1. Dr. Michael Fill, Lecturer
PHYSIOLOGY 451
RENAL PHYSIOLOGY
Dr. Michael Fill, Lecturer
Animated RBC’s

2. Renal Blood Flow, Filtration
Lecture 2
Renal Blood Flow, Filtration
and Clearance

3. Basic Renal Processes Urine Formation Filtration (F) Reabsorption (R)
Secretion (S)
Afferent Arteriole
Efferent Arteriole
Glomerulus
Bowman’s
Capsule
Excretion = F + S - R
Renal
Tubule
Peritubular
Capillary
Some Examples: Substances that are Filtered then Reabsorbed
>99.9%
799.5
∼0.5
800
Glucose mM/day
4,498 ∼2
4,500
HCO mM/day
99.3%
19,850
150
20,000
Cl mM/day
99.4%
24,850
25,000
Na mM/day
99.2%
178.5
∼1.5
180
H2O L/day
% of filtered load
reabsorbed
Amount Reabsorbed
Amount Excreted
Amount Filtered
Substance, units
This “filtered then almost completely reabsorbed” scenario is certainly not the case for all solutes.
Conceptual Point :
Filtration is the most basic “mode” of renal
substance handling.
solutes need pass the filter barrier
no specific transport processes
if there is no reabsorption or secretion,
then the substance will be excreted.
There are very few “filtered-only” solutes.
Most are also reabsorbed and/or secreted.

4. Some Important Renal Physiology Numbers Renal Blood Flow RBF 1.1 L/min
Renal Plasma Flow RPF 625 ml/min
RPF = RBF x (1 – hematocrit)
typical hematocrit is ~0.43, so RPF is 1.1x0.57.
Glomerular Filtration Rate GFR 125 ml/min
Urine Flow Rate ml/min
Filtration Fraction GFR/RPF 20%
20% of plasma entering a glomerulus is filtered.
Thus, 20% of any freely-filtered solute present enters Bowman’s space.
Note that values given above can vary in different circumstances.
Also remember that RBF far exceeds what kidney cells need to stay
alive so RBF can vary dramatically without affecting kidney cell vitality.

5. Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Fluid Filtration  Reabsorption

6. There is net filtration along glomerular capillaries
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Glomerular Capillaries
There is net filtration along
entire length of the
glomerular capillaries

7. Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Glomerular Capillaries
Point #2: Glomerular Capillaries
work at higher pressure.
(This is because efferent arteriole is
usually smaller diameter than the
afferent arteriole)

8. Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Glomerular Capillaries
Point #3: Hydrostatic pressure is
constant in glomerular capillaries.
(Most capillaries have high resistance
so pressure drops. The multiple parallel
loops provide very low
resistance.)

9. Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Glomerular Capillaries
Point #4: COP (colloid oncotic
pressure) increases in glomerular
capillaries. (This is because a huge
amount of fluid exits the blood leaving
plasma proteins behind.)
Hydrostatic pressure inside
Bowman’s Capsule is low &
constant.

10. Net Filtration Pressure
Summary of forces driving glomerular filtration
Net Filtration Pressure (NFP)
NFP = PGC – (πGC + PBS)
where,
PGC is average glomerular capillary
hydrostatic pressure.
πGC is average plasma oncotic pressure PBS is average hydrostatic pressure inside
Bowman’s capsule
Thus,
NFP = 55 – ( )
or 10 mm Hg
GFR of course depends on this value
but not just this value
GFR = Kf x NFP
Filtration Coefficient:
- Fluid permeability of Glom.Caps.
(i.e. the size of holes in filter)
- Surface area of Glom.Caps.
(i.e. the numerous parallel loops
in glomerulus)
Main Point :
Glomerular capillaries are specialized
for filtration. No reabsorption of fluid
occurs in the glomerular capillaries.

11. Factors that Influence GFR
Hydrostatic & oncotic pressures
GFR = Kf x NFP
Glomerular permeability & surface area
2001
Kidney Stone could increase hydrostatic pressure in
Bowman’s capsule reducing GFR
Renal Artery Stenosis reduced hydrostatic pressure in glomerular
capillaries will reduced GFR
Nephritic Disease reduced number of working nephrons, less
surface area for filtration and reduced GFR
Sympathetic Stimulation decreased afferent arteriole diameter will decrease
hydrostatic pressure in glomerulus, reducing GFR.
mesangial cell contraction will decrease the available
surface area for filtration and decrease GFR.
Starvation (or renal disease) decreased plasma protein content lowers plasma
oncotic pressure and this will increase GFR.
Blood Pressure (MAP) increased/decrease hydrostatic pressure in
glomerular capillaries will increase/decrease
GFR.

12. Kidney’s Resist Changes in GFR (and RBF)
Autoregulation : intrinsic property of the kidney (no nerves/hormones needed)
can be over-ridden by extrinsic factors (nerves/hormones)
1.1 L/min
125 ml/min
Mechanisms:
1) myogenic (relatively minor in kidneys)
2) tubuloglomerular feedback

13. Tubuloglomerular Feedback
Juxtaglomerular Apparatus (JGA)

14. Tubuloglomerular Feedback
Juxtaglomerular Apparatus (JGA)
Macula
Densa
Macula Densa: Cells sense fluid flow in distal tubule (involving NaCl & swelling)
& secrete vasoconstriction agent (probably ATP). This agent
diffuses to nearby afferent arteriole influencing GFR.
Note: Granular cells secrete renin which is involved in generating
extra-renal angiotensin II.
(renin does not contribute to renal autoregulation)

15. Volume of Plasma Cleared
Concept of Clearance (traditionally difficult to understand)
Clearance is just a way to quantify renal handling of a substance.
Clearance of a substance is often used to evaluate renal function.
First…. we will define clearance in words.
Clearance is defined as the volume of plasma “cleared” of a substance by the kidneys per minute. ( ml/min )
Now….Let’s see how we
can calculate clearance.
Volume of Plasma Cleared

16. Now….Let’s apply this to the real world.
Concept of Clearance
To calculate clearance of substance X (CX),
first need to calculate amount of X excreted in urine per unit time.
amount of X excreted = UX · V
Urine volume per minute (ml/min)
Urine X concentration
then simply divide this by the plasma X concentration…
CX = you will need to remember this formula
UX · V PX
This formula is convenient because UX, PX and V are easily measured.
Now….Let’s apply this to the real world.

17. Now….Let’s apply this to the renal world.
Concept of Clearance
To calculate clearance of substance X (CX),
first need to calculate amount of X excreted in urine per unit time.
amount of X excreted = UX · V
Urine volume per minute (ml/min)
Urine X concentration
then simply divide this by the plasma X concentration…
CX = you will need to remember this formula
UX · V PX
This formula is convenient because UX, PX and V are easily measured.
Now….Let’s apply this to the renal world.

18. Inulin: polysaccharide, not a naturally occurring substance in body
Inulin Clearance
Inulin: polysaccharide, not a naturally occurring substance in body
freely filtered but not reabsorbed or secreted ….so all inulin
that is filtered will end up in the urine
CINULIN is the “gold standard” for measuring GFR
Volume filtered
is volume cleared.
GFR = CINULIN =
UINULIN · V
PINULIN
V = urine produced in ml/min
UINULIN = urine inulin concentration
PINULIN = plasma inulin concentration
The main clinical drawback here is that inulin must be continuously
infused while urine is collected (this is usually a day or so).

19. “effectively” approaches
PAH Clearance
PAH: para-aminohippurate is also not naturally in the body
it is freely filtered and robustly secreted….so both filtered and
secreted PAH will end up in the urine
CPAH is clinically used to estimate RPF
Cleared volume
much larger than
filtered volume.
So large in fact that it
“effectively” approaches
RPF
RPF = CPAH =
UPAH · V
PPAH
V = urine produced in ml/min
UPAH = urine PAH concentration
PPAH = plasma PAH concentration
Recall that…. RPF = RBF x ( ) so…. RBF =
CPAH
0.57
hematocrit

20. Creatinine: produced from creatine metabolism in muscle
Creatinine Clearance
Creatinine: produced from creatine metabolism in muscle
production rate usually very constant (if muscle mass constant)
freely filtered and not reabsorbed …little bit is secreted
(this makes it a good but imperfect substitute for inulin)
CCR is clinically used to routinely access GFR
“GFR” = CCR =
UCR · V
PCR
V = urine produced in ml/min
UCR = urine CR concentration
PCR = plasma CR concentration
There is a nice inverse relationship between
PCR and “GFR”
Normal PCR = 1 mg/dl
PCR

21. Creatinine: produced from creatine metabolism in muscle
Creatinine Clearance
Creatinine: produced from creatine metabolism in muscle
production rate usually very constant (if muscle mass constant)
freely filtered and not reabsorbed …little bit is secreted
(this makes it a good but imperfect substitute for inulin)
CCR is clinically used to routinely access GFR
“GFR” = CCR =
UCR · V
PCR
V = urine produced in ml/min
UCR = urine CR concentration
PCR = plasma CR concentration
There is a nice inverse relationship between
PCR and “GFR”
Normal PCR = 1 mg/dl
If GFR drops by 50%, then PCR doubles ( 2 mg/dl ).
50% GFR
Thus, a single PCR value can be
used to roughly estimate GFR.