PHYS - Glomerular Filtration

Question 1

STARLING’S FORCES

Answer 1

• P = hydrostatic pressure → pushes H₂O
• π = oncotic pressure → pulls H₂O toward high water concentration
• K = filtration coefficient, depends on
  
  • SA of capillary
  • Permeability of capillary surface
• Utilize mean values to determine GFR/day
• Glomerular capillary
  
  • Hydrostatic P (high in capillary, low in tubule) remain constant through capillary bed
  • Oncotic P increases through length of capillary because H₂O leaves, so protein concentration increases
  • Net filtration decreases through length of capillary
  • 20% of the plasma and its contents is filtered into the tubule
• Peritubular capillaries
  
  • Increased capillary oncotic pressure (because of filtration) at beginning of capillary favors reabsorption
  • Contraction of efferent arteriole → increased R → decreased P = reabsorption
  • At end of capillary bed, oncotic pressure decreased by fluid reabsorption
• SkM capillary
  
  • Oncotic P remains constant through capillary bed
  • Hydrostatic P decreases through capillary bed, below oncotic P
    
    • Net filtration at beginning of bed
    • Net reabsorption at end of bed

Question 2

PATHOLOGY AFFECTING FILTRATION

Answer 2

• Urinary tract obstruction
  
  • Increased P_t (capillary hydrostatic pressure)
  • Decreased net filtration
• Hypoalbuminemia
  
  • Decreased π_c (capillary oncotic pressure)
  • Increased net filtration
• Diabetic nephropathy
  
  • Permeability of nephrons increased → proteins enter tubule
  • Increased π_t (tubule oncotic pressure)
  • Increased net filtration
  • Nephron damage over time → loss of nephrons = loss of SA for filtration → decreased filtration + continued proteinuria

Question 3

FILTRATION/REABSORPTION PATHWAYS

Answer 3

1. Fenestrated capillary endothelial cells
2. Fused BM of tubule/capillary – most selective barrier
   
   1. Lumina interna – most negative barrier
3. Podocytes filtration slits

• Filtration of positively charged molecules > negatively charged molecules; small > large
• Reabsorption from PCT into peritubular capillaries
  
  • Epithelial cell TJs → paracellular bulk flow
  • Transporters → transcellular from BM to apical membrane

Question 4

CLEARANCE

Answer 4

• Clearance – volume of plasma per minute from which all of a substance is removed
  
  • C_x = [U_x(V)]/P_x
  • Clearance of X = (urine[X]*urine flow rate)/plasma[X]
• Can determine GFR from inulin clearance (C_In)
  
  • C_In = GFR
  • Inulin properties
    
    • Freely filtered
    • Gets trapped in tubule/urine
      
      • No secretion
      • No reabsorption
  • IV inulin injection → steady state → measure urine [inulin] for 24h period
  • 100% excretion; therefore, amount excreted per time = filtration rate
• Can estimate GFR from creatine clearance (C_Cr)
  
  • Already produced by body; no need to wait for steady state
  • Slightly overestimates because of creatine secretion into tubule
    
    • C_Cr = 1.2C_In
    • C_Cr = (U_Cr*V)/P_Cr
    • But lab error tends to slightly overestimate P_Cr so value is a really good estimate of GFR

Question 5

SODIUM FILTRATION

Answer 5

• Filtration = 20% of blood (plasma, ions, etc.)
• Filtered load = GFR(P_X) = GFR*plasma concentration of molecule
  
  • Na+ filtration = 125 mL/min * 142 mEq/L = 3.3 lbs!
  • But sodium is reabsorbed readily
• Fractional excretion = excretion rate/filtered load
  
  • Na+ = 0.4%
• Fractional reabsorption = reabsorption rate/filtered load
  
  • Na+ = 99.6%
• Recommended amount of salt per day = 2.4g, but if you get more or less your kidneys will adjust to regulate the amount reabsorbed
  
  • HT individuals have reduced kidney function and are salt sensitive because of loss of Na+ secretion; more salt retained in body