Stress and HPA Axis

8/4/2019 Stress and HPA Axis

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Leonardi AG



Stress & Our Body Homeostasis is the term used which means the

harmonious equilibrium of many physical andemotional factors that permit the body to maintain asteady state of health.



Stress & Our Body Stress is a departure from homeostasis.

The stress response is the body's constant effort toright any physical or mental stressor to maintain

physiological, mental and emotional harmony orhomeostasis. If a person is not able to re-establishhomeostasis the typical consequence is disease.

Activation of the chemical stress pathway (gluco-

corticosteroids) tends to be associated withdepression, whereas the activation of the electricalstress pathway (adrenalin) is more frequently correlated with anxiety.



Stress & Our Body A person's level of stress must reach a certain

threshold before the stress syndrome develops.

The stress syndrome can be produced by physicalillness, chronic emotional upset, work problems,status problems, financial worries, divorce andbereavement.

Memory plays a significant role in the perpetuation of stress and people can worry themselves sick and evento death.







Stress or Anxiety?





Hypothalamic –

Pituitary –

Adrenal (HPA) Axis



HPA Axis –

What is it? The hypothalamic-pituitary-adrenal axis (HPA or

HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis), is a complex set of direct influences and feedback interactions among thehypothalamus (a hollow, funnel-shaped part of thebrain), the pituitary gland (a pea-shaped structurelocated below the hypothalamus), and the adrenal (orsuprarenal) glands (small, conical organs on top of thekidneys).



HPA Axis –

Anatomy The paraventricular nucleus of the hypothalamus, which

contains neuroendocrine neurons that synthesize andsecrete arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). These two peptides regulate:

The anterior lobe of the pituitary gland. In particular,CRH and AVP stimulate the secretion of adrenocorticotropic hormone (ACTH), once known ascorticotropin. ACTH in turn acts on:

The adrenal cortices, which produce glucocorticoidhormones (mainly cortisol in humans) in response tostimulation by ACTH. Glucocorticoids in turn act backon the hypothalamus and pituitary (to suppress CRHand ACTH production) in a negative feedback cycle.





HPA Axis The interactions among these organs constitute the

HPA axis, a major part of the neuroendocrine systemthat controls reactions to stress and regulates many body processes, including digestion, the immunesystem, mood and emotions, sexuality, and energy storage and expenditure.







HPA Axis –

Hormones The main hormones that activate the HPA axis are:

corticotropin-releasing factor (CRF),

arginine vasopressin (AVP) and

adrenocorticotropin hormone (ACTH).The loop is completed by the negative feedback of cortisol on the

hypothalamus and pituitary.

The simultaneous release of cortisol into the circulation has anumber of effects, including elevation of blood glucose for

increased metabolic demand. Cortisol also negatively affects theimmune system and prevents the release of immunotransmitters. Interference from other brain regions (eghippocampus and amygdala) can also modify the HPA axis, ascan neuropeptides and neurotransmitters.

•Primary Care Companion J Clin Psychiatry 2001;3:151–155.•Metabolism 2002;51:5–10.



HPA Axis - Hormones Vasopressin can be thought of as "water conservation

hormone" and is also known as "antidiuretic hormone." Itis released when the body is dehydrated and has potent

water-conserving effects on the kidney. It is also a potent

vasoconstrictor. Cortisol produced in the adrenal cortex will negatively

feedback to inhibit both the hypothalamus and thepituitary gland.

Epinephrine and norepinephrine are produced by the

adrenal medulla through sympathetic stimulation and thelocal effects of cortisol (upregulation enzymes to makeE/NE). E/NE will positively feedback to the pituitary.





HPA Axis - FunctionRelease of CRH from the hypothalamus is influenced by: stress

blood levels of cortisol and

the sleep/wake cycle.

An abnormally flattened circadian cortisol cycle has been

linked with chronic fatigue syndrome (MacHale, 1998),

insomnia (Backhaus, 2004) and

burnout (Pruessner, 1999)



HPA Axis - Function Increased production of cortisol mediates alarm reactions

to stress, facilitating an adaptive phase of a generaladaptation syndrome in which alarm reactions includingthe immune response are suppressed, allowing the body to

attempt countermeasures. Glucocorticoids have many important functions, including

modulation of stress reactions, but in excess they can bedamaging. Atrophy of the hippocampus in humans andanimals exposed to severe stress is believed to be caused by

prolonged exposure to high concentrations of glucocorticoids. Deficiencies of the hippocampus may reduce the memory resources available to help a body formulate appropriate reactions to stress.



Cortisol & Your BodyFunction:

1. Proper glucose metabolism

2. Regulation of blood pressure3. Insulin release for blood sugar maintenance

4.Immune function

5. Inflammatory response



Cortisol & Your BodySmall increases of cortisol have some positive effects:

A quick burst of energy for survival reasons

Heightened memory functions A burst of increased immunity

Lower sensitivity to pain

Helps maintain homeostasis in the body





HPA Axis - Antidepressants The HPA axis is involved in the neurobiology of mood

disorders and functional illnesses, including anxiety disorder, bipolar disorder, insomnia, post-traumatic

stress disorder, ADHD, major depressive disorder,burnout, chronic fatigue syndrome, fibromyalgia,irritable bowel syndrome, and alcoholism. Antidepressants, which are routinely prescribed for

many of these illnesses, serve to regulate HPA axisfunction.



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Stress and HPA Axis