Adrenals and disorderd Flashcards
Where at the adrenals located? How are they vascularised?
Directly above the kidneys-right adrenal abovze right kidney etc
Both kidneys have an extensive arterial networks leading into but only one vein going
Left adrenal drains to left renal vein
Right adrenal drains directly into inferior vena cava
What are the different zones of the adrenals? Which ones produce what?
2 main zones-cortex on the outside and and medulla inside
Medulla makes mainsly catecholamines
Cortex in 3 different zones-exterior to interior are glomerulosa, fasciculata and reticularis
Glomerulosa makes mineralocorticoids-Aldosterone, and fasciculata and reiculatris makes glucocorticoids-Cortisol
Limited amounts of sex hormones also made
How are adrenal hormones synthesised? What is the precursor and what determines which one is made in which region?
Adrenal hormones are all made from cholesterol and are C21 (sex hormones are C21, C19, C18)-stored in fatty ester vesicules, taken out with esterase into Chol, then transfered to mito by StAR
In mitochondria, enzymes determine which one is made-if those for cortisol-cortisol, and if not then other
Then hormone can naturally just release into blood
How are adrenal hormones stored and transported?
Transport is done in blood like other hormones
Stored in blood too, bound to plasma proteins
Aldo 40% free, 15% bound to binding protein and 45% bound to albumin
Cort 10% free, 80% bound to cortisol binding globulin and 10% bound to albumin
Means that a small increase of cort release has massive impacts
How do levels or cortisol and aldrosterone vary during the day?
Cortisol is maxiumum during the morning (around 140-700nM) and drops (4pm-80-330 nM)
Aldosterone is at much lower conc-but stable during day (140-560pM)
What receptors does cortisol and aldosterone affect? How is aldosterone made effective?
Aldosterone affects aldosterone/mineralocorticocoids receptors (MR) and cortisol affects Glucocorticocoids receptors (GR) AND MR
For Aldo to have a role-an enzyme in certain tissue degrades only cortisol-only aldo can make it through-like kindeys
Can you explain the regin-angiotensin-aldosterone regulatory system?
In the kindeys-at glomerula reabosrtion cells, find granular cells that can produce renin
Near there-macular densa cells measure Na+ levels-when drops causes renin release
Renin leads angiotensinogen to angiotensin I. This, with Angiotensin converting ezyme (ACE) makes angiotensin
Combining angiotensin, dropping Na and High K all regulate glomerulosa to secrete Aldosterone release
How is cortisol release regulated?
Cortisol is dependent og hypothalama-pituary ACTH release (when ACTH is released, etserase and star increase leading to more cortisol)
ACTH levels vary with the day (like cortisol)
And cortisol has a downregulatory action on ACTH and Hypothalamus
ACTH in itself regulated by CRH of hypothalamus
What are the effects of Aldosterone?
Similarly to Vasopressin-acts on late collecting duct/distal tubule
Aldosterone binds MR (cytoplasm receptor acting on DNA transcription)
Causes increases of Na+ ion channels in tubule membrane (uptake from lumen)
But also increases Na+/K+ transporters from renal cells to blood
Keep the gradient right with the antiporter + usual vasopressin action on water
How does cortisol bind receptors? What is meant by optimal binding levels?
Because cortisol can bind GR and MR (intracellular receptors then acting on DNA), its effects are maximum when fully binding MR and half binding GR
If no MR and GR-low action, if high MR and high GR-also low
List the effects of Cortisol on the body
Metabolic effects of increasing gluconeogenesis (upregulating PEPCK (rate determining) and glycogenesis (store glycogen)
=> generally want to have more available glucose for stress
Also down regulate peripheral uptake of glucose (because sotres there cannot be sued y rest of body)
so lower Glut4 in muscle and LPL in adipose tissue
At optimal levels-upregulates serotonin receptors in a particular part of the hippocampus, leading to increaes cell division and memory
Also has MANY anti-inflamatory effects and imminosupressive (why corticosteroids are treatment)
What are adverse effects of cortisol? How can they arise?
In prolonged stress, or caffeine, or alcohol, ACTS levels increase and cortisol binds MR and GR too much-bad
Memory is reduced with chronic high Cort, hipocampus shrinks, cells die
Also immunosupression in stressed patient, and metabolic imbalance
Can also affect MR in kindey tubules if too high and too much reuptake of Na
