Renal Clearance

Question 1

define filtered load and excreted load

Answer 1

• filtered load = rate at which a certain solute is being removed from the glomerular capillaries (mg/ml)
• excreted load = rate at which a certain solute is leavint the kidney (mg/ml)

Question 2

explain the “principle of mass balance” with respect to the kidney

Answer 2

says that if a substance is not reabsorbed or secreted, then at steady state, the rate at which a solute leaves the plasma (filtered load) must equal the rate at which is enters the urine (excreted load). modeled by this euqation

• VpPx = VuUx
  
  • Vp is the “hypothetical” plasma flow (ml/min)
  • Px is the plasma concentration (mg/ml
  • Vu is the rate of urine production (ml/min)
  • Ux is the urine concentration (mg/ml)

Question 3

• define clearance
• how to solve for clearance using the relationship between filtered and excreted load

Answer 3

• clearance = the volume of plasma that was cleared of solute “X” in one minute
  
  • i.e., the amount of volume containing solute “X” that leaves the glomerular capillaries per minute
• represented by Vp in filtered load
  
  • clearance = Vp = VuUx/ Px

Question 4

the use of clearance to measure GFR

• why does this work?
• what are the necessary characteristics of the cleared solute?

Answer 4

GFR is the amount of fluid removed from the glomerular capillaries into bowman’s capsule per minute

• i.e. the amount of fluid “cleared” per minute
• the clearance of a solute that is only filtered, and not reabsorbed/secreted, represents GFR

solute must

• be freely filtered: is the correct size/polarity to move thru the glomerular capillary membrane
• not reabsorbed from tubules
• not secreted into tubules
• insert: not metabolized by the kidney

Question 5

inulin

• properties
• uses

Answer 5

• a synthetic fructose polymer
• its clearance is used to estimate GFR, since it:
  
  • is freely filtered (molecular weight < 5000)
  • not secreted/reabsorbed
• thus, the rate of its filtration = rate of excretion

Question 6

creatinine

characteristics and uses

Answer 6

• like inulin, it is can be used to calculate GFR (not absorbed/secreted, freely filtered)
• but, it is a byproduct of muscle breakdown, and doesnt need to be injected

Question 7

relationship between plasma creatinine and GFR

Answer 7

• inverse relationship
  
  • an increased plasma creatinine is due to a smaller creatinine clearance, and thus indicates a smaller GFR
• non-linear relationship:
  
  • normal GFR between 90-120
    
    • plasma creatinined maintained pretty well in this range
    • as GFR decreases, smaller drops in GFR lead to higher plasma creatinine

Question 8

relationship between BUN, plasma creatinine and GFR

Answer 8

• BUN has the same relationship to GFR as creatinine
• BUN normally exists at a 10/1 ratio to creatinine
  
  • 10/1- 20/1 BUN:Plasma creatinine is clinically normal

Question 9

what demographic factors can decreased GFR?

how is this modelled clinically?

Answer 9

determining GFR would involve a urine sample (to determine excretion of solutes/per minute from the urine) to determine excreted load, and plasma sample of creatinine.

• a model generated based on collected data provides a quicker estimation
• age decreases GFR
• body mass increases GFR

Question 10

what is PAH and how is it used to measure renal function?

Answer 10

• PAH is freely filtered and completely secreted
• thus, its clearance can be used to model renal plasma flow:
  
  • renal plasma flow = all of the plasma that goes through nephron
  • since all of PAH ends up in the tubules (20% filtered at glomerulus, remainder secreted in tubule system) its clearance represents renal plasma flow

Question 11

define renal blood flow

how it can be calculated using RBF

Answer 11

= entirety of blood that moves through kidney (plasma + cellular components)

• can be calculated using RPF (indicated by PAH clearance)
• accounts for hematocrit (cellular components of blood)

Question 12

what is filtration fraction and how is it calculated?

Answer 12

• The fraction of the plasma volume entering the glomerulus that is filtered from the glomerular capillaries into Bowman’s capsule
• FF = GFR/RPF = Ccr/Cpah

Question 13

what is fractional excretion?

how can we calculate it?

Answer 13

• how much of of what is filtered gets excreted
  
  • FE = excreted load/filtered load
    
    • since filtered load = VpPx
    • and excreted load = VuUx
    • FE = VuUx/VpPx = VuUx/GRFPx
      
      • (since Vp = GFR)
  • GFR replaced with Ccr, equation rearranged such that Cx/Ccr

Question 14

what is the fractional excretion (= 1, < 1, > 1) of a solute that is reabsorbed, a solute that is secreted, and inulin?

Answer 14

• FE of inulin = 1.0
• If a solute is reabsorbed, its FE < 1.0 (more is filtered than excreted)

• If a solute is secreted, its FE > 1.0 (more is excreted than filtered)

Question 15

if solute “Y” if freely filtered and reabsorbed to some extent

• what is the relationship between filtered load and excreted load?
  
  • what can filtered/excreted load be used to determine?
• what is the relationship between filtration rate and excretion rate?
  
  • what can these rates be used to determine?

Answer 15

• Filtered load (GFR×Py) > Excreted load (Vu ×Uy)
  
  • _{GFR = rate of fluid leaving plasma in glomerulus}
  • _{Py = plasma concentration of “y”}
  • _{Vu = rate of fluid leaving kidney}
  • _{Uy = urine concentration of “y”}
• Reabsorption rate = Filtered load - Excreted load
• Filtration rate > Excretion rate (i.e., GFR > Cy)
• Excretion rate = Filtration rate - Reabsorption rate

Question 16

if solute “X” is freely filtered and secreted to some extent,

• what is the relationship between excreted load and filtered load?
  
  • what can these loads tell you?
• what is the relationship between excretion rate and filtration rate?
  
  • what can these rates tell you?

Answer 16

• Excreted load (Vu ×Ux) > Filtered load (GFR×Px)
• Secretion rate = Excreted load - Filtered load
• Excretion rate > Filtration rate (i.e., Cx > GFR)
• Excretion rate = Filtration rate + Secretion rate

Question 17

if a substance’s filtered load > excreted load

• was it reabsorbed, secreted, neither
• what is its Tx (net movement of solute) - zero, positive, or negative?
• give an example of a solute processed in this manner

Answer 17

• reabsorption = net movement
• Tx is negative
• ex: glucose

Question 18

if a substances filtered load < excreted solute

• was it reabsorbed, secreted, neither?
• what is its Tx (net movement)
• give an example of substance tha tis processed this way?

Answer 18

• net secreted
• Tx is positive
• example: PAH

Question 19

if a substances filtered load = excreted load

• was it reabsorbed, secreted, or neither?
• what is its Tx (net movement)?
• give an example of a substance processed in this manner

Answer 19

• neither reabsorbed/secreted
• Tx = 0
• example: inulin, creatinine

Question 20

what are fractional reabsorption and fractional secretion?

how can it be calculated?

Answer 20

fractional reabsorption:

• this is the amount of the filtered load the gets reabsorbed
• FR = I - FE
  
  • where FE = exceted load/filtered load
    
    • this must be < 1, since there not all of the filtered load got excreted

fractional secretion

• same equation, replace FR with FS
• FS will be a negative number
  
  • since FE = excreted load/filtered load
    
    • and in this case will be > 1, because more was excreted than originally filtered