Transcript File - Dr. Jerry Cronin

Glomerular Filtration
Normally, 3 Starling forces are at work in glomerular filtration
Glomerular Filtration
• Regulation of the GFR is critical to maintaining
homeostasis and is regulated by an assortment of
local and systemic mechanisms:
– Renal autoregulation occurs when the kidneys
themselves regulate GFR.
– Neural regulation occurs when the ANS regulates renal
blood flow and GFR.
– Hormonal regulation involves angiotensin II and atrial
natriuretic peptide (ANP).
Glomerular Filtration
• Renal autoregulation of GFR occurs by two means:
– Stretching in the glomerular capillaries triggers
myogenic contraction of smooth muscle
cells in afferent arterioles (reduces GFR).
– Pressure and flow monitored in the
macula densa provides tubuloglomerular
feedback to the glomerulus, causing the
afferent arterioles to constrict (decreasing
blood flow and GFR) or dilate (increasing
blood flow and GFR) appropriately.
Glomerular Filtration
• Neural regulation of GFR is possible because the
renal blood vessels are supplied by sympathetic
ANS fibers that release norepinephrine causing
vasoconstriction.
– Sympathetic input to
the kidneys is most
important with extreme
drops of B.P. (as occurs
with hemorrhage).
Glomerular Filtration
 Two hormones contribute to regulation of GFR
Angiotensin II is a potent vasoconstrictor of both
afferent and efferent arterioles (reduces GFR).
A sudden large increase in BP stretches the cardiac
atria and releases atrial
natriuretic peptide (ANP).
• ANP causes the
glomerulus to relax,
increasing the surface
area for filtration.
The Filtration Membrane
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule
Filtration slit
Pedicel
1
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
2
Basal lamina of glomerulus:
prevents filtration of larger proteins
3
Slit membrane between pedicels:
prevents filtration of medium-sized
proteins
(a) Details of filtration membrane
Pedicel of podocyte
Filtration slit
Basal lamina
Lumen of glomerulus
Fenestration (pore) of
glomerular endothelial cell
(b) Filtration membrane
TEM 78,000x
Glomerular Filtration
(Interactions Animation)
Renal Filtration
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Pressures That Drive Glomerular Filtration
1 GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
2 CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
3 BLOOD COLLOID
OSMOTIC PRESSURE
(BCOP) = 30 mmHg
Afferent arteriole
Proximal convoluted tubule
Efferent
arteriole
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
Glomerular
(Bowman's) Capsular
capsule
space
Tubular Reabsorption
• Tubular reabsorption is the process of returning
important substances (“good stuff”) from the filtrate back
into the renal interstitium, then into the renal blood
vessels... and ultimately back into the body.
Tubular Reabsorption
 The “good stuff” is glucose, electrolytes, vitamins, water,
amino acids, and any small proteins that might have
inadvertently escaped from the blood into the filtrate.
 Ninety nine percent of the glomerular filtrate is
reabsorbed (most of it before the end of the PCT)!
 To appreciate the magnitude of tubular reabsorption,
look once again at the table in the next slide and
compare the amounts of substances that are filtered,
reabsorbed, and excreted in urine.
Tubular Reabsorption
Amount in 180 L
of filtrate (/day)
Amount
returned to
blood/d
(Reabsorbed)
Amount in
Urine (/day)
3L
180 L
178-179 L
1-2 L
Protein (active)
200 g
2g
1.9 g
0.1 g
Glucose (active)
3g
162 g
162 g
0g
Urea (passive)
1g
54 g
24 g
30 g
(about 1/2)
(about 1/2)
0.03 g
1.6 g
0g
1.6 g
(all filtered)
(none reabsorbed)
Total
Amount in
Plasma
Water (passive)
Creatinine
Tubular Reabsorption
• Reabsorption into the interstitium has two
routes:
– Paracellular reabsorption is a passive process that
occurs between adjacent tubule
cells (tight junctions do
not completely seal off
interstitial fluid from
tubule fluid.)
– Transcellular reabsorption
is movement through an
individual cell.
Tubular Reabsorption
• It is a tremendous feat to reabsorb all of the
nutrients and fluid we must to survive, while still
filtering out, concentrating and excreting toxic
substance.
– To accomplish this, the kidney establishes a
countercurrent flow between the filtrate in the limbs of
the Loops of Henle and the blood in the peritubular
capillaries and Vasa Recta.
• Two types of countercurrent mechanisms exist in the kidneys:
countercurrent multiplication and countercurrent exchange.
Tubular Reabsorption
• Countercurrent multiplication is the process by
which a progressively increasing osmotic gradient is
formed in the interstitial fluid of the renal medulla
as a result of countercurrent flow.
• Countercurrent exchange is the process by which
solutes and water are passively exchanged between
the blood of the vasa recta and interstitial fluid of
the renal medulla as a result of countercurrent flow.
– This provides oxygen and nutrients to the renal medulla
without washing out or diminishing the gradient.
Tubular Reabsorption
 Both mechanisms contribute to reabsorption of fluid
and electrolytes and the formation of concentrated
urine.
Tubular Reabsorption
 Reabsorption of fluids, ions, and other substances occurs
by active and passive means.
 A variety of symporters and antiporters actively transport Na+ ,
Cl– , Ca2+, H+, HCO3– , glucose, HPO42– , SO42– , NH4+, urea, all
amino acids, and lactic acid.
 Reabsorption of water can be obligatory or facultative, but it
always moves by osmosis down its concentration gradient
depending on the permeability of the tubule cells (which
varies between the PCT, the different portions of the loop of
Henle, DCT, and collecting ducts).
Tubular Reabsorption
• Obligatory reabsorption of water occurs when
it is obliged to follow the solutes as they are
reabsorbed (to maintain the osmotic gradient).
• Facultative reabsorption describes variable
water reabsorption, adapted to specific needs.
– It is regulated by the effects
of ADH and aldosterone on
the principal cells of the renal
tubules and collecting ducts.
Tubular Reabsorption
• This graphic depicts the formation of a dilute urine,
mostly through obligatory
reabsorption of water.
• Compare this process to
the one depicted on the
next slide where urine is
concentrated by the action
of ADH on the DCT and
collecting ducts of
juxtamedullary nephrons.