GFR and renal clearance

Question 1

why do we measure GFR (glomerular filtration rate)

Answer 1

assesses renal function

the sum of filtration rate of each of the functioning nephrons

Question 2

what does a reduction in the number of functioning nephrons lead to

Answer 2

a fall in total GFR

Question 3

where are most drugs and certain antibiotics excreted from the body primarily from

Answer 3

glomerular filtration in the kidneys

Question 4

what happens to drugs if GFR is reduced

Answer 4

the excretion of the drug will fall

it will accumulate in the body to possible toxic levels - to prevent this - dosage must be reduced appropriately

Question 5

what are normal values for GFR in young adults (range included)

Answer 5

120 mL/min per 1.73m2 (typical value for body surface area of an adult)
range = 90-150 mL/min per 1.73m2

Question 6

how much does GFR fall by after the age of 40

Answer 6

falls by about 10 mL/min per decade

Question 7

what is the definition for glomerular filtration rate

Answer 7

GFR
the amount of fluid filtered from the glomeruli into the bowmans capsule per unit time (mL/min) - sum of filtration rate of all functioning nephrons

Question 8

what is the definition for a freely filtered substance

Answer 8

conc of x in plasma = conc of x in glomerular filtrate

a freely filtered substance may be absorbed or secreted later on, freely filtered refers to the glomerulus

Question 9

how can we measure GFR using substance Y as an eg and EQUATION

Answer 9

consider a substance Y present in the plasma (small enough to be freely filtered into Bowman’s capsules but neither reabsorbed nor secreted into the tubules) therefore the amount of Y excreted per unit time will be the same as the amount filtered per unit time

GFR x plasma conc of Y (Py) = urine flow rate (V) x urine conc of Y (Uy)
GFR (mL/min) = V x Uy all/Py

Question 10

what is an example substance we can use to measure GFR and some characteristics that allow this to occur

Answer 10

inulin
a plant polysaccharide
freely filtered 
not toxic
measurable in urine and plasma
not found in mammals - needs to be transfused

Question 11

what is the definition for renal clearance

Answer 11

the renal clearance of a substance is equal to the volume of plasma which would be required to supply that amount of the substance excreted by the kidneys per unit time - always expressed as a volume of plasma per unit time

Question 12

what is the equation to calculate renal clearance

Answer 12

for any substance Z

the renal clearance Cz is calculated as Cz = V x Uz/Pz

Question 13

when can a substances GFR = renal clearance

Answer 13

if the substance is freely filtered and neither reabsorbed nor secreted

Question 14

which one has a lower clearance - sodium or inulin

Answer 14

sodium has a lower clearance than inulin so more sodium is reabsorbed

Question 15

what is indicated by a substance whose renal clearance is higher than that of inulin

Answer 15

when a substance has a renal clearance higher than inulin - it is being secreted from the blood into tubular fluid

Question 16

what is indicated by a substance whose renal clearance is lower than that of inulin

Answer 16

if the renal clearance of a substance is lower than that of inulin - it means more of the substance is being reabsorbed than secreted

Question 17

how can we measure renal plasma flow (RPF)

Answer 17

using PAH - para amino hippuric acid

Question 18

where is PAH secreted into

Answer 18

proximal tubules

Question 19

what happens to PAH

Answer 19

if the plasma conc is not too high - the combination of filtration and secretion ensures that practically all of the PAH arriving at the kidneys in the plasma appears in the urine - and almost none leaves in the renal vein (needs to be infused)

Question 20

what can PAH clearance be used to give an estimate for

Answer 20

the volume of plasma perfusing the kidneys per unit time (renal plasma flow rate) because it is both filtered and secreted

Question 21

what is the equation for the rate at which PAH enters the kidneys per minute in the renal arteries

Answer 21

rate at which PAH enters the kidneys per minute in the renal arteries =
RPF x Ppah

determined by conc x flow

Question 22

example
if PAH clearance = 625 mL/min
inulin clearance = 125 mL/min
what proportion of the plasma entering the glomeruli is filtered

Answer 22

125/625 = 0.2 = 20%

Question 23

example 
if PAH clearance = 625 mL/min 
inulin clearance = 125 mL/min
if the arterial plasma inulin conc was 1mmol/L - what would be the plasma inulin conc in
1) the efferent arteriole
2) the renal vein

Answer 23

1) 1mmol/L as when something is freely filtered the conc does not change
2) 0.8 mmol/L as it is diluted by 20%

Question 24

why is PAH clearance rarely performed clinically when renal disease is suspected

Answer 24

• the value of using PAH relies upon it being completely cleared by filtration and secretion - these processes are not guaranteed to be working properly in renal diseases
• the kidney needs to actively secrete all PAH back into urine - the secretory mechanisms are impaired during renal disease - not diagnostic

Question 25

what are the problems when practically determining GFR using inulin clearance

Answer 25

• does not occur naturally in the body - to measure its renal clearance it has to be infused intravenously
• this causes several problems - rarely used clinically
• time consuming and tedious
• requires several blood samples and due to short duration over which measurements are made - bladder catheterisation (since voluntary bladder emptying may be incomplete)
  not given orally as it may be ingested

Question 26

how can we use creatinine clearance (Ccreatinine)

Answer 26

• it is an endogenous substance produced from the metabolism of muscle creatine
• released into the blood at a relatively constant rate - plasma conc of creatinine remains fairly stable in a given individual
• requirements : 24hr urine collection, a single plasma sample taken at some time during the clearance period
• it is freely filtered and neither reabsorbed nor metabolised by the kidneys
• however a small amount of creatinine enters the urine by secretion into the proximal tubule - the amount excreted slightly exceeds the amount filtered

Question 27

what are the problems when using inulin and creatinine to measure clearance

Answer 27

clearance of inulin is accurate but inconvenient

clearance of creatinine is convenient but not so accurate

Question 28

how can the clearance of new substances be determined

Answer 28

monitoring their disappearance from the plasma after administering a given dose (as they emit radiation) - thus eliminating the need to collect urine

Question 29

what is the substance used to measure clearance

Answer 29

EDTA
51CrEDTA - a gamma emitter
administer a single injection and then measure the plasma activity of 51Cr at subsequent intervals

Question 30

how can we measure the clearance of 51CrEDTA from the slope of the straight line

Answer 30

the greater the slope the greater the clearance

Question 31

what are the advantages of using 51CrEDTA in practice

Answer 31

requires only a single dose of 51CrEDTA
collection of 2-3 plasma samples taken at appropriate times after the injection
free to permeate the whole of the extracellular fluid
can be IV
bolus injection
high conc starts to fall as starts to be removed in kidney
if someone is suffering from severerenal failure - reduced GFR - less steep gradient - takes longer to be removed due to impaired GFR