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Transcript

The amount excreted in urine depends in
large measure on the magnitude of
tubular transport.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
1

Reabsorption involves transport
› Across the tubular epithelial membranes
into the interstitial fluid,then
› Through peritubular capillary membrane
back into blood.

Reabsorption across the tubular
epithelial membranes into the interstitial
fluid includes active and passive
transport.
› Transcellular
› Para cellular
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
2
Tubular Reabsorption
Figure 27-1;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Through the peritubular capillary walls
into the blood by ultrafiltration
 Active transport can move a solute
against electrochemical gradient and
requires energy.

› Primary active transport.
› Second active transport.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
4

Primary active transporters include:
› Na+ - K+ ATPase, H+ ATPase, H+ -
K+ATPase,Ca2+ - ATPase.

Active transport mechanism for
reabsorption of large molecules such as
protein ( Pinocytosis)
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
5
Primary Active Transport of Na+
Figure 27-2;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Mechanisms of
Secondary
Active Transport
Copyright © 2006 by Elsevier, Inc.
Figure 27-3;
Guyton and Hall

For most substances that are actively
reabsorbed or secreted, there is a limit to
the rate at which the solute can be
transported.
› Transport maximum.

Occur when tubular load exceeds the
capacity of carrier proteins and specific
enzymes involved in the transport process.
.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
8
Figure 27-4;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.




Proximal tubular fluid is essentially isosmotic
to plasma.
Overall  65% filtered solutes and water are
reabsorbed along the proximal tubule.
Na+ are major osmotically active solutes in
the plasma and glomerular filtrate.
Though the osmolality ( total solute
concentration) does not change
detectably along the proximal convoluted
tubule, the concentration of individual
solutes vary widely .
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
10

 65% of filtered Na+ is reabsorbed along
with filtered water,also 65% of K+
Creatinine and urea are very poorly reabsorbed.
PAH is secreted into tubule.
Inulin is neither reabsorbed nor secreted.
Glucose, amino acids are almost completely
reabsorbed.
› Cl and HCO3 accompany Na+ in plasma and
glomerular filtrate.
›
›
›
›
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
11
Cellular Ultrastructure and Primary
Transport Characteristics of Proximal
Tubule
Figure 27-6; Guyton and Hall
Copyright © 2006 by Elsevier, Inc.

Na+ reabsorption
› is the major driving force
› for reabsorption of solutes and water in
the proximal convoluted tubules

Na+ enters the cell from the lumen
across the luminal membrane and is
pumped out across the basolateral
cell membrane by Na+/ K+ ATPase
pump.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
13


The Na+ and accompanying anions and
water are taken up by the blood
surrounding the tubule across the interstitial
fluid.
At luminal cell membrane ( brush border),
› Na+ enter the cell down a combined electrical
and chemical potential gradient.

Na+ is reabsorbed together with
› glucose, AA; Phosphate and other solutes by way
of separate,specific contransportes.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
14

The down hill movement of Na+ drives
the up hill transport of these solutes
(secondary active transport).
› Na+ is also reabsorbed across the luminal cell
membrane in exchange for H+,
› Na± H+ exchangers is also secondary active
transport mechanism.
› Cl-are reabsorbed by way of an electrical
potential and [ Cl- ] gradient, also by
secondary active transport.(contransport of
Cl- with Na+ across luminal membrane.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
15
Accumulated K+ in tubular cells diffuse
out of the basolateral cell membrane,
mostly through K+ channels.
 Glucose and AA accumulated in the cell
because of secondary active transport
exit across the basolateral cell
membrane by diffusion.
 Bicarbonates exist together with Na+ by
an electrogenic mechanism,

Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
16
Cl- may leave the cell by way of an
electrically neutral K – Cl
cotransporter.
 Reabsorption of Na+ and
accompanying solutes establishes an
osmotic gradient across the proximal
tubule epithelium

› that is the driving force for water
reabsorption.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
17
Reasorption of Water and Solutes is
Coupled to Na+ Reabsorption
Tubular
Cells
Interstitial
Fluid
- 70 mV
Na +
K+
ATP
Na +
ATP
0 mv
Copyright © 2006 by Elsevier, Inc.
K+
Tubular
Lumen
H+
Na +
glucose, amino
acids
Na +
Urea
H20
Na +
Cl-
- 3 mV
Mechanisms by which Water, Chloride,
and Urea Reabsorption are Coupled with
Sodium Reabsorption
Figure 27-5;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.

Uptake of reabsorbed solutes and
water by peritubular capillaries involve
the usual starling forces that operate
across the capillary wall.
› Low peritubular capillaries hydrostatic
pressure.
› High peritubular capillaries oncotic
pressure
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
20

The proximal tubules secrete organic
acids and bases.
› Endogenous compounds,drugs, toxins
e.g.. Oxalate, urate, bile salts,
catecholamine.
› By secondary active transport (counter
transport).
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
21
5
4
Cretinin
e
3
Cl-
2
5
Na+
1
HCO3-
0.5
0.2
0.1
0.005
50
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
100
5/9/2017
22

Filtrate entering the loop is isosmotic to
plasma.
› Proximal straight tubule has transport
properties similar to those proximal
convoluted tubule.

Thin descending and thin ascending
segments have thin epithelia membrane,
no brush borders, few mitochondria.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
23

The descending segment is highly
permeable to water and moderate
permeable to most solutes includes urea
and Na+.
› This segment allows simple diffusion substances.
› Ascending limb is virtually impermeable to
water.
›  25% of filtered Na+, Cl-, K+ are reabsorbed by
loop of Henle, mostly in the thick ascending limb.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
24
Cellular Ultrastructure and Transport
Characteristics of Thin and Thick Loop
of Henle
very permeable
to H2O)
not permeable
to H2O)
Figure 27-8;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.

Thick ascending limb is rich of Na+K+ATPase which is the driving force for
reabsorption of other solutes.
› Movement of Na+ across the luminal
membrane is mediated primarily by 1-Na+,
2Cl-, 1K+ contransporter.
› There is also Na+ - H+ countertransport
mechanism in the luminal cell membrane
which mediates H+ secretion.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
26

Most of the water delivered to the
ascending limb remains in the tubule.
› Tubular fluid becomes more dilute as it flows
toward the distal tubule.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
27
Sodium Chloride and Potassium Transport in
Thick Ascending Loop of Henle
Figure 27-9;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
1. More solute than water is added to the renal medulla
(i.e., solutes are “trapped” in the renal medulla).
2. Fluid in the ascending loop is diluted.
3. Horizontal gradient of solute concentration established
by the active pumping of NaCl is “multiplied” by
countercurrent flow of fluid.
Copyright © 2006 by Elsevier, Inc.
First portion of Distal tubule forms part of
Juxtaglomerular complex.
 The rest of early distal tubule is
convoluted and has reabsorptive
characteristics almost the same as those
of thick ascending limb of loop of Henle.

Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
30
Sodium Chloride Transport in
Early Distal Tubule
Figure 27-10;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Sodium Chloride Reabsorption and Potassium
Secretion in Collecting Tubule Principal Cells
Figure 27-12;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.

Tubular membranes are almost
impermeable to urea
› Also the early distal tubule.

Two distinct cell types.
› Principal cells
› Intercalated cells
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
33

The principal cells reabsorb Na+ and
water from the lumen and secrete K+
› Na+ reabsorbed because of Na+/K+pump
› K+ secreted because of Na+/K+ pump in
basolateral membrane, and
concentration gradient across the luminal
membrane.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
34

Intercalated cell
› Reabsorb K+ and HCO3- and secrete H+.
› H+ secretion is mediated by H+ - ATPase
transport mechanism.( primary active
transport)
› H+ generated by action of carbonic
anhydrate H2O + CO2  H2CO3- ⇌ H+
+HCO3-.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
35
• not permeable
to H2O
• not very
permeable to
urea
• permeability
to H2O
depends on ADH
• not very
permeable to
urea
Figure 27-11; Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Na+ reabsorption and K+ secretion is
controlled by hormones,especially
aldosterone.
 Permeability of late distal tubules and
cortical collecting tubule to water is
controlled by ADH.

Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
37
Cortical Collecting Tubules
Intercalated Cells
Tubular Cells
Tubular Lumen
H20 (depends on
ADH)
H+
K+
K+
ATP
ATP
Na +
K+
H+
ATP
ATP
ATP
Cl Copyright © 2006 by Elsevier, Inc.
› Reabsorb less than 10% of filtered water and
Na+
› Permeability of membrane to water id
controlled by level of ADH.
› Medullary collecting duct is permeable to
urea.
› Capable of secreting H+ against large
concentration gradient.
Copyright © 2006 by Elsevier, Inc.
Functional anatomy of the kidney
5/9/2017
39
Cellular Ultrastructure and Transport
Characteristics of Medullary Collecting Tubules
Figure 27-13; Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Normal Renal Tubular Na+ Reabsorption
7%
(16,614 mEq/day)
25,560
mEq/d
(1789 mEq/d)
65 %
25 %
2.4%
(6390 mEq/d)
(617 mEq/day)
0.6 %
(150 mEq/day)
Copyright © 2006 by Elsevier, Inc.
Summary of Water Reabsorption and
Osmolarity in Different Parts of the Tubule
• Proximal Tubule: 65% reabsorption, isosmotic
• Desc. loop: 15-20% reabsorption, osmolarity increases
• Asc. loop: 0% reabsorption, osmolarity decreases
• Early distal: 0% reabsorption, osmolarity decreases
• Late distal and coll. tubules: ADH dependent
water reabsorption and tubular osmolarity
• Medullary coll. ducts: ADH dependent water
reabsorption and tubular osmolarity
Copyright © 2006 by Elsevier, Inc.