Role of stress in pathology of microcirculation system
Cause-effect relation between diseases and preceding emotional shock are well-known. As far back as II century Avicenna wrote in his “The Canon of Medicine”: “Diseases sometimes afflict heart... due to the influences which come to it... from the brain when the fluid of melancholy is accumulated in it and causes tremor and sudden loss of strength, and sadness with the feeling of trouble, and depression”. In the middle of XX century, after the publication of works by G. Seliet, the concept “stress” for a few years became a common term not only in science.
Stress is a non-specific common mobilization response of an organism to any irritant which violates its homeostasis. Stressors are understood to be, in the first place, irritants which seriously endanger homeostasis – pain, hypoxia, starvation, infection and a lot of other extreme factors. At the same time even “sudden big success, which leads to reconstruction of the whole lifestyle” may cause severe stress (Seliet, 1974). Therefore stress is not the synonym of a strain on the nerves and it is not always caused by some damage.
Seliet differentiated constructive and destructive kinds of stress, emphasizing that not every stress is harmful. He supposed that stress reaction can be a positive force, which activates the systems of organism adaptation – eustress. But it also can damage mechanisms of adaptation (extreme stress – distress). On one hand, stress is a mechanism of adaptation. On the other hand, it is the basis of pathology progression.
According to present ideas, any strong influences of environment – emotional, pain, mobilization kinds of stress, acute hypoxia, hard physical labour, high temperature, cold etc. – cause common stress response (Malyshev, Manukhina, 1998). Intensity of stress response is determined by the correlation of activation of stress-system, which realizes the response of an organism to stress, and stress-limiting systems, which restrict the activation of stress-system and damaging influence of stress-hormones.
Stress-system is divided into central and peripheral parts. The central part is represented by medullar and hypothalamic nuclei, the peripheral one is represented by hypothalamic pituitary-adrenal axis and efferent sympatic system. Key metabolites are adrenocorticotropin (ACT), prolactin, growth hormone, glucocorticoids, noradrenalin and adrenaline.
Stress-limiting systems are also divided into central and peripheral parts. Among stress-limiting mechanisms the key role belongs to endogenic opiates. They develop in many parts of central nervous system (CNS) and beyond it – in chromaffin tissue and adrenal medulla, diffuse endocrinocytes of gastrointestinal tract and bronchi and even in T-lymphocytes. They are found in human milk as kazomorphine, which protects in the period of overcoming of unfavourable consequences of generic stress and early neonatal adaptation. CNS and immune system are relative with regulatory action of neuropeptides and cytokines.
Structures, where all kinds of endogenic opiates are represented, are hypothalamic pituitary neurosecretary complex, limbic system, hippocamp and also components of inspiratory centre. Opiate-ergic systems restrict destructive potential of stress response, prevent distress and favour physiological recovery from acute stress. Gamma-amino-butyric acid (GABA) serves as inhibitory transmitter in stress-limiting systems of hypothalamus. Universal in its inhibitory nature, GABA is represented in almost 60% of all synaptic formations of CNS and first of all in hypothalamus. In many cases GABA secretion to CNS is modulated by opiates.
Nitrogen oxide (NO), which is a universal factor of regulation of physiological systems and genetic apparatus of cells, plays an important role in stress-response mechanisms and adaptation of an organism to stress (Malyshev et al, 1998). At short and moderate stress influences, NO production increases. It favours retroaction of constrictive effects of hormones, provides active hyperemia of tissues and favours adaptation. If stress-response is extreme and long-lasting NO output considerably decreases, which may condition the appearance of stress spasms of coronary microvessels and also stressogenic hypertensive conditions. During long-lasting intensive stress response adaptive effects are transformed into damaging ones, which may become the basis of stressogenic diseases formation. Indeed, a lot of diseases and pathological states, in which stress plays a key role (IHD, cancer, hypertension, diabetes etc.), are marked by decrease of production of NO by endothelium.
The diseases, the possibility of occurrence and severity of clinical course of which increase during stress, were called “adaptation diseases” by G. Seliet. He represented several key statements, which are constantly proved by clinical practice:
• Stress is a component of every disease, and its influence is seen on all forms of pathology, which leads to aging of an organism.
• Adaptation diseases are considered to be only those in aetiology of which the role of distress is the most important.
• Inadequate stress, refracting through genetically conditioned responsiveness, may cause various disorders: hypertension, peptic ulcer, immunity disorders, arthritis, IHD, bilious headache. But psychic disorders were considered to be one of adaptation diseases.
The analysis of the list of adaptation diseases proves that all of them are the reasons of disorders of those insulin-dependent organs and tissues, which appear to be in metabolic loss during stress-response. Stress, especially chronic one, is an important risk factor of peptic ulcer disease, immunodeficient diseases and their consequences, including infections, parasitic and oncological diseases of, osteochondrosis, arthrosis and arthritis, diabetes mellitus. At that production of interleukins, interferones, tumour necrosis factor decreases. Cumulative impact of stress hormones on immune system may cause well-marked secondary immunodeficiency, which occurs more often at chronic stress. It is experimentally proved that stress favours tumors transplantability, accelerating their growth and increasing the probability of metastasis. During stress not only alternative exudative evidences of inflammation but also proliferation, including fibroplastic processes and collagen fusion, are weakened. Wound and anabrosis repair is deteriorated. A vascular wall, as highly focused and insulin dependent connective tissular structure, is damaged with hypertension and atherosclerosis.
Disregulation of opiate stress-limiting systems is directly related to occurrence of mental distress, alcoholism, nicotine and drug addiction, chronic fatigue syndrome. It should be noted that stressogenic pathology, first of all, concerns insulin dependent organs and tissues such as skin, a vascular wall, skeletal muscles, connective tissue, leucocytes and immune system cells, skeletal system and other elements of locomotor system, bone marrow, gastrointestinal tract organs (Felig et al, 1985).
The role of stress in pathology of tissues is quite considerable. As it is known, any defense reaction does not always act reasonably; that is why there’s nothing strange that stress can be the cause of pathogenic basis of progression of many diseases (Horizontov, 1981). Major diseases, in pathogenesis of which stress and stress-caused disorders of tissular microcirculation play considerable and sometimes key role, are presented in the table 4.2.
Distress increases latent readiness for progression of neurogenic inflammatory process in loose connective tissue. As a consequence, favorable conditions for development of autoallergic and autoimmune processes and chronic diseases are formed (Gogoleva, 2001).
In terms of stress, microvasculature system is one of the most vulnerable and sensitive. One-type intra-, trans- and extravascular disorders develop there. A definite response of microvessels to stress is vasoconstriction of arterioles, precapillars, precapillary constrictors, postcapillars, venules, lymphovessels (Horizontova, 1986; Fedorov, 1990). As a result, sludges formation, vascular penetration disorder, feebleness of circulation in venules and veins and then in arterioles occur.
Table 4.2. Disorders which are associated with tissular microcirculation disorders
Locomotor system diseases
Microvascular changes of soft tissues and bones.
Myofascial pain syndrome.
Dystrophic changes of muscles, tendons, ligaments.
Back bone osteochondrosis.
Back bone hyperostosis.
Arthrosis of joints.
Somnipathy (distributions of sleep).
Chronic fatigue syndrome.
Digestive apparatus diseases.
Respiratory system diseases.
Urogenital system disorders.
Long-lasting vasoconstriction in postcapillar-venular part and in lymphoid vessels causes occurrence of stagnation of biological fluids in intravascular and interstitial space (Shuteu et al, 1981). Definitive long-lasting changes in microcirculation system lead to progression of regulatory metabolic disorders, dystrophy of tissues. Dissemination of theses processes leads to VILS syndrome, SIDST, MFPS, which are nearly always anamnestically connected with unmastered stress responses.
Long clinical author’s observations showed that as a result of impact of mental distress on some definite regions of investing tissue of a human body one can see specific dermatic vascular reactions (petechiae, local edema), which reflect microcirculatory dislocations with evidences of MFPS and concomitant dystrophic changes of tissular structures (indurations, contractures, MTD). Such regions were called stress-dependent or stress-sensitive zones. To such localizations can be referred:
The region of epicranial muscle, posterior surface of neck and shoulder joints;
Projections of deltoid and cowl muscles;
Interscapular space and scapular region;
Gluteal region, posterolateral surface of thighs;
Stern costal joint;
Face and interior surface of neck.
One may suppose that these are stress-dependent zones that one of the first acutely response to stress in common biological way – vasoconstriction. However, it is not impossible that the system of microcirculation and other regions of tissues and organs also reflects stress reaction which leads to either VILS or ischemia.