GUE Physiology

• Kidney tubules


  • Major function is to reabsorb water and solutes from the tubular fluid, which is crucial for water and electrolyte homeostasis of the body
  • Transport mechanisms for various substances are different in different parts of the kidney tubule

  
• Normal Urine output is 1 ml/min (1440 ml/day)
• Transport mechanisms across tubular epithelium

  • Passive
  • Active

  
• Passive transport mechanisms


  • Diffusion
  • Facilitated diffusion
  • Solvent drag
  • Osmosis
• Diffusion


  Solutes are transported from their area of higher concentration to the area of lower concentration
• Facilitated diffusion


  Specific carrier protein in the membrane facilitates the process of diffusion
• Examples of facilitated diffusion

  • Reabsorption of glucose via glucose transporter
  • Reabsorption of sodium and potassium ions through water-filled channels
  • Transport of glucose, proteins and urea from the tubular fluid
• Coupled transport


  A form of facilitated diffusion, where two different molecules move in the same direction (symport) or opposite directions (antiport)
• Solvent drag

  When bulk amount of water is reabsorbed, the solutes dissolved in water are also transported along with water across the tubular epithelium
• Osmosis

  When a considerable amount of osmotically active solute is transported, water is reabsorbed along with it to maintain the osmotic balance
• Osmotic diuresis typically occurs in diabetes mellitus due to glycosuria

  
• Sodium reabsorption in proximal tubule

  1. Na+ enters the tubular epithelial cells along the electrochemical gradient

  2. Na+ -K+ ATPase on basolateral surface pumps 3 Na+ out of the cell and brings in 2 K+

  3. Na+ removed from the cell enters interstitial fluid, K+ diffuses out of the cell

  4. This creates a low Na+ concentration in the tubular cells

  5. Na+ from tubular fluid enters the cells via cotransport and antiport mechanisms on the apical membrane

  
• Percentage of Na+ reabsorption in different parts of the tubule

  • 67% in proximal tubule
  • 25% in thick ascending limb of loop of Henle
  • 5% in distal convoluted tubule
  • 3% in collecting duct
• Water reabsorption in proximal tubule

  1. Transcellular and paracellular reabsorption of NaCl and other solutes increases osmolality of fluid in lateral intercellular and interstitial spaces

  2. High permeability of proximal tubule epithelium allows water to pass through aquaporin 1 channels and paracellular pathways

  3. Water flows along the osmotic gradient via transcellular and paracellular pathways

  4. Reabsorption of water is coupled with reabsorption of solutes, especially Na+ and Cl-

  5. Bulk flow of water helps transport of other ions like K+ and Ca++ (solvent drag)

  6. Accumulation of water in interstitial space increases hydrostatic pressure, favoring transfer of water into ECF

  
• Loop of Henle


  • Reabsorbs about 25% of the filtered NaCl
  • Descending limb is permeable to water but not solutes, ascending limb is impermeable to water

  
• Mechanism of water reabsorption in proximal tubule

  1. Water reabsorption is efficient despite small difference between osmolality of tubular and interstitial fluids

  2. Water is reabsorbed via both transcellular and paracellular pathways

  3. High oncotic pressure and low hydrostatic pressure in peritubular capillary favor reabsorption of water
• Loop of Henle (LOH)

  • Reabsorbs about 25% of the filtered NaCl
  • Descending limb is permeable to water but not to solutes
  • Ascending limb is impermeable to water
  • Na+, K+, and Cl- are cotransported out of the thick segments of the ascending limb
  • Fluid in terminal part of descending limb becomes hypertonic as water moves out of the tubule
  • In the thin part of ascending limb, transport mechanism is predominantly passive and permeability to water is less
  • Active transport of Na+ is almost nil in the thin part of ascending limb

  
• Mechanism of solute transport in thick portion of ascending limb of LOH

  1. Na+-K+ ATPase on basolateral membrane actively pumps Na+ out of the cell

  2. Na+ transport is coupled with K+ and Cl- via Na+-K+-2Cl- channel

  3. K+ from the cell is taken out by K+ and ROMK channels

  4. Cl- from the cell is taken out by Cl- channel and CIC-Kb channel

  5. K+-Cl- symport on basal membrane also transfers Na+ and Cl- from the cell

  
• The loop of Henle reabsorbs approximately 15% of the filtered water, which occurs exclusively in the descending limb, the ascending limb being impermeable to it
• Inspite of active transport of solutes in thick ascending limb of LOH, water is not reabsorbed
• Distal convoluted tubule (DCT)

  • Relatively impermeable to water whereas solutes are transported
  • As solute is removed in excess of solvent, further dilution of the tubular fluid occurs
  • In the initial segment, Na+ and Cl- are reabsorbed from tubular fluid into the tubular cells by Na+-Cl- symporter
  • Only about 5% of the filtered water is removed in DCT

  
• Mechanism of solute reabsorption in distal convoluted tubule

  1. Na+-K+ ATPase on basolateral membrane actively pumps Na+ out of the cell

  2. Na+ transport is coupled with Cl- via Na+-Cl- cotransporter

  
• Collecting duct (CD)

  • Responsible for 3% of Na reabsorption and 15% of water reabsorption
  • Permeable for water in the presence of ADH, while impermeable for water in the absence of ADH

  
• Mechanism of water reabsorption by epithelial cells of collecting duct

  1. ADH increases cAMP formation in the cell by acting on V2 receptors

  2. cAMP stimulates protein kinase A activity that promotes insertion of vesicles containing aquaporin 2 on cell membrane

  3. cAMP also stimulates gene transcription that promotes formation of new aquaporin 2 in the cell

  
• In the absence of ADH, the cells of collecting duct are relatively impermeable to water, therefore urine becomes hypotonic

  
• Even in complete absence of ADH, about 2% filtered water is reabsorbed in the collecting duct
• Regulation of NaCl and Water Reabsorption

  • Hormonal Factors: Angiotensin II, Aldosterone, ANP
  • Neural Factors: Activation of sympathetic fibers results in increased NaCl and water reabsorption from the proximal tubule, thick ascending limb of LOH, distal tubule, and collecting duct

  
• Neural regulation is mainly through sympathetic innervation of kidney that controls water and NaCl reabsorption