The adrenals Flashcards
Location of adrenal glands
Above kidney, surrounded by thick capsule
Zones of adrenal glands
2 zones
Inner medulla
Outer cortex
Blood supply to adrenals
Left adrenal vein drains into renal vein
Right adrenal vein drains into inferior vena cava
Both adrenals have many arteries but only one vein where everything produced from it drains into
Zones of cortex (out to in)
Produce?
Cortex produces corticosteroids
Types of corticosteroids: Mineralocorticoids (e.g. aldosterone), Glucocorticoids (e.g. cortisol), Sex steroids (e.g. androgens, oestrogens)
Zona Glomerulosa- produces aldosterone
Zona Fasciculata- produces cortisol (+ sex steroids)
Zona Reticularis- produces cortisol (+ sex steroids)
Medulla produces?
Catecholamines
Predominantly adrenaline, some noradrenaline, some dopamine
Properties of adrenal hormones
Action= complex
Lipid soluble
Powerful
Influence gene transcription and translation
Synthesis of steroid hormones
Difference between reaction mechanisms of cortisol+ aldosterone
Why low levels of sex steroids produced?
- Lipoproteins containing cholesterol enter cell
- Stored as fatty acid esters in cell
- When the right signal comes along, cholesterol liberated by esterase enzyme and moved by StAR protein into the mitochondria
- Reaction mechanisms produce cortisol/ aldosterone/ sex steroids
P450C17 enzyme is used in cortisol production not in aldosterone
Aldosterone synthase enzyme is used in aldosterone production not in cortisol
Low levels of enzymes required to produced sex steroids (e.g. 17,20 Lyase)
Transport of adrenal hormones- what binds to cortisol and aldosterone?
Differences in storage between cortisol and aldosterone
CBG (Corticosteroid binding globulin) and Albumin
Cortisol= more protein plasma bound (80% CBG, 10% albumin), aldosterone= more free (15% CBG, 45% Albumin)
Implications for something heavily protein-plasma bound
Small changes in displacement of hormone from binding proteins causes greater increase in receptor binding of the hormone
Difference in concentrations of aldosterone+ cortisol
Patterns of secretions of cortisol
Receptors that cortisol+ aldosterone bind to?
Relevance of aldosterone?
Cortisol (nmol/L)= 1000x more concentrated than aldosterone (pmol/L)
Cortisol secreted throughout the day high when you wake up and low at bed
Cortisol binds to GR (glucocorticoid receptors) and aldosterone receptors (Mineralocorticoid Receptors)
Aldosterone binds to aldosterone receptors ONLY
11b-hydroxysteroid dehydrogenase 2= enzyme that converts cortisol to cortisone (inactive), found more in kidney+ placenta (maternal cortisol= inhibitory to foetus) which are therefore protected from cortisol: those tissues require aldosterone instead
Renin production?
Stimuli?
What indicates bp decrease?
Renin production from granular cells that line the afferent arteriole in the kidney before the glomerus
1. If blood pressure in arteriole drops sensed by the granular cells= cause more renin to be produced
2. Also, renal sympathetic nervous system can lead to more renin production
3. Macular densa cells in the distal convoluted tubule (anatomically close to the Bowman’s capsule) influence renin because sense Na+:
If the Na concentration of fluid going into afferent arteriole decreases, renin produced =promotes Na reabsorption in the kidney +preserves blood pressure (because water is reabsorbed as a result)
Renal profusion pressure decreasing indicates blood pressure decreasing too.
Renin-angiotensin-aldosterone system
What else stimulates aldosterone?
- Angiotensinogen (comes from the liver) activated by renin to produce angiotensin I
- Lungs have a lot of Angiotensin converting enzyme (ACE): converts angiotensin I to angiotensin II
- Angiotensin II stimulates aldosterone production
Apart from that, low Na or high K in the blood stimulate aldosterone production.
Cortisol production (intro to endo lecture)
1.Hypothalamus releases Corticotropin releasing hormone (CRH) to anterior pituitary corticotrophs which
2. Releases adrenocorticotropin to adrenal cortex which releases cortisol
THIS CAUSES NEGATIVE FEEDBACK
Action of aldosterone Where does it act? Which hormone does it work with? Process? When is it used?
Acts at the end distal tubule to the collecting duct
Vasopressin deals with the water in the same place, and aldosterone deals with the Na in the same place.
- Na diffuses through tubule lumen to interstitium through Na channel (passive)
- Conc. gradient maintained by Na/ K pump on the basal side of the cell that pumps Na out of the cell in exchange of K (which leads to some K loss into the distal convoluted tubule naturally)
- Aldesterone increases the number of Na channels and number of Na/K pumps on the basolateral membrane of the cells
- Water will only diffuse across if there is an osmotic gradient with it so the vasopressin effect is dependent of this.
If blood pressure falls, renin-angiotensin system uses this as well.
General action of cortisol (see intro to endo lecture) Why is the action complex? What is required for normal physiology? Stress situation?
Influences transcription and translation
Binds to GR (Glucocorticoid Receptor), travels to nucleus, upregulates/ downregulates transcription/ translation
Cortisol can bind to 2 receptors (glucocorticoid and aldosterone) in most tissues.
Cortisol needs to heavily bind to the aldosterone receptor (except kidney+ placenta) to cause full mineralocorticoid receptor (MR) activation and partially activation of glucocorticoid receptor (GR)
In times of stress you want maximal GR as well as maximal MR but then turn back to normal levels ASAP.
