HPA and Stress

MCB 135K

Lecture 39

kidney

adrenal

Anterior pituitary

Posterior pituitary

hypothalamus

glucocorticoids

Figure 10.2

Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and hormones

Reminder

CRH: corticotropic releasing hormone

ACTH: adrenocorticotropic

hormone

Figure 10.6

Cortisol

Epinephrine Norepinephrine

Actions Of Glucocorticoids Actions of Adrenaline/Noradrenaline

Target

cellular

Figure 10.5 Schematic diagram of corticosteroid action in target cell

•Gene expression & new protein synthesis

•Relatively long latency of onset

•Medium & long term cell program

•Organization of cell networks for complex functions

•Activation/repression of pre-existing cell proteins

•Rapid onset of action

•Rapid adaptation to changes in the milieu

•Dynamic modifications of long term cell programs

Cortisol, norepinephrine, and epinephrine

STRESS

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.

Exposure to stress generates:

Specific responses: varying with the stimulus and generating different responses with each stimulus

Non-Specific responses:always the same, regardless of the stimulus and mediated through stimulation of

neural, endocrine & immune axes

Some Characteristics of Stress

Stress induces defense mechanisms for maintenance of homeostasis in response to environmental challenges

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

STRESS

HYPOTHALAMUS

HYPOPHYSIS

ADRENAL CORTEX

Increased production of gluccocorticoids &inhibition of gonadal hormones

GHRH GH

GnRH Gn

somatotropichormone

gonadotropic hormones

GROWTH INHIBITION

INHIBITION OF MALE SEX

ORGANS

IRREGULARITIES OF

MENSTRUAL CYCLE

FSH, LH

Releasing Hormone

CRH(cortico-releasinghormone)

ACTH(adreno cortico-tropic hormone)

– –

–

–

–

–

Shift in HPA secretory priorities during stress

Functions Stimulated or Inhibited by Physical/Psychological Stress

Functions Stimulated by Stress:

Cardiovascular Increased cardiac rate Elevated blood pressure Increased blood coagulation Redistribution of blood from

peripheral (skin) and internalsystems (gastro-intestinal) toheart, skeletal muscles, brain

Respiratory Increased respiratory ventilation

Metabolic Increased glycogen mobilization Increased glycemia Increased lipolysis

Hormonal Increased CRH, ACTH,

Glucocorticoids Increased vasopressin, NGF Increased catecholamines (E & NE)

Functions Inhibited by Stress:

All functions not immediatelynecessary for defense andsurvival are decreased:

Decreased growth Decreased appetite (anorexia) Decreased reproductive function

and sex drive Decreased circulation in tissues not

involved in stress response Decreased response to pain Decreased immune function Decreased thymus size Decreased thymic hormones and

cytokines

Table 10.7

Pathophysiologic Responses During and After Stress

During Stress

Energy storage ceases because:Sympathetic activity

Parasympathetic activityInsulin secretion

Access to energy storage is facilitated & energy storage steps are reversed:

glucocorticoid secretionEpinephrine/norepinephrine secretion

Glucagon secretion

After Stress

If physiologic responses are insufficient and adaptation is incomplete, symptoms of poor health are registered (e.g. loss of energy when freeing energy from storage

and returning to storage)

Examples of consequences:

Muscle wasting, Diabetes (Type 2), ulcers, colitis, diarrhea

Inhibition of growth (in childhood), Osteoporosis (in old age)

LHRH, testosterone

Figure 10.10Some

physiologic and pathologic

responses to stress in

selected organs

Elevated Physiologic Indices (at risk)•Systolic blood pressure: ≥148 mmHg•Diastolic blood pressure: ≥ 83 mmHg

•Waist-hip ratio: ≥ 0.94•Total cholesterol-High Density

Lipoprotein ration: ≥ 5.9•Total glycosylated hemoglobin level: ≥

7.1%•Urinary cortisol level: ≥ 25.7mg/g

creatinine•Urinary epinephrine level: ≥ 5 mg/g

creatinine•Urinary norepinephrine level: ≥

48mg/g creatinineLowered Physiologic Indices (at risk)

•HDL cholesterol level: ≤ 1.45 mmol/L

•DHEA (Dehydroepiandrosterone) level: ≤ 2.5 micro mol/L

Risk Factors (Allostatic Load) Endangering Health & Shortening Life Span

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 10.11 Progressive

stages of homeostasis

from adjustment (health) to

failure (death)