Download Tubular reabsorption

Tubular reabsorption
• Tubular Reabsorption Is Selective and Quantitatively Large
• The rate at which each of these substances is filtered is
calculated as:
• Filtration = Glomerular filtration rate x Plasma
concentration
• A 10 per cent decrease in tubular reabsorption, from 178.5 to
160.7 L/day, would increase urine volume from 1.5 to 19.3
L/day (almost a 13-fold increase) if the glomerular filtration
rate (GFR) remained constant.
Tubular Reabsorption
 Filtered substances are transferred
from the tubular lumen to the
peritubular capillaries
 This process is highly selective and
variable.
 The return of substances to the blood is needed to maintain the
composition of the ECF. Only excesses of materials are eliminated.
 Reabsorption rates are high: 124 of 125 ml of filtered fluid per minute,
 99% for water
 100% for glucose
 99.5% for salt.
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Tubular reabsorption involves transepithelial
transport
 Reabsorbed substance must cross:
1. tubule wall
2. interstitial fluid,
3. wall of the peritubular capillaries
thus entering the blood.
 The single layer of epithelial cells of
the nephron tubule has:
i. luminal membrane (facing tubule
lumen)
ii. basolateral membrane (facing the
interstitial spaces between the
tubule and peritubular capillaries)
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Active transport
A. Primary Active: Na-K, Hydrogen, H-K, and
Calcium pumps.
Sodium: on basolateral sides, Na-K pump,
creates negatives inside  increases Nainflux.
B. Secondary active : Co-transport, countertransport . Na -Glcose , Na - a.a , Na - H+
C. Pinocytosis: Proteins.
Basic mechanism for active transport of sodium
through the tubular epithelial cell
 Involves a Na-K ion ATPase
carrier in the tubular cell’s
basolateral membrane
 This pump keeps sodium
concentration low in the tubular
cells and high in the lateral
spaces outside the tubule.
 Water follows reabsorbed sodium
by osmosis. Thus, sodium
reabsorption has a main effect on
blood volume and blood pressure.
 Aldosterone promotes Na+
retention by insertion of additional
Na+ channels into the luminal
membrane, and additional
Na+/K+ ATPase into the
basolateral membrane of the
distal and collecting tubules.
Reabsorption of Na+
 Of the Na+ filtered, 99.5% is normally reabsorbed.
 Sodium is reabsorbed throughout the tubule with the exception of the
descending limb of the loop of Henle
 Of the Na+ reabsorbed, on average
• 67% in the proximal tubule (Plays an important role in the
reabsorption of glucose, amino acids, water, chloride ions, and urea)
• 25% in the loop of Henle (Plays a role in the production of varying
concentrations and volumes of the urine)
• 8% in the distal and collecting tubules (depends on hormonal control,
and plays an important role in regulating ECF volume).
Aldosterone (stimulated via renin system) increases Na+ reabsorption
Atrial Natriuretic Peptide “ANP” (released from heart) decreases Na+ reabsorption
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Mechanism of Aldosterone Action
Mechanisms of secondary active transport
Transport maximum for substances that
are actively reabsorbed
• Due saturation, when tubular load exceeds
capacity of carrier and specific enzymes.
• Transport maximums for substances actively
reabsorbed:
• Transport Maximums for Substances That Are
Actively Secreted:
– Creatinine 16 mg/min
– Para-aminohippuric acid 80 mg/min
• Tm Na+ in proximal tubule does not exist because
it is referred as (gradient-time transport) the
greater [Na+] the greater reabsorption .
– Because the rate of transport depends on the
electrochemical gradient and the time that the
substance is in the tubule, which in turn depends on
the tubular flow rate.
Gradient-time Transport
• Substances that are passively reabsorbed
usually do not demonstrate a transport
maximum because their rate of transport is
determined by other factors such as:
1. Electrochemical gradient for diffusion of the
substance across the membrane
2. Permeability of the membrane for the substance
3. Time that the fluid containing the substance
remains within the tubule
Splay
Passive Water reabsorption
• Passive water reabsorption by osmosis is coupled
mainly to sodium reabsorption
• When the interstitium is hypertonic:
– large part through tight junctions and solvent drag some
solute w/water .
• Ascending and first part of distal tubule are impermeable
for water
• ADH  ↑permeability in distal, and coll. tubule
Chloride reabsorption
• Na+ inside cells attracts (-) charge of chloride
(paracellular)
• Also Cl- passively after water influx [Cl-] out
higher
• Also secondary active transport Na+ - Cl-
Urea reabsorption
• Urea is passively
reabsorbed from the
tubule, but to a much
lesser extent than chloride
ions.
• As water is reabsorbed
from the tubules (by
osmosis coupled to
sodium reabsorption),
urea concentration in the
tubular lumen increases
 a concentration
gradient favoring the
reabsorption of urea.
Reabsorption and Secretion Along
Different Parts of the Nephron
Proximal Tubular Reabsorption
• Proximal Tubules Have a High Capacity for Active and
Passive Reabsorption.
• Special cellular characteristics.
• Highly metabolic and have large numbers of
mitochondria to support potent active transport
processes.
• Extensive brush border on the luminal membrane
• In the first half of the proximal tubule, sodium is
reabsorbed by co-transport along with glucose,
amino acids, and other solutes.
• In the second half of the proximal tubule, little
glucose and amino acids remain to be reabsorbed.
Instead, sodium is now reabsorbed mainly with
chloride ions.
Secretion of Organic Acids and Bases by the Proximal Tubule
The proximal tubule is also an important site for secretion
of organic acids and bases such as bile salts, oxalate, urate,
and catecholamines.
Concentrations of Solutes Along the Proximal Tubule
Solute and Water Transport in the Loop of Henle
• The loop of Henle consists of three
functionally distinct segments:
1. the thin descending segment,
2. the thin ascending segment,
3. and the thick ascending segment.
• The thick segment of the ascending loop
of Henle is virtually impermeable to
water.
• There is a significant paracellular
reabsorption of cations, such as Mg++,
Ca++, Na+, and K+, in the thick ascending
limb owing to the slight positive charge of
the tubular lumen relative to the
interstitial fluid.
Mechanisms of sodium, chloride, and potassium transport in the
thick ascending loop of Henle.
In the thick ascending
loop, movement of sodium
across the luminal
membrane is mediated
primarily by a 1-sodium,
2-chloride, 1-potassium
co-transporter
Distal Tubule
• The very first portion of the distal
tubule forms part of the
juxtaglomerular complex.
• The next part of the distal tubule is
highly convoluted and has many of
the same reabsorptive characteristics
of the thick segment of the ascending
limb of the loop of Henle.
• Reabsorbs most of the ions, including
sodium, potassium, and chloride
• Impermeable to water and urea.
• Referred to as the diluting segment
because it also dilutes the tubular
fluid.
Late distal tubule and collecting tubule
Principal Cells Reabsorb Sodium and Secrete Potassium
• Depend on the activity of a sodium-potassium ATPase pump in
each cell’s basolateral membrane.
• The principal cells are the primary sites of action of the
potassium-sparing diuretics.
• Aldosterone antagonists inhibit the stimulatory effects of
aldosterone on sodium reabsorption and potassium secretion.
• Sodium channel blockers directly inhibit the entry of sodium into
the sodium channels of the luminal membranes and therefore
reduce the amount of sodium that can be transported across the
basolateral membranes by the sodium-potassium ATPase pump.
Intercalated Cells Avidly Secrete Hydrogen and
Reabsorb Bicarbonate and Potassium Ions
• Hydrogen ion secretion by the intercalated cells is mediated by
a hydrogen- ATPase transport mechanism.
• Hydrogen is generated in this cell by the action of carbonic
anhydrase on water and carbon dioxide to form carbonic acid,
which then dissociates into hydrogen ions and bicarbonate
ions.
• The hydrogen ions are then secreted into the tubular lumen,
and for each hydrogen ion secreted, a bicarbonate ion becomes
available for reabsorption across the basolateral membrane.
Medullary Collecting Duct
• Reabsorb less than 10 per cent of the filtered water and sodium.
• The final site for processing the urine.
• Play an extremely important role in determining the final urine
output of water and solutes.
Characteristics of medullary collecting duct
• Its permeability to water is controlled by the level of ADH.
• Unlike the cortical collecting tubule, the medullary collecting
duct is permeable to urea. Therefore, some of the tubular urea
is reabsorbed into the medullary interstitium, helping to raise
the osmolality in this region of the kidneys and contributing to
the kidneys’ overall ability to form a concentrated urine.
• The medullary collecting duct is capable of secreting hydrogen
ions against a large concentration gradient, as also occurs in the
cortical collecting tubule. Thus, the medullary collecting duct
also plays a key role in regulating acid-base balance.
Summary of Concentrations of Different Solutes in
the Different Tubular Segments
Regulation of Tubular Reabsorption
It is essential to maintain a precise balance between tubular
reabsorption and glomerular filtration.
•Glomerulotubular Balance
• Peritubular Physical Forces
• Hormones
- aldosterone
- angiotensin II
- antidiuretic hormone (ADH)
- natriuretic hormones (ANF)
- parathyroid hormone
• Sympathetic Nervous System
• Arterial Pressure (pressure natriuresis)
• Osmotic factors.
Glomerulotubular Balance: The Ability of the Tubules to Increase
Reabsorption Rate in Response to Increased Tubular Load
• If GFR↑ to 150 ml/min so in proximal tubule reabsorption
↑ from 81 ml/min to 97.5 ml/min. (65% of GFR) . To less
extent in Loop of Henle.
• Intrinsic ability of the tubules to increase their
reabsorption rate in response to increased tubular load
(increased tubular inflow).
• The mechanisms for glomerulotubular balance can occur
independently of hormones and can be demonstrated in
completely isolated kidneys or even in completely isolated
proximal tubular segments.
• It helps to prevent overloading of the distal tubular
segments when GFR increases.
Peritubular capillary and interstitial fluid
physical forces
a.
b.
c.
d.
Hydrostatic pr. In capillary Pc opposes -13
Hydrostatic pr. In interstitium Pif favors 6
Colloid osmotic pr. in capillary πc favors 32
Colloid osmotic pr. In intrst. πif opposes -15
____
Net reab. Pr. 10 mmHg
Reabsorption = Kf x Net reabsorptive pr.
12.4 x 10 = 124 ml/min
Peritubular Capillary and Renal Interstitial Fluid Physical Forces
Reabsorption across the peritubular capillaries can be calculated as:
Reabsorption = Kf x Net reabsorptive force
A. Hydrostatic pr. depends on BP, and resistance of
aff. And eff. Arterioles:
↑Arterial pr.↑ hydrostatic decreases
reabsorption
Change in the resistance of afferent and efferent:
constriction  decreases hydrostatic ↑
reabsorption.
B. Colloid osm. Pr. depends: on [prot.]pl, and
filtration fraction.
- ↑Plasma colloid osmotic pr.↑ coll. In
perit.↑ reabs.
- ↑Filtration fraction ↑ [protein]
^reabsorption
2.
Hormonal control :
Aldosterone : Acts on the distal tubule and
collecting ducts; Na Cl , H2O reabs.
acts on principal calls of cortical coll.
tubule and increases K+ secretion.
Addison's disease : no aldosterone  loss of Na+,
accumulation of K+
Conn's syndrome : Na+ retention K+ depletion
Aldosterone actions on late distal, cortical
and medullary collecting tubules
• Increases Na+ reabsorption - principal cells
• Increases K+ secretion - principal cells
• Increases H+ secretion - intercalated cells
Angiotensin II Increases Na+ and Water
Reabsorption
• Stimulates aldosterone secretion
• Directly increases Na+ reabsorption
(proximal, loop, distal, collecting tubules)
• Constricts efferent arterioles
- decreases peritubular capillary
hydrostatic pressure
- increases filtration fraction, which increases
peritubular colloid osmotic pressure)
c. ADH : on distal and coll. duct ↑H2O
reabsorption :
- Binds V2 receptors form cyclic AMP
increase aquaporin-2 on luminal, AQP3,4
on basolateral
- When ADH decreased  AQP back to
cytoplasm
Hormonal control
d.Arterial natriuretic peptide :
Decrease Na+ and H2O reabsorption in distal
and collecting duct
e. Parathyroid hormone : - in Prox. tubule:
decreases PO4- reabsorption
- in thick ascending of L.H, distal tubule 
↑Ca++ reabsorption
3. Sympathetic N.S.
-
Sympathetic N.S. :
Stimulation ↑Na+ and H2O reabs. by
constricting afferent and efferent arterioles.