The study of pathogenesis requires investigation of all stages in the development of pathologic phenomena, their succession and interconnections. The basic factors determining the character and peculiarities of a disease are: (i) the character of cause, (ii) the localization of primary damage, (iii) the character of primary damage.
The significance of the localization of primary damage depends on (i) the vital importance of the damaged organ and (ii) the character of afferent nerve imputation from its receptor field.
The main kidns of primary damage which influence the peculiarities of the development and the course of a disease are:
1) structural damage to tissues and organ,
2) the excessive stimulation of receptors of the damaged tissue;
3) generalized disturbances in metabolism;
4) terimary disorders in the activity of regulatory systems.
A disease is the affection of total organism often characterized by predominant localization of damages to one or another organ. In some cases a damages to one or another organ. In some cases a disease may begin with local injuries, in other ones pathologic changes in tissues of organs arise after the appearance of the general manifestations of the disease.
Lozalization of pathologic changes is determined by:
1) application of primary action of the causative factor;
2) the ways of releasing of toxic substances from the organism;
3) the changes in reactivity of organs;
4) the peculiarities of biochemical processus in tissues and organs.
The significance of the site of penetration of pathogenic agents. The gate of entrance of the pathogenic agents and the site of their initial effect play a very important part in pathogenesis. For example, the perentration of gonococci to the urethral mucosa gives rise to gonorrheal urethritis, whereas the action of the same microorganism on the mucosa of the eye produces gonorrheal conjunctivitis (blennorrhea). Subsequently these two processus greatly differ in their development. Of the factors that determine the mechanism of action of pathogenic stimuli an important part is apparently played by the anatomophysiological and biochemical properties of the organs and tissues, their functional state and the characteristics of their receptor fields.
Pathologic processes predominantly affect particular organs, not only according to the point of entry of the pathogenic agent, but also to the physiological pecularities of the entire organism. For example, osteomyelitis (the inflammation of bone marrow and bone marrow and bone) most frequently begins in the metaphyses of tubular bones. This is accounted for, not only by the characteristics of capillaries, but also by the regulation of the blood flow which provides an abundant blood supply to the given part of the bone where the best conditions are apparently created for contact of the tissue with the toxins of bacteria brought in by the blood flow.
Sometimes the effect of the etiologic factor is predominantly manifested in the parts of the organism which suffered injury. By damaging tissues, injuries produce nutritional and metabolic disorders in them, reduce the general resistance of the organism and facilitate the penetration and spread of the noxious agent in it. Thus, and injury to a lung may stimulate the development of purulent inflammation in it, an injury to the limbs - development of tuberculosis of bones.
The Spreading of pathogenic agents.
To disclose the pathogenesis of diseases and understand their development it is also necessary to investigate the spread of pathogenic agents in the organism after their penetration into its internal environment. As a result of the spread of pathogenic agents the pathologic process may involve the adjacent and, not infrequently, distant organs and tissues. The pathogenic agents may spread:
1) the extension and contact,
2) through the vascular (circulatory and lysphatic) system and
3) through the nervous system.
The spread by extension occurs as a result of the action of the pathogenic agent, which affects one part of a tissue on the adjacent normal part, for example, the spread of herpes over the skin or of infection along the urinary tract.
Closely resembing the aforedescribed route of spread is the intracanalicular spread, for example, along bronchi or excretory gland ducts. Thus infected masses preading along bronchi from some tuberculous focus in the lungs cause the development of a pathologic processes in other parts of the Jungs.
The spread may also be a result of contact of an affected surface with a healthy surface. In inflammation of the gallbladder the inflammatory agent sometimes affects the serous coat of the stomach causing its inflammation (perigastritis).
The penetration of pathogenic agents (microbes, toxins and poisons, cells of malignent tumors, etc.) into the blood stream leads to their spread throuhout the organism. For example, after affecting the entire organism and weakening its defence mechanisms bacteria and toxins may at first gain entrance into the tissue fluid and then through the lymphatic vessels into the lymph nodes where they may be stopped or carried further by the lymph into the venous system. This route of spread through the lymphatic system is called lymphogenic.
In other cases bacteria and toxins penetrate, for example, together with emboli into the blood stream and are quickly transported by the latter; this route of sread by the circulatory system is known as hematogenic. Microbal metabolites or tissues catabolites may sread from the focus of infection and cause general intoxication and a febrile process. Some infectious agents, for example, the rabies virus or tetanus toxin, which act selectively on nervous tissue, spread along nerve trunks.
The spread of pathogenic agents must not be conceived mechanistically, as a phenomenon depending only on the direction of the vessels or nerves. Here we have a complicated biological process, i.e. a complex of unstable, continuously varying physiological states of the organism, particularly the environment into which the pathogenic principle gains entrance.
Interrelation between the local and the general phenomena in pathogenesis. The pathologic process may at first manifest itself in the injury of the tissue at the point of the application of the stimulus mechanical, chemical, thermal, infectious, etc. The process gives rise to disturbances in metabolism and the structure of the tissue.
Pathologic processes are never stictly localised. On the one hand, the charcter of their divelopment is determined by the properties of the organism as a whole; on the other hand, once arising, these processes also affect, in their turn, the entire organism. Such a local pathologic process as inflammation depends on its origin and development on the general condition of the organism and is a local expression of its general properties. For example, furunculosis is often a result of nutritional and metabolic disorders and concomitantly lowered immunity.
Other diseases involving changes in the entire organism also produce local changes, such as functional and structural disturbances in some particular organ. Thus, typhoid fever, although a disease of the entire organism, is characterised by peculiar changes in the small intestine. Atherosclerosis which develops as a result of general metabolism disorders is marked by changes in the walls of large arteries.
Owing to the integrity of the organism and the interaction of its parts, local processes must not be considered apart from the entire organism. At the same time, originating in a particular part of the organism, at a certain stage of its development the pathologic process becomes the starting point of new relations between the local and the general and affects of entire organism. For example, an inflammatory focus evokes a general leukocyte reaction and visibly alters the sensitivity of the entire organism to foreign proteins and infectious agents. The mechanisms of influence of local process on the entire organism:
1) reflex mechanism: CNS receives from the receptors signals pertaining to the" state of the organism internal environment and affecting state of CNS,
2) humoral mechanisms: the damaged tissue releases the biologically active substances, metabolites, changed proteins, toxins of microbes and etc., which affect the activity of regulatory systems (CNS, endocrine system).
The mechanisms of inluences of the entire organism on the local processes:
1) CNS realizes the functional and trophic influences on the damaged tissue and also affects its blood supply,
2) hormones influence the metabolism and functions of damaged tissue.
Thus, the local and the general must be understood in their dialectical unity. Disclosure of these interrelations makes it possible to gain a deeper insight into the pathogenesis of the disease.
Correlation of function and structural manifestations of disease.
Disease always manifests itself in functional disorders while structural changes often are not revealed. Lack of disparity between stuctural and functional disturbances may be explained by
1) slight expression of the structural changes,
2) their reversibility,
3) local character of the structural changes.
4) unequal significance of different organ parts for its function,
5) impossibility to reveal some structural changes in cells and tissues,
6) development of compensatory reactions.
On the basis of the expression and prevalence of structural or functional changes organic and functional diseases are distinguished. An organic disease is charcterized by expressed structural disorders which can transform into steady irreversable changes. Functional diseases develop without marked structural disorders and usually deal with temporary disturbances in nervous and humoral regulation of functions.