In acute inflammation, the pressure in postcapillary venules may overcome the osmotic pressure of plasma proteins. Therefore fluid and low molecular substances have the tendency to penetrate into the surrounding area. The vascular permeability for proteins and some smaller molecules differs from tissue to tissue. For example, the brain and thymus vessels are less permeable. The sinusoids in liver and sinuses in spleen are highly open vessels even at normal conditions.
The increased capillary permeability for plasma proteins is the key factor for the production of inflammatory exudate. In the interstitial area, high-molecular proteins may be split into smaller fragments that participate in the raising of osmotic pressure of interstitial fluid. In addition, the alteration of general matrix is observed. It becomes more fluid which helps to make easier the diffusion of exudate. On the other hand, a sudden increase of pressure in tissue is thus prevented.
There are two phases of inflammatory infiltration. The immediate temporary phase with a peak between 8 and 10 min and duration about 30 min. It is developed by the release of fluid from venules mediated by histamine. This is followed by immediate prolonged phase which is similar, only the time of duration is greater -- a few days. The second delayed phase needs a few hours for its development. The damage to capillaries and venules is observed.
In the fluid exudate, all components of plasma, including fibrinogen, kinins, complement, immunoglobulins etc., are present. Fibrinogen is important for clot formation and the prevention of further loss of blood. Fibrin, which is originated from fibrinogen, acts as the beginning of a scaffold on which tissues may subsequently be repaired and on which new capillaries can be constructed, a process known as angiogenesis. Although the rapid response of the coagulation pathway is essential, the extent of blood clothing must be limited so that it does not progress to undamaged vessels. In addition, the clots must ultimately be removed from the area of damage. This is controlled by fibrinolysis (fibrin breakdown) due to the enzyme plasmin.
The kinins are important mediators of inflammatory responses. For kinin generation to proceed efficiently, activated Hageman factor activates prekallikrein via a series of prekallikrein activators, resulting in the production of kallikrein. The generation of kallikrein triggers kinin production, including the formation of bradykinin, which is responsible for induction pain, increasing vascular permeability, and causing vasodilation. Kallikrein also activates the fibrinolytic pathway, leading to the removal of blood clots.
The complement cascade, as a part of the innate immune response, may be activated via the alternative and/or collectin (lectin) pathway to destroy some invading microorganisms. In addition, during activation of complement, important opsonins (C3b), chemotactic factors for neutrophils and mononuclear phagocytes (C5a), and anaphylatoxins (C5a, C3a) are formed. They all participate in inflammation during phagocytosis or immediate allergic reactions.
Immunoglobulins may act as specific or nonspecific opsonins facilitating thus the process of phagocytosis, or may participate in antibody-dependent cell-mediated cytotoxicity (ADCC) by which target cells are destroyed by killer cells.
In the fluid infiltrate, all components of plasma, including administered drugs, are present. Therefore it is important to administer effective antibiotic or other chemotherapy as soon as possible in order to reach the inflammatory area in the concentration similar to that in plasma.
Exudative infiltrate contributes to the general signs of inflammation. It is responsible for edema (swelling, tumour). The increased pressure in tissue may participate in the production of pain (dolor). Actually, the pain is observed before the occurrence of greater edema, since also other factors such as the acidic pH of exudate, the accumulation of potassium ions and the presence of bradykinin, serotonin or other mediators take part in this process.
