Adrenal Gland

Question 1

What in the world do these stupid adrenal glands that sit on top of the kidney even do? What parts make it up?

Answer 1

Simply put, they coordinate the body’s response to physiologic stress.

The adrenal medulla (interior core) is a functional extension of the sympathetic nervous system, secreting the catecholamines epinephrine and norepinephrine into systemic circulation.

In contrast the adrenal cortex synthesizes steroid hormones, which have diverse functions, ranging from stress responses (cortisol) to control of water and electrolyte water balance (aldosterone) to androgenizing effects (testosterone, DHEA-sulfate)

Question 2

What three arteries supply the adrenals and what are they branched from?

Answer 2

Superior adrenal arteries - Branches off of the inferior phrenic artery

Middle adrenal arteries - Originates from the abdominal aorta adjacent to the celiac trunk

Inferior adrenal arteries - Branch off of the renal artery

Question 3

Compare venous drainage of the left and right adrenals

Answer 3

Left adrenal to left adrenal vein to left renal vein to inferior vena cava

Right adrenal to right adrenal vein straight to the IVC

Question 4

To make things even more complicated, we take one of our two adrenal divisions, the cortex, and divide it up three times.

What are these layers? Discuss what makes them up and what they do for us.

Answer 4

Zona glomerulosa - A relatively thin external layer made up of cells with aldosterone synthase…they make aldosterone

Zona fasciculata - 75% of the thickness of the cortex. Cells here make glucocorticoids (cortisol)

Zona reticularis - Deepest layer of the cortex, these guys make androgens (DHEA and androstenedione)

Question 5

Ok smart guy, for shits, what does DHEA stand for?

Answer 5

Dehydroepiandrosterone

Question 6

Discuss the embryonic differences between the adrenal cortex and medulla

Answer 6

Cortex - Mesoderm

Medulla - Derived from neural crest cells, which differentiate into chromaffin cells

Question 7

What is pheochromocytoma and where do we see it? Jesus Christ, Renuka, if you get this wrong…

Answer 7

Pheochromocytoma is a rare neoplasm formed from the chromaffin cells of the adrenal medulla (90%) or extra adrenal sites (10%). It is the most common tumor of the adrenal medulla in adults.

Question 8

This is the most common tumor of the adrenal gland in kids

Answer 8

Neuroblastoma is a neoplasm formed from neural crest cells that can be found anywhere along the sympathetic chain, including the adrenal medulla. It is the most common tumor of the adrenal gland in kids.

Question 9

Steroid hormones of the adrenal cortex are synthesized using cholesterol as the precursor. Where do we get this cholesterol from?

Answer 9

About 20% is produced denovo fwithin adrenal cortical cells. The remainder is acquired from circulating LDL.

Question 10

What controls the three layers of the adrenal cortex?

Answer 10

The outer layer, the glomerulosa, which makes aldosterone, is controlled by Angiotensin II and potassium. Loss leads to hyponatremia and hypovolemia, (remember salt follows water) and hyperkalemia (don’t have time to get that potassium out)

The fasciculate and reticularis which make cortisol and androgens respectively, are controlled by ACTH. A lack of cortisol means you can’t compensate for physiologic stress or mobilize glucose. Androgen issues as you might expect means sex characteristics, so gynecomastia and delayed puberty in males.

Question 11

Free cholesterol within the adrenal cortical cells is transported where for steroid synthesis?

Answer 11

Mitochondria

Question 12

What is the first step of steroid synthesis from free cholesterol? What can affect this very first step?

Answer 12

This first step is rate limiting and is in all layers of the cortex. Cholesterol desmolase turns cholesterol to pregnenolone.

ACTH and angiotensin II stimulate this reaction while ketoconazole inhibits it.

Question 13

Discuss the pathway for making DHEA.

Answer 13

Cholesterol to pregnenolone as discused before by desmolase. Then, with 17a-hydroxylase, we turn pregnenolone to 17-Hydroxypregnenolone, and use this same enzyme again to make DHEA.

Question 14

We use 17a-hydroxylase for something else besides DHEA. Discuss the other connections 17 a makes

Answer 14

So at the beginning, before we add the 17a, we can turn out pregnenolone to progesterone. Then when we add 17a we get 17a-hydroxyprogesterone, and after another round get androstenedione.

Androstenedione can turn to Estrone or to testosterone.

Testosterone can be turned by 5a reductase to DHT (active form) or by aromatase to estradiol.

Question 15

How do we make cortisol?

Answer 15

This is where the pathways really start intersecting. After we treat pregnenolone with 17a to get 17-hydroxypregnenolone, we can turn it to 17a-hydroxyprogesterone instead of DHEA. Recall we can also get 17a Hydroxyprogesterone by giving progesterone 17a.

17A-Hydroxyprogesterone gets turned to 11-Deoxycortisil by 21a-hydroxylase, and then to cortisol by 11B-hydroxylase.

Question 16

How do we make Aldosterone?

Answer 16

If we give progesterone some 21a, we get the 11 Deoxycorticosterone. Follow up like with cortisol synthesis with a little 11B and you get corticosterone.

Aldosterone synthase, which is stimulated by Angiotensin II, turns corticosterone to aldosterone.

Question 17

What happens with 21-Hydroxylase deficiency?How does it present?

Answer 17

Most common form of congenital adrenal hyperplasia, leads to decreased levels of both glucocorticoids and mineralcorticoids with a concomitant rise in adrenal androgens.

Patients will be hypotensive, hyponatremic, hyperkalemic, and have virilization.

Question 18

What happens with 17a-hydroxylase deficiency? How does it present?

Answer 18

These individuals lack the enzyme to make cortisol or androgens, resulting in accumulation of pregnenolone, which gets shunted to aldosterone.

Patients are hypertensive and hypokalemic.

Question 19

What triggers glucocorticoid production? Discuss what occurs to make the glucocorticoids.

Answer 19

Stress and inflammation (specifically, hypoglycemia, trauma, fever, psychological distress, etc) trigger the hypothalamus to release CRH (corticotropic releasing hormone).

This stimulates the Anterior pituitary to make ACTH which upregulates desmolase to churn out cholesterol and pregnenolone to make cortisol.

Negative feedback means cortisol inhibits this process.

Question 20

Cortisol is called a glucocorticoid because of its effects on maintaining blood glucose. What does it do specifically to handle this?

Answer 20

• Increases gluconeogenesis
• Decreases glucose uptake by cells
• Increases lipolysis
• Increases protein catabolism

Question 21

What other effects does cortisol have besides the glucose maintenance ones?

Answer 21

Antiinflammatory effects

• Stabilizes lysosomes (stops them from leaking proteolytic stuff to reduce inflammation)
• Inhibits Phospholipase A2
• Inhibits IL-2 (slows down T-Cell proliferation)
• Blocks release of histamine from mast cells and serotonin from platelets

Vasoconstriction
- Increases a1-receptors

Question 22

We discussed that one of the functions of cortisol is to inhibit phospholipase A2. How does this occur and what does it do for us?

Answer 22

It promotes the synthesis of lipocortin, an inhibitor of phospholipase A2. Phospholipase A2 normally supplies arachidonic acid for the synthesis of prostaglandins and leukotrienes.

Lack of these local inflammatory mediators decreases capillary permeability and the recruitment of leukocytes to the inflamed tissue.

Question 23

What causes the synthesis of aldosterone? What about its release?

Answer 23

ACTH promotes aldosterone synthesis, but has little to no effect on secretion. Secretion is increased or decreased based on changes in the ECF volume, sodium and potassium concentrations in the ECF, and arterial pressures. Important determinants on secretion are:

• Increased K+ increases secretion
• The RAS increases secretion
• High sodium decreases secretion

Question 24

Three major functions of aldosterone

Answer 24

Increase sodium reabsorption, increase arterial pressure and increase potassium secretion

Question 25

How does aldosterone increase sodium reabsorption?

Answer 25

Aldosterone stimulates the synthesis of new sodium channels in the principal cells of the collecting tubules to promote reabsorption.

Question 26

How does aldosterone increase arterial pressure?

Answer 26

By increasing absorption of sodium, water follows to increase arterial pressure.

Question 27

How does aldosterone increase potassium secretion?

Answer 27

Aldosterone induces the opening of large numbers of sodium and potassium channels in the principal cells of the collecting ducts. Enhanced sodium reabsorption is accompanied by increased potassium secretion into the tubule lumen (Sodium-potassium pump, remember?)

Question 28

Menopause means no more estrogens. How come women don’t just become men at that point?

Answer 28

They still have the weak androgen androstenedione made by the ovaries and adrenals, converted to estrone by aromatase.

Question 29

Discuss what happens with folks who are 11B deficient

Answer 29

Can’t make normal levels of cortisol or aldosterone, and the precursors go towards making a lot of sex hormones.

These patients are hypertensive and females are virilized.