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BIOLOGY OF STRESS. Stress is an enescapable fact of life. What is STRESS ?. Stress is a state resulting from events (stimuli) of external or internal oringin, real or imagined that tend to affecct the homeostatic state. Stressors.
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Stress is an enescapable factof life What is STRESS ? Stress is a state resulting from events (stimuli) of external or internal oringin, real or imagined that tend to affecct the homeostatic state.
Stressors Stimuli (events) that challenge homeostasis. Stress response. Body’s response to a stressor.
HISTORY Selye (1937) pioneered the field “Stress research” Nonspecific,stereotypic resoponses to adverse conditions. General adaptation syndrome.
Christian (1950s) Relationship between stressors & population density. Association between increased population density and activation of the pituitary-adrenal axis . Since then, growing awareness of influence of stress on physiology and behavior.
OBJECTIVE To alleviate negative health implications of stress. Stress : Acute or Chronic.
Physical Psychological Failure to achive goals. Events having direct physical threat. Dath of loved ones, Job demands, interpersonal problems, financial problems, etc. Cold, heat,infection, toxic substance, etc.
Sub-Types Social : Financial problems, dominance , hierarchy insult, loss of self esteem. Occupational : Work place problems, insufficient pay, uneasy relationship with coworkers. Life stressors: Parking place problems, running late, dealing Spouse/children, divorce, isolation. Philosophical/ Spiritual : Meaning and purpose of life, belief in higher power, loss of values. Physical and Psychological stressors are often intertwined.
METABOLIC Digestion is inhibited (Enzyme action inhibited) CARDIOVASCULAR REPRODUCTIVE GROWTH AND REPAIR IMMUNE STRESS RESPONSE GASTROINTESTINAL METABOLIC CARDIOVASCULARGASTRO INTESTINAL GROWTH & REPAIR IMMUNE REPRODUCTIVE Triglycerides, glycogen and proteins are degraded and converted in to carbohydrates to provide immediate energy. Increased heart rate and blood pressure to speed delivery of glucose and oxygen to tissues that need it Digestion is inhibited (Enzyme action inhibited) Inhibition of growth hormone and other anabolic processes Inhibition of reproductive functions Depletion of lymphocytes (suppression of immune response)
How these changes are induced ? CNS : Activation of Sympathetic nervous system, catecholamines excite cells/tissues. (Sympatho-adrenal system) Endocrine: CRH, ACTH, Glucocorticoids, Adrenalin, vassopressin, endorphins.
Stress Brain areas PVN Preganglionic Fibers B-endorphin CRH/AVP Behavior Pituitary ACTH Adrenal Medulla Adrenal cortex Glucocorticoids Adrenalin Peripheral sites
What is the role of -endorphin? A natural pain killer. Inhibits synaptic transmission to prevent pain perception. In the absence of -endorphin stress response exaggerated.
GASTROINTESTINAL RESPONSES • Suppression of appetite- CRH mediated. • Inhibition of GI tract enzymes, hormone and peristalsis : SNS mediated. • Dry mouth : SNS • Promotes formation of peptic ulcers.
Gastric ulcers: Several theories regarding causative facotors 1. Acid rebound 2. Helicobacter pylori Infection coupled with acid secretion. 3.Dramatic decrease in blood flow: strokes due to oxygen deficiency, dead tissue building block for ulcers. 4.Decreased Immunity : Increase in H. pylori infection. 5. Insufficient prostaglandins : No healing of ware & tare.
Metabloic responsesDERRANGEMENT OF HORMONE DEPENDENT INTERMEDIARY METABOLISM. Proteolysis Lipolysis Glycogenolysis (adrenalin) Aminoacids Glycerol+FFA (adrenalin) Gluconeogensis GLUCOSE
The gluconeogenic pathway Alanine Lactate Pyruvate Pyruvate carboxylase Oxaloacetate Phosphoenol pyruvate carboxikinase Phosphoenol pyruvate Glycerol Trisoe - PO4 Aldolase Fructose - 1,6-DI PO4 Fructose - 6 PO4 Fructose-1,6-diphosphatase Glucose - 6-PO4 Glucose-6-phosphatase Glucose
RESULT Increased blood glucose level IMPLICATION Acute effect: Increased availability of fuel for energy. Chronic effect: Diabetes, muscle atrophy.
Our study: Chronic stress in rats • Increase in gluconeogenesis as revealed by increased PEPCK and G6Pase activity, increased pyruvate and lactate concentration. • Decrease in glycolysis, as revealed by decrease in activity of pyruvate kinase. • Decrease in flow of substrate to Kreb’s cycle. • Overall result : Hyperglycemia
CARDIOVASCULAR RESPONSES Acute stress: Increased heart rate, cardiac out put & blood volume. (catecholamines) Logic: To pump energy rich blood to bring body out of harm /potential danger. Chronic stress: Hypertension Atherosclerosis Heart attacks
Growth/Repair Normal physiology Stress GRH CRH (Somatostin) Inhibition Growth hormone ACTH Inhibition Growth factors Glucocorticoids Cellular effects Chronic effects: Childhood - Dwarfism Adults - Loss of bone density & muscle.
Immuno responses:Suppresion Students have more illness and increased BP during examination period. Stress in workplace increases suceptibility to illness. People going through divorce or people with few social relationships have increased incidence & duration of infectious diseases as well as shorter life expectancy.
HOW ? Glucocorticoids adversely affect immune system by: Degrading lymphocytes. Inhibiting production of antibodies. Preventing formation of new lymphocytes. • Inhibiting chemical messengers - interlukins & interferons.
Molecular mechanism Cytoplasmic Membrane
STRESS AND ANTIOXIDANT STATUS • ROS are produced due to the biological reactions and Antioxidant system scavenge these and prevent oxidative damage to various cellular components. Stressful conditions lead to more formation of ROS which overpower the antioxidant system and lead to damage of lipids ,proteins and nucleic acids.
Reproductive responces Serious negative impact on sex and reproduction. • PHYSICAL DANGER such as military threat, periods of prolonged exertion and sleep deprivation lower testosterone levels. 2.PSYCOLOGICAL STRESS such as constant vigilance reduces testosterone levels.
3. PHYSICAL EXERTION and severe EMOTIONAL STRESS interferes with reproductive cycle in women. 4. Severe stress may lead to a syndrome referred to as functional hypothalamic amenorrhea or functional hypothalamic chronic anovulation, Characterized by ovarian quiescence, amenorrhea and infertility in women.
Stress and male infertility • Many studies have shown higher stress levels among infertile men than fertile controls. In men, emotional and physical stressors contribute to male infertility.
Infertility is due to decreased sperm production, sperm count and motility and testicular shrinkange and the condition is accompanied by high levles of adrenal steroids.
Our studies : • Neonatal stress or stress during pre-pubertal period reduces the follicular reserve and causes early reproductive senescence in rats. Far reaching implications in commercially important species as stress reduction follicular reserve lead to decrease in reproductive potential.
Studies in lower vertebrates: • Studies in fish, amphibians, reptiles and birds reveal inhibition of gonadal functions due to environmental and • social stressors. • Our studies in lizards, reveal stress inducedk
HOW ? Normal Stress GnRH Inhibits CRH B-endorphin FSH/LH ACTH Gonads Adrenal cortex (Gametogenesis & hormone production) Glucocorticoids
WHY ? To avoid investment of energy under unfavorable conditions.
To sum up the effects Due to prolonged chronic stress the individual turns into a diabetic, hypertensive, atherosclerotic, protein deficient & immunologically compromised state.
Whether stress response is undesirable ? If so why is it retained during evolution of human species ?
However, the acute stress responses mobilize, more oxygen and glucose to the organs which need them most and enable to survive or escape dangerous/life threatening situations. Hence stress response has survival value.
Stress and Ageing Psychological stress is linked to oxidative damage of DNA and other cellular components Experimental Evidence Study of Blackburn & her colleagues Selected 58, normal, healthy mothers 19 Controls : Problem free children 39 Stress group: Chronically ill child Blood samples were drawn and 3 parameters of cellular ageing analyzed:
1. Telomere length : Women with perceived stress had shorter telomeres, extent of shortening was equal to 10 years of additional aging 2. Telomerase activity : About 50% less in stressed women 3. Oxidative stress : Higher in stressed women
Stress Management 1. Proper diet, exercise & relaxation. Avoid hurry, Worry & curry. 2. Yoga: Flexing & bending of body parts along with controlled breathing does not cause fatigue like aerobic exercise. 3. Pranayama: Regulated deep breathing, rich oxygen supply - relieves of stress.
4. Meditation: Relaxation of body & mind : reduces excitation. 5. Accept reality, accept you can not change. 6. Avoid personal confrontation. 7. Humor: Takes sting out of stress.
8.Laughter: Physical & emotional effects : Muscular activity burns calories, reduces stress hormone levels, increases endorphins, boosts immunity. 9. Music : Soothing effect. 10. Sports, Games, Hobby.