The Nephron: Functional Unit of the Kidney — Structure and Filtration Process

Each kidney contains ~1 million nephrons, the microscopic units that filter blood, regulate fluid/electrolyte/acid-base balance, and produce urine.

Nephron Segments & Functions

Segment	Key Transport Processes
Glomerulus	Filtration: Hydrostatic pressure forces plasma water + solutes (<70 kDa) into Bowman's space. GFR ~125 mL/min. Retains cells, proteins.
Proximal Tubule (PCT)	Reabsorbs 65% filtered Na⁺, H₂O, Cl⁻, K⁺, HCO₃⁻, glucose, amino acids, phosphate. Secretes H⁺, drugs, toxins. Generates NH₄⁺ for acid excretion.
Loop of Henle	Descending limb: H₂O permeable (aquaporin-1) → concentrates tubular fluid. Ascending limb (thick): Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) → dilutes fluid; generates medullary gradient. Impermeable to H₂O.
Distal Convoluted Tubule (DCT)	Na⁺-Cl⁻ cotransporter (NCC); regulated by aldosterone (ENaC), PTH (Ca²⁺), thiazides act here.
Collecting Duct	Principal cells: Aldosterone → ENaC (Na⁺ reabs, K⁺/H⁺ secre). ADH → aquaporin-2 (H₂O reabs). Intercalated cells: Acid-base (H⁺/HCO₃⁻). Final urine concentration.

Two Nephron Types

• Cortical (85%): Short loops; mainly regulate plasma volume/composition.
• Juxtamedullary (15%): Long loops deep into medulla; generate osmotic gradient for concentrated urine.

Integrated Regulation

• RAAS: Low perfusion → renin → angiotensin II → aldosterone → Na⁺/H₂O retention, vasoconstriction.
• ADH (vasopressin): High osmolality/low volume → posterior pituitary → H₂O reabsorption in CD.
• ANP/BNP: Volume expansion → natriuresis, vasodilation.
• Tubuloglomerular feedback: Macula densa senses distal NaCl → adjusts afferent/efferent arteriolar tone → stabilizes GFR.

Clinical Relevance

• Diuretics target specific transporters (loop: NKCC2; thiazide: NCC; K⁺-sparing: ENaC/aldosterone antagonist).
• AKI: Tubular necrosis (ischemia/toxins) → loss of reabsorption → granular casts.
• Genetic tubulopathies: Bartter (NKCC2), Gitelman (NCC), Liddle (ENaC gain), Pseudohypoaldosteronism (ENaC loss).

The nephron's segmental specialization enables precise, regulated urine formation from an ultrafiltrate of plasma.