Adrenal/Aldosterone & Catecholamines

Question 1

What is the mechanism of action of aldosterone? It binds to its receptor in the cytosol and then….

Answer 1

1. Aldosterone+receptor dimer goes to the nucleus
2. Leads to the expression of genes that make protein Na+ receptors and enzymes needed to fuel those receptors.
3. Na+ receptors inserted into the cell wall of the renal distal tubule

Question 2

What is the effect of Na+ reabsorption on K+ excretion?

Answer 2

As Na+ is actively pumped back into the cell, an electrochemical gradient forms that allows for the PASSIVE diffusion of K+ out of the cell and into the lumen for excretion. So aldosterone effects both Na+ AND K+ levels in the cell.

Question 3

What are the stimuli that tell your body’s juxtaglomerular cells to secrete that sweet sweet renin

Answer 3

1. Blood pressure: the juxtaglomerular cells sense decreases in systemic volume or pressure from the afferent arterioles (baroreceptor function)
2. Ionic composition: the macula densa cells of the distal tubule sense Na+ and Cl- ions (chemoreceptor function)
3. Sympathetic innervation: decrease in blood volume causes the increase firing of sympathetic nerves that cause vasoconstriction and release of renin.

Question 4

What is the effect of K+ on aldosterone release?

Answer 4

K+ directly simulates the release of aldosterone from the zona glomerulosa of the adrenal gland

Question 5

What effect does ACTH have on the release of aldosterone?

Answer 5

ACTH doesn’t directly effect aldosterone release (it’s baby is cortisol) but deficient ACTH causes zona glomerulosa atrophy, which makes it less responsive to angiotensin II. Can you guess what happens when you’ve got the Cushing’s disease? Yup–zona glomerulosa hypertrophy. Good job.

Question 6

Tumors of the adrenal gland will cause excess aldosterone. Although rare, this condition can cause hypertension and hypokalemia. Why?

Answer 6

1. Hypertension: increase aldosterone–>increase Na+ reabsorption–>increased water reabsorption–>increased plasma volume–>hypertension
2. Hypokalemia: more Na+ reabsorption–>more K+ passively diffusing in the lumen for excretion–>hypokalemia.

Question 7

One of the secondary signs of edema is hyperaldosteronism. Discuss.

Answer 7

In conditions like CHF or ascites, fluid is constantly building up in extravascular places and not staying put in the circulatory system. This means the body constantly thinks it’s in a fluid loss state and keeps secreting aldosterone through activation of the renin-angiotensin system, although BP remains low-normal.

Question 8

What other places other than the kidneys does aldosterone work on Na+ excretion regulation

Answer 8

Sweat, stool and saliva

Question 9

What is the embryological origin of the adrenal medulla?

Answer 9

Neural crest cells

Question 10

What kind of cells do you find in the adrenal medulla?

Answer 10

These cells are basically postganglionic sympathetic neurons with no axons

Question 11

What does the adrenal medulla secrete and what enzyme is important in this process?

Answer 11

Chromaffin cells of the medulla secrete epinephrine and norepinephrine and the enzyme phenyl-N-methyl-transferase (PNMT) converts norepinephrine to epinephrine.

Fun fact: cortisol activates PNMT, which is why the medulla needs to be in the adrenal gland

Question 12

Where does all the norepinephrine and epinephrine in your body come from?? WHEREEEEE

Answer 12

Norepinephrine: 80% comes from sympathetic neurons innervating vascular smooth muscle. 20% comes from the adrenal medulla
Epinephrine: 100% from the adrenal medulla

So: circulating NE is a measure of vascular tone, whereas circulating Epi is a measure of “fight or flight” stress response

Question 13

Remember catecholamine synthesis? Walk me through that for old times sake.

Answer 13

1. Tyrosine –>Dopa (tyrosine hydroxylase) rate limiting enzyme***
2. Dopa–>DA
3. DA–>NE
4. NE–>Epi (PNMT)

I didn’t put enzyme for #2 or 3 because it’s low yield. #onlyhighyieldfacts

Question 14

Ok so now you’ve got your NE and Epi made. Where is it stored and how does it get released?

Answer 14

Stored: in secretory granules duh
Release: Preganglionic neurons innervate the medulla and release Ach, which depolarizes the medullary cells causing the exocytosis of NE (20%) and Epi (80%)

Question 15

Now you’ve released all your NE and Epi, how do you make it stoppppp. Name 3 ways, go.

Answer 15

1. reuptake into the chromaffin cell for reuse or metabolism
2. uptake into the cells the catecholamine is acting on
3. enzymatic metabolism to inactive products that are peed out

Question 16

What is a pheochromocytoma?

Answer 16

This is a catecholamine secreting tumor of the adrenal medulla. This causes hypertension and other sx associated with too much fight or flight response.