RENAL SYSTEM
PHYSIOLOGY
Dr Shahab Shaikh PhD, MD
Lecture – 2: Glomerular Filtration
••••••••••••••••••••••••••••••••••
College of Medicine
Al Maarefa Colleges of Science & Technology
OBJECTIVES
• Identify three basic processes involved in urine
formation.
• Define GFR and quote normal value
• Describe the composition of the glomerular filtrate
• Detect the structural & functional peculiarities of the
glomerular filtration membrane
• Outline the factors controlling GFR
• Understand the concept of Net filtration pressure.
• Correlate between net filtration pressure along
glomerulus and plasma flow
• List the characteristics that a compound must have
before it can be used for measuring GFR e.g. Inulin,
creatinine etc.
Urine Formation
• Three Basic Mechanisms
(Renal Processes) of
Urine Formation include:
1.Glomerular filtration - GF
2.Tubular reabsorption - TR
3.Tubular secretion - TS
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Urine Formation
• Renal Handling of different substances during
Urine Formation:
Urine
•
•
•
•
Substance
Z
Substance
Y
Substance
X
Substance
W
Urine
Urine
Urine
W: filtered & secreted, but not reabsorbed (e.g. H+ ions)
X : filtered & partially reabsorbed ( e.g. Urea, Na+ etc.)
Y : filtered & completely reabsorbed (e.g. Glucose)
Z :filtered but neither reabsorbed nor secreted (e.g. Creatinine)
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Glomerular Filtration
• The first step in urine formation is the Glomerular
filtration during which, large quantity of water and
solutes pass through the filtration membrane from
the blood into the Bowman’s Capsule due to
pressure gradient.
• The glomerular capillaries are relatively impermeable
to plasma proteins, so the filtered fluid (glomerular
filtrate) is free from :
– Blood cells
– Protein
– Protein-bound molecules (calcium, fatty aids, amino acids)
• The glomerular filtrate contains crystalloids in
virtually the same concentrations as in the plasma.
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Glomerular Filtration
• Thus essentially the composition of Glomerular
filtrate is similar to plasma (except Plasma Proteins)
and consists of:
• Water
• Electrolytes
• Glucose, Amino Acids
• Urea
• Creatinine
• Uric Acid
• Urobilinogen etc.
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Glomerular Filtration
• Proteinuria:
– means the presence of an excess of serum proteins in
the urine.
• An increase in the level of urine albumin between
30–300 mg/24 hours is called as Microalbuminuria
• Value higher than 300mg/24 hours is called as
Macroalbuminuria.
• Clinical Significance of Proteinuria:
– Early detection of renal disease in at-risk patients
- Hypertension: Hypertensive Renal Disease
- Diabetes: Diabetic Nephropathy
- Pregnancy: Pre-eclampsia
– Assessment and monitoring of known renal disease
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Glomerular Filtration
Glomerular Filtration Rate (GFR):
• Definition:
– It is the Volume of plasma filtered by all nephrons of
both kidneys per unit time.
• Normal GFR = 125ml/min or 180L/day.
• Determined By:
– Sum of the hydrostatic and colloid osmotic pressures
across the glomerular membrane, called the NET
FILTRATION PRESSURE.
– The Capillary Filtration Coefficient (Kf)
• Thus GFR = Kf x Net Filtration Pressure
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Glomerular Filtration
Filtration coefficient (Kf):
• “Surface Area” available for filtration and
“Membrane Permeability” determine Filtration
Coefficient (Kf).
• The normal Membrane Permeability of glomerular
capillaries is very high as compared to other
capillaries in body.
• Normally it is not highly variable.
• Disease that can reduce Kf and thus GFR are:
– chronic hypertension
– obesity / diabetes mellitus
– glomerulonephritis
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Glomerular Filtration
Net filtration Pressure:
• The net filtration pressure is the sum of the
hydrostatic and colloid osmotic pressures that
either favor or oppose filtration across the
filtration membrane.
• These pressures are:
– Glomerular hydrostatic pressure (PG)
– Glomerular colloid osmotic pressure (πG)
– Bowman’s capsular hydrostatic pressure (PB)
– Bowman’s capsular colloid osmotic pressure (π B).
• It is approximately 10 mmHg
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Glomerular Filtration
Net filtration Pressure: 10mmHg
• Forces Favoring filtration
– Glomerular hydrostatic pressure PG = 60 mmHg
• Due to high renal blood supply and high efferent arteriolar
resistance
– Bowman’s capsular colloid osmotic pressure πB = 0 mmHg
• Due to absence of proteins in the Bowman’s capsular space
• Forces Opposing filtration
– Bowman’s capsular hydrostatic pressure PB = 18 mmHg
• Due to filtered fluid in the Bowman’s capsule
– Glomerular colloid osmotic pressure πG = 32mmHg
• Due to the osmotic pressure exerted by the plasma proteins.
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Glomerular Filtration
Net filtration Pressure:
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Being Curious …
Can you think of some situations where there may
occur Increase/Decrease in following Pressures and
what might be the effect?
1.
2.
3.
4.
Glomerular hydrostatic pressure (PG)
Bowman’s capsular colloid osmotic pressure (πB)
Bowman’s capsular hydrostatic pres sure (PB)
Glomerular colloid osmotic pressure (πG)
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Glomerular Filtration
Factors affecting GFR:
• Changes in renal blood flow
• Changes in glomerular capillary hydrostatic pressure
– Changes in systemic blood pressure
– Afferent or efferent arteriolar resistance
• Changes in hydrostatic pressure in Bowman’s capsule
– Ureteral obstruction
– Edema of kidney inside tight renal capsule
• Changes in concentration of plasma proteins:
– Dehydration
– Hypoproteinemia, etc.
• Changes in Kf
– Changes in glomerular capillary permeability
– Changes in effective filtration surface area
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Glomerular Filtration
Glomerular Capillary Hydrostatic Pressure (PG):
• It is the primary means for physiologic regulation
of GFR.
• Increase PG  raises GFR, and vice versa.
• It is determined by three variables:
1. Arterial Pressure
2. Afferent Arteriolar Resistance
3. Efferent Arteriolar Resistance.
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Glomerular Filtration
Regulation of GFR:
• Glomerular capillary hydrostatic pressure can
be controlled to adjust GFR to suit body’s needs
• Two major control mechanisms
1. Extrinsic control by adjusting the constriction of
afferent/efferent arterioles
• Mediated by sympathetic nervous system input to
arterioles
• Baroreceptor reflex
2. Autoregulation
• Myogenic mechanism
• Tubuloglomerular feedback (TGF)
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Glomerular Filtration
Effect of Afferent and Efferent
Constriction on Glomerular Pressure:
Arteriolar
Ra
Re
Blood Flow
PG
Blood Flow
GFR
GFR
Ra
GFR +
PG
Renal
Blood Flow
Re
GFR +
Renal
Blood Flow
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Glomerular Filtration
Autoregulation of GFR:
• Feedback mechanisms intrinsic to the kidneys
normally keep the renal blood flow and GFR
relatively constant, despite marked changes in
arterial blood pressure.
• Autoregulation involves two mechanisms:
– Tubuloglomerular Feedback Mechanism
– Myogenic Mechanism
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Glomerular Filtration
TubuloGlomerular Feedback:
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance
GFR (return toward normal)
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Glomerular Filtration
Myogenic Mechanism:
Arterial
Pressure
Stretch of
Blood Vessel
Cell Ca++
Permeability
Blood Flow
Vascular
Resistance
Intracell. Ca++
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Glomerular Filtration
Filtration Fraction (FF) :
• Filtration Fraction is the ratio of the GFR to the
renal plasma flow (GFR/TRPF).
• Renal blood flow is 20-25% of total cardiac output.
Thus it is approximately = 1.1 L/min
• Thus of the 625 ml of plasma which enters the
glomeruli via the afferent every minute, 125 (the
GFR) filters in the Bowman’s capsule, the
remaining passing via efferent arterioles into the
peritubular capillaries
• Filtration fraction = (GFR/TRPF) = 0.2
• So, GFR is About 20% of the Renal Plasma Flow
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Glomerular Filtration
Measurement of GFR:
• Characteristic of
measurement:
–
–
–
–
–
substance
used
for
Freely filtered (not reabsorbed and not secreted)
Not metabolized by the kidney
Not toxic and stable
Not bound to plasma protein
Does not change renal plasma flow
• The substance used to measure GFR is Inulin, a
polysaccharide.
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References
• Human physiology by Lauralee Sherwood, 8th
edition
• Text Book Of Physiology by Guyton & Hall, 11th
edition
• Review of Medical Physiology by Ganong. 24th
edition
THANK YOU
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