MEDICAL BIOLOGY, HUMAN ANATOMY, PHYSIOLOGY AND PATHOLOGY - Ya.I. Fedonyuk 2010

ANATOMY, PHYSIOLOGY, PATHOLOGY

SECTION 1. ORGAN. ORGAN SYSTEM. ORGANISM

INFLAMMATION

1. STAGES AND MECHANISMS OF INFLAMMATION

In classical pathology, it is customary to divide inflammation into three stages: 1) alteration; 2) exudation; 3) proliferation. This Classification remains relevant today.

Stage I (Stage of Alteration). Inflammation always begins with tissue damage, known as alteration. Following The impact of a damaging factor, structural and metabolic changes occur within Cells, The Nature of which depends on the severity of the injury, the type of cells (their degree of maturity), and other factors. Some cells perish, others remain viable, while still others become activated and begin producing BIOLOGICALLY ACTIVE SUBSTANCES, recruiting new cells into the inflammatory process both within the lesion and beyond it. These are known as inflammatory cells.

Key Inflammatory Cells. Macrophages. Active macrophages synthesize a specific substance known as interleukin-1. Released by macrophages, interleukin-1 spreads throughout the body to find its targets, which include Cells of the muscular, osseous, nervous, and other Tissues. Its effects manifest in any inflammatory disease, particularly in the early stages. There is good reason to believe that early symptoms of illness (headache, Muscle and joint pain, drowsiness, fever, leukocytosis) are precisely due to the action of interleukin-1.

Tissue basophils (mast cells) release histamine and heparin contained within their granules upon injury. Since A large number of these cells are located in the vessel walls, the effects of histamine and heparin will primarily impact the Blood Vessels (hyperemia).

Neutrophilic granulocytes. The primary function of these cells is phagocytosis. Having entered the bloodstream from the Bone Marrow, they emigrate from the vessels and accumulate in large numbers at the site of inflammation.

Platelets are the most consistent and universal inflammatory cells. They contain substances that affect vascular wall permeability, elasticity, Cell GROWTH AND REPRODUCTION, and, most importantly, blood clotting.

Fibroblasts manifest in The final stage of inflammation, accumulating in the lesion and increasing the synthesis of Collagen and glycosaminoglycans.

Inflammatory mediators are biologically active substances synthesized in cells or Body Fluids that exert a direct effect on the inflammatory process. The primary cause of the appearance (or increase in quantity) of these substances is alteration. Specifically, cell damage triggers the release and activation of lysosomal Enzymes, which in turn activate Other Enzymes, including those contained in Blood Plasma, thereby Setting off biochemical reactions.

Inflammatory Mediators. Histamine is found in the granules of tissue basophils in an inactive form.

In its free state, it causes dilation of small vessels (capillaries, venules), increasing the permeability of their walls. In small doses, histamine dilates arterioles, while in large doses, it constricts venules.

The second cellular mediator is serotonin, which is released upon cell destruction and causes increased vascular permeability.

The Role of heparin is that it prevents The formation of fibrin on the inner lining of capillaries and causes an increased permeability of their walls. Blood Cells (leukocytes, platelets) produce Prostaglandins, Leukotrienes, and Cyclic NUCLEOTIDES, which play a crucial role in the dynamics of inflammation.

Humoral inflammatory mediators are synthesized in blood plasma and tissue fluid As a result of the action of specific enzymes. Among them, kinins are of the greatest significance.

Stage II (Stage of Exudation). Inflammation is characterized by disturbances in local BLOOD AND LYMPH Circulation, primarily microcirculation. Microcirculation refers to the movement of blood within the terminal vascular bed (in arterioles, capillaries, and venules), as well as The transport of various substances across the walls of these vessels.

Arterial hyperemia initially develops at the site of inflammation. It is the result of The production of a large quantity of vasoactive substances—inflammatory mediators—which relax the muscular elements of the arteriolar walls. This leads to an increased influx of arterial blood, accelerates its flow, opens previously non-functioning capillaries, and increases pressure within them.

Arterial hyperemia is followed by venous hyperemia. At this point, the blood flow velocity decreases, and the nature of blood flow changes.

One of the characteristic signs of inflammation is exudation and leukocyte emigration.

Exudation is the escape of the fluid portion of the blood, electrolytes, Proteins, and cells from the vessels into the tissues. Leukocyte emigration occupies a special place in this process. The fluid (exudate) escaping from the vessels infiltrates the inflamed tissue or accumulates in a cavity, such as the pericardial cavity or the anterior chamber of the eye.

The primary cause of exudation is an increase in the permeability of vessel walls, primarily capillaries and venules. If the vessel wall is mildly damaged, albumins and globulins typically pass into the exudate. With significant permeability disorders, high-molecular-weight proteins (fibrinogen) escape from the plasma into the tissue. Gradually, the permeability of the vascular wall increases to such an extent that not only proteins but also cells begin to pass through it. This is facilitated by the fact that during venous hyperemia, leukocytes position themselves along the inner lining of small vessels, adhering more or less firmly to the endothelium (The phenomenon of leukocyte margination).

Emigration is the exit of leukocytes from the vascular lumen through their wall into the surrounding tissue. This process also occurs under normal conditions, but in the case of inflammation, it takes on a much larger scale. The Essence of emigration is that a sufficient number of cells accumulate at the site of inflammation to play a definitive role in its development.

In the inflammation zone, the primary function of leukocytes is to engulf and digest foreign particles (phagocytosis).

I.I. Mechnikov divided all cells capable of phagocytosis into macro- and microphages. Microphages (polymorphonuclear neutrophils) phagocytose microorganisms, whereas macrophages (monocytes, histiocytes) ingest larger particles, including whole cells and their fragments. During phagocytosis, oxygen consumption increases significantly, a phenomenon known as the "respiratory burst".

Metabolic disturbances in the inflammation focus. Inflammation always begins with an upsurge in METABOLISM, which largely explains one of the hallmark signs of the process—local hyperthermia. To describe the metabolism within the inflammation site, the traditional term "metabolic fire" has long been used: metabolic rate is drastically elevated, and "combustion" is incomplete, leading to the accumulation of under-oxidized products. Subsequently, metabolic intensity declines, accompanied by a shift in its direction. While breakdown processes initially predominate during the acute phase of inflammation, synthesis processes take over later on, although clearly separating them in time is practically impossible.

Impaired tissue oxidation and the accumulation of under-oxidized metabolic products lead to The Development of acidosis. The hydrogen ion concentration increases in proportion to the intensity of the inflammation. Along with elevated acidity, the osmotic pressure in the inflamed tissue also rises. Acidosis causes Swelling of Connective Tissue elements, while increased osmotic pressure enhances exudation and local edema. This accounts for the cardinal signs of inflammation—swelling and pain—the latter also being triggered by the resulting tissue tension.

Stage III (Proliferation stage). Destructive processes gradually subside and give way to reparative ones, primarily cell proliferation and defect compensation. Concurrently with cell proliferation—and often slightly preceding it—the inflammatory process is resolved through Enzyme Inhibition as well as the breakdown and clearance of toxic products. The activity of inflammatory cells is also suppressed; they cease producing certain mediators and begin synthesizing others.

Phagocytic activity increases toward the end of inflammation. As a result, the affected area is cleared of necrotic cells, foreign bodies, and toxic substances.

Once the inflammatory agent has been neutralized or localized, subsequent processes are directed toward walling off the affected zone from the surrounding tissue and replacing it with new, healthy tissue. This is achieved through the proliferation of surviving resident cells, as well as cells that have migrated from adjacent areas (migrant cells).

In cases of minor tissue damage or wounds healing by primary intention, the inflammatory process concludes with complete regeneration. However, if a significant number of cells are destroyed, the damaged area is replaced by connective tissue, resulting in scar formation. This typically marks the end of the inflammatory response. Nevertheless, excessive scar tissue formation can occasionally occur, leading to organ deformation and impaired function. This is particularly dangerous in inflammation of The Heart Valves, Meninges, and similar critical structures.