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

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 www.MedicineNet.com

Aldosterone – the background Aldosterone promotes the renal excretion of K+,H2 and retention of sodium and hence water 1 Primary action of the Aldo. is the long term regulation of BP and plasma volume 2 Its secretion is associated with Renin Angiotensin system which is activated in hypotension It has significant role in CV health www.freemedical dictionary.com. www.hormone.org

Actions of Aldo

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 15- 20 mints It is metabolized in liver and excreted via kidneys

Aldosterone C25H28 O5

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

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

Aldosterone – the biosynthesis

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

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

Regulation of Aldo - ACTH

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

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

Regulation of Aldo

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)

Renin – Angiotensin- Aldosterone system

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

Aldo- mechanism of action

Metabolic actions of Aldosterone The primary action of the Aldosterone is through renal reabsorption, excretion and Angio. 11 To promote sodium and water retention 1 Excretion of K+ and H+ ions 2 ↑ plasma volume and BP via↑ vasoconstriction 3 ↑ force of cardiac contraction- direct effect 4

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)

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 1 Low K+ leads to muscle weakness, muscle cramps and cardiac arrhythmias 2 Diagnosis : low Renin and high Aldo. Normal K+ : 4.6 – 5.4meq/L www,mayoclinic.org

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 3.6-5.4) WWW.Wikepedia.com

Jan F Kennedy with Addison's disease

Addison's disease - MK Gandhi