INFLAMMATION. FEVER.
The
inflammation is the most often pathological process, which arises in a human
organism. It is a typical pathological
process, which arises after damage of tissues and consists of three main
vessel-tissues components: alteration, violation of microcirculation with
exudation and emigration of leucocytes and proliferation. 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
suffix “it” is the common.
The
suffix “it” means inflammation.
The
inflammation can arise in various organs.
Examples
of the localisation of inflammation
In langs
Localised
inflammation of the nail fold (paronychia) is relatively common in
infants. Before secondary infection (usually with Staphylococcus aureus
or Streptococcus pyogenes) occurs, there is an initial separation of the skin
from the nail fold. This may be exacerbated by the baby sucking their
fingers or by overzealous trimming of the infant's finger nails.
Most
often, the infection can be treated with oral or - in severe cases -
intravenous antibiotics (our first line is usually flucloxacillin).
Occasional infants may need drainage of large collections, which may be
achieved by pushing the skin away from the nail fold.
Inflammation of the skin
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.
Etiology of inflammation
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 external causes of an inflammation are classified as follows: the
physical factors (foreign bodies, strong pressure on a tissue, high and low
temperature, ionizing and ultra-violet rays, high and low barometric pressure,
electrical current); chemical factors (acid, alkali, salts of heavy metals);
biological factors (microorganisms – bacteria, viruses, fungi; animal organisms
– worms, insects). The internal factors are the factors, which arise in
organism, as the result of any other diseases, for example cholic acids,
complex antigen-antibody and others.
Signs of inflammation
There
are five classical local signs of the inflammation.
The
Roman physician Celsus described four signs, such as: swelling (tumor), redness
(rubor), heat (calor), pain (dolor)
Greek
physician Galen added fifth sing – loss of the function (functio laesa).
Swelling is the result of the vessels
permeability increase. Redness is the result of local arterial hyperemia.
Heat (the
local rise of temperature) is the result of arterial hyperemia and impermanent
intensification of metabolism in the center of inflammation. The pain is the
result of the painful receptors irritation by biological active substances,
metabolites, and pressing. The loss of the function is the result of the
functional active tissue injury.
1
2
Fig.
Unchanged timpana
(1) and inflammation of timpana
(2), which is swollen and red.
GENERAL SIGNS OF INFLAMMATION
FIVER –
results from IL-1 influence on centre of thermoregulation (excreted by
macrophages and neutrophyles)
LEUCOCYTOSIS
– is the result of leucocytes outcome from depot, leucocytes proliferation
PROTEINS
OF AQUTE FASE of inflammation – its content increases in the blood on 50 %,
they are synthesized mainly in liver, play protective role (inhibitors of
proteinases – antitripsine; antioxidants – haptoglobin, ceruloplasmin; IgG, Ñ-
reactive proteinå)
ESR
increases – inflammation couses accumulation of big mass proteins in the blood
(globulines, fibrinigen), they adsorb on erythrocytes, decrease surface
negative charge and conduce erythrocytes aggregation
INTOXICATION
– is the result of necrotic substances income in the blood from area of
inflammation
Increasing of ESR
in blood testonduce
Classification of an
inflammation
Depending
on clinical course, there are two kinds of inflammation:
Acute
Chronic
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.
There
are normoergic, hyperergic and hypoergic inflammation when taking into account
intensity of local and general changes in 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.
During
the inflammation one of stages of an inflammation can prevail, therefore there
can be alterative inflammation, exudative inflammation and proliferative
inflammation. The alterative inflammation is characterized by hard damage of
tissues (dystrophy, necrosis), the exudative inflammation is characterized by
derivation of big quantity of exudates, and the proliferative inflammation is
characterized by reproduction of cells.
Pathogenesis of inflammation
The inflammation, as typical pathological
process, consists of three stages: the first is the alteration stage; the
second is violation of microcirculation with exudation and emigration of
leucocytes in the center of an inflammation and the third – proliferation.
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)
ñàn 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.
There
are two type of the alteration: primary and secondary.
The
primary alteration is the result of the influence of the pathological
(flogogenic) agent on a tissue. Metabolic and structural changes arise
therefore. Various cells react differently: some cells perish, others – remain
alive, and others become activated. The activated cells are responsible for the
creation of following stages of an inflammation.
The secondary alteration is the consequence of the primary
alteration and it arises even at the absence of the damaging agent.
The
signs of cells damage are the follows: the lessening ðÎ2; limitation or termination
of Î2 consumption by cells; the decrease of ÀÒÐ and ÀDÐ and the increase of the
inorganic phosphorus concentration; the intensification of glycolysis, which
cause the accumulation of lactic acid and piruvate acid; the decrease of cells
ðÍ. The decrease of ÀÒÐ concentration reduces the activity of ionic pumps of
cells membranes, the parity of Na, K, Ca and Mg in cytoplasm is violated, and
the activity of biochemical systems of cells is violated too. Then content of
water in cells changes, the synthesis of protein decreases, the density of
cytoplasm raises, the amount of Í+ increases, the outlines of the cell change.
These changes are reversible.
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 ÀÒÐ 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 ÑÎ2 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 ðÍ) 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
an inflammation mediators (biological active substances, which generate in
inflammation area).
Mediators of the inflammation are united in
groups of substances with defined chemical structure: biogenic amines
(histamine, serotonine); polipeptides (bradykinine, kallidine); proteins
(complement’s system and lysosomal enzymes); derivatives of arachidonic acid
(prostaglandines and leucotriens).
Mediators
of the inflammation are divided into humoral mediators (proteins of
complement’s system, bradykinine, kallidine) and cellular ones (histamine,
serotonine, lymphokines, prostaglandines). This classification is based on an
origin of these substances. Humoral mediators are characterized by the
widespread effects, spectrum of their influence is very wide.
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 effects of histamine are mediated by histamine
receptors (Í1 and Í2).
The
main effects of histamine are the result of irritation Í1-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, causes a pain.
The
neurons, labrocytes, basophiles and thrombocytes contain of serotonin, which
couses arterioles constriction, shortening of venules walls myocytes and
promote the stagnation of blood in venous.
There
are three most important blood systems, which play main role during
inflammation:
kinines,
hemostasis,
fibrinolysis
complement’s
systems.
The ÕII factor of blood coagulation activates
derivation such kinines as the bradykinine and kallidine. Their main effects
are pain, dilatation of vessels, rise of vascular wall permeability, activation
of hemostasic and fibrinolysis systems.
The
system of hemostasis and fibrinolysis directly participate in the generation of
highly active mediators. The appearance of fibrinopeptides promotes the
increase of microvessels permeability, activation of chemotaxis. Plasmine plays
the main role in the system of fibrinolysis; it promotes the derivation of
biological active substances, which increase of vessels permeability.
The
system of complement is the complex of plasma proteins (C1-C9). Their main
function is the destruction of alien and own changed cells. Activated Ñ2
operates as kinines; Ñ3 raises vascular permeability and stimulates the motion
of phagocytes; Ñ5 has properties of Ñ3 (but is more active) and stimulates the
selection of leucocytes of lysosomic enzymes; Ñ5-Ñ9 is provided by the
reactions of alien and own cells lysis; Ñ5 stimulates the splitting of
arachidonic acid and the synthesis of leucotriens, promotes the forming of
oxygen radicals and hydroperoxides of lipids.
Derivatives of arachidonic acid include
prostaglandines (PG), thromboxan A2 (TXA2) and leucotriens (LT). PG and TXA2 are formed as the result of
splitting of arachidonic acid, which is allocated from phospholipids of
membranes cells, by cycloxigenase. Endothelial cells of vessels synthesize PG,
thrombocytes synthesize TXA2. PGÅ2 promotes the dilatation of vessels and the
increase of their permeability, and also stimulates the excretion of histamine.
Leucotriens are formed as the result of splitting of arachidonic acid by
lipoxygenase. The leucotriens LÒÑ4, LÒD4, LÒÅ4 are excreted from labrocytes and
basophiles and promote the increase of permeability of vessels (especially of
venules). LÒÂ4 is excreted by endotheliocytes and promotes chemotaxis of
leucocytes, causes adhesion and aggregation of neutrophiles.
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.
Granulocytes
excret the platelet-activating factor, which stimulates the excretion
serotonine, adrenalin from the thrombocytes.
Main effects of the platelet-activating factor are the intensification of
microvessels permeability, strengthens the exudation of the blood plasma and
the emigration of leucocytes out the vessels.
Polymorphonuclearic
leucocytes excrete kationic proteins, neutral and acidic proteases. Kationic
proteins can release histamine and raise of vessels permeability, to strengthen
the reactions of phagocytes. Neutral
proteases (elastase, collagenase, katepsies) destroy the proteins of basal
membrane and raise of vascular wall permeability. Acidic proteases acts in
conditions of low ðÍ and destroy membranes of microorganisms and own tissues.
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.
Therefore inflammation has stereotyped
components, such as alteration, vascular response, exudation, phagocytosis, and
proliferation. The inflammation has some stages, which arise consistently. A
principal value for each stage has the defined group of mediators. Histamine
and serotonine play the main role on the initial stage of the acute inflammation
development. These mediators increase the permeability of microvessels walls,
strengthen the exudation, and start the system of kinines, complement and
hemostasis. Then the cascade of reactions of arachidonic acid transformation
and the derivation of prostaglandines and leucotriens is stimulated. Then the
cellular mechanisms of protection start very actively. At the beginning,
polimorphonuclearic leucocytes then monocytes and lymphocytes accumulate in the
center of the inflammation, and the damaging agent or the products of tissues
disintegration are destroyed and eliminated from an organism. The excretion of
the inflammation mediators is cascade process. The question about the
limitation of their excretion and action is really important. High concentration
in blood can cause shock, collapse, DIC-syndrome. In the center of the
inflammation, the substances, which block redundant accumulation and stop their
influence, are excreted. Such processes take place during all stages of the
inflammation.
All these substances are united in the system of
antimediators. Enzymes are the main antimediators: histaminase destroys the
histamine; carboxypeptidase destroys the kinines; esterases inhibits the
complement proteins; prostaglandindehydrogenase destroys the prostaglandines;
superoxyddismutase and catalase neutralize radicals of oxygen (eosinophiles are
the important cells, which generate and delivery antimediators). Cortisole,
cortisone, corticosterone have antimediator’s activity too. They weaken vascular
reactions, stabilize membranes of microvessels cells, reduce the exudation and
the emigration of leucocytes, weaken phagocytosis, reduce the excretion of
histamine, stabilize of lysosomes membranes, reduce activity of lysosomic
enzymes and the derivation of kinines and prostaglandines. These effects of
corticosteroides doctors use for patients treatment. The inflammation is
characterized by local violation of blood and lymph of circulation, especially
microcirculation (in terminal vessels – arterioles, metarterioles, capillaries
and venules).
The
most impotent mediator of the inflammation is HISTAMINE
Histamine
is an organic nitrogen compound involved in local immune responses as well as regulating
physiological function in the gut and acting as a neurotransmitter. Histamine
triggers the inflammatory response. As part of an immune response to foreign
pathogens, histamine is produced by basophils and by mast cells found in nearby
connective tissues. Histamine increases the permeability of the capillaries to
white blood cells and some proteins, to allow them to engage pathogens in the
infected tissues.
Most histamine in the body is
generated in granules in mast cells or in white blood cells called basophils.
Mast cells are especially numerous at sites of potential injury — the nose,
mouth, and feet, internal body surfaces, and blood vessels. Non-mast cell
histamine is found in several tissues, including the brain, where it functions
as a neurotransmitter. Another important site of histamine storage and release
is the enterochromaffin-like (ECL) cell of the stomach.
The most important pathophysiologic
mechanism of mast cell and basophil histamine release is immunologic. These
cells, if sensitized by IgE antibodies attached to their membranes, degranulate
when exposed to the appropriate antigen. Certain amines and alkaloids,
including such drugs as morphine, and curare alkaloids, can displace histamine
in granules and cause its release. Antibiotics like polymyxin are also found to
stimulate histamine release.
Histamine release occurs when
allergens bind to mast-cell-bound IgE antibodies. Reduction of IgE
overproduction may lower the likelihood of allergens finding sufficient free
IgE to trigger a mast-cell-release of histamine.
Histamine exerts its actions by
combining with specific cellular histamine receptors. The four histamine
receptors that have been discovered in humans and animals are designated H1
through H4, and are all G protein-coupled receptors (GPCR).
Histamine biology is a series of
weak interactions. In all of the known physiological reactions, the histamine
backbone is unchanged.
In the H2 receptor mechanism,
histamine is protonated at the end-chain amine group. This amine group interacts
with aspartic acid in the transmembrane domains of cells. The other nitrogens
in the molecule interact with threonine and aspartic acid in different
transmembrane domains. This is a three-pronged interaction. It brings the
transmembrane domains close to each other, causing a signal transduction
cascade.
Histamine receptors in insects, like
Drosophila melanogaster, are histamine-gated chloride channels that function in
inhibition of neurons. Histamine-gated chloride channels are implicated in
neurotransmission of peripheral sensory information in insects, especially in
photoreception/vision. Two receptor subtypes have been identified in
Drosophila: HClA and HClB. There are no known GPCRs for histamine in insects.
Another
very impotent mediator of the inflammation is INTERLEUKINE-1
Julius
Friedrich Cohnheim (July 20, 1839 – August 15, 1884)
has described the stages of disturbance of the microcirculation in the
inflammation area.
At the
Pathological Institute,
Cohnheim
served as professor of pathology at the universities of
The
first stage is the short-term spasm of vessels (arterioles), the second is the arterial hyperemia, the
third stage is the venous hyperemia, the fourth stage is the prestasis, and the
stasis is the fifth stage. Spasm (constriction) of arterioles is a result of
vasoconstrictive adrenergic nerves stimulation by the catecholamines.
Catecholamines stimulate a-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.
VIOLATION OF MICROCIRCULATION AND BLOOD CIRCULATIONS IN AREA OF
INFLAMMATION
The
effects of arterial hyperemia are the increase of blood flow speed, the
increase of functioning capillaries amount, and the rise of blood pressure,
strengthens of the tissues oxygenation.
Arterial
hyperemia
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), and 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 factors: ² – intravascular, ²² – vascular, Ø –
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 cause the development of
stasis, which is characterized by the stop of blood movement, swelling and
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.
Lymphatic
system also participates in mechanisms of the inflammation. In a healthy
organism lymphatic system executes the drainage function. Their major functions
are the extract of microparticles, macromolecules, detritus of the cells and
the exchange of liquid between blood and tissues. The inflammation involves
many sites of lymph system. Edematic liquid compress lymph capillaries and
changes local lymphatic circulation. The damage of cells membranes breaks the
pump function of lymphatic collective vessels. The inflammation is accompanied
by the increase of lymphatic capillaries permeability and their overflow. The
detritus of the damaged cells and proteins get into lymph. The injurious
factors can cause the inflammation of lymphatic vessels and lymphatic nodes.
Due to the drainage function of lymphatic system the amplification of
lymphcirculation promotes the decrease of swelling and carry antigens to the
lymphatic nodes. Besides the amplification of the drainage function of
lymphatic vessels can promote the distribution of the infectious agent and the
toxic products of proteins disintegration. Spasm of the lymphatic vessels,
which usually arises proximately from the area inflammation and inflammation of
the lymphatic nodes deepen the swelling in the area inflammation and evidence
development of lymphatic circulation insufficiency. The principal value of the
alteration and violations of microcirculation is the creation of unfavorable
conditions for further penetration of the pathological agent into the organism.
Exudative and
proliferative processes
The
increase of vascular wall permeability provokes exudation (penetration of a
liquid from the blood into the tissue), emigration of leucocytes.
The
permeability of microvessels increases first of all (especially of venules).
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.
There
are three ways penetration of fluid through the vessel wall (exudation). 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 second 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.
Various substances can pass without any control through channels (microvesicle
transport). The third way of the exudation is the vessels wall area, where are
injure endoteliocytes.
The
development of the inflammation promotes the amplification of the exudation and
the output of blood plasma and the mediators outside the vessels. 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 vascular permeability. They are lysosomes hydrolytic
enzymes of various phagocytes and parenchimal cells (collagenase, elastase) and
bacterial enzymes (hyaluronidase), lactic acid and piruvate acid, another
non-oxidated substances, which are the result of tissues hypoxia, adenosine, Í+
and K+, especially during the decrease of Ñà2+ level. First of all albumins, than globulins and
fibrinogen, which promotes the formation of fibrins clots, penetrate 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,
second type – immediate-continuous, third type – deferred-prolonged increase of
permeability of walls of vessels 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 venue 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, hemoconcentration,
derivation of thrombus. But at the same time the
pathological factor operation weakens due to injuries area.
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 Í+, Ca2+, Ìg2+, 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
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.
In most
cases of acute inflammation neutrophyles emigrate the first (that process lasts
6-24 hours). In 24-48 hours monocytes emigrate most actively. Lymphocytes
emigrate a little bit later. Lymphocytes can immigrate the first during virus
infection and tuberculosis, and eosinophiles – during allergic reactions.
Leukocytes regulate of the cells cooperation and delete the alien agents or the
detritus of defective tissues. The neutrophiles (microphages) destroy
pathological agents due to the following properties: the absorption of the
foreign agent (phagocytosis), the microbicydity and cytotoxicity (these are the
mechanisms of the foreign agent destroy by such biooxidants as superoxide
anions, hydroxyl- radicals, singlet oxygen, peroxide), the intra- and
extracellular lysis.
The
neutrophiles excrete the proteolytic enzymes and oxidants into the phagosoma
and destroy pathological agent. The excretion of proteolytic enzymes,
biooxidants, thromboxans, prostaglandines, leucotriens out the neutrophiles
promotes a self-regulation of the inflammation.
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 Fñ-fragment
of immunoglobuline G and ÑÇ 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).
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 Fñ-receptors of immunoglobuline
G and C- receptors of complement.
Types
of exudates
The
inflammation is named the exudative if this component is expressed stronger
than others. The exudate type determines type of an inflammation. There are serous,
fibrinous, purulent, decaying, hemorrhagic and combination 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
serous exudate promotes washing off of microorganisms and their toxines from
the damaged surfaces. But the serous exudate in brain coats can squeeze the
brain and violate its function. The serous infiltration of lungs alveolar septs
can cause the development of acute respiratory insufficiency syndrome.
The
fibrinous exudate contains a plenty of fibrinogen, which forms clots of fibrin
in tissues. Such inflammation occurs when an organism is affected by
corinebacterium diphtheriae, pneumococcus, Fridlander's bacillus, Frencel's
diplococcus, streptococcus, and mycobacterium of tuberculosis. Such type of an
inflammation occurs on mucous or serous coats more often.
The
causes of purulent inflammation are staphylococcus, streptococcus, gonococcus,
meningococcus, and Frenkel’s diplococcus.
Purulent exudate consists of many viable leukocytes and purulent bodies
(perishing leukocytes), cells detritus, microorganisms, plenty of proteins (especially
globulines).
1
2
Pural
bodies (destroing of neutrophyle – 1, destroing
of monocyte - 2)
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.
The
hemorrhagic inflammation, as the form of the serous, the fibrinous or the
purulent inflammation, is characterized by erythrocytes impurity to the
exudate (Siberian ulcer, natural
smallpox, influenza).
The
combination forms of inflammation are characterized by connection of one type
of exudate to another. Any combinations are possible. Such forms usually
develop as the result of connection of a new infection to the lasting process.
The tissues damage and the process of inflammation cause the restoring of
broken structure and function (reparative regeneration).
INFLAMMATION. PHENOMENON
EXUDATIVE. THE SORTS OF EXUDATES
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.
An
exudate is any fluid that filters from the circulatory system into lesions or
areas of inflammation. It can apply to plants as well as animals. Its
composition varies but generally includes water and the dissolved solutes of
the main circulatory fluid such as sap or blood. In the case of blood it will
contain some or all plasma proteins, white blood cells, platelets, and in the
case of local vascular damage: red blood cells. In plants, it can be a healing
and defensive response to repel insect attack, or it can be an offensive habit
to repel other incompatible or competitive plants. Organisms that feed on
exudate are known as exudativores; for example, the Vampire Bat exhibits hematophagy,
and the Pygmy marmoset is an obligate gummivore (primarily eats tree gum).
In
humans, exudate can be a pus-like or clear fluid. When an injury occurs,
leaving skin exposed, it leaks out of the blood vessels and into nearby
tissues. The fluid is composed of serum, fibrin, and white blood cells. Exudate
may ooze from cuts or from areas of infection or inflammation.
Types
Purulent or suppurative exudate
consists of plasma with both active and dead neutrophils, fibrinogen, and
necrotic parenchymal cells. This kind of exudate is consistent with more severe
infections, and is commonly referred to as pus.
Fibrinous exudate is composed mainly
of fibrinogen and fibrin. It is characteristic of rheumatic carditis, but is
seen in all severe injuries such as strep throat and bacterial pneumonia.
Fibrinous inflammation is often difficult to resolve due to blood vessels
growing into the exudate and filling space that was occupied by fibrin. Often,
large amounts of antibiotics are necessary for resolution.
Catarrhal exudate is seen in the
nose and throat and is characterized by a high content of mucus.
Serous exudate (sometimes classified
as serous transudate) is usually seen in mild inflammation, with relatively low
protein. Its consistency resembles that of serum, and can usually be seen in
certain disease states like tuberculosis. (See below for difference between
transudate and exudate)
Malignant (or cancerous) pleural
effusion is effusion where cancer cells are present. It is usually classified
as exudate.
There is an important distinction
between transudates and exudates. Transudates are caused by disturbances of
hydrostatic or colloid osmotic pressure, not by inflammation. They have a low
protein content in comparison to exudates. Medical distinction between transudates
and exudates is through the measurement of the specific gravity of extracted
fluid. Specific gravity is used to measure the protein content of the fluid.
The higher the specific gravity, the greater the likelihood of capillary
permeability changes in relation to body cavities. For example, the specific
gravity of the transudate is usually less than 1.012 and a protein content of
less than 2 gm/100mL (2 gm%). Rivalta test may be used to differentiate an
exudate from a transudate. It is not clear if there is a distinction in the
difference of transudates and exudates.
Transudate is extravascular fluid
with low protein content and a low specific gravity (< 1.012). It has low
nucleated cell counts (less than 500 to 1000 /microlit) and the primary cell types
are mononuclear cells: macrophages, lymphocytes and mesothelial cells. For
instance, an ultrafiltrate of blood plasma is transudate. It results from
increased fluid pressures or diminished colloid oncotic forces in the plasma.
The most common causes of pathologic
transudate include: conditions that increase hydrostatic pressure in vessels,
left ventricular heart failure, decrease in colloid oncotic pressure in blood
vessels, cirrhosis (Cirrhosis leads to hypooalbunism and decreasing of colloid
oncotic pressure in plasma that causes edema.), and Nephrotic syndrome (also
due to hypoalbuminaemia caused by proteinuria)
|
Transudate vs. exudate |
||
|
|
Exudate |
|
|
Main causes |
Increased hydrostatic |
|
|
Appearance |
Clear[10] |
Cloudy[10] |
|
< 1.012 |
> 1.020 |
|
|
Protein content |
< 25 g/L |
|
|
fluid protein |
< 0.5 |
> 0.5[12] |
|
Difference of |
> 1.2 g/dL |
< 1.2 g/dL[13] |
|
fluid LDH |
< 0.6 or < ⅔ |
|
|
Cholesterol content |
< 45 mg/dL |
> 45 mg/dL[11] |
The
process of cells proliferation is regulated by substances, which can stimulate
(mitogens) or oppress (keilones) the reproduction of cells. Cambial cells are
the tissues source of regeneratory material. The damage of tissues causes
intensive proliferation trunk cells. The reparative stage of inflammation
begins when phagocytes actively swallow the microorganisms or the tissues
detritus. At that time labrocytes activate interaction with macrophages,
fibroblasts, and intercellular matrix, clotting blood system and promote the
excretion and the synthesis of substances, which stimulate proliferative
processes.
Thrombocytes
produce substances, which strengthen the proliferation and the chemotaxis of
fibroblasts to the injurious area: the thrombocytal factor growth of
fibroblasts, the factor of epidermis and fibroblasts growth, the peptide, which
activates connective tissue etc.
The
labrocytes excrete histamine and leucutrien Â4, 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.
GRANULOUS
TISSUE
Young
connective tissue with lot of vessels
This
tissue covers of wound and ulcer skin defects, it is formed during the damage of
mucous membranes and internal organs, during bones fractures, hematoma
organization, at necrosis (infarction), and during chronic inflammation.
FUNCTIONS:
covering
of defect
trophy
(microcirculation regulation, oxygen and metabolites transport, filtering of
substances)
morphogenetic
(influence on epithelium and muscular tissue differentiation).
incapsulation
(closing) of necrosis area and alien bodies
reconstruction
of anatomic and functional structure of injurious tissues
GRANULOUS 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, hematomes
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
influence of endocrine system on the inflammation is proved by numerous
clinical observations. Hyperthyroidism
amplifies manifestations of the inflammation and hypothyroidism is
characterized by the insignificant sings. Mineralocorticoids
promote the development of inflammatory reaction and glucocorticoids
weaken it. The ability of glucocorticoids
to weaken the inflammation is constantly used in clinics because they reduce
the amount of tissues basophiles, increase the activity of
histaminase (enzyme, which
destroys histamine), reduce serotonine
formation, stabilize lysosome
membranes and inactivate
their enzymes. Glucocorticoids
induce synthesis of proteins, which block prostaglandines
and leucotriens synthesis. Mineralocorticoids
are capable to strengthen the exudation,
to accelerate the reproduction of cells, the derivation of new capillaries, and
synthesis of the connective tissue.
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.
The
temperature within the deep tissues of the body (core temperature) is normally
maintained within a range of
One
of the most important examples of homeostasis is the regulation of body
temperature. Not all animals can do this. Animals that maintain a fairly
constant body temperature are called homeotherms, while those that have a
variable body temperature are called poikilotherms. The homeotherms maintain
their body temperatures at around
Human
organs and the organs of warm-blooded animals also can be divided into two
groups:
à)
organs with permanent and high temperature;
b)
organs with changeable and more lower temperature.
So,
our organism consists of two parts: warm-blooded and cold-blooded. To the first
part one belong the inner organs. The highest temperature has a liver. Then
blood comes in aorta, after that the organs of pectoral and abdominal cavity,
brain and spinal cord. These organs and tissues aresituated in deep areas of
the body. They have permanent temperature and are called by coore, kernel.
Other organs have a more low temperature. It depends on temperature of
envirenment and easely changes. These organs are situated on periphery, they
are called as envelope. To these organs one belong, first of all a skeletal
muscles and skin. Conditional middle temperature of the skin in axillary domain
is 37 °C.
It is taken as a norm.
Regulation
of body temperature realizes by the centre of thermoregulation. It is situated in
arterior part of the hypothalamus in bottom of its third ventricle. A centre
coordinates thermogenesis and delivery of the heat. It provides maintenance of
temperature of inner organs (kernel) in necessary limits.
A centre
of thermoregulation consists of a few anatomic and functional units. The main
of them are
sensative
area (thermostat),
thermoestablishing
area (adjusting point)
and
two effector areas (centres of thermogenesis and delivery of the heat).
Mechanisms of fever.
(1) Release of endogenous pyrogen from inflammatory cells, (2) resetting
of hypothalamus thermostatic set point to a higher level (prodrome), (3)
generation of hypothalamicmediated responses that raise body temperature
(chill), (4) development of fever with elevation of body to new thermostatic
set point, and (5) production of temperaturelowering responses (flush and
defervescence) and return of body temperature to a lower level.
Body
temperatures under different conditions.
Thermostat
is a part of brain, which takes temperature of the body with very high
exactness (0,01 °Ñ). The neurons of this area register
the temperature of arterial blood, which flows over brain straightly. Besides,
they receive signals from receptors of skin and from thermoreceptors of inner
organs. The neurons of thermostat analyse and integrate all this temperature
signalling. They determine a middle temperature of inner organs (kernel)
continously and pass this information on adjusting point.
Adjusting
point is a group of neurons, which determine a necessary temperature of the
body at this moment. It reconstructs the center of thermogenesis and delivery
of the heat. If a temperature of the body is low, a centre of thermogenesis
becomes excited. If temperature of the
body is high, centre of delivery of the heat become excited.
A
centre of thermogenesis regulates a temperature by rising of general metabolic
activity. The most quantity of heat is maked in skeletal muscles. At the
lowering of body temperature in cold regions at first rises muscules tone,
îäíàêî ýòîò ìåõàíèçì not always can give sufficient amount of supplementary
heat. In these cases starts muscular trembling. This is spontaneous rhythmic
abbreviations is skeletal muscules. They can raise a metabolism speed in five
times (retractive thermogenesis). Forming energy partially comes on mechanical
work, but more part of it disengages in the form of the heat. Body temperature
rises. Essential significance in maintenance of body temperature has a liver.
In usual conditions in liver about 30 % of heat are maked.
A heat
emission centre regulates a heat exchange by following ways:
separate
of sweat and evaporation of water over skin and respiratory organs;
radiation
is lossing of heat in form of electromagnetic waves without contact with
surrounding objects;
conduction
is loss of warm at straight contact with objects;
convection
is heat transfer by air molecules or liquid.
Centre
of thermoregulation receives input from two sets of thermoreceptors: receptors
in the hypothalamus itself monitor the temperature of the blood as it passes
through the brain (the core temperature), and receptors in the skin monitor the
external temperature. Both pieces of information are needed so that the body
can make appropriate adjustments. The thermoregulatory centre sends impulses to
several different effectors to adjust body temperature:
The
thermoregulatory centre is part of the autonomic nervous system, so the various
responses are all involuntary. The exact responses to high and low temperatures
are described in the table below. Note that some of the responses to low
temperature actually generate heat (thermogenesis), while others just conserve
heat. Similarly some of the responses to heat actively cool the body down, while
others just reduce heat production or transfer heat to the surface. The body
thus has a range of responses available, depending on the internal and external
temperatures.
|
Effector |
Response
to low temperature |
Response
to high temperature |
|
Smooth
muscles in peripheral arterioles in the skin. |
Muscles
contract causing vasoconstriction. Less heat is carried from the core
to the surface of the body, maintaining core temperature. Extremities can turn
blue and feel cold and can even be damaged (frostbite). |
Muscles
relax causing vasodilation. More heat is carried from the core to the
surface, where it is lost by radiation. Skin turns red. |
|
Sweat glands |
No sweat produced. |
Glands
secrete sweat onto surface of skin, where it evaporates. Water has a high
latent heat of evaporation, so it takes heat from the body. |
|
Erector pili
muscles in skin (attached to skin hairs) |
Muscles
contract, raising skin hairs and trapping an insulating layer of still, warm
air next to the skin. Not
very effective in humans, just causing "goosebumps". |
Muscles
relax, lowering the skin hairs and allowing air to circulate over the skin,
encouraging convection and evaporation. |
|
Skeletal muscles |
Muscles
contract and relax repeatedly, generating heat by friction and from metabolic
reactions. |
No shivering. |
|
Adrenal and thyroid glands |
Glands
secrete adrenaline and thyroxine respectively, which increase the metabolic
rate in different tissues, especially the liver, so generating heat. |
Glands
stop releasing adrenaline and thyroxine. |
|
Behaviour |
Curling
up, huddling, finding shelter, putting on more clothes. |
Stretching
out, finding shade, swimming, removing clothes. |
The thermoregulatory centre normally
maintains a set point of 37.5 ±
Body temperature
reflects the difference between heat production and heat loss. Body heat is
generated in the tissues of the body, transferred to the skin surface by the
blood, and then released into the environment surrounding the body. The
thermoregulatory center in the hypothalamus functions to modify heat production
and heat losses as a means of regulating body temperature.
Mechanisms
of Heat Production
Metabolism
is the body’s main source of heat production. The sympathetic
neurotransmitters, epinephrine and norepinephrine, which are released when an
increase in body temperature is needed, act at the cellular level to shift
metabolism so energy production is reduced and heat production is increased.
This may be one of the reasons fever tends to produce feelings of weakness and
fatigue. Thyroid hormone increases cellular metabolism, but this response
usually requires several weeks to reach maximal effectiveness. Fine involuntary
actions such as shivering and chattering of the teeth can produce a threefold to
fivefold increase in body temperature. Shivering is initiated by impulses from
the hypothalamus. The first muscle change that occurs with shivering is a
general increase in muscle tone, followed by an oscillating rhythmic tremor
involving the spinal-level reflex that controls muscle tone. Because no
external work is performed, all of the energy liberated by the metabolic
processes from shivering is in the form of heat. Physical exertion increases
body temperature. With strenuous exercise, more than three quarters of the
increased metabolism resulting from muscle activity appears as heat within the
body, and the remainder appears as external work.
Mechanisms
of Heat Loss
Most of
the body’s heat is produced by the deeper core tissues (i.e., muscles and viscera),
which are insulated from the environment and protected against heat loss by the
subcutaneous tissues. Adipose tissue is a particularly good insulator,
conducting heat only one third as effectively as other tissues. Heat is lost
from the body through radiation and conduction from the skin surface; through
the evaporation of sweat and insensible perspiration; through the exhalation of
air that has been warmed and humidified; and through heat lost in urine and
feces. Contraction of the pilomotor muscles of the skin, which raises the skin
hair and produces goose bumps, reduces the surface area available for heat
loss. Of these mechanisms, only heat losses that occur at the skin surface are
directly under hypothalamic control. Most of the body’s heat losses occur at
the skin surface as heat from the blood moves to the skin and from there into
the surrounding environment. There are numerous arteriovenous (AV) shunts under
the skin surface that allow blood to move directly from the arterial to the
venous system (Fig. 9-13). These AV shunts are much like the radiators in a
heating system. When the shunts are open, body heat is freely dissipated to the
skin and surrounding environment; when the shunts are closed, heat is retained
in the body. The blood flow in the AV shunts is controlled almost exclusively
by the sympathetic ner-vous system in response to changes in core temperature
and environmental temperature. The transfer of heat from the skin to the
environment occurs by means of radiation, conduction, convection, and
evaporation.
Radiation.
Radiation involves the transfer of heat through the air or a vacuum. Heat from
the sun is carried by radiation. The human body radiates heat in all
directions. The ability to dissipate body heat by radiation depends on the
temperature of the environment. Environmental temperature must be less than
that of the body for heat loss to occur.
Conduction.
Conduction involves the direct transfer of heat from one molecule to another.
Blood carries, or conducts, heat from the inner core of the body to the skin
surface. Normally, only a small amount of body heat is lost through conduction
to a cooler surface. However, loss of heat by conduction to air represents a
sizable proportion of the body’s heat loss.
The
conduction of heat to the body’s surface is influenced by blood volume. In hot
weather, the body compensates by increasing blood volume as a means of
dissipating heat. Exposure to cold
produces a cold diuresis and a reduction in blood volume as a means of
controlling the transfer of heat to the body’s surface.
Convection.
Convection refers to heat transfer through the circulation of air currents.
Normally, a layer of warm air tends to remain near the body’s surface;
convection causes continual removal of the warm layer and replacement with air
from the surrounding environment. The wind-chill factor that often is included
in the weather report combines the effect of convection
caused
by wind with the still-air temperature.
Evaporation.
Evaporation involves the use of body heat to convert water on the skin to water
vapor. Water that diffuses through the skin independent of sweating is called
insensible perspiration. Insensible perspiration losses are greatest in a dry
environment. Sweating occurs through the sweat glands and is controlled by the
sympathetic nervous system. In contrast to other sympathetically mediated
functions, sweating relies on acetylcholine, rather that the catecholamines, as
a neurotransmitter. This means that anticholinergic drugs, such as atropine,
can interfere with heat loss by interrupting sweating.
Evaporative
heat losses involve insensible perspiration and sweating, with 0.58 calories
being lost for each gram of water that is evaporated.12 As long as body
temperature is greater than the atmospheric temperature, heat is lost through
radiation. However, when the temperature of the surrounding environment becomes
greater than skin temperature, evaporation is the only way the body can rid
itself of heat. Any condition that prevents evaporative heat losses causes the
body temperature to rise.
Etiology
and pathogenesis of the fever
Rise of
body temperature is very frequent symptom attached to much diseases. There are
two type of rising temperature: a fever and hyperthermy.
Fever is
typical pathological process. He describes by change of thermoregulation and
rise of body temperature, irrespective of temperature of environment. Attached
to fever thermoregulation centre oneself aspires to rise of temperature.
Hypothermy
is a fortune, when body temperature rises under dominance of external and
inlying factors. Thermoregulation centre tackles body temperature within the
pale of normal sizes, however this to him does not turn out well.
On
origin distinguish two fevers – appearance infectious and uninfectious.
Evolutional fever arose as reaction on penetration in microorganisms organism
and their toxins, therefore she most typical for infectious illnesses.
Infectious
fever. microorganisms contain the pyrogenetic matters (exogenous pyrogens).
They go into composition of toxins of mycroorganisms. Most are studied the
endotoxins of Gramnegative bacterium. They consist of three parts: lipid,
polysacharid and albuminous. Pyrogenetic properties has lipid fraction (lipoid
A).
Under
influence lipoid À in organism forms endogenous pyrogen – interleukin 1. It
exudes by neutrophils, monocytes, macrophags and with by other cells, that is
apportionment of interleukin 1 is function of phagocyting cells. Attached to
contact exogenous pyrogens with these cells acceterate the genes, which encode
synthesis of interleukin 1. It immediatly influences on thermoregulation
centre.
Many
microorganisms do not pick out the endotoxins, but are followed with fever (flu
exciters, diphtheria, stupor). Here displays general conformity to natural
laws: any phagocytosis stimulates apportionment inlying of pyrogen. Bacterium
and viruses actively eliminate from blood by system of mononuclear phagocytes
cells. These cells initiate production inlying of pyrogen in liver, spleen and
other organs.
The
uninfectious fevers divide by two hinds appearance on origin: fever attached to
allergy and fever attached to aseptical inflammation. Their pathogeny
identical: they call inlying by pyrogen. Attached to aseptical inflammations (myocardium
heart attack, illness of connecting tissue) takes place phagocytosis of lost
and damaged cells and ferments. Attached to allergies phagocytes eat the
complexes of antigen-antibody.
Interleukin
1 acts on thermosensitive neurons of thermoregulation centre, that is on thermostat. These neurons have on
its membranes the sensible receptors. After their irritation activates
adenilatecyclase thermostat neurons system.
In them grows cyclic adenosinemonophosphate. It changes sensitiveness of
these neurons to cold and thermal signals. To cold signals sensitiveness grows,
and to thermal – falls.
In
these conditions adjusting of thermoregulation centre point values blood-heat
of inlying organs as low. Referenting temperature of adjusting point displaces
up starts to fever. Transmission of information from thermostat neurons on
neurons of adjusting point performs with the help of prostaglandins.
Fever stages
Pick out three fever stages:
stage of temperature rising (stadium incrementi),
stage of high temperature standing (stadium fastigii),
stage of temperature lowering’s (stadium decrementi) .
In the
first stage of heat production prevails over heat emission. Mechanisms of heat
production and heat emissions reform like so, to retain body temperature on
more high level. Foremost, heat emission limits. This mechanism matters
decisive. The peripheral vessels narrows, diminishes an influx of warm blood to
peripheral tissues, diminishes sweat separate and evaporation. In-parallel with
that increases heat production. Grows muscles tone. Appears muscles thremor.
Grows heat production in liver. Rising of body temperature is attended with
shivering. By this term designate strong of cold feel in combination with
intensive thremor.
Body
temperature gradually rises. It reaches referenting temperature of adjusting
point, that is necessary temperature. On this level it holds on a few hours or
days. This is the second stage (stage of high standing). In this stage heat
production anew becomes equal as heat emission. However an equilibrium supports
on more higher level. Sick feels a heat’s flow (heat). Rises not only the
temperature of inlying organs, but the skin’s temperature also.
On
temperature up degree in second stage distinguish such types of fever:
subfebrile
– to 38 °C,
moderate
– 38-39 °C,
high –
39-41 °C,
hyperpiretic
– above 41 °C.
In
third stage the action of interleukin 1 on thermoregulation centre ceases.
Referenting temperature of adjusting point anew goes down. The centre of heart
production oppresses. Heat emission centre,
inside out, activates. Diminishes heart production in muscles and hepar.
Heat return grows on all possible ways. Lowering of body temperature is gradual
(lytical) or rapid (critical).
Rapid (critical) (À) and gradual (lytical) (HB) lowering of body temperature on
third stage
of fever reaction
Types
of the temperature curves
Nature
of curve depends on two factors – illness exciter peculiarities and organism
reactivity. Major types of temperature curves:
Febris continua
– permanent fever. Oscillations between morning and evening temperature do not
exceed 1 °C. Such temperature curve is observed
on the first period of abdominal typhus, attached typhus, crupose pneumonia.
Febris
remittens – indulgence fever. Oscillations between morning and evening
temperature exceeds 1 °C. Such type of curve observes
attached to viral infections, sepsis, in second half of abdominal typhus.
Febris
intermittens. It is alternating fever. Describes ot the rising periods of
temperature (paroxysmuses) right alternate with the periods of normal
temperature (apirrhexions). Temperature of the body rises to the level of 40 °C and higher, holds on a few hours,
goes down to the norm and rises again. This fever type is observed to the
malaria. The paroxysmuses can arise every fourth day (febris quartana), every
third day (febris tertiana) or daily (febris quotidiana). Periodicity of the
temperature rise depends on duration of development cycle of malarial
plasmodium. Paroxysmuses coincide in course of the time of destruction of
erythrocytes (after completion of cycle).
Febris recurrens. It is recurrent fever. Describes
by more protracted periods of rising temperature (5-8 days) and lack of clear
regularity in beginnings of paroxysmuses. Example is recurrent typhus.
Febris
hectica. It is exhausting fever. Daily oscillations of it are equal 2-3 °C and more. Sometimes temperature
goes down below the norm. Such fever is typical to sepsis, tuberculosis.
Febris
undulans. It is undulating fever. It is typical for brucellosis.
Later clean types of temperature
curves are rare. This related to wide antibiotics application and antipyretics.
Types
of the temperature curves: a - Febris continua, b - Febris remittens, c - Febris intermittens, d - Febris recurrens
Biological
role of the fever
Fever,
as regulations, renders positive influence on sick organism. It is instrumental
in convalescence. In the same time fever is followed with undesirable changes
in the organism. At first we will bring arguments to the fever benefit as
protective, adaptated reaction.
Fever
is negatively for the growing and reproduction of some microorganisms. For
example, gonococcuses and treponems perish at the temperature of 40-40,1 °C. Fever creates inauspicious sfere
for development of some types of the pneumococcuses, prevents to reproduction
of some pathogenic viruses. Typical example is oppression of the reproduction
of poliomyelitis virus
Fever
decrease resistibility of microorganisms to medical preparations, stimulates
immunological answer of the organism on encroachment of infectious agent. The
fever activates phagocytosis, antibodies synthesis rises, T-lymfocytes increase
the multiply synthesis and secretion of interferon, which makes antiviruses
action.
Fever is
a strong stressor. Attached to fever rises activity of hypothalamic kernels,
àfter takes place an activation of front pituitary gland part and of suprarenal
glands cortices. These phenomena is
typical for general adaptation syndrome. In-parallel rises activity of
sympathetic-adrenal system.
Becomes
stronger disintegration of glycogen, appears hyperglycemia. In conditions of
raised metabolism and raised thermogeneration it provides to the tissues
energy.
Fever
is followed with much effects positive for organism. They served by foundation
for elaboration and inculcation in practice of special cure appearance
pyrotherapy.
Fever
is absolutely adaptation reaction. But it is not always useful. In dependence
on illness nature, age, to individual
reactivity she can begin undesirable, even harmful.
Fever
makes worse sick state of hereth, followed with discomfort. It is attended with
shivering, general indisposition, headache, heat sense, sometimes – delirium.
Fever
inauspiciously affects metabolic processes. It sharply raises the basic
metabolism. Such rules is established conformity to natural laws: increases of
body temperature on 1 °C conforms to rise of basic
metabolism exemplarily on 10 %.
Diverse
types of cargo exchangevariously react on fever. Not single conformity to
natural laws in interchange changes of carbohydrates, fats, proteines. These
changes depend on fever causes, stage of
feverish reaction, power reserves of organism,
reliability of regulation systems, nourishment character and other
factors.
Attached
to some infectious illnesses disorder of carbohydrates and fatty metabolism are
very big. Carbohydrates backlogs are exhausted fully. By energy sources begin
fat acids. Surplus receipt of fat acids in lever brings about surplus generation
of ketone bodies. Develops metabolic acidosis.
The
violations of albuminous exchange attached to fever are more various. Attached
to infectious diseases smart few protein disintegration in organism reinforced.
It does not compensate by protein receipt with food. Arises the negative
nitrous balance. Heightened albuminous exchange attached to fever interconnect
with action of microbic toxins and tissues disintegration products. Toxic
protein disintegration in experiment is observed, for example, attached to
introduction of dysenteric toxin, fresh pus, streptococci culture, blue pus
bacillus. It typical, foremost, for
sharp infectious diseases.
Fever
inauspiciously affects cardio-vascular system. As a regulations, frequency of
cardiac abbreviations increases (tachycardia). It conditioned by much factors:
a) rise
of activity of sympatical nervous system;
b)
straight hormones dominance of thyroid on heart;
c)
dominance of warm blood on sinus knot;
d)
lowering of peripheral vessels resistance.
By
Libermayster, rise of body temperature on 1 °C
is attended with speed up of pulse on ten beat in one min. Except of
tachycardia, rises a shock heart volume. Cardiac output increases on 25-30 %.
Change
of arterial pressure depends on fever stage.
In first stage it rises, in second stage
will normalize or will bit lowers. Lowering of arterial pressure in
third stage depends on temperature degradation speed. Attached to slow temperature (lysis)
degradation pressure lowers gradually and moderately. Attached to rapid temperature
(crisis) degradation pressure lowers rapidly and sharply. In this case is
possible collapse development.
Changes
blood circulation. On periphery of the body it limits. But in inlying organs
(buds, liver, spleen) resistance of vessels lowers, and circulation of the
blood becomes stronger.
Breathing
attached to rise of temperature becomes more frequent (tachypnoe). High
frequency of breathing are accounted for by straight dominance of high
temperature on respiratory centre.
Permanent
fever satellite – violation of function of digestive organs. Function of
alimentary canal strongly disturbs attached to abdominal typhus, diphtheria,
measles, less - attached to flu, recurrent typhus, tuberculosis. Nature of
these similar violations attached to fever of any origin. The very frequent
displays: appetite loss, lowering of
saliva secretion, bowels atony (constipation, flatulency), lowering of pancreas excretory function,
lowering of motored and secretory function of stomach.
Disorders
of digestion unconnected immediately with fever. They related to water loss and
chlorids. Therefore antipyretics do not give medical effect. For removal of
digestion disorders it is need a special diet.
Heavy
fever oppresses the central nervous system. In sick appear such symptoms, as
leading pain, weariness, insomnia. Attached to expressed intoxication are the
hallucinations, delirium, consciousness loss,
in children – the cramp. In pathogenesis of these symptoms an essential
significance has brain anoxaemia.
If
disease flows with high temperature, always stands up a question of medical
tactics: as will make away fever or not? Absolute testimonies for symptomatic
cure fevers following: body temperature sick above 39 °C,
cramps presence in anamnesis, concomitant heart diseases and vessels, sharp
neurulogic diseases, sepsis, shock.
For
wrestling with fever adapt antipyretics. Mechanism of their action is very
various: braking of synthesis leukocytes pyrogen interleukin 1, oppression of
synthesis of fever mediator – prostaglandins,
oppression of thermoregulation centre excitability, lowering of
intensity of oxydizing processes and diminution of heat making, augmentation of blood flow in peripheral
vessels, reinforcement of sweat separate processes.