HRR: aldosterone and RAAS

Question 1

Where is aldosterone synthesized?

Answer 1

The zona glomerulosa in the cortex of the adrenal gland

Question 2

What does aldosterone do?

Answer 2

Regulates renal handling of sodium and potassium to impact water balance and blood pressure homeostasis

Question 3

How do mineralocorticoids work?

Answer 3

Bind to mineralocorticoid receptors in various tissues

Question 4

Adrenal cortical hormones are synthesized from?

Answer 4

Cholesterol

Question 5

Describe the synthesis of aldosterone.

Answer 5

Cholesterol is taken up via endocytosis into adrenal cells, or adrenal cells synthesize cholesterol de novo.

Question 6

What does the enzyme StAR do?

Answer 6

Transfer cholesterol from the cytoplasm to the inner mitochondrial membrane to make it available for aldosterone synthesis.

Question 7

Name the steroids formed in the pathway to aldosterone formation.

Answer 7

1. Pregnenolone

Question 8

What is desmolase?

Answer 8

Enzyme that forms pregnenolone

Question 9

What is CYP11B2?

Answer 9

It converts DOC to corticosterone, then the 18-hydroxy form. The 18-hydroxy form will become aldosterone.

Question 10

CYP11B2 is expressed exclusively in?

Answer 10

The zona glomerulosa

Question 11

What are the rate limiting steps in aldosterone formation?

Answer 11

Transfer of cholesterol by StAR and conversion of cholesterol to pregnenolone

Question 12

How are steroid hormones stored after synthesis?

Answer 12

They’re not!! They diffuse freely through the plasma membrane

Question 13

What protein does aldosterone bind to in the blood?

Answer 13

Albumin

Question 14

Where is the primary site of aldosterone metabolism?

Answer 14

The liver

Question 15

What are the primary molecules that regulate aldosterone production and synthesis?

Answer 15

Ang II, extracellular K, ACTH

Question 16

How does reduction in renal perfusion center impact aldosterone?

Answer 16

The kidney stimulates the RAAS system to release renin, ang II, and then aldosterone. This will result in raised GFR and BP

Question 17

How does hyperkalemia impact aldosterone?

Question 18

Where is renin stored?

Answer 18

JG cells

Question 19

Describe the actions of renin after it is secreted.

Answer 19

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.

Question 20

What blocks renin?

Answer 20

Aliskiren

Question 21

What is the main receptor for ang II?

Answer 21

AGTR1

Question 22

What stimulates aldosterone release?

Answer 22

Ang II

Question 23

How does ang II stimulate aldosterone release/synthesis?

Answer 23

It activates desmolase and increases the transcription of CYP11B2 to stimulate conversion from corticosterone to aldosterone.

Question 24

How does high potassium stimulate aldosterone release?

Answer 24

Via direct action on glomerulosa cells; the cells sense elevations in potassium and secrete more aldosterone.

Question 25

What can inhibit aldosterone secretion at the adrenal gland?

Answer 25

ANP

Question 26

Most of the filtered load of sodium is reabsorbed in?

Answer 26

Proximal tubule, TAL of the loop of Henle

Question 27

Where are the sites of action for aldosterone?

Answer 27

Cortical/medullary collecting ducts and late distal tubule segments

Question 28

Describe aldosterone’s impact on sodium-potassium ATPase.

Answer 28

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.

Question 29

What is ENaC?

Answer 29

An epithelial sodium channel in the apical membranes of collecting tubules/ducts

Question 30

How does aldosterone impact ENaC?

Answer 30

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.

Question 31

What does aldosterone do to the ROMK channel?

Answer 31

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.

Question 32

In addition to K+, what other ion is lost as a result of aldosterone? How?

Answer 32

H+; upregulated ROMK also leads to upregulation of proton ATPase.

Question 33

How does increased aldosterone impact blood pH and urine pH?

Answer 33

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.

Question 34

How is cortisol prevented from binding MR receptors?

Answer 34

Local action by 11B-HSD2 converts cortisol to cortisone. Cortisone does not bind to MR, so it is biologically inactive.

Question 35

What converts cortisone back to cortisol?

Answer 35

11B-HSD1

Question 36

Licorice root inhibits?

Answer 36

11B-HSD2. This can lower potassium by blocking conversion of cortisol to cortisone. This increases actions of MR receptors and pushes out more potassium.

Question 37

Does the SNS stimulate or inhibit renin release?

Answer 37

Stimulate (B1) via epi and norepi.

Question 38

What are classic lab signs of high aldosterone?

Answer 38

Blood pressure resistance (high), high pH, elevated sodium, low potassium, high bicarb.