Hypothalamic Pituitary Adrenal (HPA) axis

• Endocrine Glands Locations 

  
• Hypothalamic Pituitary Adrenal (HPA) axis

  
• •The HPA axis consists of a cascade of endocrine pathways that respond to specific negative feedback loops involving the hypothalamus, anterior pituitary gland, and adrenal gland.
• •A major component of the homeostatic response is the hypothalamic-pituitary-adrenal (HPA) axis, an intricate, yet robust,
• The Hypothalamic-Pituitary-Adrenal Axis (HPA axis)

  •neuroendocrine mechanism

  •It plays an important role the body's response to stress.

  •The pathway of the axis results in the production of cortisol

  •that mediates the effects of stressors by regulating numerous physiological processes, such as metabolism, immune responses, and the autonomic nervous system (ANS).
• What hormones does the HPA axis release?

  •The neuroendocrine adaptation component of the stress response.

  •This response is characterized by hypothalamic release of corticotropin-releasing hormone (CRH).

  
• What hormones does the HPA axis release?

  A) CRH

  B) ACTH

  C) cortisol

  
• The releasing hormones of the HPA

  The Activation of the HPA axis

  •Fight or Flight response

  •body produces stress hormones Cortisol (glucocorticoids)and Catecholamines such as adrenaline and norepinephrine

  •in response to a threat or fear, (either real or perceived)

  
• Endorphins are chemicals (hormones) your body releases when it feels pain or stress. They're released during pleasurable activities such as exercise, massage, eating and sex too.
• Endorphins help relieve pain, reduce stress and improve your sense of well-being. endorphin release occurs after 30 minutes of moderate exercise.
• The pituitary is a small gland that is positioned in the base of the brain.

  The pituitary controls the function of most other endocrine glands, secreting the hormones shown here, which each act on distinct target organ(s) or tissues.

  It integrates signals and releases hormones that regulate the function of other endocrine glands.
• Proopiomelanocortin (POMC) is the pituitary precursor of circulating melanocyte stimulating hormone (α-MSH), adrenocorticotropin hormone (ACTH), and β-endorphin

  
• •Cortisol, a steroid hormone, is synthesized from cholesterol. It is synthesized in the zona fasciculata layer of the adrenal cortex. 
• Cortisol

  •Circadian rhythm- Cortisol levels will be high in the morning and low at night
• Cortisol

  •Sets off a cascade of hormones that results in the release of cortisol
• •Cortisol has many functions in the human body, such as mediating the

  stress response

  regulating metabolism

  the inflammatory response

  immune function
• •The human body is continually responding to internal and external stressors. The sympathetic nervous system (SNS) gets activated. The SNS is responsible for the fight or flight response, which causes a cascade of hormonal and physiological responses.
• •The amygdala is responsible for processing fear, arousal, and emotional stimuli to determine the appropriate response. If necessary, the amygdala sends a stress signal to the hypothalamus.
• Cortisol (glucocorticoid)

  •Synthesised and released by zona fasciculata

         - Contains 17 hydroxylase enzyme
• Cortisol (glucocorticoid)

  •Acts on glucocorticoid receptors (GR) to regulate transcription
• Cortisol (glucocorticoid)

  •3 main effects

  -Metabolic (physiological)

  -Anti-inflammatory (supraphysiological)

  -Immunosuppressive (supraphysiological)
• Metabolic effect - Receptors are present on the following cells and thus exert the effects. - (mobilisation of energy stores in time of stress)

  •Liver

   -Glucose production (gluconeogenesis)

  •Skeletal muscle

   -Increase in protein degradation

  Increased a.a.

  •Adipose tissue

  -Increased lipolysis

  Increased free fatty acids and glycerol for gluconeogenesis

  •Bone

  -Matrix protein breakdown

  Increased a.a. for gluconeogenesis
• Cortisol

  Anti-inflammatory & immunosuppressive effects

  •These effects occur at supraphysiological levels

  •Inhibits all levels of inflammation

  -Acute (rubor, calor, tumor, dolor)

  -Chronic (repair and cell proliferation)

  
• Describe the role of the HPA in control of other glands

  Immune Response

  Glucocorticoids have a number of actions in the immune system.

  •Induce apoptosis of proinflammatory T cells,

  •suppress B cell antibody production

  •reduce neutrophil migration during inflammation

  •Anti-inflammatory
• Describe the role of the HPA in control of other glands - Stress Response

  •The hypothalamus subsequently activates the SNS, and the adrenal glands release a surge of catecholamines, such as epinephrine.

  •This results in effects such as increased heart rate and respiratory rate.

  •As the body continues to perceive the stimuli as a threat, the hypothalamus activates the HPA axis.

  •Cortisol is released from the adrenal cortex and allows the body to continue to stay on high alert. Cortisol’s catabolic mechanisms provide energy to the body
• Describe the role of the HPA in control of other glands

  Cortisol is an essential hormone that affects almost every organ and tissue in your body. It plays many important roles, includes:

  •Regulate body’s stress response

  •Help control body’s use of fats, proteins and carbohydrates, or your metabolism

  •Suppress inflammation 

  •Regulate blood pressure

  •Regulate blood sugar  

  •Help control sleep-wake cycle
• Cortisol levels to maintain steady levels (homeostasis)

  Higher-than-normal or lower-than-normal cortisol levels can be harmful to health
• Effect of HPA activation

  Stress activates a complex network of hormones known as the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models.

  
• Effect of HPA activation

  
• Corticotropin releasing hormone

  A) Corticotrophs

  B) Adrenocorticotrophic hormone

  C) Adrenal cortex

  D) Glucocorticoids (cortisol)

  E) mineralocorticoids

  F) Androgens

  G) stress response

  H) sodium retention

  I) Cushing disease

  J) Adrenal insuffiency

  
• Negative feedback of Hypothalamic-Pituitary-Adrenal Axis

  cortisol acts as a negative feedback loop

  A) CRH

  B) ACTH

  C) cortisol

  
• What causes pituitary disorders?

  •Caused by tumours (benign or malignant);

  •Infarction or genetic disorders

  •Injury and trauma

  •The anterior pituitary is more commonly affected

  •Effects can include hypo- or hyper pituitary problems (although the effect of tumours is usually hypersecretion)

  •May affect specific cell types or all of them
• Cushing's syndrome is a disorder that occurs when your body makes too much of the hormone cortisol over a long period of time.
• cushings syndrome

  A) Hyperglycemia

  B) CNS Irritability

  C) edema

  D) Thin Extermities

  E) thin skin

  F) Purple Striae

  G) Bruises & Petechiae

  H) Amenorrhea, Hirsutism

  I) Osteoporosis

  J) Personality Change

  K) moon face

  L) infection

  M) Gynecomastia

  N) fat deposits

  
• Addison's disease, also known as primary adrenal insufficiency or hypoadrenalism, is a rare disorder of the adrenal glands.

  
• Addison's disease

  A) Weight Loss

  B) Postural Hypotension

  C) Hypoglycemia

  D) Bronze Pigmentation of Skin

  E) Changes In Jistribution of Body Hair

  F) Gl Disturbances

  G) weakness

  
• Addison's disease

  A) Anxiety & low mood

  B) dizzy

  C) nausea and vomiting

  D) salt cravings

  E) stomach pain

  F) pigmentation

  G) weight loss

  H) exhaustion

  I) body aches

  J) muscle cramps

  
• Hyper-pigmentation

  •Lack of secretion of adrenal hormones results in failure of the feedback cycle for Adrenocorticotropin (ACTH)

  •High plasma ACTH level results in hyperpigmentation of the skin especially under nails, buccal mucosa and palm creases

  
• Hyper-pigmentation why?

  •Melanocyte Stimulating Hormone is a by-product of ACTH production