The Renal System
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Lecture 1: organization of the renal system
Lecture 2: Reabsorption, secretion and excretion
Lecture 3: control of salt and water balance
Lecture 4: Acid-base balance
Lecture 5: clinical scenarios
Professor Veronica Campbell
Department of Physiology
[email protected]
https://medicine.tcd.ie/physiology/student/
Suggested Reading
•  Sherwood
•  ‘Principles of Renal Physiology’
by Christopher Lote, 4th Edition, Kluwer Academic Publishers
Lecture 1: The renal system
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Components of renal system
Structure of nephron
Basic renal functions
Filtration
Assessment of filtration
Functions of kidney
–  Maintain H2O and salt balance in the body
–  Maintain proper osmolarity of body fluids, primarily through
regulating H2O balance
–  Regulate the quantity and concentration of most ECF ions
–  Maintain proper plasma volume
–  Help maintain proper acid-base balance in the body
–  Excreting (eliminating) the end products (wastes) of bodily
metabolism
–  Excreting many foreign compounds
–  Producing erythropoietin
–  Producing renin
–  Converting vitamin D into its active form
Urinary System
–  Urine forming organs
•  Kidneys
–  Structures that carry urine from the kidneys to the
outside for elimination from the body
•  Ureters
•  Urinary bladder
•  Urethra
Branches of renal artery
Interlobar
Arcuate
Interlobular
Afferent arteriole
Congenital abnormalities
Renal agenesis – failure of kidney to develop
1:2500
Unilateral agenesis – development of 1 kidney
1:1000
Ectopic kidney – abnormal location in pelvis
1:800
Horseshoe kidney - fused
Ureters
•  Smooth muscle-walled duct
•  Exits each kidney at the medial border in
close proximity to renal artery and vein
•  Carry urine to the urinary bladder
Urinary Bladder
•  Temporarily stores urine
•  Hollow, distensible, smooth muscle lining
wall
•  Periodically empties to the outside of the
body through the urethra
Urethra
•  Conveys urine to the outside of the body
•  Urethra is straight and short in females
•  In males
–  Much longer and follows curving course from
bladder to outside
–  Dual function
•  Provides route for eliminating urine from bladder
•  Passageway for semen from reproductive organs
Kidney
NEPHRON
•  Functional unit of the kidney
•  ~ 1 million nephrons/kidney
•  Each nephron has two components
–  Vascular component
–  Tubular component
•  Arrangement of nephrons within kidney gives rise to two
distinct regions
–  Outer region
•  Renal cortex
–  Inner region
•  Renal medulla
Proximal convoluted
tubule
Glomerulus
Arcuate vein
Efferent arteriole
Afferent arteriole
Distal convoluted tubule
Arcuate artery
Collecting duct
Vasa recta
Descending limb
loop of Henlé
Thick ascending limb
of the loop of Henlé
Thin ascending limb
of the loop of Henlé
Nephron
•  Two types of nephrons
•  Distinguished by location and length of
their structures
–  Juxtamedullary
nephrons (long Loops of Henle; 15%)
–  Cortical
nephrons (short Loops of Henle)
Nephron
•  Vascular component
Glomerulus
•  Ball-like tuft of capillaries
–  From renal artery, inflowing blood passes through
afferent arterioles which deliver blood to glomerulus
–  Efferent arteriole transports blood from glomerulus
–  Efferent arteriole breaks down into peritubular capillaries
which surround tubular part of nephron
–  Peritubular capillaries join into venules which transport
blood into the renal vein
•  Water and solutes are filtered through glomerulus
as blood passes through it
Approx 25% C.O
200µm
Renal artery
Efferent arteriole
Afferent arteriole
Glomerulus
FILTRATION
PTC
Renal vein
2
1
4
5
•  Tubular component
–  Hollow, fluid-filled tube formed by a
single layer of epithelial cells
–  Components
1.Bowman’s capsule
2. Proximal tubule
3. Loop of Henle
–  Descending limb
–  Ascending limb
4. Juxtaglomerular apparatus
5. Distal tubule
6. Collecting duct or tubule
3
6
Distal convoluted
tubule
Proximal
convoluted
tubule
- Convoluted apical surface
- ↑ sa
Descending
thin limb of
loop of Henlé
- Max water permeability
Collecting duct
Basic Renal Processes
•  Glomerular filtration
•  Tubular reabsorption
•  Tubular secretion
Glomerular Filtration
•  Fluid filtered from the glomerulus into
Bowman’s capsule pass through three layers
of the glomerular membrane
–  Glomerular capillary wall
•  Single layer of endothelial cells
•  More permeable to water and solutes than capillaries
elsewhere in the body - highly fenestrated
–  Basement membrane
•  Acellular gelatinous layer
•  Composed of glycoproteins, collagen IV, laminin
–  Inner layer of Bowman’s capsule
•  Consists of podocytes that encircle the glomerulus tuft
Phagocytosis of macromolecules
4. Mesangial cells – phagocytic; contractile and modify SA for filtration
Glomerular Filtration
-The glomerular filtration rate (GFR) is about 125 ml/min in a normal adult
- Ultrafiltrate is cell and protein-free and the concentration of small solutes are
the same as in plasma
- The filtration barrier restricts movement of solutes on a basis of size and
charge.
- Serum albumin has a radius if about 3.5 nm (69kDa) but its negative charge
prevents its movement across basement membrane
- In some diseases the negative charge on the filtration barrier is lost so that
proteins are more readily filtered - a condition called proteinuria
Forces Involved in Glomerular Filtration
•  Three physical forces
–  Glomerular capillary
pressure
–  Plasma-colloid
pressure
–  Bowman’s capsule
pressure
involved
blood
osmotic
hydrostatic
FILTRATION FRACTION
fraction of renal plasma flow that is filtered at the glomerulus
Renal blood flow
1100 ml/min
glomerulus
RPF
600 ml/min
= Glomerular filtration rate
Renal plasma flow
20%
GFR
125 ml/min
Efferent
Arteriole
475 ml/min
tubule
renal
vein
124 ml/min
Urine 1 ml/min
Assessment of GFR using inulin
•  Vol. plasma inulin cleared/min = vol. plasma filtered/min (GFR)
e.g Inulin clearance rate = 30mg/ml urine x 1.25 ml urine/min
0.30 mg/ml plasma
= 125 ml plasma/min
[U].V
[P]
Clinical note: creatinine clearance used to estimate GFR
Assessment of renal plasma flow with PAH
- para-aminohippuric acid
- Freely filtered and non-reabsorbed
- Any PAH not filtered is secreted from peritubular capillary
PAH clearance = renal plasma flow
[U].V
[P]
600ml/min
Glomerular filtration rate depends on:•  Net filtration pressure
•  How much glomerular surface area is available for penetration
•  How permeable the glomerular membrane is
Glomerular Filtration Rate
Pathologically, plasma-colloid osmotic pressure and
Bowman’s capsule hydrostatic pressure can change
Plasma-colloid osmotic pressure
- Dehydrating diarrhea
-  Relative increase in colloid pressure in glomerulus
-  increase in pressure opposing filtration
↓ GFR
Bowman’s capsule hydrostatic pressure
- kidney stone/obstruction of tubule with enlarged prostate
-  increase in capsular hydrostatic pressure
- ↓ GFR
RENAL BLOOD FLOW (RBF)
Renal blood flow is approx 25% of the cardiac output (1.1 l/min )
- RBF determines GFR
- Renal blood flow is
autoregulated between 90
and 180 mm Hg
Flow l/min
1.5
1.0
0.5
0
Renal blood flow
GFR
0
100
200
Arterial blood pressure, mm Hg
How is GFR maintained at 125ml/min?????
1.
2.
Myogenic response
Tubuloglomerular feedback
RENAL BLOOD FLOW - AUTOREGULATION
Autoregulation uncouples renal function from arterial blood pressure
and ensures that fluid and solute excretion is constant.
1.  Myogenic hypothesis
When arterial pressure increases the renal afferent arteriole is stretched
Increase of
Flow
arterial pressure
increases
Vascular smooth muscle contracts to increase resistance
Increase of
vascular tone
Flow
returns to
normal
RENAL BLOOD FLOW - AUTOREGULATION
2. Tubuloglomerular feedback
Alteration of tubular flow is sensed by the macula densa of the
juxtaglomerular apparatus (JGA) and produces a signal that alters
GFR.
Juxtaglomerular
(granular) cells
Efferent
Arteriole
Macula
Densa
Afferent
Arteriole
Distal
tubule
capillaries
Endothelin
Mesangial Cell Contraction
•  Mesangial cells are modified
smooth muscle cells located on
glomerular capillaries.
Large Surface
Area for Filtration
Filtration
slits
•  They contract in response
to an increase in MAP
resulting in a decrease in
surface area available for
filtration.
Capillary
lumen
Bowman’s
capsule
Relaxation of afferent
arteriole
Bradykinin