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General body responses to noxas Prof. Tatár Dept. of Pathophysiology • Injurious influences of noxas do not only produce local cell´s injury, but also elicit general body responses • Physiological reactivity – pathological reactivity • Responses to stressors: 1. Mobilisation of defensive and regulatory mechanisms and reserves to overcome harmful effects of noxas 2. To maintain morphological and functional integrity of the organism, but there is temporary disturbed homeostasis - allostasis • Integration of various components of living organisms becomes essential to their survival • Integration is effected by: 1. Central nervous system – coordinates, interprets, and control the interaction between the individual and the environment 2. Endocrine system – mobilization of metabolic reserves 3. Integrated cooperation of CNS and ES helps minimise the response of the organism to stressful stimuli • W.B. Cannon – 1914 : applied the engineering concept of stress in a physiologic context • H. Selye – 1946 : Stress = the physiologic changes that follow the application of a stressor to an living organism; non-specific physiologic response Stages of stress • Alarm stage sympathetic n. s. and pituitary gland are aroused and the body´s defences are mobilised • Stage of resistance hyperactivity of the axis hypothalamus-pituitary gland-suprarenal cortex • Stage of exhaustion continuous stress causes the progressive breakdown of compensatory mechanisms and homeostasis – allostatic overload impairment of body systems can lead to death Important stressors Somatic physical effects: cold, heat, radiation, hypo- and hyperbaric conditions, noise pathologic states: hunger, thirst, hemorrhage, physical exertion, hypoxia, hypoglycaemia, sepsis; anaesthesia, surgery Psychological (typically human) individual: mental tension, public speech group: family troubles, neighbourly stress social: work overload, joblessness, go into retirement, social tension Tissue damage Peripheral nociceptors Hypoxemia Hypercapnea Chemoreceptors Hemorrhage Hypovolemia Fluid shifts Arterial baroreceptors Atrial baroreceptors Thalamus Medula Cardiovascular reflexes Respiratory reflexes Systemic inflammation Fear and Emotion Thalamus Leukocytes Paleocortex Limbic system IL-1 PGs Medulla Hypothalamus CRH Pituitary CRH ACTH Adrenal Sympathetic efferents Catecholamines Cortisol Essential physiologic actions of adrenergic receptors 1 glycogenolysis, vascular muscle contraction 2 GIT muscle relaxation, inhibition of insulin secretion 1 lipolysis, inotropic myocardial effect 2 release of glucagon and renin, bronchial relaxation Physiological effects of catecholamines Cardiovascular system rate and force of contraction peripheral vasoconstriction Pulmonary system bronchodilation Skeletal muscles glycogenolysis, contraction Liver glucose production, glycogen Adipose tissue lipolysis, fatty acids and glycerol GIT protein synthesis, motility Physiological effects of cortisol 1. gluconeogenesis, inhibition of the uptake of glucose by tissues 2. protein catabolism – muscles, lymphoid tissue, skin, bone negative nitrogen balance 3. promotes lipolysis in some areas of the body 4. immunosuppressant Other stress hormones Endorphins stres-induced analgesia positive well-being, euphoria Glucagon hormone of energy shortage secretion is stimulated by catecholamines gluconeogenesis and glycogenolysis Growth hormone stimulates proteosynthesis and transport of AA into the muscles Multiple hormones cooperates to bring about appropriate metabolic response 1. Hyperglycemia a) glycogenolysis and gluconeogenesis in liver b) glucose uptake in muscles, insulin release glucose is preserved for CNS 2. Free fatty acids mobilization metabolised in muscles Stress and immune system 1. immune system synthetizes cytokines activating HPA system 2. immune cells possess receptors for hormones of HPA system 3. stress hormones can influence immune functions Stress-related diseases and conditions Cardiovascular system coronary artery disease hypertension arrhythmias Pulmonary system hypersensitivity reactions (asthma) Immune system immunosuppression or deficiency GIT system ulcer, irritable bowel syndrome Genitourinary system impotence, frigidity Skin eczema Endocrine system diabetes mellitus CNS fatique, letargy, depression overeating insomnia Increased plasma level of „stress hormones“ Hyperglycemia + hyperlipemia advantageous for wild animals (fight or flight, starvation) man supplied with excessive food resources and living usually in hypodynamic conditions cannot utilise accumulated energetic substrates such repeated and long acting situations promote some pathophysiological states: catecholamines heart dysturbances ca + cortisol hypertension rate of coagulation thrombosis hyperlipidemia premature atherosclerosis glucose utilisation insulin resistant diabetes mellitus protein synthesis muscular athrophy, osteoporosis endorphins obesity stress ulcer dysruption of barrier function and poor perfusion