Renal Physiology

1. RENAL PHYSIOLOGY

2. SESSION OUTCOMES
At the end of the lecture, the group should be able to:
1. describe the general principle;
2. understand the concept of glomerular filtration and clearance
and;
3. explain the autoregulation of GFR/RBF.

3. ESSENTIAL
QUESTIONS:
HOW IS URINE PROCESSED?
HOW IS GFR ESTIMATED?
HOW IS GFR/RBF REGULATED?

6. N B Y L A
E C T E A
B A L N
A C E

7. R W S P A
E Q T X B
W A S E
T

8. S F E D O
L K W H B
F L O W

9. P R Z Y E
T M P A J
R A T E

10. B F R A T
L C I E O
F I L E
T R

11. E S T K R
N M P I O
R O T E
P N
I

12. S I P X A
C L T M A
P L A M
S A

13. I S T D N
C R I N I
T R I N
N
I S I C

14. S A N E E
C L C R A
E A R N
A
L
C C E

15. WASTE
UREA
FLOW
FILTER
BALANCE
PLASMA
CLEARANCE
RATE
INTRINSIC
KIDNEY

16. HOMEOSTASIS
Excretion of
metabolic
waste product
Regulation
of Arterial
Pressure
Regulation
of water
and
electrolyte
Regulation
of acids and
bases
Glucose
synthesis
Regulation
of RBC
production
Regulation
of fluid
osmolality

17.  A retroperitoneal organ
 T11-L3
 Normal size: 11-15cm in
adults.
 Right kidney usually
shorter than the left
(upper limit of variation
in length between right
& left 1.5 cm)

18. Nephron:
functional unit of the kidney
 The nephron consists of:
 Vascular components
 Afferent & efferent arterioles
 Glomerulus
 Peritubular capillaries
 Vasa recta
 Tubular components
 Proximal convoluted tubule
 Distal convoluted tubule
 Nephron loop (loop of
Henle)
 Collecting duct
 Tubovascular component
 Juxtaglomerular apparatus

19. Cortical and Juxtamedullary nephron segments

20. Renal blood supply RENAL
ARTERY
SEGMENTAL
ARTERY
INTERLOBAR
ARTERY
ARCUATE
ARTERY
INTERLOBULA
R AFFERENT
ARTERIOLE
GLOMERULU
S
EFFERENT
ARTERIOLE
PERITUBULAR
CAPILLARIES/VASA
RECTA
INTERLOBULA
R
VEIN
ARCUATE
VEIN
INTERLOBAR
VEIN
RENAL
VEIN

21. Renal blood flow
𝑄 =
Δ𝑃
𝑅
Where: Q = Flow
R = vascular resistance
Δ𝑃 = pressure gradient

24. Basic Mechanisms
of Urine Formation
GLOMERULAR FILTRATE:
 fluid that filters through the glomeruli into
Bowman's capsule
 =PLASMA –PROTEINS(plasma proteins,
plasma proteins binded substances &
substances with a MW > 70.000 Da).
GLOMERULAR FILTRATION RATE(GFR):
The quantity of glomerular filtrate formed in all
nephrons of both kidneys / min.
- normal value: 125ml/min or 180 Liters/day.

25. GLOMERULAR FILTRATION BARRIER

26. GLOMERULAR FILTRATION BARRIER

27. The Ability of a Solute to Penetrate the
Glomerular Membrane Depends on:
Molecular size ( small molecules > filterability)
Ionic charge (cations > filterability)

28. Substance MW Filterability
Water 18 1.0
Sodium 23 1.0
Glucose 180 1.0
Insulin 5 500 1.0
Myoglobin 17 000 0.75
Albumin 69 000 0.0075
Filterability of Substances by Glomerular Capillaries
Based on Molecular Weight

29. Effects of Size and Electrical Charge of
Dextran on Filterability by Glomerular
Capillaries

30. 30
GFR DETERMINANTS
Balance of hydrostatic and colloid osmotic forces acting
across the capillary membrane
Capillary filtration coefficient (Kf), the product of the
permeability and filtering surface area of the capillaries)
GFR =Kf x Net Filtration Pressure

32. GLOMERULAR HYDROSTATIC
PRESSURE (PG)
• the determinant of GFR most subject
to physiological control
• Factors that influence PG
- arterial pressure (effect is buffered by autoregulation)
- afferent arteriolar resistance
- efferent arteriolar resistance

33. Re
Effect of Afferent and Efferent Arteriolar
Constriction on Glomerular Pressure
PG
GFR
Ra
Ra GFR + Renal
Blood Flow
Blood Flow
GFR
PG
Re GFR + Renal
Blood Flow
Blood Flow
𝑄 =
Δ𝑃
𝑅

34. Effect of changes in afferent arteriolar or efferent
arteriolar resistance

35. Kf GFR
PB GFR
G GFR
PG GFR
RA PG
RE PG
Summary of determinants of GFR
GFR
GFR
(as long as RE < 3-4 x normal)

37. • Clearance is a general concept that describes the rate
at which substances are removed (cleared) from the
plasma.

38. Clearance Technique
Renal clearance of a substance is the volume of
plasma completely cleared of a substance per min.
Cs = Us x V
Ps
Cs x Ps = Us x V
Where: Cs = clearance of substance S (mL/min)
Ps = plasma conc. of substance S (mg/mL)
Us = urine conc. of substance S (mg/mL)
V = urine flow rate (mL/min)

39. For a substance that is freely filtered, but not reabsorbed or
secreted (inulin, 125 I-iothalamate, ~creatinine), renal clearance
is equal to GFR
Use of clearance to measure GFR
amount filtered = amount excreted
GFR x Pin = Uin x V
GFR =
Pin
Uin x V

40. Calculation of GFR:
Pinulin = 1.0 mg / 100ml
Uinulin = 125 mg/100 ml
Urine flow rate = 1.0 ml/min
GFR =
125 x 1.0
1.0
= 125 ml/min
GFR = Cinulin =
Pin
Uin x V

41. Creatinine clearance
Creatinine, endogenously released into plasma by skeletal
muscle, is used to measure GFR
 Not as accurate as inulin
 amount excreted > amount filtered
 Reasonably accurate measurement of GFR
GFR = PCr=
PCr
Ucr x V

44. GFR/RBF
autoregulation
Myogenic
mechanism
Tubuloglomerular
feedback
mechanism

45. MYOGENIC
MECHANISM
INCREASE ARTERIAL
PRESSURE
AFFERENT
ARTERIOLES
STRETCHES
VASCULAR SMOOTH
MUSCLE CONTRACTS
ARTERIOLE
RESISTANCE
INCREASES
NORMALIZE GFR and
RBF

46. 46
TUBULOGLOMERULAR FEEDBACK
MECHANISM

47. STRUCTURE OF JG APPARATUS

48. JG FEEDBACK
MECHANISM INCREASED ARTERIAL
PRESSURE
INCREASE PG
INCREASE GFR
INCREASE TUBULAR FLOW
Increase Macula Densa
stimulation
Increase AFFERENT
arteriole resistance
-

49. INCREASE GFR
INCREASE NaCl Macula densa
Increase uptake through 1-Na-1-K-
2Cl symporter
Increase production of ATP and
adenosine
ATP and adenosine binds to their
specific receptors
Increase intracellular calcium ion
Increase Afferent arteriole resistance
-

50. JG FEEDBACK
MECHANISM

53. Stimulus Effect on GFR Effect of RBF
Vasoconstrictor
Angiotensin II ECFV
Endothelin Stretch, Ang II, Epi, Bradykinin
Vasodilator
PGE ECFV, Shear stress, Ang II
Nitric oxide Shear stress, ACh, Histamine
Bradykinin PGE ACE
HORMONES THAT INFLUENCE GFR
AND RBF

54. “The kidney presents in the highest degree the phenomenon of
sensibility, the power of reacting to various stimuli in a direction,
which is appropriate for the survival of the organism; a power of
adaptation which almost gives one the idea that its component
parts must be endowed with intelligence.”
E. STARLING—1909