HRR: aldosterone and RAAS Flashcards
Where is aldosterone synthesized?
The zona glomerulosa in the cortex of the adrenal gland
What does aldosterone do?
Regulates renal handling of sodium and potassium to impact water balance and blood pressure homeostasis
How do mineralocorticoids work?
Bind to mineralocorticoid receptors in various tissues
Adrenal cortical hormones are synthesized from?
Cholesterol
Describe the synthesis of aldosterone.
Cholesterol is taken up via endocytosis into adrenal cells, or adrenal cells synthesize cholesterol de novo.
What does the enzyme StAR do?
Transfer cholesterol from the cytoplasm to the inner mitochondrial membrane to make it available for aldosterone synthesis.
Name the steroids formed in the pathway to aldosterone formation.
- Pregnenolone
What is desmolase?
Enzyme that forms pregnenolone
What is CYP11B2?
It converts DOC to corticosterone, then the 18-hydroxy form. The 18-hydroxy form will become aldosterone.
CYP11B2 is expressed exclusively in?
The zona glomerulosa
What are the rate limiting steps in aldosterone formation?
Transfer of cholesterol by StAR and conversion of cholesterol to pregnenolone
How are steroid hormones stored after synthesis?
They’re not!! They diffuse freely through the plasma membrane
What protein does aldosterone bind to in the blood?
Albumin
Where is the primary site of aldosterone metabolism?
The liver
What are the primary molecules that regulate aldosterone production and synthesis?
Ang II, extracellular K, ACTH
How does reduction in renal perfusion center impact aldosterone?
The kidney stimulates the RAAS system to release renin, ang II, and then aldosterone. This will result in raised GFR and BP
How does hyperkalemia impact aldosterone?
Where is renin stored?
JG cells
Describe the actions of renin after it is secreted.
It is secreted as prorenin. It can bind to a prorenin receptor that allows it to become functioning renin or can have a part of its structure cleaved to become renin.
What blocks renin?
Aliskiren
What is the main receptor for ang II?
AGTR1
What stimulates aldosterone release?
Ang II
How does ang II stimulate aldosterone release/synthesis?
It activates desmolase and increases the transcription of CYP11B2 to stimulate conversion from corticosterone to aldosterone.
How does high potassium stimulate aldosterone release?
Via direct action on glomerulosa cells; the cells sense elevations in potassium and secrete more aldosterone.
What can inhibit aldosterone secretion at the adrenal gland?
ANP
Most of the filtered load of sodium is reabsorbed in?
Proximal tubule, TAL of the loop of Henle
Where are the sites of action for aldosterone?
Cortical/medullary collecting ducts and late distal tubule segments
Describe aldosterone’s impact on sodium-potassium ATPase.
Once aldosterone enters the cell and translocates to the nucleus, it stimulates the actions of the ATPase. This keeps intracellular potassium low in order to drive reabsorption of sodium.
What is ENaC?
An epithelial sodium channel in the apical membranes of collecting tubules/ducts
How does aldosterone impact ENaC?
It stimulates SGK1 to increase ENaC activity by blocking its ubiquitination. This prevents removal of the channel from the membrane, letting it bring more sodium in. It also upregulates production of ENaC.
What does aldosterone do to the ROMK channel?
Upregulates its expression to allow it to push out more potassium. Aldosterone raising the sodium brought in by ENaC also helps ROMK push out more sodium.
In addition to K+, what other ion is lost as a result of aldosterone? How?
H+; upregulated ROMK also leads to upregulation of proton ATPase.
How does increased aldosterone impact blood pH and urine pH?
Blood pH increases via lost H+ and increased bicarb from the actions of the proton ATPase, urine pH decreases from extra H+ in the urine.
How is cortisol prevented from binding MR receptors?
Local action by 11B-HSD2 converts cortisol to cortisone. Cortisone does not bind to MR, so it is biologically inactive.
What converts cortisone back to cortisol?
11B-HSD1
Licorice root inhibits?
11B-HSD2. This can lower potassium by blocking conversion of cortisol to cortisone. This increases actions of MR receptors and pushes out more potassium.
Does the SNS stimulate or inhibit renin release?
Stimulate (B1) via epi and norepi.
What are classic lab signs of high aldosterone?
Blood pressure resistance (high), high pH, elevated sodium, low potassium, high bicarb.
