5. IDENTIFY THE PARTS
1
Proximal convoluted tubule.
Loop of Henle
Distal convoluted tubule.
Collecting duct.
Glomerular
1capsule.
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.
8. C HARAC TERISTIC S OF FILTRATION
MEMBRANE
SITE OF FILTRATION
Glomerulus
The site of filtration
Mechanism is sieve-like
Layers:-
1 foot processes of podocytes.
2Lamina rara externa or
outer cement layer.
3 Lamina densa.
4Lamina rara interna or
inner cement layer.
5 Endothelial cell layer.
13.
C HARAC TERISTICS 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.
19. FILTRATION
Analysis of Glomerular Capillary Dynamics
GFR
=
KF [(p G
c – pBS)-(ΠGc- ΠBS)]
KF -- filtration coeffiecient = 12.5
pG
c - Hydrostatic Pressure Of Glomerular
Capillary = 60.0 mm Hg
pBS – Hydrostatic pressure of bowmans space =
18 mm Hg
ΠG
c -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
2
3
Total filtration.
180 L / 20 L. per day.
Filtration coefficient (Kf).
100 times in glomerulus.
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.
25. REGULATION OF GFR
Auto regulation
Hormonal regulation
Nervous regulation
26. GFR DEPENDS ON DIAMETERS OF
AFFERENT AND EFFERENT ARTERIOLES
G F R GF
R
Glomerulus
Afferent arteriole Efferent arteriole
Glomerular filtrate
Aff. Art. dilatation
Eff. Art. dilatation
Eff. 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.
29. HORMONAL REGULATION
HORMONES
Vasoconstrictors
1 NE
2 Angiotensin II
3Endothelin
VASODIALATORS
1 PG
4 NO
5 ANP
6 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
= UWV ……………….. 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 = UWV
------------
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= UinV / 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
2
Maximal :- urine output > 2 ml.
CU = UV/ P
Normal value = 75 ml / min
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 P
A
H
BUT UV / P P
A
H= PAH Clearance
So RPF = PAH Clearance.
ERPF = PAH Clearance.
TRUE ERPF = CP
AH/ 0.9
