Well, thank you, Johannes, for the introduction. The next two days are going to be more clinical,

and this will be a very basic introduction to acid-base, and it's not my area of research,

so there's much greater experts in acid-base sitting in the audience, and I'll divert the

questions to them. But thinking back, my first research project was actually an acid-base

project, my first project as a student, and it's shown here, that's when I started working

with Peter Aaronson. I was supposed to look at the effect of metabolic acidosis on trans-celluloclore

transport. I can tell you I worked on this for 10 months, nothing came out of it, other

than that the media turned purple when we induced acidosis and the cells started dying.

The other thing I noted is that Peter is really known for his clarity of thinking and analyzing

things, but I don't think it's really reflected well in his handwriting skills. So this will

get me to my topic. What we will be doing is we're going to be touring along the nephron,

what we've been doing in the last two days, and now we're going to apply that, how that

is relevant to acid-base homeostasis. And then, as mentioned, the next two days, beginning

today, will be more clinical. So in the second part, I'll be talking how this is relevant

to clinical practice, what we see every day. So again, starting very basic, as you know,

we define the, when we measure the pH, it's really the extracellular pH, and when we are

on rounds and we see a gas and the pH is 7.1, oftentimes people then say, well, it's acidosis.

It's not absolutely correct because really it should be acidemia because we refer to

a low pH as acidemia and vice versa when the pH is high as alkalemia. And acidosis is really

the process leading to the stage of low pH and vice versa. Why is this important? Because

you may have concomitant acidosis and alkalosis, but for example, when the acidosis overweighs,

the pH will be acidemic. So the classical acid-base approach, we focus around CO2 and

bicarbonate and we'll be hearing a different approach as well presented by Dr. Rastegar.

And the strength of this system, as many of you know, of course, is that it's an open

system. And when you gas a solution with CO2, the CO2 will dissolve based on Henry's law.

And then this step, actually, the hydration of CO2 to form carbonic acid is extremely

slow unless it's metabolized by or it's processed by carbonic anhydrase. And the net reaction

is when CO2 forms with water that a proton is being generated and a weak base. And this

brings us to the classical formula that we use when we approach acid-base disorders.

And that's the Henderson-Hasselbalch equation, which is really the logarithmic restatement

of the CO2-bicarbonate equilibrium. And what is so central to this equation is that it

says that the pH is not per se defined by the bicarbonate in itself. So it's really

not the CO2, it's the relationship between the two. And what are the main organs regulating

this? Surprisingly, of course, it's the kidney that's involved. And as you know, the CO2

is really regulated by respiration and the bicarbonate by the kidney. And when you look

at chronic respiratory disorders, the pH hardly changes. And that's because the kidney really

sets the bicarbonate so that there's hardly any change in pH. So let me ask you, what

would happen if you take a healthy person, you take out both kidneys, you perform a dual

nephrectomy, and you keep living a normal life, let's say for two days, what would happen

to your pH? So that is partially true, because on a normal diet that we all eat, that's true,

that you would become asedemic. And that's because the diet we eat is usually an acid

diet. And when you eat protein, what happens, methionine and cysteine and lysine and arginine

gets metabolized to protons. So if you eat a meat diet, there's a net acid production.

It's not only diet, but also of course, it can be generated as part of ketoacidosis and

lactic acidosis, which we'll be hearing about in the third talk by Ben Walsh, where a proton

is being generated. So however, if you would be on a vegetarian diet, for example, that

is very high in glutamate, bicarbonate is being generated. So if you would take out

the kidneys and eat a vegetarian diet, you might as well turn alkylenic. But the answer

is true that for the majority and the diet that we've been feeding you over the last

two days, you would certainly turn asedemic. Important to note as well, lactate and acetate