47. Circulatory changings during inflammation.

Conheim’s vascular theory. Stages of circulatory changings:

1. Short-termed ishemia (its duration is from 10-20 sec to several minutes).

2. Arterial hyperemia (it is lasted 20-30 min, maximally up to 1 hour).

3. Venous hyperemia.

4. Stasis.

First (in 1867) these changings were described by Yu. Konheim while circulation study in frog’s mesentery at inflammation.

Short-termed ishemia mechanism.

1. Arterioles reflectory spasm causes such ishemia at inflammation beginning. It is connected with vasoconstrictory adrenergic nerves excitement and catecholamines releasing with them. The lattest ones while their action to alpha-adrenoreceptors cause vascular wall smooth myocytes contraction.

2. Ishemia is short-termed because catecholaminic depot exhaustion in nervous endings occurs quickly and released mediators are decomposed by monoaminooxidase and other enzymes.

3. Besides, vasoconstriction in some organs can interphere with cholinergic nerves vasodilating influence which is realized by axon-reflex type.

Arterial hyperemia developmental mechanisms:

1. Neurogenic and neuroparalytic – see their description at arterial hyperemia dscription – they are actual in arterial hyperemia development first minutes.

2. Physical-chemical factors influence: acidosis, potassium level increasing in tissues, hypoxy and others.

3. Metabolism products influence: lactic acid, ADP, AMP, adenosine.

4. Inflammation mediators action:

   1. histamine and serotonine;

   2. kinines (bradykinine and kallydine);

   3. prostaglandines and prostacyclines.

Factors determining arterial hyperemia transfer to venous:

1. Intravascular:

   1. blood viscosity increasing;

   2. microthrombi formation;

   3. blood coagulation;

   4. leucocytes marginal state;

   5. erythrocytes aggregation;

   6. endotheliocytes swelling.

2. Extravascular:

   1. veins pressure with oedematic fluid;

   2. elastic features loss with veins due to collagen and elastine decomposition with lysosomal enzymes.

48. Fever aethiology. Pyrogens classification.

Fever is typical pathological process which is developed in the highest homoiothermal organisms as answer reaction to pyrogen stimuli and is expressed as thermoregulation reconstruction directed to body temperature active increasing.

Pyrogenes are substances which are fever reason.

Classification principles:

1. 1) infectional:

1. gram-negative bacteria endotoxins (lipoid A – toxin fragment – possesses pyrogenic action);

2. gram-positive bacteria (diphtheria, tetanic) exotoxins;

3. pathogenic fungi activity products;

4. rikketsias;

5. viruses;

2) non-infectional:

1. components of transfused blood incompatible by groups (transfusional fever);

2. exogenous proteins (milk proteins at its parenteral infusion);

3. tissues decomposition products.

2. 1) Natural – pyrogens existing in nature or forming from non-pyrogenic substances naturally;

2) Artificial – are received by natural bacterial toxins processing; they are used for treatment (pyrotherapy); the most known are following: pyrogenal (from Pseudomonas aeruginosa) and pyrexal (from Salmonella abortus equi).

3. 1) Exogenic – are passing or are injected from outside; at parenteral injection fever appears in 45-90 minutes;

2) Endogenous –are produced inside organism:

1. primary and secondary alteration products being formed in inflammation focus;

2. products coming to blood from necrosis focus (for example, at myocardial infarction);

3. steroid hormones metabolites;

4. antigen-antibody complexes;

5. leucocytic pyrogens – neutrophils and macrophags activity products.

4. 1) Primary – pyrogens which do not influence directly on thermoregulation center; their pyrogenic action is realized through formation and releasing of so-called leucocytic pyrogens.

2) Secondary – leucocytic pyrogens which are produced and released by leucocytes under primary pyrogens action; secondary pyrogens have the ability to influence on hypothalamic thermoregulative center directly and cause fever development; interleukin-1 is secondary pyrogen, it is released by neutrophils and macrophags during phagocytosis activation.

Infectious pyrogens belong to primary ones. Infectious fevers are the mostly widely-spread fevers. They accompanie the biggest amount of infectious diseases. Though direct connection between pyrogenic features and infectious agent pathogeneicity is absent sometimes. Infectious agents contain (as metabolism products or structural elements) so-called primary pyrogens (lipopolysaccharides, proteinic substance and nucleic acids). Primary pyrogens also can be formed as a result of host own tissues injury with infectious process.

Non-infectious (aseptic) fevers are appeared:

1. at tissues mechanical injuries (at cuttings, traumas, ruptures, overpressuring);

2. at necroses (myocardial infarction);

3. aseptic inflammation;

4. haemolysis.

At non-infectious fever pyrogens are formed by cellular-tissular structures of the organism itself. Special group is the fevers occurring at some immunopathological and allergical states as well as sera injection into organism for treatment or diagnostics, blood transfusion and other proteins-containing liquids. Fever at non-infectious processes is also connected with primary proteinic pyrogens and, probably, nucleic acids action.

During immune reactions IL-1 (secondary pyrogen) is released. Doctor should remember that at body temperature more than 40°C phagocytosis is weakened, lymphocytes functional activity is inhibited; resistance to some exotoxins is reduced.