Glomerular filtration, Determinants
of GFR and FF
Dr. shafali singh
Learning objectives
1. Restate the four basic elements of renal function, including: glomerular
2.
3.
4.
5.
6.
7.
filtration, tubular reabsorption, tubular secretion, and endocrine
function.
Recognize the structural features of the glomerular capillary wall.
Describe the determinants of glomerular filtration rate (GFR),
including glomerular capillary hydrostatic and oncotic pressures,
intratubular pressure, and the ultrafiltration coefficient and be able
to calculate GFR given values for the determinants of GFR.
Define the concept of filtration fraction and how changes in the
filtration fraction influence the net reabsorptive pressure in the
peritubular capillaries.
Describe the effects of changes in pre- and postglomerular resistances
on renal blood flow (RBF) and GFR.
Restate RBF autoregulation and tubuloglomerular feedback
mechanisms.
Identify the effects of the sympathetic nervous system and vasoactive
humoral factors on GFR and RBF.
kidneys function
• As excretory organs, the kidneys ensure that
those substances in excess or that are harmful
are excreted in urine in appropriate amounts.
• As regulatory organs, the kidneys maintain a
constant volume and composition of the body
fluids by varying the excretion of solutes and
water.
• As endocrine organs, the kidneys synthesize and
secrete three hormones: renin(enzyme),
erythropoietin, and 1,25-dihydroxycholecalciferol
Renal blood flow
• About 20% of cardiac output(kidneys only 0.4% of
BW)
• Very low oxygen extraction
• 2 capillary beds arranged in series, separated by
efferent arterioles• High hydrostatic pressure in the glomerular
capillaries( about 60 mm of Hg) favors filtration;
low hydrostatic pressure ( about 13 mm of Hg) in
peritubular capillaries favors reabsorption.
Renal artery interlobar artery arcuate artery Interlobular
artery afferent arteriole glomerular capillaries efferent
arterioles peritubular capillaries
In the cortex, the proximal and distal tubules, as
well as the initial segment of the collecting duct,
are surrounded by a capillary network, and the
interstitium is close to an isotonic environment
(300 mOsm).
The medullary region instead has capillary loops
organized similar to the loops of Henle. The slow
flow through these capillary loops preserves the
osmolar gradient of the interstitium. However,
this slow flow also keeps the PO2 of the medulla
lower than that in the cortex.
Even though the metabolic rate of the medulla is
lower than in the cortex, it is more susceptible to
ischemic damage
Glomerular filtration: 1st step in urine
formation
• Structure of the filtering membrane
• Composition of the glomerular filtrate:
ultrafiltrate of plasma devoid of protein and
cells
• The basement membrane has strong negative
charge (Proteoglycans) –prevents filtration of
Plasma proteins
GLOMERULAR FILTRATION
Filtration membrane
The Filtering Membrane
The membrane of the glomerulus consists of 3 main structures:
Capillary endothelial wall with fenestrations that have a
magnitude greater than proteins. In addition the wall is
covered with negatively charged compounds.
A glomerular basement membrane made up of a matrix of
extracellular negatively charged proteins and other
compounds.
An epithelial cell layer of podocytes next to Bowman’s space. The
podocytes have foot processes bridged by filtration slit
diaphragms.
Around the capillaries is the mesangium containing
mesangial cells, which are similar to monocytes.
They can contract and affect GFR and renal blood
flow.
Materials Filtered
The following are easily or freely filtered:
Major electrolytes: sodium, chloride, potassium,
bicarbonate
Metabolic waste products: Urea Creatinine
Metabolites: glucose, amino acids, organic acids (ketone
bodies)
Nonnatural substances: inulin, PAH (p-aminohippuric
acid)
Lower-weight proteins and peptides: insulin, myoglobin
The following are not freely filtered:
Albumin and other plasma proteins
Lipid-soluble substances transported in the plasma
attached to proteins such as lipid-soluble bilirubin, T4
(thyroxine), other lipid-soluble hormones
Determinants of GFR
• GFR=K f X Net filtration pressure
• Forces favoring Filtration (mm g Hg)
Glomerular hydrostatic pressure: 60
Bowmans capsule colloid osmotic pressure:0
• Forces opposing filtration
Bowmans capsule hydrostatic pressure: 18
Glomerular capillary colloidal osmotic pressue: 32
•Net filtration pressure???
Kf is the filtration coefficient of the
glomerular capillaries.
The product of permeability
and
filtering surface area of the capillaries.
Size of the Capillary Bed
• Kf can be altered by the mesangial cells, with
contraction of these cells producing a
decrease in Kf that is largely due to a reduction
in the area available for filtration.
For protein
Net Filtration pressure
1. Hydrostatic pressure of the glomerular
capillaries
• PGC: The hydrostatic pressure of the
glomerular capillaries is the only force that
promotes filtration. Under normal conditions,
this is the main factor that determines GFR.
2. Oncotic pressure of the plasma
• πGC: The oncotic pressure of the plasma
varies with the concentration of plasma
proteins. Because fluid is filtered but not
protein, oncotic pressure, which opposes
filtration, will increase from the beginning to
the end of the glomerular capillaries
• The increased concentration of protein will be
carried into the peritubular capillaries and will
promote a greater net force of reabsorption
100/100 ml 100/80
100/100ml 100/70
100/100ml 100/90
3. Hydrostatic pressure in Bowman’s space
• PBS: The hydrostatic pressure in Bowman’s
capsule opposes filtration. Normally, it is low and
fairly constant and does not affect the rate of
filtration. However, it will increase and reduce
filtration whenever there is an obstruction
downstream, such as a blocked ureter or urethra
(postrenal failure).
4. Protein or oncotic pressure in Bowman’s space
• πBS: This represents the protein or oncotic
pressure in Bowman’s space. Very little if any
protein is present, and for all practical purposes
this factor can be considered zero
GFR Formula
GFR = Kf [(Pgc +Pbs) - (Pgc + Pbs)]
• Where
– Kf = glomerular filtration coefficient (product of
glomerular surface times hydraulic conductivity)
– Pgc = glomerular hydrostatic pressure
– Pbs = hydrostatic pressure in Bowman’s Space
- Pgc = glomerular capillary oncotic pressure
- Pbs = Bowman’s Space oncotic pressure
(negligible)=0
Use the values below to answer the following question.
Glomerular capillary hydrostatic pressure = 47 mm Hg
Bowman’s space hydrostatic pressure = 10 mm Hg
Bowman’s space oncotic pressure =0 mm Hg
At what value of glomerular capillary oncotic pressure
would glomerular filtration stop?
(A) 57 mm Hg
(B) 47 mm Hg
(C) 37 mm Hg
(D) 10 mm Hg
(E) 0 mm Hg
Q Given the following values, calculate the net
filtration pressure:
glomerular blood hydrostatic pressure = 40
mmHg,
capsular hydrostatic pressure = 10 mmHg,
blood colloid osmotic pres-sure =30 mmHg.
(a) 20 mmHg (b) 0 mmHg (c) 20 mmHg
(d) 60 mmHg (e) 80 mmHg
NEPHRON HEMODYNAMICS
• The individual nephrons that make up both
kidneys are connected in parallel.
• However, the flow through a single nephron
represents2 arterioles and 2 capillary beds
connected in series
If Pin and Pout are kept constant, the following will
occur if the central resistance,increases:
• Flow through R1, R2, and R3 will decrease equally.
• Pb pressure downstream decreases.
• Pa pressure upstream increases.
If Pin and Pout are kept constant, the following will
occur if the central resistance decreases:
• Flow through R1, R2, and R3 will increase equally.
• Pb pressure downstream increases.
• Pa pressure upstream decreases.
Connected in series are the high-pressure filtering capillaries of
the glomerulus and the low pressure reabsorbing peritubular
capillaries.
Determina
nts of GFR
Consequences of Independent Isolated Constrictions
or Dilations of the Afferent and Efferent Arterioles
• The amount of filtrate formed in all the
renal corpuscles of both kidneys each
minute is the glomerular filtration rate
(GFR).
• In adults, the GFR averages 125 mL/min
or about 180 L/day
Filtration fraction
Glomerular filtration rate would be decreased
by
a. Constriction of the efferent arteriole
b. An increase in afferent arteriolar pressure
c. Compression of the renal capsule
d. A decrease in the concentration of plasma
protein
e. An increase in renal blood flow
Glomerular filtration rate (GFR) and renal blood
flow (RBF) will both
be increased if
a. The efferent and afferent arterioles are both
dilated
b. The efferent and afferent arterioles are both
constricted
c. Only the afferent arteriole is constricted
d. Only the efferent arteriole is constricted
e. The afferent arteriole is constricted and the
efferent arteriole is dilated
The glomerular filtration rate will increase if
a. Sympathetic nerve activity to the kidney
increases
b. The afferent arteriolar resistance increases
c. The efferent arteriolar resistance decreases
d. The plasma protein concentration decreases
e. Urine flow through the urethra is blocked
Three mechanisms control GFR:
• renal autoregulation
myogenic

tubuloglomerular feedback
• neural regulation
• hormonal regulation
I. Renal autoregulation
consists of two mechanisms—
1. myogenic mechanism
2. tubuloglomerular feedback.
Working together, they can maintain nearly
constant GFR over a wide range of systemic
blood pressures.
Autoregulation of Renal Blood Flow
and GFR
1.myogenic mechanism
• As blood pressure rises, GFR also rises because renal
blood flow increases. However, the elevated blood
pressure stretches the walls of the afferent arterioles.
• In response, smooth muscle fibers in the wall of the
afferent arteriole contract, which narrows the
arteriole’s lumen. As a result, renal blood flow
decreases, thus reducing GFR to its previous level.
• Conversely, when arterial blood pressure drops, the
smooth muscle cells are stretched less and thus relax.
The afferent arterioles dilate, renal blood flow
increases, and GFR increases.
• The myogenic mechanism normalizes renal blood flow
and GFR within seconds after a change in blood
pressure.
2. tubuloglomerular feedback.
Three points concerning autoregulation
should be noted:
• Autoregulation is absent when arterial
pressure is less than 90 mm Hg.
• Autoregulation is not perfect; RBF and GFR do
change slightly as arterial blood pressure
varies.
• Despite autoregulation, RBF and GFR can be
changed by certain hormones and by changes
in sympathetic nerve activity
Renin release from the juxtaglomerular
apparatus is inhibited by
a. Beta-adrenergic agonists
b. Prostaglandins
c. Aldosterone
d. Increased pressure within the afferent
arterioles
II. Neural Regulation of GFR
• Kidneys are supplied by sympathetic ANS
fibers that release norepinephrine.
• Norepinephrine causes vasoconstriction
through the activation of α 1 receptors, which
are particularly plentiful in the smooth muscle
fibers of afferent arterioles.
• At rest, sympathetic stimulation is moderately
low, the afferent and efferent arterioles are
dilated, and renal autoregulation of GFR
prevails.
• With moderate sympathetic stimu, both
afferent and efferent arterioles constrict to
the same degree. Blood flow into and out of
the glomerulus is restricted to the same
extent, which decreases GFR only slightly.
• With greater sympathetic stimulation,
however, as occurs during exercise or
hemorrhage, vasoconstriction of the afferent
arterioles predominates. As a result, blood
flow into glomerular capillaries is greatly
decreased, and GFR drops.
III. Hormonal Regulation of GFR
1. Angiotensin II normalises GFR.
• Angiotensin constricts the efferent more than the
afferent arterioles.
2. Atrial natriuretic peptide (ANP) increases GFR.
causes relaxation of the glomerular mesangial cells,
and increases the capillary surface area available for
filtration. Glomerular filtration rate rises as the
surface area increases.
The ANP receptor has intrinsic guanylyl cyclase
activity that dilates the afferent arteriole and
increases RBF
Which of the following is most likely to cause an
increase in the glomerular filtration rate?
a. Contraction of mesangial cells
b. Blockage of the ureter
c. Release of renin from the juxtaglomerular
apparatus
d. Dilation of the afferent arterioles
e. Volume depletion
A 69-year-old man presents with symptoms of thirst and
dizziness, and physical evidence of orthostatic hypotension
and tachycardia, decreased skin turgor, dry mucous
membranes, reduced axillary sweating, and reduced jugular
venous pressure. He was recently placed on an angiotensinconverting enzyme (ACE) inhibitor for his hypertension.
Urinalysis reveals a reduction in the fractional excretion of
sodium and the presence of acellular hyaline casts. The
internist suspects acute renal failure of prerenal origin
associated with increased renin secretion by the kidney. A
stimulus for increasing renal renin secretion is an increase in
which of the following?
a. Angiotensin II
b. Atrial natriuretic peptide (ANP)
c. GFR
d. Mean blood pressure
e. Sympathetic nerve activity
Calculate
• Filtered load of a compound: Plasma
concentration of the compound X GFR
• Excretion load: Urine Concentration X Volume
of urine ml/min
• Filtration fraction (FF= GFR/RPF)
• RBF and RPF (RBF=Renal Plasma flow/1-Hct)
• If plasma concentration of glucose is
100mg/100 ml and GFR is 125ml/min.
Calculate Filtered load of glucose?
125mg/min
question