Stress Ⅰ. Introduction • Stress • Stressor • Classification of stress response • Significance of stress
Necrosis stimulate burn operation fester infection acidosis hypoxia injury nonspecific and common response noise Redistribution of blood Increased heart rate fear Stress anxiety Stress 1．Stress Stress is defined as a state of tension that can lead to disharmony or threaten the homeostasis of body. Specific response not directly related to the nature of stimulus
Stress 2．Stressor The stimuli or agents that induce stress are termed stressor. The same stimuli， the same response？ Stressor External environment（Physical, chemical, biological） Cold, heat, toxins, drugs, bacteria. Intrinsic factor of body Homeostasis, Acid-base disturbances,shock, cancer. Psychological or socio-cultural Threat to self esteem, relationships with other people.
4．Significance of stress ■ Eustress:Normal stress is necessary for an active, healthy life, increase mental and physical alertness and can enhance certain abilities. (Fight or flight). ■ Distress: if the stress response is excessive or prolonged, it may eventually result in diseases, such as ulcers, et al. Stress 3．Classification of stress response Physical, chemical Stress response Physical stress Psychological or socio-cultural Psychological stress
neuroendocrine response Cellular stress Cellular stress Effects of stress on the body Stress Ⅱ. stress response and pathogenesis stressor
1.neuroendocrine response Nervous System Endocrine System
Stress [Neuroendocrine responses to stress] Neuroendocrine responses Locus ceruleus (LC) - norepinephrine neurons(NE)-sympathetic/adrenal medulla axis （LC-NE）excitatory hypothalmus-pituitary-adrenal axis (HPA) excitatory Other hormonal responses to stress
Zona fasciculata Zona reticularis Zona glomerulosa adrenal medulla Adrenal cortex
Locus ceruleus (LC) - norepinephrine neurons(NE)-sympathetic/adrenal medulla axis （LC-NE）excitatory Neuroendocrine responses Catecholamine (CA) secretion↑ hypothalmus-pituitary-adrenal axis (HPA) excitatory Glucocorticoid (GC) secretion↑ Other hormonal responses to stress Stress [Neuroendocrine responses to stress]
Psychological stress Emotio-nal reaction Physical stress CRH ACTH adrenal medulla CA GC Locus ceruleus - Norepinephrine （LC-NE） Stress 1. LC-NE Composition CortexLimbic system PVN Pituitary adrenal cotex
Plasma CA increase stimuli NE Epinephrine cold, hypoxia 10－20 fold 4－5 fold Hemorrhagic shock 50 fold 10 fold execution 45 fold 6 fold 2. Effects of CNS ■ induce excitement, alertness, anxiety and other emotional reactions ■ rapid response system while stress occurs the key to start the HPA stress axis 3. Effects of peripheral ■ CA (include Ad、NE、Dopamine) concentration increase
Stress 4. Functional and metabolic responses of CA in body (1) compensatory significance ■ cardiovascular system stressCA↑ Heart rate↑,myocardial contractility↑,cardiac output↑ peripheral resistance↑ redistribution of blood flow ■ respiratory system stress increased respiration↑ oxygen supply ↑
increased secretion of ACTH, GH, EPO, T3\T4 and renin • other hormones secretion ■Material energy metabolism stress CA↑ receptor in A cells（+） glucagon↑ receptor in B cells（+） insulin↓ blood glucose↑ glycogenolysis, lipolysis ↑ Meet the energy needs of the body
Stress (2) Negative aspects of the body ■continued contraction of abdominal organs vessels ↓ gastrointestinal mucosal erosion and bleeding ■ vasoconstriction and heart rate↑ essential hypertension ■ increased energy consumption ■CA↑ thrombosis Type A
Hippocampus, amygdala , Limbic system PVN LC-NE CRH↑ pituitary ACTH↑ Adrenal cortex GC↑ Hypothalamic-pituitary-adrenal，HPA 1. HPA Composition HPAis composed of PVN、 anterior pituitary and adrenal cortex. Physical stress Emotional reaction
2. Effects of CNS Physical stress PVN Limbic system ② ③ β-EP↑ CRH↑ amygdala ① pituitary CA ADH↑ ACTH↑ sympathetic - adrenal medulla excite Adrenal cortex GC↑ 3. Effects of peripheral ●moderate CRH↑ adaption excited, memory enhancement ●excess CRH ↑ adaption disorder anxiety, depression, loss of appetite Stress
Negative aspects ● Suppression of immune response; ● Growth retardation; behavior change● Gonadal axis suppression, thyroid axis suppression ● abnormal behavior ● excessive protein breakdown, negative nitrogen balance 4.physiological significance of increased GC (GC↑>25-37mg/d) compensatory significance ●increase protein catabolism ●increase mobilization of fatty acids from adipose tissue ● permissive action: enhancement of the arteriolar response to CA ● stable lysosomal membrane stability ● anti-inflammatory
Stress other hormonal responses to stress hormone secretion site change -Endorphineanterior pituitary increase ADH hypothalamus increase AldAdrenal cortex increase Glucagons cells increase Prolactin anterior pituitary increase Growth hormone anterior pituitary acute↑, chronic↓ Insulin βcells decrease TRH hypothalamus decrease TSH anterior pituitary decrease T3, T4 Thyroid decrease GhRH hypothalamus decrease
Characteristic Significance Stress [General adaptation syndrome, GAS] Certain changes take place within the body during stress that disrupt normal physiologic mechanisms and trigger an array of diseases. rapid response , short duration sympathetic - adrenal medulla excite General mobilization of all the body’s defenses Alarm stage Body has adapted to the stessor and resistance is above normal Resistance stage CA decline and GC increase Response becomes general again and signs of alarm reaction reappear. Adrenocortical hormones in the blood rises once more. Body’s resources are completely exhausted and death occurs. Exhaustion stage
Stress [Acute phase proteins] 【Acute phase response】 The acute phase response is a quickly mobilized, non-specific defensive response elicited in response of the host to infection, tissue injury or inflammation, etc.. 【Acute phase proteins, APP】 APP have been defined as one whose plasma concentration increases (positive acute phase proteins) or decreases (negative acute phase proteins) during the acute phase responses.
Stress 1. Origin of APP APP is synthesized by the liver, VEC, Mo, fibroblasts。 2．Classification of APP ■ Protease inhibitor protein ■ Related proteins of coagulation and fibrinolysis ■ Complement components↑ ■ Transporter protein↑ ■ other proteins
Stress 3．Function ofAPP ■ Inhibition of protease activation：reduce tissue injury ■ Remove foreign bodies and necrotic tissue ■ Inhibit free radical production ■ Other functions
Stress Ⅲ. Cellularresponses to stress In responses of cellular-molecular level to more stressors (mai- nly non-psychogenic stressors), cell arouse a series of intracellu- lar signal transduction and activation of correlative gene and syn- thesize some protective protein, which mainly are heat shock pro- tein and acute phase protein.
【HSP生物学特点】 • Non-specific inducement • ■Widespread • ■ Housekeeping Stress [Heat shock protein，HSP] 【Concept ofHSP】 HSP are a class of functionally related proteins whose expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated.
Stress 1. Factor of induced HSP production • different kinds of environmental stress conditions: infection, inflammation, exercise, exposure of the cell to toxins (ethanol, arsenic, trace metals and ultraviolet light), • Others: starvation, hypoxia (oxygen deprivation), nitrogen deficiency (in plants), or water deprivation.
Stress 2．Classification of HSP apparent molecular weight HSP110, HSP90, HSP70, HSP60and small molecule HSP.
3．Function of HSP Stress • Heat shock proteins function as intra-cellular chaperones for other proteins. They play an important role in protein-protein interactions such as folding and assisting in the establishment of proper protein conformation (shape) and prevention of unwanted protein aggregation. By helping to stabilize partially unfolded proteins, HSPs aid in transporting proteins across membranes within the cell。
S S S H H H P P P ubiquitin S H P
Stress Ⅳ. Effects of stress on the body
Stress 1. Effects on metabolism ■ High metabolic rate stress CA、GC↑ Catabolism↑ Weight loss, weakness, decreased resistance↓ ■ Changes in glucose metabolism stress insulin↓, CA、GH、GC↑ Glycogenolysis ↑ stress hyperglycemia ■ Changes in fat metabolism ■ Changes in protein metabolism
2. Effects of stress on the organs and systems ■Change of CNS ▲ LC-NE axis activation caused excitement, nervousness, anxiety, fear, anger, etc.。 ▲HPA axis moderate activation caused excitement, proper mood and learning ability ▲ HPA axis excess activation caused CNS dysfunction, depression, anorexia, and even suicidal. ■Change of cardiovascular system ■Change of gastrointestinal
Stress ■Change of immunity ▲Acute stress response stress number of peripheral blood phagocytic cells↑，APs↑ receptors in Mф、TC、BC GC、CA↑ binding immunity function↓ ■Change of blood WBC, Plt↑, Blood coagulation ↑, viscosity ↑, ESR↑thrombosis ■Change of kidney and procreation
2．Mechanisms ■ mucosal ischemia ■ increased GC secretion ■ other factors ▲ acidosis ▲ bile acid and lysolecithin This patient with no Helicobacter infection got this ulcer during a period of severe somatic stress due to a heart disease. Stress [Stress ulcer] 1．Concept Stress ulcer is the term given to mucosal damage or lesions of the stomach or duodenum in critically ill or stress- ed otherwise healthy patients.
[Essential hypertension] sympathetic - adrenal medulla excite Emotion Noises Exertion Tension Stressor Hypothalamus Sympathetic impulse↑ Ald ↑ Renin ↑ Angiotensin Ⅱ ↑ Adrenal catecholamines↑ Retention of water and sodium Vasoconstriction Hypertension Elevated arterial pressure Stress