8/12/2019 Homestasis and allostasis

1/17

Homeostasis&

Allostasis

Vitruvian Man

Leonardo Da Vinci

8/12/2019 Homestasis and allostasis

2/17

Stress:In biology, any change (stressor) in the

environment that may tend to alter anexisting 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 intrieuris to remain constant to allow for optimal function and survival.

8/12/2019 Homestasis and allostasis

3/17

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, StressRelated Diseases, and Coping, W.H. Freeman and Co., New York, 1998

8/12/2019 Homestasis and allostasis

4/17

HomeostasisFrom 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)

8/12/2019 Homestasis and allostasis

5/17

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 theGeneral Adaptation Syndrome and the Diseases of Adaptation, Acta Inc.,

Montreal, 1950.

8/12/2019 Homestasis and allostasis

6/17

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.

8/12/2019 Homestasis and allostasis

7/17

Homeodynamics

A constantenvironment obtained through a series ofdynamic 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 -- adeclining ability to adapt and/or an increased pathology

and disease

*Prof. T. Seeman, Geriatrics, UCLA (UCB alumna)

8/12/2019 Homestasis and allostasis

8/17

Functional Competence or Impairment

HealthDisturbedFunction Disease Death

Failu

re

Breakdown

Compensation

Normal

Adjustment

homeostasis

normal functionmaintained without

significant cost

limit of compensatory processes

fatal

Pre

vention

Treatment

permanent disability

repair

Figure 10.11

Progressivestages of

homeostasis

from

adjustment

(health) to

failure (death)

10

8/12/2019 Homestasis and allostasis

9/17

Funct ions Stimulated or Inhibit ed by Physical/ Psychological Stress

Functi ons St imulat ed by St ress:

Cardiovascular

Increased cardiac r ate Elevat ed blood pr essure Increased blood c oagulat ion

Redist ribut ion of b lood f romperipheral ( skin) and internal

syste ms (gast ro-int est inal) to

heart, skeleta l muscles, brain

Respiratory Increased respirator y vent ilat ion

Met abolic

Increased glycogen mobilizat ion

Increased glycemia Increased lipolysis

Hormonal

Increased CRH, ACT H,

Glucoc ort icoids Increased vasopressin, NGF Increased catecholamines (E & NE)

Functi ons Inhibit ed by St ress:

All funct ions not immediately

necessary for defense and

survival are decreased:

Decreased growth Decreased appeti t e ( anorexia) Decreased reproduct ive funct ion

and s ex dr ive

Decreased circulat ion in t issues not

invo lved in st ress r esponse Decreased response to p ain Decreased immune f unct ion Decreased th ymus s ize Decreased th ymic hormones and

cyto kines

Table 10.7

8/12/2019 Homestasis and allostasis

10/17

Table 10.6

Pathophysiologic Responses During Stress

During Stress

Energy st orage ceases because:

sympathetic activity(i.e. increased vigilance/ arousal)

parasympathet ic act ivityinsulin secret ion

Access t o energy storage is facilitat ed

and energy storage steps are reversed because of:

glucocorticoid secret ionepinephrine/ norepinephrine secret ion

glucagon secret ion glucagon secretion

8/12/2019 Homestasis and allostasis

11/17

Patho physiologic Responses After StressIf physiologic respon ses are insuf f icient and ad apt at ion is inco mplet e,

sym pto ms of poor health are regist ered (e.g. loss of energy when

f reeing energy f rom st orage and retu rning to st orage)

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

8/12/2019 Homestasis and allostasis

12/17

Figure 10.10

Some

physiologicand pathologic

responses tostress in

selected organs

8/12/2019 Homestasis and allostasis

13/17

Risk Factor s ( Allostat ic Load)

Endangering Health and Short ening Life Span

Elevat ed Physiologic Ind ices (at r isk)

Syst olic b lood pr essur e: 14 8 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 creat inine Urinary epinephrine level: 5 m g/ g creat inine Urinary no repinephrine level: 48 mg/g creat inine

Low ered Ph ys iologic Ind ices (at r isk)

HDL cho lest erol level: 1.4 5 mm ol/ L DHEA ( Dehyd roepiandro st eron e) le vel: 2.5 mol/ L

Table 10.9

8/12/2019 Homestasis and allostasis

14/17

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 gatesof 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.

8/12/2019 Homestasis and allostasis

15/17

Moderate stressof short duration

Allostatic Loadweak or absent

Severe andprolonged stress

Allostatic Loadprogressive & severe

Incidence of Cardio- vascular Diseases

Moderate stressof short duration

Excessive stressof long duration

vigilance

attention

memory

storage

number of neurons

neurotransmitter balance

memory

storage

stimulate: reduce:

Cognitive Alterations

Figure IV.3 Protection contre Pathologie: fonction crbrale et mmoir

Allostatic Load

weak or absent

Allostatic Load

progressive & severe

8/12/2019 Homestasis and allostasis

16/17

Moderate & RegularPhysical Exercise

Allostatic Loadweak or absent

Allostatic LoadProgressive & increasing

Excessive & prolonged

physical exercise or lackof regular exercise

Cardiovascular function

Energy

mobilizationImmune efficacy

Cognition & vigilance

Mass & strength

of muscle & bone

Atherosclerosis

Obesity

Incidence of cardio-

vascular diseases

Immunosuppression

Depression, anxiety, memory loss

Bone fragility

Muscle atrophy & weakness

Physical Exercise

8/12/2019 Homestasis and allostasis

17/17

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