L3 Adrenal Gland Physiology

Question 1

Where does Mineralocorticoid Synthesis Occur?

Answer 1

Zona Glomerulosa of the Adrenal Cortex

Question 2

What regulates natriuresis in renal distal tubules and collecting ducts?

Answer 2

Aldosterone plays an essential role in the regulation of plasma electrolytes, plasma volume and blood pressure

Primary:

• Increases Na+ absorption
• Increases K+ excretion

Secondary:

• Increases H2O absorption
• Increases Cl-absorption - electrostatic attraction

Question 3

Aldosterone’s Action in Principal Cells?

Answer 3

Increased activity of Na/K+ ATPase pumps on basolateral

Increased number of NA+ and K+ Channels inserted on apical: Facilitates increased absorption of Na+ and excretion of K+ from the distal tubule/collecting duct

• => increased reabsorption of water (Water follows Na+)
• => Cl- reabsorption - electrostatic attraction

Question 4

Aldosterone’s Action in Intercalated Cells?

Answer 4

Favors excretion of protons and retention of bicarbonate

Question 5

Process of RAAS stimulation of Aldosterone?

Answer 5

Angiotensinogen released by liver => converted by the Renin (Peptidase released by kidneys in response to decreased renal perfusion) to Ang I => Ang I converted to Ang II by ACE (surface of pulmonary/renal epithelium) => Ang II stimulates the release of Aldosterone from adrenal cortex => Tubular Na+ and Cl+ reabsorption, Water retention and K+ Excretion => effective circulating volume increases=> juxtaglomerular perfusion increases (Neg feedback on system)

Question 6

Syndrome associated w/ Primary Hyperaldosteronism?

Causes?

Effects on renal electrolytes/H2O absorption:

• Muscle Cramps and weakness due to: _________
• Metabolic ________ due to effect on intercalated cells
• ___________ plasma-free calcium levels
• ___________ H2O reabsorption

Answer 6

Conn’s Syndrome (Extreme Aldosterone Production):

Caused by:

• Adenoma: Aldosterone-secreting adrenal tumor (50-60%)
• Adrenal hyperplasia (40-50%)

Effects on renal electrolytes/H2O absorption:

• Muscle Cramps and weakness due to: hypernatremia, hypokalemia
• Metabolic Acidosis due to effect on intercalated cells: increased H+ excretion and HCO3- production
• Decreased plasma-free calcium levels (more bound to albumin)
• Increased H2O reabsorption => hypertension

Question 7

How are aldosterone-specific actions exerted despite their similarity with glucocorticoids?

Answer 7

Hydroxysteroid Dehydrogenase 11ß2 (Oxidase) is widely expressed in MINERALCORTICOID responsive tissue to convert CORTISOL to CORTISONE preventing minimizing unwanted activation of mineralocorticoid receptor by cortisol

Question 8

Consequences of 11β-Hydroxysteroid Dehydrogenase II insufficiency?

Answer 8

Syndrome of Apparent Mineralocorticoid Excess (SAME):

Chronic ingestion of glycyrrhetinic acid (licorice) => inhibition of 11HSDß2 activity => CORTISOL (glucocorticoid) no longer inactivated to CORTISONE => able to exert affects on mineralocorticoid (aldosterone) receptors =>hypertension and hypokalaemia

Question 9

___________________Caused by autoimmune-mediated loss of adrenal cortex tissue => mineralocorticoid and glucocorticoids deficiency

Hypoaldosteronsm leads to:

• _____natremia
• ______kalemia
• ______ plasma volume
• Cardiac _____________

Hyporcortisolism leads to:

• ______glycemia
• ______ hypotension
• ______=> Hyperpigmentation!!

Answer 9

Addison’s DiseaseCaused by autoimmune-mediated loss of adrenal cortex tissue => mineralocorticoid and glucocorticoids deficiency

Hypoaldosteronsm leading to:

• Hyponatremia
• Hyperkalemia
• Decreased plasma volume
• Cardiac arrhythmias

Hyporcortisolism leading to:

• Hypoglycemia
• Postural hypotension
• MSH Excess=> Hyperpigmentation!!

Question 10

Aldosterone Synthesis is upregulated by ________ and ________, mediated through _____________ receptors

Answer 10

Aldosterone Synthesis is upregulated by Angiotensin II and K+, mediated through mineralocorticoid receptors

Question 11

Cortisol synthesis is stimulated by _________from ____________ , mediated by ______________ receptor

Answer 11

Cortisol synthesis is stimulated by ACTH from the anterior pituitary gland, mediated by glucocorticoid receptor

Question 12

HPA Axis Contribution to Cortisol Secretion

Stress leads to ______________ release from Hypothalamus => _________ stimulates _________ secretion from the ___________ pituitary => ________ stimulates _________ production in Zona _____ of the adrenal cortex

• Regulated by negative feedback inhibition by __________

Answer 12

Stress leads to Corticotrophin Releasing Hormone (CRH) release from Hypothalamus => CRH stimulates ACTH secretion from the Anterior Pituitary => ACTH stimulates Cortisol production in Zona Fasciculate of the adrenal cortex

• Regulated by negative feedback inhibition by Cortisol on CRH and ACTH

Question 13

Decscribe the Cortisol Awakening response (CAR)?

Answer 13

Cortisol Awakening response (CAR):Pulsatile secretion w/ peak in cortisol shortly after waking

Circadian Rhythm: Suprachiasmatic Nucleus (light/dark responsive)

Question 14

Primary Metabolic Actions of Cortisol?

________ muscle protein catabolism

_______ triglyceride breakdown (Adipose Tissue)

________ hepatic gluconeogenesis

_________ muscle insulin sensitivity => _________________

Answer 14

INCR muscle protein catabolism => INCR plasma amino acids

INCR triglyceride breakdown (Adipose Tissue)=> INCR fatty acids and glycerol

INCR hepatic gluconeogenesis=> INCR plasma glucose

DECR muscle insulin sensitivity => brain glucose sparing (muscles less likely to take up glucose preserving available reserves for use by other tissues)

Question 15

Secondary Physiological Actions of Cortisol?

Answer 15

Suppresses Immune and Inflammatory responses
Maintains normal BP and cardiac output
Water/electrolyte balance (Binds some mineralocorticoid receptors despite 11HSDß2 activity)
Stress response

Question 16

Primary/Secondary Causes of Cushing’s Syndrome?

Symptoms?

Answer 16

Primary:

• Cortisol secreting adrenal tumor - adenoma
• Idiopathic adrenal hyperplasia

Secondary:

• Ectopic tumors that secrete ACTH => Acts on adrenal gland INCR cortisol production
• Pituitary ACTH excess (Cushing’s DISEASE)

Symptoms relate to METABOLIC actions:

• Hyperglycemia => glycosuria
• Insulin resistance
• Obesity

Question 17

Condition associated with excessive anterior pituitary ACTH production?

Answer 17

Cushing’s Disease: Leads to excessive cortisol release from Zona Faciculate of adrenal cortex

Question 18

Acute crisis caused by significant loss of both glucocorticoid and mineralocorticoid production

Answer 18

Addisonian Crisis

Caused by autoimmune-mediated loss of adrenal cortex tissue => mineralocorticoid and glucocorticoids deficiency

Question 19

Site of Adrenal Androgen/Estrogen Synthesis?

What regulates this?

Answer 19

Zona Reticularis:
Innermost Cortical Layer adjacent to Medulla
10-15% of the adrenal cortex
Doesn’t become functional until early childhood (age 6)

ACTH controls the regulation of:
DHEA (dehydroepiandrosterone) –most abundant circulating androgen
Small amounts of estrone and estradiol17b

Question 20

Where does glucocorticoid (cortisol) synthesis occur?

Answer 20

Zona Fasciculata:
75% of the adrenal cortex
Site of Glucocorticoid synthesis (Cortisol)
Stimulated by ACTH from the pituitary gland

Question 21

Most abundant circulating androgen? Where does it originate?

Answer 21

DHEA (dehydroepiandrosterone): from Zona Reticularis of Adrenal Cortex

Question 22

Role/Regulation of DHEA?

Answer 22

Weak Androgen=> can be converted to more potent form (Testosterone)

Important role in:

• Development of secondary sexual characteristics in females
• Development of Male Sex Organs

Regulated by ACTH (NOT pituitary gonadotrophins)

Question 23

From where is the Adrenal Medulla derived?

Answer 23

Derived from embryonic neural crest

Question 24

The Adrenal Medulla contains _________________ (modified postganglionic sympathetic neuron). What are they responsible for?

Answer 24

The Adrenal Medulla contains Chromaffin Cells (modified postganglionic sympathetic neuron)

• Releases epinephrine (80%) and norepinephrine (20%) into bloodstream when stimulated

Question 25

Secretions of Adrenal Medulla?

Answer 25

Releases epinephrine (80%) and norepinephrine (20%) into the bloodstream when stimulated (sympathetically from the spinal cord)

Question 26

Differing Actions of Epinephrine and Norepinephrine?

Answer 26

a-adrenergic receptors preferentially bind norepinephrine

b-adrenergic receptors preferentially bind epinephrine

Question 27

Hormones released by the Adrenal Cortex?

Answer 27

Zona Glomerulosa (Mineralocorticoid Synthesis)

Zona Fasciculata (Glucocorticoid Synthesis)

Zona Reticularis ( DHEA/Estrogen Synthesis)