Illness

Inflammation

= reaction of normal tissues to cell damage; non-specific local reaction, with a defensive character.

• It may be accompanied by general reactions such as: fever, leukocytosis, changes in intermediate metabolism, which in turn, influence the development of the local process

• Clinical signs of inflammation: redness, heat, pain, tumor, lesa function.

Etiology

• Exogenous agents:

1. mechanics

2. physical

3. chemicals

4. biological

• Endogenous agents:

1. activation of endogenous proteases

2. hereditary lack of protease inhibitors

3. gained lack of protease inhibitors

4. movement disorders

5. the activating effect of immune complexes

6. activating effect of micromolecules

Pathogenesis of inflammation

I. Acute inflammation

- has 2 phases that take place simultaneously

1. Vascular phase

 Under the action of flocogenic agents, vasoactive mediators are released that produce a local vasodilation.

 Hyperemia is followed by a slowdown in circulation (sometimes even stasis).

 There is also an increase in permeability, which may affect some segments (post-accumulation veins), or the entire microcirculation.

 Orifices form between adjacent endothelial cells, as a result of their contraction, produced by histamine.

2. Cellular phase

 Following exudation, the cells concentrate in the inflamed area.

 PMNs and monocytes migrate.

 Leukocytes emit pseudopods, and then the whole cell slides out of the vessel.

 In the inflammatory exudate from the early stages, mainly leukocytes (PMN) grow, then macrophages.

 Migrated leukocytes and macrophages participate in phagocytosis => released metabolites cause damage to inflamed tissue.

Vasoactive mediators

1. Biogenic amines

a. Histamine

o It is formed by the decarboxylation of histidine

o Produced by mast cells, PMN, platelets, monocytes.

o Important vasoactive mediator.

o It acts through H1 receptors (it causes the dilation of the terminal arteriole and the contraction of the endothelial cell, participating in the increase of the permeability and in the triggering of the sensation of pain); H2 (causes the production of IL1, TNF, complementary factors).

b) Serotonin

o It comes from the decarboxylation of 5-hydroxytryptophan.

o It has the same effects as histamine, but of lower intensity.

2. Plasma kinin system

o Kallikrein (resulting from pre-kallikrein), acts on kininogen with high or low GM, resulting in plasma kinins: bradykinin, lysyl-bradykinin, methionine-lysyl-bradykinin.

o Bradykinin => has the strongest vasodilating effect among the vasoactive mediators released in the inflammatory process; most important in modulating inflammation and pain.

3. Arachidonic acid derivatives

 Arachidonic acid results from phospholipids under the action of phospholipase A2.

 It has 2 metabolic pathways:

a. under the action of cyclooxygenase => prostaglandins (E, D, I) + thromboxane.

b. Under the action of lipooxygenase => leukotrienes + hydroxyheicosatetraenoic acid (HETE).

A. Prostaglandins

- contributes to the formation of inflammatory edema (E, D)

- vasodilation

- contributes to hyperalgesia

- antiplatelet effect (I)

- modulates the febrile reaction (E)

B. Thromboxane

- antagonistic effect

C. Leukotrienes

- chemoattractant effect

- produce the aggregation of granulocytes, macrophages, monocytes

- releases lysosomal enzymes

- activates the suppressor T lymphocyte

- they intervene at the level of basophils and favor the release of histamine (slow reaction substance of anaphylaxis).

4. Cytokines

= mediators who ensure the transmission of information between cells.

- represented by: interleukins (IL 1 to 13) with pro or anti-inflammatory effect

, TNF (tumor necrosis factor), CSF (cell colony stimulating factor), chemotactic factors, interferons, growth factors, adhesion molecules.

General reactions that accompany inflammation

Febrile reaction

= a general, nonspecific reaction, which within certain limits and duration has the meaning of a defense reaction.

- It is nonspecific because it can be triggered by a wide variety of etiological agents.

- The character of defense is due to the following situations:

 there is the activation of general, non-specific defense mechanisms (leukocytosis, phagocytosis, activation of macrophage system).

 Increases AC synthesis.

 The penetration of medicinal substances into the tissues is favored.

 Unfavorable conditions are created for the development of microorganisms.

- the limits of the defense character of the febrile reaction are in relation both to its duration and to its intensity.

- Pyrethroid therapy = artificial production of fever by administering foreign proteins.

Phases of the febrile reaction

1. Latency phase

- From contact with pyrethroid agent to rising temperature.

2. Temperature rise phase

- there is a temporary imbalance between thermogenesis and thermolysis.

- The patient is pale, has the sensation of chills (chills). = Cold stage

- Cardiac activity intensifies, glomerular filtration decreases, diuresis is reduced.

3. The state phase

- after reaching the new homeothermal point, a balance is established between thermogenesis and thermolysis.

- The patient has rosy skin, well irrigated, with a feeling of warmth.

4. Defervescence phase

- a new imbalance in which, this time, the thermogenesis decreases and the thermolysis increases.

II. Chronic inflammation

- refers to the duration of the inflammatory process.

Characteristics :

a. the etiological agent persists for a long time

b. The mediators of the released inflammation act on the cells in the inflamed tissue or on some distant cells.

c. has 3 phases:

1. Inflammatory phase - endothelial cells, pmn, lymphocytes, monocytes macrophages, platelets are important.

2. Proliferation phase - connective tissue cells migrate, proliferate and synthesize components of the extracellular matrix.

3. The recovery phase and / or fibrosis - the continuous release of inflammatory cytokines takes place, the cellular processes are amplified, leading to the perpetuation of chronic inflammation.