General body responses to noxas

1. General body responses to noxas Prof. Tatár Dept. of Pathophysiology in Martin

2. Injurious influences of noxas do not only produce local cell´s injury, but also elicit general body responses • Physiological reactivity – pathological reactivity • Responses to stress: • Mobilisation of defensive and regulatory mechanisms and reserves to overcome harmful effects of noxas • To maintain morphological and functional integrity of the organism, but there is temporary disturbed homeostasis

3. Integration of various components of living organisms becomes essential to their survival • Integration is effected by: • Central nervous system – coordinates, interprets, and control the interaction between the individual and the environment • Endocrine system – mobilization of metabolic reserves • Integrated cooperation of CNS and ES helps minimise the response of the organism to stressful stimuli

4. 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

5. 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; impairment of body systems can lead to death

6. 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

7. Tissue damage Peripheral nociceptors Thalamus Hypoxemia Hypercapnea Chemoreceptors Hemorrhage Hypovolemia Fluid shifts Arterial baroreceptors Atrial baroreceptors Medula Cardiovascular reflexes Respiratory reflexes

8. Infection Fear and Emotion Leukocytes Paleocortex Limbic system Thalamus IL-1 PGs Medulla Hypothalamus Pituitary CRH CRH ACTH Adrenal Sympathetic efferents Catecholamines Cortisol

9. 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

10. Physiological effects of catecholamines Cardiovascular system  rate and force of contraction  peripheral vasoconstriction Pulmonary system bronchodilation Skeletal muscles  glykogenolysis,  contraction Liver  glucose production,  glygogen Adipose tissue  lipolysis,  fatty acids and glycerol GIT  protein synthesis,  motility

11. Physiological effects of cortisol • gluconeogenesis, inhibition of the uptake of glucose by tissues • protein catabolism – muscles, lymphoid tissue, skin, bone  negative nitrogen balance • promotes lipolysis in some areas of the body • immunosuppressant

12. 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

13. Multiple hormones cooperates to bring about appropriate metabolic response • Hyperglycemia a) glycogenolysis and gluconeogenesis in liver b)  glucose uptake in muscles,  insulin release  glucose is preserved for CNS 2. Free fatty acids mobilisation metabolised in muscles

14. Stress and immune system • immune system synthetizes cytokines activating HPA system • immune cells possess receptors for hormones of HPA system • stress hormones can influence immune functions

16. 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

17. Increased plasma level of „stress hormones“ Hyperglycemia + hyperlipemia advantageous forwild 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

19. TRAUMA -SHOCK CATECHOLAMINES CORTISOL GROWTH HORMONE INSULIN GLUCAGON 0 1 2 3 4 5 6 7 days increased plasmic level decreased plasmic level