1. Aldosterone – A Mineralocorticoid Lecture NO : - 2nd MBBS
Dr Muhammad Ramzan

2. Aldosterone – the definition
Aldosterone is a steroid hormone , secreted from the outermost portion of the adrenal cortex – Zona Glomeruloza
Aldosterone regulates the :
Water and electrolyte balance in the body and is classified as Minerolocorticoid

3. Aldosterone – the background
Aldosterone promotes the renal excretion of K+,H2 and
retention of sodium and hence water
Primary action of the Aldo. is the long term regulation of BP and plasma volume
Its secretion is associated with Renin Angiotensin system which is activated in hypotension
It has significant role in CV health
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4. Actions of Aldo

5. Aldosterone -the properties
Aldosterone is available both in free and bound form
Bound form is associated with plasma globulin
free form is 30-50% and bound form 5-10%
Half life of Aldosterone is mints
It is metabolized in liver and excreted via kidneys

6. Aldosterone C25H28 O5

7. Aldosterone – The target tissues
Target organs are the ones with Aldo. receptors
The major ones are:
Renal: Distal convoluted tubules and collecting ducts
GIT: Salivary glands colon
Skin: Sweat glands

8. Aldosterone - Biosynthesis
Cholesterol is the precursor for all steroids
Most of the reactions are catalyzed by the enzymes of the mitochondria Cytochrome 450
Adrenodoxin acts as co factor
The pathway is mediated by Aldosterone Synthase

9. Aldosterone – the biosynthesis

10. Regulation of Aldo secretion
4 factors are important in regulation of Aldo.secretion
Adrenocoticotropin – ACTH
Potassium
Sodium and
Angiotensin 11

11. Aldo synthesis - Stimulators and Inhibitors
Stimulators : Angio 11; high K+, Low Na++ and ACTH
Inhibitors: ACEI; low K+ , high Na++
ACEI ) - Angiotensin converting enzyme inhibitors)

12. Regulation of Aldo. ACTH (2 pathways) A minor role
ACTH plays a minor role in Aldo Synthesis
However, physiologically it responds to the fluctuations of the serum levels of Aldosterone
Aldo is regulated through 2 pathways
Neuroendocrine regulation
Pituitary – Adrenal axis

13. Regulation of Aldo - ACTH

14. Aldo secretion and K+ ↑K+ ↑ Aldo synthesis
Serum K+ level is the key player in Aldo synthesis compared to other stimuli like ACTH infusion
Elevated K+ stimulates the Aldosterone synthesis
Low K+ inhibits the Aldo synthesis

15. Regulation of Aldo. Sodium low Na↑ Aldo secretion
Changes in the dietary sodium alters the Aldo. Secretion
Low sodium promotes the Aldo synthesis as it stimulates the conversion of corticosterone to Aldo
The reaction is catalyzed by Aldo Synthase
Corticosterone is a precursor in the Ado. Synthetic pathway

16. Regulation of Aldo

17. Regulation of Aldo. Angiotensin11(8 AAs) COOH terminal activates RA system
Angio11 is a peptide derived from the Angiotensinogen protein produced by the liver
Angio11 promotes the Aldo secretion through activation of Renin- Angiotensin – system (RAS)
COOH terminal of the Angio11 is suggested to stimulate the activity of Renin- Angio11- system
Aldo secretion is inhibited by the Angiotensin converting enzyme inhibitors (ACEI)

18. Renin – Angiotensin- Aldosterone system

19. Aldo. mechanism of action Activation of genes
Aldosterone is a steroid hormone and its mechanism of action is like ones - Activation of genes
The Minerolocorticoid receptors(MR) are located in the cytoplasm of the target organs – Renal tubules
Aldo binds with receptors to form HRC - translocated to the nucleus – HRE – transcription of mRNA – enters the
Cytoplasm- Translation of Proteins/enzymes for hormonal action

20. Aldo- mechanism of action

21. Metabolic actions of Aldosterone
The primary action of the Aldosterone is through renal reabsorption, excretion and Angio. 11
To promote sodium and water retention
Excretion of K+ and H+ ions
↑ plasma volume and BP via↑ vasoconstriction
↑ force of cardiac contraction- direct effect

22. Aldo – Secretion abnormalities
Aldosterone may be secreted in excess or there may be deficiency of its secretion
Both give rise to important clinical conditions that are not compatible with comfortable life
Excess is primary hyperadrenolism / hypokalemia .Conn's syndrome
Deficiency : Hypoaldosteronism is commonly associated with deficiency of Cortisole (Addison's disease)

23. Excess of Aldo- Conn's disease ↓K+ ↑BP
Major cause is adrenal adenoma
Retention of Sodium, water and hypertension leads to
Strokes; MI, heart failure and renal failure
Low K+ leads to muscle weakness, muscle cramps and cardiac arrhythmias
Diagnosis : low Renin and high Aldo.
Normal K+ : 4.6 – 5.4meq/L
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24. Aldo deficiency – Addison's disease
Aldo deficiency is commonly due to congenital adrenal hypoplasia or Aldo Synthase deficiency
Is commonly associated with Cortisole deficiency. Addison's disease
There ↑ in excretion of Sodium and water leading to ↓ in blood volume, BP and fatal shock
K+ is retained leading to hyperkalemia with nausea, muscle fatigue and paralysis (K+ > 7meq/L) normal )

25. Jan F Kennedy with Addison's disease

26. Addison's disease - MK Gandhi