Good evening my dear friends. Today, I invite you to become the Knights of a fair lady. The name of of that lady, which would like to knight you like in this picture, her name is Pathophysiology. For the ladies of her circle, basic medical disciplines, she is relatively young, slightly above two centuries of age. She was born in 1791. 1791 is the time of Catherine the Great. That's why you can see here, monument to that fair lady which is standing in my city of St. Petersburg, not far from my university. And you can see that fair lady, Catherine the Great, is surrounded by 12 knights. She knighted them and these 12 men served for her during all their subsequent life. These were her ministers and military leaders, her lovers and they created the prosperity of her country, Russia. I hope that at least some of you will serve to fair lady of Pathophysiology for all subsequent life. Although, I do understand that majority of you are knighted only until the day of getting MD Diploma. So, the fair lady of Pathophysiology, her name in different languages sounds differently and even is written differently. In Russian, it is Pathophysiologe; in English, Pathophysiology; in French, Physiopathologie; in German, Pathologische Physiologie; in Chinese, five Chinese characters Bin Lee Shin Lee Sue, which means literally physiology of disease; and in some other languages which I cannot even pronounce. But, everywhere in the world, Pathophysiology is essential for a clinical reasoning of medical doctor. That's why it is mandatory for medical curriculum. The story started in 1791 in the state of Prussia and you can see here enigmatic person. We could not even find his portrait. That's why you can see just the debris of his figure in black. It is physician of Prussian King, August Friedrich Hecker. August Friedrich Hecker, in 1791, published in Prussia the first ever written textbook in Pathophysiology. You can see here his hand script that is his letter to editor, with the request to publish it. But in fact, the story of Pathophysiology starts even before that and it is rooted into 16th century because the idea of pathophysiology appeared much earlier than this book was published. Their idea appeared in early 16th century. And, in early 16th century the person whom you can see here, genius French physician, Jean François Fernel. It was a really clever man. In that period, no one did not understand what is respiration, what is biological oxidation, even oxygen was not yet discovered. But this particular man, Jean François Fernel already wrote genius sentence, "Life is weak fire burning without flame". Now, four and a half centuries after him, we can confirm that he was absolutely right. And he was absolutely right not only in that but also in his other prognosis and his prognosis was there must be a special kind of physiology designated for life of a sick person distinct from healthy person. So, the idea of pathophysiology dates back to 1542. Another person, also legendary figure, which stands in the beginning of pathophysiology is a Flemish or Franco-Flemish physician, Dean of Medical Faculty at Montpellier University, Johannes Varandaeus or Varandal. He lived in late 16th, early 17th century. And, in his book about the diseases of the ladies in 1617, he first coined in the term Physiopathologie, which is Pathophysiology in French. So he's the author of that word. Also clever men, I need to say those who never studied Pathophysiology and never graduated from medical school, they mistakenly believe that it was Sigmund Freud, who in 20 century linked suppressed sexuality and mechanisms of diseases, but in fact. This idea came much earlier three centuries before Sigmund Freud. Varandal, author of the pathophysiology term, already insisted that certain diseases of young girls, like anemia of young girls, may be related with suppressed sexuality. So you can see that very clever people invented the idea of pathophysiology and even the very term of pathophysiology. First, specialized monograph in pathophysiology was published also in France in 1819 by L. Cailliot, Elemen de Pathologie Generale et de Physiologie Pathologique, with my terrible Russian accent. Well, now the story comes from France to Germany because first the Department of Alegemene Pathologie, first academic institute of pathophysiology and second in the world, still existing and still published scholar journal in pathophysiology, all that is related to these genius man, Rudolf Ludwig Karl Virchow. In Western texts, sometimes, he is characterized as farther of pathology but in fact, this father gave birth not to one daughter but to twin children. You can see here two childs, twin or even Siamese twin because there is some connection between them like isthmus or like umbilicus, which joins them together. These two children of one the father are two branches of pathology. These branches are two sister sciences, very close in their subject but quite different in their methods. One sister, you already know her, it is fair lady of pathophysiology. And another sister is also a good woman. Her name is anatomic pathology. So one father of two sisters, pathophysiology and anatomic pathology. Virchow is very, very great man contributed greatly into both these sciences. I will not go into details. You will look it through making yourself studies with this picture. But believe me, he was not only a great pathologist but also very, very kind man. He said, "Medical doctors are natural advocates of the poor." And that is good principle not only in science, in social life also. So Virchow not only gave birth to these two daughters. He understood that very soon, they will separate, very soon they will develop and they will perform a diverse. And he said, "Pathophysiology never can be constructed upon anatomic pathology. Pathophysiology has only two pathways, clinical observations and experiments. That's why pathological physiology does not flow out of anatomic pathology. It is great autonomous and extremely important science based on clinical facts and experiments." Please note this. Father not only gave birth to these two sciences. He understood that they will diverse in future. And probably he even understood that in a remote, remote future, they will again integrate. Now, I must say about two opposite views, two opposite approaches to the subject of pathophysiology. And there are different approaches as regards to the relations between normal physiology and pathological physiology. You can see here two persons equally famous, equally contributed into medicine. One of them, French scientist, Claude Bernard, insisted that spatial pathological physiology is useless and unnecessary. Normal physiology and pathology have the same lobes. He said there is only one physiology for health and disease because a house destructs in a fire according to the same laws of physics and chemistry, which its construction was based on. So when you construct a house, you used physical laws and chemical laws and during the destruction of this house in some calamity, in earthquake, the same rules are in action. So why do you need spatial physiology for the sick person use the same which you use for healthy person? German scientist, Virchow, was his opponent, and he expressed his opponents very brightly. He said, "There are different conditions and different limits for display of the same laws and for display the same mechanisms. Disease is a life of an organism under abnormal conditions." And relation of physiological and pathological is the same as relation of smooth running and the steeplechase in sports. Please look at this picture. You can see one sportsman and another sportsman, but they are involved in different kinds of sports, and this different kind of sports, they require different limits of their function. That's why- Organism behaves not identically and behaves differently in the state of health and in the state of disease. Disease, in Virchow's understanding, is a life of an organism under abnormal conditions but in different conditions. Organism may mobilize the mechanisms, which in normal life, are silent, not functioning so we all have insisted that there is a difference between normal physiology and pathophysiology because relation of physiological to pathological is the same as a relation of smooth running and steeplechase running. Look at this picture. You can see two Olympic sportsmen. By the way, Virchow was one of the members of the first Olympic committee for the first Olympic games. So one makes smooth running and other one must jump across the barriers and it requires another muscles, it requires another kind of movement. And the second person in steeplechase, mobilize the functions which are silent or not used in first case. That's the difference. Disease is a life across barriers or against obstacles. I will give you very simple example. Every medical student who learned normal physiology knows very well the hormone named anti-diuretic hormone or vasopressin and even the name of this hormone says about its biological effects. At least about effects demonstrated in normal healthy organism. One effect is to decrease diuresis and activate reabsorption of water in kidney and another effect of this and displayed in normal state vasopressin is to squeeze the blood vessels and to tend the blood pressure up. But listen, all these belongs to the situation of health and let us take the situation of disease, heavy disease, severe disease. Let us take a person who is under severe combined trauma. For example, a soldier wounded and damaged. And this organism now, because of trauma is in the status of so-called traumatic shock. If I will measure the level of a vasopressin in blood plasma of that person, I will be very surprised because in severe traumatic shock, the concentration of these hormone may increase 1,000 times, even 10,000 times. These creates absolutely different and absolutely new situation. Imagine that you have a sugar, crystallized sugar, and you have tea. You may put one teaspoonful of sugar into your tea and that will be sweet tea. You may put two spoons, three spoons, and it is still will be tea, sweetened. But if you will take 10 kilos of sugar, and if you will try to put that 10 kilos of sugar into your tea, the result will be no longer tea, no longer tea. It will be either syrup, or even brown stained crystals of sugar. So the increase in hormone, 10,000 time entirely changes its biological effects, and the effects which were not observed in healthy range, they became obvious when the organism goes beyond the range of norm and beyond the range of health. And it is in severely damaged and shocked persons that we understood that vasopressin or anti-diuretic hormone is also very strong provocateur of blood clotting, the system of vasopressin regulation is very sensitive. Even one cigarette smoke increases the concentration of the hormone five times. Not speaking about such a severe disorder as combined trauma and in the status of severe combined trauma, extremely high concentrations of vasopressin, they render absolutely different biological effects. It is from these studies that we know, that vasopressin hormone is not only a regulator of urination and regulator of blood pressure, but also very potent and very strong stimulator of blood coagulation. It is able to stimulate the production and the release of blood clotting factors from endothelial cells. It is able to stimulate thrombosis platelet function. And one of the catastrophic complications of severe trauma and shock disseminated intravascular coagulation results from extremely high concentrations of vasopressin in blood. As soon as medicine understood that, new drugs were invented, which can block these effects of vasopressin and save the life of that severely damaged person. So, of course, there are laws of physics and the laws of chemistry are the same in the status of health and in the status of disease but they ranges different. In different conditions, organism can mobilize or vice versa ton of different programs, different mechanisms can be either put in function or turned off. That's why, sometimes, in the status of disease, you can see much more, and you can reveal much more potential possibilities of the living body. And if you will ask me who was right, Claude Bernard or Rodulf Virchow? I will insist that Rodulf Virchow was closer to the truth. Pathophysiology is equally important as normal physiology in medical education.
