HPA axis

Clinic

Hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components:

• Hypothalamus
• Pituitary gland
• Adrenal

Central control

HPA axis is a major neuroendocrine system that controls reactions to stress and regulates many body processes, including

• Digestion
• Immune system
• Mood and emotions
• Sexuality
• Energy storage and expenditure.

HPA Symptoms

• Sleep problems: Insomnia, Difficulty getting up in the morning
• Thyroid dysfunction
• Blood pressure problems/ Poor circulation
• Lowered immune system
• Blood sugar problems
• Increase in abdominal fat
• Brain fog/ Fatigue (esp during the morning and mid-afternoon)

General Adaptation Syndrome

HPA is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate General Adaptation Syndrome (GAS).

• While steroid hormones are produced mainly in vertebrates, the physiological role of HPA axis and corticosteroids in stress response is so fundamental that analogous systems can be found in invertebrates and monocellular organisms as well.

3 major endocrine system controls

HPA axis is one of four axis through which Hypothalamus–pituitary control endocrine system.

1. HPA axis: Pigmentation, Chronic fatigue syndrome, Insomnia , Hypotention (CMV)
2. Hypothalamic–pituitary–gonadal axis (HPG) (Infertility,
3. Hypothalamic–pituitary–thyroid axis (HPT) (Hypothroidism

Hypothalamic–neurohypophyseal system is another circuit between Hypothalamus ans pituitary

Anatomy

The key element of HPA axis is Paraventricular nucleus of the hypothalamus, which secrete vasopressin and CRH. These two peptides regulate:

• Anterior lobe of pituitary by stimulating secretion of ACTH which in turn acts on:
• Adrenal cortex produces cortisol which in turn act back on Hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.

Function

• Release of CRH from hypothalamus is influenced by
  • Stress
  • Physical activity
  • Illness
  • Blood levels of cortisol
  • Circadian rhythm

• In healthy individuals, cortisol rises rapidly after wakening, reaching a peak within 30–45 minutes. It then gradually falls over the day, rising again in late afternoon. Cortisol levels then fall in late evening, reaching a trough during the middle of the night.
• This corresponds to the rest-activity cycle of the organism.
• An abnormally flattened circadian cortisol cycle has been linked with chronic fatigue syndrome, insomnia and burnout.

Homeostasis

HPA axis has a central role in regulating many homeostatic systems including

• Metabolic system
• Cardiovascular system
• Immune system
• Reproductive system
• CNS

Psychosocial

• HPA axis integrates physical and psychosocial influences in order to allow an organism to adapt effectively to its environment, use resources, and optimize survival.

• Anatomical connections between brain areas such as the amygdala, hippocampus, PFC and hypothalamus facilitate activation of the HPA axis.
• Sensory information arriving at the lateral aspect of the amygdala is processed and conveyed to the amygdala's central nucleus, which then projects out to several parts of the brain involved in responses to fear.
• At the hypothalamus, fear-signaling impulses activate both the sympathetic nervous system and the modulating systems of HPA axis.
• Increased production of cortisol during stress results in an increased availability of glucose in order to facilitate fighting or fleeing.
• As well as directly increasing glucose availability, cortisol also suppresses the highly demanding metabolic processes of the immune system, resulting in further availability of glucose.
• Glucocorticoids have many important functions, including modulation of stress reactions, but in excess they can be damaging. Atrophy of the hippocampus in humans and animals 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.

Immune system

• There is bi-directional communication and feedback between the HPA axis and the immune system.
  • A number of cytokines can activate HPA axis, although IL-1 is the most potent.
  • HPA axis in turn modulates the immune response, with high levels of cortisol resulting in a suppression of immune and inflammatory reactions. This helps to protect the organism from a lethal overactivation of the immune system, and minimizes tissue damage from inflammation.

• CNS regulates the immune system through neuroendocrine pathways, such as the HPA axis.
• Deficiencies in the HPA axis may play a role in allergies and inflammatory/ autoimmune diseases, such as RA and MS.

Stress

• Stress activates the HPA-axis and thereby enhances the secretion of glucocorticoids from the adrenals.

• HPA axis is involved in the neurobiology of mood disorders and functional illnesses, including anxiety disorder, bipolar disorder, insomnia, PTSD, borderline personality disorder, ADHD, MDD, burnout, CFS, fibromyalgia, IBS, and alcoholism.
• Antidepressants serve to regulate HPA axis function.

Stress and development

• There is evidence that prenatal stress can influence HPA regulation.
• Prolonged maternal stress during gestation is associated with mild impairment of intellectual activity and language development in their children, and with behaviour disorders such as attention deficits, schizophrenia, anxiety and depression
• Self-reported maternal stress is associated with a higher irritability, emotional and attentional problems.
• Exposure to mild or moderate stressors early in life has been shown to enhance HPA regulation and promote a lifelong resilience to stress.
• In contrast, early-life exposure to extreme or prolonged stress can induce a hyper-reactive HPA axis and may contribute to lifelong vulnerability to stress.

Conditions:

• Addison's disease
• Adrenal insufficiency
• Cushing disease