This document provides an overview of urine formation and glomerular filtration rate. It discusses the key parts of nephron involved including glomerulus, Bowman's capsule and different segments of nephron. The three main steps in urine formation are glomerular filtration, tubular reabsorption and tubular secretion. Glomerular filtration is the process by which plasma is filtered into Bowman's space to form primary urine. The rate of glomerular filtration is regulated by various factors like hydrostatic and oncotic pressures in the glomerular capillaries. Glomerular filtration rate can be measured by using clearance of substances like inulin, creatinine and urea that are freely filtered but neither re

1. URINE
FORMATION.
Dr. Nilesh N. Kate.
M.D.
ASSOCIATE PROFESSOR
DEPARTMENT OF
PHYSIOLOGY.

2.  The composition of the blood ( internal
environment ) is determined not by
what the mouth ingest but by what the
kidney keep.
------- SMITH.

3. OBJECTIVES
 Filtration
 Characteristics of filtration membrane
 Composition of Glomerular filtrate
 Dynamics Of Glomerular Filtration
 Glomerular filtration rate
 Filtration fraction
 Factors affecting Glomerular filtration
 Regulation of Glomerular filtration
 Measurement of Glomerular filtration.

4. IDENTIFY THE PARTS
2
3
4
5
1

5. IDENTIFY THE PARTS
11
Proximal convoluted tubule.
Loop of Henle
Distal convoluted tubule.
Collecting duct.
Glomerular
capsule.

6. INTRODUCTION
 Process concerned with
urine formation
 Glomerular filtration..
 Tubular reabsorption..
 Tubular secretion..
 GFR is very high: ~180L/day.
 IMP:-It is the ECF that is
being regulated, NOT the
urine.

7. BOWMAN’S CAPSULE &
GLOMERULUS
Wednesday, June 1, 2016

8. CHARACTERISTICS OF FILTRATION
MEMBRANE
SITE OF FILTRATION
 Glomerulus
 The site of filtration
 Mechanism is sieve-like
 Layers:-
 1 foot processes of podocytes.
 2 Lamina rara externa or
outer cement layer.
 3 Lamina densa.
 4 Lamina rara interna or
inner cement layer.
 5 Endothelial cell layer.

9. Wednesday, June 1, 2016

10. GLOMERULAR
FILTRATION MEMBRANE

11. ELECTRON MICROGRAPH OFELECTRON MICROGRAPH OF
PODOCYTE COVERINGPODOCYTE COVERING GLOMERULAR
CAPILLARY LOOP.CAPILLARY LOOP.

12. ELECTRON MICROGRAPH OFELECTRON MICROGRAPH OF
GLOMERULAR MEMBRANE.GLOMERULAR MEMBRANE.

13. CHARACTERISTICS OF FILTRATION
MEMBRANE (Cont..)
 Endothelial capillary pores -- Large fenestrae.
 High permeability:- 100-400 times more permeable to plasma,
H20, and dissolved solutes than capillaries of skeletal muscles.
 Permeability selectivity :-
Pore size
Electrical charge
 Pores are small enough to prevent RBCs, platelets, and WBCs
from passing through the pores.

14. CHARACTERISTICS OF FILTRATION
MEMBRANE (Cont..)
Pore size.
Glomerular capillary – 8 nm.
podocyte filtration slits – 25 nm.
< 4 nm -- freely filtered.
4-8 nm -- inversely proportional to
diameter
> 8 nm – not filtered.
Electrical charge.
Negatively charged – Glycoproteins rich in sialic acid.
so cationic & neutral particals – more
permeability

15. APPLIED PHYSIOLOGY.
 Albumin –
size 7 nm, still not
filtered.
reason – why ?
 Loss of negativity
Glomerular diseases
– loss of Negativity
so loss of albumin in
urine. -- ALBUMINURIA

16. COMPOSITION OF GLOMERULAR FILTRATE
(GLOMERULAR ULTRA FILTRATE)
 Ultra filtration.– Filtration under pressure.
 Composition – same like that of plasma except for
proteins & cells.
 Glomerular filtration:
 Mechanism of producing ultra filtrate under
hydrostatic pressure of the blood.
 Process similar to the formation of tissue
fluid by other capillary beds.

17. DYNAMICS OF GLOMERULAR
FILTRATION
GFR = KF [(pGc † ΠBS)-(ΠGc † pBS)]

18. EFFECTIVE FILTRATION
PRESSURE ( EFP)
EFP=
[(pGc † ΠBS)-(ΠGc † pBS)]
GFR= KF × EFP
= 12.5 [(60 + 0) – (32+18)]
= 12.5 × 10
= 125 ml/min

19. FILTRATION
 Analysis of Glomerular Capillary Dynamics
GFR = KF [(pGc – pBS)-(ΠGc- ΠBS)]
KF -- filtration coeffiecient = 12.5
 pGc - Hydrostatic Pressure Of Glomerular
Capillary = 60.0 mm Hg
 pBS – Hydrostatic pressure of bowmans space =
18 mm Hg
 ΠGc -oncotic pressure of glomerular cappilary =
32 mm Hg
 ΠBS - Oncotic pressure of Bowmans space = 0 mm Hg

20. NORMAL GLOMERULAR
FILTRATION RATE
 Glomerular filtration rate (GFR):
 Volume of filtrate produced by both kidneys each
minute.
 Averages 115 ml/min. in women;
 125 ml/min. in men.
 7.5 L/hr.
 180 L/ day i.e.
 In one day
 4 times total body water,
 15 times ECF, &
 60 times plasma volume.

21. FILTRATION FRACTION
 DEF:- Ratio of GFR to the renal plasma flow
FF = GFR / RPF
= 125 / 650
= 0.2 % ( 20 % RPF filtered / min)
 Glomerular versus systemic filtration
1 Total filtration.
180 L / 20 L. per day.
2 Filtration coefficient (Kf).
100 times in glomerulus.
3 Hydrostatic pressure. 2 / 1

22. FILTRATION FRACTION
4 Total capillary exchange area.
1.6 m2
(2-3 %) / 1000 m2
(25 %)
500 to 810 cm2
/ 250 m2
5 Balance of starling forces..

23. FACTORS AFFECTING GLOMERULAR
FILTRATION RATE
 Age –
 Filtration Coefficient (Kf).
 Kf = permeability × filtration area
Permeability -- hypoxia & toxic agents
thickening of capillary
membrane
 Filtration area Relaxation of Mesangial cells
Vasodilators – Dopamine , cAMP, ANP, NO, PG.
 Contraction of Mesangial cells
Vasoconstrictors – Angiotensin II,
NE,
Endothelins,
TXA2, Leukotrienes & histamine.

24. FACTORS AFFECTING GLOMERULAR
FILTRATION RATE
 Hydrostatic pressure in bowman’s space fluid (PBS). --
acute obstruction – stone.
 Glomerular capillary hydrostatic pressure.
Arterial pressure – except 80 to 200
Renal blood flow
Afferent & Efferent arteriolar resistance.
 Glomerular capillary oncotic pressure.
Hyperproteinaemia
Hypoproteinaemia

25. REGULATION OF GFR
 Auto regulation
 Hormonal regulation
 Nervous regulation

26. GFR DEPENDS ON DIAMETERS OF
AFFERENT AND EFFERENT ARTERIOLES
GFR GF
R
Glomerulus
Afferent arteriole Efferent arteriole
Glomerular filtrate
Aff. Art. dilatation
Eff. Art. dilatationEff. Art.
constriction
Aff. Art.
constriction
Prostaglandins,
Kinins, Dopamine
(low dose), ANP,
NO
Angiotensin II
(low dose)
Angiotensin II
blockade
Ang II (high dose),
Noradrenaline (Symp
nerves), Endothelin, ADH,
Prost. Blockade)

27. AUTO REGULATION
 Mechanism of Auto-regulation
1 Myogenic mechanism ( Respond to
change in arterial pressure).
2 Tubuloglomerular feedback
mechanism ( Respond to change in NaCl
concentration of tubular fluid.

28. TUBULOGLOMERULAR FEEDBACK
MECHANISM
 Renal arterial pressure
GFR
NaCl conc. in tubular fluid
Stimulate macula densa cells
Renin release
Afferent arteriole constriction /
dilation
Renal arterial pressure

29. HORMONAL REGULATION
 HORMONES
Vasoconstrictors
1 NE
2 Angiotensin II
3 Endothelin
VASODIALATORS
1 PG
2 NO
3 ANP
4 Bradykinin
 STIMULUS GFR
ECV
ECV
ECV
ECV, stretch NC
stretch, Ach, histamine
ECV
PG, ACE

30. NERVOUS REGULATION
 Afferent & efferent – sympathetic from T4-L2
through splanchnic nerves.
 Normally sympathetic tone minimum.
 Mild to moderate stimulation – mild effect.
 Strong acute stimulation – Fall in RBF due to
constriction of both afferent & efferent arterioles.

31. MEASUREMENT OF GFR
 If a substance (W) is neither reabsorbed nor secreted
by tubule:
 The amount excreted in urine/min. will be equal
to the amount filtered out of the glomeruli /min.
 Amount of substance excreted in urine/min
= UW V ……………….. 1
UW–Urine conc of w
V – Urine volume per unit time

32. MEASUREMENT OF GFR
 Rate at which a substance is filtered by the glomeruli
can be calculated:
Quantity filtered = GFR x PW …………… 2
 P = Concentration in plasma.
 Amount filtered = amount excreted
GFR x PW= UW V from eq 1 & 2
GFR = UW V
------------
PW

33. CRITERION FOR W
 Freely filterable at renal corpuscle
 Not reabsorbed
 Not secreted.
 Not synthesized by renal tubules.
 Not metabolized by renal tubules.
only one substance --- INULIN

34. CLEARANCE
 Definition :-
Amount of plasma completely cleared of the
substance by kidney in unit time by excretion of that
substance in urine.
Basic clearance formula
Cw = mass of w excreted / time
---------------------------
Pw
= Uw V
----------------------
Pw

35. INULIN CLEARANCE
 Inulin –
dye, fructopolysaccharide,
does not exist naturally,
measure of GFR – not reabsorbed, nor secreted, nor-
metabolized, non-toxic,
Method – single bolus dose
i/v infusion,
urine/ plasma conc,
urine flow rate,
Cin = Uin V / Pin

36. CLINICAL APPLICATION
 An indicator of plasma clearance mechanism.
 Cw = Cin clearance ratio 1
e.g. mannitol, sorbitol, vit B12, sucrose
 Cw < Cin clearance ratio < 1
e.g. Glucose, xylose, fructose
 Cw > Cin clearance ratio > 1
e.g. Para-amino hippuric acid (PAH),
phenol red

37. CREATININE CLEARANCE
 Adv.– More preferred
No intravenous dose needed.
Endogenous substance from metabolism of muscle
creatine
Filtered & marginally secreted
Method:-
24 hr urine collection, urine conc,
mid-point plasma conc sample,
Normal Value – 130 ml/min

38. UREA CLEARANCE
 Urea- End product of protein metabolism.
 Filtered & partly reabsorbed
 Clearance less than GFR
 Influenced by protein content of diet.
METHOD :-
Empty bladder,
urine collected at the end of 1 hour,
blood sample collected at mid point
estimate blood & urine urea.

39. UREA CLEARANCE
 Urea clearance drastically changes – urine output <
2ml /min
 So 2 urea clearance values
1 Maximal :- urine output > 2 ml.
CU = UV/ P
Normal value = 75 ml / min
2 Standard :- urine output < 2 ml.
CU = U √ V/ P
Normal value = 54 ml / min

40. MEASUREENT OF RENAL PLASMA
FLOW
 FICK’S Principle to kidney
“ Amount of substance excreted by
the kidney per unit time (UV) is equal
to the product of renal plasma flow
(RPF) and arteriovenous difference in
its plasma concentration.”
UV = RPF (Pa- Pv)
RPF = UV / (Pa-Pv)……………(1)

41. PAH CLEARANCE – TO
MEASURE RPF
 PAH clearance is used to measure
RPF
b’coz–
1 Completely extracted.
2 Neither metabolized nor
reabsorbed.
3 Does not affect RBF.
4 Actively secreted.
5 Conc. easily measured.

42. METHOD
 RPF = UV/ (Pa – Pv)
 All PAH excreted in urine nothing returned
so Pv is 0
RPF = UV / Pa
 Also PAH not excreted by any other organ so plasma PAH
conc can be used.
RPF = UV / P PAH
 BUT UV / P PAH= PAH Clearance
So RPF = PAH Clearance.
ERPF = PAH Clearance.
TRUE ERPF = CPAH / 0.9

43. Wednesday, June 1, 2016

44. THANK YOUTHANK YOU