Homeostasis & Allostasis Vitruvian Man Leonardo Da Vinci Stress: In biology, any change (stressor) in the environment that may tend to alter an existing equilibrium and trigger counteracting responses at molecular, cellular, and systemic levels to preserve/reestablish such an equilibrium and insure adaptation. Claude Bernard, (1813-1878, Prof. of Physiology at the Collège de France, Paris), suggests that the equilibrium or steady state of the “milieu intérieur” is to remain constant to allow for optimal function and survival. Types of Stress • Examples of Physical/Chemical Stress – High/low extreme temperatures – Physical injury – Hemorrhage – Hypoglycemia, etc. • Examples of Psychological/Emotional Stress – Fear – Cognition of danger – Memories – Sorrow or joy – Hate or love, etc. Sapolsky, R.M., Why Zebras Don’t Get Ulcers: An Updated Guide to Stress, Stress Related Diseases, and Coping, W.H. Freeman and Co., New York, 1998 Homeostasis From Walter B. Cannon (1871-1945) Wisdom of the Body, 1932 From Greek: homeo “the same” stasis “state” Indicates that for optimal function of the organism, a steady state (or equilibrium) must be achieved This “constancy” of the internal environment allows survival despite continuing changes in the external environment (stress) From left to right: H. Selye, C. Fortier, P.S. Timiras H. Selye (1907-1982, Director of the Institute of Experimental Medicine and Surgery, Univesity of Montreal, Que. Canada) focuses on the HPA axis as the main regulator of non-specific stress responses. His major book is: The Physiology and Pathology of Stress: A Treatise Based on the Concept of the General Adaptation Syndrome and the Diseases of Adaptation, Acta Inc., Montreal, 1950. From left to right: F. Skelton, R. Guillemin (Nobel Prize 1977), Prof. C. LeBlond, P.S. Timiras The Nobel Prize was awarded for the identification of the hypothalamic hypophysiotropic hormones. Homeodynamics A constant environment obtained through a series of dynamic adjustments This continual need for adjustment is implicated in the term “allostasis” (From Greek allo “different” stasis “state”) Emphasizes the dynamism of adaptive responses to stress This adaptation to stress is often achieved with a price -- a declining ability to adapt and/or an increased pathology and disease *Prof. T. Seeman, Geriatrics, UCLA (UCB alumna) Functional Competence or Impairment Disturbed Health Function Disease Death Figure 10.11 Progressive t stages of homeostasis Prevention homeostasis Normal Adjustmen from adjustment normal function (health) to maintained without failure (death) significant cost Compensation limit of compensatory processes Tr repair e a t m e Breakdown permanent disability n t re u fatal Fail Table 10.7 Funct ions Stimulat ed or Inhibit ed by Physical/ Psychological Stress Functi ons Stimulat ed by St ress: Functi ons Inhibit ed by Stress: Cardiovascular All funct ions not immediat ely • Increased cardiac rate necessary for defense and • Elevated blood pr essure survival are decreased: • Increased blood c oagulat ion • Redist ribut ion of b lood from • Decreased growth peripheral (skin) and int ernal • Decreased appeti t e ( anorexia) syste ms (gast ro-int est inal) to • Decreased repr oduct ive funct ion heart, skeleta l m uscles, brain and s ex drive • Decreased circulat ion in t issues not Respirat ory invo lved in st ress r esponse • Increased respirator y vent ilat ion • Decreased response to p ain • Decreased immune funct ion Met abolic • Decreased th ym us s ize • Increased glycogen mobilizat ion • Decreased th ym ic hormones and • Increased glycemia cyto kines • Increased lipolysis Hormon al • Increased CRH, ACTH, Glu coc o rt ic o id s • Increased vasopr essin, NGF • Increased catecholamines (E & NE) Table 10.6 Pathophysiologic Responses During Stress During Stress Energy st orage ceases because: ↑ sympathetic act ivit y (i.e. increased vigilance/ arousal) ↓ parasympathet ic act ivity ↓ insulin secret ion Access t o energy stor age is facilitat ed and energy sto rage st eps are reversed because of: ↑ glucocorticoid secret ion ↑ epinephrine/ norepinephrine secret ion glucagon secret ion glucagon secretion Table 10.6 Patho physiologic Responses Aft er Stress If physiologic respon ses are insuff icient and ad apt at ion is inco mplet e, sympto ms of poor health are regist ered (e.g. loss of energy when freeing energy from st orage and retu rning to st orage) Examples of consequences: Muscle wast ing Diabet es (T ype 2) Ulcers, colitis, diarrhea Inhibit ion of growth ( in childhood) Ost eoporo sis ( in old age) ↓ LHRH, ↓ testosterone Figure 10.10 Some physiologic and pathologic responses to stress in selected organs Table 10.9 Risk Factors (Allostatic Load) Endangering Health and Short ening Life Span Elevat ed Physiologic Ind ices (at r isk) • Syst olic b lood pr essur e: ≥ 148 m m Hg • Diasto lic blood pressure: ≥ 83 mm Hg • Waist -hip rat ion: ≥ 0.9 4 • Tot al cho lest erol-High Densit y Lipopr ot ein r at io: ≥ 5.9 • Tot al glycosylat ed h em oglobin level: ≥ 7.1 % • Urinary co rt isol l evel: ≥ 25. 7 mg/ g cr eat inine • Urinary epinephrine level: ≥ 5 m g/ g creat inine • Urinary no repinephrine level: ≥ 48 mg/g creat inine Low er ed Ph ys iologic Ind ices ( at r isk) • HDL cho lest erol level: ≤ 1.4 5 mm ol/ L • DHEA ( Dehydroepiandrost eron e) level: ≤ 2.5 µmol/ L Janus is the Roman God of gates and doors, of beginnings and endings and, hence, is represented by a double faced head; generally placed on the gates of the city,the menacing face looking towards the outside of the city ready to defend it against any attackers, the benevolent face turned towards the city is a protector and promoter of prosperity and good health. Figure IV.3 Protection contre Pathologie: fonction cérébrale et mémoire Moderate stress Severe and of short duration prolonged stress Incidence of Cardio- vascular Diseases Allostatic Load Allostatic Load weak or absent progressive & severe Moderate stress Excessive stress of short duration of long duration Allostatic Load Allostatic Load weak or absent progressive & severe stimulate: reduce: vigilance number of neurons neurotransmitter attention Cognitive Alterations balance memory memory storage storage Excessive & prolonged Moderate & Regular physical exercise or lack Physical Exercise of regular exercise Allostatic Load Allostatic Load weak or absent Progressive & increasing Cardiovascular Atherosclerosis function Obesity Energy Physical Exercise Incidence of cardio- mobilization vascular diseases Immune efficacy Immunosuppression Cognition & vigilance Depression, anxiety, Mass & strength memory loss of muscle & bone Bone fragility Muscle atrophy & weakness Hormesis • A new term, from the Greek “I excite.” – Excitation induced by physical or psychological stress • Stimulation of any system by a stimulus of relatively moderate intensity & short duration – In contrast to a strong stimulus of long duration that will induce destabilization • Recently, several lines of research indicate that hormesis may promote longevity.