Nephron

1. Overview

The nephron is the microscopic structural and functional unit of the kidney responsible for filtering blood, reabsorbing essential substances, and forming urine. Each human kidney contains approximately 1 to 1.5 million nephrons, and they collectively perform the critical task of maintaining homeostasis by regulating fluid, electrolytes, pH, and waste removal. Nephrons work continuously to filter about 180 liters of blood plasma daily, producing about 1 to 2 liters of urine.

2. Location

Nephrons are distributed throughout the renal cortex and renal medulla:

• Renal corpuscles (glomerulus + Bowman’s capsule) are located in the renal cortex.

• Tubular components extend variably into the medulla depending on nephron type.

Types of Nephrons:

• Cortical nephrons (85–90%): Short loops of Henle, primarily in the outer cortex.

• Juxtamedullary nephrons (10–15%): Long loops of Henle that extend deep into the medulla; crucial for urine concentration.

3. Structure

A nephron consists of two main parts:

1. Renal Corpuscle:

• Glomerulus: A tuft of capillaries where blood filtration begins.

• Bowman’s Capsule: A double-walled epithelial cup that encloses the glomerulus and collects the filtrate.

2. Renal Tubule:

• Proximal Convoluted Tubule (PCT): Major site of reabsorption of water, electrolytes, and nutrients.

• Loop of Henle: U-shaped structure with descending and ascending limbs; creates a medullary concentration gradient.

• Distal Convoluted Tubule (DCT): Involved in fine-tuning sodium, potassium, and pH balance.

• Collecting Duct (CD): Drains multiple nephrons and participates in final water and solute adjustments; influenced by ADH and aldosterone.

Associated Structures:

• Juxtaglomerular Apparatus (JGA): Regulates blood pressure and GFR via renin secretion and tubuloglomerular feedback. Includes:

  • Macula densa (in DCT)

  • Juxtaglomerular cells (in afferent arteriole)

4. Function

The nephron’s primary functions include:

• Filtration: Blood plasma is filtered in the glomerulus to form the filtrate (without proteins or blood cells).

• Reabsorption: Vital substances (e.g., glucose, amino acids, sodium, water) are reclaimed into the bloodstream, mainly in the PCT.

• Secretion: Additional wastes (e.g., hydrogen ions, potassium, drugs) are secreted into the tubule from peritubular capillaries.

• Excretion: The final urine is formed and delivered to the collecting ducts for transport to the renal pelvis and ureter.

5. Physiological Role(s)

Nephrons are essential for systemic physiological balance:

• Homeostasis: Maintain constant internal fluid environment (volume, pH, osmolarity).

• Blood pressure regulation: Through sodium balance and renin release (RAAS system).

• Acid-base balance: Secrete H⁺ and reabsorb HCO₃⁻ to regulate pH.

• Erythropoietin signaling: Via interstitial cells adjacent to nephrons in response to hypoxia.

• Calcium and phosphate regulation: Through vitamin D activation and PTH-mediated reabsorption in the DCT.

6. Clinical Significance

Acute Kidney Injury (AKI)

Sudden nephron dysfunction (e.g., due to ischemia, toxins) leads to reduced GFR and impaired fluid/electrolyte regulation. Nephrons may recover if basement membranes remain intact.

Chronic Kidney Disease (CKD)

Progressive nephron loss over time (e.g., due to diabetes, hypertension, glomerulonephritis). Symptoms appear when >50% of nephrons are nonfunctional. Leads to uremia, anemia, and bone disease.

Glomerular Disorders

Damage to the glomeruli (e.g., nephrotic or nephritic syndromes) leads to proteinuria, hematuria, and altered filtration. Biopsy often required for diagnosis.

Tubular Disorders

Defects in tubular transport mechanisms can lead to:

• Fanconi syndrome (PCT dysfunction)

• Bartter or Gitelman syndrome (loop/DCT disorders)

• Type I or IV renal tubular acidosis (DCT/CD dysfunction)

Diuretics

Medications targeting various nephron segments:

• Loop diuretics: Inhibit Na⁺/K⁺/Cl⁻ transport in thick ascending limb.

• Thiazides: Act on DCT to reduce Na⁺ reabsorption.

• K⁺-sparing diuretics: Affect collecting duct (e.g., aldosterone antagonists).

Kidney Transplant and Regeneration

Transplanted kidneys contain functioning nephrons that restore renal function. Research into nephron regeneration and stem cell therapy is ongoing but not yet clinically available.