Glomerular filtration

Dr. Dinesh Veera

(MBBS, MSc Medical Physioloy)
AIMST University
At the end of the lecture, students should be able to:
• 8.1 Define glomerular filtration rate, filtration fraction
and state the normal values.
• 8.2 Describe the principle and methods to determine the
glomerular filtration rate.
• 8.3 Describe the main determinants and the Starling’s
forces that affect the net filtration pressure.
• 8.4 Describe the factors regulating the glomerular
filtration rate.
• 8.5 Relate renal blood flow to glomerular filtration rate
 Glomerular Filtration
• It is the first step in the formation of urine.
• As the RBF enters the glomerular capillaries, a
portion of that blood is filtered into Bowman’s
space, the first part of the nephron.

• Ultrafiltration of plasma in the glomerulus

 Characteristics of the Glomerular
Filtration Barrier
• The physical characteristics of the glomerular
capillary wall determine both the rate of
glomerular filtration and the characteristics of
the glomerular filtrate.
• These characteristics determine what is
filtered and how much is filtered into
Bowman’s space.
• ENDOTHELIUM
• BASEMENT MEMBRANE
• EPITHELIUM (Podocytes)
• ENDOTHELIUM
• has pores
• fluid, dissolved solutes, and plasma proteins
all are filtered through
• Blood cells cannot be filtered.
• BASEMENT MEMBRANE
• has three layers.
• The multilayered basement membrane does
not permit filtration of plasma proteins
• an important barrier to filtration.
• EPITHELIUM
• consists of specialized cells called podocytes---
have foot processes.
• Between the foot processes are small sized
filtration slits
• an important barrier to filtration.
• Negative Charge on the Glomerular Capillary
Barrier
• presence of negatively charged glycoproteins.
• fixed negative charges are present on all the
three structures till the filtration slits
• Positively charged large solutes will be more
attracted and negatively charged will be less
attracted (Ex; 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
• Hydrostatic pressure in glomerular capillaries
is a force favoring filtration.
• When compared with systemic capillaries, HP
is relatively high (45 mm Hg).
• The HP remains constant along the entire
length.
• Hydrostatic pressure in Bowman’s space, is a
force opposing filtration.
• The origin of this pressure (10 mm Hg) is the
fluid present in the lumen of the nephron.
• Oncotic pressure in glomerular capillaries, is
another force opposing filtration (the protein
concentration of glomerular capillary blood)
• It does not remain constant along the entire
capillary length
• What is filtration equilibrium?
Pressure Gradient
Glomerular filtration
= Kf [(PGC-PT) – (πGC- πT)]
 Composition of the filtrate

The content and

concentrations of salts
and organic molecules,
are similar
to the concentrations in
the plasma.

Just that the ultrafiltrate

is devoid of plasma
proteins and blood cells
 Glomerular Filtration Rate (GFR)
• The rate at which plasma is filtered by the kidney
glomeruli.

• An important measurement in the evaluation of kidney

function

• GFR = 125 mL plasma/min or, 180 L/day

• Plasma volume (70-kg young adult man) = about 3L,

the
kidneys filter the plasma some 60 times in a day.
 Factors affecting GFR
1. Change in renal blood flow
2. Glomerular capillary hydrostatic pressure
3. Change in capsular hydrostatic pressure
4. Oncotic pressure
5. Glomerular capillary permeability
6. Effective filtration surface area
7. Size, shape and electrical charge of the
macromolecules
 GFR Measurement
• measured by the clearance of a glomerular
• marker.
• A glomerular marker has the following three
• characteristics:
• (1) It must be freely filtered across the glomerular
capillaries, with no size or charge restrictions;
• (2) it cannot be reabsorbed or secreted by the renal tubule;
• (3) when infused, it cannot alter the GFR.
• Thus the properties of the ideal glomerular marker differ
from those of a marker substance used to measure RPF
 Clearance of Inulin

• The “gold standard” glomerular marker is inulin, a

fructose polymer
• Inulin is not bound to plasma proteins, nor is it
charged, and appropriate molecular size
• Inulin is completely inert in the renal tubule: It is
neither reabsorbed nor secreted by the renal tubular
cells.
• Thus the amount of inulin filtered across the
glomerular capillaries is exactly equal to the amount
of inulin that is excreted in the urine.
 Inulin Clearance (Gold Standard)

Reasons:
• freely filterable
• not reabsorbed or secreted
•not synthesized, destroyed,
or stored in the kidneys.
• nontoxic.
• concentration in plasma and
urine can be determined
by simple analysis.

Inulin clearance : highest standard

highly accurate
Others : iothalamate, an iodinated organic compound, EDTA, Vit B12
Not commonly used in the clinical practice.
1. infused intravenously
2. inconvenient
 Other markers of importance
• Creatinine
• slightly overestimates the GFR- Why?
• more advantageous? endogenous substance
 The Endogenous Creatinine Clearance Is Used
Clinically to Estimate GFR

Creatinine
-slightly overestimates the GFR
-more advantageous?
 BUN/Creatinine
• Both blood urea nitrogen (BUN) and serum
creatinine concentration can be used to
estimate GFR because both urea and
creatinine are filtered across the glomerular
capillaries.
• BUN/Creatinine Ratio (More or less than 20)
can suggest the type of renal insult – How?
 Filtration fraction
• The filtration fraction expresses the
relationship between the GFR and RPF.
• It is that fraction of the RPF that is filtered
across the glomerular capillaries.
• Filtration fraction= GFR/RPF

• Normal Value 0.20 or 20%.

 Renal Blood flow
• The kidneys receive about 25% of the
• renal blood flow (RBF) is 1.25 L/min or 1800
L/day
• RBF (Q) is directly proportional to the pressure
gradient (ΔP) between the renal artery and
renal vein
• Inversely proportional to the resistance (R) of
the renal vasculature
• The kidneys are unique
• there are two sets of arterioles, the afferent
and the efferent.
• The major mechanism for changing blood flow
is by changing arteriolar resistance.
 Regulation of GFR
Myogenic
mechanism
Intrinsic
mechanism
Tubuloglomerular
feedback

Neural
mechanism
Extrinsic
mechanism
Hormonal
mechanism
Autoregulation
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

Two Theories!

Autonomic
Nervous System
not involved!
 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
Tubuloglomerular feedback mechanism
Juxtaglomerular Apparatus
Neural mechanism
 Hormonal mechanisms
Regulation Major Stimulus Mechanism Effect on
GFR
Angiotensin II Decreased blood Constriction of Decreases
volume or both afferent GFR
decreased blood and efferent
pressure arterioles
Atrial Stretching of the Relaxation of Increases
natriureti arterial walls the mesangial GFR
c peptide due to increased cells increasing
blood volume filtration
surface
 Regulation Mechanism Effect on GFR
Histamine Contraction of mesangial cells
Dopamine • Vasodilate
• Decrease Renin and
angiotensin II production
• Relax mesangial cells
Bradykinin Release of NO and
prostaglandin
Prostaglandin • Decrease vasoconstrictor
effect of catecholamines and
angiotensin II
• Relax mesangial cells
Nitirc oxide Vasodilate afferent and effernt
arteriole
Endothelin Vasoconstrict afferent and
effernt arteriole
Adenosine Vasoconstrict afferent
arteriole
 Self Assessment
• 1. Describe the auto-regulatory process of
Renal Blood Flow
• 2. Describe the way to measure GFR
• 3. What are the special characteristics of
glomerular filtration barrier
 Challenge questions
• 1. Why Nonsteroidal anti inflammatory drugs
(NSAIDs) are contraindicated AKI following
hemorrhage?
• 2. What is the significance of a BUN/Creatinine
ratio of more than 20?
• What is the cut off GFR used to define Chronic
Kidney Disease and ESRF?
 Reference
• Physiology, Linda S. Costanzo 6th Edition
• Guyton and Hall 14th Edition