Adrenal glands part 1: stress

Structure
1. Located above the kidneys - however, they are not renal tissue
2. Two distinct parts
  1. The cortex (outside)
    1. Develops from mesodermal tissue
    2. Purely endocrine tissue
    3. Three distinct regions of cells
      1. Zona glomerulosa (outermost)
        Produces mineralocorticoids
      2. Zona fasiculata (middle zone)
        Produces glucocorticoids
      3. Zona reticularis (innermost)
        Produces androgens (DHEA-sulphate)
      4. Foetus adrenal glands feature an extra zone (foetal zone) which is lost at 1yo
    4. Produces steroid hormones only
      1. Once synthesised the adrenals do not store the steroid hormones
  2. The medulla (inside) - composed of chromaffin cells
    1. Develops from neural crest cells which migrate to be within the cortex during foetal development
    2. Effectively modified neural tissue (combination of neural and endocrine tissue)
      1. Receives direct nerve stimulation from the sympathetic NS (the medulla is essentially a type of sympathetic ganglion)
        Directly releases catecholamines into the blood
        Catecholamines are also neurotransmitters (very fast acting and short lived)
        Adrenaline
        Noradrenaline
        Dopamine
        All from the same biosynthetic pathway starting with tyrosine: Tyr -> L-DOPA -> dopamine -> NA -> adrenaline
        Rate limiting step = tyr -> L-DOPA (by tyrosine hydroxylase)
        Conversion of NA to adrenaline is regulated by glucocorticoids
Catecholamines - adrenaline (Short term response to stress)
1. Actions on adrenaline
  1. Metabolic
    1. Mobilises fuel reserves
      1. Icreased glycogenolysis (breakdown of glycogen in liver and muscle)
      2. Decrease insulin secretion
      3. Catabolic
  2. Respiratory
    1. Bronchodilation - increases O2 supply and CO2 removal
  3. Cardiovascular
    1. Increase heart rate and contraction force
      1. Increases cardiac output
    2. Diverts blood away from skin and gut (vasoconstriction) and towards skeletal muscles (vasodilation)
  4. Net effect
    1. Prepares body for activity (by skeletal muscle) - skeletal muscle
    2. Increased availability of nutrients
    3. Reversal of a failing cardiac output
    4. Increased blood supply to muscle (brings nutrients and O2 and removes waste material)
  5. Binds to its target receptor - G protein coupled Adrenoreceptors
    1. Very short action, with a half life of a few seconds n blood
2. Rapid response to stress (fight or flight)
  1. Stress stimulant can be psychological, in response to potential imminent threat or systemic stress (e.g. Trauma -> blood loss)
What is stress?
1. A stimulus that forces a biological component out of its tolerated paramters
2. Any input that causes an imbalance of some form; can be physiological or psychological
Glucocorticoids - cortisol (Long term response to stress)
1. Synthesis of corticosteroids
  1. Cholesterol ester (from cell stores)
    1. Cholesterol (C27)
      1. Progesterone (C21)
        Mineralocorticoids (C21) - aldosterone
        Androgens (C19)
        Glucocorticoids (C21) - cortisol
2. Regulation of cortisol secretion
  1. SUtimuli: exercise, stress, hypoglycaemia, infection, cold, emotions, shock (trauma, burns, haemorrhage)
    1. Hypothalamus: recognises stimuli and secretes CRH (Arg-vasopressin also released)
      1. Ant. pituitary: CRH stimulates ACTH secretion into the portal system
        Adrenal cortex (zona fasiculata): ACTH stimulates the synthesis and release of cortisol
        Cortisol
        -
        -
        Cortisol secretion also occurs in a natural diurnal rhythym (pea of secretion in the morning)
        ACTH
        Synthesised in corticotrophs (ant. Pituitary)
        As large precursor protein (POMC)
        Processing produces ACTH and beta-endorphin (opiate-like activity in the brain)
        ACTH contains sequence of melanocyte stimulating hormone (MSH)
        Interacts with receptors in the zona fasiculata
        Actions of ACTH
        Immediate increase in adrenal blood flow
        Stimulates cortisol and aldosterone
        Maintains expression of the enzymes of steroid biosynthesis
    2. +
3. Action of cortisol
  1. Binds intracellular recptor and causes transcriptn of hormone-asscoaited genes
  2. Part of the normal response to chronic stress
    1. Metabolic
      1. Adispose tissue: stimulates lipolysis
        Excess cortisol causes lipogenesis in face, neck and trunk
      2. Anti-insulin - maintains blood glucose
      3. Muscle: stmulates proteolysis
      4. Liver: stimulates gluconeogenesis
    2. Suppressn of body's defence mechanisms
      1. Anti-inflammatory
      2. Immnosuppressive
      3. Anti-allergic
      4. By inhibiting the enzyme PLA2
        Inhibits prostaglandin/leukotriene production
      5. Reduces pain
        Reducing the sensation of injury severity
        Allows individual to continue despite injury
        Steroid injections used in sports
    3. Mineralocorticoid effects
      1. Increases Na(+) and H2O retention
  3. Deactivated in liver by C17 hydroxylation (increases solubility)
    1. Excretion via kidneys
      1. Used to test for excess cortisol secretion
4. Therapeutic uses of glucocorticoids
  1. Iflammatroy diseases (rheumatoid arthritis, asthma, eczema)
  2. Several synthetic glucocorticoids used (prednisolone, dexamethasone, betamethadone)
  3. Excess use suppresses the hypothalamic-pituitary axis causing cushings
Blood supply
1. Adrenal glands are highly vascular
2. Recieves seven-fold more of the cardiac output than expected for its size
  1. Only the brain has a more tightly reserved blood supply
  2. Why?
    1. For delivery of substrate and oxygen
    2. Effective removal and distribution of hormonal products
    3. Rapid response to physiological stimulus
    4. Reflects importance of the adrenal gland, particularly in the stress response (both physiological and psychological)
3. Blood flow to the adrenals is tightly regulated

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Adrenal glands part 1: stress

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