1. General nosology

• Health (norm): a state of full physical, mental and social well-being, with preserved adaptation and homeostasis. It is not just the absence of disease.
• Disease: life under damaging conditions, in which the organism's structure and function are disturbed and its adaptation is reduced. It has three parts:
  • damage
  • protective-compensatory responses
  • reduced capacity to adapt and work
• Pre-disease: a borderline state with a risk of disease, such as a genetic predisposition or a reduced reserve.
• Pathological reaction: a short-lived, inadequate response to a stimulus (e.g., a transient rise in blood pressure).
• Pathological process: a stereotyped combination of damage and adaptive responses (see section 3).
• Pathological state: a slowly developing or stable deviation from the norm (e.g., a scar, an amputation stump, an acquired valve defect).
• Nosological unit (nosological form): a disease with its own cause, mechanism, and clinical and morphological picture (e.g., lobar pneumonia). Diseases are classified by cause, organ system, mechanism and course (ICD).
• Etiology: the cause and the conditions under which a disease develops.
  • A cause is necessary and gives the disease its specificity.
  • Conditions and risk factors only help or hinder the cause.
  • Three historical views: monocausalism, conditionalism, and constitutionalism. The modern view is multifactorial.
• Pathogenesis: the mechanisms of development, course and outcome of a disease.
• Symptom and syndrome: a symptom is a single sign. A syndrome is a recurring set of symptoms that share a mechanism.
• Sanogenesis: the mechanisms of recovery.

2. Periods (stages) of disease

• Recovery:
  • complete (restitutio ad integrum)
  • incomplete (with residual effects)
• Remission: symptoms fade, which may be complete or partial.
• Relapse: symptoms return after a remission.
• Complication: a new process linked to the main disease.
• Chronic course: the disease persists.
• Death: it comes through the terminal states:
  • preagony
  • terminal pause
  • agony
  • clinical death (reversible, about 5 to 6 min in normothermia)
  • biological death (irreversible)

3. Typical (standard) pathological process

• Nonspecific etiology: different causes produce the same process.
• A universal sequence of events, which can be local or general.
• A building block of many diseases. One disease can contain several typical processes (pneumonia involves inflammation, hypoxia, fever and intoxication).
• It does not need to be a disease on its own. Some are adaptive, some are damaging, and many are both.

1. Circulatory disorders: arterial and venous hyperemia, ischemia, stasis, thrombosis, embolism, bleeding.
2. Cell and tissue damage: dystrophy, necrosis and apoptosis, atrophy, hypertrophy and hyperplasia.
3. Inflammation: alteration, exudation and proliferation.
4. Fever and other thermoregulation disorders.
5. Hypoxia.
6. Disorders of metabolism, water-electrolyte balance and acid-base balance (edema, acidosis and alkalosis).
7. Tumor growth.
8. Immunopathological processes: allergy, autoimmunity, immunodeficiency.
9. Extreme states: stress, shock, collapse, coma, DIC.

• A trigger (infection or trauma) causes alteration (tissue damage).
• This releases mediators (histamine, cytokines, prostaglandins).
• Vasodilation and increased permeability follow, with exudation and leukocyte emigration.
• Proliferation and repair end the process.
• The same sequence occurs in the skin, lung or liver, whatever the cause.

4. Main principles of studying pathogenesis

• Trigger (initial link): the first change caused by the etiologic factor.
• Leading (main) link: the one that determines the course and must be treated first.
• Cause-effect chain: each change causes the next.
• Vicious circle (positive feedback): the effect strengthens its own cause, as in shock and heart failure.
• Damage and defense: every pathogenetic link has both parts (adaptive and pathological).
• Local and general: local processes affect the whole body and the reverse.
• Specific and nonspecific mechanisms, and reversible and irreversible phases.

1. Determinism (causality): every change has a cause.
2. Unity of structure and function: molecular, cellular, organ and systemic levels are studied together.
3. Dialectic of damage and adaptation: compensation can also become pathological.
4. Unity of the organism and its environment, including the effect of nervous, humoral and immune regulation.
5. Dynamic approach: the disease is studied in stages, from early to late.
6. Systemic approach: disease is a change in the whole system, not an isolated organ.
7. Individual approach: the course depends on genes, age, sex, constitution and reactivity. This underlies precision medicine, as Robbins notes. - Robbins & Kumar Basic Pathology, p. 16

• Clinical observation: history, signs, laboratory and imaging data.
• Morphological studies: biopsy and autopsy.
• Experiment:
  • Acute or chronic.
  • Models: reproducing disease in animals, isolated organs, cell cultures, or computer simulation (in silico).
  • Genetic: gene knockout and transgenic models.
  • Biochemical and molecular: omics, imaging.
• Limits of experiment: extrapolation from animals to humans is only partial. The sequence of events in experiment is compared with clinical data.