Nephron Secretion and Reabsorption by Segment
The nephron performs both reabsorption and secretion at distinct anatomical segments, with the proximal tubule handling approximately 65% of filtered load reabsorption, the loop of Henle reabsorbing the majority of remaining filtered potassium, and the distal nephron/collecting duct providing fine-tuned regulation through aldosterone-mediated mechanisms.
Glomerulus
- Filtration only - blood is filtered free of cells and large proteins to produce an ultrafiltrate containing smaller circulating elements 1
- Potassium is filtered through the glomerulus as the initial step in renal potassium handling 2
Proximal Tubule (Proximal Convoluted Tubule and Proximal Straight Tubule)
Reabsorption
- Reabsorbs approximately 65% of the filtered load of water and sodium 2, 3
- Reabsorbs most or all filtered amino acids, glucose, solutes, and low molecular weight proteins 3
- Reabsorbs approximately 80% of filtered bicarbonate, playing a key role in acid-base balance 3
- Potassium is reabsorbed in the proximal tubule, with less than 10% of filtered K+ reaching the distal nephron in normal kidney function 2
- Alpha-ketoglutarate shows approximately 75% reabsorption in the proximal tubule under normal conditions 4
Secretion
- Organic anions (including diuretics, urate, and other anions) are secreted via organic anion transporters (OAT) from blood into the tubular lumen through MRP4 (multidrug resistance-associated protein 4) 2
- Alpha-ketoglutarate can undergo net secretion in the early proximal convoluted tubule during alkalotic states 4
Loop of Henle
Descending Limb
- Participates in countercurrent exchange mechanisms for urea reabsorption in the inner medulla 5
Thick Ascending Limb (Loop of Henle)
- Reabsorbs potassium - the majority of remaining filtered K+ is reabsorbed here, with less than 10% reaching the distal nephron 2
- Site of action for Na⁺-K⁺-2Cl⁻ cotransporter, the primary target of loop diuretics 2
- Approximately 20% of filtered alpha-ketoglutarate is reabsorbed in the pars recta and/or loop of Henle 4
- Can show net secretion of alpha-ketoglutarate in alkalotic states 4
Secretion
- Ammonia secretion occurs in the thick ascending limb as part of outer medullary countercurrent flux 5
Distal Convoluted Tubule
Reabsorption
- NaCl reabsorption through the sodium-chloride cotransporter (NCC) 2
- Site of distal tubular hypertrophy and hyperplasia with chronic diuretic use, leading to compensatory increases in sodium reabsorption and contributing to diuretic resistance 2
- This segment is the primary site of thiazide diuretic action 2
Secretion
- Potassium secretion occurs in the distal nephron, stimulated by aldosterone, increased urine flow, and increased sodium delivery 2
Collecting Duct
Reabsorption
- Sodium reabsorption mediated by aldosterone via epithelial sodium channels (ENaC) in principal cells 2
- Water reabsorption regulated by antidiuretic hormone (ADH) through aquaporin-2 channels 6
- Additional sodium reabsorption through pendrin and sodium-dependent chloride/bicarbonate exchanger in intercalated cells 2
Secretion
- Potassium secretion in the collecting duct is stimulated by aldosterone, increased urine flow, and increased sodium delivery to this segment 2
- Hydrogen ion secretion increases when ENaC-mediated sodium reabsorption is enhanced, contributing to metabolic alkalosis 7
Clinical Pitfalls
Avoid assuming uniform function along the nephron - transport capacity varies dramatically by segment, with proximal tubule dominance for bulk reabsorption but distal segments providing critical fine-tuning 3
Recognize that secretion and reabsorption can occur at the same site - the proximal tubule can switch from net reabsorption to net secretion of alpha-ketoglutarate depending on acid-base status 4
Remember that chronic diuretic use fundamentally alters nephron function - distal tubular hypertrophy increases reabsorptive capacity and creates resistance to further diuretic therapy 2, 7