Specific and nonspecific links of pathogenesis

Specific and nonspecific mechanisms

The development of any disease is a cascade of reactions in which unique and universal mechanisms naturally combine. It is their combination and degree of severity that determine the clinical manifestation of the pathology in the patient.

Let us examine this ratio using hereditary hemoglobinopathies (anemias) as an example:

• Specific links are absolutely unique to each type of disease. In thalassemias, there is unbalanced synthesis of one of the globin chains. In sickle cell anemia, a specific genetic defect occurs: the replacement of the amino acid glutamine with valine strictly at the sixth position of the globin molecule. In the case of unstable hemoglobin anemias, the replacement of a specific amino acid inevitably causes aggregation of molecules directly within the erythrocyte cytoplasm.
• Nonspecific links are typical processes characteristic of all types of anemia without exception. They act as significant mechanisms in the development of pathology. Traditionally, these links include the development of tissue hypoxia, a shift in acid-base balance toward acidosis, a pronounced imbalance of ions and water, and the pathological activation of lipid peroxidation (LPO) reactions.

Interrelation of local and systemic processes

Pathogenesis always includes a complex of closely interconnected local and general (systemic) links. Their significance changes dynamically as the disease progresses.

1. Dynamics of transition from local to general. This scenario is typical for diseases starting with local tissue damage (glomerulonephritis, liver cirrhosis). Initially, exclusively local mechanisms dominate. However, as the disease progresses and organ function failure develops, general links rapidly come to the fore, determining the disruption of the whole organism's vital activity.
2. Primary systemic lesions. Such a picture is characteristic of endocrinopathies, in which generalized changes flare up at early stages. A striking example is hypercorticism (Cushing's syndrome). The essence of the pathology lies in the excessive secretion of corticosteroids. Local changes are limited to the adrenal cortex tissue, but the systemic links turn out to be colossal: arterial hypertension, hyperglycemia, profound immunosuppression, Na⁺ and K⁺ ion imbalance, and cardiopathies develop.
3. Interdependence (vicious circles). Regional processes are capable of causing systemic changes, and vice versa. When the systemic provokes the local, we see how general immunodeficiency leads to the emergence of local neoplasms or foci of inflammation. In the reverse situation, active tumor growth in a specific organ naturally leads to the formation of total immune system failure.

Pathogenic and adaptive reactions

The pathogenesis of absolutely all forms of pathology includes two groups of reactions, the balance of which is strictly individual:

• Pathogenic links are directly the mechanisms of damage that destroy normal physiology.
• Adaptive links are compensatory, protective, reparative, and sanogenetic processes aimed at survival.

Let us analyze this dualism using bronchial asthma as an example. Pathogenic effects here include acute bronchospasm, severe impairment of pulmonary ventilation and perfusion, and decreased gas diffusion across the blood-air barrier. Simultaneously, adaptive effects are triggered: the immune system attempts to detect and eliminate the allergen, and the body strives to compensate for shifts in the acid-base balance (ABB) and increase the efficiency of oxygen delivery to suffering tissues.

Principles of pathogenetic treatment

A deep understanding of the links of pathogenesis allows the physician to set correct goals in treatment. The main tasks are to stop the action of damage mechanisms and activate sanogenetic reactions.

The following main types of therapy are distinguished:

• Pathogenetic therapy is aimed at interrupting pathogenic processes. A classic example is the use of antihistamines in allergic reactions or inflammation. Inhibiting the synthesis or blocking the effects of histamine produces a significant therapeutic effect.
• Sanogenetic therapy works through the activation of adaptive processes. This includes the use of immunomodulating drugs. They prevent the formation of severe immunopathological conditions (used in bronchial asthma, diffuse glomerulonephritis, rheumatoid arthritis).
• Replacement therapy is aimed at eliminating a deficiency or complete absence of any factor in the body. Examples: prescribing hormones in diabetes mellitus or adrenal insufficiency; using enzymes in malabsorption syndrome (impaired cavitary or membrane digestion); administering vitamins in dysvitaminosis.

The effectiveness of treatment increases manifold with the combined use of etiotropic (eliminating the cause) and pathogenetic principles. Such a comprehensive approach is necessary in the treatment of inflammation, fever, hypoxia, and immunopathological processes.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of tissue hypoxia development
• The role of lipid peroxidation (LPO) in pathogenesis
• Etiology and the etiotropic treatment principle
• Compensatory shifts in acid-base balance (ABB)

Other topics in "Chapter 2. GENERAL NOSOLOGY"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.