Integrated nephron function

Integrated nephron function

Integrated nephron function

On this page

Glomerular Filtration - The Kidney's Sieve

  • Function: Ultrafiltration of blood to produce a protein-free filtrate. Normal GFR ≈ 125 mL/min or 180 L/day.
  • Filtration Barrier (Size & Charge Selectivity):
    • Fenestrated Capillary Endothelium: Blocks cells.
    • Glomerular Basement Membrane (GBM): Fused basal laminae with negative charge (heparan sulfate) repels albumin.
    • Podocyte Foot Processes: Slit diaphragms form the final barrier.
  • Starling Forces: GFR is governed by hydrostatic and oncotic pressure gradients. $P_{GC}$ (Glomerular Capillary Hydrostatic Pressure) is the main driver.

⭐ Loss of the GBM's negative charge (e.g., Minimal Change Disease) causes selective albuminuria, even without major structural changes on light microscopy.

Glomerular filtration barrier: endothelium, GBM, podocytes

Proximal Tubule - The Bulk Reabsorber

  • Workhorse of the nephron; reabsorbs ~65-80% of filtered solutes and water.
  • Fluid leaving is isotonic to plasma (~300 mOsm/L).

Key Functions:

  • Reabsorption: All glucose & amino acids; most $Na^+$, $Cl^-$, $K^+$, $H_2O$, and $HCO_3^-$.
    • $HCO_3^-$ reabsorption depends on carbonic anhydrase.
  • Secretion: $H^+$, $NH_4^+$, organic acids (PAH, urate), and bases (creatinine).

Proximal tubule cell: apical and basolateral transporters

High-Yield: Parathyroid hormone (PTH) inhibits the $Na^+/PO_4^{3-}$ cotransporter, causing phosphate excretion (phosphaturia). Carbonic anhydrase inhibitors (e.g., acetazolamide) act here, causing $HCO_3^-$ wasting.

Loop of Henle - Salty Medulla Maker

  • Primary Function: Establishes a hypertonic medullary interstitium via countercurrent multiplication, crucial for concentrating urine.
  • Descending Limb:
    • Highly permeable to H₂O, impermeable to NaCl.
    • H₂O passively flows out into the salty medulla.
    • Tubular fluid osmolarity ↑.
  • Ascending Limb:
    • Impermeable to H₂O.
    • Thin Ascending: Passive NaCl reabsorption.
    • Thick Ascending Limb (TAL): Actively reabsorbs NaCl via the Na-K-2Cl (NKCC) cotransporter. This is the engine of the system.
    • Tubular fluid becomes dilute (hypotonic).
  • Vasa Recta: Countercurrent exchange prevents washout of the medullary gradient.

Renal countercurrent mechanism

⭐ The Thick Ascending Limb's Na-K-2Cl (NKCC) cotransporter is the target for loop diuretics (e.g., Furosemide). Inhibition leads to potent diuresis by disrupting the medullary gradient.

Distal Nephron - Hormonal Fine-Tuning

The final, precise regulation of urine composition, primarily influenced by aldosterone and ADH to manage electrolyte and water balance.

  • Principal Cells: Major site of Na⁺/K⁺/H₂O regulation.

    • Aldosterone: Binds mineralocorticoid receptor → upregulates basolateral Na⁺/K⁺-ATPase and apical channels (ENaC, ROMK) → ↑Na⁺ reabsorption, ↑K⁺ secretion.
    • ADH (Vasopressin): Binds V2 receptor (Gs) → ↑cAMP → PKA activation → insertion of AQP2 channels into apical membrane → ↑H₂O reabsorption.
  • Intercalated Cells: Manage acid-base balance.

    • α-cells: Secrete H⁺ via H⁺-ATPase.
    • β-cells: Secrete HCO₃⁻.

image

K⁺-Sparing Diuretics: Amiloride and triamterene directly block the ENaC channel. Spironolactone and eplerenone are competitive aldosterone antagonists, preventing its nuclear action. Both mechanisms reduce Na⁺ reabsorption and K⁺ secretion.

High‑Yield Points - ⚡ Biggest Takeaways

  • Aldosterone (acting on the DCT/CD) and ADH (acting on the CD) are the principal regulators of volume and osmolarity.
  • The PCT is the bulk reabsorber: nearly all glucose/amino acids and ~65% of Na+ and H₂O.
  • The Loop of Henle generates the medullary gradient via countercurrent multiplication, essential for concentrating urine.
  • The DCT fine-tunes electrolytes: Aldosterone reabsorbs Na+, while PTH reabsorbs Ca²⁺.
  • The Collecting Duct controls final urine concentration via ADH-regulated aquaporins.

Practice Questions: Integrated nephron function

Test your understanding with these related questions

Which region of the nephron reabsorbs the highest percentage of filtered bicarbonate?

1 of 5

Flashcards: Integrated nephron function

1/10

The bulk of Na+ reabsorption occurs in the _____ (67%)

TAP TO REVEAL ANSWER

The bulk of Na+ reabsorption occurs in the _____ (67%)

proximal convoluted tubule

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial