1. Glomerular Filtration
URINE FORMATION
Nov-18
Glomerular Filtration

2. Glomerular Filtration
Urine formation
Urine formation include
glomerular filtration
tubular reabsoption
tubular secretion
Urinary excretion of substance
is the sum of these 3 renal processes.
Nov-18
Glomerular Filtration

3. Glomerular Filtration
Urine formation
Urine formation begins with ultrafiltration
from glomerular capillaries
into Bowman’s capsule
Most substances in the plasma
except protein
are freely filtered
Nov-18
Glomerular Filtration

4. Glomerular Filtration
Urine formation
Ultrafiltration refers to
the passive movement
of an essentially protein free fluid
from the glomerular capillaries into Bowman’s capsule
Nov-18
Glomerular Filtration

5. Glomerular Filtration
Urine formation
As filtrate leaves capsule
and passes through renal tubules
it is modified
By reabsorption of water and specific solutes
by secretion of other substances
from peritubular capillaries into the tubules
Nov-18
Glomerular Filtration

6. Glomerular Filtration
Urine formation
In general tubular reabsorption is
quantitatively more important
than tubular secretion
but secretion plays important role
in determining amount of K+ and H+
and few other substances that are excreted in the urine
Substances that must be cleared
from the blood especially the end products
of metabolism are poorly reabsorbed.
Nov-18
Glomerular Filtration

7. Glomerular Filtration
Urine formation
Electrolytes
Na+,K+, Cl-,HCO3-, Ca2+
are highly reabsorbed
Nutritional substance
eg glucose, AA, are completely reabsorbed
Each of the process
filtration, reabsoption, secretion
is regulated according to the needs of the body.
Nov-18
Glomerular Filtration

8. Glomerular filtration
1st step in urine formation
large amount of fluid
is filtered through glomerular capillaries
into Bowman’s capsule
glomerular capillaries
are relatively impermeable to proteins
so that the glomerular filtrate is protein free
concentration of other plasma constituents
including salt and organic molecules
that are not bound to plasma proteins
are similar in plasma and glomerular filtrate
Nov-18
Glomerular Filtration

9. Glomerular filtration
Nov-18
Glomerular Filtration

10. Glomerular filtration rate (GFR)
determined by
starling forces
capillary filtration coefficient ( kf ) Kf
= permeability x filtering surface area of the capillaries
Glomerular capillaries have
large kf and
high glomerular hydrostatic pressure
thus high GFR.
Nov-18
Glomerular Filtration

11. Glomerular filtration rate (GFR)
GFR ≈ 125ml/min or 180 liters/day
GFR ≈ % renal plasma flow.
Nov-18
Glomerular Filtration

12. Glomerular Filtration
Filtration fraction
Not all of the plasma entering the kidney
and therefore the glomerulus is filtered
The portion of plasma
that is filtered
is termed filtration fraction
Filtration fraction = GFR/RPF
Nov-18
Glomerular Filtration

13. Glomerular filtration rate (GFR)
Rate of filtration of solutes is determined by
molecular size
electrical charges.
Nov-18
Glomerular Filtration

14. Glomerular Filtration
GFR
Substance
Mwt
Filterability
water 18
1.0
Na+ 23
Glucose
180
Inulin
5,500
Myoglobin
17,000
0.75
Albumin
69,000
0.005
Nov-18
Glomerular Filtration

15. Glomerular Filtration
GFR
Negatively charged large molecules
are filtered less easily
than positively charged molecules
of equal molecular size.
Molecular diameter of Albumin is
only ≈ 6nm where as the
glomerular membrane pores
are thought to be ≈ 8nm
Nov-18
Glomerular Filtration

16. Glomerular Filtration
GFR
Albumin is restricted from filtration however because of
its negative charges
the electrostatic repulsion exerted by negative charges of the basement membrane poteoglycan.
Nov-18
Glomerular Filtration

17. Glomerular Filtration
Determinants of GFR
The sum of starling forces
gives net filtration pressure
GFR = Kf ⅹ( net filtration pressure)
Nov-18
Glomerular Filtration

18. Glomerular Filtration
Determinants of GFR
Glomerular capillary hydrostatic pressure
(≈ 60mmHg)
promotes filtration
Bowman’s capsule hydrostatic pressure
(≈ 18mmHg)
Oppose filtration
Nov-18
Glomerular Filtration

19. Glomerular Filtration
Determinants of GFR
Glomerular capillary oncotic pressure
( ≈ 32mmHg)
Oppose filtration
Glomerular filtrate oncotic pressure
( ≈ zero)
Promote filtration
Net filtration pressure
= 10mmHg
Nov-18
Glomerular Filtration

20. Glomerular capillary filtration coefficient (Kf )
can not be measured directly
estimated experimentally by
GFR/net filtration pressure
= 125ml/min/10mmHg
=12.5ml/min/mmHg
Nov-18
Glomerular Filtration

21. Glomerular capillary filtration coefficient (Kf )
Increased Kf
leads to increased GFR
and decrease in Kf reduces GFR
Some diseases lower Kf
by reducing number of functional glomerular capillaries
reducing surface area
Nov-18
Glomerular Filtration

22. Glomerular capillary filtration coefficient (Kf )OR
by increasing thickness
of glomerular capillary membrane
and reducing its permeability
eg chronic uncontrolled hypertension, DM
Nov-18
Glomerular Filtration

23. Glomerular capillary hydrostatic pressure
GFR
determined by
arterial pressure
Afferent arteriole resistance
Efferent arteriole resistance
Nov-18
Glomerular Filtration

24. Glomerular capillary hydrostatic pressure
Constriction of afferent arterioles
always reduces GFR
However the effect of efferent arteriolar constriction
depends on the severity of constriction
Nov-18
Glomerular Filtration

25. Glomerular capillary hydrostatic pressure
Modest efferent constriction
raises GFR
but severe efferent constriction
(more than 3 fold increase in resistance)
tends to reduce GFR
Nov-18
Glomerular Filtration

26. Glomerular capillary colloid osmotic pressure
 Glomerular capillary oncotic pressure
 GFR
Influenced by
the arterial plasma colloid osmotic pressure (p )
and fraction of plasma filtered by the glomerular capillaries (filtration fraction)
Increased p
leads to an increase in gc
which in turn reduces GFR
Nov-18
Glomerular Filtration

27. Glomerular capillary colloid osmotic pressure
Increase in the filtration fraction
concentrates the plasma proteins
and raises the gc
Filtration fraction
can be increased either
by an increased GFR
or reduced RBF
Nov-18
Glomerular Filtration

28. Glomerular capillary colloid osmotic pressure
Even with a constant glomerular hydrostatic pressure
a greater rate of RBF
into the glomerulus
tends to increase GFR
and a lower rate of RBF into the glomerulus tends to reduce GFR
Nov-18
Glomerular Filtration

29. Bowman’s capsule hydrostatic pressure
 Bowman’s capsule hydrostatics pressure
GFR
increased by obstruction of urinary tract
eg precipitation of calcium, uric acid
Nov-18
Glomerular Filtration

30. Physiological control of GFR and renal blood flow
The determinants of GFR
that are most variable and subject
to physiological control include
the glomerular hydrostatic pressure
and glomerular capillary colloid osmotic pressure
Nov-18
Glomerular Filtration

31. Physiological control of GFR and renal blood flow
These variables in turn
are influenced by
sympathetic nervous system
hormones and autacoids
and other feedback control
that are intrinsic to the kidney
Nov-18
Glomerular Filtration

32. Sympathetic nervous system
SNS activation
decreases GFR
strong activation of renal sympathetic nerves
constrict renal arterioles
decrease renal blood flow
decrease GFR
Nov-18
Glomerular Filtration

33. Sympathetic nervous system
moderate or mild stimulation has
little influence on renal blood flow and GFR
renal sympathetic nerves seem to be
most important in reducing GFR
during severe, acute disturbances
lasting for few min to few hours.
Nov-18
Glomerular Filtration

34. Hormones and autacoids
Noradrenaline and adrenaline
constrict afferent and efferent arterioles
causing reduction in GFR.
Angiotensin II constricts efferent arterioles
raise glomerular hydrostatic pressure
reduce renal blood flow
Nov-18
Glomerular Filtration

35. Hormones and autacoids
Angiotensin II associated with
decreased or volume depletion
helps to prevent decreases
in glomerular hydrostatics pressure and GFR.
Nov-18
Glomerular Filtration

36. Hormones and autacoids
Endothelial derived NO
decrease renal vascular resistance
and increases GFR
basal level of NO
prevent excessive vasoconstriction
of the kidneys and allowing them to excrete
normal amounts of Na+ and water.
Nov-18
Glomerular Filtration

37. Hormones and autacoids
PGE2,PGI2 and bradykinin
increase renal blood flow and GFR
Not of major importance in regulating
renal blood flow or GFR in normal conditions
Nov-18
Glomerular Filtration

38. Autoregulation of GFR and RBF
Feedback mechanism
intrinsic to the kidneys
keeps the renal blood and GFR
relatively constant
despite marked changes in BP
Nov-18
Glomerular Filtration

39. Autoregulation of GFR and RBF
The major function of autoregulation
in the kidney
is to maintain a relatively constant GFR
allow precise control of renal excretion of water and solutes.
Changes of BP 80 –170mmHg
cause only slight changes in GFR
Nov-18
Glomerular Filtration

40. Autoregulation of GFR and RBF
The mechanisms are not 100% perfect
but prevent potentially large changes in GFR
and renal excretion of water and solutes
that would otherwise occur with changes in BP
Changes in BP exert much less of an effect
on urine volume
Autoregulation
glomerulotubular balance
tubuloglomerular feedback
Nov-18
Glomerular Filtration

41. Tubuloglomerular feedback
mechanism links changes in [NaCl]
at the macula densa with the control
of renal arteriolar resistance
Helps to ensure relatively constant
delivery of NaCl to the distal tubule
and helps to prevent great fluctuations
in renal excretion
Nov-18
Glomerular Filtration

42. Tubuloglomerular feedback
In many circumstances this feedback
autoregulates renal blood flow and GFR in parallel.
The feedback mechanism
has 2 components that work together
to control GFR.
Afferent arteriolar feedback mechanism.
Efferent arteriolar feedback mechanism.
Nov-18
Glomerular Filtration

43. Tubuloglomerular feedback
They depend on special anatomical
arrangements of the juxtaglomerular complex.
Decreased macula densa NaCl
causes dilatation of afferent arterioles
and increased rennin release.
 GFR
 Na reabsoption
Nov-18
Glomerular Filtration

44. Tubuloglomerular feedback
BP
Glomerular hydrostatic
pressure
GFR  
Rennin
Macula densa NaCl
 Angiotensin II
Efferent arteriolar
resistance
Afferent arteriolar
resistance
Nov-18
Glomerular Filtration

45. Glomerolotubular balance
is adaptive mechanism
in the renal tubules which allow them
to increase their reabsoption rate
when GFR rise
The tubules increase reabsoption rate
in response to increased tubular load
Nov-18
Glomerular Filtration

46. Glomerulotubular balance
For example
if GFR is increased from 125 to 150ml/nim,
the absolute rate of proximal tubular reabsorption
also increases from about 81 to 97.5ml/min.
The total rate of reabsorption
increases as the filtered load increases
even though the % of GFR reabsorbed
remains relatively constant .
Nov-18
Glomerular Filtration

47. Glomerolotubular balance
Some degree of glomerulotubular balance
also occur in other tubular segments
especially loop of Henle
Can occur independent of hormones
Help to prevent overloading
of distal tubules when GFR increases.
Nov-18
Glomerular Filtration

48. Myogenic autoregulation of GFR&RBF
Ability of individual blood vessels
to resist stretching
during increased arterial pressure.
Helps to prevent excessive increases
in renal blood flow and GFR
when arterial pressure increases.
Nov-18
Glomerular Filtration

49. Physiological control of GFR&RBF
High protein intake
and increased blood glucose
increase RBF and GFR
Nov-18
Glomerular Filtration