PHYS - Tubular Transport

Question 1

TRANSPORT RATES

Answer 1

• T_M = the highest rate at which the renal tubules can move substances from the tubule lumen to the interstitial space and vice versa
• Reabsorption rate = filtered load – excretion rate
  
  • RR = T_X = (GFR*P_X) – (U_X*V)
• Secretion rate = excretion rate – filtered load
  
  • SR = T = (U_X*V) – (GFR*P_X)

Question 2

RENAL HANDLING OF GLUCOSE

Answer 2

• Na+ electrochemical gradient is used to pull glucose into the epithelium of the tubule with Na+ → Na+/glucose transporter
• Glucose then diffuses down its concentration gradient into the interstitial space
• Excess glucose, transporter maximum exceeded, glucose remains in high in urine
  
  • Below T_M
    
    • 20% of glucose filtered into nephron (80% remains in plasma)
    • Transporter → 100% reabsorbed into blood
    • No glucose in urine
  • Above T_M
    
    • 20% filtered into nephron (filtration fraction still 20%, but mg in that 20% is much higher)
    • Tubule transporter maxed out and less than 20% is reabsorbed
    • Remaining percentage = excreted in urine
• Percent of glucose filtered = 20% (filtration fraction)
• Filtration rate = amount (mg) of glucose filtered = directly related to plasma concentration of glucose
• Excretion rate = 0 below T_M
  
  • When T_M is exceeded, splay (increasing amount in urine)
  • Above splay, direct relationship between excreted amount and plasma glucose concentration
• Reabsorption rate = directly related to plasma concentration, and plateaus above T_M
• Sodium-Glucose co-Transporter 2 (SGLT2) is a new target for antidiabetic drugs that try to shift the excretion rate relationship left (increase amount of glucose secreted in urine)
  
  • Urine flow increased with DM because increased Na+ reabsorption in PCT → decreased Na+ sensed by macula densa cells in DCT → increased GFR
  • Increased GFR = increased filtration fraction = increased glucose in the tubules = osmotic diuresis = increased urine flow

Question 3

CLEARANCE

Answer 3

• A measure of renal handling of substances
• Given that C_In = GFR
  
  • C_X < C_In → substance is being reabsorbed or cannot be freely filtered, not fully cleared
    
    • Ex: RBCs, C_RBC = 0, unless pathology
    • Ex: C_Glu < C_In because glucose is reabsorbed
  • C_X > C_In → substance is being fully filtered and being secreted

Question 4

RENAL HANDLING OF PAH

Answer 4

• Para-aminohippurate
• 100% secreted into tubule by the organic anion transporter below T_M → allows determination of renal blood flow
  
  • C_PAH = RBF
  • Not produced by body; therefore, amount excreted is directly related to amount injected via IV at steady state
  • 20% filtered, last 80% secreted
• Above T_M = clearance decreases (less PAH removed from blood relative to amount still in blood, but amount of PAH in urine increases)
• C_PAH > C_In because of secretion of PAH into tubule

Question 5

RENAL HANDLING OF VARIOUS MOLECULES

Answer 5

• Decreased U_X = reabsorbed = glucose, proteins, AA, HCO₃, Na+
• Increased U­_X
  
  • Inulin – no reabsorption
  • Creatinine, PAH – no reabsorption, plus secretion, higher concentration in urine than inulin
• Filtration Fraction = GFR/RBF = 20%
  
  • Should be approximately equal to C_In/C_PAH = 21%

Question 6

GOUT

Answer 6

• Too much uric acid in blood → reduced clearance →uric acid crystal formation in tissues and joints
• Normal uric acid is about 99% freely filtered → reabsorption in PCT brings it to 1% → reabsorption/secretion in DCT brings it to 10% excreted
• Probenicid blocks reabsorption transporter and increases percent excreted
  
  • But can lead to uric acid crystal formation in tubules → kidney stones
• Allopurinol blocks uric acid production and is more often prescribed

Question 7

PASSIVE TRANSPORT OF UREA

Answer 7

• Urea is freely filtered and about 60% is passively reabsorbed by paracellular diffusion (between cells with wate)
• Factors affecting passive reabsorption
  
  • Tubular area
  • Urea permeability
  • Urea concentration gradient
    
    • Remove water = increased urea concentration = increased urea passive reabsorption
  • Tubular flow
    
    • Increased tubular flow = decreased urea reabsorption = increased urea clearance
• Hydration vs C_urea
  
  • Drinking water = increased flow = increased clearance!
  • Dehydration = decreased flow = increased reabsorption