Disorders of the Adrenals

Adrenal Medulla

- Secretes catecholamines (epinephrine, norepinephrine, and dopamine)

Histology
- Preganglionic fibers use acetylcholine as NTs to directly make contact with
postganglionic cells, which secrete catecholamines (mainly epinephrine) into circulation.
- Medullary parenchymal cells accumulate and store their hormone products in dense
secretory granules.
o These cells and granule have a high affinity for chromium salts, and are called
chromaffin cells (which contain chromaffin granules: containing catecholamines)
o Types:
 Epinephrine secreting cells: larger, less dense granules; M.C. 90%
 Norepinephrine secreting cells: smaller, very dense granules; 10%

Physiology
- Help regulate metabolism, contractility of cardiac and smooth muscle and
neurotransmission.
- Catecholamines have short half-life (2 min) once in circulation
o Secretion is ↓ in basal state and even further reduced while sleeping
o In emergency situations, there is ↑ adrenal catecholamine secretion
 Part of the sympathetic “fight or flight” response
 Other physiologic stress (physical, metabolic, etc.) leads to secretion

- Norepinephrine and epinephrine are mediated by two classes of receptors:

o Alpha:
 Alpha 1: mediate smooth muscle contraction in blood vessels and GU
tract and increase glycogenolysis (breakdown of glycogen to glucose)
 ↑ intracellular calcium
 Alpha 2: mediate smooth muscle relaxation in the GI tract and
vasoconstriction in some blood vessels; also ↓ insulin secretion
 ↓ Intracellular cAMP

o Beta:
 Beta 1: mediate an increased rate and force of myocardial contraction
and stimulate lipolysis and renin release
 ↑ Intracellular cAMP
 Beta 2: mediate smooth muscle relaxation in the bronchi, vasodilation,
GU tract, and GI tract, and increase hepatic gluconeogenesis (generation
of glucose) and glycogenolysis, muscle glycogenolysis, and ↑ insulin and
glucagon.
 ↑ Intracellular cAMP
 o Alpha 1 + Beta 1: generally found in organs and tissues (eg, heart and gut)
heavily innervated by sympathetic nerves; preferentially stimulated by
norepinephrine (especially if release from nerve endings)

o Alpha 2 + Beta 2: situated in post-junctional sites in organs and tissues (eg,

uterine and bronchial skeletal muscle) remote from sites of norepinephrine
release; preferentially stimulated by circulating catecholamines, especially
epinephrine.


Effects of Catecholamines
- Termed “fight or flight” hormones; due to effects on heart, blood vessels, smooth
muscles, and metabolism  response to stress

- In peripheral circulation:
o Norepinephrine  produces vasoconstriction in most organs (a1)
o Epinephrine  produces vasodilation receptors in skeletal muscle and liver and
vasoconstriction everywhere else (b2) – vasodilatory effects are generally
greater (lowers total peripheral resistance)

- Effects on metabolism: (mediated by alpha and beta receptors)

o Action  increases level of circulating glucose and free fatty acids
(metabolic fuel)
 Glycogenolysis (breakdown of glycogen to form glucose)
 Lipolysis (lipid breakdown)
 Insulin secretion
o Primarily epinephrine: action on 4 target tissues
 Liver
 Muscles
 Pancreas
 Adipose tissue

- Effects of Dopamine
o Centrally: inhibits prolactin secretion
o Peripherally: (injected)
 Small dose  renal vasodilation
 Moderate dose  vasodilation of mesenteric and coronary circulation
and vasoconstriction peripherally
 Large dose increase systolic BP without affecting diastolic
o Positive ionotropic effect (increase speed or force) on the heart (Beta 1)
Adrenal Cortex

- Secretes steroid hormones – including

1. Glucocorticoids (cortisol, corticosterone)
 Immunosuppressive and anti-inflammatory effects
 used to treat diseases and autoimmune
disorders
 Deleterious effects in states of hypercortisolism
2. Mineralocorticoids (aldosterone)
3. Androgens (DHEA)
- Help regulate carb, protein, and fat metabolism
- Help regulate Na+ and K+ balance and ECF volume
- Glucocorticoids and mineralocorticoids are ESSENTIAL for
survival
- Major disorders:
o Hypercortisolism (Cushing’s)
o Adrenal insufficiency (Addison Disease)
o Hyperaldosteronism
o Hypoaldosteronism
o Androgen excess

Anatomy
- Three layers
o Zona glomerulosa: columnar or pyramidal cells in clusters;
secrete mineralocorticoids – primarily aldosterone
o Zona fasciculata: polyhedral shaped cells in columns;
secrete glucocorticoids and androgens
o Zona reticularis: small cells, irregularly arranged; secrete
glucocorticoids and androgens

Physiology:
- Control of ACTH and CRH involves:
1. Episodic secretion and daily rhythm of ACTH
2. Stress response of HPA axis
 Emotional stress, bodily injury, hypovolemia (stimulates vasopressin)
3. Negative feedback inhibition of ACTH secretion by cortisol

A. GLUCOCORTICOIDS: ↑ hepatic glucose; breakdown fat and protein for hepatic

gluconeogenesis; ACTH  very short half-life (10min); mainly cortisol
- In tissues: (mostly) glucocorticoids have a catabolic effect  promote degradation of
protein and fat to provide substrate for intermediary metabolism
- In liver: gluocorticoids have a synthetic (anabolic) effect  promoting uptake and use
of carbohydrates (to sunthesize glucose and glycogen), amino acids (to synthesize RNA
and protein enzymes), and fatty acids (as energy source)
* Glucocorticoids: antagonize the effects of insulin in peripheral tissues
NOT GOOD FOR DIABETICS  inhibits glucose uptake and metabolism

- In pts without diabetes, this stimulates an ↑ in insulin secretion as a compensatory

mechanism that prevents sequelae

B. MINERALCORTICOIDS: regulate Na+ excretion and maintain normal intravascular volume

- Aldosterone – principle mineralocorticoid; bound to plasma proteins; short half-life (20-
30 min); secretion regulated by RAAS, but also by pituitary ACTH

o RAAS: ↑ in K+ OR ↓ in Na+ = Stimulates aldosterone release

 RENIN excreted by the juxtaglomerular cells of kidneys in response to ↓
renal perfusion pressure
 Renin converts ANGIONTENSINOGEN to ANGIOTENSIN I
 In lunges, ANGIOTENSIN I is converted to ANGIOTENSIN II by ACE
 ANGIOTENSIN II binds to zona glomerulosa receptors and stimulate
synthesis and secretion of ALDOSTERONE  promotes water and Na+
retention
 ALDOSTERONE has negative feedback on RENIN
 Secretion of aldosterone and renin is highest in the early morning
- Target organs for aldosterone include:
o Kidney
 Works in the distal renal tubules and collecting ducts; acts to promote
exchange of Na+ for K+ and H+  ↑ Na+, ↓ K+ and H+ = ↑ urine acidity
 In BRAIN CELLS: do opposite  ↑K+ and ↓ Na+
o Colon
o Duodenum
o Salivary glands
o Sweat glands