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 Collge de France, Paris), suggests that the equilibrium or steady state of the milieu intrieur 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 Dont 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

Health Normal Adjustment Disturbed Function Disease Death

homeostasis
Prevention

Compensation

normal function maintained without significant cost

Figure 10.11 Progressive stages of homeostasis from adjustment (health) to failure (death)

limit of compensatory processes

Breakdown

repair permanent disability

Treatment

Failure

fatal

Funct ions Stimulat ed

or Inhibit ed by Physical/ Psychological

Table 10.7

Stress

Functi ons St imu lat ed by St ress:

Cardiovascu lar Increased cardiac r at e Elevat ed blood pr essure Increased blood c oagulat ion Redist ribut ion of b lood f rom peripheral ( skin) and int ernal syste ms ( gast ro-int est inal) to heart, skele ta l m uscles, brain Respirat or y Increased respirator y vent ilat ion Met abolic Increased glyc ogen m ob ilizat ion Increased glyc emi a Increased lipo lysis Hormonal Increased CRH, ACT H, Glucoc ort icoids Increased vasopr essin, NGF Increased cat echolamines ( E & N E)

Functi ons Inhibit ed by St ress:

All funct ions not immediat ely necessary for defense and survival are decreased:

Decr eased growth Decr eased app eti t e ( anorexia) Decr eased repr oduct ive funct ion
and s ex dr ive Decr eased circ ulat ion in t issues not invo lved in st ress r espons e Decr eased respons e to p ain Decr eased immune f unct ion Decr eased th ym us s ize Decr eased th ym ic hormones and cyto kines

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: glucocorti coid secret ion epinephrine/ norepinephrine secret ion glucagon secret ion glucagon secretion

Patho physiologic Responses Aft er Stress If physiologic respon ses are insuf f icient and ad apt at ion is inco mplet e, sym pto ms of po or health are regist ered ( e.g. loss of energy wh en f reeing energy f ro m st or age and retu rning to st or age) Examples of consequences: Muscle wast ing Diabet es (T ype 2 ) Ulcers, colit is, diarrh ea Inhibit ion of growth ( in childhood) Ost eoporo sis ( in old age) LHRH, t est ost erone

Table 10.6

Figure 10.10 Some physiologic and pathologic responses to stress in selected organs

Table 10.9
Risk Factor s ( Allost at ic Load) Endangering Heal th and Short ening Life Span Elev at ed Physiologi c Ind ices ( at r isk) Sy st olic b lood pr essur e: 1 4 8 m m Hg Diasto lic blood pressur e: Waist -hip rat ion : 0.9 4

8 3 mm Hg

Tot al cho lest er ol-High Densit y Lipopr ot ein r at io: Tot al glycos yl at ed h em oglobin level: 7.1 % Urinary co rt iso l l ev el: 25. 7 mg/ g cr eat inine Urinary epinep hrine level: 5 m g/ g creat inine Urinary no rep ineph rine level:

5.9

48

mg/g creat inine

DHEA ( Dehyd roepiandro st eron e) le vel: 2.5 mol/ L

Low er ed Ph ys iologic Ind ices ( at r isk) HDL cho lest erol level: 1.4 5 mm ol/ 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 crbrale et mmoire

Moderate stress of short duration Incidence of Cardiovascular Diseases Allostatic Load weak or absent Allostatic Load progressive & severe Severe and prolonged stress

Moderate stress of short duration Allostatic Load weak or absent stimulate: vigilance attention memory storage Cognitive Alterations

Excessive stress of long duration Allostatic Load progressive & severe reduce: number of neurons neurotransmitter balance memory storage

Moderate & Regular Physical Exercise Allostatic Load weak or absent

Excessive & prolonged physical exercise or lack of regular exercise Allostatic Load Progressive & increasing

Cardiovascular function Energy mobilization Immune efficacy Cognition & vigilance Mass & strength of muscle & bone Physical Exercise

Atherosclerosis Obesity Incidence of cardiovascular diseases Immunosuppression Depression, anxiety, memory loss 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