Adrenal glands part 1: stress

Adrenal glands part 1: stress

1. Structure

   • Located above the kidneys - however, they are not renal tissue
   • Two distinct parts
     • The cortex (outside)
       • Develops from mesodermal tissue
       • Purely endocrine tissue
       • Three distinct regions of cells
         • Zona glomerulosa (outermost)
           • Produces mineralocorticoids
         • Zona fasiculata (middle zone)
           • Produces glucocorticoids
         • Zona reticularis (innermost)
           • Produces androgens (DHEA-sulphate)
         • Foetus adrenal glands feature an extra zone (foetal zone) which is lost at 1yo
       • Produces steroid hormones only
         • Once synthesised the adrenals do not store the steroid hormones
     • The medulla (inside) - composed of chromaffin cells
       • Develops from neural crest cells which migrate to be within the cortex during foetal development
       • Effectively modified neural tissue (combination of neural and endocrine tissue)
         • 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

2. Catecholamines - adrenaline (Short term response to stress)

   • Actions on adrenaline
     • Metabolic
       • Mobilises fuel reserves
         • Icreased glycogenolysis (breakdown of glycogen in liver and muscle)
         • Decrease insulin secretion
         • Catabolic
     • Respiratory
       • Bronchodilation - increases O2 supply and CO2 removal
     • Cardiovascular
       • Increase heart rate and contraction force
         • Increases cardiac output
       • Diverts blood away from skin and gut (vasoconstriction) and towards skeletal muscles (vasodilation)
     • Net effect
       • Prepares body for activity (by skeletal muscle) - skeletal muscle
       • Increased availability of nutrients
       • Reversal of a failing cardiac output
       • Increased blood supply to muscle (brings nutrients and O2 and removes waste material)
     • Binds to its target receptor - G protein coupled Adrenoreceptors
       • Very short action, with a half life of a few seconds n blood
   • Rapid response to stress (fight or flight)
     • Stress stimulant can be psychological, in response to potential imminent threat or systemic stress (e.g. Trauma -> blood loss)

3. What is stress?

   • A stimulus that forces a biological component out of its tolerated paramters
   • Any input that causes an imbalance of some form; can be physiological or psychological

4. Glucocorticoids - cortisol (Long term response to stress)

   • Synthesis of corticosteroids
     • Cholesterol ester (from cell stores)
       • Cholesterol (C27)
         • Progesterone (C21)
           • Mineralocorticoids (C21) - aldosterone
           • Androgens (C19)
           • Glucocorticoids (C21) - cortisol
   • Regulation of cortisol secretion
     • SUtimuli: exercise, stress, hypoglycaemia, infection, cold, emotions, shock (trauma, burns, haemorrhage)
       • Hypothalamus: recognises stimuli and secretes CRH (Arg-vasopressin also released)
         • 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
       • +
   • Action of cortisol
     • Binds intracellular recptor and causes transcriptn of hormone-asscoaited genes
     • Part of the normal response to chronic stress
       • Metabolic
         • Adispose tissue: stimulates lipolysis
           • Excess cortisol causes lipogenesis in face, neck and trunk
         • Anti-insulin - maintains blood glucose
         • Muscle: stmulates proteolysis
         • Liver: stimulates gluconeogenesis
       • Suppressn of body's defence mechanisms
         • Anti-inflammatory
         • Immnosuppressive
         • Anti-allergic
         • By inhibiting the enzyme PLA2
           • Inhibits prostaglandin/leukotriene production
         • Reduces pain
           • Reducing the sensation of injury severity
             • Allows individual to continue despite injury
               • Steroid injections used in sports
       • Mineralocorticoid effects
         • Increases Na(+) and H2O retention
     • Deactivated in liver by C17 hydroxylation (increases solubility)
       • Excretion via kidneys
         • Used to test for excess cortisol secretion
   • Therapeutic uses of glucocorticoids
     • Iflammatroy diseases (rheumatoid arthritis, asthma, eczema)
     • Several synthetic glucocorticoids used (prednisolone, dexamethasone, betamethadone)
     • Excess use suppresses the hypothalamic-pituitary axis causing cushings

5. Blood supply

   • Adrenal glands are highly vascular
   • Recieves seven-fold more of the cardiac output than expected for its size
     • Only the brain has a more tightly reserved blood supply
     • Why?
       • For delivery of substrate and oxygen
       • Effective removal and distribution of hormonal products
       • Rapid response to physiological stimulus
       • Reflects importance of the adrenal gland, particularly in the stress response (both physiological and psychological)
   • Blood flow to the adrenals is tightly regulated