Endocrine Aldosterone and Cortisol Flashcards
Recall: What hormones do adrenal glands secrete? What are their functions?
adrenal cortex:
1. zona glomerulosa –> aldosterone
2. zona fasciculata + zona reticularis –> cortisol, androgens
adrenal medulla - adrenaline, noradrenaline
Aldosterone - maintains electrolyte balance by promoting Na+ retention and K+ excretion
Cortisol - regulate BMR
Androgens - regulation of sexual characteristics
Explain some ways low volume state can cause hyponatremia.
(1) LOW BP
- ADH secreted to maintain BP by increasing AQP-2 channels –> Na+ osmotically active and will be excreted along with water
(2) ADRENAL INSUFFICIENCY
- cortisol has inhibitory effect on ADH –> lack of cortisol increases ADH
(3) HYPOTHYROIDISM
- low thyroid –> SIADH
Explain how aldosterone is synthesised in the zona glomerulosa.
- CHOLESTEROL acts as a precursor for all steroidal hormones and is stimulated by ANG II and ACTH
- CHOLESTEROL converted to PREGNENOLONE and PROGESTERONE which act as precursors for cortisol and sex steroids
- PREGNENOLONE and PROGESTERONE are converted to CORTICOSTERONE, 11-DEOXYCORTICOSTERONE AND 18-HYDROXYCORTICOSTERONE through actions of ALDOSTERONE SYNTHASE to form ALDOSTERONE
What are the 2 factors that stimulate aldosterone secretion.
- low BP (hypotension)
- hyperkalaemia (high serum K+ levels)
RECAP: What is the function of aldosterone?
How is aldosterone production regulated during HYPOTENSION?
Aldosterone –> maintains electrolyte balance by promoting Na+ retention and K+ excretion
HYPOTENSION
1. Low BP sensed by baroreceptors and stimulates JG cells in glomerulus to produce renin which converts ANGIOTENSINOGEN to ANG I (angiotensin I)
2. ACE (angiotensin converting enzyme) from lungs converts ANG I to ANG II
3. ANG II stimulates constriction of blood vessels (efferent and afferent arterioles) at different times to maintain GFR
4. ANG II is converted to aldosterone which stimulates sodium retention at the collecting ducts –> fluid follows sodium ions to be reabsorbed into system –> increased ECF volume to raise BP back to homeostatic levels
5. Negative feedback control acts to decrease renin secretion to prevent continuous expansion of ECF volume
RECAP: What is the function of aldosterone?
How is aldosterone production regulated during HYPERKALAEMIA?
Aldosterone –> maintains electrolyte balance by promoting Na+ retention and K+ excretion
HYPERKALAEMIA
1. High [K+] is sensed by mineralocorticoid receptors in adrenal cortex and stimulates aldosterone production at the zona glomerulosa
2. Aldosterone increases the number and activity of potassium channels (ROMK channels) at collecting ducts to increase secretion of K+ from system
3. Increased excretion of K+ through urine results in decreased serum K+ levels back to homeostatic level
Summarise the action of aldosterone. (2)
- increase BP <– increased sodium reabsorption in collecting ducts increases ECF volume as fluid follows osmotically-active Na+
- decrease serum K+ level <– enhance potassium secretion in collecting ducts to increase K+ excretion
Why does renal tubular fluid become more electrically negative upon action of aldosterone.
More Na+ is reabsorbed (Na+ retention) than K+ and H+ excreted –> loss of positive charges
Explain the independent action sof hypovolaemia and hyperkalaemia on ALDOSTERONE PRODUCTION. Do they result in the same result?
The action of increasing BP by increasing sodium reabsorption in collecting ducts to increase ECF volume is INDEPENDENT to decreasing serum K+ levels by enhancing K+ secretion in collecting ducts.
HYPOVOLEMIA:
1. Stimulates renin to stimulate angiotensiogen to ANG I –> ANG I converted to ANG II by ACE
2. Stimulates aldosterone to STIMULATE NCC (Na+-Cl–cotransporter) and ENaC (epithelial Na+ channel) to reabsorb Na+ –> fluid follows to increase BV and BP
3. ALSO INHIBITS ROMK channels from excreting K+ –> allow focus on NCC and ENaC to increase Na+ reabsorption to increase blood volume –> prevents hypokalaemia
HYPERKALAEMIA:
1. Inhibits renin and stimulates aldosterone
2. Stimulates ROMK to secrete K+ and stimulates SOME ENaC to absorb Na+
3. Low ANG II levels due to low renin + high K+ concentration inhibits NCC from uptake of Na+
4. Prevents excessive reabsorption of Na+ –> prevents fluid from following –> prevents hypovolemia
State the test used to determine pathology relating to hyperaldosteronism.
check renin:aldosterone ratio
- autonomous pathology should show LOW renin:aldosterone ratio
State some symptoms related to hyperaldosteronism (4)
- hypertension
- hypokalaemia
- metabolic alkalosis (related to loss of H+ from K+ excretion)
- pedal oedema
Using the HPA axis, explain how cortisol production is regulated.
- Stimuli: High stress/mornings
- Hypothalamus signalled to produce more CRH (corticotropin-releasing hormone)
- CRH is transported to anterior pituitary gland via the hypothalamic hypophyseal portal system (vascular link) to signal anterior pituitary to produce more ACTH (adrenocorticotropin hormone)
- ACTH is transported to adrenal cortex via the bloodstream and signals the zona fasciculata to produce more cortisol
State the actions of cortisol (5)
- Intermediary metabolism - raise blood glucose levels, maintain calcium-phosphate levels
- Survival during stress - mobilise energy reserves, maintain homeostatic control
- Vascular reactivity to catecholamines (E, NE)
- Immune suppression - focus on FoF reaction
- Anti-inflammatory effects - inhibits pro-inflammatory factors (cytokines, chemokines, TNF, IL-2, T and B cells) + promote anti-inflammatory factors (IL-1 antagonist)
State some symptoms related to hypercortisolism. (6)
- Hypertension
- Diabetes (intermediary metabolism patho)
- Osteoporosis (dysregulation of calcium-phosphate levels - bone resorption)
- Easy bruising
- Hypokalaemia
- High cortisol levels present in urine and plasma
In the scenario,
‘ HIGH CORTISOL, LOW ACTH’, state the level of pathology
PRIMARY ADRENAL PATHOLOGY!
- Physiologically, high cortisol levels should be corrected by negative feedback signal to anterior pituitary gland to lower levels of ACTH which then corrects excess cortisol
- Low ACTH achieved unable to effectively correct excess cortisol –> adrenal gland unable to respond/detect change in ACTH levels –> possible TUMOUR
In the scenario,
‘ HIGH CORTISOL, NOT LOW ACTH’, state the level of pathology
ANTERIOR PITUITARY PATHOLOGY!
- Physiologic negative feedback is evaded since ACTH levels shoudl be low to compensate for excessive cortisol
- Anterior pituitary is unable to respond to high cortisol levels to bring levels down to homeostatic level by decreasing production of ACTH –> possible CUSHING’S DISEASE
