Local Manifestations of Inflammation
The classic picture of tissue inflammation consists of several interrelated processes.
Swelling (tumor) manifests as tissue edema and elevation. It arises due to a sharp increase in blood supply (development of arterial and venous hyperemia), enhanced lymph formation, the escape of the fluid part of the blood into the interstitium, and active cell proliferation in the focus.
Temperature elevation in the damage zone is driven by three factors:
- Influx of warmer arterial blood from the body core.
- Sharp activation of local metabolism.
- Uncoupling of oxidation and phosphorylation. Due to an excess of free fatty acids and calcium ions, energy is not stored in ATP molecules but is dissipated as heat.
Receptor irritation (the basis of the pain syndrome) has a chemical and mechanical nature. Nerve endings react to inflammatory mediators (histamine, serotonin, kinins, prostaglandins) and tissue acidosis caused by the accumulation of acidic metabolites (lactate and pyruvate). In addition, accumulating exudate compresses tissues mechanically.
Impaired function (functio laesa) is the fifth local sign. Function suffers both from the direct damaging action of the phlogistic factor and from subsequent vascular reactions, alteration, and exudation. The scale of the problem depends on localization: usually a specific organ suffers, but during inflammation in vital structures (brain, heart, liver, endocrine glands), the vital activity of the entire organism is threatened.
Systemic Body Reactions
The response to injury is not limited to a single area. The sympathoadrenal system and the hypothalamic-pituitary-adrenal axis are involved, which is a classic component of the stress response.
Seven main general (systemic) signs of inflammation are distinguished:
- Leukocytosis (in rare cases, leukopenia).
- Fever.
- Elevated ESR (erythrocyte sedimentation rate).
- Dysproteinemia (shift in blood protein fractions).
- Dysfermentemia (changes in enzyme activity in biological fluids).
- Shifts in the hemostasis system (clotting, anticoagulant, and fibrinolytic links).
- General life activity disorders (intoxication, general malaise).
Pathophysiology of Key Systemic Signs
Leukocytosis is an increase in the number of white blood cells. The process is triggered by the phlogistic agent itself (especially of bacterial nature) and the breakdown products of own tissues. These substances block proliferation inhibitors and stimulate the production of leukopoietins. Leukocytosis plays a crucial adaptive role: cells migrate to the focus, localize and destroy pathogens, clear away dead tissue, and secrete biologically active substances to regulate immunity. Evaluation of shifts in the leukocyte formula is critical for diagnosis and prognosis.
Fever develops under the action of pyrogenic substances (interleukins 1 and 6, tumor necrosis factor alpha, prostaglandins). A moderate temperature rise is beneficial: it hinders microbes from multiplying, reduces their resistance to drugs, activates the immune system, and boosts metabolism. However, excessive fever depletes reserves and lowers the body's resistance.
Dysproteinemia reflects the restructuring of protein metabolism. The globulin fraction increases due to the activation of the humoral link of immunity, while hepatic albumin synthesis drops in severe inflammation.
Accelerated ESR is associated with the appearance of substances with pro-aggregant action in the blood. The mechanism includes several links:
- Effect of high-molecular-weight proteins: acute-phase proteins (fibrinogen, C-reactive protein, ceruloplasmin, globulins) adsorb onto erythrocytes, accelerating their sedimentation.
- Effect of cations: hydrogen, potassium, and calcium ions eliminate the natural negative charge of intact erythrocytes. Charge reversal occurs, and oppositely charged cells are drawn to each other (coulombic attraction).
- Effect of glycoproteins: adhesive transmembrane molecules additionally glue cells together (especially in immunopathological conditions and tumor growth).