Endocrinology: Adrenal Glands and the Physiological Response to Stress

Question 1

Define the term stress

Answer 1

Stress: the non-specific response of the body to any demand made upon it.
A stress response can be elicited by stimuli (stressors) that disrupt or threaten to disrupt homeostasis.

Question 2

Examples of stressors

Answer 2

• Physical (trauma, surgery, intense temps)
• Chemical (toxins, reduced oxygen supply)
• Physiological (heavy exercise, pain)
• Psychological (anxiety, fear, grief)
• Social (personal conflicts, change in lifestyle)

Question 3

What do stressors cause?

Answer 3

Each stressor can cause specific reactions (e.g., oedema in the case of a broken leg, GIT upset in response to food poisoning).
There will also be non-specific reactions of the whole organism (e.g., increased output of adrenal cortical steroids) which aren’t dependent on the nature of the stimulus.

Question 4

Outline the 3 stages of the General Adaption Syndrome as proposed by Hans Seyle, and the revised concepts

Answer 4

Hans Selye’s General Adaption Syndrome:
1. Alarm reaction: immediate (acute) ‘fight or flight’ response. Higher brain centres informed to send signals in attempt to restore stability (allostasis)
a. Revised: this response varies depending on the biological sex and the nature and severity of the stressor
2. Resistance stage: as stressor persists defence and adaptation strategies are optimised and sustained. If stressor still continues…
3. Exhaustion: adaptive response ceases due to depletion of resources. Long term damage and chronic symptoms – ulcers, depression and other mental illnesses and cardiovascular problems
a. Revised: allostatic overload: stress mediators can have both protective and damaging effects. Thus chronic problems can arise due to the stress mediators themselves rather than the exhaustion of defence mechanisms per se

Question 5

What is the alarm reaction?

Answer 5

fight or flight response

Question 6

Hypothalamic activation of the sympathetic nervous system

Answer 6

• Release of noradrenaline from sympathetic nerve terminals: spill-over into the blood vessels also increases circulating levels of noradrenaline
• Secretion of adrenaline and noradrenaline from the adrenal medulla: ‘sympathetic adrenomedullary system’

Question 7

Hypothalamic-pituitary-adrenal (HPA) axis

Answer 7

• In a stress response, the actions of catecholamines are supported by the glucocorticoids (mainly cortisol)
• Hypophysiotropic hormone corticotropin releasing hormone (CRH) stimulates secretion of adrenocorticotrophic hormone (ACTH) from anterior pituitary
• ACTH acts primarily on zona fasciculate to stimulate the release of glucocorticoids (mainly cortisol)
• Secretion of cortisol is regulated by negative feedback loops involving both CRH and ACTH

Question 8

What hormones are released in response to stress? What tissues do they affect, and what is the effect?

Answer 8

Stress and circadian rhythm trigger CRH release from the hypothalamus, which acts on the anterior pituitary to release ACTH, which triggers release of cortisol from the adrenal cortex.
Cortisol acts on the immune system (suppresses), liver (gluconeogenesis), muscle (protein catabolism) and adipose tissue (lipolysis)

Question 9

Where are adrenal glands located?

Answer 9

Above each kidney

Question 10

Layers of the kidney

Answer 10

• Medulla (inner layer)
  o Central region of adrenal gland is a modified sympathetic ganglion
  o Sympathetic stimulation  in response to acetylcholine (Ach) released from pre-ganglionic sympathetic neurons chromaffin cells release catecholamines (5x more adrenaline than noradrenaline in the body)
  o Catecholamines act on multiple and distinct targets
• Cortex (outer layer): consists of three zones
  o Zona reticularis
  o Zona fasciculata
  o Zona glomerulosa

Question 11

Adrenal hormones

Answer 11

adrenal glands are essential for life, 4 distinct zones but often act as one functional unit to cope with stress
catecholamines (medulla), androgens, glucocorticoids, mineralcorticoids (cortex)

Question 12

What hormones are secreted from the medulla? What are their function?

Answer 12

• Medulla = catecholamines (e.g., adrenaline)
  o Secretion increased by sympathetic nervous system
  o Major function to resist stress

Question 13

What hormones are secreted from the zona reticularis? What are their function?

Answer 13

• Zona reticularis = androgens (e.g., dihydro-epiandosterone – DHEA)
  o Secretion increased by adrenocortico-tropic hormone (ACTH – from the pituitary)
  o Major function is as a ‘male’ sex hormone

Question 14

What hormones are secreted from the zona fasciculate? What are their function?

Answer 14

• Zona fasciculate = glucocorticoids (e.g., cortisol)
  o Secretion increased by: adrenocortico-tropic hormone (ACTH)
  o Major function to help resist stress. Also has a role in metabolism of carbohydrate, protein and fat
  o Cortisol levels have a circadium diurnal rhythm (supports nocturnal fasting – gluconeogenesis, lipolysis), plasma cortisol concentration also increases in response to stressors

Question 15

What hormones are secreted from the zona glomerulosa? What are their functions?

Answer 15

• Zona glomerulosa – mineralocorticoids (e.g., aldosterone)
  o Secretion increased by angiotensin II and plasma [K+]
  o Major function in electrolyte balance and BP

Question 16

Acute stress response

Answer 16

• Increase HR, BP And glycogenolysis
• Dilation of bronchioles
• Blood flow pattern (alertness, decreased digestion and urinary output)
• Increase metabolic rate

Question 17

Longer term stress response

Answer 17

• Increase gluconeogenesis, proteolysis, lipolysis
• Decreased immune system
• Increased retention of sodium and water, increased blood volume and BP
• Steroid hormones synthesised and secreted by adrenal cortex, support actions of catecholamines

Question 18

Actions of cortisol on metabolism

Answer 18

• Primary role is to increase blood glucose at the expense of fats and protein
• Stimulates hepatic gluconeogenesis (amino acids  glucose)
• Inhibits glucose uptake in tissues (except for brain and liver)
• Inhibits protein synthesis and stimulates protein degradation in many tissues (especially muscle), increasing blood amino acids
• Facilitates lipolysis (in adipose tissue) providing free fatty acids as an alternative fuel
• Cortisol is antagonistic to actions of insulin – long term it induces insulin resistance
• It is permissive for the actions of glucagon and growth hormone

Question 19

Actions of cortisol on cardiovascular function

Answer 19

• Cortisol increases the sensitivity of the heart and vasculature to adrenaline, noradrenaline and angiotensin II and thus contributes to the maintenance of cardiac contractility, vascular tone and BP
• Cortisol is permissive for the actions of these hormones; increases synthesis of hormone receptors (e.g., beta-adrenergic receptors), increases synthesis of catecholamines and Na/K ATPase pumps
• Decreases synthesis of NO (vasorelaxant and modulator of vascular permeability)

Question 20

Actions of cortisol on immune response/ inflammation

Answer 20

• Decreases formation of prostaglandins and leukotrienes, decrease vasodilation, decrease capillary permeability, decreased mobility of WBCs
• Inhibit the accumulation of macrophages and neutrophils into areas of inflammation
• Stabilises lysosomal membranes (proteolytic enzymes are confined to lysosomes)
• Decreases production of T cells and B cell proliferation (decreased antibody production)
• Reduces fever by decreasing release of interleukin-1 (IL-1) and other inflammatory cytokines from WBCs
• Therapeutic utility in allergies, autoimmune diseases and transplantation

Question 21

Actions of cortisol on bones, blood, memory

Answer 21

• Inhibits bone formation, stimulates bone resorption
• Alters mood and behaviour
• Affects memory and learning
• Stimulates RBC production
• Stimulates gastric acid secretion

Question 22

Effects of aldosterone

Answer 22

• Increases the reabsorption of sodium whilst increasing the excretion of potassium
• RAAS system: ACE = angiotensin converting enzyme (angiotensin I –> II)