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Physiology of the Kidneys
Major Functions of the Kidneys
1. Regulation of:
body fluid osmolarity and volume
electrolyte balance
acid-base balance
blood pressure
2. Excretion of
metabolic products
foreign substances (pesticides, chemicals etc.)
excess substance (water, etc)
3. Secretion of
erythropoitin
1,25-dihydroxy vitamin D3 (vitamin D activation)
renin
prostaglandin
Structure of the Kidney
• Outer cortex:
• Contains many
capillaries.
• Medulla:
• Renal pyramids
separated by
renal columns.
• Pyramid
contains minor
calyces which
unite to form a
major calyx.



Major calyces form renal pelvis.
Renal pelvis collects urine.
Transports urine to ureters.
1. Nephron and
Collecting Duct
Nephron: The functional
unit of the kidney
Each kidney is made up of
about 1 million
nephrons
Each nephrons has two
major components:
1) A renal corpuscle
2) A renal tubule
Renal corpuscle
Shumlyansky-Bowman’s
Glomerulus (1)
Capsule (2)
3
Proximal tubule
1
8
2
convoluted section (3)
7
9
4
descending limb
(5)
straight section(4)
Loop of Henle
thick ascending
loop(6)
thick ascending
loop(7)
Distal convoluted tubule
(8)
6
5
Collecting ducts
10
cortical part (9)
medullary part(10)
Renal Blood Vessels
• Afferent arteriole:
• Delivers blood into the
glomeruli.
• Glomeruli:
• Capillary network that
produces filtrate that enters
the urinary tubules.
• Efferent arteriole:
• Delivers blood from
glomeruli to peritubular
capillaries.
• Peritubular capillaries:
• Deliver blood to vasa recta.
Insert fig. 17.5
Characteristics of the
renal blood flow:
1, high blood flow. 1200
ml/min, or 21 percent of
the cardiac output. 94%
to the cortex
2, Two capillary beds
Vesa Recta
High hydrostatic pressure
in glomerular capillary
(about 60 mmHg) and
low hydrostatic pressure
in peritubular capillaries
(about 13 mmHg)
Type of Nephrons
• Cortical nephron:
• Originates in outer 2/3 of cortex.
• Osmolarity of 300 mOsm/l.
• Involved in solute reabsorption.
Cortical nephron – glomeruli
in outer cortex & short loops
of Henle that extend only
short distance into medulla-blood flow through cortex is
rapid – majority of nephrons
are cortical – cortical
interstitial fluid 300
mOsmolar
Insert fig. 17.6
Type of Nephrons
• Juxtamedullary nephron:
• Originates in inner 1/3 cortex.
• Important in the ability to produce
a concentrated urine.
• Has longer LH.
Juxtamedullary nephron –
glomeruli in inner part of cortex &
long loops of Henle which extend
deeply into medulla.– blood flow
through vasa recta in medulla is
slow – medullary interstitial fluid
is hyperosmotic – this nephron
maintains osmolality in addition
to filtering blood and maintaining
acid-base balance
Insert fig. 17.6
The juxtaglomerular apparatus
macula densa,
extraglumerular
mesangial cells,
and
juxtaglomerular
(granular cells) cells
Juxtaglomerular apparatus
• The juxtaglomerular cells are cells that synthesize, store, and
secrete the enzyme renin.
• Specialized smooth muscle cells in the wall of the afferent arteriole
that are in contact with distal tubule.
• Have mechano-receptors for blood pressure
• The macula densa is an area of closely packed specialized cells
lining the distal convoluted tubule where it lies next to the
juxtaglomerular apparatus.
• Cells of macula densa are taller and have more prominent nuclei than
surrounding cells.
• Sensitive to the concentration of sodium ions in the fluid.
• The specific function of Extraglomerular mesangial cells (or lacis cells) is
not well understood. Although is it has been associated with the
secretion of Erythropoietin.
URINE FORMATION
The rates at which different substances are excreted in
the urine represent the sum of three renal processes,
• (1) glomerular filtration,
• (2) reabsorption of substances from the renal tubules
into the blood, and
• (3) secretion of substances from the blood into the
renal tubules.
Processes, ensuring the formation of
urine
фильтрация
Glomerular
filtration
primary urine
Tubular
вторичная
моча
Reabsorption
Secretion
secondary urine
– Filtration:
– First step in urine formation (primary
urine)
– Bulk transport of fluid from blood to
kidney tubule
» Isosmotic filtrate
» Blood cells and proteins don’t filter
– Result of hydraulic pressure
– GFR = 180 L/day
Second step in urine formation
(secondary urine)
– Reabsorbtion:
• Process of returning filtered material to bloodstream
• 99% of what is filtered
• May involve transport protein(s)
• Normally glucose is totally reabsorbed
– Secretion:
– Material added to lumen of kidney from blood
– Active transport (usually) of toxins and foreign
substances
» Saccharine
» Penicillin
Glomerular Capsule
• Bowman’s
capsule:
• Surrounds the
glomerulus.
• Location where
glomerular
filtration
occurs.
• Filtrate passes
into the urinary
space into PCT.
Insert fig. 17.6
Glomerular Filtration Membrane
• Endothelial capillary pores are large fenestrae.
• 100-400 times more permeable to plasma, H20, and dissolved solutes
than capillaries of skeletal muscles.
• Pores are small enough to prevent RBCs, platelets, and WBCs from
passing through the pores.
–Loss of fluid from body in form of urine
Amount = Amount + Amount -- Amount
of Solute
Filtered
Secreted
Reabsorbed
Excreted
Glomerular Filtration
Glomerular filtration
Occurs as fluids move
across the glomerular
capillary in response
to glomerular
hydrostatic pressure
– blood enters glomerular capillary
– filters out of renal corpuscle
• large proteins and cells stay behind
• everything else is filtered into nephron
• glomerular filtrate
– plasma like fluid in glomerulus
Filtration Membrane
– One layer of glomerular capillary cells
– Basement membrane(lamina densa)
– One layer of cells in Bowman’s capsule: Podocytes have
foot like projections(pedicels) with filtration slits in between
C: capillary
BM: basal membrane
P podocytes
FS: filtration slit
Factors that determining the
glomerular filterability
1.Molecular weight
Protein filtration:
influence of negative charge on glomerular wall
Filterablility of plasma constituents vs. water
Constituent
Mol. Wt.
Urea
Glucose
Inulin
Myoglobin
Hemoglobin
Serum albumin
60
180
5,500
17,000
64,000
69,000
Filteration
ratio
1.00
1.00
1.00
0.75
0.03
0.01
Factors that determining the
glumerular filterability
1.Molecular weight
2.Charges of the molecule
Dextran filterability
Stanton BA & Koeppen BM:
‘The Kidney’ in Physiology,
Ed. Berne & Levy, Mosby, 1998
2934
Glomerular filtration
• Mechanism: Bulk flow
• Direction of movement: From glomerular capillaries to
capsule space
• Driving force: Pressure gradient (net filtration pressure, NFP)
• Types of pressure:
Favoring Force: Capillary Blood Pressure (BP),
Opposing Force: Blood colloid osmotic pressure(COP) and
Capsule Pressure (CP)
Glomerular filtration rate (GFR)
• Amount of filtrate produced in the kidneys
each minute. 125mL/min = 180L/day
• Factors that alter filtration pressure change
GFR. These include:
– Increased renal blood flow -- Increased GFR
– Decreased plasma protein -- Increased GFR. Causes
edema.
– Hemorrhage -- Decreased capillary BP -- Decreased
GFR
GFR regulation : Adjusting blood
flow
• GFR is regulated using three mechanisms
1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation
All three mechanism adjust renal blood pressure
and resulting blood flow
a. Renal autoregulation
In the autoregulatory range,
renal blood flow and GFR stay
relatively constant despite
changes in arterial blood
pressure.
ERPF: experimental renal plasma flow GFR: glomerular filtration rate
1) Myogenic Mechanism of
the autoregulation
• This is accomplished by changes in
the resistance (caliber) of
preglomerular blood vessels.
• The circles indicate that vessel radius
(r) is smaller when blood pressure is
high and larger when blood pressure
is low.
• Since resistance to blood flow varies
as r4, changes in vessel caliber are
greatly exaggerated in this figure.
Blood Flow = Capillary Pressure / Flow resistance
b. Tubuloglomerular feedback
• When single nephron GFR is increased—for example, as a
result of an increase in arterial blood pressure—more NaCl
is delivered to and reabsorbed by the macula densa, leading
to constriction of the nearby afferent arteriole.
• This negative-feedback system plays a role in renal blood
flow and GFR autoregulation.
2. Neural regulation of GFR
• Sympathetic nerve fibers innervate afferent and
efferent arteriole
• Normally sympathetic stimulation is low but can
increase during hemorrhage and exercise
• Vasoconstriction occurs as a result which
conserves blood volume(hemorrhage)and permits
greater blood flow to other body parts(exercise)
3. Hormonal regulation of GFR
• Several hormones contribute to GFR regulation
• Angiotensin II. Produced by Renin, released by
JGA cells is a potent vasoconstrictor. Reduces
GFR
• Atrial natriuretic peptide ANP (released by atria
when stretched) increases GFR by increasing
capillary surface area available for filtration
• NO
• Endothelin
• Prostaglandin E2
Reabsorption in Proximal Tubule
Insert fig. 17.13
Reabsorption of Salt and H20
• Return of most of the molecules and H20 from the urine
filtrate back into the peritubular capillaries.
• About 180 L/day of ultrafiltrate produced; however, only 1–2 L
of urine excreted/24 hours.
• Urine volume varies according to the needs of the body.
• Minimum of 400 ml/day urine necessary to excrete
metabolic wastes (obligatory water loss).
•GFR  125 ml/min (180L/day)
•(about 1% is excreted)
PCT
• Total [solute] is = 300 mOsm/L.
• Reabsorption of H20 by osmosis, cannot occur without active
transport:
• [Na+] in glomerular ultrafiltrate is 300 mOm/L.
• PCT epithelial cells have lower [Na+].
• Due to low permeability of plasma membrane to Na+.
• Active transport of Na+ out of the cell by Na+/K+ pumps.
• Favors [Na+] gradient:
• Na+ diffusion into cell.
PCT
(continued)
• Na+/K+ ATPase pump located in basal and lateral
sides of cell membrane, creates gradient for
diffusion of Na+ across the apical membrane.
• Na+/K+ ATPase pump extrudes Na+.
• Creates potential difference across the wall of the
tubule, with lumen as –pole.
• Electrical gradient causes Cl- movement towards
higher [Na+].
• H20 follows by osmosis.
Salt and Water Reabsorption in Proximal Tubule
Insert fig. 17.14
Significance of PCT Reabsorption
• 65% Na+, Cl-, and H20 reabsorbed across the PCT into the vascular
system.
• 90% K+ reabsorbed.
• Reabsorption occurs constantly regardless of hydration state.
• Not subject to hormonal regulation.
• Energy expenditure is 6% of calories consumed at rest.
Countercurrent Multiplier
• In order for H20 to be reabsorbed, interstitial fluid
must be hypertonic.
• Osmotic pressure of the interstitial tissue fluid is 4
x that of plasma.
• Results partly from the fact that the tubule bends
permitting interaction between the descending and
ascending limbs.
Ascending Limb LH
• (sodium chloride) is
actively extruded from
the ascending limb into
surrounding interstitial
fluid.
• Na+ diffuses into tubular
cell with the secondary
active transport of K+ and
Cl-.
• Occurs at a ratio of 1 Na+
and 1 K+ to 2 Cl-.
Insert fig. 17.15
Ascending Limb LH
• Na+ actively transported
across the basolateral
membrane by Na+/ K+
ATPase pump.
• Cl- passively follows Na+
down electrical gradient.
• K+ passively diffuses back
into filtrate.
• Ascending walls are
impermeable to H20.
(continued)
Insert fig. 17.15
Descending Limb LH
• Deeper regions of medulla reach
1400 mOsm/L.
• Impermeable to passive
diffusion of NaCl.
• Permeable to H20.
• Hypertonic interstitial fluid
causes H20 movement out of the
descending limb via osmosis,
and H20 enters capillaries.
• Fluid volume decreases in
tubule, causing higher [Na+] in
the ascending limb.
Insert fig. 17.16
Countercurrent Multiplier System
• Multiplies the [interstitial
fluid] and [descending limb
fluid].
• Flow in opposite directions
in the ascending and
descending limbs.
• Close proximity of the 2
limbs:
• Allows interaction.
• Positive feedback.
Insert fig. 17.16
Vasa Recta
• Countercurrent exchange.
• Recycles NaCl in medulla.
• Transports H20 from
interstitial fluid.
• Descending limb:
• Urea transporters.
• Aquaporin proteins (H20
channels).
• Ascending limb:
• Fenestrated capillaries.
Insert fig. 17.17
Vasa Recta
(continued)
• Vasa recta maintains hypertonicity by countercurrent
exchange.
• NaCl and urea diffuse into descending limb and
diffuse back into medullary tissue fluid.
• At each level of the medulla, [solute] is higher in the
ascending limb than in the interstitial fluid; and higher
in the interstitial fluid than in descending vessels.
• Walls are permeable to H20, NaCl and urea.
• Colloid osmotic pressure in vasa recta > interstitial
fluid.
Osmolality of Different Regions of the Kidney
Insert fig. 17.19
Collecting Duct
• Medullary area impermeable to high [NaCl] that
surrounds it.
• The walls of the CD are permeable to H20.
• H20 is drawn out of the CD by osmosis.
• Rate of osmotic movement is determined by the # of
aquaporins in the cell membrane.
• Permeable to H20 depends upon the presence of
ADH.
• When ADH binds to its membrane receptors on CD, it
acts via cAMP.
• Stimulates fusion of vesicles with plasma membrane.
• Incorporates water channels into plasma membrane.
Glucose and Amino Acid Reabsorption
• Filtered glucose and amino acids are normally
reabsorbed by the nephrons.
• In PCT occurs by secondary active transport with
membrane carriers.
• Carrier mediated transport displays:
• Saturation.
• Tm.
• [Transported molecules] needed to saturate carriers and
achieve maximum transport rate.
• Renal transport threshold:
• Minimum plasma [substance] that results in excretion of
that substance in the urine.
• Renal plasma threshold for glucose = 180-200 mg/dl.
Secretion
• Secretion of substances from the peritubular capillaries into
interstitial fluid.
• Then transported into lumen of tubule, and into the urine.
• Allows the kidneys to rapidly eliminate certain potential
toxins.
Proximal Tubule
Secretion
Insert fig. 17.13
K+ Secretion
• 90% filtered K+ is reabsorbed in early part of the
nephron.
• Secretion of K+ occurs in CD.
• Amount of K+ secreted depends upon:
• Amount of Na+ delivered to the region.
• Amount of aldosterone secreted.
• As Na+ is reabsorbed, lumen of tubule becomes –charged.
• Potential difference drives secretion of K+ into tubule.
• Transport carriers for Na+ separate from transporters for K+.
K+ Secretion
(continued)
• Final [K+] controlled
in CD by
aldosterone.
• When aldosterone
is absent, no K+ is
excreted in the
urine.
• High [K+] or low
[Na+] stimulates the
secretion of
aldosterone.
• Only means by
which K+ is
secreted.
Insert fig. 17.24
Renal Acid-Base Regulation
• Kidneys help regulate blood pH by excreting H+
and reabsorbing HC03-.
• Most of the H+ secretion occurs across the walls of
the PCT in exchange for Na+.
• Antiport mechanism.
• Moves Na+ and H+ in opposite directions.
• Normal urine normally is slightly acidic because
the kidneys reabsorb almost all HC03- and excrete
H+.
• Returns blood pH back to normal range.
Reabsorption of HCO3• Apical membranes of tubule cells are impermeable
to HCO3-.
• Reabsorption is indirect.
• When urine is acidic, HCO3- combines with H+ to
form H2C03-, which is catalyzed by ca located in the
apical cell membrane of PCT.
• As [C02] increases in the filtrate, C02 diffuses into tubule
cell and forms H2C03.
• H2C03 dissociates to HCO3- and H+.
• HCO3- generated within tubule cell diffuses into
peritubular capillary.
Acidification of Urine
Insert fig. 17.28
Urinary Buffers
• Nephron cannot produce a urine pH < 4.5.
• In order to excrete more H+, the acid must be buffered.
• H+ secreted into the urine tubule and combines with
HPO4-2 or NH3.
• HPO4-2 + H+
H2PO4• NH3 + H+
NH4+