Lecture 6-Adrenal Glands

Question 1

Summarize adrenal gland form and function

Answer 1

Z. Glomerulosa= releases aldosterone, zone regulated by AGII, K+

Z. fasciculata= releases cortisol and androgens regulated by ACTH

Z. Reticularis=releases cortisol and androgens regulated by ACTH

Medulla= epinephrine and Norepinephrine—> sympathetic control

Question 2

Summarize distribution blood supply of adrenal glands

Answer 2

Superior, middle, and inferior suprarenal arteries supply the adrenal gland. Venous drainage to IVC and renal vein.
• Arteries form plexus & perfuse the gland from periphery to the center.
• Medulla receives dual blood supply enriched with hormones.

Question 3

What is the role of CRH & ACTH in the hypothalamic-pituitary-adrenal axis ?

Answer 3

Paraventricular nucleus neurons secrete CRH, which targets corticotropes.

Corticotropes secrete ACTH, which targets the adrenal cortex

Question 4

What are the negative feedback of the hypothalamic-pituitary-adrenal axis?

Answer 4

CNS experiences biochemical, psychological, and physical stress+ circadian rhythms stimulate hypothalamus releases CRH

Anterior pituitary secretes ACTH

ACTH stimulates adrenal cortex to secrete cortisol

Cortisol inhibits anterior pituitary + hypothalamus

ACTH inhibits hypothalamus

Question 5

What is the stress and role of cortisol?

Answer 5

• Any type of physical or mental stress can lead within minutes to greatly enhanced secretion of ACTH and consequently cortisol.

• Cortisol is essential to deal with the various physical & mental stresses of life.
– Intense heat or cold
– Minor or debilitating illnesses
– Infections
– Trauma / surgery
– Fasting / starvation

Question 6

What is the mechanism of action of CRH to promote ACTH synthesis?

Answer 6

CRH binds receptor to increase cAMP

cAMP dependent PKA causes increased Ca2+ influx

Fusion of ACTH containing vesicles , leading to exocytosis of ACTH

Corticotroph cell in anterior pituitary

Question 7

What is ACTH?

Answer 7

• ACTH is secreted as a large preprohormone
“Proopiomelanocortin”

• ACTH is the main physiologic product:
• a MSH is contained in the sequence of ACTH
• In physiologic range  MSH is not significant
• Excess ACTH secretion results in hyper pigmentation

Question 8

What is StAR?

Answer 8

Steriodogenic active regulatory protein

Question 9

What is the short term and long term role of ACTH mechanism of action?

Answer 9

• Short-term role: ↑Conversion of cholesterol to pregnenolone
• Long-term role: ↑number of LDL receptors and ↑synthesis of mRNAs
leading to enzymes

Question 10

How is aldosterone regulated?

Answer 10

Renin-angiotensin system (major)

Hypothalamic-ACTH loop(minor)

Angiotensin II K+ increase + ACTH stimulates Adrenal Cortex (Z. Glomerulosa) to stimulate aldosterone

Question 11

What is the regulation of aldosterone-Angiotensin II -Z. Glomerulosa?

Answer 11

Ang II binds to receptor (decreased blood vol.)

Leading to increased DAG + IP3 leading to Ca2+—> stimulation of aldosterone synthesis

increased DAG + IP3 leads to activation of PKC and stimulation of aldosterone synthesis

Aldosterone —> increase renal Na+ resorption (restore blood vol.)

Question 12

What is the role of aldosterone- K+-Zona glomerulosa?

Answer 12

Hyperkalemia (K+)—> depolarization causing increased Ca2+ and activation of aldosterone synthesis

Aldosterone leads to increased renal K+ secretion and restore serum [K+]

Question 13

Why do we need aldosterone?

Answer 13

Maintain blood volume
•Stimulates K+ excretion into urine •Stimulates Na+ resorption into blood
– Via kidneys (less regulatory - saliva, sweat & GIT)
– Water follows sodium ions causing an increase in blood volume that will raise the blood pressure.
Regulate H+ secretion
• Renalsecretion–(detailsinlaterslides)

Question 14

Explain in detail aldosterone regulation -renin angiotensin & aldosterone

Answer 14

1. Decrease in Na+ concentration, decrease in ECF volume
2. Kidney JGA releases renin
3. Aniotensinogen reacts with renin to form angiotensin I
4. Angiotensin reacts with converting enzymes in lungs to form angiotensin II
5. AGII stimulates adrenal cortex to release aldosterone
6. Aldosterone reacts with kidney DCT to reabsorb Na+ retain water and excrete K+
7. Increase in Na+ concentration. Increase in ECF volume.
8. This inhibits kidney JGA from releasing renin

Question 15

What is hyper aldosterone?

Answer 15

Cause: Increased secretion of aldosterone from adrenal cortex. Symptoms: Hypertension, dec K+, metabolic alkalosis. (No edema due to
aldosterone escape mechanism…”backflow”.)

Question 16

Differentiate primary (Conn’s syndrome) and secondary hyper aldosteronism

Answer 16

Primary (Conn’s syndrome)- Adrenal adenoma (tumor) or idiopathic hyperplasia of zona glomerulosa. (Increased aldosterone, decreased renin)

Secondary- Reno-vascular hypertension (renal artery stenosis), juxtaglomerular cell tumor- (activation of RAAS). (Increased aldosterone, increased renin)

Question 17

Explain the primary hyperaldosteronism symptoms

Answer 17

•Hypertension: K+ exchange for Na+
– ↑ Na+ & H2O resorption from tubulesinc. ECF
– Hypertension/inc. BP leads to increased ECF volume

•Hypokalemia: K+ secreted into urine
– hypokalemia causing muscle weakness & arrhythmias.

• Alkalosis: H+ influx instead of K+ as a result of lost K+ in urine and present hypokalemia.
• Dec. renin (1o): increased BP—>inhibited secretion.

Question 18

Give the lab analysis of primary aldosteronism

Answer 18

↑Aldosterone ↑Sodium(hypertension) ↓Potassium
↓Renin
Metabolic Alkalosis

Question 19

Give the lab analysis of secondary hyperaldosteronism

Answer 19

↑Aldosterone ↑Sodium(hypertension) ↓Potassium
↑Renin
Metabolic Alkalosis

Question 20

What are the triggers of the Catecholamines release?

Answer 20

Stress
Increased exercise
Exposure to cold
Hypoglycemia

Question 21

Outline the mechanism of ACh in the adrenal medulla

Answer 21

ACh stimulates nicotine receptors

Sodium influx into the chromaffin cell—> depolarization of chromaffin cell —> Ca2+ influx—> fusion of vesicles—> release of epinephrine and norepinephrine

Question 22

What are the functions of Catecholamines?

Answer 22

Epi/NE:
-Adipose tissue increased lipolysis—> free fatty acids+ glycerol is used for glycogenolysis in liver

-glycogenolysis on skeletal and liver increased

Glycogenolysis in liver, allows glucose to be used for energy for fight or flight

Question 23

Whaat are the physiological effects of stress?

Answer 23

Stress-hypothalamus stimulates pituitary-adrenal cortex to release mineral corticoids to increase blood pressure for long term purposes

Pituitary adrenal cortex releases glucocorticoids to stimulate protein breakdown , fat lipolysis, and immune suppression for both long and short term responses

Hypothalamus stimulates ANS/Adrenal medulla to release Catecholamines

This increasss HR & BP blood glucose, metabolic rate, bronchodilation for a short term basis

Question 24

How is Addison treated?

Answer 24

Replacement of glucocorticoids and mineralcorticoids

Question 25

Whaat are the clinical features of Addison’s?

Answer 25

Hypoglycemia
Anorexia, weight loss, nausea, vomitting
Weakness
Hypotension
Hyperkalemia
Metabolic acidosis
Decreased pubic and axillary hair fin females 
Hyperpigmentation

ACTH levels increased( negative feedback effect of decreased cortisol)

Question 26

What is the treatment of Conn syndrome (aldosterone-secreting tumor)?

Answer 26

Aldosterone antagonist (e.g. spironolactone) surgery

Question 27

What are the clinical features of Conn syndrome?

Answer 27

Hypertension
Hypokalemia
Metabolic alkalosis
Decreased renin levels