Renal Clearance, Renal Blood Flow, and Glomerular Filtration Rate

Question 1

Clearance Equation

Answer 1

-Indicates volume of plasma cleared per unit time
-units: mL/min and mL/24hr
C=UV/P
-C is clearance
-U is urine concentration
-V is urine volume/time
-P is plasma concentration

Question 2

Renal Blood Flow

Answer 2

• 25% or cardiac output
• Directly proportional to pressure difference b/t renal artery & vein
• Inversely proportional to renal vascular resistance
• Vasoconstriction leads to decreases RBF
  
  • Activation of the renal sympathetic nerves
  • Angiotensin II
• Angiotensin II preferentially constricts the efferent arterioles
  
  • Protects GFR
  • ACE inhibitors dilate efferent arterioles and decrease GFR
• Vasodilation leads to increased RBF
  
  • Prostaglandins E2 and I2, bradykinin, NO, and dopamine

Question 3

Autoregulation of Renal Blood Flow

Answer 3

• Accomplished by changing renal vascular resistance
• BP change-> renal vascular resistance change to maintain GFR
• RBF remains constant w/ arterial pressures b/t 80 and 200mmHg
• Mechanisms for autoregulation are myogenic and tubuloglomerular feedback

Question 4

Myogenic Mechanism of RBF Autoregulation

Answer 4

• Renal afferent arterioles contract in response to stretch
• Increased renal artery pressure stretches arterioles
• Arterioles respond by contracting to increase resistance
  
  • Maintains RBF

Question 5

Tubuloglomerular Feedback Mechanism for Autoregulation of RBF

Answer 5

• Increased renal arterial pressure leads to increased delivery of fluid to the macula densa
• Macula densa senses increased load
  
  • Causes constriction of afferent arteriole

Question 6

Measurement of Renal Plasma Flow: Clearance of para-aminohippuric acid (PAH)

Answer 6

-PAH filtered and secreted by renal tubules
-Clearance of PAH used to measure RPF
-PAH clearance measures effective RPF and underestimates true RPF by 10%
-Doesn’t measure regions that don’t filter/secrete PAH
RPF=C-PAH=([U-PAH]V)/[P-PAH]
C-PAH is clearance of PAH
[U-PAH] is urine concentration of PAH
V is urine flow rate
[P-PAH] is plasma concentration of PAH

Question 7

Measurement of Renal Blood Flow

Answer 7

RBF=PRF/(1-hematocrit)

1-hematocrit represents the fraction of blood volume occupied by the plasma

Question 8

Measurement of GFR: Clearance of Inulin

Answer 8

-Inulin is filtered, but not reabsorbed or secreted
GFR=([U]-inulinV)/[P]-inulin
[U]-inulin is urine concentration of inulin
V is urine flow rate
[P]-inulin is plasma concentration of inulin

Question 9

Estimates of GFR w/ BUN and serum creatinine

Answer 9

• Both Blood urea nitrogen (BUN) and serum creatinine increase when GFR decreases
• In pre-renal azotemia (hypovolemia/hypoprofusion) BUN increases more than creatinine
  
  • BUN/Creatinine ratio increased (>20:1)
• GFR decreases w/ age but serum creatinine remaines constat b/c decreased muscle mass

Question 10

Filtration Fraction

Answer 10

-Fraction of RPF filtered across the glomerular capillaries
FF=GFR/RPF
-Normally about 0.2: 20% of RPF is filtered
-Remaining 80% leaves glomerular capillaries by efferent arterioles & becomes the peritubular capillary circulation
-Increased FF produces increased protein concentration of peritubular capillary blood
-leads to increased reabsorption in the proximal tubule
-Decreased FF produces decreased protein concentration of peritubular capillary blood
-leads to decreased reabsorption in the proximal tubule

Question 11

GFR Starling Forces

Answer 11

-Driving force for glomerular filtration is net ultrafiltration pressure across glomerular capillaries
-Filtration ALWAYS favored in glomerular capillaries b/c net ultrafiltration pressure always favors mov’t of fluid out of capillary
GFR=Kf[(Pgc-Pbs)-(πgc-πbs)]
-Kf is filtration coefficient
-barrier of endothelium, BM, podocytes
-Anionic glycoproteins line barrier restricting proteins
-glomerular disease disrupts anions->proteinuria
-Pgc is glomerular capillary hydrostatic pressure
-constant along length of capillary
-Increased by dilating afferent arteriole or constrict efferent
-Increases->increase in net ultrafiltration pressure & GFR
-Pbs is Bowman’s space hydrostatic pressure
-analogous to Pi in systemic capillaries
-Increased by constriction of ureters
-Increase->decrease in net ultrafiltration pressure & GFR
-πgc is glomerular capillary oncotic pressure
-increases along length of glomerular capillary
-Increase by increased protein concentration
-Increase->decrease ultrafiltration pressure and GFR
-πbs is Bowman’s space oncotic pressure
-usually zero b/c only small amt of protein normally filtered