Good morning everybody. I'm very impressed that so many people are still here on the

last day of this wonderful but also exhausting meeting. After a lot of discussion about tubular

function, I will try to give you a slightly different perspective, but I will come also

to what's tubular function. Now before diving into the kidney, I would like to draw your

attention and in particular the attention of our students to something completely different.

You may have noticed that we are a little bit concerned about the air conditioning here

in this room during these days, so we have these air conditioning machines here that

are running during the breaks and we kept the doors open. And I believe that it is not

unlikely that while we kept the door open, we invited a number of insects to come into

this room. And as we are around 90 people here, I believe that we probably also have

at least 90 small insects in this room. And we don't really notice, we don't bother.

And the reason for that is because these animals are small. Unless they are mosquitoes and

bite us, we don't really care. But imagine for a moment that these 90 insects, let's

assume they are 90, would be as large as humans. That's a scary perspective. That's pure science

fiction. But the reason why I'm mentioning it is that I learned that there was indeed

a time when on this earth the insects were almost of the same size as human beings are

nowadays. There were these dragonflies which you see on the left-hand side, which had about

the same size. So why was that and why are insects so much smaller today? The answer

is simple. The insects were so large at a time when the oxygen pressure in our atmosphere

was very much higher than it is today. And the reason why this is important is that insects

rely entirely on oxygen, on diffusion to supply their cells with oxygen. And so when the oxygen

concentration in the atmosphere came down, they had no other means to adapt to this rather

than to become so small that the diffusion distance was still sufficient to receive enough

oxygen for their cells because insects were not clever enough to develop a circulatory

system as many other species, including human beings, have done. With this circulatory system,

we have become somewhat independent from oxygen diffusion through our outside surface. But

of course, everything in nature and in life comes with a price. And although we could

maintain our size, it means we are now very much dependent on our circulatory system.

And if you would go to the hospital here a couple of yards from this place, at least

50% of the hospital beds are being filled with individuals who have a problem with their

circulation in one or the other way. The second price that we have to pay is that circulation,

of course, in itself is not helpful unless we can transport oxygen. And for oxygen transport,

we have developed these nice shuttles called red blood cells. And that is the other price

that comes with this. If we want to rely on a circulatory system with red blood cells,

we have to control the number of red blood cells. If there are not enough red blood cells,

oxygen supply will be insufficient. If there are too many, that is even more dangerous

because viscosity will increase, clotting risk rises. So the price that comes with this

independence from diffusion is the need to fine tune the red blood cell number. And the

way, interestingly, the way that nature has chosen to regulate this is not to maintain

the number of red blood cells constants. It's not to maintain viscosity within a specific

range. But actually, the mechanism has been designed in a way that the final step in what

we want to achieve, optimal oxygen supply to tissues, is being regulated through the

number of red blood cells. And this is simply shown here. This is achieved in a way that

the hormone, which is essential for production of red blood cells, erythropoietin, is being

produced in an oxygen-dependent fashion in a very elegant feedback loop where the number

of red blood cells plus the oxygen loading of these red blood cells, in other words,

the oxygen content of blood determines the production of erythropoietin. And erythropoietin

then stimulates red cell production. And this is in all our textbooks.

Now the organ, and now we come to the kidney, that is mainly responsible for this adjustment,

at least in adults, is the kidney. And during fetal life, the liver is the main production