Glomerular Filtration Rate

GFR

Filtration barrier

3 layers

• endothelium
• basement membrane - negative charge 
• epithelial cells with slit pores

Ultrafiltrate Composition

• Large proteins and cells excluded at endothelium.
• Electrolytes and small molecules are filtered.
• Negatively charged barrier inhibits filtration of negatively charged substances.
• Filtrate formed at rate of 100 to 140 ml/min
• Filtrate = Plasma - Proteins (and proteinbound substances)
• • Filtrate volume average 125 ml/min, 180 l/day.
• • 99% filtrate reabsorbed

GFR = Starling Equation

Filtration Coefficient (Kf)

• Measure of permeability of membrane

• Normal value = 12.5 ml/min/mmHg

• Mesangial cells can regulate Kf

• Hormones and disease can alter Kf including mutations of nephrin

• Mesangial cell contraction decreases Kf

• Oncotic pressure in BS normally = zero

GFR = Kf[(PGC - PBS) - (piGC)

GFR Regulation

• AT2 - low dose increases GFR (efferent arteriole constricts) - high dose decreases GFR by decreasing Kf)
• Renin 
• Glomerular tubular balance - filtrate reabsorbed (follows Na) at proximal tubule (passive)

Clearance

simplified = mass balance

• amount of substance into kidney = amount out of kidney.  amount of any substance = concentration x volume (C x V)
• one way into kidney (renal artery)
• two ways out of kidney (renal vein and urine)
• If substance is filtered freely but not secreted  or reabsorbed, then amount filtered = amount in urine.
• Cp x Vp = Cu x  Vu   rearrange of Vp 
• Vp = (Cu x Vu)/Cp
• Vp = GFR
• creatinine and inulin obey the rules
• for creatinine Cp x Vp = Cu x  Vu  = 1 mg/dL x 125 ml/min = 125 mg/dL x 1 ml/min  ---- note that creatine is concentrated 125 fold and H2O is conserved.
• Clearance of creatinine = GFR
• clearance of PAH = renal plasma flow (RPF)  (PAH filtered and completely secreted, so amount in urine = amount of renal artery plasma flow)

Body Fluid Compartments

• 60 - 40 - 20 rule
• measure using dilution of substances "trapped" in a compartment
• AMOUNT = C x V    so V = Amt/C

Plasma osmolality = 2 x PNa + [glucose]/18 + BUN/2.8

• Protein is ignored since it usually contributes less than 1 mOsm

• [glucose] is divided by 18 and BUN by 2.8 to convert from mg/dL to mmol/L

• PNa is multiplied by 2 to account for the accompanying anion (usually Cl- or HCO3-)

• 2 x PNa gives an estimate of plasma osmolality • (will give a low value if glucose, BUN or organic acids are elevated.)

isotonic versus isosmotic clarification

• isotonic = solution in which cell size doesn't change  
• isosmotic = solutions with same number of particles
• Two solutions are isosmotic when they have the same number of dissolved particles, 
  regardless of how much water would flow across a given membrane barrier. In contrast, 
  two solutions are isotonic when they would cause no water movement across a 
  membrane barrier, regardless of how many particles are dissolved.
  
  
  In the example given above, a 150 mM NaCl solution would be isosmotic to the
   inside of a cell, and it would also be isotonic--the cell would not swell or shrink 
  when placed in this solution (cell is normally ~300 mM). On the other hand, 
  a 300 mM urea solution, while still isosmotic would cause the cell to swell 
  and burst (due to its permeability). This isosmotic urea solution is not isotonic. 
  Instead it has a lower tonicity (hypotonic).
• http://www.flashcardmachine.com/membrane-transport-.html