Inflammation, as typical pathological process has common regularities, which always are present and don’t depend on the cause, localization, species of an organism and its individual features. The inflammation can arise in various organs. Each concrete case has it’s own features, but the scheme of the inflammatory reaction response will always be identical, that is typical. The inflammation is the local process, but all organism reacts definitely too. Immune, endocrine and the nervous systems are main engaged systems inflammation. ADVANTAGES: It causes destruction of microbes. Causes detoxification of toxins. Clears infections. Helps in healing process. Causes repair of damaged tissues.
During the acute inflammation the pathological agent is destroyed completely and the process ends in liquidation of the inflammation and reparation of full value. The chronic inflammation develops as the result of persistent influence of the pathological agent on an organism, organ, and tissue, which cannot be destroyed and eliminated by the organism. The normoergic inflammation is characterized by the adequate reaction of organism, as the response to the invasion of the pathological agent. The hyperergic inflammation is characterized by a very strong reaction of organism even on an insignificant influence of the pathological agent. The hypoergic inflammation is characterized by insignificant changes in tissues. The alterative inflammation is characterized by hard damage of tissues (dystrophy, necrosis) The exudative inflammation is characterized by derivation of big quantity of exudates. The proliferative inflammation is characterized by reproduction of cells.
The inflammation can arise as result of influence of any agent. Force and duration of such influence should be stronger, than adaptive possibilities of the tissue, organ.
The general signs of inflammation: 1. Fever develops as a result of production by neutrophiles and macrophages endogenous pyrogens (e.g., IL 1 and 6, tumor necrosis factor, interferon). 2. From the blood side: leukocytosis shift of the leukocytes fofmula to the left (increase in the peripheral blood of juvenile and stab neutrophils); the increase of ESR (erytrocyte sedimentation rate); increase in blood acute-phase proteins, such as: С-reactive protein; ceruloplasmine; γ-globulins.
The first stage is a stage, with which all forms of an inflammation begin. This stage is characterized by the violation of cells structure and function, of fibrous structures, of the microcirculatory system, nervous derivations. The damages of tissues are characterized by the disorder of proteins, fats, and carbohydrates metabolism, physical-chemical and morphological changes of tissues. The more complicated protein fibrous derivations (collagen, elastin) саn also be destroyed. Necrobiosis and necrosis can take place in tissues. It is the reversible (sublethal) damage of cells, if they can adapt and restore their structure and function, and the irreversible (lethal) damage of cells, which is characterized by irrevocable change of cells structure.
The constant deficiency of energy provokes the rise of permeability of organelles membranes and swelling of the cell takes place. These changes are the result of the significant damage of cells membrane structures. Free radicals and peroxides play the significant role in this process. They are the result of hypoxia of the damaged tissues and the violation of biochemical processes in cells. The accumulation of free radical substances exceeds the possibility of the cell to neutralize them. Therefore these substances damage membrane structures of the cell. Especially dangerous is a damage of lysosomic membranes. Enzymes, which are localized in lysosomes, can acts on all kinds of macromolecules of cytoplasm. Primary lysis of the cell can be result of the lysosome membrane destruction by the pathological agent. Lysosome enzymes can get in the intracellular space. The secondary lysis of cells is the result of destruction of lysosomal membrane by free radicals. There is protein complex in blood of the man, which consists from 20 proteins (complement’s system). These proteins are activated during the invasion of microorganisms, promote damage of cells membranes and stimulate the protective phagocytic response. The main task of the complement’s system is destruction of all foreign agents, which get or derivate in human organism. These proteins, as well as lysosomes enzymes, promote development of the first stage of an inflammation. The damage of cells is accompanied by disorder of metabolism. Lisosomal enzymes uncontrol destroy of carbohydrates, proteins, fats, nuclear acids, and the activity of enzymes of glycolysis raises. The consumption of oxygen in this stage of inflammation is increased. But it lasts not for long (2-3 hours). Then the alteration of cells provokes the damage of mytochondries membranes. The Krebs cycle is violated; the АТР derivation is sharply oppressed, so the energy deficiency and accumulation of toxic substances, such as polypeptides, fatty acids, and ketone bodies take place. Simultaneously derivation of СО2 is violated, and the respiratory coefficient decreases. The inflammation always begins with the rise of metabolism! The main characteristic of this stage is the activation of metabolism; this is process of substances disintegration and as result destruction of glycoproteins and glicosaminoglican’s complexes, formation of free aminoacids, polypeptides. Some of these substances are mediators of inflammation, and determine dynamics of inflammatory process. The accumulation of partly-oxidated products in cytoplasm, as the result of violation of Krebs cycle, is accompanied by the development of metabolic acidosic (decrease of рН) and the conditions which are necessary for enzymes systems operation are also violated. The tissue destruction is accompanied by the release of Na+, K+, Ca2+ out the cells and the rise of osmotic pressure (hyperosmia, the increase of proteins concentration, as the result of katabolism intensification), causes the oncotic pressure increase (hyperonkia). The swelling, pain, violation of organ’s functions are the result of these changes! The secondary alteration is the result of disorder metabolism, the derivation of free radicals, the influence of lysosomic enzymes, local acidosis, hyperonkia, hyperosmia and the influence of inflammatory mediators (biological active substances, which generate in inflammation area).
Mediators of an inflammation, as the signal’s system, provide the exchange of the information between the cells, which cooperate and destroy the pathological agent. The system of mediators not only provokes various responses of tissues, but also is responsible for their interrelation.
The effects of cellular mediators are local. Histamine (most important mediator) is found in high concentration in platelets, basophils and mast cells granules together with heparine and factor of thrombocytes activation. The main effects of histamine are the result of irritation Н1-histamine receptors of vessel wall (especially in venous). Histamine causes vasodilation and increased permeability of capillaries (main effects of histamine), promotes emigration of leucocytes, stimulates phagocytosis, increases adhesive property of vessels endothelium, and causes a pain.
Protein cell products that act as a message to other cells, telling them how to behave. Increase endothelial cell adhesion molecule expression, activation and aggregation of PMNs, etc. Lymphocytes excret lymphokines, which play main role during the immune inflammation. Among them, lymphotoxines realize killer activity of monocytes and lymphocytes and destroy cells-target. The migration-inhibiting factor (MIF) promotes accumulation leucocytes-phagocytes in the center of the inflammation. The factors of blasttransformation provide the reproduction of immunocytes and the excretion of interleukines (IL-1, IL-2, IL-3 etc.). Very important for immune inflammation is an interferone. This protein brakes compilation m-RNA of viruses or cells, this effect promotes the oppression of cells reproduction. The effects of interferone can be realized by means prostaglandins. Sensibilizated T- and B-lymphocytes excret γ-interferone, which regulates the macrophagocytes activity.
Cascade of plasma proteases Hageman factor (factor XII) Collagen, basement membrane, activated platelets converts XII to XIIa (active form) Ultimately converts soluble fibrinogen to insoluble fibrin clot Factor XIIa simultaneously activates the “brakes” through the fibrinolytic system to prevent continuous clot propagation
Spasm (constriction) of arterioles is a result of vasoconstrictive adrenergic nerves stimulation by the catecholamines. Catecholamines stimulate ά-adrenoreceptors and promote the contraction of smooth muscles of vascular wall. The duration of first stage is short, because the depot of catecholamines in the nervous endings is exhausted very fast and monoamineoxydase destrois the released mediators. The activation of cholinergic nerves and the excretion of acetylcholine promote the development of the second stage of microcirculation violation – the arterial hyperemia. This mechanism is short-term, because acetylcholinesterase destrois acetylcholine. The significant duration of this stage is stipulated by the excretion of vasoactive mediators of the inflammation, which influences on the walls of arterioles and precapillaries (histamine, serotonine, bradykinine, kallidine, prostaglandines).
The change of metabolism in the inflammation area and the damage of cells promote the increase of lactic acid, adenosinemonophosphatic acids, potassium ions concentration and the violation of the functional condition of the connective tissue, surrounding the vessels. The connective tissue becomes less elastic and it promotes the extension of vessels. The effects of arterial hyperemia are: the increase of blood flow speed, the increase of functioning capillaries amount, the rise of blood pressure, strengthens of the tissues oxygenation. Arterial hyperemia promotes: the derivation of the oxygen radicals for the protection of the organism against the microorganisms, forming of humoral plasma factors of the organism protection (complement, properdine, fibronectine), causes the movement of leucocytes into the area of injury. Arterial hyperemia causes the redness and warmth of the injurious area. Venous hyperemia is characterized: by the deceleration of blood circulation, the change of blood viscosity (it’s a result of exudation), the chaotic placement of blood cells. Blood becomes very viscous; erythrocytes swell and move slowly, sometimes they stick in capillaries The development of venous hyperemia is promoted by three groups of actors: І – intravascular, ІІ – vascular, III – extravascular. Intravascular factors are follows: erythrocytes swelling and blood viscousness, which are the result of the increase vessels permeability; the forming of mycrothrombuses, the disposition of the leucocytes near the vessel wall. Vascular factors: the development of venous hyperemia is promoted by the increase of endoteliocytes sizes and as a result the diameter of capillaries decreases. The elasticity of venal and lymph vessels decreases as a result of collagen and elastine destroy caused by lysosomic enzymes. Extravascular factors: edematic fluid easily squeezes vessels and deepens the violation of blood circulation. Venous hyperemia, which lasts very long time, creates conditions for the development of prestasis. The movements of blood are similar to the movements of a pendulum: blood moves from arteries to veins during systole of the heart and comes back during diastole of the heart. The increase of blood viscosity, platelets aggregation causes the development of stasis, which is characterized by: the stop of blood movement, swelling aggregation of erythrocytes and their destruction. Changes of the erythrocytes membrane cause the aggregation of erythrocytes. The erythrocytes during the inflammation becomes swollen; the decrease of the blood albumins amount, as the result of the amplified penetration of blood plasma out the vessel, causes the decrease of negative charge of membrane erythrocytes and their conglutination.
The amplification of exudation provokes: of reologic properties blood change and microperfusion as the result of blood condensation; of laminar blood stream violation; of plasma structure change after the output into the tissue proteins; of microvessels compression by the edematic liquid. These processes provide of phagocytosis (protective process); it is sufficient activity and restoring of the injury tissue. In a stage of arterial hyperemia and especially in venous hyperemia stage fluid with the proteins and salts, dissolved in it, penetrates out the vessel. The high hydrodynamic pressure in vessels and the low colloid-osmotic pressure of blood increase of the vessels permeability and penetration of plasma proteins into the tissue.
The development of the inflammation promotes the amplification of the exudation and the output of blood plasma and the mediators outside the vessels. The serious damage of vessels wall is accompanied with the erythrocytes diapedesis (penetration through the vessel wall) and the bleeding. The exudation peculiarity and its structure depend on osmotic, oncotic and hydrodynamical factor of inflammation. Hyperosmia (high osmotic pressure) and hyperoncia (high oncotic pressure) of the tissue in the area inflammation) and osmotic-oncotic pressure of blood are differed, so fluid penetrates out the vessels and amplifies swelling. Hyperosmia is the result of the accumulation osmotic active particles (K+, Na+, salts, light-weight organic substances) of injurious tissue. Hyperoncia is the result of the macromolecules disintegration substances of the injurious tissue accumulation. There are three types of microvessels permeability change. The first type is the immediate-transient, second type – immediate-continuous, third type – deferred-prolonged increase of permeability of vessels walls during inflammation. The first type is called the immediate-transient and occurs during weak damages. The main cause of it is the release of histamine, serotonine, and bradykinine. The contraction of endothelial cells and extension of interendothelial slots in small and average venue occurs under the influence of histamine. The permeability of walls of capillaries does not change. Endothelial cells of small and average venue have more histaminic receptors, than the similar cells of capillaries and arterioles; therefore only venule are involved in the process of such type. The second type of vessels permeability violation arises during hard tissue damages (for example, extensive serious burn). The sharp increase of microvessels permeability arises immediately after damage and lasts up to five day, because endothelial cells of microvessels perish and is characterized by plasmorrhea. The third type of vessel permeability changes is characterized by the lasting latent period after the damage. After that the permeability of vessels sharply increases and last for some hours or days. This type of vessels response is the most frequently with the human being (thermal damages, tissues injury by ionizing and ultra-violet rays, operation of bacterial toxines, delayed type of the allergy). In these cases endothelial cells don’t round, but juncture between endotheliocytes of the capillaries and venules is broken. The combination of several mechanisms in dynamics the inflammation is possible. Amplified exudation promotes the development of edema, pain and the function violation. The pain is the result of the nervous ending compression caused by exudates. The violation of the organ or tissue function is the result of the increase of diffuse distance between the capillary and parenchymal cells, and also their compression. The exudation deepens negative effects of the inflammation: the disorder of metabolism and microcirculation of the injurious tissue, haemoconcentration, derivation of thrombus. But at the same time the pathological factor operation weakens due to injuries area.
Main differences of exudation and transudate: an exudation contains more albumens (over 2%), transudate – to 2%; specific gravity of exudation - 1027, transudate - 1015; an exudation contains a lot of blood cells (first of all leucocytes), transudate - few.
The penetration of leukocytes through the vessels wall is promoted by the alteration of leukocytes, endotheliocytes, interendothelial contacts basal membrane and perivascular tissue states. After the adhesion of the leukocyte to the endotheliocytes membrane it moves on its surface and goes to the interendothelial slot. The leukocyte forms a pseudopodium, which moves through the interendothelial slot into the underendothelial space. All contents of leukocyte move into the pseudopodium, and the leukocyte places in between the endothelial cells and the basal membrane of the microvessel. Then the leukocyte excretes collagenase and elastase, partly alters basal membrane and passes through the vessel wall and gets out the vessel.
Defects of adhesion: LFA-1 and Mac-1 subunit defects lead to impaired adhesion (LAD-1) Absence of sialyl-Lewis X, and defect in E- and P-selectin sugar epitopes (LAD-2)
Vascular changes and the blood stream deceleration promote the reallocation of blood cells: leucocytes move to the vessel wall and begin to attach to it. Then, leucocytes adhere on the endotheliocytes and form the cover along the vessels walls. The process of the edge standing of leucocytes is necessary two following conditions: the increase of endothelial cells adhesive properties and the activation of leucocytes. The increase of adhesive properties of endotheliocytes is promoted by the lowering of their negative membrane charge (it’s the result of the accumulation in the area of inflammation Н+, Ca2+, Мg2+, Mn2+, cationic proteins, excreted by activated leucocytes). These ions reduce the leucocytes negative charge too, and also activate leucocytes enzymes, which increase adhesive properties of these cells. Complement, fibronectine, immunoglobulins, histamine, interleukines, leucotriens are the most important initiators of the activation of leucocytes adhesive properties. C5, IgG (Fc-fragment) and IL-8 (chemotactic factors) promote the activation of these cells and their movement to endotheliocytes. Gradually leucocytes begin to pass through the vascular wall and to emigrate into the tissues (positive chemotaxis).
The neutrophiles excrete the proteolytic enzymes and oxidants into the phagosoma and destroy pathological agent. The excretion of proteolytic enzymes, biooxidants, thromboxans, prostaglandines, and leucotriens out the neutrophiles promotes a self-regulation of the inflammation. The lymphocytes play the main role during virus infections. The mowing of lymphocyte out the vessel is promoted by substances (monokines), which are secreted by blood and tissues macrophages. The cooperation of T- and B-lymphocytes with phagocytes is necessary for immune reaction stimulation and phagocytosis activation with the involvement of complement system. All inflammation effectors cells have Fс-receptors of immunoglobuline G and C- receptors of complement.
The main functions of the monocytes (macrophages) are the phagocytosis of foreign agent or damaged tissue and the immune reactions stimulation. The high-specifically phagocytosis of the foreign object is carried out due to the electrostatic interaction forces, and especially due to the membranes receptors for Fс-fragment of immunoglobuline G and СЗ component of the complement system, which taking part in a destruction of foreign agent too. The fastening and phagocytosis of the microorganisms promotes stimulation of macrophage, its oxidizing processes and secretion of the bactericide products (lysosomal enzymes, cationic non-enzyme proteins). But some of the particles, especially the inorganic ones, can be stable against such effect and even can cause damage of macrophage. So, the condition of the impossibility of pathological agent elimination is created. In such situation the macrophages execute their protective function in another way: they surround the hard-phagocytible particles and form a cellular conglomeration–node or a granuloma. The macrophages also excrete the factors, which stimulate or inhibit the cellular prolipheration and regulate the regeneration processes (tissues structure restoring).
Defects of chemotaxis/phagocytosis: Microtubule assembly defect leads to impaired locomotion and lysosomal degranulation (Chediak-Higashi Syndrome)
The labrocytes excrete histamine and leucutrien В4, which activate fibroblasts proliferation. The neutrophiles excrete peptide, which activates the growth of fibroblasts and leucotrien, which cause the migration of fibroblasts into the injurious tissue. The macrophages are the main cells, which regulate the reparative processes. Macrophages enclose (segregate) of the injurious tissue, form neutrophile-macrophagal, macrophagal and macrophagal-fibroblasts barriers – the granulating tissue. The macrophagal-fibroblastic interaction conduces migration, proliferation, and differentiation of fibroblasts, synthesis and secretion of collagen and other components of tissues matrix. The accumulation of fibroblasts in the inflammation site inhibits their growth and stimulates the biosynthesis of collagen. Fibroblasts contact interaction stimulates the production of keilons. The macrophages, lymphocytes, neutrophiles produce the intercellular matrix (collagen, fibronectine). The further stage of connective tissue growth autoregulation is characterized by the collagen synthesis inhibition, the destruction of the majority cells, the transformation of the fibroblasts in fibrocytes (inactive cells). The fibroblasts destroy unnecessary collagen fibres by means of their phagocytosis, or the secretion of collagenase. All of these promote the stop of connective tissue growth.
Granulation tissue one of the very important products of inflammatory-reparative process is, this is a young connective tissue with a plenty of vessels. This tissue fills wound and ulcer skin defects; it is formed during the damage of mucous coats and internal organs, during bones fractures, haematomes organization, at necrosis and infarctions sites, and during chronic inflammation. The functions of granulation tissue are as follows: mechanical (filling of defect), trophic (microcirculation regulation, oxygen and metabolites transport, filtering of substances), morphogenetic (influence on epithelium and muscular tissue differentiation). But the main function of the granulation tissue is the protection against unfavorable influences of the external environment, against infection and intoxication, incapsulation (closing) of necrosis area and alien bodies, and also reconstruction of anatomic and functional structure of injurious tissues. During the proliferative processes activation, the cells, which are constantly stimulated by mitogens, become very sensitive to carcinogenic substances. Abnormal mitosis can lead to tumour formation.
The course of inflammatory reaction depends on: the organism reactivity, on the nervous, endocrine and immune systems condition. The meaning of the nervous system in the dynamics of the inflammation proves to be true by numerous cases of inflammation sings development in the patients under the influence of suggestion during hypnosis. The occurrences of hyperergic inflammation during the local action of the damaging factor at maniac excitement are often in psychiatric clinic, and at serious depressions the inflammatory reaction proceeds very languidly. The change of nervous – impulse and nervous – trophic influences on the damaged tissue promotes the amplification of exudative processes and the violation of microcirculation. Neuromediators and trophogens, activate the phagocytosis and the free-radical processes. The violation of afferent innervation strengthens alteration processes and decelerates the reparation of parenchymal cells. Proliferative processes pass most actively on the periphery of the inflammation area, because just there nervous fibres regenerate first and anabolic processes on the periphery proceed more actively. Neuropeptides take active part in the regulation of proliferative-regeneratory processes in tissues of organs, especially the opiod peptides. The stimulation of C-fibres opioid receptors by these peptides weakens the pain, reduces the release of noradrenalin from sympathetic nervous endings, the activation of labrocytes and trombocytes stops, the disorders of microcirculation and violation of hemostasis are eliminated. The inflammatory reaction in the process of phylogenesis has arisen as a protective response of the organism of hot-blood biological individuals. The organism protects itself from the influence of the pathological factor due to limitation of the inflammatory area from the whole organism. The barrier is formed around the inflammation area; it allows various substances to flow in one direction (to the centre of the inflammation site) due to blockade of lymphatic and blood vessels. The unfavorable conditions for microorganisms are created in the centre of the inflammation. But in the conditions of significant tissues damage or microcirculation violations, the hard metabolism disorder in the damaged tissue or organ, hypoxia and the common intoxication strengthening patient’s sufferings can be provoked. The inflammation is the example, which connects both the elements of injury and the elements of organism protective forces.
1. Inflammation. Deffinition.
2. Signts of inflammation.
3. Etiological factors of inflammation.
4. Stages of inflammation.
5. Alteration. Mediators of inflammation.
6. Exudation. Mechanisms.
7. Phagocytosis. Disorders of phagocytosis.
9. Significance of inflammation.
The survival of all organisms requires that they eliminate foreign invaders,
such as infectious pathogens, and damaged tissues. These functions
are mediated by a complex host response called iinnffllaammmmaattiioonn.
IInnffllaammmmaattiioonn is a protective response intended to eliminate the initial
cause of cell injury as well as the necrotic cells and tissues resulting
from the original insult. Inflammation accomplishes its protective mission
by diluting, destroying, or otherwise neutralizing harmful agents (e.g.,
microbes and toxins). It then sets into motion the events that eventually
heal and repair the sites of injury.
WWiitthhoouutt iinnffllaammmmaattiioonn, infections would go unchecked and wounds would
never heal. In the context of infections, inflammation is part of a broader
protective response that immunologists refer to as iinnnnaattee iimmmmuunniittyy.
Inflammatory conditions are named by adding the suffix --iittiiss to the
affected organ or system. For example, appendicitis refers to
inflammation of the appendix, pericarditis to inflammation of the
pericardium, and neuritis to inflammation of a nerve.
11)) BByy cclliinniiccaall ccoouurrssee::
22)) BByy rreeaassoonn::
a) uninfectious origin (banal or unspecific) – caused uninfectious factors;
b) infectious origin which includes for itself specific inflammations
(tuberculosis, syphilis, lepra, scleroma, glanders).
33)) BByy cchhaarraacctteerr ooff pprreeddoommiinnaattiinngg pphhaassee ooff iinnffllaammmmaattiioonn::
c) proliferative inflammation.
44)) IInn ddeeppeennddeennccee oonn rreeaaccttiivviittyy ooff oorrggaanniissmm ooff iinnffllaammmmaattiioonn ccaann bbee::
• a) nnoorrmmooeerrggiicc - adequate after the displays of factor which caused it;
• b) hhyyppeerreerrggiicc - is stormy (violent) course of inflammation, for example, on a
background (against a background) sensitizing;
• c) hhyyppooeerrggiicc – with insignificant displays (for the children of 1th month of life,
in senile age, at considerable exhaustion of organism).
AAlltteerraattiioonn is the first component of
inflammation, which is characterized by the
injury of structurally-functional unit of an
Alteration iiss ddiivviiddeedd oonn
PPrriimmaarryy alteration is the result of the influence
of the pathological (flogogenic) agent on a
tissue. Metabolic and structural changes arise
SSeeccoonnddaarryy alteration is the self-injury which
takes place under the action of biological
active substances (BAS) which are produced in
consequence of primary alteration.
MMeeddiiaattoorrss ooff iinnffllaammmmaattiioonn – it is
biologically active substances, which
appear in the place of inflammation and
determine the pathogenesis of
Distinguish two main groups of mediators
from their origin:
appear and activated in
appear in cells, but activated in
plasma of blood
TToollll--lliikkee rreecceeppttoorrss ((TTLLRRss))
1. Present on cells of the innate immune system :
2. Activated by pathogen-associated molecular patterns (PAMPs) that
are commonly shared by microbes
CD14 (a TLR) on macrophages recognizes lipopolysaccharide (a
PAMP) on the outer membrane of gram-negative bacteria.
3. TLR activation results in upregulation of
NF-kB, a nuclear transcription factor that
activates immune response genes leading
to production of multiple immune
4. TLRs are also present on cells of
adaptive immunity (e.g., lymphocytes)
and, hence, play an important role in
mediating chronic inflammation.
1. Inactive proinflammatory protein produced in
2. Activated upon exposure to subendothelial or
tissue collagen; in turn, activates:
I. Coagulation and fibrinolytic systems
III. Kinin system — Kinin cleaves high-molecular-
weight kininogen (HMWK) to
bradykinin, which mediates vasodilation and
increased vascular permeability (similar to
histamine), as well as pain.
• Leads to formation of bbrraaddyykkiinniinn from
cleavage of precursor
• Vascular permeability
– Arteriolar dilation
– Non-vascular smooth muscle contraction
(e.g., bronchial smooth muscle)
– Causes pain
– Rapidly inactivated (kininases)
DDiissttuurrbbaannccee ooff tthhee mmiiccrroocciirrccuullaattiioonn iinn
tthhee iinnffllaammmmaattiioonn aarreeaa
The ffiirrsstt ssttaaggee is the sshhoorrtt--tteerrmm ssppaassmm of vessels (arterioles),
the sseeccoonndd is the aarrtteerriiaall hhyyppeerreemmiiaa,
the tthhiirrdd ssttaaggee is the vveennoouuss hhyyppeerreemmiiaa,
the ffoouurrtthh ssttaaggee is the pprreessttaassiiss, and the ssttaassiiss is the ffiifftthh ssttaaggee.
1. Irrespective of the type of injury, immediate vascular response is of
transient vasoconstriction of arterioles. With mild form of injury, the
blood flow may be re-established in 3-5 seconds while with more severe
2. Next follows persistent progressive vasodilatation which involves
mainly the arterioles, but to a lesser extent, affects other components
of the microcirculation like venules and capillaries. This change is
obvious within half an hour of injury. Vasodilatation results in increased
blood volume in microvascular bed of the area, which is responsible for
redness and warmth at the site of acute inflammation the
vvaassooccoonnssttrriiccttiioonn mmaayy llaasstt ffoorr aabboouutt 55 mmiinnuutteess..
Mechanism Microvasculature Response Type Pathogenesis Examples
1 contraction Venules (15-30 min)
bradykinin, others Mild thermal injury
2 Endothelial cell
Somewhat delayed (in
4-6 hrs) prolonged (for
24 hrs or more)
IL-1, TNF-α In vitro only
3 Direct endothelial
(hrs to days), or
delayed (2-12 hrs)
prolonged (hrs to
Cell necrosis and
Moderate to severe
Venules, capillaries Delayed, prolonged Leukocyte
5 Neovascularisation All levels Any type
a liquid from
the blood into
There are three ways penetration of fluid through the vessel wall
The 1st way is interendotelial (between nearby endotheliocytes).
Histamine promotes contraction of endothelial cells, the slots between
nearby endotheliocytes extend, and basal membrane is exposed.
The 2nd way of exudation is transendotelial (through the
endoteliocytes cytoplasm). Vesicles pinocytosis activity (the catch of
fluid) of the endoteliocytes increases. The blood plasma is inside
vesicles, which move through the cell and some time form channels.
can pass without any
The 3rd way of
the exudation is the
vessels wall area,
where are injured endoteliocytes.
The main cause of the exudation is mediators of
inflammation, but amplifying disorder of the
metabolism, the injury cells and leucocytes promotes
other pathological mechanisms, which increase
They are lysosomes hydrolytic enzymes of various
phagocytes and parenchimal cells (ccoollllaaggeennaassee,,
eellaassttaassee) and bacterial enzymes (hhyyaalluurroonniiddaassee),
llaaccttiicc aacciidd aanndd ppiirruuvvaattee aacciidd, other non-oxidated
substances, which are the result of tissues hypoxia,
adenosine, Н+ and K+, especially during the
decrease of Са2+ level. First of all albumins, than
globulins and fibrinogen, which promotes the
formation of fibrins clots, penetrate outside the
The inflammation is named the eexxuuddaattiivvee if this
component is expressed stronger than others. The
exudate type determines type of an inflammation.
There are next types of the exudates and inflammation:
The serous inflammation develops in mucous and
serous coats, interstitial tissue, skin, and kidneys
glomes capsules. The amount of cells in the serous
exudate is not large.
The fibrinous exudate
contains a plenty of
fibrinogen, which forms clots
of ffiibbrriinn iinn ttiissssuueess.
Such inflammation occurs
when an organism is
affected by corinebacterium
Such type of an
inflammation occurs on
mucous or serous coats
Porcine Heart/Pericardium - fibrinous exudate (Mulberry Heart Disease)
The causes of purulent
inflammation are staphylococcus,
meningococcus, and Frenkel’s
Purulent exudate consists of
many viable leukocytes and
purulent bodies (perishing
leukocytes), cells detritus,
microorganisms, plenty of proteins
• The decaying inflammation develops after the
invasion of decaying microflora into the purulent
inflammation site. During this type of inflammation
necrosis of injurious tissues progresses, the
inflammation area doesn’t localize, and this provokes
the arrival of alien and toxic products into vessels and
the development of intoxication due to which the
patients usually dies.
TThhee iinnffllaammmmaattiioonn pprroolliiffeerraattiivvee pphhaassee
• The inflammation proliferative phase is simultaneously a phase
of the reparatory regeneration. The restoring of the damaged
tissues structure depends on the interaction of connective
tissues cells among themselves (fibroblasts, macrophages,
labrocytes, lymphocytes, endotheliocytes), on the interaction of
connective tissues cells with the intercellular matrix (collagen,
proteoglicans, fibronectine), on the interaction of connective
tissue cells with blood cells and parenchymal ones.
1. Replacement of damaged tissue with ffiibbrroouuss ssccaarr
2. Occurs when regenerative stem cells are lost (e.g.,
deep skin cut) or when a tissue lacks regenerative
capacity (e.g., healing after a myocardial infarction)
3. Granulation tissue formation is the initial phase
Consists of ffiibbrroobbllaassttss (deposit type III collagen),
ccaappiillllaarriieess (provide nutrients),
mmyyooffiibbrroobbllaassttss (contract wound)
4. Eventually results in scar formation, in which type III
collagen is replaced with type I collagen
1). TTyyppee IIIIII ccoollllaaggeenn is pliable and
present in granulation tissue,
embryonic tissue, uterus, and
2). TTyyppee II ccoollllaaggeenn has high
tensile strength and is present in
skin, bone, tendons, and most
3). CCoollllaaggeennaassee removes type III
collagen and requires zinc as a
III. Dehiscence iiss rruuppttuurree ooff aa wwoouunndd;;
most commonly seen after abdominal surgery
IIVV.. HHyyppeerrttrroopphhiicc ssccaarr is excess production of scar tissue
that is localized to the wound
VV.. KKeellooiidd is excess production of scar tissue that is out of
proportion to the wound
1. Characterized by excess type III collagen
2. Genetic predisposition (more common in African Americans)
3. Classically affects earlobes, face, and upper extremities
Negative significance of
• alteration is the injury →
dysfunction of organs;
• exudate results in compression
of arterial, venous and
lymphatic vessels → hypoxia;
• the fibroplasia results in the
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