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_6 "Specific and Non-Specific in Pathogenesis: is There Any Real Need in That Division?"
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Do curso por Saint Petersburg State University
General Pathophysiology
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General Nosology. Health and Disease
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Churilov Leonid PavlovichAssociate Professor, Full Member of International Academy of Sciences (Health and Ecology)
Department of Pathology, Faculty of Medicine
The next thing we shall discuss is the relation of
specific and nonspecific components to pathogenesis of diseases.
Traditionally, it is believed that you can find in mosaic of
any disease more specific constituents which are typical only for this disease,
only for a short list of diseases,
and less specific components,
which are universal and observed in people with many other diagnoses.
Is it really necessary to separate nonspecific links
and specifically links in pathogenesis? Look at this picture.
This is a face of a patient,
lady patient, with systemic lupus erythematosus.
This is autoimmune disease.
And you can see the pathognomonic
or almost absolutely specific external manifestation of this disease,
butterfly rash or malar rash on the face of a patient.
If medical doctor can see that,
he can suggest the diagnosis of systemic lupus.
It means that specific symptom,
the symptom is evaluated as specific one.
But if we will explore the mechanism,
the main instrument which acts in pathogenesis of systemic lupus are auto-antibodies,
and the most characteristic kind of auto-antibodies in this disease,
auto-antibodies against double strand DNA.
Of course, interaction between antibody and antigen is highly specific.
Although, by the way,
it is not absolutely specific because the specificity of immunoglobulin,
the specificity of T-cell receptor,
should not be overestimated.
There are criss-cross reactions,
and there are non-organospecific antibodies and so forth,
but here, we can see the symptom which is regarded as specific one.
But antibodies responsible for that and
the many other symptoms are absolutely nonspecific,
because double strand DNA exists in every nucleated cell of our organism.
That's why in systemic lupus,
not only skin is involved,
brain is involved, lung is involved,
even joints, heart, abdominal organs,
everything is involved, and the symptomatic of this disease is extremely versatile.
Although antibodies of concrete specificity are responsible for a major part of symptoms.
Why?
Because although the interaction of antibody and antigen is specific,
but the distribution of auto-antigen is universal.
Double stranded DNA exist in very many organs and tissues.
So the gradation between specifical and nonspecifical components of pathogenesis,
of course, is relative.
Although it is of some worth,
because you know it is obvious that certain components of disease like stress,
which exist in the beginning of every disease like hypoxia,
which sooner or later develops in every severe disease for some organ or for some tissue,
like inflammation, which is imbedded into pathogenesis of very different disorders,
and we will speak about that in next lectures.
Many components of pathogenesis are universal or versatile,
and some components depend on
specific interactions between certain antibody and certain antigen,
certain enzyme and certain substrate,
certain receptor and certain hormone.
These are specific components of pathogenesis.
And they are of great help in diagnoses.
You know, such traditional division on
specific and nonspecific component probably is a little bit outdated,
because it is not possible to act or to signal generally.
Every signal and every action in organism has precise address.
Another thing is that many addresses are universally distributed.
They exist in different organs,
in different tissues, like double stranded DNA.
And I would like to remind you,
in conclusion of this part of our talk,
I would like to remind you the principle coined by Paul Ehrlich,
the father of immunology.
Paul Ehrlich said in Latin,
"Corpora non facit nisi fixata."
It means that nothing can act by other means than to bind to something.
The basis for specific interaction in organism is
a binding between molecules, ligands and receptors.
And in major parts of diseases,
this principle is responsible for most important specific manifestations.
For example, in generalized myasthenia,
severe disease with progressive respiratory failure,
person experiences severe muscular weakness.
And the reason is specific antibody,
antibody against nicotine cholinergic receptor in skeletal muscle.
No antibody, no symptom, no disease.
That's why not only in infectious diseases which result from concrete microbe,
but in overwhelming majority of somatic disorders,
we always can look for some specific interaction which is responsible for major symptoms.
Let's look at one more picture with part of pneumonic symptom of an autoimmune disease.
This is so-called "symptom of seal's flippers" in advanced rheumatoid arthritis.
And you know, eastern medicine, Chinese medicine.
Knew long ago about that specific interaction principle.
Look at Chinese pictogram of yin-yang interaction.
It seems that ancient Chinese knew very well this principle of
specific interaction as a basis of disease.
Even all know specific processes like stress, like inflammation.
They depend on hormone receptor interactions.
They depend on interaction of cytokines,
for example, and cytokine receptors like inflammation.
So specific interaction, we can always find even
in the mechanisms of so called nonspecific processes.
Now, a few words about outcomes of disease.
In fact, there are three principle outcomes: full recuperation,
partial or incomplete recuperation, and death.
Full recuperation, it means that after some process,
after some disease, an organism have restored its health and its potential.
When it is possible,
overwhelming majority of the processes
after which we can get full recuperation are acute ones.
Process should be acute.
After acute disease, full entire recuperation is possible.
And next condition, organ which is involved must have good redundant excess,
or redundant potentially substituting excess of functional elements.
A good example is kidney.
Kidney consists of nephrons.
And minimally, 20 percent of nephrons we have
is enough to establish basic functions of kidney.
So if for example a person experiences shock,
severe acute circulatory shock,
of course kidney is damaged and acute
renal insufficiency occurs.. And for some period for several days,
major part of nephrons do not function.
But step by step, after several month,
full recuperation is possible because even if some nephrons irreversibly
damaged and perished once and for ever after such an acute shock,
the remaining nephrons step in function, substitute,
and even part of nephrons is absolutely
enough to establish the organ functions in whole scale.
That would be entire recuperation.
After episode of acute renal failure,
entire recuperation may occur after 8 or 12 months.
The next category is absolutely undesirable for medicine. It is death, fatal outcome.
In which case, fatal outcome occurs.
If pathogenesis of disease involves and irreversibly
spoils vitally important function, respiration and circulation.
It means that in every case of death,
regardless of the reason, immediately before death,
there is hypoxia because there is disorder
of respiration and there is a disorder of circulation.
That's why there exist a big huge branch of medicine, resuscitation.
And the whole branch of resuscitation deals
with severe acute hypoxia and its consequences.
The next outcome is incomplete healing.
Incomplete healing means that some structural changes and
some functional limitations stay in involved organs after the end of disease.
It can be, for example in a personal experience,
acute myocardial infarction and survived,
it can be cardiosclerosis,
focal cardiosclerosis remaining there after the outcome of acute disease.
And speaking about incomplete healing,
it can be manifested in relapses,
in exacerbations, in complications, and in disability.
Relapses are exacerbations after periods of remission.
It is the same disease which returns after some period of relief or episodes of symptoms.
A good example is schizophrenia,
which proceeds with exacerbations and reliefs.
Another good example is chronic leukemia.
Patients may have complete relief and after that new attack,
because as soon as you extinguished major part of malignant clone of leukemic cells,
you have induced relief.
As soon as the remaining cells again proliferate,
patient will experience the next exacerbation.
You need to understand the difference between relapse and complication.
Relapse is returning of the same disease but complication is
a new disease caused by old one or by treatment of old one,
unfortunately iatrogenic or iatrogenic diseases or diseases
produced by treatment or by drugs also exist in healthcare.
And, complication can be joining of
some process which is not obligatory for a typical course of initial main disease.
For example, many people suffered from scarlet fever but
only five percent of them give post scarlet fever immune complex glomerulonephritis.
Why only five percent?
Because they have different reactivity.
They have poor clearance of immune complexes.
In every case of scarlet fever,
we have immune response.
In every case, we have immune complexes,
but only five percent are of those whose organism cannot deal with
that immune complexes properly and they give
complication post scarlet fever, glumerulonephritis.
It is complication.
It is not obligatory for a regular course of disease.
Finally, outcome of disease,
a kind of incomplete healing,
can be manifested in disability like
limb amputation after anaerobic infection and so on and so forth.
These are the main outcomes of any disease.
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