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Mat Did 909273
Mat Did 909273
Mat Did 909273
Introduction
Inflammation is the response of living tissue to damage.
The cause of acute inflammation may be due to physical damage, chemical substances, micro-organisms or
other agents. The inflammatory response consist of changes in blood flow, increased permeability of blood
vessels and escape of cells from the blood into the tissues. The changes are essentially the same whatever the
cause and wherever the site.
Acute inflammation is short-lasting, lasting only a few days. If it is longer lasting however, then it is referred
to as chronic inflammation. Various examples of acute inflammation that you may be aware of are sore throat,
reactions in the skin to a scratch or a burn or insect bite, and acute hepatitis and so on. However, there are
occasional historical exceptions such as pneumonia, inflammation of the lung rather than pneumonitis and
pleurisy, inflammation of the pleura, rather than pleuritis .
Clinical Aspects of Acute Inflammation
The four principal effects of acute inflammation were described nearly 2,000 years ago by Celcus:
Swelling (tumor)
RIGONFIAMENTO
Swelling results from oedema, the accumulation of fluid in the extra vascular space as part of the fluid exudate, and to a
much lesser extent, from the physical mass of the inflammatory cells migrating into the area.
Microbial infections
One of the commonest causes of inflammation is microbial infection. Viruses lead to death of individual cells by
intracellular multiplication . Bacteria release specific exotoxins - chemicals synthesised by them which specifically
initiate inflammationÑor endotoxins, which are associated with their cell walls. Additionally, some organisms cause
immunologically-mediated inflammation through hypersensitivity reactions. Parasitic infections and tuberculous
inflammation are instances where hypersensitivity is important.
Hypersensitivity reactions
A hypersensitivity reaction occurs when an altered state of immunological responsiveness causes an inappropriate or
excessive immune reaction which damages the tissues. The types of reaction are classified here, but all have cellular or
chemical mediators similar to those involved in inflammation.
Physical agents
Tissue damage leading to inflammation may occur through physical trauma, ultraviolet or other ionising radiation, burns
or excessive cooling ('frostbite').
Tissue necrosis
Death of tissues from lack of oxygen or nutrients resulting from inadequate blood flow (infarction) is a potent
inflammatory stimulus. The edge of a recent infarct often shows an acute inflammatory response.
COMPONENTI CELLULARI E NON CELLULARI CHE PARTECIPANO
ALLO SVILUPPO DEL PROCESSO INFIAMMATORIO
Figure 2-1 The components of acute and chronic inflammatory responses: circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular
matrix.
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MEDIATORI DELL’INFIAMMAZIONE
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Figura 13.34 - Effetti locali e sistemici delle citochine infiammatorie.
In the early stages, oedema fluid, fibrin and neutrophil polymorphs accumulate in the extracellular spaces of
the damaged tissue. The presence of the cellular component, the neutrophil polymorph, is essential for a
histological diagnosis of acute inflammation. The acute inflammatory response involves three processes:
•changes in vessel calibre and, consequently, flow
•increased vascular permeability and formation of the fluid exudate
•formation of the cellular exudate by emigration of the neutrophil polymorphs into the extravascular
space.
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Figure 2-3 Blood pressure and plasma colloid osmotic forces in normal and inflamed microcirculation. A, Normal hydrostatic pressure (red arrows) is about 32 mm Hg at
the arterial end of a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is
equal to the mean capillary pressure. Although fluid tends to leave the precapillary arteriole, it is returned in equal amounts via the postcapillary venule, so that the net
flow (black arrows) in or out is zero. B, Acute inflammation. Arteriole pressure is increased to 50 mm Hg, the mean capillary pressure is increased because of arteriolar
dilation, and the venous pressure increases to approximately 30 mm Hg. At the same time, osmotic pressure is reduced (averaging 20 mm Hg) because of protein
leakage across the venule. The net result is an excess of extravasated fluid.
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Figure 2-3 Blood pressure and plasma colloid osmotic forces in normal and inflamed microcirculation. A, Normal hydrostatic pressure (red arrows) is about 32 mm Hg at
the arterial end of a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is
equal to the mean capillary pressure. Although fluid tends to leave the precapillary arteriole, it is returned in equal amounts via the postcapillary venule, so that the net
flow (black arrows) in or out is zero. B, Acute inflammation. Arteriole pressure is increased to 50 mm Hg, the mean capillary pressure is increased because of arteriolar
dilation, and the venous pressure increases to approximately 30 mm Hg. At the same time, osmotic pressure is reduced (averaging 20 mm Hg) because of protein
leakage across the venule. The net result is an excess of extravasated fluid.
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Figure 2-4 Diagrammatic representation of five mechanisms of increased vascular permeability in inflammation (see text).
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Fattori condizionanti l’accumulo di fluido in un tessuto
+ 8.3 - 6.7
PATOGENESI EDEMI TRASUDATIZI
LOCALIZZATO GENERALIZZATO
Trombosi venosa
Ridotto drenaggio linfatico Ipervolemia: aumentato riassorbimento
Acqua per riduzione della P arteriosa
(insufficienza cardiaca)
Entry of antibodies. Increased vascular permeability allows antibodies to enter the extravascular space, where they may lead either
to Iysis of microorganisms, through the participation of complement, or to their phagocytosis by opsonisation. Antibodies are also
important in neutralisation of toxins.
Drug transport. The fluid carries with it therapeutic drugs such as antibiotics to the site where bacteria are multiplying.
Fibrin formation. Fibrin formation from exuded fibrinogen may impede the movement of micro-organisms, trapping them and so
facilitating phagocytosis.
Delivery of nutrients and oxygen. Delivery of nutrients and oxygen, essential for cells such as neutrophils which have high
metabolic activity, is aided by increased fluid flow through the area.
Stimulation of immune response. The drainage of this fluid exudate into the Iymphatics allows particulate and soluble antigens to
reach the local Iymph nodes where they may stimulate the immune response.
The role of neutrophils in the cellular exudate is described here. They have a life-span of only 13 days and must be constantly
replaced. Most die locally, but some leave the site via the Iymphatics. Blood monocytes also arrive at the site and, on leaving the
blood vessels, transform into macrophages, becoming more metabolically active, motile and phagocytic. Phagocytosis of micro-
organisms is enhanced by opsonisation by antibodies or by complement. In most acute inflammatory reactions, macrophages play a
lesser role in phagocytosis compared with that of neutrophil polymorphs. They appear late in the response and are usually
responsible for clearing away tissue debris and damaged cells. Both neutrophils and macrophages may discharge their Iysosomal
enzymes into the extracellular fluid by exocytosis, or the entire cell contents may be released when the cells die. Release of these
enzymes assists in the digestion of the inflammatory exudate.
Effects of Acute Inflammation
Harmful effects
The release of Iysosomal enzymes by inflammatory cells may also have harmful effects:
Digestion of normal tissues. Enzymes such as collagenases and proteases may digest normal
tissues, resulting in their destruction. This may result particularly in vascular damage, for
example in type III hypersensitivity reactions and in some types of glomerulonephritis.
Swelling. The swelling of acutely inflamed tissues may be harmful: for example, the swelling of
the epiglottis in acute epiglottitis in children due to Haemophilus influenzae infection may
obstruct the airway, resulting in death. Inflammatory swelling is especially serious when it
occurs in an enclosed space such as the cranial cavity. Thus, acute meningitis or a cerebral
abscess may raise intracranial pressure to the point where blood flow into the brain is impaired,
resulting is ischaemic damage, or may force the cerebral hemispheres against the tentorial
orifice and the cerebellum into the foramen magnum (pressure coning).
Inappropriate inflammatory response. Sometimes, acute inflammatory responses appear
inappropriate, such as those which occur in type I hypersensitivity reactions (e.g. hay fever)
where the provoking environmental antigen (e.g. pollen) otherwise poses no threat to the
individual. Such allergic inflammatory responses may be life-threatening, for example extrinsic
asthma.
Figure 2-8 Schematic and histologic sequence of events following acute injury. The photomicrographs are representative of the early (neutrophilic) (left) and later
(mononuclear) cellular infiltrates (right) of infarcted myocardium. The kinetics of edema and cellular infiltration are approximations. For sake of simplicity, edema is shown
as an acute transient response, although secondary waves of delayed edema and neutrophil infiltration can also occur.
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Figure 2-6 The multistep process of leukocyte migration through blood vessels, shown here for neutrophils. The leukocytes first roll, then become activated and adhere to
endothelium, then transmigrate across the endothelium, pierce the basement membrane, and migrate toward chemoattractants emanating from the source of injury.
Different molecules play predominant roles in different steps of this process-selectins in rolling; chemokines in activating the neutrophils to increase avidity of integrins (in
green); integrins in firm adhesion; and CD31 (PECAM-1) in transmigration.
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Figure 2-6 The multistep process of leukocyte migration through blood vessels, shown here for neutrophils. The leukocytes first roll, then become activated and adhere to
endothelium, then transmigrate across the endothelium, pierce the basement membrane, and migrate toward chemoattractants emanating from the source of injury.
Different molecules play predominant roles in different steps of this process-selectins in rolling; chemokines in activating the neutrophils to increase avidity of integrins (in
green); integrins in firm adhesion; and CD31 (PECAM-1) in transmigration.
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Figura 13.31 - Patogenesi della risposta infiammatoria acuta e cronica.