Renin Angiotensin System – Juxtaglomerular Apparatus – Acid Base Balance
Renin Angiotensin System (RAS)
The Renin-Angiotensin System (RAS) plays a crucial role in regulating blood pressure, blood volume, and sodium-water balance. It is primarily controlled by the kidneys through the release of the enzyme renin.
Activation of the Renin-Angiotensin System
- When blood volume and blood pressure decrease, the walls of the afferent arterioles are stretched less, prompting the juxtaglomerular (JG) cells to secrete renin into the bloodstream.
- Sympathetic nervous stimulation also triggers the release of renin from the JG cells.
- Renin acts on angiotensinogen (produced by the liver), converting it into angiotensin I, a 10-amino acid peptide.
- Angiotensin I is then converted to angiotensin II by the angiotensin-converting enzyme (ACE), mainly in the lungs. Angiotensin II is the physiologically active form of the hormone.
Functions of Angiotensin II
Angiotensin II affects renal and cardiovascular physiology in three major ways:
- Decreases Glomerular Filtration Rate (GFR): Causes vasoconstriction of the afferent arterioles, reducing blood flow into the glomeruli.
- Enhances Reabsorption of Na⁺ and Water: Stimulates Na⁺–H⁺ antiporters in the proximal convoluted tubule, promoting sodium and water reabsorption.
- Stimulates Aldosterone Secretion: Triggers the adrenal cortex to release aldosterone, which acts on the collecting ducts to reabsorb more Na⁺ and excrete more K⁺. This increases water reabsorption, raising blood volume and blood pressure.
Juxtaglomerular Apparatus (JGA)
The juxtaglomerular apparatus (JGA) is a specialized structure in the nephron that plays a central role in regulating blood pressure and GFR through the renin-angiotensin system.
Structure and Location
- The JGA is located where the afferent arteriole and the distal convoluted tubule (DCT) come in direct contact.
- It is composed of:
- Juxtaglomerular (JG) cells: Found in the walls of the afferent arteriole; secrete renin in response to low blood pressure.
- Macula densa: Specialized cells of the DCT that detect Na⁺ concentration in the filtrate.
- Mesangial cells: Supportive cells that transmit signals between the macula densa and JG cells.
Functions of JGA
- The JG cells release renin when glomerular blood flow or pressure decreases.
- Renin converts angiotensinogen → angiotensin I → angiotensin II.
- Angiotensin II acts as a potent vasoconstrictor, increasing glomerular blood pressure and GFR.
- It also stimulates the adrenal cortex to release aldosterone, which increases sodium and water reabsorption in the DCT and collecting duct.
- This mechanism, known as the Renin-Angiotensin Mechanism, ultimately helps restore blood pressure and blood volume.
Acid-Base Balance
The kidneys play an essential role in maintaining the body’s acid-base balance. Proper pH regulation is vital for enzyme activity, nerve conduction, and muscle contraction. A disturbance in this balance can lead to acidosis or alkalosis, causing severe effects such as arrhythmias or seizures.
Mechanisms Maintaining Acid-Base Balance
There are three main renal mechanisms responsible for maintaining acid-base balance:
- Excretion of Hydrogen (H⁺) Ions
- Bicarbonate (HCO₃⁻) Reabsorption
- Bicarbonate (HCO₃⁻) Production
1. Excretion of Hydrogen (H⁺) Ions
Hydrogen ions are actively secreted into the tubular lumen to regulate blood pH. This occurs via two main mechanisms:
- As Dihydrogen Phosphate (H₂PO₄⁻): H⁺ ions are secreted by hydrogen-ATPase pumps in α-intercalated cells. Excess phosphate in the lumen binds these H⁺ ions to form H₂PO₄⁻, which is excreted. This increases blood pH.
- As Ammonium (NH₄⁺): In the proximal convoluted tubule (PCT), glutamine is metabolized into ammonium (NH₄⁺) and bicarbonate. Ammonium ions carry hydrogen into the urine, increasing blood pH. Ammonia also buffers H⁺ ions secreted later in the collecting duct.
2. Bicarbonate (HCO₃⁻) Reabsorption
Bicarbonate reabsorption mainly occurs in the PCT and helps maintain plasma buffering capacity.
- H⁺ ions are secreted into the lumen through the Na⁺–H⁺ exchanger, where they combine with filtered bicarbonate to form carbonic acid (H₂CO₃).
- Carbonic anhydrase catalyzes the breakdown of H₂CO₃ into CO₂ and H₂O, which diffuse into tubular cells.
- Inside the cell, carbonic anhydrase reforms H₂CO₃, which dissociates into H⁺ and HCO₃⁻.
- HCO₃⁻ is reabsorbed into the blood, while H⁺ is secreted back into the lumen, maintaining the cycle.
3. Bicarbonate (HCO₃⁻) Production
The kidneys can also produce new bicarbonate ions, which help neutralize acid and maintain pH balance.
- Cellular metabolism produces CO₂, which reacts with water to form H₂CO₃, dissociating into H⁺ and HCO₃⁻.
- The HCO₃⁻ enters the plasma, while the H⁺ is secreted into the tubular lumen.
- Bicarbonate can also be produced from amino acids like glutamine, generating ammonium ions (NH₄⁺) that are excreted in urine.
Detailed Notes:
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