What is the function of the nephron and how is it maintained?

Nephron Function and Maintenance

The nephron is the basic functional unit of the kidney responsible for filtering blood, regulating fluid balance, removing waste products, maintaining electrolyte homeostasis, and contributing to acid-base balance through the processes of filtration, reabsorption, and secretion.

Structure and Components of the Nephron

The kidney contains over 1 million nephrons, each consisting of:

• Glomerulus: Filters blood free of cells and large proteins, producing an ultrafiltrate
• Tubular system: Processes the ultrafiltrate through specialized segments
  • Proximal convoluted tubule
  • Loop of Henle
  • Distal convoluted tubule
  • Collecting duct

Core Functions of the Nephron

1. Filtration

• Occurs at the glomerulus where blood is filtered across the glomerular filtration barrier
• Filtration barrier consists of:
  • Endothelial cells of glomerular capillaries
  • Basement membrane
  • Podocytes (specialized epithelial cells)
• Glomerular filtration rate (GFR) is the volume of blood/plasma filtered per minute, normally 90-120 ml/min/1.73m² 1
• Prevents filtration of cells and large proteins while allowing water and small solutes to pass

2. Reabsorption

• Process of removing substances from the tubular fluid back into the bloodstream
• Majority of filtered water (99%) and sodium (99.5%) are reabsorbed
• Different segments of the tubule specialize in reabsorbing specific substances:
  • Proximal tubule: Glucose, amino acids, sodium, water
  • Loop of Henle: Sodium, chloride, water
  • Distal tubule: Sodium, calcium
  • Collecting duct: Water (regulated by ADH)

3. Secretion

• Process of adding substances from peritubular capillaries into the tubular fluid
• Important for eliminating waste products and regulating acid-base balance
• Examples: Hydrogen ions, potassium, and certain drugs

Regulatory Mechanisms

Renal Autoregulation

• Maintains relatively constant renal blood flow and GFR despite fluctuations in systemic blood pressure 1
• Two primary mechanisms:
  1. Myogenic response: Afferent arterioles constrict in response to increased pressure
  2. Tubuloglomerular feedback: Macula densa cells sense sodium chloride delivery and signal afferent arterioles to adjust tone

Hormonal Regulation

• Renin-Angiotensin-Aldosterone System (RAAS):
  • Regulates blood pressure and fluid balance
  • Activated by decreased renal perfusion pressure
  • Results in vasoconstriction and sodium retention 1
• Antidiuretic Hormone (ADH):
  • Controls water reabsorption in collecting ducts
• Natriuretic Peptides:
  • Promote sodium excretion and vasodilation

Maintenance of Nephron Function

Preserving Renal Perfusion

• Adequate renal perfusion pressure (difference between mean arterial pressure and central venous pressure) should be maintained above 60 mmHg 2
• Reduced cardiac output or increased venous pressure can compromise renal perfusion 2

Protection from Hypertensive Damage

• Afferent arteriolar constriction protects glomeruli from high systemic pressure 1
• Impaired autoregulation (as in diabetes or CKD) can lead to glomerular hypertension and progressive kidney damage 1

Avoiding Nephrotoxic Agents

• Certain medications, contrast agents, and toxins can damage nephrons
• Preservation of residual kidney function is critical in patients with kidney disease 2

Clinical Implications

Assessment of Kidney Function

• GFR is the primary measure of kidney function
• Chronic kidney disease is classified based on GFR categories 2:
  • G1: Normal GFR (≥90 ml/min/1.73m²) with kidney damage
  • G2: Mildly decreased GFR (60-89 ml/min/1.73m²)
  • G3a: Mildly to moderately decreased GFR (45-59 ml/min/1.73m²)
  • G3b: Moderately to severely decreased GFR (30-44 ml/min/1.73m²)
  • G4: Severely decreased GFR (15-29 ml/min/1.73m²)
  • G5: Kidney failure (<15 ml/min/1.73m²)

Impact of Heart Failure on Nephron Function

• Heart failure can impair nephron function through:
  • Decreased cardiac output reducing renal perfusion
  • Increased venous pressure reducing filtration gradient
  • Neurohormonal activation (RAAS, sympathetic nervous system) 2

Pathophysiological Considerations

Nephron Loss and Adaptation

• Total nephron number varies widely among individuals (approximately 1 million per kidney) 3
• Lower nephron numbers may predispose to hypertension and chronic kidney disease 3
• Remaining nephrons adapt to loss by hyperfiltration, which may eventually lead to glomerulosclerosis

Cardio-Renal Interactions

• Bidirectional relationship between cardiac and renal function
• Decline in cardiac function can decrease renal perfusion
• Kidney dysfunction can contribute to volume overload and hypertension 2

Understanding nephron function and the mechanisms that maintain it is essential for preserving kidney health and managing kidney disease effectively.