L9: Mineralocorticoids

What is the primary mineralocorticoid produced in the adrenal cortex?

Aldosterone

Which kidney structures are the main targets of aldosterone action?

Distal tubules and collecting ducts of the nephron.

what type of hormone is aldosterone?

steroid hormone

How is aldosterone typically transported in the bloodstream?

Mostly bound to proteins; only a small fraction is free.

List the key homeostatic processes regulated by aldosterone.

1. Regulation of Na+, K+, and H+

2. water homeostasis

3. blood volume and blood pressure

4. pH

Which receptor mediates aldosterone’s intracellular effects?

Mineralocorticoid receptor (MR).

what are the main stimulus of RAAS?

1. hypotension

2. hyperkalemia

what else can stimulate RAAS?

1. hyponatremia

2. increase sympathetic activation

what stimulus will activate the juxtaglomerulus apparatus?

1. hypotension

2. hyponatremia

3. increase sympathetic activation

what does hyerkalemia stimulate in RAAS?

adrenal cortex to produce more aldosterone

what is responsible for converting angiotensin 1 to 2?

ACE

what stimulates aldosterone secretion?

angiotensin II

where is the juxtaglomerular apparatus of RAAS located?

in the kidneys

how does aldosterone affect the kidneys?

leads to salt and water retention = increased blood pressure

what produces angiotension?

the liver

what are the target tissues of aldosterone?

epithelial cells in the distal tubules and collecting ducts of nephron

where is the site of action of aldosterone?

1. Bowman’s capsule

2. proximal convoluted tubule

3. distal convoluted tubule

4. ascending limb

5. collecting duct

Where is the mineralocorticoid receptor located and what happens after aldosterone binds it?

MR is in the cytoplasm; the aldosterone-MR complex modulates gene transcription.

What membrane channels and pumps are upregulated by aldosterone to increase Na+ reabsorption?

Epithelial Na+ channels (ENaC) on the apical membrane and Na+/K+-ATPase on the basolateral membrane.

What happens to water when aldosterone promotes Na+ reabsorption?

Water follows Na+ via osmosis, increasing water reabsorption.

What are the renal and electrolyte effects of aldosterone on K+ and H+?

Increases excretion of K+ and H+ in the distal nephron.

What system stimulates the release of aldosterone?

Renin-angiotensin-aldosterone system (RAAS).

What is the role of renin in RAAS?

Renin cleaves angiotensinogen to form Angiotensin I.

what is expressed after aldosterone and MR have bound to DNA?

1. Na+/K+ ATPase

2. Na+ channels on apical membrane

3. K+ channels

4. H+ ion pumps and exchangers

Which adrenal zone produces mineralocorticoids like aldosterone?

Zona glomerulosa

what does aldosterone stimulate?

1. reabsorption of Na+ and water

2. K+ excretion

3. H+ excretion

What happens if aldosterone is deficient?

1. Sodium and water loss (dehydration, hypovolemia)

2. potassium and hydrogen ion retention (hyperkalemia, metabolic acidosis).

What is Addison’s disease?

Hypoadrenocorticism; deficient production of cortisol followed by aldosterone

What is a common nickname for Addison’s disease?

The Great Pretender

why can blood glucose not be maintained during cortisol deficiency?

impaired gluconeogenesis

What are the main symptoms of cortisol deficiency in Addison’s disease?

1. Poor stress response

2. weakness

3. hypoglycemia

4. lethargy

What percentage of the adrenal cortex is often destroyed in Addison’s crisis?

About 90%.

What is the emergency management for Addison’s crisis?

Glucocorticoid and mineralocorticoid replacement, fluid therapy, supportive care.

What electrolyte changes accompany aldosterone deficiency?

1. Hyperkalemia

2. metabolic acidosis

3. dehydration

4. hypovolemia

What cardiac effect can result from hyperkalemia associated with aldosterone deficiency?

Bradycardia due to effects on pacemaker cells.

why do cats with excessive aldosterone production get hypertension?

increase in water retention increases blood volume

why do cats with excessive aldosterone production get muscle weakness?

loss of potassium reduces muscle function

why do cats with excessive aldosterone production get hypokalemia?

increase in potassium loss through urine

What signs are typical in feline hyperaldosteronism?

1. Hypertension

2. hypokalemia

3. muscle weakness

4. hypervolemia

5. metabolic alkalosis

6. reduced neuromuscular excitability

What drug antagonizes the mineralocorticoid receptor to treat hyperaldosteronism?

Spironolactone

What is spironolactone’s mechanism of action?

block aldosterone MR in the distal tubule and collecting duct of nephron

What is the therapeutic effect of spironolactone?

Control of hypertension and hypokalemia in hyperaldosteronism.

What is the primary effect of aldosterone on the luminal side of principal cells?

Upregulation of ENaC channels to increase Na+ entry from the lumen.

What is the primary effect of aldosterone on the basolateral side of principal cells?

Increases Na+/K+-ATPase activity to reabsorb Na+ and export K+.

What is the overall effect of aldosterone on blood pressure?

Increases blood pressure by expanding blood volume via Na+ and water reabsorption.

Besides the kidney, which other tissues are affected by aldosterone?

Salivary glands, sweat glands, gastric mucosa, and the large intestine.

What is the role of aldosterone in water balance?

Promotes water reabsorption by driving Na+ reabsorption.