cup-like sack called the Bowman's Capsule. The stuff that gets squeezed out is no longer blood, it is now called filtrate. It's made up of water, urea, some smaller ions and molecules like sodium, glucose, and amino acids. 

The bigger stuff in your blood, like red blood cells and the larger proteins, they don't get filtered.

 Proximal Convoluted Tubule


(04:49)

Now the filtrate is ready to be processed, from the Bowman's Capsule it flows into a twisted tube called the proximal convoluted tubule, which means the tube near the beginning, and that is all windy. Why are we so bad at naming things!

Anyway, this is the first of two convoluted tubules in the nephron, and these, along with other tubules we're talking about are where the osmoregulation takes place. With all kinds of tricked-out, specialized pumps and other kinds of active and passive transport, they reabsorb water and dissolved materials to create whatever balance your body needs at the time.

In the proximal tubule, it's mainly organic solutes in the filtrate that are reabsorbed like glucose, and amino acids, and other important stuff that you want to hang on to. But it also helps to recapture some sodium and potassium and water that we're going to want later.

From here, the filtrate enters the loop of Henle, which is a long, hairpin shaped tubule that passes through the two main layers of the kidney. The outermost layer is the renal cortex - that's where the glomerulus and the Bowman's Capsule and both convoluted tubules are - and the layer below that is the renal medulla which is the center of the kidney.

Cortex, by the way, is Latin for "tree bark", so whenever you see it in biology, you know that it's the outside of something. Medulla, on the other hand, meaning "marrow" or "pith", so you know that it's the inside, just to help you remember this stuff. 

But before we take a tour of this amazing loop, I have to do a couple of things. First, go pee, because this is, y'know, and second, a biolography, so I'll be right back. 

 Biolography


(06:16)

The Loop of Henle was discovered by nineteenth century German physician and anatomist Friedrich Gustov Jakob Henle, and I'm pretty sure he was just one of those guys that you can't gross out, because he spent most of his career dissecting kidneys and eyeballs and brains and also seemed to be a huge fan of mucus and pus. He was, by far, the most important anatomist of his time. His three volume handbook of Systematic Human Anatomy was recognized as the definitive anatomy textbook of its day and was famous for its exquisite attention to detail and its intricate, even beautiful illustrations. 

Not only did Henle discover the loop of Henle, arguably the lynchpin of kidney function in mammals, he was also an early adopter of the wildly unpopular germ theory of disease. His student Robert Koch is considered to be one of the founders of microbiology, and the two worked together to formulate the Henle-Koch postulates, which today remain the four conditions that must be met to establish a causal relationship between a microbe and a disease.

Henle taught the world so much about the human body that there are right now in you no fewer than nine features that bare his name. From the Henle's Fissures between the muscle fibers of your hear to the Crypts of Henle, which are microscopic pockets in the whites of your eyes, also the name of my Cradle of Filth cover band.

 Loop of Henle


(07:36)

All right, so review time, we've squeezed some filtrate out of the blood and reabsorbed some of the important organic molecules we want to keep, but most of the reabsorption action happens here, in the Loop of Henle, which does three really important things.

One, it extracts most of the water than we need from the filtrate as it travels down to the medulla. Two, it pumps out the salts that we want to keep on the way back up to the cortex. And three, in the process of doing all that it makes the medulla hypertonic or super salty relative to the filtrate, creating a concentration gradient which will allow the medulla to draw out even more water one last time from the filtrate before the final journey to the toilet begins.

It's complicated and again, kind of janky, but it's what allows us mammals to create urine that's as concentrated as necessary using only the amount of water that our bodies can spare at the time.

So first, filtrate starts going down the loop and the thing to know here is that the membrane is highly permeable to water. Not so much to salt, or anything else, mainly water. Now compared to the filtrate, the tissue of the medulla is already pretty salty, and as the filtrate processes, the surrounding tissue becomes increasingly hypertonic. The farther down you go, the saltier it gets.

So applying everything that we've learned about osmosis, you know that as the filtrate moves along, it loses more and more water through the membrane. By the time the filtrate gets to the bottom of the loop, it's highly concentrated.

And now the filtrate enters the ascending end of the loop, and here it's basically the same but in reverse. The membrane is not permeable to water and instead it's lined with channels that transport ions such as sodium, potassium, and chlorine. And because the filtrate is so concentrated now, it's actually hypertonic compared to the fluid outside in the medulla. So as it ascends, huge amounts of salt start flowing out of the filtrate which makes the renal medulla really, really, really salty.

This salty medulla also creates a concentration gradient between the medulla and filtrate which we're going to need in the final step of pee-making.

 Distal Convoluted Tubule


(09:23)

But first, once the filtrate is back up in the cortex and out of the loop, it enters the second of our convoluted tubules, called the distal convoluted tubule, or farther away curly tube. While the first tubule worked mostly in the reabsorbing of organic compounds in the filtrate, here the focus is on regulating levels of potassium, sodium, and calcium.

This work is mainly done by pumps and hormones that regulate the reabsorption process. By the time it's done, we have finally taken everything we want to keep out of the filtrate, so now, its mainly just excess water, urea, and other metabolic waste. 

 Collecting Ducts


(09:57)

This stuff all gets dumped into collecting ducts that channel it back down into the center of the kidney, the medulla. And remember, the medulla is super salty, right, so now more hormones kick in that tell the collecting ducts how porous to make their membranes. If the membranes are made very porous, more water is absorbed into the medulla, which makes the urine - yes we can start calling it urine now - even more concentrated.

And here's a fun fact, if you've ever had one drink too many, you might have noticed that you start to pee a lot and your pee is clear. That's because alcohol interferes with these hormones, especially one called Anti-diuretic Hormone which tells the collecting ducts to be very porous so that you absorb most of the water. With those hormones all confused and out of commission, you just start peeing out all kinds of water, which also means you're getting dehydrated, which means you're officially on a one-way trip to hangover city. So now you know why that happens.

 Ureters, Bladder, and Urethra


(10:45)

Now at this point, the urine leaves both kidneys and flows down to the urinary bladder by tubes called ureters. Once in the bladder the urine just sits around waiting for us to decide when it's time to find a bathroom and when that time comes, the little sphincter muscle relaxes and releases the urine from the bladder into a tube called the urethra which empties out wherever you point it. 

So that's how your excretory system works, and that's basically how it works for most mammals, although some modifications are made based on, again, where they live and what they do. For instance, kangaroo rats, which are tiny and adorable and live in the desert, have the most concentrated urine of any animal anywhere because it can't spare the water. So it has a very, very long loop of Henle that reabsorbs most of the water from the filtrate.

On the other end of the spectrum, we have the beavers who have very short loops of Henle because they're like water reabsorption, shmater reabsorption, do you see what I do all day?

And so now you know the true origins of pee. Thank you for coming to learn with us here at Crash Course Biology. We hope that you learned something. You can go to youtube.com/crashcourse and subscribe for more biology and history videos. Thanks to everyone who helped put this video together. There's a table of contents over there you can click on and review stuff that you didn't get and of course, if you have any questions for us, you can leave them in the comments or on Facebook or Twitter and we will endeavor to answer. Goodbye.