Renal System Physiology:

Glomerular Filtration and

Renal Blood Flow

Mohammad Rudiansyah

Division of Nephrology and Hypertension - Department of Internal Medicine

Medical Faculty of Lambung Mangkurat University Ulin Hospital
Gross Anatomy of the Kidney
 The functional unit of the kidney:
the nephron

Total of about 2.5 million

in the 2 kidneys.
Each nephron consists of
2 functional components:
The tubular
component
The vascular
component (blood
supply)
The mechanisms by
which kidneys perform
their functions depends
upon the relationship
between these two
components.
Each KIDNEY consists of 1 million NEPHRONS
Each nephron consists of a:
GLOMERULUS (found in cortex)
forms a protein-free filtrate from blood
TUBULE (found in medulla)
processes the filtrate to form urine

Each TUBULE consists of several segments:

Proximal tubule
Loop of Henle
Distal Tubule
Collecting Ducts.
 KIDNEY: Blood flow 1

Inter-lobar artery
2

Arcuate artery
3 Renal
artery
1

Inter-lobular artery
4
 KIDNEY: Blood flow 2

Inter-lobular artery
4

Cortico-medullary
6 junction is the site
Glomerulus of both arcuate
arteries & veins
Afferent arteriole
5 7 8
Efferent arteriole feeding tortuous capillaries
(cortex) or straight capillaries (medulla)
 KIDNEY: Blood flow 3
Efferent arteriole
5 7
Afferent arteriole

Glomerular Straight medullary

capillary tuft vessels (Vasa recta)
8
6
Veins

Contorted capillary plexus

8
 Cortical
nephrons have
short loops with
abundant
peritubular
capillaries.
Juxtamedullary
nephrons have
long loops and
the vasa recta
Structure of the Bowmans (glomerular) capsule

Parietal layer of
Afferent
glomerular capsule
arteriole
Juxtaglomerular
cell

Capsule
space
Efferent
Proximal arteriole
convoluted
tubule

Endothelium
Podocyte of glomerulus
Pedicel
 Glomerulus and Bowmans capsule
Glomerular filtrate drains into
Bowmans space, and then into
proximal convoluted tubule.
Endothelium has pores to allow
small molecules through.
Podocytes have negative charge.
This and the basement membrane
stops proteins getting through into
tubular fluid.
Macula densa senses GFR by
[Na+]
Juxtaglomerular (JG) apparatus
includes JG cells that secrete
renin.
JGA helps regulate renal blood
flow, GFR and also indirectly,
modulates Na+ balance and
systemic BP
 RENAL CORPUSCLE
Afferent Efferent arteriole
arteriole
Mesangial cells & matrix
between roots of
capillaries

Visceral epithelium
Glomerular of podocytes
capillary tuft

Capsular Bowmans capsule

space with simple
squamous parietal
epithelium

Start of Proximal tubule

 Kidney Functions

1. Regulation of water, electrolyte balance, pH

2. Removal of waste from blood and excretion
of urine.
3. Secretion of hormones
- Erythropoietin
- Renin
- Vitamin D3
 Excretion of waste products

Urea (aas metabolism)

Creatinine (muscle creatine)
Uric acid (nucleic acids)
Hemoglobin breakdown products (bilirubin)
Hormone metabolites
Toxins
 Regulation of water and electrolyte

Excretion must match intake

Several control mechanisms

Can match 10-1500 mEq/day Na+ intake

Response to Fluid and Electrolyte Load

The renal response

to a fluid/salt load is
measured in days
but balance is
completely attained.
Regulation of arterial pressure
 Acid-Base Balance

Along with lungs and buffers

Excretion of acids
Regulating buffer stores
Excretion of sulfuric and phosphoric acid
(protein metabolism)
Erythropoietin secretion
Active form of Vitamin D
 Gluconeogenesis

Glucose from aas and other precursors during

prolonged fasting
Urine formation
Three step process:

Product of glomerular filtration

Tubular reabsorption into the blood

Tubular secretion from the blood into renal

tubules

Urinary excretion rate = Filtration rate -

Reabsorption rate + Secretion rate
 kidney
Glomerular
Filtration
System
Glomerulus

Glomerular capillary

Slit diaphragm

Filtration barrier

GBM
Fenestrated endothelium
 Glomerular Filtration

Depends on:
Pressure gradient across the filtration slit
(endothelium, basal membrane, epithelium =
podocytes)
Blood circulation throughout the kidneys
Permeability of the filtration barrier
Filtration surface

The solution after filtration is very similar like

plasma, but should be without proteins
 Clearance
The ability of kidneys to clear plasma from different
products.
GLOMERULAR FILTRATION RATE (GFR)
can be measured by measuring the excretion and plasma
level of a substance that freely filtered through the glomeruli
and neither secreted nor reabsorbed by the tubules, such
as INULIN (polymer of fructose).
GFR = U x V/P
U = concentration of inulin in urine
V = volume of the urine
P = concentration of inulin in plasma
Normal GFR is around 125 ml/min (7.5 l/h)
Renal Handling of Substances
Four Classes of
substances
A - Filtered, not
reabsorbed
(creatinine, inulin, uric
acid)
B - Filtered, partly
reabsorbed (Na+, Cl-,
bicarbonate)
C - Filtered, totally
reabsorbed (amino
acids, glucose)
D - Filtered, totally
secreted (organic acids
and bases)
Inulin clearance
Glucose clearance
Urea clearance
 Renal Hemodynamics

GFR is determined by:

Hydrostatic and colloid osmostic forces
Capillary filtration coefficient (Kf)

Glomerular Capillaries
Higher filtration rate
hydrostatic pressure and large Kf
 Renal Hemodynamics

Renal Blood Flow (RBF) is 20% of Cardiac

Output (CO) -- 0.5% total body weight

GFR is 20 % of RPF

Filtration fraction (FF) = GFR / RPF

 FILTRATION FRACTION
Filtration fraction is an important expression of the extent of
glomerular filtration.
GFR
It is the ratio: Filtration fraction =
RPF

Renal blood flow

1250 ml/min
RPF
750 ml/min
It is the fraction of
glomerulus renal plasma flow
that is filtered at
GFR Efferent
Arteriole the glomerulus
150 ml/min
600 ml/min renal

tubule vein

~149 ml/min

Urine ~1 ml/min
 FILTRATION FRACTION
an example

Glomerular filtration rate (GFR)

is about: 150 ml/min
Remember: plasma volume
is about 60% of total blood
Renal blood flow volume
is about: 1250 ml/min
Renal plasma flow (RPF)
is about: 750 ml/min

Thus, in this example filtration fraction is: 150 0.2

750
This means that 20% of the plasma flowing through the kidneys is filtered

GFR and RPF can be measured separately using clearance methods

Filtration Process

Glomerular
membrane is
similar to other
capillary
membranes except
for the presence of
the Podocytes
 Effect of charge on filtration
Albumin = 6 nanometers vs glomerular membrane = 8 nanometers

In some kidney disease negative charges are lost from membrane and
albumin appears in urine Proteinuria or Albuminuria
The glomerular filtration surface showing the inner layer of fenestrated
endothelium, the GBM, and the outer layer of podocyte foot processes
between which he filtrate passes.
 Filtration Process

Bowmans
space pedicel Capillary
endothelium has
fenestra which
pass plasma
filtration proteins easily.
slit Barrier is
associated with
(-) charged
proteoglycans in
capillary the basement
membrane.
 Filterability of the Membrane

Filterability is a term used to describe membrane

selectivity based on the molecular size and charge

Pore size would favor plasma protein (albumin)

passage, but negative charge on protein is repelled
by the (-) charged basement membrane
(proteoglycan filaments & podocytes)

Loss of this (-) charge causes proteinuria condition

called minimal change nephropathy
Determinants of GFR
 Glomerular Hydrostatic Pressure

Determined by:
Arterial Pressure
Afferent Arteriolar Resistance
Efferent Arteriolar Resistance

Hydrostatic Pressure GFR,

Hydrostatic Pressure GFR
Ra and Re effect on GFR

GFR changes are

inversely
proportional to Ra
changes. Increase
in Re causes
increase in GFR to
a point then GFR
decreases to very
low value
 Renal Blood Flow
(Renal artery pressure-Renal vein pressure)

(Total Renal Vascular Resistance)

Greatest vascular resistance:

Interlobular arteries
All controlled by the Sympathetic
Afferent arterioles Nervous System, Hormones and
local mechanisms
Efferent arterioles
 RENAL BLOOD FLOW (RBF)

Renal blood flow is about 20% of the cardiac output

This is a very large flow relative to the weight of the kidneys (350 g)

RBF determines GFR Flow, l/min

1.5
RBF also modifies solute and
water reabsorption and delivers Renal blood flow
1.0
nutrients to nephron cells.

RBF is autoregulated between 0.5

90 and 180 mm Hg by varying
GFR
renal vascular resistance (RVR)
i.e. the resistances of the 0
interlobular artery, afferent 0 100 200
arteriole and efferent arteriole Arterial blood pressure, mm Hg
Autoregulation of RBF & GFR

Note:
Autoregulation
is important to
prevent large
changes in GFR
that would
greatly affect
urinary output.
 Impact of autoregulation

Autoregulation:
GFR=180L/day and tubular
reabsorption=178.5L/day
Results in 1.5L/day in urine

Without autoregulation:
Small in BP 100 to 125mm Hg, GFR by 25% (180
to 225L/day)
If tubular reabsorption constant, urine flow of 46.5
L/day

What would happen to plasma volume?

 Renal Blood Flow - Autoregulation
1. Myogenic hypothesis
When arterial pressure increases the renal afferent arteriole is stretched

Increase of Flow
arterial pressure increases
Vascular smooth muscle responds by contracting
thus increasing resistance

Flow
Increase of
returns to
vascular tone
normal
 Renal Blood Flow - Autoregulation

2. Tubuloglomerular
feedback 4. Ra
3.signal from
JGA
GFR
Alteration of tubular flow
(NaCl ) is sensed by the
GFR
macula densa of the
juxtaglomerular
apparatus (JGA) and
produces a signal (renin)
that alters GFR 2. filtrate
 The juxtaglomerular apparatus
Including macula densa, extraglumerular mesangial cells, and
juxtaglomerular (granular cells) cells
Feedback mechanism for GFR

Decreased NaCl in
macula densa is
due to increased
reabsorption
resulting from the
slower tubular flow
 Regulation of GFR

Sympathetic nerves (GFR)

Angiotensin II (GFR)
Hemorrhage (GFR)
ANP (GFR)
ADH (GFR)
Glucocorticoids (GFR)
NO (GFR)
Endothelin (GFR)
Prostaglandins and Bradykinin (GFR)