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1. 1
RENAL PHYSIOLOGY
(II)
m
GLOMERULAR
STRUCTURE & FILTRATION
Mohammed Abdel Gawad

2. OBJECTIVES
2
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

3. OBJECTIVES
3
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

4. NEPHRON
(Renal malpighian corpuscle & Renal tubules)
4

5. RENAL CIRCULATION
5

6. OBJECTIVES
6
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

7. Formation of URINE in 3 steps
7
Tubular Tubular
Reabsorption Secretion
Glomerular Excretion
Filtration

8. Formation of URINE in 3 steps
8

9. Formation of URINE in 3 steps
9

10. OBJECTIVES
10
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

11. Glomerular Filtration Barrier
11

12. Glomerular Filtration Barrier
12
 A. The endothelial cells of the glomerulus;
 1. pore (fenestra) (70-100 nm)
 B. Glomerular basement membrane:
 1. lamina rara interna
 2. lamina densa
 3. lamina rara externa
 C. Podocytes:
 1. enzymatic and structural protein
 2. filtration slit (20-30 nm)
 3. filtration diaphragm (nephrin)

13. Glomerular Filtration Barrier
13

14. GLOMERULAR BASEMENT MEMBRANE
STRUCTURE
14
 Formed of:
 Collagen type IV
 Triple helix: 3 α-peptide chains with globular non collagenous
domain (NC1)
 Abnormalities:
 Mutation in α-peptide chains → no proper helix → hereditary nephritis
 Antibodies against NC1 in kidney → anti GBM disease
 Antibodies against NC1 in kidney & lung → Goodpastuer Syndrome

15. OBJECTIVES
15
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

16. 16
Glomerular Filtrate & GFR
 Glomerular filtrate:
 fluid that filters through the glomeruli into
Bowman's capsule
= plasma – (plasma proteins, plasma
proteins binbed substances & substances
with a MW > 70.000).
 Glomerular Filtration Rate (GFR):
 - definition: The quantity of glomerular
filtrate formed in all nephrons of both
kidneys / min.
 - normal value: 125ml/min. 180 Liters/day.

17. 17
Glomerular Filtrate & GFR

18. OBJECTIVES
18
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

19. Movement of water:
Starling’s Forces & Membrane Permeability
19
 The amount of water in each body compartment is
dependent on:
 1- osmotic pressure
 2- hydrostatic pressure
 + Membrane characteristics

20. Total body water Compartments

21. Osmolality
 is the number of particles (mmol) contained in
one liter of water, so measured in mmol/L.
 i.e. it is the concentration by number

22. Starling’s Forces – Osmotic pressure
22

23. Starling’s Forces – Osmotic pressure
23

24. Starling’s Forces – Hydrostatic pressure
24

25. Starling’s Forces

26. Membrane Factors
 Membrane permeability (s) is clinically relevant in disorders which
disrupt membrane integrity (e.g., sepsis).
 Permeability of a membrane ranges from zero, completely
permeable, to one, completely impermeable.

27. Starling’s Forces – Net Filtration Pressure
27

28. Starling’s Forces – Net Filtration Pressure
28

29. Hydrostatic Pressure in Renal Circulation
29

30. DYNAMICS OF GLOMERULAR FILTRATION
(STARLING FORCES)
(NET FILTRATION PRESSURE)
30

31. DYNAMICS OF GLOMERULAR FILTRATION
(STARLING FORCES)
(NET FILTRATION PRESSURE)
31

32. GFR & Filtration Coefficient (Kf)
32
 Glomerular Filtration Rate:
 - definition: The quantity of glomerular filtrate formed in all nephrons of
both kidneys / min.
For the 10 mmHg
 - normal value: 125ml/min. 180 Liters/day.
 Filtration coefficient (Kf):
 It is the GFR for both kidneys per mmHg of filtration pressure.
 Normally = 12.5 For 1 mmHg
 GFR = 12.5 X 10 = 125 ml/min

33. OBJECTIVES
33
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

34. Autoregulation of GFR
34
 Under normal conditions (MAP= 80-
180mmHg) renal autoregulation maintains
a nearly constant glomerular filtration rate
 A- Myogenic mechanism:
 Laplace law:
 Vessel wall tension
α Distending pressure X radius of the vessel.
 When arterial pressure rises →
afferent arteriole stretches → vascular
smooth muscles contract → arteriole
resistance offsets pressure increase →
RBF (& hence GFR) remain constant &
vise versa

35. Autoregulation of GFR
35
 B- Tubuloglomerular feed back mechanism

36. Autoregulation of GFR
36
 B- Tubuloglomerular feed back mechanism

37. Autoregulation of GFR
37
 B- Tubuloglomerular feed back mechanism
Juxtaglomerular Apparatus or Complex:
is a specialized region of a nephron where the afferent arteriole and Distal Convoluted
Tubule (DCT) come in direct contact with each other. Juxtaglomeruar Apparatus (JGA)
consists of:
1) Juxtaglomerular cells (modified smooth muscle cells) of afferent
arteriole including renin containing (synthesizes and stores renin) and sympathetically
innervated granulated cells which function as mechanoreceptors to sense blood
pressure.
2) Macula densa cells (Na+ sensors) of Distal Convoluted Tubule (DCT) which
function as chemoreceptors to sense changes in the solute concentration and flow rate
of filtrate.

38. Autoregulation of GFR
38
 B- Tubuloglomerular feed back mechanism

39. Autoregulation of GFR
39
 B- Tubuloglomerular feed back mechanism

40. Autoregulation of GFR
40
 B- Tubuloglomerular feed back mechanism
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41. OBJECTIVES
41
 Be sure that you know what is NEPHRON
 Be sure that you know RENAL CIRCULATION
 Formation of URINE Steps (General Aspect)
 Glomerular Filtration Barrier
 Glomerular Filtrate & GFR (definitions)
 Starling’s Forces & Membrane Permeability
 Dynamics of Glomerular Filtration
 Glomerular Filtrate & Kf (definitions)
 Autoregulation of GFR
 Factors affecting GFR

42. Factors Affecting GFR
1. Renal Blood Flow :
42
- increase blood flow
through the nephrons →
elevates the glomerular
pressure → increases
the glomerular filtration
rate.

43. Factors Affecting GFR
2. Diameter of glomerular blood vessels:
43
Glomerulus
Afferent arteriole Efferent arteriole
GFR GFR
Glomerular
filtrate
Eff. Art. Aff. Art. Eff. Art. dilatation
Aff. Art. dilatation
constriction constriction
?
Prostaglandins Angiotensin II Adrenaline & Angiotensin II
E2 & Noradrenaline (Symp blockade
I2, Kinins, Dopa nerves), Endothelin,
mine (low

44. Factors Affecting GFR
2. Diameter of glomerular blood vessels:
44
i- mild constriction → increases the
glomerular pressure → increases the
Eff. Art. filtration rate.
constriction
ii- severe or moderate constriction →
decreases the glomerular flow rate →
decreases the filtration rate, because the
plasma will remain for a longer period of
time in the glomerulus → extra large
amounts of plasma will filter out →
increases the plasma colloid osmotic
pressure → paradoxical decrease in
GFR occurs despite the increase in
glomeular pressure.

45. Factors Affecting GFR
3. Factors affecting Net Filtration Pressure:
45
I. Arterial blood pressure:
-a rise in the systemic blood pressure →
an auto-regulatory mechanism (automatic
afferent arteriolar constriction) →
prevents the rise in the glomerular
pressure
II. Colloid osmotic pressure:
-Hypoproteinaemia will increase the
filtration rate.
III. Post renal obstruction makes back
pressure and increases the Bowman’s
capsule hydrostatic pressure which leads to
decreasing GFR.

46. Factors Affecting GFR
4. Factors affecting filtration coefficient (Kf):
46
 I. Permeability of Glomerular capillaries
(hydrolic conductivity):
 - Increase permeability of glomerular capillaries →
increases the GFR.
 - Normally the permeability of the glomerular
capillaries and Bowman's capsule is absent for
substances of molecular weight higher than 70,000.
 - MW:
 Albumin: 70,000
 Globulin: 165,000
 Fibrinogen: 200,000
 Hb:68,000
 II- Surface area of the membrane:
 if decrease, it will decrease GFR
 e.g.
 Chronic pyelonephritis
 Chronic GN

47. The Concept Of Plasma
47
Clearance
 Inulin clearance
 Creatinine clearance
 PAH clearance

48. 48
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49. 49
Gawad