Dear listeners! Warning: this course contains shocking materials and is not recommended for viewing to persons with weak psyche, minors and pregnant women. The course describes subject and methods of Pathophysiology, its place within system of biomedical sciences and history. It includes General Nosology (concept of health and disease, general etiology and pathogenesis, pathological processes and states, role of causal factors, conditions, reactivity and somatotype in pathology). It gives systematic of locally and centrally driven typical pathological processes: arterial, venous and combined hyperemiae, stasis, inflammation, immunopathological processes (including allergy and autoimmune disorders) acute phase response, fever, stress, shock, etc. Course deals with functional, metabolic and informational aspects of typical pathologic processes, like disorders of signaling, reception, post – receptor translation, programming and program archiving, conflicts of programs in living systems. It contains the consequent analysis of the injury and defensive responses as regards separate cells, organs and tissues and the whole organism. The lectures based on author’s original three-volumed textbook and workshop in Pathophysiology republished in Russia many times.
2_4 "What is a Disease?"
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來自 Saint Petersburg State University 的課程
General Pathophysiology
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從本節課中
General Nosology. Health and Disease
與講師見面
Churilov Leonid PavlovichAssociate Professor, Full Member of International Academy of Sciences (Health and Ecology)
Department of Pathology, Faculty of Medicine
The next question we shall discuss,
what is a disease?
And probably the best way to start is to give
you the opinions of very informative persons.
First definition I would like to give you is
from German biologist, evolutionist Ernst Haeckel.
Listen to his definition: a disease is a dangerous adaptation.
Very wise, very clever man.
By the way, he invented the term Pithecanthropus.
Health is also adaptation and disease is adaptation,
but these are different adaptations.
In health, adaptation is affordable,
not very expensive, not dangerous.
In disease, adaptation is costly,
and because of that, adaptation is dangerous.
So as soon as adaptation became dangerous,
it creates not health but disease.
The next person, we shall respect very much,
also already mentioned many times, Rudolf Virchow.
You already know that.
His opinion was that disease is "Steeplechase running."
or disease is life across the barriers, life with obstacles.
The next person who will contribute is very well
known not only in my country and your countries also,
it is Karl Marx.
Here you can see him very younger,
junior year students and the very famous definition of
disease by Karl Marx: disease is nothing but "A life constrained in its liberty."
Constrained life, very interesting point of view.
He wrote that not about medical problems,
he wrote that in his paper dedicated to journalism in Germany.
But that great philosopher could see everything in
every detail and he says if life is not constrained,
if you have freedom, you're healthy.
But if you are constrained, constrained in choice,
limited in your options,
that are signs of disease.
The next person is from my university,
it is famous systemic biologist, Lev Semyonovich Berg.
Lev Berg said, disease is just "a step of evolution."
Also very interesting point of view although a little bit cynical,
which is catastrophe for an individual,
may be step of evolution and even the future for the remaining biological species,
which is vicious for individual,
maybe useful for biological species as a whole.
Disease maybe is a variant of evolution,
trying what will happen if we will try that,
although of course individual is victimized in this situation.
And finally, let me give you my definition,
not so wise and maybe not so short and concentrated but I think that disease is
a forced unstable form of living process and disease is
always in discrepancy in some mismatch with the concrete situation.
If there is discrepancy between
the mechanisms of adaptation which organisms apply and the situation,
if mechanism of defense is not in accordance with situation not in full accordance.
As soon as we have this discrepancy or this mismatch between
concrete situation and mobilized defensive programs, we have disease.
It can be a discrepancy in time,
in place or in scale.
For example, in anaphylaxis,
it is like to shoot from cannons into sparrow because stimulus is very weak,
it is just a small molecule of antigen which is not so vicious,
not so dangerous for your body but your organism gives hyperergic,
strong allergic reaction and person may die as a result of that defense,
not as a result of the vicious stimuli.
So if the response of organism is in discordance with the situation,
in discordance with stimuli in time,
in place or in scale,
that is a soil for disease growing.
Disease decreases the efficiency of living system,
diminishes the resources reserves,
functional reserves of organism.
Disease can result from technical error or from technological fault in
organism in its software or in its hardware or in both.
That's probably the main characteristics of disease in general.
A disease can result from problems with fuel,
problems with bricks out of which body is constructed.
And finally, disease can result from problems with information.
Three possible areas which can cause the disorder in organism:
not enough fuel or improper
disposal of fuel like in diabetes mellitus and you have disease,
not enough bricks or improper distribution of bricks.
Like in iron deficient anemia, which is by the way,
the most prevalent metabolic disease all over the world,
we have one billion and a half of persons in the world with iron deficiency.
So, that is example of disease from the problems with bricks.
But organism is not only fuel and bricks,
organism is also a huge system of information.
And I can give you many examples how the misinformation or
lack of information creates disease in living body.
Metabolites are not only bricks and firewood like in previous pictures,
metabolites are also templates like DNA and signals like hormones.
And Pathophysiology first gave birth to
Pathochemistry as you remember from my first lecture,
but nowadays, it also gives birth to Pathoinformatics.
Look at this person.
It is German pathologist Gustav Wilhelm August Joseph Ricker.
He lived long ago,
long before the EPO of cybernetics.
And he insisted that,
disease can be not only because of
structural disorders or because of energetic disorders,
disease can also result from the pathology of relations as he call that,
pathology of relations between the elements of organism.
Every element at first glance is more or less all right,
but the link between them is spoilt.
That was early protocybernetic idea,
the Pathology of Relations and now we call that, Pathoinformatics.
And in next part of my talk,
I will explain to you some details about cellular Pathoinformatics.
You have already seen this picture in my previous lecture.
We'll now talk about dualistic nature of any pathological process about
disorders of hardware versus disorders of software in living cells.
Every cell is like a liquid or semi-liquid computer.
We have programming, reception,
transmission of signals, archiving,
retrieving programs and so on and so forth.
That's why the nature of any pathological process is
dualistic and current Pathophysiology deals not only with hardware,
with substantial and energetic side of disease in terms of molecules,
in terms of fuel and bricks.
But also, we can analyze every disease in terms of its informational side,
software side in terms of signaling,
reception, translation of signal,
mimicry of signals when cell mistakenly interprets one signal instead of another one.
And all taken together,
it creates the Pathoinformatics of living cells.
Look at this table please.
We have here from left side in the first column,
we have types of chemical driving signals in organism.
It seems that we have endless number of driving signals.
But in fact, only few types of them: hormones, neurotransmitters,
antibodies, substrates like glucose for example which
can drive the behavior of beta cell in langerhans islets, and ions.
Ions also can rule and can drive the cell behavior like calcium ion for example.
And in horizontal row above,
we have different types of disorder or diseases.
Disease can be created,
can be resulted from excess of signal,
from the lack of signal or deficiency of certain message or certain signal,
and finally which is most interesting,
disease can result from mistake of our software,
when the cell mistakenly confuses
two different signals and takes one signal for absolutely another one.
And in this table in its cells,
you can see, well, approximately 15 examples.
Every example is example of a
disorder-related to excess or deficiency or mimicry of signals.
For example with hormones,
you can have disease because of too much hormone,
like in Cushing's syndrome or Itsenko-Cushing's disease with
pathologic increase in adrenocorticotropic hormone concentration
and all metabolism comes in disorder.
You can have disease because of deficiency of certain hormonal signal
like an insulin dependent diabetes mellitus type 1 with absolute insulin deficiency.
And all metabolism comes in disorder.
And finally, you can have mimicry of signals when cells are deceived.
They are duped.
They mistakenly took one signal for absolutely another one,
and now I will explain you the details.
I will tell you about
highly spread endocrine disease named in Russia and in Germany Von Basedow disease,
and in English speaking countries,
they call that Graves disease, in Italy,
it is Flajani disease,
in Ireland, it is Parry disease.
The sense is not in the name,
the sense is in pathogenesis.
In Graves Von Basedow disease,
thyroid gland grows and produces goiter.
And not only cell growth and cell proliferation is pathologically accelerated.
Cell function is also pathologically increased and there is hyperthyroidism plus goiter.
Hyperthyroidism plus goiter gives you Graves form Basedow disease.
What is the main pathogenic mechanism?
The main pathogenic mechanism is immunologic.
This disease is autoimmune.
What is the situation?
The situation is mimicry of signals.
Normally, thyroid-stimulating hormone produced by pituitary
should drive thyroid function and thyroid growth.
And there is [inaudible] and feedback because of
that concentration of TSH and concentrations of thyroid hormones are always in balance.
But in this particular case,
in case of out immunity Graves Von Basedow disease,
there is new player, antibody.
This is antibody against the receptor of TSH on thyroid cells.
It is like to put in keyhole,
well, a screwdriver instead of a normal key.
But this is very,
very skillfully designed screwdriver.
It can serve instead of key and that is
the case when antibody does not block the receptor,
but [inaudible] stimulate it instead of hormone.
And a person, a patient has
almost zero level of thyroid-stimulating hormone, but nevertheless,
the growth and function of thyroid gland is
over active with goiter, with hyperthyroidism,
and it is antibody which is blamed for that because antibody is
able to stimulate cellular receptor instead of hormone.
That is typical mimicry of signals.
So, you can see now that mimicry of signal can also create a kind of pathology.
