Renal Physiology Part 3: Renin-angiotensin-aldosterone system, Chronic kidney diseases, Micturition control

Renin-Angiotensin-Aldosterone System (RAAS)

  • The renin-angiotensin-aldosterone system (RAAS) regulates arterial blood pressure.
  • The RAAS is initiated by the juxtaglomerular apparatus in the kidneys.

Juxtaglomerular Apparatus

  • The juxtaglomerular apparatus is where the distal tubule passes between the afferent and efferent arterioles of the same nephron.
  • It consists of granular cells and macula densa cells.
Granular Cells
  • Granular cells secrete renin.
  • They act as intrarenal baroreceptors; when blood pressure decreases within the afferent arteriole, they secrete more renin.
  • They are innervated by the sympathetic nervous system; increased sympathetic activity stimulates renin secretion.
Macula Densa
  • The macula densa senses sodium and chloride concentrations in the distal tubule.
  • If sodium and chloride concentrations decrease, the macula densa cells stimulate the granular cells to secrete more renin.

RAAS Cascade

  1. Renin Release:
    • Renin is released from the kidney in response to decreased blood pressure, decreased sodium/chloride in the distal tubule, or increased sympathetic activity.
  2. Angiotensinogen Conversion:
    • Renin converts angiotensinogen (produced by the liver) into angiotensin I.
  3. Angiotensin I to Angiotensin II:
    • Angiotensin-converting enzyme (ACE), primarily in the lungs, converts angiotensin I into angiotensin II.
  4. Aldosterone Release:
    • Angiotensin II stimulates the adrenal cortex to release aldosterone.

Aldosterone's Effects

  • Aldosterone increases sodium reabsorption in the distal tubules and collecting ducts.
  • It promotes the insertion of additional sodium channels (ENaC) in the luminal membrane of tubular cells.
  • It also promotes the insertion of additional Na+−K+Na^+-K^+-ATPase pumps into the basolateral membrane.
  • Chloride follows passively to maintain charge equilibrium.
  • Increased sodium and chloride in the bloodstream and tissues lead to an increase in ECF volume as water follows to maintain osmotic balance.

Overall Effects of RAAS Activation

  • Increased total peripheral resistance.
  • Increased sodium chloride reabsorption.
  • Increased ECF volume.
  • Increased arterial blood pressure.
  • Decreased blood pressure sensed by stretch receptors in the heart and artery walls inhibits the system (negative feedback).

Chronic Kidney Disease (CKD)

  • Chronic kidney disease (CKD) is a condition lasting 3 months or more.
  • It involves progressive and irreversible loss of kidney structures.
  • Approximately 10% of the UK population has CKD.
  • It cannot be prevented by vaccines or cured by medication, nor does it disappear.
  • Symptoms often appear only after the disease is well-advanced, hence referred to as the "Quiet Disease".

Causes of CKD

  • Variety of kidney diseases (e.g., genetic, polycystic kidney disease, cancer).
  • Secondary to another disease (e.g., diabetes or hypertension).
Polycystic Kidney Disease
  • Characterized by the growth of numerous cysts in the kidneys.

Symptoms of End-Stage Renal Disease

  • Dehydration, thirst
  • Electrolyte imbalance
  • Acid-base disturbances
  • Anorexia, nausea (due to accumulation of metabolic wastes)
  • Anemia (due to decreased erythropoietin secretion), bleeding
  • Hypertension & oedema (due to RAAS system activation, resulting in increased plasma volume)
  • Weakened muscles & bones (due to calcium and other mineral imbalance, and impaired activation of vitamin D)
  • Uremic encephalopathy (accumulation of ammonia and nitrogenous waste leading to delirium, seizures, & coma)

Treatment for CKD

  • Kidney transplant:
    • Optimal treatment, but limited availability of kidneys.
  • Dialysis:
    • Prolongs life while waiting for a kidney transplant.
    • Uses a semipermeable membrane to allow small solutes to exchange between blood and a dialyzing solution.
    • Eliminates contaminants from the blood (e.g., excess solutes, metabolites).
    • Two types: haemodialysis and peritoneal dialysis.
Haemodialysis
  • Uses a haemodialysis system/artificial kidney.
  • Involves an arterial blood line to the apparatus and a venous blood line from the apparatus.
  • Heparin is used to prevent clotting.
  • Blood is pumped through a cellophane membrane (tubing containing blood) surrounded by dialyzing solution.
  • A constant-temperature bath is used.
Peritoneal Dialysis
  • Uses the peritoneum as a dialysis membrane.
  • The peritoneal cavity is the space between the wall of the abdomen and the abdominal organs.
    • The peritoneum is the serous membrane that surrounds the internal organs (visceral peritoneum) and the abdominal wall (parietal peritoneum).
  • Dialysis fluid (2-3 L) is introduced into the abdomen over 10-15 minutes.
  • The fluid remains in the cavity, and waste products diffuse across the peritoneum from the underlying blood vessels.
  • After 4-6 hours, the fluid is removed and replaced with fresh fluid; several cycles are needed.

Urine Storage and Micturition

  • Urine, eliminated by the collecting ducts, is collected in the renal pelvis and then leaves the kidney through the ureter.
  • Newly formed urine is collected in the bladder.

Anatomy of the Bladder

  • Ureters connect to the bladder.
  • The urethra leads from the bladder to the external urethral orifice.
  • The bladder wall consists of smooth muscle.
  • There are ureteral openings and an internal sphincter.
  • The pelvic diaphragm and external sphincter control urine flow.

Micturition

  • Initiated when stretch receptors within the bladder wall are stimulated, sending impulses into the spinal cord.
  • The micturition reflex governs bladder emptying in infants.
  • Perception of bladder fullness appears before the external sphincter relaxes.
  • Voluntary control can override the micturition reflex, but urination cannot be indefinitely delayed.