Stages and course of the wound process

Speaking of local reactions, various authors agree that it is necessary to distinguish 3 main stages of the wound process. So Chernuk AM (1979) distinguished the stage of damage, the stage of inflammation and the stage of recovery. Serov V.V. And Shekhter AB (1981), the wound process was divided into stages: traumatic inflammation, proliferation and regeneration, scar formation.

From our point of view, the isolation of these stages is conditional, since in the bowels of the previous stage, conditions are created for the formation of the subsequent stage. In addition, the healing process of the cutaneous wound depends and quite radically, on many factors. In particular, on the nature of the damaging agent; place, depth and area of damage: dissemination of pyogenic flora; adaptive abilities and immunity; age and concomitant diseases. Therefore, the course of the wound process with the same trauma in different people, can go in different ways and, in the end result, lead to a completely different outcome - group 1 scarring or keloid and hypertrophic.

The most severe injuries are related to:

• with the effect on the skin of physical (thermal, cold, radiation) and chemical (acid, alkali) factors;
• with the soft tissue softening;
• with infection of wounds;
• with soil contamination by wounds;
• with injuries on the background of stress;
• with disturbed neurohumorrhagic and endocrine regulation in patients.

As a rule, such injuries give a protracted process of tissue repair and as a result - keloid or hypertrophic scars, scar scarring and contractures.

Inflammation

Inflammation is the stereotyped protective-adaptive local vascular-tissue reaction that emerged during evolution in living systems to the action of pathogenic stimuli that caused damage.

As the main components, it includes changes in blood circulation, mainly the microcirculatory bed, increased vascular permeability, migration of leukocytes, eosinophils, macrophages, fibroblasts to the damage zone and their active activity in it, aimed at eliminating the damaging factor and restoring (or replacing) damaged tissues . Thus, inflammation in its biological essence is a protective reaction of the body. Inflammation of the skin is conventionally divided into immune and non-immune. Trauma to the skin, cause the development of non-immune inflammation. Since any trauma to the skin is accompanied by an inflammatory reaction, the stages of the wound process can be equated to the stages of inflammation. According to the form of the inflammatory reaction, this inflammation is referred to as an inflammatory reaction, since it is characterized by acutely occurring skin damage.

Stages of inflammation

According to many researchers, the most accurate course of the wound process and inflammatory reaction reflects the classification of Strukov AI. (1990), who identified 3 phases of inflammation:

1. The phase of damage or alteration.
2. Exudation phase (vascular reaction).
3. Recovery or proliferation phase

The first phase of damage or alteration is characterized by a destructive process, accompanied by the death of cells, vessels and the release of a large number of mediators of inflammation and blood into the wound. Mediators of inflammation are a widely distributed group of biologically active substances, which include substances such as serotonin, histamine, interleukins, lysosomal enzymes, prostaglandins, Hageman factor, etc. The most important of them are eicosanoids, the precursor of which is arachidonic acid - an essential fatty acid, which is part of the phospholipids of cell walls. In case of trauma, cell membranes are destroyed with the appearance of a large number of "raw materials" for the formation of inflammatory mediators. Eicosanoids have an extremely high biological activity. In the development of inflammation, such types of eicosanoids as prostaglandins of type E, prostacyclin (prostaglandin I), thromboxanes, leukotrienes take part. They contribute to vascular dilatation, thrombosis; increase the permeability of the vascular wall, increase the migration of leukocytes, etc.

Damage to the endothelium of the capillaries causes the appearance of substances that stimulate polymorphonuclear leukocytes, which in turn increase the damage to the vascular wall. All this leads to a slowing of the blood flow, and then to its complete stop.

The second phase or phase of exudation is characterized mainly by the reaction from the vascular bed and cells, the release of the formed elements and the liquid part of the blood and lymph into the extravascular region. Leukocytes, erythrocytes, lymphocytes appear in the wound along with cellular detritus and connective tissue cellular and structural elements. Cellular clusters are an inflammatory infiltrate, consisting mainly of polymorphonuclear leukocytes, lymphocytes, macrophages, mast cells. In the wound there is active multiplication of cells taking part in the inflammatory process - mesenchymal, adventitial, endothelial, lymphocytes, fibroblasts, etc. The cleansing of the wound from tissue detritus and bacterial flora continues. There is a neoformation of the vessels, which are the basis of the granulation tissue.

In more detail, this phase can be divided into several stages:

Vascular stage. It is characterized by a short-term spasm (up to 5 minutes) and subsequent expansion of the capillaries of the skin, which is accompanied by an increase in the permeability of capillaries and postcapillary venules of the interested area. The stasis in the vessels, which occurs after the slowing of the blood circulation, leads to the marginal standing of leukocytes, the formation of aggregates, their adhesion to the endothelium, and the release of leukokinins into the contact zone with the endothelium, which increase the permeability of microvessels and create conditions for the filtration of plasma chemotaxins and the release of the formed elements of blood into the inflammatory focus. The neutrophils themselves release pseudopodia (cytoplasmic processes) and are selected from the vessel outward, helping themselves with enzymes (cathexin, elastase, etc.). Clinically, this stage is manifested by edema.

Cell stage. It is characterized by diapedesis, through extended intercellular cracks of capillaries, into the wound of neutrophilic leukocytes, the process of accumulation of which in the skin defect begins already in 2-3 hours after trauma. Polymorphonuclear leukocytes have an extremely high phlogogenic potential, manifested by hyperproduction and hypersecretion of lysosomal hydrolases (prostaglandins), leukotrienes, active forms of oxygen, causing additional damage to the endothelium and microcirculation disorder. Along with this, neutrophils are a source of factors by which other cells, including platelets, mast cells, eosinophils, mononuclears are connected to the process of inflammation. They also have special receptors for IgG and C, so at this stage of exudative-destructive inflammation, cooperative links between polymorphonuclear leukocyte effector and humoral mediators and, first of all, a complement system are formed. This is due to the autoactivation of factor XII or factor Hageman (HF), which induces blood clotting, fibrinolysis, activation of the kallikrein-kinin system. Of all the mediator systems of plasma involved in damage to the endothelium, the complement system is of primary importance. Its activation occurs by binding C, with IgG after which C, becomes an active serine proteinase. However, the activation of the complement can also be plasmin, C-reactive protein, crystals of monosodium salt of uric acid, some bacterial glycolipids. Binding and activation of C leads to the formation of C1 esterase (CI _s ), which cleaves the second protein of the cascade-C into C4a and C4b. The third protein that takes part in the activation of complement is C2. It is also cleaved by activated C1, attaching to fragment C4b. The resulting C2a fragment, which combines with C4b, acquires enzymatic activity (C3-convertase) and cleaves C3 into 2 fragments - C3a and C3b.

SZb connected to the complement component C ₅ which splits into C5a and C5b and C5a as SZb passes into the liquid phase. Thus, fragments С5а and СЗb, possessing chemotactic properties, which become plasma mediators of inflammation, are formed. Through C5a and C3a, mast cells, releasing histamine, serotonin, chemotaxin for eosinophils, are connected to inflammation. C5a causes an increase in vascular permeability, initiates chemotaxis of neutrophils and monocytes, aggregation of neutrophils and attachment to the walls of capillaries. The phlogogens released by polymorphonuclear leukocytes, including thrombogenic factors, contribute to thrombosis of microvessels, which leads to rapid necrosis of perivascular tissues and the formation of reactive polynucleolateral infiltrates. Tissue disintegration products, auto and xenoantigens in turn activate polymorphonuclear leukocytes, monocytes, macrophages and mast cells, which causes degranulation of neutrophils, secretion of biologically active substances by monocytes, macrophages and polymorphonuclear leukocytes. Protein kinases accumulating in the wound cause further degranulation of mast cells, activation of complement, platelet activation factor, interleukins of alpha and beta interferons, prostaglandins, leukotrienes. The entire cascade of biologically active molecules activate fibroblasts, T and B lymphocytes, neutrophils, macrophages, which leads to stimulation of enzymatic and antibacterial activity in the wound. Promoting to some extent the necrosis of tissues, at the same time, neutrophils cleans the zone of damage from the infection and the decomposition products of autolytic cells. When the inflammation process is tightened, possibly at the level of a genetically determined defect, the inflammation focuses on the torpid current, "chronizes" it, the period of the cell stage and the fibroplastic process is inhibited.

Prevalence in the wound of neutrophils is replaced by the predominance of macrophages, the migration of which into the wound is provoked by neutrophils.

Mononuclear phagocytes, or macrophages, provide a largely non-specific defense of the body due to its phagocytic function. They regulate the activity of lymphocytes, fibroblasts. Nitric oxide (NO) is excreted, without which epithelial cells can not start migration, despite the presence of growth factors in the medium. The wound contains a large number of growth factors. Platelet growth factor stimulates the proliferation of mesenchymal cells, such as fibroblasts. The transforming growth factor-beta stimulates the chemotaxis of fibroblasts and the production of collagen by them. Eidermal growth factor enhances the proliferation and migration of keratinocytes, the transforming growth factor-alpha affects angiogenesis, the keratinocyte growth factor stimulates wound healing. The main factor in the growth of fibroblasts - positively affects the growth of all types of cells, stimulates the production of proteases, chemotaxis of fibroblasts and keratinocytes, the production of extracellular matrix components. Secreted by cells in the wound, cytokines, activated by proteases and other biologically active molecules, perform effector and regulatory functions. In particular, interleukin-1 promotes the activation of T-lymphocytes, affects the production of fibroblasts proteoglycans and collagen. Activated T-lymphocyte produces and secrets interleukin-2, a stimulating T-lymphocyte. In turn, the T-lymphocyte produces interferon-alpha, which activates the function of macrophages and the production of interleukin-1.

Recovery or proliferation phase

This phase is also called reparative, since the multiplication of cells and the secretion of collagen are continuing at the site of injury, aimed at restoring homeostasis and closing the wound defect. The focus of the cellular spectrum in this phase shifts towards proliferation, differentiation and transformation of fibroblasts and proliferation of keratinocytes. It is known that the faster the inflammation is blocked, as the body responds to damage to the integrity of the skin and the wound defect is closed by the fibrous and cellular structures of the connective tissue followed by epithelization, the more favorable the appearance of the scar. The granulation tissue that formed on the site of the former skin defect healing with secondary tension is a loop of newly formed vessels surrounded by glycosaminoglycans and cellular elements. In the process of completing inflammation and as a result of fibrotic changes, it is organized into cicatricial.

The less deep the injury, the quicker the inflammation stops, the response of the body to damage, the faster the epithelization of the wound defect, the more favorable the scar appears. With infected, long-term non-healing wounds, as well as in the presence of predisposing factors, the inflammatory reaction is chronicized and the transition of adequate inflammation into an inadequate one occurs. Local immune shifts in the body of such patients are manifested in a decrease in the number of obese, plasma and lymphoid cells in the granulating wound. Inadequate inflammation does not separate itself, has a protracted course, is characterized by excessive formation of inflammatory mediators, hypoxia, a decrease in phagocytic activity of cells, proliferation of certain populations of fibroblasts that are characterized by high metabolism and collagen synthesis. As a result, this inflammation results in the formation of keloid or hypertrophic scars.

[1], [2], [3], [4]