Download Tubular Reabsorption

TUBULAR REABSORPTION
LEARNING OBJECTIVES:
At the end of the lecture, the student should be able to describe :
• Tubular reabsorption: An overview
• General structure of tubular system
• Mechanism of transport
• Tubular reabsorption at different renal segments
• Effect of tubular reabsorption on concentration of urine
• Role of ADH and urea
TUBULAR REABSORPTION: OVERVIEW
• Tubular reabsorption: occurs as filtrate flows through the lumens of
proximal tubule, loop of Henle, distal tubule, and collecting ducts.
• Processes used in reabsorption include:
– Diffusion
– Facilitated diffusion
– Active transport
– Co transport
– Osmosis
• Reabsorbed substances are transported to interstitial fluid and reabsorbed
into peritubular capillaries.
TUBULAR REABSORPTION AND SECRETION:
MECHANISMS OF REABSORPTION IN THE PROXIMAL
CONVOLUTED TUBULE
PERITUBULAR CAPILLARIES:
• Blood has unusually high COP here, and BHP is only 8 mm Hg
– This favors reabsorption
• Water absorbed by osmosis and carries other solutes with it (solvent
drag)
REABSORPTION OF SALT & H20:
• The PCT returns most molecules & H20 from filtrate back to
peritubular capillaries
– About 180 L/day of ultrafiltrate produced; only 1–2 L of urine
excreted/24 hours
• Urine volume varies according to needs of body
• Minimum of 400 ml/day urine necessary to excrete
metabolic wastes (obligatory water loss).
PCT:
• Filtrate in PCT is isosmotic to blood (300
mOsm/L)
• Thus reabsorption of H20 by osmosis
cannot occur without active transport
(AT)
– Is achieved by AT of Na+ out of
filtrate
• Loss of + charges causes Cl- to
passively follow Na+
• Water follows salt by osmosis.
GLUCOSE & AMINO ACID REABSORPTION:
• Filtered glucose & amino acids are normally 100% reabsorbed from
filtrate
– Occurs in PCT by carrier-mediated cotransport with Na+
• Transporter displays saturation if ligand concentration in
filtrate is too high
– Level needed to saturate carriers & achieve maximum
transport rate is transport maximum (Tm)
– Glucose & amino acid transporters don't saturate under normal
conditions.
• TUBULAR MAXIMUM
TM: Defined as
• Maximum rate at which a substance can be actively absorbed
– Each substance has its own
tubular maximum
– Normally, glucose concentration
in the plasma (and thus filtrate) is
lower than the tubular maximum
and all of it is reabsorbed.
– In diabetes mellitus, tubular load
exceeds tubular maximum and
glucose appears in urine.
– Urine volume increases because
glucose in filtrate increases osmolality of filtrate reducing the
effectiveness of water reabsorption .
SIGNIFICANCE OF PCT REABSORPTION:
• ≈65% Na+, Cl-, & H20 is reabsorbed in PCT & returned to bloodstream
• An additional 20% is reabsorbed in descending limb of the loop of
Henle
• Thus 85% of filtered H20 & salt are reabsorbed early in tubule
– This is constant & independent of hydration levels
– Energy cost is 6% of calories consumed at rest
– The remaining 15% is reabsorbed variably, depending on level of
hydration
MEDULLARY CONCENTRATION GRADIENT:
• In order to concentrate urine (and prevent a large volume of water from
being lost), the kidney must maintain a high concentration of solutes in
the medulla
• Interstitial fluid concentration (mOsm/kg) is 300 in the cortical region
and gradually increases to 1400 at the tip of the pyramids in the
medulla
• Maintenance of this gradient depends upon
– Functions of loops of Henle
– Vasa recta flowing countercurrent to filtrate in loops of Henle
– Distribution and recycling of
urea
DESCENDING LIMB:
• Is permeable to H20
• Is impermeable to salt
• Because deep regions of medulla are
1400
mOsm, H20 diffuses out of filtrate until
it equilibrates with interstitial fluid
– This H20 is reabsorbed by
capillaries .
Ascending Limb LH:
• Has a thin segment in depths of
medulla & thick part toward cortex
• Impermeable to H20
• Permeable to salt
• Thick part ATs salt out of filtrate
– AT of salt causes filtrate to
become dilute (100
mOsm) by end of LH.
AT IN ASCENDING LIMB:
• NaCl is actively extruded from
thick ascending limb into
interstitial fluid
• Na+ diffuses into tubular cell with secondary active transport of K+ and
Cl- .
• Na+ is AT across basolateral mem-brane by Na+/ K+ pump
• Cl- passively follows Na+ down electrical gradient
• K+ passively diffuses back into filtrate
COUNTERCURRENT MULTIPLIER SYSTEM:
• Countercurrent flow & proximity allow descending & ascending limbs
of LH to interact in way that causes osmolarity to build in medulla
• Salt pumping in thick ascending part raises osmolarity around
descending limb, causing more H20 to diffuse out of filtrate
– This raises osmolarity of filtrate in descending limb which causes
more concentrated filtrate to be delivered to ascending limb
– As this concentrated filtrate is subjected to AT of salts, it causes
even higher osmolarity around descending limb (positive
feedback)
– Process repeats until equilibrium is reached when osmolarity of
medulla is 1400.
VASA RECTA :
• Is important component of
countercurrent multiplier
• Permeable to salt, H20 (via aquaporins),
& urea
• Recirculates salt, trapping some in
medulla interstitial fluid
• Reabsorbs H20 coming out of descending limb
• Descending section has urea transporters
• Ascending section has fenestrated capillaries.
EFFECTS OF UREA:
• Urea contributes to high
osmolality in medulla
– Deep region of collecting
duct is permeable to urea
& transports it.
OSMOTIC GRADIENT IN THE
RENAL MEDULLA:
URINE CONCENTRATING MECHANISMS:
COLLECTING DUCT (CD):
• Plays important role in water conservation
• Is impermeable to salt in medulla
• Permeability to H20 depends on levels of ADH.
ADH:
• Is secreted by posterior pituitary in response to dehydration
• Stimulates insertion of aquaporins (water channels) into plasma
membrane of CD
• When ADH is high, H20 is drawn out of CD by high osmolality of
interstitial fluid
– & reabsorbed by vasa recta.
FORMATION OF CONCENTRATED
URINE:
• ADH-dependent water
reabsorption is called facultative
water reabsorption
• ADH is the signal to produce
concentrated urine
• ADH stimulates formation of
aquaporins in membrane of tubule cells. Increases water reabsorption
from filtrate
• The kidneys’ ability to respond depends upon the high medullary
osmotic gradient.
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