RENAL

PYSIOLOGY
PY 7.1 and & 7.3
Describe the structure and functions of
kidney
List the functions of kidney.
Compare the structure and functions of
cortical and juxtamedullary nephrons.
Steps and overview of urine formation
Describe the mechanism of formation of
urine involving processes of filtration,
tubular reabsorption and concentrating
and diluting mechanisms
Mr SM, A 11 -year-old was brought to the hospital
after it was noticed that the child had swelling in
both legs since the past 2 weeks. On physical
examination the patient is afebrile and has
normal blood pressure . There is periorbital
edema. A urinalysis shows 4+ proteinuria but no
hematuria, glucosuria, or ketonuria. The serum
cholesterol is 250 mg/dL. A renal biopsy is
performed and on light microscopy no abnormal
findings are noted. On electron microscopy there
is effacement of podocyte foot processes. A
diagnosis of minimal change nephropathy – a
disease that causes loss of negative charge of the
glomerular basement membrane, is made
Adrenal gland

Renal artery & vein

Kidney

Ureter

Urinary bladder

Urethra
 Functions of the
kidney
• Excretion of metabolic waste products and
foreign chemicals
• Regulation of water and electrolyte
balance
• Regulation of acid - base balance
• Regulation of arterial pressure
• Endocrine functions
 Pyramid Calyx
Medulla Renal
column
Renal

Papilla pelvis
Ureter
Cortex
 5.Interlobular
artery
and vein
3.Interlobar
artery
and vein Renal
vein

1.Renal
artery
2.Lobar artery
Segmental
4.Arcuate artery artery
& vein
Renal capsule
 Structure of
nephron

• Nephron is the structural

and functional unit of
kidney
• Each kidney contains
approximately one
million nephrons
 Types of nephrons
• Cortical nephrons • Juxta medullary
nephrons
• Comprises 85% of total
nephrons • Comprises 15% of total
• Glomeruli in the outer nephrons
portion of renal cortex • Glomeruli in the juxta
• Short loops of henle medullary region of the
cortex
• Longer loop of henle-
has thin ascending limb
•Vascular supply is by •Vascular supply is
peritubular by vasarecta
capillaries •Almost equal
•Diameter of efferent
arteriole is slightly smaller
than afferent
 Mechanisms of Urine Formation
• Urine formation
and adjustment of
blood
composition
involves three
major processes
– Glomerular
filtration
– Tubular
reabsorption
– Secretion
 Glomerular Ultrafiltrate

• Is fluid that
enters
glomerular
capsule, whose
filtration was
driven by
blood pressure

Fig
17.10
 Glomerular
Filtration
• Glomerular capillaries &
B o w m a n ' s capsule form a
filter for blood
– Glomerular Caps are fenestrated--
have pores between endothelial
cells
• 100-400 times more permeable than
other Caps
• Small enough to keep RBCs,
platelets, & W BC s from passing
• Pores lined with negative charges to
 Glomerular
Filtration
• To enter
tubule
filtrate
must pass
through
narrow
filtration
slits formed
between
pedicels of
podocytes
of
Bowman’s
Nephrotic syndrome

• Increase in permeability of
the glomerular capillaries to
proteins
• Loss of normal podocyte
structure with effacement of
foot processes
• Hypoalbunemia with
proteinuria
• generalised edema
What will be the effect of removal of
negative charges from the filtration
barrier?
A. The molecules less than 20
A will not be filtered
B. The molecules greater than
42 A will be filtered
C. Proteins will be filtered
solely based on the charge
D. Proteins will be filtered
solely based on effective
molecular radius
 GLOMERUL AR FILTRATION
RATE (GFR)
• Volume of plasma filtered across
the filtration membrane of all the
nephrons in both the kidneys per
minute.

• In an average adult human, the

GFR is about 125ml/min, or 1 8 0
L/day.
 Factors governing
filtration are
• Size of the capillary bed
• Permeability of the capillary
• Hydrostatic & osmotic
pressure gradients across the
capillary wall
• G F R = K f * x EFP*
• *K f =Glomerular ultra
filtration coeffi cient
• (permeability X Surface area)
• *EFP=Eff ective filtration
pressure
 Glomerular capillary
Afferent arteriolar
resistance R A Efferent arteriolar
resistance R E

PGC
Afferent Blood flow Efferent arteriole
П GC
arteriole (QA)

Glomerular capillary basement membrane

Kf

Bowman’s space
PBS

No ПBS

GFR=Kf (PGC-PBS- ПGC)

45

25

10
• Fa c t o r s • Fa c t o r s
favoring opposing
fi ltration fi ltration
• Glomerular • Hydrostatic
capillary pressure in
hydrostatic bowman's capsule
pressure ( P B C ) = 1 0 m m of
(PG C )=45mm of Hg.
Hg. • Colloidal osmotic
• Colloidal osmotic pressure in
pressure in glomerular
bowman 's capillary(ПGC)=25
• Effective filtration pressure
=[(PG C + π BC ) – ( P B C + π GC )]

= P G C – P B C – πG C

=45-10-25
=10mmHg

• G F R = K f X E.F.P.

• G F R = K f [(P G C + π BC ) – (PB C +
 STARLING FORCES & FILTRATION EQUILIBRIUM
Glomerular hydrostatic pressure,
PGC , is high and relatively
constant at ≈45 mm Hg
mm Hg throughout the glomerular
40 capillary
PGC-PBC
This is opposed by Bowman’s
30 capsular pressure PBC of ≈10 mm
∏ GC Hg
20
& colloidal osmotic pressure ∏
GC of 25 mm Hg
10
Net filtration pressure is:
0 ≈ 10 mm Hg at the afferent end
aff. art eff. art. of glomerular capillary
 STARLING FORCES & FILTRATION EQUILIBRIUM
Colloidal osmotic pressure ∏
GC increases from 25 mm Hg to

35 mm Hg along the
mm Hg glomerular capillary because
40 plasma water by filtration &
of loss of
PGC-PBC
concentration of plasma proteins
30 Therefore the Net filtration
∏ GC pressure is zero at the efferent
20 end of glomerular capillary &
the filtration stops there
10 (Filtration equilibrium)

0
aff. art eff. art.
 Glomerular filtration Rate (GFR)
• GFR is the volume of filtrate formed by all the
nephrons of both the kidneys in one minute
• It is about 125 mL/min (180 L/min)
• GFR is calculated by the following formula

GFR = Kf x net filtration pressure

= Kf x [PGC - PB– πGC]
where = Filtration coefficient
K (depends
Permeability
f of theon
filtration barrier & the total
surface area of glomerular capillary bed)
 Factors affecting
• Changes in GFR
systemic arterial blood
pressure P GC
• Afferent or efferent arteriolar
constriction PB
• Edema of kidney within tight
• capsule
Ureteral obstruction
• Changes in plasma protein ΠGC
• concentration
Changes in glomerular capillary
• Renal blood flow
permeability Kf
• Changes in surface area of filtration
bed
 Factors affecting
• Changes in GFR
systemic arterial blood
pressure P GC
• Afferent or efferent arteriolar
constriction PB
• Edema of kidney within tight
• capsule
Ureteral obstruction
• Changes in plasma protein ΠGC
• concentration
Changes in glomerular capillary
• Renal blood flow
permeability Kf
• Changes in surface area of filtration
bed
 Filtration
fraction
• Is the fraction or percentage of
plasma that forms the filtrate
GRF 125
• FF= 20%
=
RPF
625
Regulation of renal blood
flow
Pressure gradient
(between
renal artery &
vein)
Blood flow = Renal vascular
resistance
(provided by 2 sets of
arterioles)
 Regulation of
RBF
• neural factors- stim of renal
sympathetics causes vc that
reduces RBF
– Symp stim RAS & causes vc & reduces
RBF
• Hormonal factors
– Vc- E, NE, Ang II, vasopressin,
adenosine
–Vd- dopamine, histamine, kinins, PGE , PGI
2 2
100%
 Autoregulation of
• renal blood
RBF is kept flowover a wide
constant
range of mean arterial pressure (80
to 200 mm Hg)
• Renal vascular resistance changes
proportionately as the MAP changes
(recall that Q=ΔP/R)
• Afferent arteriole is the seat of
resistance
• Explained by ‘Myogenic’ &
‘Tubuloglomerular feedback’
mechanisms
Autoregulation of GFR and RBF
 Tubuloglomerular feedback
Refers to the feedback regulation of the GFR in a single nephron
based on sensory information about the distal tubule fluid.
TG feedback keeps single nephron GFR from getting too high.
 Intrinsic mechanism-
Autoregulation
• RBF remains constant when
Mean arterial blood pressure is
between 80- 1 6 0 m m H g
• Myogenic theory – stretch of
smooth muscle lining
arteriole ,leads to contraction -
Exp evidence,
paralyzing the smooth muscles
by Papavarine.
• Tubulo - glomerular feedback
 Measurement of Effective renal plasma flow
(ERPF) used is ‘Fick principle’
• Principle
• Substance used is ‘Para-aminohippuric acid’ (PAH)
because it
– Is filtered & secreted & has a high extraction ration
– Is not metabolized
– Is Not stored
– Is not produced by kidneys
– Does not affect the blood flow
– Is not toxic
– Can be easily measured in A & V blood
• Clearance of PAH gives ERPF
 Calculation of
RBF 1
RBF = RPF x
1- Hematocrit

• Hematocrit is determined by centrifuging

blood sample
• RPF is measured by clearance of PAH
 Measurement of Renal blood
flow
Urinary PAH conc. (U ) x Urine flow rate (V)
PAH

ERPF =

Plasma concentration of PAH (PPAH)

= Clearance of PAH (CPAH)

Problem:
Let conc. of PAH in urine (UPAH) be 12.4 mg/ml
Let urine flow (V) be 1 ml/min
Let conc. of PAH in plasma (PPAH) be 0.02 mg/ml
12.4 x 1
ERPF = ---------------- =
620 ml/min 0.02
 Measurement of Renal blood
ERPF isflow
converted to RPF as
ERPF 620
Actual RPF =--------------------- = -------- = 689
ml/min
extraction ratio 0.9

Let Hct. be
47% 1
RBF
Therefore,= RPF x --------- = 689 x ----------- =
689 x1--------- 1- Hct 1- 0. 47
0.53
1
=1300 ml/min
 Concept of renal
• clearance
Clearance refers to a theoretical volume of
plasma from which a substance is removed
over a period of time
• It can also be defined as ‘The volume of plasma
that is completely cleared of a substance by
the kidneys in one minute’
For example, if the plasma concentration of substance ‘X’
is 4 molecules per liter & the excretion rate of ‘X’ is 4
molecules per minute, then the volume of plasma cleared
of ‘X’ (clearance of ‘X’) is 1liter per minute
 What happens to the clearance
of X
• If the excretion • If the plasma
rate of ‘X’ concentration of
decreases to 2 ‘X’ decreases to
molecules per 2 molecules per
minute? liter & the
• ANSWER: 0.5 L/min excretion rate
remains at 2
molecules per
minute?
• ANSWER: 1 L/min
 Name the TWO factors that determine the
clearance of a substance

1. Plasma concentration of the substance

[Px]
2. Urinary excretion rate of the substance
[Ux.V]
(Urinary concentration of the substance x Urine flow
rate)
Therefore,
[Ux.V]
Clearance [Cx] =
 Given the following data, calculate
the clearance of substances X,Y
&Z
V =2
mL/min
Ux = 1.2 mg/mL Px = 0.02
mg/mL
Uy = 12 mg/mL Py = 0.04
Uz= 0 mg/mL Pz = 0.60
mg/mL
mg/mL

Answers: Cx = 120
mL/min Cy = 600
mL/min
 Inulin clearance as an index of GFR

• Inulin is a polysaccharide & when

infused slowly into the body, it
attains a constant plasma
concentration and eventually gets
excreted by kidneys.
• Inulin is freely filtered, but does
not undergo any further tubular
modification (neither reabsorbed
nor secreted)
• So, the excretion rate of inulin is
same as the rate at which it is
 Inulin clearance as an index of
GFR
Filtered load of inulin = Excretion rate of
inulin GFR x concentration of inulin in filtrate =
Excretion rate of inulin GFR x Plasma concentration of
inulin = Excretion rate of inulin,
since inulin is freely filtered (recall the term, ‘Freely
filtered’) i.e.,

GFR x Pinulin = Uinulin x V

x V
Uinulin
GFR = --------------- = Cinulin

Pinulin
 Inulin & Creatinine
clearance
Inulin clearance
• Represents GFR •
Creatinine clearance
Also a rough
• Always parallel to X- estimate of GFR
axis • Slightly greater than
inulin clearance since
small amounts are
• secreted
Creatinine
• endogenously
produced
Clinically preferred
for GFR estimation
 Plasma creatinine as an index of renal function

• Since all the creatinine that is produced is

excreted, plasma creatinine level rises as the
GFR (CCr) decreases
UCr. V
CONSTANT

GFR (CCr) =
--------- PCr
• Therefore plasma creatinine level (PCr) can be taken as
an index of renal function; but this has limitation since
PCr increases slightly even if there is a large reduction in
GFR
 Net effects of reabsorption &
secretion
Net transport = Filtered – Rate of
load excretion
GFR
If the value is positive, then. the
Px substance
- Umust
x .V
have got reabsorbed.
i.e., Filtered load > Rate of
excretion Ex: Sodium,
glucose, urea
If the value is negative, then the substance must have got
secreted i.e., Rate of excretion > Filtered load
Ex: PAH, creatinine
If the value is zero, then the substance is neither
reabsorbed nor secreted
i.e., Filtered load = Rate of excretion
Ex: Inulin
A 11 -year-old was brought to the hospital after it was
noticed that the child had swelling in both legs since
the past 2 weeks. On physical examination the patient
is afebrile and has normal blood pressure . There is
periorbital edema. A urinalysis shows 4+ proteinuria but
no hematuria, glucosuria, or ketonuria. The serum
cholesterol is 250 mg/dL. Blood pressure was estimated
to be 138/ 80 mm Hg. GFR was found to be 110 ml/min.
A renal biopsy is performed and on light microscopy, no
abnormal findings are noted. On electron microscopy
there is effacement of podocyte foot processes. A
diagnosis of minimal change nephropathy – a disease
that causes loss of negative charge of the glomerular
basement membrane, is made.
A) Draw diagram to depict the structure of the glomerular
filtration barrier.

A) Using a graph, explain the functional properties of the filtration

barrier. Explain how changes in the filtration barrier have led to
proteinuria in this patient.

C) Draw Explain how starling’s forces and filtration co-efficient

in a glomerular capillary are different from that of a regular
tissue capillary such as that of a skeletal muscle. Explain the
cause and consequences of these differences.

D) Classify causes for edema. Explain the causes for edema in

this patient.

E) Explain the concept of filtration equilibrium.

F)‘Even with a constant glomerular hydrostatic pressure, a
greater rate of blood flow into the glomerulus tends to increase
the GFR and a lower rate of blood flow into the glomerulus tends
to decrease the GFR’ – Substantiate this statement with
appropriate explanation

G)Draw graphs and explain the effects of changes in the

efferent and afferent arteriolar resistances on GFR.

H)Summarize the various factors that influence GFR and filtration

fraction.

I)Define renal clearance. Clearance of which substance can help

estimate GFR? Justify your answer.

J)Explain how GFR is kept constant despite changes in mean

arterial pressure within a certain range.