PATHOPHYSIOLOGY OF INFLAMMATION
INTRODUCTION, GENERALITIES, DEFINITION:
Any multicellular organism, in order to maintain its integrity, must have not only processes for repairing damaged tissues but also mechanisms ensuring its protection against external agents, living or chemical, threatening its internal balance (its homeostasis). These multiple mechanisms, which affect blood circulation, leukocyte activity, antibody formation, and wound healing, are part of the phenomena known as inflammation.
Inflammation can be defined as the set of vascular, tissue and humoral modifications produced in living multicellular organisms by any attack on their tissue integrity, whatever the cause. Far from being a disease, the inflammatory reaction corresponds to a mode of expression of the body’s defenses.
It is a localized reaction of a tissue, following an exogenous or endogenous aggression. It is a normal and beneficial reaction of the body against an aggression. Its goal is to eliminate the pathogen and repair tissue damage. Sometimes inflammation can be harmful or pathological in certain situations: the aggressiveness of the pathogen, its persistence, its location, abnormalities in the regulations of the inflammatory process or by the quantitative or qualitative abnormality of the cells involved in the inflammation.
The inflammatory process takes place within living, vascularized connective tissue. Non-vascularized tissues such as cartilage, meniscus, and cornea are unable to develop a full inflammatory response.
Disorders of inflammatory reactions are dominated by cellular (immune) deficits and the excess formation of antibodies that become harmful to the host (hypersensitivity or allergy phenomenon).
I. CAUSES AND ETIOLOGY OF INFLAMMATION: The causes of the inflammatory reaction are multiple and represent pathogenic agents.
1. Exogenous pathogens:
* physical: trauma, heat, cold, electricity, foreign bodies and ionizing radiation
* chemical: acids, bases and toxic substances: venoms, caustics and even medicines.
* Do not forget exogenous foreign bodies (wood splinter, safety glass, etc.)
* infectious: viruses, bacteria, fungi and parasites.
2. Endogenous pathogens:
* trophic causes (disorders or defects in vascularization, innervation, etc.): defects in vascularization lead to an inflammatory reaction which is itself secondary to necrosis by tissue ischemia.
* cholesterol and atheromatous plaques
* glandular stones
* degenerative lesions (osteoarthritis)
* immune conflicts (autoimmune diseases, immune deficiencies, allergies)
* tumor lesions, especially malignant ones
II. ELEMENTS INVOLVED IN THE INFLAMMATORY REACTION
These are the body’s means of defense. On the one hand, there are specialized cell lines (specific and non-specific) and the substances they produce, and on the other hand, humoral mediators. There are also elements of connective tissue (fibroblasts, histiocytes, collagen fibers, etc.)
1. Cellular systems and their elaborated substances (Cytokines):
1.1. Phagocytes : They have the particularity of being attracted by various substances exerting a positive chemotactic effect and of being capable of neutralizing pathogenic formed bodies by phagocytosis. They are responsible for non-specific primary immunity or innate immunity.
1.1.1. Substances released by phagocytes:
* Pro-inflammatory and anti-inflammatory substances (cytokines): some of these substances are released into the connective tissue and will participate in triggering and maintaining the inflammatory process.
These substances are:
– lysozymes;
– prostaglandins;
– thromboxanes;
– lymphocyte activators;
– tumor cell inhibitory factors;
– the interfering one;
– endogenous pyrogens.
PATHOPHYSIOLOGY OF INFLAMMATION
1.1.2. The different types of phagocytes
* The mononuclear phagocyte system : the activated mononuclear leukocyte in the blood becomes a monocyte; when it passes into the tissue it becomes a histiocyte and when it exercises its phagocytosis property it becomes a macrophage.
* Polymorphonuclear leukocytes or granulocytes : they contain a segmental nucleus and granules with dye affinity (neutrophils, eosinophils or basophils).
1.2. Lymphocytes : They are responsible for secondary or specific immune reactions which are triggered after cooperation with histiomonocytes (the lymphocyte is activated by the interleukin released by the histiocyte).
There are two types of immune cells:
* T lymphocyte = cell-mediated immunity
* B lymphocyte = humoral-mediated immunity: Immunoglobulin (Ig) = Antibody (Ab)
1.3. NK (Natural Killer) cells : These are cells defined by their property of lysing cancer cells, cells infected by various pathogenic agents, foreign hematological cells (sickle cells), etc.
2. Humoral mediators:
* There are many endogenous mediators of inflammation. Some are of cellular origin, others of plasma origin. Their actions can be summarized in 3 important effects:
– Induction of vascular modifications (vasodilation, increased permeability), by histamine and bradykinin.
– Induction of leukocyte infiltration (leukocyte diapedesis) by positive chemotaxis.
– The production of tissue lesions.
2.1. Mediators of local cellular origin : In addition to substances of lysosomal origin and those produced by T-lymphocytes, mediators of tissue origin are essentially represented by amines and acidic lipids. They have an essentially vascular effect.
a. Amines: These are stored in the lysosomal sacs of various cells. We find:
– Histamine: this is the first mediator released during an inflammatory process. It causes an increase in capillary permeability as well as the formation of edema.
– Serotonin.
b. Acidic lipids (fatty acids) = eicosanoids
These pro-inflammatory substances act in the vascular-blood phase (vasodilator) and sometimes slow down the release of histamine.
2.2. Plasma mediators : When activated, they have vasodilatory effects or develop a positive chemotactic effect on leukocytes.
a. Kinin system : it is dominated by bradykinin which has an effect:
– Vasodilator.
– Increase in capillary permeability greater than that induced by histamine.
– Severe local pain: kinins share this effect with histamine, acetylcholine and serotonin.
b. Serum complement : complement activates antibodies released by B lymphocytes (plasma cells)
c. Factor XII (or Hageman factor ):
III. CONCEPTS OF ACUTE INFLAMMATION AND CHRONIC INFLAMMATION
1. Acute inflammation: it represents the immediate response to an aggressive agent, of short duration (a few days or weeks), often of sudden onset and characterized by intense vascular-excessive phenomena. Clinical signs (local and general) and biological signs are often present. The four cardinal signs of acute inflammation are: pain, heat, tumor or swelling and redness.
Acute inflammation heals spontaneously or with treatment, but can leave sequelae if tissue destruction is significant.
2. Chronic inflammation : this corresponds to inflammation that has no tendency to spontaneous healing and which evolves by persisting or worsening for several months or several years. General clinical signs are absent or minimal.
Histopathologically, this type of inflammation is characterized by the presence of granulomatous cellular tissue rich in collagen fibers.
Chronic inflammation can follow acute or subacute inflammation or even appear spontaneously.
IV. THE DIFFERENT TIMES OF THE INFLAMMATORY REACTION OR GENERAL COURSE OF THE DIFFERENT STAGES OF THE INFLAMMATORY REACTION
The inflammatory reaction is a dynamic process involving several successive and different stages involving cellular and humoral systems.
The four main successive phases are:
1. Vasculo-blood or vasculo-exudative reactions: this initial phase involves three basic modifications:
* active congestion;
*inflammatory edema;
* leukocyte diapedesis.
During this initial phase, the four cardinal signs of acute inflammation appear: pain, heat, swelling and redness. It can last from 10 minutes to several days.
1.1. Active congestion: this involves arteriolar and then capillary vasodilation in the affected area. Locally, this results in an increase in blood supply and a slowing of the circulatory current. Congestion is rapidly triggered by a nervous mechanism and the action of pro-inflammatory chemical mediators (histamine, serotonin, etc.).
1.2. Inflammatory edema: it results from the passage into the interstitial connective tissue or serous cavities of a liquid called exudate consisting of water and plasma proteins.
Its clinical translation is tissue swelling and pain caused by compression of nerve endings in addition to the action of algogenic substances.
Inflammatory edema results from an increase in hydrostatic pressure due to vasodilation and especially from an increase in the permeability of the wall of small blood vessels under the effect of chemical mediators.
Role and consequences of edema:
* local supply of chemical mediators and defense mechanisms (immunoglobulins, complement factors, etc.);
* dilution of toxins accumulated in the lesion;
* limitation of the inflammatory focus by a fibrin barrier, which prevents the spread of infectious microorganisms;
* slowing of the circulatory current, which promotes leukocyte diapedesis.
1.3. Leukocyte diapedesis: this corresponds to the migration of leukocytes outside the microcirculation and their accumulation in the lesion focus.
It first affects polymorphonuclear cells (during the first 6 to 24 hours), then a little later (in 24 to 48) monocytes and lymphocytes.
2. Cellular reactions: constitute the 2nd phase , they result in the formation of the inflammatory granuloma made up of:
* cells from the blood (neutrophils and eosinophils, monocytes and lymphocytes);
* cells from connective tissue (histiocytes, mast cells, fibroblasts and macrophages).
Role of inflammatory granuloma:
*ensure detersion by phagocytes (polymorphonuclear cells and macrophages);
* develop a B and/or T lymphocyte immune reaction;
* secrete multiple mediators involved in cell recruitment, phagocytosis, immune defense and modification of the connective matrix.
During chemotaxis and phagocytosis, activated leukocytes can release toxic metabolites and proteases into the extracellular space, causing tissue damage.
3. Detersion: it gradually follows the vasculo-excudative phase, and is contemporary with the cellular phase. It is the elimination of tissue debris, necrosis products, dead cells, germs and possible foreign bodies and edema fluid. This phase can be internal or external, spontaneous (fistulization) or induced (drainage).
Debridement necessarily prepares the final phase of repair-healing. If debridement is incomplete, acute inflammation will develop into chronic inflammation.
4. Repair and healing: tissue repair follows complete debridement. Debridement allows the formation of new tissue (the regeneration blastema) also called fleshy bud which will result in healing and perfect recovery of the damaged tissue.
V. DIFFERENT TYPES OF INFLAMMATION or MORPHOLOGICAL VARIETIES OF ACUTE AND CHRONIC INFLAMMATIONS:
Sometimes one of the successive phases of the inflammatory process may predominate or persist for a long time.
1. When vascular and exudative phenomena are in the foreground, the inflammation is said to be acute. This type of inflammation includes:
* congestive and edematous inflammation;
* hemorrhagic inflammation;
* thrombosing inflammation ;
* fibrinous inflammation;
* purulent or suppurative inflammation;
* necrotizing or gangrenous inflammation;
2. When cellular tissues predominate, the inflammation is said to be subacute.
3. When abundant connective or sclerotic tissue predominates (appearance of fibrosis), the inflammation is said to be chronic.
PATHOPHYSIOLOGY OF INFLAMMATION
VI. CONCEPTS OF IMMUNOPATHOLOGY AND PATHOLOGICAL INFLAMMATION:
The purpose of the immune system is to rid the host of any agent known to be foreign or no longer part of the “self”. There are diseases that are linked to this immune reaction rather than to the pathogenic action of the agent in question, others are the consequence of an immunity directed against the host’s own constituents.
Some of them show a more or less significant failure of the immune system.
We will successively consider:
* hypersensitivity reactions (allergy);
* pathology related to organ transplants (rejection phenomena and graft-versus-host disease);
* autoimmune diseases;
* immune deficiencies.
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PATHOPHYSIOLOGY OF INFLAMMATION
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