Renal Physiology: The Nephron

Functions of the Nephron

  • Filter
  • Reabsorb
  • Secrete

Electrochemical Potential (ECP)

  • Definition: Combination of electrical and chemical gradients affecting ion movement.
  • Components:
    • Electrical gradient
    • Chemical (concentration) gradient
  • Key Concept: Gradient + Driving Force = Direction of ion flow through the cell.

Electrochemical Driving Force

  • VDF: Electrochemical driving force value expressed in millivolts (mV).
  • Vm (Membrane potential): Determined via measurements or GHK equation.
  • Veq (Equilibrium potential): Determined using the Nernst equation.
  • Direction of Ion Flow: Depends on VDF's sign and the ion’s valence.

Membrane Potential and Ion Contributions

  • Major Contributors: K+, Na+, Cl-
  • Driving Forces:
    • If ion channels are closed, their relative permeability is set to zero.
  • Equations:
    • For typical neurons: pK : pNa : pCl = 1 : 0.05 : 0.45
  • Gas Constant (R): 8.314 J.K-1.mol-1
  • Faraday's Constant (F): 96485 C.mol-1

Nephrons

  • Segments:
    • Proximal tubule
    • Loop of Henle
    • Distal tubule
    • Collecting tubule
  • Approximately 106 nephrons per kidney, spanning renal cortex and medulla.

Nephron Epithelium

  • Structure: Lined with a single layer of epithelial cells (apical and basolateral sides).
  • Functionality Depends On: Type of epithelial cells which dictate ionic and water flow.

Permeability and Transport Mechanisms

General Rules for Movement:

  • Na+ Flow: Primarily dictates ionic movements; water follows sodium.

Proximal Tubule: Reabsorption and Secretion

  • Reabsorption:
    • Na+ (~66%), HCO3- (~85%), K+ (~65%), Water (~60%), Organic substrates (sugars, amino acids).
  • Secretion:
    • H+, Cl-, Uric acid, and exogenous agents.

Active Transport in Proximal Tubule

  • Na+-K+ ATPase:
    • Pumps 3 Na+ out per 2 K+ in; requires ATP, establishes ECP gradient.
    • Coupled transport mechanisms for organic molecules with Na+ reabsorption.

HCO3- Reabsorption and H+ Secretion

  • Mechanism: Na+ Entry via Na+-H+ exchanger (1:1 ratio); lowers pH (more acidic).
  • Buffering Mechanism: H+ buffered by HCO3- to generate carbonic acid.
  • Carbonic Anhydrase: Breaks down H2CO3 into H2O and CO2 allowing HCO3- export.

Uric Acid Secretion

  • Source: Metabolized from purines in the liver.
  • Transporters: URAT1, OAT1, OAT4 handle uric acid's secretion and reabsorption.
  • Clinical Note: Build-up can lead to gout or kidney stones.

Loop of Henle Summary

  • Main Actions: NaCl & K+ Reabsorption; Water remains due to impermeability of the ascending limb.
  • Segment Specialization: Thin descending limb permeable to water (aquaporins); ascending limb is a diluting segment (impermeable to water).

Distal Tubule and Collecting Tubule

  • Distal Tubule Functions: Continued Na+ and Cl- reabsorption with Ca2+ actively transported and hormone-regulated.
  • Collecting Tubule Role: Less than 5% NaCl reabsorption with significant hormonal control affecting water and ion transport.
  • Cell Types: Principal cells (involved in Na+, K+, and water transport) and intercalated cells (H+ secretion).

Diuretics

  • Mechanism: Diuretics alter kidney function to enhance urine output by affecting nephron segments, mainly targeting Na+ reabsorption processes in specific segments.

Summary

  • Proximal tubule serves as a bulk reabsorber with unchanged composition in tubular fluid further down, while the loop of Henle dilutes urine significantly. The distal and collecting tubules function under hormonal modulation for precise ion and fluid balance.