GFR
3 processes
involved in Urine
formation
1.Glomerular
filtration
2.Tubular
reabsorption
3.Tubular
secretion
GFR
The amount of the glomerular filtrate formed by all the nephrons of both the
kidneys in a one minute is called GFR
In the average human adult, the GFR is about 125 ml / min. or 180 L / day
Filtration fraction – the fraction of the renal plasma which becomes the filtrate
Filtration fraction = GFR / RPF
Dr. Ashok Solanki
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 > 8nm).
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.
GLOMERULAR FILTRATION
BARRIER
Glomerular Capillary
- The capillary endothelium is perforated by thousands of
small holes called fenestrae
- Although the fenestrations are relatively large, endothelial
cells are richly endowed with fixed negative charges that
obstruct the passage of plasma proteins.
- The basement membrane consists of a meshwork of
collagen and proteoglycan fibrillae that have large spaces
through which large amounts of water and small solutes can
filter.
- The basement membrane effectively prevents filtration of
plasma proteins because of strong negative electrical
charges associated with the proteoglycans.
Glomerular Capillary
- The final part of the membrane is a layer of epithelial
cells that line the outer surface of the glomerulus.
- These cells are not continuous but have long foot like
processes (podocytes) that encircle the outer surface
of the capillaries.
- The foot processes are separated by gaps called slit
pores through which the glomerular filtrate moves.
- The epithelial cells also have negative charges, provide
additional restriction to filtration of plasma proteins.
Glomerular Filtration
• Ultrafiltration of plasma in the glomerulus
Governed by 2 major factors:
1. Filtration coefficient (Kf)
2. Pressure gradient/ Starling forces (hydrostatic
and osmotic pressure gradients)
Mechanism of Glomerular Filtration
Filtration coefficient
1. Capillary permeability
2. Size of the capillary bed
Capillary permeability
Filtration depends on the size and shape of the molecules and
the electric charge they carry.
1. Molecular size:
Neutral substances with molecular diameter of less than 4nm
are easily filtered and substances with diameter with more
than 8nm are not filtered
2. shape: the elongated particles with large molecular weight can
pass easily, whereas globular particles of same molecular
weight cannot pass through
3. Electrostatic charge: particles with positive charge are easily
filtered than the negatively charged particles.
SIZE OF THE CAPILLARY BED
The surface area for filtration of the capillary bed depends on
the size of messengial cells.
The contractility of messengial cells decreases the area for
filtration and relaxation of messengial cells increases the area for
filtration.
The factors that alter messengial cell activity are
Factors that produce contraction of messengial cells
Norepinephrin, endothelins, PDGF, Histamine,
Thromboxane A2,
The factors that produce relaxation of messengial cells
Dopamine, ANP, Camp, Bradykinin, Nitric oxide
GFR
-
GFR is determined by
-
(1) the balance of hydrostatic and colloid osmotic forces
acting across the capillary membrane and
(2) the capillary filtration coefficient (Kf), the product of the
permeability and filtering surface area of the capillaries.
-
-
-
In the average adult human, the GFR is about 125 ml/min, or
180 L/day.
The fraction of the renal plasma flow that is filtered (the
filtration fraction) averages about 0.2;
this means that about 20 per cent of the plasma flowing
through the kidney is filtered
Filtration fraction = GFR/Renal plasma flow
Pressure Gradient
Determinants of the GFR
- The GFR is determined by
- (1) the sum of the hydrostatic and colloid osmotic
forces across the glomerular membrane, which gives
the net filtration pressure,
- (2) the glomerular capillary filtration coefficient,
Kf.
- GFR = Kf X Net filtration pressure
- The net filtration pressure represents the sum of
the hydrostatic and colloid osmotic forces that
either favor or oppose filtration across the
glomerular capillaries
Determinants of the GFR
- (1) hydrostatic pressure inside the glomerular
capillaries (glomerular hydrostatic pressure, PG),
which promotes filtration;
- (2) the hydrostatic pressure in Bowman’s capsule
(PB) outside the capillaries, which opposes filtration;
- (3) the colloid osmotic pressure of the glomerular
capillary plasma proteins (µG), which opposes
filtration; and
- (4) the colloid osmotic pressure of the proteins in
Bowman’s capsule (µB), which promotes filtration.
Determinants of the GFR
- (Under normal conditions, the concentration
of protein in the glomerular filtrate is so
low that the colloid osmotic pressure of
the Bowman’s capsule fluid is considered to
be zero.)
- The GFR can therefore be expressed as
- GFR = Kf X (PG – PB – µG + µB)
Net filtration pressure
• Forces favoring filtration (mm Hg)
glomerular hydrostatic pressure - Pgc
60
bowmen’s capsule colloid
osmotic pressure –
πbc
0
• Forces opposing filtration (mm Hg )
bowmen’s capsule hdrostatic
pressure - Pbc
18
glomerular capillary colloid
osmotic pressure – πgc
32
Net filtration pressure = 60 – 18 – 32 = +10 mmof Hg
Dr. Ashok Solanki
Determinants of the GFR
- Increased
Bowman’s
Pressure Decreases GFR
Capsule
Hydrostatic
- In certain pathological states associated with
obstruction of the urinary tract, Bowman’s
capsule pressure can increase markedly - serious
reduction of GFR.
- Precipitation of calcium or uric acid may lead to
“stones” that lodge in the urinary tract, often in
the ureter, thereby obstructing outflow of the
urinary tract and raising Bowman’s capsule
pressure.
GLOMERULARHYDROSTATIC
PRESSURE (PGC)
• 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
Effect of Afferent and Efferent
Arteriolar Constriction on
Glomerular Pressure
R
a
Blood
Flow
R
a
P
P
Blood
Flow
G
GF
R
GFR
+
Renal
Blood
F
R
e
Δ
𝑄 𝑃
𝑅
=
Re
G
GF
R
GFR
+
Renal
Blood
F
Determinants of the GFR
- Increased Glomerular Capillary Colloid Osmotic Pressure
Decreases GFR
- As blood passes from the afferent arteriole through the
glomerular capillaries to the efferent arterioles,
- the plasma protein concentration increases about 20 %
- (1) the arterial plasma colloid osmotic pressure and
- (2) the fraction of plasma filtered by the glomerular
capillaries (filtration fraction).
- Increasing the arterial plasma colloid osmotic pressure
raises the glomerular capillary colloid osmotic pressure decreases GFR.
Determinants of the GFR
- Increased Glomerular Capillary
Osmotic Pressure Decreases GFR
Colloid
- Increasing the filtration fraction also
concentrates the plasma proteins and raises
the glomerular colloid osmotic pressure
- a greater rate of blood flow into the
glomerulus tends to increase GFR, and a
lower rate of blood flow into the glomerulus
tends to decrease GFR.
Determinants of the GFR
- Increased Glomerular
Pressure Increases GFR
Capillary
Hydrostatic
- Increased arterial pressure tends to raise
glomerular hydrostatic pressure and so increases
GFR.
- Increased resistance of afferent arterioles
reduces glomerular hydrostatic pressure and
decreases GFR.
- dilation of the afferent arterioles increases
both glomerular hydrostatic pressure and GFR
Determinants of the GFR
- Increased Glomerular
Pressure Increases GFR
Capillary
Hydrostatic
- Constriction of the efferent arterioles increases
the resistance to outflow from the glomerular
capillaries.
- This raises the glomerular hydrostatic pressure,
and as long as the increase in efferent
resistance does not reduce renal blood flow too
much, GFR increases slightly
Determinants of the GFR
- Increased Glomerular Capillary Hydrostatic Pressure
Increases GFR
- Efferent arteriolar constriction reduces renal blood flow
- the filtration fraction and glomerular colloid osmotic
pressure increase
- So, if the constriction of efferent arterioles is severe, the
rise in colloid osmotic pressure exceeds the increase in
glomerular capillary hydrostatic pressure caused by
efferent arteriolar constriction.
- When this occurs, the net force for filtration actually
decreases, causing a reduction in GFR.
Determinants of the GFR
- Increased Glomerular
Pressure Increases GFR
Capillary
Hydrostatic
- constriction of afferent arterioles reduces GFR.
- the effect of efferent arteriolar constriction
depends on the severity of the constriction;
- moderate efferent constriction raises GFR,
- severe efferent constriction reduces GFR.
Factors affecting GFR
GFR is influenced by factors that alter renal blood flow, Pressure
gradients, glomerular capillary permeability and surface area for
filtration
1. Change in renal blood flow:
2. Glomerular capillary hydrostatic pressure
3. Bowmans capsule hydrostatic pressure
4. Glomerular capillary oncotic pressure
5. Glomerular capillary permeability
6. Effective filtration surface area
7. Size, shape and electric charge
Conditions that alter GFR
1.
2.
3.
4.
5.
6.
7.
8.
EXERCISE
PREGNANCY
POSTURE
SLEEP
WEATHER
GENDER
AGE
FOOD INTAKE
Regulation of
GFR
Myogenic
mechanism
Intrinsic
mechanism
Extrinsic
mechanism
Tubuloglomerular
feedback
Neural
mechanism
Hormonal
mechanism
Physiologic Control of GFR and
- Sympathetic NervRouBsFSystem Activation
Decreases GFR
- Strong
activation
of
the
renal
sympathetic nerves can constrict the renal
arterioles and decrease renal blood flow and
GFR
- Norepinephrine,
Epinephrine
and
Endothelin Constrict Renal Blood Vessels
and Decrease GFR
Physiologic Control of GFR and
- Angiotensin II ConstrR
icB
ts F
Efferent Arterioles
- raise glomerular hydrostatic pressure while
reducing renal blood flow - helps prevent
decreases in glomerular hydrostatic pressure and
GFR
- Endothelial-Derived Nitric Oxide Decreases
Renal Vascular Resistance and Increases GFR
- Prostaglandins and Bradykinin Tend to Increase
GFR
Autoregulation of GFR and
- Feedback mechanR
isB
msF intrinsic to the
kidneys normally keep the renal blood flow
and GFR relatively constant, despite marked
changes in arterial blood pressure.
- Role of Tubuloglomerular
Autoregulation of GFR
Feedback
in
- Decreased Macula Densa Sodium Chloride
Causes Dilation of Afferent Arterioles and
Increased Renin Release
Autoregulatio
n
Despite changes in
mean arterial blood
pressure (from 80
to 180 mm Hg),
renal blood flow is
kept at a relatively
constant level, a
process known as
autoregulation
Myogenic mechanism
BP
Stretching of blood vessels (afferent arteriole smooth muscle)
Opening of cationic channels
Depolarization
Opening of voltage-dependent calcium channels
Calcium influx
Increased intracellular calcium
vasoconstriction
Myogenic Autoregulation
- the ability of individual blood vessels to
stretching during increased arterial pressure.
resist
- Arterioles respond to increased wall tension or wall
stretch by contraction of the vascular smooth muscle.
- Stretch of the vascular wall allows increased movement
of calcium ions from the ECF into the cells, causing
them to contract
- This contraction prevents overdistension of the vessel
and raises vascular resistance - prevent excessive
increases in RBF and GFR when arterial pressure
increases.
GFR/RBF
autoregula
tion
Myoge
nic
mechani
sm
Tubuloglome
rular
feedback
mechanism
MYOGENI
C
MECHANI
SM
INCREASE
ARTERIAL
PRESSUR
E
AFFERENT
ARTERIOLES
STRETCHE
S
VASCULAR
SMOOTH
MUSCLE
CONTRACTS
ARTERIOL
E
RESISTAN
CE
TUBULOGLOMERULAR
FEEDBACK
MECHANISM
JG
MECHANI
FEEDBAC
SM
K
INCREASED
ARTERIAL
PRESSURE
INCREASE PG
INCREASE GFR
-
INCREASE TUBULAR
FLOW
Increase Macula
Densa
stimulation
Increase
AFFERENT
arteriole resistance
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
JG
FEEDBAC
K
MECHANIS
M
HORMONES THAT
INFLUENCE GFR AND RBF
Stimulus
Vasoconstric
tor
Angiotensin II
Endothelin
Vasodilator
PGE
Nitric oxide
ECFV
Stretch, Ang II, Epi,
Bradykinin
ECFV, Shear stress,
Ang II
Shear stress, ACh,
Histamine
Effect on
GFR
Effect of
RBF
•Clearance is a general concept that
describes the rate at which substances are
removed (cleared) from the plasma.
Clearance Technique
Renal clearance of a substance is
the volume of plasma completely
cleared of a substance per min.
C
= Us x V
Cs x Ps =
s
Ps
Us
x V
Wher Cs = clearance of substance S
e:
(mL/min)
Ps = plasma conc. of
substance
S
(mg/mL) Us = urine conc. of
Use of clearance to
measure
GFR
For a substance that is freely filtered, but not
reabsorbed or secreted (inulin, 125 Iiothalamate, ~creatinine), renal clearance is
equal to GFR
amount filtered = amount excreted
GFR x Pin =
Uin
GFR
x
Pi
=
V
n
Uin x V
Calculation of
GFR:
Pinulin = 1.0 mg /
100ml Uinulin = 125
mg/100 ml Urine
flow rate = 1.0
ml/min
GFR = Cinulin = Uin
x
125 x 1.0 = 125
GFR
ml/min
=V
1.0
Creatinine
clearance
U x
GFR = C
cr
r
P
PVC
=
r
 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
Clearance Methods
- The rates at which different substances are “cleared”
from the plasma provide a useful way of quantitating the
effectiveness with which the kidneys excrete various
substances.
- The renal clearance of a substance is the volume of
plasma that is completely cleared of the substance by
the kidneys per unit time
- renal clearance of a substance is calculated from the
urinary excretion rate (U X V) of that substance divided
by its plasma concentration (P).
C =U X V/P
Inulin Clearance
- If a substance is freely filtered and is not
reabsorbed or secreted by the renal tubules,
- then the rate at which that substance is excreted in
the urine is equal to the filtration rate of the
substance by the kidneys
- Inulin, a polysaccharide molecule with a molecular
weight of about 5200.
- Inulin is not produced in the body, is found in the
roots of certain plants and must be administered
intravenously to a patient to measure GFR.
Inulin Clearance
- (1) if the clearance rate of the substance
equals that of inulin, the substance is only
filtered and not reabsorbed or secreted;
- (2) if the clearance rate of a substance is less
than inulin clearance, the substance must have
been reabsorbed by the nephron tubules; and
- (3) if the clearance rate of a substance is
greater than that of inulin, the substance
must be secreted by the nephron tubules.
Creatinine Clearance
- Creatinine is a by-product of muscle metabolism
and is cleared from the body fluids almost entirely
by glomerular filtration.
- Because measurement of creatinine clearance does
not require intravenous infusion into the patient,
this method is much more widely used than inulin
clearance for estimating GFR clinically.
- creatinine clearance is not a perfect marker of
GFR because a small amount of it is secreted by the
tubules, so that the amount of creatinine excreted
slightly exceeds the amount filtered
Creatinine Clearance
GFR = CCreatinine = Ucreatinine X V / Pcreatinine
- If GFR suddenly decreases by 50%, the
kidneys will transiently filter and excrete only
half as much creatinine,
- causing accumulation of creatinine in the
body fluids and raising plasma concentration
- plasma creatinine concentration is inversely
proportional to GFR
GLOMERULAR DISEASES
- Glomerular diseases include a large and clinically
significant group of renal diseases.
- Glomerulonephritis (GN) is the term used for
diseases that primarily involve the renal glomeruli.
- I. Primary glomerulonephritis in which the
glomeruli are the predominant site of involvement.
- II. Secondary glomerular diseases include certain
systemic and hereditary diseases which secondarily
affect the glomeruli.
GLOMERULAR DISEASES
- The clinical presentation of glomerular
disease is quite variable but in general
four features—proteinuria, hematuria,
hypertension and disturbed excretory
function
- nephritic and nephrotic syndromes;
- acute and chronic renal failure;
- asymptomatic
proteinuria
and
haematuria
ACUTE NEPHRITIC
is the acSutYe NonsDet RofOhaMemEaturia, proteinuria,
-
This
hypertension, oedema and oliguria following an infective
illness about 10 to 20 days earlier.
-
1. The haematuria is generally slight giving the urine
smoky appearance and erythrocytes are detectable by
microscopy
2. The proteinuria is mild (less than 3 gm per 24 hrs)
and is usually non-selective
(nephritic
range
proteinuria).
3. Hypertension is generally mild.
4. Oedema in nephritic syndrome is usually mild and
results from sodium and water retention.
5. Oliguria is variable
-
-
NEPHROTIC SYNDROME
- it is characterised by findings of massive proteinuria,
hypoalbuminaemia, oedema, hyperlipidaemia, lipiduria,
and hypercoagulability.
-
1. Heavy proteinuria (protein loss of more than 3 gm
per 24 hrs) is the chief characteristic of nephrotic
syndrome (nephrotic range proteinuria).
-
A highly-selective proteinuria consists mostly of loss
of low molecular weight proteins, while a poorlyselective proteinuria is loss of high molecular weight
proteins in the urine.
In nephrotic syndrome, proteinuria mostly consists of
loss of albumin (molecular weight 66,000) in the urine.
-
NEPHROTIC SYNDROME
- 2.
Hypoalbuminaemia
is produced primarily
consequent to urinary loss of albumin, and partly
due to increased renal catabolism and inadequate
hepatic synthesis of albumin.
- 3. Oedema in nephrotic syndrome appears due to
fall in colloid osmotic pressure resulting from
hypoalbuminaemia.
- 4. Hyperlipidaemia - the liver faced with the
stress of massive protein synthesis in response to
heavy urinary protein loss, also causes increased
synthesis of lipoproteins
NEPHROTIC SYNDROME
- 5. Lipiduria occurs following hyperlipidaemia
due to excessive leakiness of glomerular
filtration barrier.
- 6. Hypercoagulability –
- increased urinary loss of antithrombin III,
- hyperfibrinogenaemia
from
synthesis in the liver,
- decreased fibrinolysis,
- increased platelet aggregation and
- altered levels of protein C and S.
increased
Thank You…