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.
5_5 "Barrier Function of Inflammation. Part 1"
Loading...
来自 Saint Petersburg State University 的课程
General Pathophysiology
29 个评分
Explore Related Videos
At Coursera, you will find the best lectures in the world. Here are some of our personalized recommendations for you
从本节课中
Pathophysiology of inflammation. Part 1
与讲师见面
Churilov Leonid PavlovichAssociate Professor, Full Member of International Academy of Sciences (Health and Ecology)
Department of Pathology, Faculty of Medicine
[MUSIC]
Barrier function of inflammation was understood initially
in the terms of mechanics, in the sense of mechanical barriers.
And it was done long ago in previous century.
But in the end of 20th century, part of physiology came to
conclusion that barrier of inflammation should be understood,
not only in the terms of mechanics, but
also in the sense and terms of informatics.
There are conclusive data on the development of classical
acute inflammation is in isolated, denervated organs in chick embryo
chorioallantoic membrane, which is devoid of neural elements.
You can observe, for example placentitis, typical inflammation of placenta.
But placenta is not innervated, neither from maternal nor from fetal side.
So I already talked about that, but I will repeat.
The nervous system is of some influence on inflammation,
but of course, not decisive and not principal.
It may exert a certain influence, especially in course of
some inflammatory components such as vascular reaction.
It provides also reception for the sense of pain and
for the sense of itching, which may accompany inflammatory foci.
And this is important for the overall picture of inflammatory
manifestation, but especially important is normal reflex.
Non-reflex paracrine activity
of sensory neurons, because they are also endocrine cells,
they are not only elements of relay in CNS.
Sensory neurons are endocrinocytes,
and they are able to secrete in impulsless
mode via antidromal pathway.
Some peptides or autacoids like neurokinins,
for example, substance P and other neurokinins.
And these neurokinins from sensory neurons, innervating the foci or
areas of inflammation, they may influence the mechanisms of exudation.
Moreover, sometimes the sensory neuropeptide
action of sensory neurons may even elicit information.
It would be so called neurogenic inflammation, but
these neurogenic mechanisms are not reflectory.
They are also humoral.
Neuron works not as a source of neural impulse and neural transmitter.
Neuron in that case works as a source of autacoid signal,
like other cells of inflammatory focus.
In other words, basically, the focus of inflammation is delimited
in getting information from the neuroendocrine system.
It is delimited with oedema, with slowing of blood flow,
with functional sympatholysis, which was discussed
in one of my previous lectures, and so on and so forth.
Now I would like to give you very bright example of how local and
systemic mechanisms interact through the acute inflammation..
Look at this picture.
You can see unhappy person, who probably was ironing his trousers.
And occasionally,
he has got a burn with that hot iron,
a burn of elbow area of his left arm.
So this burned person, he has in that burned area
typical zone of acute inflammation with strong and
bright dynamics of this process, with a huge amount
of inflammatory autacoids produced or activated.
But at the same time, because of that accident, this person has stress.
And stress goes in parallel as a systemic response for extraordinary stimulus.
And because of stress, if you will measure the content of
glucocorticoids like cortisol in systemic blood of that burned person,
you can find it 6 times, 8 times, 10 times elevated.
If you will measure the blood content of catecholamines in that person,
it can be elevated 20 times, even 50 times.
But listen, both glucocorticoids and
catecholamines are potent and key inflammatory regulators.
Glucocorticoids may inhibit virtually all facets of the acute inflammation.
Catecholamines, well, if you have rhinitis, if you have cold in your nose,
you take drops like Xymelin,
Naftizin, and so and so forth, very many commercial means.
But the acting ingredient is catecholamine.
And by means of that catecholamine, dropping it into your
inflamed nostril, you get inflammatory signs down.
You decrease the intensity of hyperaemia, of oedema, and so on and so forth.
How it is possible in one alive person, at the same time,
locally, you have huge inflammation.
But systemically,
you have huge concentration of anti-inflammatory mediators.
And they do not prevent the full local dynamic of inflammation.
They do not stop local reactions.
It means that local zone and systemic zone of regulation are somehow separated.
They are delineated informationally.
Informational isolation of the burn focus by means of stasis,
by means of renal congestion, oedema, and other barrier functions.
And these barriers, they establish non-sensitivity or
decreased sensitivity of local targets to systemic and inflammatory signals.
All that systemic signals can just to delineate inflammation,
prevent its spread.
But within that extraordinary damaged zone,
there will be extraordinary situation and special laws, special laws of war.
The constitution of organism is created for peaceful situation, it acts for peace.
But in that area, another matter of regulation acts,
extraordinary laws of emergency.
They are dictated by local inflammatory mediators.
And these inflammatory mediators, they overcome the anti-inflammatory
systemic effects, but within the limited area only.
That is very important.
It means that the isolation in
inflammatory barriers is bilateral.
Not only organism is afraid to spread something out
of the inflammatory focus into the whole organism.
Body also prevents excessive systemic action on that
zone of extraordinary laws.
Not only germs should be delimited from spreading
by the barrier function of inflammation.
For many years, pathologists traditionally taught their students that,
listen, there are barriers, and the barriers prevent the spread of infection
beyond the borders of inflammatory focus in order to prevent sepsis.
And it is the truth.
There are different barriers, slowing of venous flow,
complete stasis in the center of inflammation in microcirculatory band.
Fibrin deposits leukocyte shaft,
the formation of granular matter in so
called delayed hypersensitivity.
Pyogenic membranes of abscesses, sequestration
of damaged area, for example, in osteomyelitis.
All these are manifestations of physical barriers
preventing from systemic spread of infection
out of the focus of inflammation and to the neighboring tissues.
I can remind that it includes also function of regional lymph nodes,
filtering and inactivating dangerous components of fluid
drained by the lymphatic vessels from the inflamed area.
So all that above-mentioned mechanisms, they prevent the spread and
generalization of infectious germs from the foci of inflammation.
But what the body is afraid of
in case of sterile aseptic inflammation?
Inflammation can be aseptic very often.
For example, auto-immune inflammation can be aseptic.
But nevertheless, non-infectious cases of inflammation,
they also create barriers and barrier function is also realized.
So what the body is afraid of?
Well, it surrounds with barriers foci of aseptic
inflammation with no germs in them.
Not only germs should be delimited from spreading.
The most important thing is to delimit inflammatory
mediators from systemic spreading.
They should act within inflammatory foci.
But if they will act too actively in systemic circulation on non-damaged
organs, they may cause severe systemic complications.
First of all, excessive systemic action of inflammatory mediators may cause shock.
Here you can see the researchers,
who first contributed into that idea of
the bilateral character of inflammatory barriers.
Not only inflammation does not let out, but it also does not let in.
Some barriers prevent zone of inflammation from excessive systemic control.
The person whom you see in the right picture
is Polish pathologist of 19th century, Rudolf Klemensievicz.
As early as in 1893, he said, in the development of inflammation,
neurogenic factor in the time of maximum disappears,
giving way to the phenomena of the vessels themselves.
In that period, local autacoids driving the inflammation were not yet discovered.
Much later, Soviet scientists Leon Orbeli and
Alexandr Ginetsinskiy discovered so-called functional sympatholysis.
They have shown that in inflammation, the blood vessels and
smooth muscle cells within their wall become non-sensitive
to systemic vasoconstrictive neural signals.
Because they are under prevailing influence
of antagonistic local vasodilatory mediators.
So we may say that physical and informational barriers,
they provide relative separation of the areas
relevant predominantly to local control and
predominantly to systemic regulation.
