The Adrenal Glands Flashcards
Where are the adrenal glands located?
On top of the kidneys - in very close proximity.
But, it is a separate tissue to the kidney with a different function.
What are the layers of the kidney and what are the hormonal products of these layers?
- Capsule
- Cortex
- Zona Glomerulosa - Mineralcorticoids (aldosterone)
- Zona Fasiculata - Glucocorticoids (cortisol)
- Zona Reticulatis - Glucocorticoids and small amount of androgens
- Medulla
- Chromaffin cells - Adrenaline (80%) and Noradrenaline (20%)
Cortex = G,F,R and “salt, sugar, sex.. the deeper you go the sweeter it gets”
What hormones are secreted by the adrenal cortex?
Discuss Steroid Hormones
- Synthesised from cholestrol in adrenal glands and gonads
- Lipid soluble hormones
- Bind to receptors of the nuclear receptor family to modulate gene transcription.
- Effects of steroid hormones are slower than that of lipid soluble hormones (steorids)
- Glucocorticoids
- Mineralocorticoid
- Androgens
- Oestrogens
- Progestins
21-hydroxylase deficiency causes congenital adrenal hyperplasia. This is a genetic condition resulting in ambiguous sex organs.
How do corticosteroids exert their actions?
Corticosteroids exert their actions by regulating gene transcription
- Corticosteroids readily diffuse across plasma membrane
- Bind to glucocorticoid receptors
- Binding causes dissociation of chaperone proteins (e.g. heat shock protein 90)
- Receptor ligand complex translocates to nucleus
- Dimerisation with other receptors can occur
- Receptors bind to glucocorticoid response elements (GREs) or other transcription factors.
What is aldosterone?
- Most abundant mineralocorticoid
- Synthesised and released by Zona glomerulosa of adrenal cortex
- Steroid hormone = Lipophilic.
- Carrier protein = mainly serum albumin and to a lesser extent transcortin
- Adosterone receptor is intracellular and exerts its actions by regulating gene transciption
- Plays central role on regulation of plasma Na+, K+ and artrial blood pressure
- Main actions in distal tubules and collecting ducts of nephron where is promotes expression of Na+/K+ pump promoting reabsorbtion of Na+ and excretion of K+ thereby influencing water retention, blood volume anf therefore blood pressure.
- It is a central component of renin-angiotensin-aldosterone system (RAAS)
Explain the renin-angiotensin-aldosterone system (RAAS)
- Hypotension or hypovolaemia leads to renin release
- Renin cleaves angiotensionogen (a precursor hormone released by the liver- no action in itself) into angiotensin I
- ACE then cleaves angiotensin I to angiotensin II in lung endothelial cells.
- Angiotensin II causes:
- Vasoconstriction of the arterioles
- Increase production of aldersterone so increased expression of NaKATPase where increases reabsorbtion and Na and water back into blood
- Stimulate ADH to be produced by the hypothalamus and get released by the posterior pituitary. This leads to translocation of aquaporins to allow reabsorbtion of water back into the blood.
What is a primary hyperaldosteronism?
Defect in the adrenal cortex itself
- Bilateral idiopathic adrenal hyperplasia (most common)
- Aldosterone secreting adrenal adenoma (Conn’s syndrome)
- Low renin levels (high aldosterone : renin ratio)
What is secondary hyperaldosterorism?
Due to over activity of the RAAS
- Renin prodicing tumour (rare) e.g. juxtaglomerular tumour
- Renal artery stenosis
- High renin levels (low Aldosterone : Renin ratio)
What are the signs of and treatment for hyperaldosteronism?
Signs:
- High blood pressure
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia
- Hypokalaemia
Treatment:
- Depends of the type
- Aldosterone-producing adenoma removed by surgery
- Spironolactone (mineralcorticoid receptor antagonist)
What is cortisol?
- Most abundant corticosteroid and accounts of glucocortocoid activity
- Synthesised and released by Zona fasciculata in response to ACTH
- Negative feedback to hypothalamus inhibits CRH and ACTH release
- Steroid hormone.
- Carrier protein in plasma = transcortin
- Cortisol receptor exerts its actions by regulating gene transciption
What are the actions of cortisol?
- Increased protein breakdown in muscle (catabolic)
- Increased lipolysis in fat (catabolic)
- Increased gluconeogenesis in liver
- Resistancy to stress (increased supply of glucose, raise BP by making vessles more sensitive to vasoconstrictors)
- Anti-inflammatory effects (inhibits macrophage activity and mast well degranulation)
- Depression of immune response (prescribes to organ transplant patients)
Descibe the HPA axis
What actions to glucocoricoids have on metabolism?
Net effect:
- Increased glucose production
- Breakdown of protein
- Redistribution of fat
Muscle: Cortisol inhibits insulin-induced GLUT4 translocation in muscle (prevents glucose uptake so has glucose sparing effect)
Fat: Chronic high levels of cortisol can result in redistribution of far especially in abdomen, suptraclavicular fat pads, Dorso-cervical fat pad, (“Buffalo hump”) and on face (“Moon face”)
What is Cushing’s syndrome?
Chronic excesive exposure to cortisol.
Mainly caused externally by prescirbed glucocorticoids but, it can be caused (rarely) by endogenous things.
- Benign pituitary tumour secreting ACTH (Cushing’s syndrome)
- Excess cortisol produced by adrenal tumour (Adrenal Cushing’s)
- Non pituitary-adrenal tumours producing ACTH (&/or CRH) e.g. small cell lung cancer.
Why does Addison’s result in hyperpigmentation?
- Decreased cortisol
- Negative feedback on anterior pituitary reduced
- More POMC required to sythesise ACTH
- ACTH and more MSH produced.
- Increased MSH as consequence of increased POMC in Addison’s lads to hyperpigmentation. ACTH itself can also activate melanocortin receptors on melanocytes so will also contribute to hyperpigmentation.
What are Adrenergic receptors?
They are all GPCRs
- Ligand
- Receptor
- G protein
- Effector Protein
- Second Messenger
- Later Effector
- Cellular resonse.
Q a1
I a2
S B1
S B2
What are the hormonal actions of adrenaline?
Fight or flight repsonse.
How does adrenaline increase heart rate?
- Direct activation of cAMP of hyperpolarisation-activated, cyclic nucelotide gated (HCN) channels (responsible for If - funny current)
- PKA phosphorylation of HCN channels modulates function
- PKA phosphorylation of L-type Ca2+ channels potentiates opening, increasing the slope of the upstroke of the action potential.
Compare corticosteroids with catecholamines
