Physiological basis

of evaluation of
renal function

An Introduction to the Urinary System

Produce urine

Transports urine
Toward bladder

Temporarily store
urine

Conduct urine
to exterior

The Function of Urinary System

A) Excretion & Elimination:
removal of organic wastes
products from body fluids (urea,
creatinine, uric acid)

B) Homeostatic regulation:
Water -Salt Balance
Acid - base Balance
C) Endocrine function:
Hormones

Formation of urine
Urine is formed by the help of nephrons
About 1 million nephrons are present in one kidney
Nephron contains bowmens capsule, proximal convoluted tubule,
loop of Henle , distal convoluted tubule and collecting tubule
blood supply high-1200ml/min
120-125ml/min is filtered which is known as glomerular filtration rate
(GFR)

Urine formation

Why Test Renal Function?

To identify renal dysfunction.
To diagnose renal disease.
To monitor disease progress.
To monitor response to treatment.
To assess changes in function that may impact on therapy
(e.g. Digoxin, chemotherapy).

Renal function tests

Analysis of urine
Analysis of blood

Renal clearance test

Radiology and renal imaging
Renal biopsy

ANALYSIS OF URINE
1)Volume
2)Colour
3)Osmolality & sp. Gravity
4)PH
5)Abnormal urinary constituents
6)Microscopic examination
7)Bacteriological examination

1)Volume
N

800 2500 ml /day

Polyuria more than 3 L / day

Oliguria less than 500 ml / day
Anuria no urine (less than 50 ml /day )

2)Colour
Light yellow
Brownish yellow conj. Bilirubin

Cloudy appearance alkaline urine (ca phosphate ppt.)

Frothy appearance proteinuria
Red-dark brown tinge - porphyria

3)Osmolality & Sp. Gravity

50 mOsm / kg 1200 mOsm / kg
1.003 1.030
Methodearly morning urine sample > 600 mOsm/kg , > 1.018
Fixed osmolality 300 mOsm/kg,1.010 advance urinary failure
Persistent low osmolality ( less than 100 mOsm/kg) even after 8 hr
of water deprivation - DI

4)PH
4.5 8.0 (slightly acidic)

Infection with urea spitting bacteria

Impairment of tubular acidification

5)Abnormal urinary constituents

1) Proteinuria > 150 mg/day
Mild transient proteinuria congestive heart failure

Orthostatic proteinuria
Glomerular proteinuria( permeability) nephrotic syndrome , acute GN
Tubular proteinuria(tubular reabsorption of low mol. Wt. protein
affected) tubulointerstitial disorder and fanconis syndrome

2)Glycosuria
DM , renal glycosuria , alimentary glycosuria
Inborn error in metabolism other sugar also present in urine

3)Ketonuria
Ketone bodies in sever DM or prolong starvation( acetoacetic acid ,
beta hydroxyl butyric acid , acetone )

4)Bilrubinuria
Presence of conj. Bilirubin in urine hepatic or post hepatic jaundice
Exessive urobilinogen ( normal 1 -3.5 mg /daily ) haemolytic anemia

5)Haemoglobunuria
Intravascular hemolysis ( black water fever )
6)Porphobilinogen in urine
Acute intermittent porphyria
Red brown colour (burgundy wine ) IN STANDING URINE

7)Haematuria
Acute GN , renal stone , malignancy
8)Aminoaciduria
Congenital tubular disorder

Microscopic examination(centrifuged
sediment)
1) Cast
Renal tubule epithelium-----Tamm Horsfall protein ------coagulated
and washed out by tubular flow
Non cellular cast
Hyaline and granular

Cellular castRed cell cast acute GN

Leucocytic casts acute bacterial pyelonephritis
Epithelial cast acute tubular necrosis
Fatty cast nephrotic syndrome

2)Crytal
When uric acid cystal and cysteine crystal present in excess have clinical
significance
3)Cells
Already covered

Bacteriological examination
Mid stream sample of urine for pus + bacteria
Urinary tract inf.

Analysis of blood
This sub. Excreted by kidney
1)Blood urea
20-40mg% , blood urea when 50% glomerular damage occur
2)Plasma creatinine conc.0.6 1.5 mg % , 50% GFR function

then significant change in level

3) Serum protein level

Total protein 6.7- 8 gm%(A/G 1.7:1)
NEPHROTIC SYNDROME REVERSAL OF A/G ratio
4)Serum cholesterol
150 200% , in nephrotic syndrome
5) Serum electrolyte
Value varies with renal disease
Chr. Renal failure high k+,PO4 but low Na+ , Ca++

Renal clearance test

Volume of plasma that is cleared of sub. In one minute by excretion of
substance in urine.
C = Renal clearance
U = urine conc. Of substance
V = rate of flow of urine
P = plasma conc. of substance

UV
C=
P

PRINCIPLE GOVERNING RENAL

CLEARANCE
1) Freely filtrated , not reabsorbed and secreted (inulin)
Cin = GFR
2)Freely filtrated , partially reabsorbed
Cx < GFR
3) Freely filtrated , completely reabsorbed(Na+,glucose,A.A.,Cl-)
Cx(lowest)
4)Freely filtrated , secreted by tubules not reabsoebed (PAH,diotrast)
Clearance depends on range of blood flow

GFR
1) C inulin
Inulin
1)Not exist in body naturally
b)Freely filtered by glomeruli , no absorption or secretion
c)Biologically inert , non toxic
d)Not metabolise or store by kidney
e)Easily lab reading

 Method iv single bolus , followed by continuous constant i.v inf.

Cin (GFR )= Uin V

Pin
Applicaion
1)GFR
2)Indicator of plasma clearance mechanism
3)For comparing clearance of given sub.

2) C creatinine (as index of GFR , preferred over inulin )

Creatinine
endogenous sub.
0.6 1.5 mg/dl constant plasma value
Marginally secreted by tubules
Method 24 hr urine collected
Plasma conc. Measure at midpoint of urine collection

C creatinine 80 -110 ml / min (normal)

Age muscle mass

GFR

C creatinine

3) C urea
Urea
end product of protein metabolism
Clearance depend on diet
Partially reabsorb by tubule

Method
Completely void urine and time recorded
After 1hr asked to void again measure conc. in urine
Blood sample collected at midpoint of test

Maximum urea clearance( C urea(m) )

Standard urea clearance( C urea(s) )

When urine volume more than

2ml / min

When urine volume less than 2

ml/min

UV
C=
P

75 ml / min

U V
C=
P

54 ml / min

 C urea below 75 % consider serious indicator of renal damage

40% urea reabsorb constantly
so, { C urea 1.2 } in % = GFR

TUBLAR SECRETORY CAPACITY

PAH
Secretion to tubular fluid via carrier in PCT by Tm
when Tm reaches C PAH become more function of glomerular filtration

C PAH
T m (PAH)

C IN

RENAL PLASMA FLOW

FICK PRINCIPE
Amount of substance excreted by kidney per unit time ( UV ) is equal to
renal plasma flow(RPF) multiply by arteriovenous difference in plasma
conc.

UV = RPF ( Pa Pv )
RPF = (Pa Pv ) / UV

 PAH used for RPF

1)Completely extracted from kidney during each passage via kidney
2)Not metabolise , store or produce by kidney
3)Not affect renal blood flow
4)Conc. Can measure easily
5)Not affect renal flow
6)actively secret by tubules in lumen

 Method
PAH continuous low dose infusion
So, RPF = Pa(PAH) - Pv(PAH) / U PAH . V

But at low dose Pv (PAH) = 0 ( all excreted in urine )

PAH excreted only by kidney so peripheral arterial blood conc. As value
of Pa(PAH)

RPF = P PAH / U PAH . V -----------------------------------------(1)

C (PAH) = P PAH / U PAH . V -------------------------------------(2)

By eq.1 and eq.2
RPF = C (PAH)

About 10% of total RPF perfuse to non excretory portion of kidney I.e
Renal capsule,renal pelvis

so, effective RPF = C PAH

i.e. True RPF = C PAH / 0.9

From haematocrit value (Hct) we can also determine the value of Renal
Blood Flow (RBF)
RBF = RPF (1/1-Hct)
NORMAL
ERPF = 650 ml/min/1.73 m2 BODY SURFACE AREA (BAS) (M)
ERPF = 600 ml/min/1.73 m2 BODY SURFACE AREA (BAS) (F)

Cosm and C H2O

1)Osmotic clearance ( Cosm )

Amount of plasma(ml) completely cleared of osmotically active solutes

that appear in urine each minute
C osm =

Uosm V
Posm

3 ml / min
in osmotic diuresis

fasting or diet deficient in protein

2)Free water clearance ( C H2O )

Volume of pure water that must be removed from or added to , the
flow of urine ( ml/min) to make it iso osmotic with plasma
Free water generate at ( thick ascending limb and early distal tubule )
NaCl reabsorb and free water left in tubules

ADH ABSENT solute free water excreted , C H20 is positive

ADH PRESENT water reabsorbed in late DT & CT , C H20 is negative
C H20 = V - Cosm

Relationship between C H20,V & C osm

1) Iso osmotic urine
V = C osm
AS C H20 = V C osm = 0
Loop diuretics ---- inhibit TAL(THICK ASC. LOOP)--- inhibit dilution(TAL
inhibition) and conc.(abolish corticopapilary gradient) Capacity of
urine---isosmotic urine

2)Hypo osmotic urine

Two virtual volume will form
Cosm contain solute iso osmatic to plasma
C H20 free solute water positive
V = Cosm + C H20
Excess water intake , central DI , nephrogenic DI

3)Hyperosmotic urine
-C H20(T CH2O/free water reabsorption) volume of free water
needed to make urine iso osmotic with plasma negative
Cosm = V + T C H2O
Water deprivation, SIADH

TEST FOR TUBULAR FUCTION

1)Urine conc. Test
Measure ability of tubules to conc. Urine
Measure sp.gravity of urine after either 12 hr of water deprivation or
12 hr of vasopressin inj.
Sp. Gravity above 1.020 is normal tubular function

2)Urine acidification test

NH4Cl orally 0.1 gm/kg----urine sample tested for PH after 6 hr.---PH

should below 5.3(because of liver NH4Cl NH3 + HCl)
If more PH inability to excrete H+

3)Urine dilution test

Pt. ask to drink 1 lit water-----sample collected for every hr. for 4hr
Total 750 ml urine should be excreted
At least one sample should be osmolality less than 100 mOsm/Kg or
specific gravity less than 1.004

4)Tubular secretory capacity

Phenolsulphonepthalein Px (PSP) excretion test
PSP inj. i.v. and checked first appearance in urine and quantity
eliminate in defined period measure functional capacity of kidney

25% dye excreted in 15 min,75% in 2hr (normal)

Slight impairment 59 - 40%
Moderate impairment 39 25%
Marked impairment 24 - 11%

5)Other method to study tubular function

Micro puncture technique analyse tubular fluid at different levels
Microcryoscopic study renal tissue slice at different dept
Microelectrode study measure membrane potential of tubular cells

RADIOLOGY AND RENAL IMAGING

1)Plain radiograph of abdomen
Useful to detect radiopaque stone(Ca++ containing )
2)Intravenous pyelography (IVP)
Inj. i.v. Radiopaque dye ( urographin ) ----- take radiograph of abd. At
short interval ( 1,5,10 ,30 min.) -----visualisation of glomeruli, renal
tubule ultimately renal parenchyma----visualisation of pelvicalyceal
system

3) Ultrasonography
Quick , non expensive , non invasive method
4)Computed tomography
Detect abnormality in and around of kidney
5)Radionuclide studies
Inj. Of radioactive compound which conc. and excreted by kidney(using
gamma camera)

Renal biopsy
Vim Silverman needle
UseTo diagnose proteinuria of unknown origin
Unexplained renal failuar
Systemic disease asso. With kidney
Light , electron , immunofluorescence microscopic study

SUMMARY

THANK YOU

Analysis of urine
1)Volume 2)Colour 3)Osmolality and Specific gravity 4)PH 5)Chemical analysis of abnormal urinary constituents6)Microscopic examination 7) Bacteriological examination

Countercurrent exchange vs multiplayer

Formation of urine
Process of urine formation basically involves two steps
Glomerular filtration: formation of ultrafiltrate
waste materials of plasma are filtered

Tubular reabsorption: formation of pure urine

PCT & DCT retain water and most of the soluble constituents
of the glomerular filtrate by reabsorption

Renal Functions
Production of urine
Elimination of metabolic
end products
(Urea/Creatinine)
Elimination of foreign
materials (Drugs)
Control of volume &
composition of ECF
Water and electrolyte
balance
Acid/Base status

Endocrine Functions
Vit D, Erpo, Renin

Renal threshold
Renal threshold of a substance is the concentration in
blood beyond which it is excreted in urine
Renal threshold for glucose is 180mg/dL
Tubular maximum (Tm): maximum capacity of the
kidneys to absorb a particular substance
Tm for glucose is 350 mg/min