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Excretory

Physiology
----------------Dr Sanjay Kumar Sood
Professor and Chairman,
Department of Physiology

Learning outcomes
Introduction to renal system & glomerular
filtration: Functional anatomy of the kidney,
glomerular filtration, renal blood flow.

List the major function of the kidney


Outline the function of the different parts of the
nephron
Describe the filtration process at the glomerulus
and factors influencing it
Describe the features, regulation and significance
of the renal circulation

Anatomy of Kidneys
Bean shaped in
retroperitoneal cavity
Cortex is the outer
region
Medulla central region
with inner and outer
segments
Papilla is Innermost tip
of inner medulla
opening into calyces
which continue as
ureter

Functions of the kidney

Regulation of volume and composition of extra


cellular fluid
Regulation of water & electrolyte balance
Regulation of body fluid osmolality and electrolyte
concentration
H+ homeostasis
Excretion of metabolic waste products
Excretion of foreign chemicals & drugs
Regulation of arterial blood pressure
Endocrine functions
Regulation of erythropoiesis
Regulation of vitamin D and calcium metabolism
Gluconeogenesis

Regulation of extra cellular fluid


Kidney
Maintenance of
ECF volume and
composition

Endocrine,
Metabolic and
Regulatory
functions

Nephron

Filtration Glomerulus

Modification of
filtrate - Tubule

Regulation of extra cellular fluid


Glomerulus
Filtration
Provides the tubules with fluid so that the
volume and composition can be modified
Tubules
Modify the composition of extra cellular
fluid by reabsorbing what is needed which
allows what is extra to be excreted
Secrete substances into the fluid more
than the amount that is filtered can be
excreted

Structure of nephrons

The nephron the functional unit of the


kidney
1-1.2 million nephrons per kidney
Glomerulus is capillary network
emerging from afferent arterioles
Glomerulus capillaries surrounded by
Bowmans capsule or space. Blood is ultra
filtered into this space (First step in the
formation of urine)

Nephron

Nephron

Nephron
Each segment of the
nephron is functionally
distinct with distinct
epithelial lining
Superficial cortical
nephrons have their
glomeruli in outer cortex
Juxtamedullary nephrons
have their glomeruli near
corticomedullary border;
they are larger with long
loop of henle descending
deep into inner medulla
and papilla and is essential
for urine concentration

Renal vasculature

Superficial nephrons have


peritubular capillaries for
supplying nutrients to
epithelial cells
Whereas in the
juxtamedullary nephrons
peritubular capillaries are
known as vasa recta
which are long hairpin
like following the loops of
henle (For concentrating
urine)

Renal vasculature

The glomerulus

Glomerulus is composed
of capillary loops
invaginated in Bowman's
capsule
Glomerulus also contains
mesangial cells in a central
glomerular tuft
These contain
myofilaments and may
contract - reducing the
surface area of the
capillaries
Bowman's capsule joins the
proximal tubule, a single
layer of epithelial cells lying
on a basement

The filtration barrier

Structure of the glomerular


capillary wall

The glomerulus
The filtration barrier
1. Capillary endothelium - fenestrated
2. Basement membrane - homogeneous
glycoprotein/mucopolysaccharide
3. Capsular epithelial cells - podocytes & foot
processes

Glomerular Filtration
Composition of filtrate depends on the filtration barrier
The filtration barrier is

Freely permeable to water and crystalloids, MW 30,000

Virtually impermeable to colloids but small quantities,


mainly of albumin (~ 50 mg/l in the filtrate) are filtered
There is no hindrance to molecules of MW < 7,000, (~ 4-8
m)
Any crystalloid that is protein bound is only partially
filterable
Small proteins are filterable, eg. myoglobin, Hb, light chains
etc

The filtration barrier

Foot processes are


covered with
glycosialoproteins which
partially occlude the slits
These are negatively
charged, hence present a
charge-selective barrier
At any molecular weight,
filtration of anions is
selectively restricted
Loss of the anion coat
result in increase of some
substances filtered e.g.
proteins

Starling forces

Fluid movement across glomerular capillary


wall is glomerular filtration
Driven by starling pressures across the wall
Hydrostatic pressure in glomerular
capillaries (PGC) remains same in the

entire length of capillaries (Because of


the constriction of efferent arterioles)

Hydrostatic pressure in bowmans capsule


(PBS) is due to fluid in the lumen of the
nephron
Oncotic pressure in glomerular capillaries
( GC) is due to proteins. It progressively
increases as fluid is filtered out of the
capillaries. GC eventually increases to the
point where net ultrafiltration pressure
becomes zero and filtration stops
(Equilibrium)
Oncotic pressure in bowmans capsule (BS :
zero because no proteins in the bowmans
capsule)
Figure A: Net filtration at the beginning of
capillaries
Figure B: Filtration equilibrium at the end of
the capillaries

Starling forces
GFR= Kf [(PGC-PBS)- GC
Kf is filtration coefficient. Its the water
permeability or hydraulic conductance of the
capillary walls.
Its is dependent on water permeability per
unit surface area and total surface area
Higher in glomerulus than other systemic
capillaries
GFR is 180 L/day

Effects of constricting afferent (A) and efferent (B) arterioles on renal plasma
flow (RPF) and glomerular filtration rate (GFR). PGC, Hydrostatic pressure in
the glomerular capillary.

Renal Blood Flow (RBF)

In an adult is approximately 1.2 L/min or


about 20-25% of the cardiac output
Much in excess of the metabolic demands
of the kidneys
90% of the blood flows to the cortex
Amounts to a plasma flow of about 600625 ml/min
Of the plasma flow approximately 20% is
filtered into the Bowman capsule
filtration fraction

Renal blood flow


Kidneys receive 25% of cardiac output
Blood flow = Pressure gradient/Resistance
Major mechanism for blood flow change in kidney
is changing arteriolar resistance (Afferent or
efferent)
Vasoconstrictors = Sympathetic (both afferent
and efferent; so blood flow and GFR decreases),
Angiotensin II (more efferent arteriole; so blood
flow and GFR decreases), Endothelins
Vasodilators = Prostaglandins (Protective for
blood flow), Nitric oxide, Dopamine (Small dose
cause vasodilatation)

Auto regulation of blood flow


Mainly regulated by
mean arterial pressure
(Pa)
Renal arterial pressure
can vary from 80 to 200
mmHg but renal blood
flow is constant because
of the change in
arteriolar diameter
Myogenic hypothesis;
Stretching of vessels due
to increased pressure
cause vasoconstriction
which keeps the RBF
constant

Auto regulation of blood flow

Tubuloglomerular
feedback: increased
arterial pressure cause
increased RBF and GFR,
which cause more load
of water and solute at
macula densa
(juxtaglomerular
apparatus) which results
in release of
vasoconstrictors which
cause constriction of
afferent arterioles and
thus the RBF and GFR is
maintained constant

Measuring RBF
Fick's principle: amount of
a substance entering organ
equals amount leaving the
organ (Substance neither
synthesized nor degraded
by organ)
Amount of substance
entering kidney via renal
artery equals the amount
of substance leaving the
kidney via renal vein plus
excreted in the urine
Paraamino Hippuric acid
(PAH) is used to measure
RBF because filtered and
secreted by kidney

Measuring RBF
Amount of PAH entering kidney = RA PAH
x Renal plasma flow (RPF)
Amount of PAH leaving kidney = RV PAH x
RPF + Urine PAH x V (Urine flow)
RA PAH x RPF = RV PAH x RPF+ UPAH x V
RPF= UPAH x V / RA PAH - RV PAH
Renal blood flow = RPF/1-PCV

Measuring RBF

Thank You!

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