The kidneys play a crucial role in maintaining body homeostasis through tubular reabsorption. This process involves the selective recovery of essential substances from the filtrate, preventing their loss in urine. Various transport mechanisms and membrane proteins work together to regulate this complex process.

Tubular reabsorption occurs along different segments of the nephron, each with unique characteristics. From the proximal convoluted tubule to the collecting duct, specific transport systems and hormones fine-tune the reabsorption of water, ions, and organic compounds to meet the body's needs.

Tubular Reabsorption

Transport mechanisms in nephron segments

• Proximal convoluted tubule (PCT)
  • Primary active transport utilizes Na+/K+ ATPase pumps to establish electrochemical gradients
  • Secondary active transport mechanisms include Na+/glucose cotransporter (SGLT) for glucose reabsorption, Na+/amino acid cotransporter for amino acid uptake, Na+/phosphate cotransporter for phosphate recovery, and Na+/H+ exchanger (NHE) for pH regulation
  • Passive transport occurs through facilitated diffusion of urea and water and osmosis of water via aquaporin channels
• Loop of Henle
  • Thin descending limb allows passive water reabsorption through osmosis due to the hyperosmotic interstitium
  • Thick ascending limb actively transports Na+, K+, and Cl- using the Na+/K+/2Cl- cotransporter (NKCC2) and facilitates secondary active transport of Ca2+ and Mg2+ via the paracellular pathway
• Distal convoluted tubule (DCT)
  • Active transport of Na+ and Cl- occurs through the thiazide-sensitive Na+/Cl- cotransporter (NCC)
  • Active Ca2+ reabsorption is mediated by the transient receptor potential vanilloid 5 (TRPV5) channel
• Collecting duct
  • Antidiuretic hormone (ADH) regulates water reabsorption through aquaporin-2 (AQP2) channels
  • Aldosterone stimulates Na+ reabsorption via the epithelial Na+ channel (ENaC)
  • Passive K+ secretion takes place through the renal outer medullary potassium (ROMK) channel

Membrane proteins for tubular reabsorption

• Na+/K+ ATPase establishes the electrochemical gradient for Na+ reabsorption and is located on the basolateral membrane of tubular cells
• Aquaporins (AQP) are water channels that facilitate osmotic water reabsorption, with AQP1 present in the PCT and thin descending limb and ADH-regulated AQP2 in the collecting duct
• Na+/glucose cotransporter (SGLT) reabsorbs glucose in the PCT by harnessing the Na+ gradient
• Na+/H+ exchanger (NHE) reabsorbs Na+ in exchange for H+ in the PCT, contributing to acid-base balance
• Na+/K+/2Cl- cotransporter (NKCC2) reabsorbs Na+, K+, and Cl- in the thick ascending limb, playing a role in the countercurrent multiplication system
• Epithelial Na+ channel (ENaC) reabsorbs Na+ in the collecting duct under the regulation of aldosterone

Passive vs active tubular reabsorption

• Passive reabsorption
  • Driven by concentration or electrochemical gradients without requiring cellular energy expenditure
  • Examples include osmosis of water through aquaporins and facilitated diffusion of urea
• Active reabsorption
  • Requires cellular energy in the form of ATP to move substances against their concentration or electrochemical gradients
  • Primary active transport directly utilizes ATP (Na+/K+ ATPase)
  • Secondary active transport relies on the electrochemical gradient created by primary active transport (Na+/glucose cotransporter, Na+/H+ exchanger)

Nephron permeability in urine formation

• Proximal convoluted tubule (PCT) is highly permeable to water, glucose, amino acids, and ions, reabsorbing ~65% of the filtrate volume through isotonic reabsorption
• Loop of Henle's thin descending limb is highly permeable to water but not solutes, while the thick ascending limb is impermeable to water but permeable to ions, creating a medullary concentration gradient
• Distal convoluted tubule (DCT) is relatively water-impermeable but selectively reabsorbs ions like Na+, Cl-, and Ca2+
• Collecting duct's water permeability is regulated by ADH (high ADH = concentrated urine, low ADH = dilute urine), and Na+ permeability is regulated by aldosterone (high aldosterone = increased Na+ and water reabsorption, reduced urine volume)

Reabsorption along the nephron

• Proximal convoluted tubule (PCT)
  • Water: Passively reabsorbed via osmosis through aquaporins
  • Organic compounds: Glucose and amino acids reabsorbed by secondary active transport, urea reabsorbed by facilitated diffusion
  • Ions: Na+ actively reabsorbed via Na+/K+ ATPase and secondary active transport, Cl- passively reabsorbed via paracellular pathway, HCO3- reabsorbed through Na+/H+ exchanger and H+ secretion
• Loop of Henle
  • Water: Passively reabsorbed in the thin descending limb
  • Ions: Na+, K+, and Cl- actively reabsorbed in the thick ascending limb via NKCC2
• Distal convoluted tubule (DCT)
  • Ions: Na+ and Cl- actively reabsorbed via NCC, Ca2+ actively reabsorbed via TRPV5
• Collecting duct
  • Water: Reabsorption regulated by ADH and aquaporin-2
  • Ions: Na+ reabsorption regulated by aldosterone and ENaC, passive K+ secretion via ROMK channels

Urine concentration by loop of Henle

• Loop of Henle
  • Countercurrent multiplication system: Thick ascending limb actively transports Na+, K+, and Cl- into the interstitium, creating a concentration gradient; thin descending limb is water-permeable, allowing osmotic water reabsorption and concentrating the tubular fluid
  • Countercurrent flow: Tubular fluid flows in opposite directions in the descending and ascending limbs, maintaining the medullary concentration gradient
• Vasa recta
  • Countercurrent exchange system: Hairpin-shaped capillaries run parallel to the loop of Henle with blood flowing in opposite directions in the descending and ascending portions
  • Passive exchange of solutes and water helps maintain the medullary concentration gradient and prevents washout by removing excess solutes and water
• Urine concentration: The medullary concentration gradient enables osmotic water reabsorption in the collecting duct, with ADH increasing water permeability to produce concentrated urine

Sites of tubular secretion

• Proximal convoluted tubule (PCT)
  • Organic anions (PAH, bile acids, uric acid) transported via organic anion transporters (OATs)
  • Organic cations (creatinine, histamine) transported via organic cation transporters (OCTs)
  • H+ secretion via Na+/H+ exchanger and H+-ATPase
  • K+ secretion via the apical K+ channel
• Distal convoluted tubule (DCT) and collecting duct
  • K+ secretion via the renal outer medullary potassium (ROMK) channel
  • H+ secretion via H+-ATPase and H+/K+-ATPase
  • NH4+ secretion for acid-base balance

Reabsorption regulation and efficiency

• Glomerular filtration rate (GFR) influences the amount of filtered substances entering the tubules for reabsorption
• Renal threshold is the plasma concentration above which a substance appears in the urine (e.g., glucose)
• Tubular maximum (Tm) represents the maximum rate of reabsorption for a specific substance
• Obligatory reabsorption occurs continuously and is not regulated by hormones (e.g., Na+ in PCT)
• Facultative reabsorption is hormone-regulated and adjusts to the body's needs (e.g., water reabsorption in collecting duct regulated by ADH)