How increase of body temperature happen in 1-th clinical stage of fever.

Fever

15.1. What is fever?

Fever is a typical pathological process, which develops in higher homoeothermic animals as a result of pyrogenous matters and it shows in reorganization of thermoregulation, directed on active increase of body temperature.

15.2. What substances are pyrogens? How are they classified?

Pyrogens are substances which cause development of fever. They are divided into:

1) infectious and uninfectious

2) natural and artificial

3) exogenous and endogenous

4) primary and secondary

15.3. Give examples of infectious and uninfectious pyrogens:

Infectious pyrogens are:

1) endotoxins of gram-negative bacteria (lipoid A (fragment of toxin) processes pyrogenic action).

2) exotoxins of gram-negative bacteria (diphtheria, clostridium tetani)

3) products of pathogenic fungus activity

4) Rickettsias

5) viruses.

Uninfectious pyrogens are:

1) components of transfused blood, incompatible by groups (transfusion fever)

2) exogenous proteins (proteins of milk at their parenteral introdusing)

3) products of tissue disintegration.

15.4. What pyrogens are natural and what are artificial?

Pyrogens which exist in nature or appear in natural way from non pyrogenic substances are named natural.

Artificial pyrogens are obtained by processing native bacterial toxins and are used with a medical purpose (pyrotherapy). Pyrogenal, obtained from pseudomonas aeroginosa, and pyreksal educed from salmonella abortus equi.

15.5 What pyrogens are named exogenous and endogenous?

Exogenous pyrogens realize their influence or are delivered from outside. At parenteral injection of exogenous pyrogen fever develops in 45 - 90 minutes.

Endogenous pyrogens are generated in an organism.They are:

1.Products of primary and secondary alteration formed in inflammation focus.

2.Products, which come into blood from focus of necrosis (for example at infarction of myocardium).

3.Metabolites of steroid hormones

4.antigen – antibody complexes

5.leucocytic pyrogens, that are products of activation of neutrophiles and macrophages

15.6. What are primary and secondary pyrogens?

Pyrogens, which does not influence directly on the thermoregulation center named primary. Their pyrogenic influence is mediated by formation and releasing of the so-called leucocytic pyrogens.

Leucocytic pyrogens, which are formed and secreted by leucocytes, under influence of primary pyrogens are named secondary. Secondary pyrogens possess ability to influence directly on the center of thermoregulation and cause fever development.

It is shown today, that interleukin-1 is secondary pyrogen. This substance is formed and secreted by leucocytes (neutrophiles and macrophages) in the processes of phagocytosis activation.

Along with action on the thermoregulation center interleukin-1 processes the whole row of other effects determining clinical symptoms of fever (see paragraph 14).

15.7. What proves of primary pyrogens influence relates to formation of secondary do you know?

1. Primary pyrogens have enough latent period of action (at a man 45 minutes and more), while latent period of secondary pyrogens influence is 10 minutes and less.

2. tolerance develops to influence of primary pyrogens, it means it is necessary to increase close of pyrogen to cause fever with every subsequent injection. At the same time at repeated injection of secondary pyrogens tolerance does not develop.

3. If phagocyte function of neutrophiles and macrophages is broken (for example, at leucopenia, filling of phagocytes by Indian ink), fever does not develop at injection of primary pyrogens.

4. Fever does not develop at direct injection of primary pyrogens into thermoregulation centers of hypothalamus, while injection into that center of leukocyte pyrogens is appropriately accompanied by increase of body temperature.

15.8. What consecutive processes make essence of fever pathogenesis?

It is possible to mark out the row of stages in fever pathogenesis.

1. Induction of formation and releasing of secondary leucocytic pyrogen (interleukin-1) by primary pyrogens

2. Interleukin-1 influence on thermoregulation center and reorganization of its work.

3. Stage of clinical symptoms of fever (change of body temperature)

15.9. Where is thermoregulation center located and what is it from the functional point of view?

Neurons of thermoregulation center are in front (preoptic area) and back (dorso- and ventromedial nuclei) hypothalamus. Processed from functional characteristics, four groups of neurons are marked out:

1. Neurons of “thermostat” are the group of thermosensetive neurons, directly perceiving temperature of blood, which flows through hypothalamus. Information from skin and internal themoreceptors is receipted there. “Thermostate” conclude middle temperature of body nucleus.

2. Neurons of adjusting point are the group of thermounsensetive neurons which set the level of temperature of body core. Information from “thermostat” is receipt by the neurons of “adjusting point”, where comparison of present temperature of core with the programmed level takes place. If the middle temperature of nucleus becomes higher than temperature of “adjusting”, it generates signals braking the center of heat producing and excitant center of heat emission.

3. Center of heat production. Its neurons are in the back hypothalamus. Their excitation causes increase of heat formation.

4. Center of heat emission is in the preoptical area of front hypothalamus. At its excitation emission of heat by organism increases.

15.10. What is the mechanism of interleukin-1 influence on center of thermoregulation?

Interleukin-1 cooperates with specific receptors on the membrane of neurons which are included in group of cells of “adjusting point”. In consequence of receptors activation activity of related to them enzyme (phospholipaze A2) increases. This enzyme releases arachidonic acid from phospholipids of plasmatic membrane. Prostaglandins of group E are formed from arachidonic acid, they diminish sensitiveness of neurons of “adjusting point” to the impulses coming from neurons of “thermostat” In result of it ordinary signals about the normal temperature of nucleus are perceived by the neurons of “adjusting point” as information about decrease of temperature. It, in one’s turn, causes the standing reaction directed on the increase of temperature: activating of center of heat producing and braking of center of heat emission.

15.11. What proofs of prostaglandins E role in fever pathogenesis do you know?

1. Microinjections into the thermoregulation center (into the region of “adjusting point” of hypothalamus) causes increase of body temperature.

2. Pharmacological preparation, which inhibit cycloxygenase (enzyme of prostaglandins synthesis) render a febrifuge effect at fever. Acetylsalicylic acid, indometacin belong(s) to such preparations.

3. The same preparations do not influence on normal level of body temperature. Conclusion, that prostaglandins E does not participate in regulating of temperature homeostasis in a norm, and forms only at fever, follows from that.

4. Glucocorticoids, repressing phospholipase A₂ activity through lipocortin mechanisms (see paragraph 14) decrease formation of prostaglandin E, in favor of fever development is broken.

15.12. Name clinical stages of fever:

Three stages of fever are marked out clinically:

1. increase of temperature (stadium incrementi)

2. stage of high temperature (stadium fastigii)

3. stage of temperature decreasing (stadium decrementi)

How increase of body temperature happen in 1-th clinical stage of fever.

Acute decrease of heat emission takes place right in beginning. As a result of sympathoadrenal system activation blood vessels of skin and extremities are narrowed, smooth muscles raising hairs contracts (hair rises at animals, a man has a signs of “goose pimples”). Those changes have two consequences. From one side, sharp limitation of heart emission itself conduces to increase of temperature of core. From other side, decreasing of skin temperature causes excitation of cold receptors information about decrease of temperature of “outward firm” enters the termoregulative center, and from there to the cortex, so a man has feeling of cold. Excitation of sub-cortical centers takes place in addition, as a result tone of skeletal muscles rises, trembling develops (chill). Retractive thermogenesis increases.

Side by side with that, activation of unretractive thermogenesis, related to the increase of speed of oxidizing processes takes place. Increase of intensity of cellular respiration in brown adipose tissue under influence of cathecholamines has great importance. So, increase of body temperature in the beginning is conditioned by decrease of heat emission and then by increase of heat producing.

15.14. Explain mechanisms of falling of body temperature at fever completion. What variants of such falling exist?

As soon as interleukin-1 influence on the thermoregulative center is halted, content of prostaglandins E in neurons of “adjusting pint” decreases. That concludes to renewal of cells sensitiveness to the signals received from “thermostat”. Core temperature begins to be perceived as high, as a result of that center of heart emission is activated, and the centre of thermoproduction is oppressed. Two physiological reactions: extending of blood vessels of skin and extremities and increase of sweat forming and secretion are the most important. These reaction lead to increase of heat emission, and as a result to decrease of body temperature.

There are two variants of falling of temperature:

1. Critical falling. Is sharp decrease of temperature during few hours

2. Lytic falling is gradual decrease of temperature during few days. Critical falling can be dangerous, especially at elder patient and at patient with cardiovascular diseases because of possible falling of arterial pressure and collapse development.

15.15. What types of temperature curves can be characteristic for the fever. What factors influence on the dynamics of body temperature changing at fever?

Basic types of temperature curves are:

1. febris intermittens. Temperature is normalized one or several times a day (festering infection, abscesses, tuberculosis)

2. febris remittens. Fluctuation in temperature are more than 1^o C a day, however it does not go back to norm (most virus and many bacterial infections).

3. febris continua. Day’s fluctuations in temperature are less than 1⁰ C (enteric fever, spotted fever)

4. febris recurens. Attack of increasing of temperature are alternated with periods of its normalization few day last. (recurrent typhus, malaria). The dynamics of temperature changes at fever is determined from one side by features and characteristics of life cycle of pathogen, from other by circumdaily biological rhythms of organism.

15.16. Why is fever a pathological process?

Fever is pathological process because two type of opposite phenomena (on) are combined in it: actually pathological and protective-compensating. Their correlation depends on the level of increase of temperature.

15.17. What is the protective-compensative importance of fever?

Unfavorable conditions for development of infectious pathogen and increase of mechanisms of unspecific and specific resistance of the organisms are created at fever.

In particular:

a)Reproduction of many viruses is oppressed, interferons formation increases.

b) Phagocytic activity of macrophages and neutrophiles increases

c)Intensity of antibodies synthesis increases

d) Sensitiveness of many infectious pathogens to medicinal substances increases

15.18. What pathological changes can develop at fever?

a) Disturbances of general condition (indisposition, headache, fever)

b) Disturbances of metabolism

c) Increase of loading on heart (tachycardia, increase of cardiac output) or decrease of arterial pressure at the critical falling of temperature.

d) Disorders of the central nervous system. They can manifest in delirium, hallucinations, cramps development at a children from 5 months to 5 years, epilepsy attacks can be provoked at a temperature exceeding 39⁰C

e) Phagocytosis is weakened, vital functions and functional activity of lymphocytes are disturbed, sensitiveness of organism to action of some exotoxis increases at a temperature exceeding 40⁰C.

15.19. What is the influence of fever on metabolism?

Foremost, basic metabolism increases (on 10 – 12 % at the increase of temperature on 1⁰ C). It causes increase of consumption of oxygen and nutritions. Using of endogenous sources goes and a man loses in weight because appetite at a patient is absent.

The necessity of organism in water increases, as insensitive losses of water through skin and respiratory tract increase. According to this fact dehydratation can develop at little children and seriously sick. To prevent it abundant drink is recommended. At the moderate fever (38 - 39 ⁰ C) breathing frequency and alveolar ventilation increase in a greater measure, than formation of carbon dioxide. So, hypocapnia can develop, and gas alkalosis, as a result. To prevent it drinking of acidified liquid is recommended. At the high fever (above39⁰C) mobilization of free fat acids and formation of ketonic bodies in liver increases. Ketonaemia can results in no gas acidosis development.

The negative nitrous balance conditioned by predominance of catabolism of proteins above their synthesis develops at fever.

15.20. What are the principal differences between fever and hyperthermia?

Not disturbance, but reorganization of thermoregulation takes place at fever. An organism itself supports a high temperature, as the “adjusting point” of thermoregulative center is adjusted on higher level. At cooling of fevering animal, its temperature do not decreases, it is saved high at hyperthermia thermoregulation is broken. Body temperature rises despite organism aspiration to support temperature homeostasis. The “adjusting point” of thermoregulative center does not change. At cooling of animal with hyperthermia, body temperature begins to decrease, as a result of sharp increase of heat emission.

15.21. What is the basic pathogenic principle of pyrotherapy?

Decrease of “adjusting point” of thermoregulative center is basic pathogenic principle of febrifuge therapy. That is achieved by oppressing of prostaglandins E formation by means of cycloxygenase (acetylsalicylic acid, indometacin, paracetamol) and phospholipase inhibitors.

Дата добавления: 2015-10-30