General theory of pathogenesis (from the Greek pathos - suffering, genesis - the origin) - section of pathological physiology, studying general regularities of the origin, development, course and outcome of disease or mechanisms of disease development. It is based on pooled data study of certain types of diseases and groups (private pathology and clinical sciences), as well as on the results of experimental reproduction (modeling) of diseases or their individual traits in humans and animals. This sets the sequence of changes in the body for each disease; identify causal relationships between the different structural, metabolic and functional changes.
In other words, so-called pathogenic factors of the disease - the changes in this body, which arise in response to the main etiological factor in the future (even disappearance of the disease agent), dictate the disease.
Thus, if the study of etiology allows you to answer the question: "Why is there disease", the final result of the study of the pathogenesis has to be an answer to the question: "How is it developing?"
Main (specific) etiological factor acts as a trigger of the disease. The pathogenesis of the disease begins with any primary damage (Virchow) or "destructive process" (Sechenov), "damage" (Pavlov) of the cells in a particular part of the body (a pathogenetic factor of the first order). In some cases, the initial damage can be rough, well distinguishable to the naked eye (injuries, burns, wounds, etc.). In other cases the damage unnoticeable without special methods of detection (damage at the molecular level). Between these extremes there are all sorts of transitions.
The initial link of pathogenesis - development of mechanisms of damage every disease starts with the effects of the damaging environmental factor (the cause of the disease), which causes initial damage to the body portion. This leads to the development of subsequent damage mechanisms - pathogenetic factors.
Changes occurred first, immediately after exposure to the causative agent, are pathogenetic factors of the first order. In the future, products of tissue damage become sources of new violations in the course of the disease, so there pathogenetic factors of the second, third, fourth ... order and formed the causal relationships between them.
The cause - effect relationship pathogenetic factors, where each prior is like a "cause" of the following (the "investigation").
Defining a coherent chain of cause-and-effect relationship with the disease it is essential to carry out a rational symptomatic and pathogenetic therapy.
By their nature, pathogenetic factors are divided into humoral (such mediators damaged as histamine, serotonin, proteolytic enzymes), physical and chemical changes (blood pH shift toward acidosis or alkalosis, decreased oncotic pressure, hyper hypoosmia), violation of the neuroendocrine regulation of functions organism (pathological reflexes, neuroses development, hormonal imbalances), and others.
The main link and the "vicious circle" in the pathogenesis of diseases
In the study of the mechanism of the disease it is extremely important to identify the basic, most important link in the chain occurring disorders - the change in the body (one of the pathogenic factors), which determines the development of the remaining stages of the pathological process.
The main link of pathogenesis - a mechanism that eliminated with the help of therapeutic measures can stop the development of the following mechanisms of damage and lead to recovery of the sick person.
For the rational pathogenetic therapy is necessary to assess the value of each of the pathogenic factors, among them how to identify major and minor changes. Pathogenetic therapy - a set of measures designed to interrupt the chain of cause-and-effect relationship between the different structural, metabolic and functional disorders that occur in the body due to the impact of the main etiological factor by eliminating the main component of the pathogenesis. Removing the main violation leads to recovery of the body.
For example, stenosis of the left atrioventricular opening is the main link in the chain of many subsequent violations: enlargement of the left atrium, the blood stagnation in a small circle, dysfunction of the right ventricle, and then stagnation in the systemic circulation, oxygen starvation circulatory type, dyspnea, etc. The removal of this link. by mitral commissurotomy eliminate all such violations.
Encountered during the development of the disease or organ dysfunction system itself often becomes a factor (cause) that supports this violation, in other words, the causal relationships are reversed. This provision in medicine called "vicious circle." The vicious circle in which the subsequent pathogenetic factor ("investigation") can amplify the previous pathogenetic factor ("cause"), and the previous follow-up may intensify again.
For example, the sharp deterioration in the transport of oxygen in blood loss leads to heart failure, which further impairs the transport of oxygen. There is a "vicious circle".
Under normal conditions, the regulation of any process based on the fact that the deviation of a controlled parameter is an incentive to return it to normal. In the pathology appeared deviation level of functioning organ or system can, on the contrary, to maintain and strengthen itself.
Local and general, specific and non-specific reactions in the pathogenesis
In the complex chain of cause-and-effect relationships in the development of the disease was isolated, local and general changes. At the same time it should be stressed that it is absolutely local (LAN) processes in the whole organism does not happen. Practically any seemingly local pathology (boil, pulpit, felon, etc.) In the pathological process of the disease involves the entire body. Nevertheless, the role of local and general effects in the pathogenesis of very different.
There are 4 variants of the relationship of local and general processes in the pathogenesis:
1. In response to the local damage to an organ or tissue as a result of the general reactions of the organism are mobilized tissue adaptive mechanisms aimed at the delimitation of lesion (eg, granulating shaft in inflammation, the barrier function of the lymph nodes). As a result, the basic parameters of homeostasis (body temperature, white blood cell count and leukocyte formula, erythrocyte sedimentation rate (ESR), metabolism) can not be changed.
2. The local process through the receptor apparatus and entry into the blood and lymph systems of biologically active substances cause a generalized reaction, and certain changes in the main parameters of homeostasis. In this case, includes adaptive reactions aimed at preventing the development of the common pathological changes in the body.
3. Generalization of local process in severe cases can lead to failure of adaptive and protective reactions, and ultimately - to the general intoxication, sepsis, or death.
4. Local pathological changes in organs and tissues may develop secondarily on the basis of primary generalized process (such as boil in a patient with diabetes, leykemidy in the skin in some types of leukemia, and others.).
With the development of almost any disease can distinguish specific and nonspecific mechanisms of its formation.
For nonspecific mechanisms include typical pathological processes such as inflammation, disorder lymphocirculation, fever, thrombosis, et al., As well as the generation of reactive oxygen species increase membrane permeability and so forth.
Specific mechanisms include activation of systems of cellular and humoral immunity, which provides specific protection in the fight against once ingested foreign object.
Protective and compensatory processes
An important manifestation of each disease are reactive changes in the cells, organs and systems, which always arise again, in response to the damage caused by the pathogenic factors. These include inflammation, fever, swelling, etc.
These reactive changes in the body are referred to as protective and compensatory processes, or "physiological measure" of protection (IP Pavlov), as a "pathological (or emergency) regulation function" (VV Pidvysotsky, NN Anichkov) "the healing powers of the body" (II Mechnikov). During the development of the disease processes of damage and recovery are in close interaction, and as pointed out, IP Pavlov, it is often difficult to separate from one another.
Compensatory devices - an important part of the adaptive response of the body to injury. They can be expressed in the development of both functional and structural changes in some way liquidating disorders of organs and systems caused by damage. Compensation thus becomes one of the main factors of clinical recovery. In addition to the compensatory process, an important role is played in the recovery and other adaptive reactions of the body of the patient to ensure the removal of the causative agent (antibody production, phagocytosis, protective inhibition). Thus, compensatory process is not to be confused with the whole complex of protective and adaptive reactions on the part of the body.
Compensatory processes can evolve and take place at various levels, from the molecular and ending with the whole organism sick person. At the beginning of the disease compensatory processes develop at the molecular and cellular levels. If the action of pathogenic causes of mild and short-lived, and the disease can not develop. This happens in cases falling not too virulent germs, poisons in small doses at low doses of ionizing radiation, weak trauma, etc. Significant damage caused stronger responses on the part of regulators and their systems.
Initial responses to injury are to mobilize the relevant functional reserves, providing adaptation, and can be implemented on intraorganic, intra and intersystem level as follows:
- Reserve stocks include diseased organ (it is known that only 20-25% of the lung surface respiratory used in healthy organism, 20% of the capacity of the heart muscle, kidney glomerular 20-25% vehicle, 12-15% of the liver parenchymal cells, etc.). Under load, this percentage increases that can be used to assess the state of a functional organ samples. For example, the destruction of the kidney nephrons occurs intraorganic compensation due to the fact that the surviving nephrons increase their function and hypertrophy;
- Developing vicarious hyperactivity. This type of compensation is carried out in case of damage of any of the paired organs, with the possible full implementation of the remaining body of the function with the loss of one. Thus, after the removal of or turning off of the work light (or a single kidney) arises compensatory hyperfunction of the remaining light (or other kidney). Mobilization of all the functional reserves of a single working body at first is imperfect, but as a result of the subsequent increase in the mass of its cell body again regains its activity almost to normal;
- Increases the intensity of the organs and systems, similar in function to a damaged organ or tissue, which in some degree disturbed homeostasis restores and extends the life of the organism.
An example of such inter-system of compensation - allocation of nitrogenous wastes through the sweat glands, the mucous membrane of the digestive tract and respiratory tract, strengthen the liver detoxification function in kidney damage. When you remove the stomach implemented internal system compensation, which provides increased secretory function of the lower parts of the digestive system.
It is important to emphasize that only the appearance of functional compensation does not provide a sustainable adaptation to the effects of the damaging agent. If hyperfunction of any organ or system enough to eliminate the defect, then it may be a compensatory process and limit. However, if homeostasis violations persist, the compensatory reactions continue to evolve. Long term compensatory hyperfunction organ systems entails the activation of the synthesis of nucleic acids and proteins in the cells of these organs and results in the formation of corresponding structural changes. There are the following compensation structure:
1. Hypertrophy - an increase in body weight by increasing the amount of its constituent functional units. An example is the hypertrophy of the heart, skeletal muscle, kidney etc.
2. Hyperplasia - increase in body by increasing the number of its functional units. They are prone to hyperplasia lymphoid tissue, the tissue of the mucous membranes.
3. Regeneration - the recovery process of organ or tissue after injury (Can be physiological and pathological, see Section 13.2.2), is carried out by:
a) restitution, ie, filling defect by dividing parenchymal cells of damaged tissue;
b) substitution when healing damage is due to the division of the connective tissue cells.
4. Compensatory distortion - for example, changing the location of the chest with a pronounced scoliosis of the thoracic spine, or kyphosis, as well as the expansion of the esophagus above the narrowing section with achalasia.
5. Development of collaterals in violation of blood flow in the major blood vessels that feed the body.
In the process of compensating structural changes occur not only in the cells of the executive body, which accounts for increased load, but also at all levels of the compensation system. This is the basis of the transition from emergency to long-term adaptation.
Sanogenesis term derived from the Latin sanitas (health) and the Greek genesis (origin) and meaning literally "the origin of health", one of the youngest in the pathophysiological science. The doctrine of sanogenesis dates back to 1966, when the definition of this concept was formulated by SM Pavlenko.
Sanogenesis - a dynamic complex of protective and adaptive mechanisms of physiological and pathophysiological nature, developing as a result of effects on the body of an extreme irritant, operating throughout the pathological process (from pre-disease until recovery) and aimed at restoring the disturbed self-regulation body.
Sanogenesis - a dynamic complex mechanisms. In this part of the definition emphasizes that sanogenetic mechanisms are not something constant. They change throughout the disease process. If a malicious agent has not yet penetrated into the interior of the body Wednesday, sanogenesis mechanisms will prevent its penetration, if the agent has already penetrated into the body, they will seek to bring it or break if the pathogenic stimulus has already caused in the body any "floor" that sanogenetic mechanisms are directed to the compensation or restoration of the lost function. In other words sanogenesis - is constantly changing (more dynamic) set of protective and adaptive mechanisms.
Sanogenesis - a complex physiological and pathophysiological mechanisms of nature. It highlights the fact that in sanogenesis involves not only the mechanisms that have emerged in the course of the disease, but the physiological reactions that occur in the intact organism, and only under the influence of pathogenic factors come into play sanogenetic.
Sanogenesis develops when exposed to the body of an extreme irritant, ie only when there is (or may be) disease. The body normally has a number of mechanisms that are specific function (providing excretion, selection, etc.). In a normal body, they do not perform any safety functions and only when exposed to the body of an extreme irritant transformed into sanogenetic.
Sanogenesis - a complex mechanism of action throughout the pathological process (from pre-disease until recovery). A characteristic feature of sanogenetic forces is that their mechanisms begin to function at a time when the body acted extraordinary stimulus and finish its function only when the body has recovered. In other words sanogenesis and pathogenesis - two parallel proceeding, closely related, but the opposite process for its biological orientation.
Sanogenesis aimed at restoring the disturbed self-regulation body. Self-regulation of the body - is its ability to rebuild their functions with a view to adapt to changing environmental conditions. In the pathology of this ability of the organism to an adequate self-regulation is violated, that is, the body can not fully adapt to environmental changes. The whole complex sanogenetic reactions and is aimed at the restoration of the self-regulation of disturbed relationships.
Classification sanogenetic mechanisms.
Firstly, mechanisms sanogenetic divided into primary and secondary. The difference between these two groups from each other is as follows. The primary (physiological) mechanisms sanogenesis exist in a healthy body, and only when exposed to the body of an extreme irritant into play sanogenetic. Secondary (pathophysiological) sanogenetic mechanisms occur in the body in the development of a pathology that is generated based on the problems in the body "floor."
Primary sanogenetic mechanisms.
Adaptation mechanisms. The term "adaptation" means adaptation to the changing conditions of the external and internal environment. In the normal body functions are a number of mechanisms. For example palpitations on exertion, sweating when the ambient temperature increases, increased urination when receiving large quantities of liquid.
However, these arrangements can not be called sanogenetic as they carry out adaptation within the physiological regulation of functions. Adaptation is sanogenetic mechanisms are the only ones that adapt the body to the action of an extreme irritant, preventing the development of disease (for example, a sharp spasm of peripheral blood vessels when exposed to body low temperatures, the opening of the blood depot and release into the bloodstream an additional amount of red blood cells in insufficient oxygen in the inspired air etc.).
Thus, the primary sanogenetic adaptation mechanisms - are mechanisms to adapt the body to function normally when exposed to extreme irritant. If coping mechanisms are effective, the disease does not occur.
Protective mechanisms. The second group of primary sanogenetic mechanisms designed to prevent the organism or pathogen to quickly put out of his body, to prevent development of pathological process. For example, in each organism are normal antibody; in saliva and tears has bactericidal factor - lysozyme; trachea and bronchi mucous membranes cells are provided with fibers that do not allow light to get into the fine alien bodies. These mechanisms prevent the penetration into the body of the pathogenic agent. If it has penetrated into the body (or formed in it), the protective organisms may destroy or remove it from the body before the agent will have time to initiate the disease process. For example, in the liver are destroyed some toxic substances, or caught in the body, or formed in it. By the protective mechanisms excretory nature include, for example, cough, vomiting, ie complex reflex acts aimed at the removal of the respiratory tract (cough) or stomach (vomiting), foreign bodies or harmful to the body.
Thus, the primary defense mechanisms sanogenetic - are mechanisms or inhibit penetration into the body of a pathogenic agent or destroy it, or deducing it from the body until it causes the development of the pathological process.
Compensatory mechanisms, if the primary adaptation and protective mechanisms are not able to prevent the development of pathological process, however, the disease process can not occur if the initial turn on the compensatory mechanisms that can adequately replace the impaired function. For example, the weakening of the contractile function of its ear auricle may be an additional pump, thereby compensating for a drop of atrial contractility. Thus, the primary sanogenetic compensatory mechanisms - these are processes, complementary function, impaired pathogenic agent, and not giving manifest the pathological process. It turns out that is successfully functioning primary sanogenetic mechanisms, there is no disease, but can only be a state of pre-disease which either disappears or goes into a state of disease in the event that the primary sanogenetic mechanisms overstrained, exhausted and can not be to the extent necessary to fulfill its function.
Secondary mechanisms sanogenetic
If there was a pathological process, then begin to function sanogenetic secondary mechanisms, developing on the basis formed in the body, "Paul." These mechanisms may be protective, compensatory and terminal. Adaptation mechanisms in this group are not available, because if I have a pathological process, adapting the body is no longer held.
Safety mechanisms prevent the progression of the pathological process: either neutralize or destroy a pathogenic agent, or impede its spread throughout the body, or remove it from the body. For example, antibodies produced by the microbe caught in the body can be destroyed or neutralized; inflammatory process, creating around taken root pathogen powerful barrier, including edema, leukocyte shaft, prevents the dissemination of the agent; diarrhea resulting from intestinal mucosal inflammation removed malicious factor from the digestive tract.
Thus, the secondary protective sanogenetic mechanisms - is the localization mechanisms, destruction or removal from the body, penetrated into it pathogenic agent.
Compensatory mechanisms. If the pathogen entered the body, it usually causes damage to organs and tissues and thus leads to a loss of a particular function that can cause serious disorders of vital activity. But this often does not happen, as the secondary compensatory mechanisms include processes, replacing impaired function. A classic example of such mechanisms is a compensatory hypertrophy of the heart muscle, which occurs when a significant and prolonged increase of the incident heart hemodynamic load (for example, valvular heart disease). If the increased load on the heart is the myocardium to cope with it in cardiomyocytes is to increase energy production. This leads to additional energy supply not only the contractile act and protein synthesis in cardiac cells. As a result, increased myocardial mass, and load per unit of its weight returns to normal.
Secondary sanogenetic compensatory mechanisms - mechanisms to fill this disturbed as a result of pathological process functions.
Terminal (extreme) arrangements. This group of mechanisms included in the critical (extreme) situations for the body and is the last reserve, allowing at least delay his death. Since these mechanisms are activated in the closing periods of the disease, they tend themselves associated with severe disease. There is a seemingly paradoxical situation - a severe pathological changes are beginning to play a protective role for the body. For example, when developing a massive myocardial infarction, heart failure, protects the heart muscle: the weakening of the contractile function of the heart can prevent his break on the background myomalacia (melting necrotic) by 5-9 hours from the time of heart attack.
The result of increased activity of the terminal bulbar centers is occurring in a period of agony clarification of consciousness in the dying. Although in this case, death still occurs, however - this is an example of action of the terminal sanogenetic mechanism associated with increased activity of regulatory centers in a critical situation.
Thus, the terminal (extreme) secondary sanogenetic mechanisms come into play at the final stage of the organism protection from exposure to pathogenic agents and develop most commonly as a result of coming in critical conditions of gross violations of the structure and function of organs and tissues.
As mentioned above, the sano - and pathogenetic mechanisms developed in the dynamics of the disease process in parallel and often pathogenic changes in the body begin to play a role, and vice versa sanogenetic inclusion of some sanogenetic mechanisms may lead to the weighting and the progression of the pathological process.
Sanogenetic role of pathogenetic mechanisms.
In medicine, there are many examples where the pathological process can bring the body to use. For example, such a serious disease like sickle-cell anemia, resulting from a hereditary defect in hemoglobin synthesis, plays a role in malaria sanogenetic. A patient with sickle cell anemia, along with normal hemoglobin A, A2 and F hemoglobin has pathological S, the reduced form of which has a much lower solubility than that of normal hemoglobin. As a result, in the venous part of the capillary bed, where the oxygen partial pressure is sharply reduced hemoglobin enters the semi-crystalline state and takes the form of so-called tactoids having the form of a crescent. This leads to distortion of the shape of red blood cells (a type of sickle), their destruction and the emergence of severe hemolytic anemia. However, if the hemoglobin S concentration in the blood does not exceed 45% of the total hemoglobin. These changes will occur only if the inhaled air dramatically decrease the partial pressure of oxygen (mountain climbing, diving, etc.). In ordinary conditions, this disease is reduced to asymptomatic carriage of hemoglobin S. Sickle-cell anemia is common in so-called "malarial" zone of the Earth. And I noticed that her ill have an increased resistance to the malaria parasite. The fact is that the malaria parasite for their development requires a large amount of oxygen. In connection with what in erythrocytes, which is Plasmodium, hypoxia. In these circumstances, there is loss of hemoglobin in the form of tactoids, red blood cells die, and with them and die of malaria. Thus, in this case there is a genetically fixed sanogenetic role pathogenetic mechanism.
The phenomenon sanogenetic role of pathogenetic mechanisms can give the following explanation. On the body in a number of pathogenic factors affect the course of his life. What if he had not developed in the evolution of sufficiently reliable mechanisms of adaptation and protection, he could not have survived. In the event of sickness claims increased sharply in the body protection reliability. Since starting to operate in unusual conditions for him. In order not to die body has developed over the evolution of the ability to use even appearing in it "Paul" in their own interests. Sanogenetic role pathogenetic mechanisms - is the highest reflection of the body's ability to adapt to the environment.
Pathogenic role sanogenetic mechanisms.
Quite often there is a reverse pattern when sanogenetic mechanisms play a pathogenetic role, that is a situation where the protection of the other party turns itself leads to the progression of the disease process or the death of the organism. This may occur, for example, in the following situations. The reaction of the protective systems are not the cause, but one of the consequences of exposure to a pathogenic factor. In this case, the point is. What is most different in etiology of disease processes can have a common pathogenetic link, and such, which can initiate the reaction sanogenetic standard, whereby sanogenetic enters pathogenetic mechanism, such as in reducing blood flow in the renal vascular spasm and enhance production of renin.
Lack of differentiation sanogenesis mechanisms. When exposed to the pathogenic organism antigenic variation factor structures of some proteins can occur, causing them to destroy their produced antibodies. However, due to the fact that the antigenic structure modified and normal protein has a lot in common, antibodies raised to the modified proteins can react with and destroy them unchanged. Develop the autoimmune process, which is based on the transition sanogenetic pathogenetic mechanism.
Local development sanogenetic mechanisms. In acute focal ischemia (infarction) of the myocardium in the area of the heart muscle, deprived of blood flow, hence, oxygen, compensatory enhanced glycolysis, which is undoubtedly sanogenetic character, because it allows the muscle fibers of the ischemic area of the heart to receive a certain amount of energy. However, this gain in glycolysis areas of cardiac muscle ischemia surrounding area occurs. Consequently, the area between and surrounding ischemic tissue there is a high electrical potential difference, which may lead to the development of cardiac arrhythmias, including inevitably leading to death ventricular fibrillation. Thus, local development sanogenetic mechanism caused the violation of the functions of the body as a whole system can lead to the eventual death of the organism.
Genetically determined deficiency of protective mechanisms. This type of transition sanogenesis mechanisms in the pathogenesis can be illustrated by the so-called "storage diseases" associated with genetic defects in lysosomal system.
One of the main functions of lysosomes is the implementation of intracellular digestion and the cells get rid of ballast substances. This process is carried out mainly through the formation of intracellular digestive vacuoles, which merges with a lysosome: the latest releases in the cavity of the vacuole corresponding enzymes that perform splitting and got in the vacuole of the substrate. In that case, if the substrate is not subjected to cleavage, it remains in the cavity of the digestive vacuoles and eventually all the vacuole (lysosome merged with it) is filled with this substrate. If you have a genetically based lysosomes lack of a particular enzyme, is trying to carry out their inherent function of digesting foreign substrates for cell lysosomes die, turning into "bags" with uncleaved substrate. These "bags" filled the entire cell, which also killed. It is in this way develops a number of serious diseases (mucopolysaccharidosis), in which the central nervous system cells are filled with undigested mucopolysaccharides. The same mechanism underlies the development of atherosclerosis, and (as a result of genetically determined defect of enzymes that break down the cholesterol in the lysosomes of cells of the vascular wall). Thus, as a result of a genetic defect in defense mechanism becomes a severe pathology.
These are just some of the reasons for the transition sanogenetic pathogenetic mechanisms.