L3 Adrenal Gland Physiology Flashcards
Where does Mineralocorticoid Synthesis Occur?
Zona Glomerulosa of the Adrenal Cortex
What regulates natriuresis in renal distal tubules and collecting ducts?
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
Aldosterone’s Action in Principal Cells?
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
Aldosterone’s Action in Intercalated Cells?
Favors excretion of protons and retention of bicarbonate
Process of RAAS stimulation of Aldosterone?
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)
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
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
How are aldosterone-specific actions exerted despite their similarity with glucocorticoids?
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
Consequences of 11β-Hydroxysteroid Dehydrogenase II insufficiency?
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
___________________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!!
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!!
Aldosterone Synthesis is upregulated by ________ and ________, mediated through _____________ receptors
Aldosterone Synthesis is upregulated by Angiotensin II and K+, mediated through mineralocorticoid receptors
Cortisol synthesis is stimulated by _________from ____________ , mediated by ______________ receptor
Cortisol synthesis is stimulated by ACTH from the anterior pituitary gland, mediated by glucocorticoid receptor
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 __________
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
Decscribe the Cortisol Awakening response (CAR)?
Cortisol Awakening response (CAR):Pulsatile secretion w/ peak in cortisol shortly after waking
Circadian Rhythm: Suprachiasmatic Nucleus (light/dark responsive)
Primary Metabolic Actions of Cortisol?
________ muscle protein catabolism
_______ triglyceride breakdown (Adipose Tissue)
________ hepatic gluconeogenesis
_________ muscle insulin sensitivity => _________________
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)
Secondary Physiological Actions of Cortisol?
Suppresses Immune and Inflammatory responses
Maintains normal BP and cardiac output
Water/electrolyte balance (Binds some mineralocorticoid receptors despite 11HSDß2 activity)
Stress response
Primary/Secondary Causes of Cushing’s Syndrome?
Symptoms?
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
Condition associated with excessive anterior pituitary ACTH production?
Cushing’s Disease: Leads to excessive cortisol release from Zona Faciculate of adrenal cortex
Acute crisis caused by significant loss of both glucocorticoid and mineralocorticoid production
Addisonian Crisis
Caused by autoimmune-mediated loss of adrenal cortex tissue => mineralocorticoid and glucocorticoids deficiency
Site of Adrenal Androgen/Estrogen Synthesis?
What regulates this?
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
Where does glucocorticoid (cortisol) synthesis occur?
Zona Fasciculata:
75% of the adrenal cortex
Site of Glucocorticoid synthesis (Cortisol)
Stimulated by ACTH from the pituitary gland
Most abundant circulating androgen? Where does it originate?
DHEA (dehydroepiandrosterone): from Zona Reticularis of Adrenal Cortex
Role/Regulation of DHEA?
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)
From where is the Adrenal Medulla derived?
Derived from embryonic neural crest
The Adrenal Medulla contains _________________ (modified postganglionic sympathetic neuron). What are they responsible for?
The Adrenal Medulla contains Chromaffin Cells (modified postganglionic sympathetic neuron)
- Releases epinephrine (80%) and norepinephrine (20%) into bloodstream when stimulated
Secretions of Adrenal Medulla?
Releases epinephrine (80%) and norepinephrine (20%) into the bloodstream when stimulated (sympathetically from the spinal cord)
Differing Actions of Epinephrine and Norepinephrine?
a-adrenergic receptors preferentially bind norepinephrine
b-adrenergic receptors preferentially bind epinephrine
Hormones released by the Adrenal Cortex?
Zona Glomerulosa (Mineralocorticoid Synthesis)
Zona Fasciculata (Glucocorticoid Synthesis)
Zona Reticularis ( DHEA/Estrogen Synthesis)
