HUMAN physiology

1. HPA axis Activation, Role of
Neuronal Communication in
HPA axis, Disturbances in HPA
axis, Treatment
Presented By-
Manju
Devinder
Kritika
Gaurav

2. HPA AXIS ACTIVATION
Presented by-
Manju

3. HPA axis
• The HPA axis is a term used to represent the
interaction between the hypothalamus, pituitary
gland, and adrenal glands; it plays an important
role in the stress response.
• The HPA axis is responsible for the
neuroendocrine adaptation component of the
stress response.
• The major pathway of the axis results in the
production and secretion of cortisol.

4. HPA axis - Activation
When someone experiences a stressful event
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the amygdala (an area of the brain that contributes to emotional
processing) sends a distress signal to the hypothalamus
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the hypothalamus activates the sympathetic nervous system
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which triggers the fight-or-flight response by sending signals through the
autonomic nerves to the adrenal glands.
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Adrenal glands respond by pumping the hormone epinephrine (also
known as adrenaline) into the bloodstream.
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Epinephrine triggers the release of blood sugar (glucose) and fats from
temporary storage sites in the body.
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As the initial surge of epinephrine subsides, the hypothalamus activates
the second component of the stress response system — known as the
HPA axis.

5. HPA axis - Activation
Hypothalamus releases corticotropin-releasing hormone (CRH) in response to
the stress.
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CRH then acts on the pituitary gland, causing it to release adrenocorticotrophic
hormone (ACTH)
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ACTH which acts on adrenal gland and causing it to release cortisol
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Cortisol then release glucose into the bloodstream in order to facilitate the
"flight or fight" response
• The combined system of CRH-ACTH-cortisol release is referred to as the
hypothalamic-pituitary-adrenal axis (or HPA axis).
• The HPA axis has a central role in regulating many homeostatic systems in the
body, including the metabolic system, cardiovascular system, immune system,
reproductive system and central nervous system.

6. Once a sensory input is received, the stress response may take either or both of two forms,
which act via different systems one acting quickly (within seconds) via sympathetic nervous
impulses and the monoamines adrenaline and noradrenaline, and the second acting more
slowly (within minutes or hours) via corticosteroids.
sympatho-
adrenomedulary
(SAM) axis
hypothalamicpituitary
-adrenal (HPA) axis
CRH

7. ROLE OF NEURONAL COMMUNICATION
IN HPA AXIS
Presented by-
Devinder yadav

8. Initiation of the HPA stress response: The role of neural
communication
8

9. • The first step in the activation of this pathway is the innervation of the
parvocellular neurons(PN) of paraventricular nucleus (PVN) of the
hypothalamus, which is achieved by several processes.
• The primary regulators of the hypothalamusare the amygdala – which
stimulates the PVNand secondly the hippocampus which inhibits it.
• Sensory information from the prefrontal cortex (PFC)is received, processed and
sent from the amygdala, which innervates and stimulates the PVN.
• CRH& AVP(arginine vasopressin) expressing PNin PVNproject to pituitary
where they stimulate ACTHsynthesis and secretion, subsequently triggering
corticosteroid synthesis and release from the adrenalcortex.
• Besides acting in the brain to regulate various behaviors, corticosteroids fine-tune the
amplitude and duration of corticosteroid secretion; they activate their cognate
receptors (GR)in the pituitary, hypothalamus and hippocampus and bed nucleus of
the stria terminalis (BNST)to restrain, and in the amygdala to enhance,
adrenocortical secretion. Monoamines, NE,E,Dopamine & serotonin released from
midbrain nuclei (the locus coeruleus [LC], raphé and ventral tegmental area [VTA] and
substantia nigra [SN], respectively) exert modulatory effects on all brain regions
involved in the control of the HPAaxis.
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10. • There are two types of receptors for cortisol—mineralocorticoid (type-I) and
glucocorticoid (type-II) receptors—both of which participate in the negative-
feedback mechanisms.
• Cortisol binds more strongly (i.e., has higher binding affinity) for the
mineralocorticoid receptors (MRs) >>glucocorticoid receptors (GRs).
• Because of this difference in binding affinity, the MRs help maintain the
relatively low cortisol levels circulating in the blood during the normal daily
(i.e., circadian) rhythm.
• Only when the cortisol concentration is high (e.g., during a stressful situation)
does it bind to the GRs with lower affinity; the resulting activation of the GRs
terminates the stress response.
• This delicate negative feedback control mechanism maintains the secretion of
ACTH and cortisol within a relatively narrow bandwidth. This is an extremely
important homeostatic mechanism because too much or too little exposure to
cortisol can have adverse consequences to health and well being
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11. 11

12. HPA AXIS
DISTURBANCES
Presented by-
kritika

13. Hpaaxis
disturbances
Traumatic
brain injury
Prenatal
stress
Early life
stress
Genetic
background
Current
stress
Neurodege-
nerativedis
ease
Potential causes

14.  Traumatic brain injury (TBI), represented as a
lightning bolt, induces hypopituitarism and results in
suppressed HPA activation in response to a stressor,
represented by dotted black lines.
 Hypopituitarism indicates decreased production of
ACTH, thus there is decreased stimulation of the
adrenal glands and less CORT production.
 Suppressed CORT levels cannot inhibit continued
HPA activation through GR-mediated negative
feedback, as depicted by dashed red lines, resulting
in impaired GR-mediated negative feedback and
perpetuation of the stress response that leads to
longer recovery time after exposure to a stressor.
 Decreased CORT is associated with increased
inflammation, thus injury-induced suppression of
the HPA axis depicts a mechanism through which
post-TBI consequences may occur.
Traumatic brain injury

15. Currentstress
Metabolic syndrome
Insulin resistance
Decreased
immunity
 Obesity
 Cardiovascular disease
 Gastrointestinal problems
High levels of fatty acids,
caused by the effect of
glucocorticoids to mobilize
lipids from fat depots, may
impair insulin’s actions on the
tissues, and this condition is
called adrenal diabetes.
Atrophy of all the lymphoid
tissue, which in turn decreases
the output of both T cells and
antibodies from the lymphoid
tissue. As a result, the level of
immunity for almost all foreign
invaders of the body is
decreased.

16. Prenatal and early life stress
Maternal stress or prenatal
exposure to high levels of
glucocorticoids reduces birth
weight. These offspring are also
at an increased risk of cardio-
metabolic disease, HPA axis
perturbations, and affective
disorders in later life.
Childhood trauma can be
mental or physical. The
response in some people is a
higher basal cortisol level. This
increases the risk of depression,
anxiety, diabetes and PTSD.
Treating depression can reduce
elevated cortisol levels.

17. Genetic factors
Neurodegenerative diseases
Variability in HPA
axis reactivity is
believed to arise from
DNA variations (i.e.,
polymorphisms) in the
genes encoding
neurotransmitters
involved in HPA axis
regulation.
PVN GR deletion—Loss of PVN GR prevents cort-feedback inhibition of the HPA axis and
leads to increased PVN CRH and increased plasma ACTH that further elevate cort levels.
Alzheimer’s disease
• the early accumulation of the
pathological forms of Aβ, and
• Depression as a co-morbid symptom
Are likely to contribute to overall
dysregulation of the HPA-axis.

18. Symptoms of hpa axis disregulation
•Sleep problems
•Thyroid dysfunction
•Blood pressure problems
•Lowered immune system
•Blood sugar problems
•Increase in abdominal fat
•Brain fog
•Fatigue
•Inflammation
•Slow wound healing
•Cravings for salt or salty foods
•Dizziness
•Dry skin
•Low libido
•Poor muscle tone
•Poor circulation
•Anxiety
•Depression

19. TREATMENT OF
DISREGULATED HPA AXIS
Presented by–
Gaurav singh

20. HPA = Make deal with stress
• HPA axis is modulated by variety of brain signal like neurotransmitters
and hormone.
• HPA axis physiologically comes in action during stress response.
• HPA action is tightly regulated to ensure that the body can response
quickly to stressfull events and return to a normal state rapidly.
• Hormones of HPA axis act to maintain homeostasis( by increasing
glucose absorption and increasing blood pressure) in the presense of
stress.

21. Treatments
• Detection of HPA disregulation is mainly done by detecting cortisol
level in serum.
•Lifestyle interventations
• Increase engagement in pleasurable activity.
• Reduce exposure to stressors
• Approppiate level of physical activities.
• Decrease drug and alcohol use.
• Increase social support.

22. Nutrional treatments
• Improve diet
• Increase meal frequency
• Reduce exposure to intollerent/allergic foods
• Increase anti inflammatory and high antioxidant foods
• Nutritional supplementation and herbal remedies.
• By taking some antidepressant drugs like celexa,Lexapro, luvox.
• By taking sublingual pregenolone(used for fatigue and increasing
energy)

24. Suppliments
• Ashwgandha( withania somnifera)- clinicaly shown to reduce stress
and occasional anxiety in adults.
• Vitamin B6( pyridoxine) – play a role in the production of
neurotransmitters such as serotonin, ephinephrine and dopamine.
• Meltonin – secreted from pineal gland research shows that melotonin
supplement promote sleep,improve sleep quality.

25. References
• Textbook of Medical Physiology 11th edition, Arthur C. Guyton, M.D.
• Review- Stress and the HPA Axis: Balancing Homeostasis and Fertility, Dana N. Joseph ID and
Shannon Whirledge
• Stress and the HPA Axis, Role of Glucocorticoids in Alcohol Dependence, Mary Ann C. Stephens,
Ph.D.
• Review article- Is dysregulation of the HPA-axis a core pathophysiology mediating co-morbid
depression in neurodegenerative diseases?, Xin Du and Terence Y. Pang.
• Stress and the HPA Axis Role of Glucocorticoids in Alcohol Dependence ,Alcohol Res. 2012; 34(4):
468483.PMCID: PMC3860380 PMID: 23584113
• Journal of chronic fatigue syndrome. Volume 14:3(pub) 2008
• Intgretive therapeutics- Amy Doyle M.S.CNS.
• Marksteniner, K. Schoenfold ,L.(2013).

26. Thank you