GFR,Pl,Tl.plasma clearence.free water clearence ccr,egfr,acer

1. GFR,Plasma Load,Tubular
Load,Transport Maximum,Renal
Threshold,Concept of Plasma
Clearence,Osmolar Clearence &Free
Water Clearence ,CCR,eGFR,ACR
DR.TASNIM ARA JHILKY
MD Part II
Phase A
DEPARTMENT OF BIOCHEMISTRY
SIR SALIMULLAH MEDICAL COLLEGE
MIDFORD,DHAKA

2. GFR
• It is the amount of glomerular filtrate
produced by all functioning nephrons of both
kidneys per minute.
• It is about 125ml/min or 180L/day in adult
male
• In female 10% less.

3. Factors affecting GFR
GFR=(Net filtration pressure×Kf)
1. Net filtration pressure at glomerular membrane
2. Permeability coefficient of glomerular
membrane(Kf)
3. Sympathetic nervous system activity
4. Renal vasoconstrictors(decrease)
5. Renal vasodialators (increase)

4. Plasma load(PL)
It depends on RPF
• Plasma load of a substance is the total amount of
that substance present in the plasma passing
through both kidneys per minute.
• Pl=RPF×plasma con. Of the subs.
• If blood glucose con.is 100mg/dl & RPF=650ml/min
,then plasma load of glucose 650mg/min.

5. Tubular Load(TL)
It depends on GFR
• Tubular load of a substance is the total amount of
that substance present in the filtrate produced by
all nephrons of both kidneys per minute.
• Tubular load=GFR×plasma con.of the substance
• If blood glucose con is 100mg/dl
&GFR=125ml/min,then tubular load will be
125mg/min

6. Transport maximum(Tm)
• It the maximum amount and constant rate at which
every actively reabsorbed or secreted substance is
transported by tubular cells per minute.
• Subs showing transport maximum are
glucose,aa,protein,uric acid, ketone
body,phosphate,creatinine.
• Tm of glucose is 375mg/min in male,300mg/min in
female
• Tm for creatinine 16mg/min

7. ..
• If TL>Tm, the substance will appear in urine.
• If TL=Tm or TL<Tm there is no chance of
appearing of that substance In urine.

8. Renal threshold
• It the plasma concentration of actively reabsorbed
substance at or below which substance will not appear
in urine ,but above which substance will appear in
urine.
• It is 180mg% for glucose.
• Above the threshold value ,the TL of the subs excceds
its Tm ,so the subs fails to be completely reabsorbed
and appears in urine.
• Below the threshold value,TL expected to be well below
its Tm.so subs completely reabsorbed & does not
appear in urine.

9. Con………..
• Tm of glucose 375mg/min for male &300mg/min
,so to produce glycosuria TL of glucose should be
more than these respectively.
• Against the TL of glucose 300mg/min in female
&375mg/min in male their predicted renal
threshold of glucose need to be 240% in female
&same shuold be 300mg% in male .

10. ….
• Practically renal threshold for glucose is180%
• Glycosuria occurs at plasma con of 180mg% when the
TL of glucose is only 225mg/min(less than Tmax)
• This phenomenon of glycosuria in spite of smaller TL
compared to Tmg at the renal threshold of glucose
180mg% is known as sply
Non uniformity of Tmg among the nephrons
Nephrons with low Tmg usually spill glucose in
urine at a lower plasma con than the predicted value of
240mg% or 300mg%.

11. Plasma clearance
• Plasma clearance of a substance is the virtual volume of
plasma that contains the amount of that substance
excreted through urine per minute.
• It is virtual volume of plasma that is cleared of that
substance by renal excretion per minute
• C=UV/P
C=Plasma clearance of the subs(ml/min)
U=Urinary concentration of the subs.(mg/ml)
V=Urinary flow rate(ml/min)
P=Plasma con of the subs(mg/ml)

12. .
• Plasma clearance of a subs becomes less than GFR if
the subs is partially reabsorbed(urea)
• It becomes more than GFR if the subs partially
secreted.
• Plasma clearance is zero if completely
reabsorbed(glucose)
• Plasma clearance of creatinine =70-140ml/min
• Urea clearance 60-70 ml/min
• Glucose clearance 0 ml/min

13. Importance of plasma clearence
• It acts as a marker of renal function.
• It is used for measurement of GFR & RPF.
• It is used as a guide to determine the
effective dose of drugs which are cleared by
kidney
• In glomerular impairment the renal clearance
of creatinine &urea decreases.

14. Osmolar Clearence
1. It is the virtual of plasma which contains all the
osmotically active solutes excreted through urine per
minute.
2. Cosm=(Uosm×V)/Posm
Cosm=osmolar clearance(ml/min)
Uosm=Urinary osmolarity(mosm/L)
V=Urinary flow rate (ml/min)
Posm=plasma osmolarity(mosm/l)
Cosm=(900×1.0)÷300=3ml/min
It indicates that the amount of solutes excreted by an
individual through urine in each minute in fact lies with 3
ml of plasma within blood vessel.

15. Free water clearence
• It is the volume of solute free water excreted or
retained per minute during formation and excretion of
urine.
• CH2O=V-Cosm
Cosm=Osmolar clearance(ml/min)
V=Urinary flow rate(ml/min)
CH2O=Free water clearance(ml/min)
• In a normal individual V=I ml/min,Cosm=3ml/min.so
free water clearance=1-3=-2
• It is usually negative,because urine is much more
concentrated than plasma.

16. ….
• In hypertonic urine-(urinary osmolarity>300mosm)
free water clearance negative,because here urinary
solutes are excreted with less water volume then their
osmolar clearance.
• Hypotonic urine-(urinary osmolarity<300mosm/L)
free water clearance becomes positive.
• Isotonic urine-(urinary osmolarity=300mosm)free
water clearance becomes zero.

17. ….
Concept of free water clearance is used to assess
the
• Volume of free water excretion during hypotonic
urine formation.
• Volume of free water retention during hypertonic
urine formation.
• Renal concentrating &diluting power

18. Measurement of GFR by plasma clearance
of inulin.
• Any substance which is freely filtered from plasma
into the filtrate,the filtrate con.will be equal to its
plasma con. In circulation
• the subs.neither reabsorbed nor secreted,not
metabolized or produced in kidney,passing through
tubular system totally appears in urine.

19. • so the amount of that subs present in filtrate will
be equal to its amount in urine.
infact calculate the plasma clearance of that
substance which will represent the GFR
• GFR=UV/P
• Infused intravenously at a constant rate.
• Not endogenously produced within the body
• Others sub. are mannitol,sorbitol.

20. CCR
• Creatinine is endogenously produced & released
into the circulation at a constant rate.its plasma
load is maintained at a narrow range.its clearance
can be measured as an indicator of GFR.Creatinine
is not reabsorbed &a small quantity is secreted and
appears in urine(7-10%)
• Ccr=(Uc×V)/Pc
Uc=urinary con.of creatinine
Pc=plasma con.of creatinine
V=volumetric flow rate of urine ml/min

21. CCR …..
• Creatinine clearance may be defined as
the volume (ml) of plasma that would be
completely cleared of creatinine per
minute.
• 24 hrs urine collected
• Plasma sample is measured
• Reference value=70-140ml/min

22. ….
• Diagnostic importance:
• A decrease in creatinine clearance value
(<75 % normal) serves as sensitive indicator
of a decreased GFR, due to renal damage.
• It is useful for early detection of
impairment in kidney function.

23. .
Disadvantage
• Requires fixed specimen.
• Highly susceptible to error because of incomplete
& inaccurate urine collection.
• Only provide a crude index of GFR.

24. • ADVANTAGE OF CREATININE CLEARANCE;
– A)It is a normal metabolite of the body
– B)It does not require I.V. administration
– C)Estimation of creatinine is simple
– D)In early stages it has got advantage over
S.Creatinine

25. eGFR
• An alternative &more convient method is to use to
calculate the creatinine clearance &GFR by using
serum creatinine level,age,sex &body wt of the pt.
• Does not require a timed urine collection.
• It can be calculated by using several formula,of
which the most widely used is the Cockcroft-Gault
equation,according to it

26. COCKCROFT-GAULT equation
• eGFR = K x (140-age in year) x weight(kg)
Serum creatinin (µmol/L)
K=(1.23 for male &1.04 for female)

27. ….

28. Stage of Chronic kidney disease by
eGFR

29. ACR
• Albumin/creatinine ratio (ACR) is used to screen
people with chronic conditions, such as diabetes
and hypertension that put them at an increased
risk of developing kidney disease.
• Most of the time, both albumin and creatinine
are measured in a spot urine and an
albumin/creatinine ratio (ACR) is calculated.

30. .

31. .

32. Evaluation of PCR and ACR
Tests
(urine analysis)
Normal MAU
(MPU)
Macro Albuminuria
(Macro
proteinuria)
24 hrs urine < 30 mg /day 30-300 mg/day >300 mg/day
Timed
(overnight)Urine
<20 µg/min 20-200
µg/min
>200 µg/min
Spot
urine for ACR or
PCR
<30
(mg/g or
µg/mg)
30-300 (mg/g or
µg/mg)
>300 (mg/g
or µg/mg)
<3 (mg/m
mol)
3-30 ( mg/m
mol)
>(30 mg/m
mol)

33. Continued..ACR (mg/ m mol) Significance
<3.5 (Female)
<2.5 (Male)
Normal
3.5-15 Microalbuminuria
15-50 Dipstick positive,equivalent to 24
hr protein excretion <0.5 gm
50-200 Glomerular disease more likely
>200 Neprotic rang, always Glomerular
disease, equivalent to 24 hr
protein excretion >3 gm

34. .
Advantage of ACR
• Albumin creatinine ratio and protein
creatinine ratio is easier laboratory method to
evaluate proteinuria
• Creatinine excretion is fairly constant
throughout the 24hrs period,measurement of
albumin creatinine ratio allows correction for
variation in urinary concentration.

35. Cont…
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