Physiology 4.

November 18, 2011

Dr. Jerez

Reabsorption and Secretion

OUTLINE
I. Tubular Reabsorption
A. Substance Of Tubular Reabsorption
B. Na Reabsorption
C. Water Reabsorption
D. Protein Reabsorption
E. Mechanisms of Tubular Reabsorption
F. Countercurrent Mechanisms to Increase Water
Reabsorption
G. Obligatory and Facultative Water Transport
H. Transport Maximum
I. Hormones in Tubular Reabsorption
II. Tubular Secretion
A. Segments
B. K Regulation
C. Substances Secreted
D. Role of Urea

I.

o Reabsorption of NaHCO3 and Na -organic solutes establishes a

transtubular osmotic gradient provides the driving force for
the passive reabsorption of water by osmosis.
o Because more water than Cl is reabsorbed, the [Cl ] in tubular
fluid rises along the length of the proximal

TUBULAR REABSORPTION

A. SUBSTANCE OF REABSORPTION: PROXIMAL TUBULE

Main reabsorption site for most of the substances found in the
ultrafiltrate
+
- +
Reabsorbs approximately 67% of filtered water, Na , Cl , K , and
other solutes
Figure 2. Sodium Reabsorption

Figure 1. Sites of Reabsorption and Secretion in the Proximal Tubule

B. NA+ REABSORPTION
Na+ passes through apical membrane and into the cell by
symporter (coupled with organic molecules) or antiporter
(coupled H+) proteins
1st half reabsorbed primarily with HCO3- or organic molecules
like glucose, amino acids and lactate
+
o Specific transport proteins mediate entry of Na into the cell
across the apical membrane.
+ +
+
+
Na -H antiporter couples entry of Na with extrusion of H
from the cell results in reabsorption of sodium
bicarbonate (NaHCO3)
+v
+
Entry of Na ia several symporter mechanisms: Na -glucose,
+
+
+
Na -amino acid, Na -Pi, and Na -lactate
o The glucose and other organic solutes that enter the cell with
+
Na leave the cell via passive transport mechanisms.
+
o Any Na that enters the cell across the apical membrane leaves
+
+
the cell and enters the blood via Na , K -ATPase.
Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

Figure 3. Bicarbonate Reabsorption

2nd half reabsorbed mainly with Cl- by both paracellular and

trancellular pathway
o Paracellular NaCl reabsorption occurs because the rise in [Cl ] in
tubule fluid in the first half of the proximal tubule creates a [Cl ]
gradient
o Reabsorption of NaCl establishes a transtubular osmotic
gradient that provides the driving force for the passive
reabsorption of water by osmosis.

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Figure 4. Sodium Reabsorption

Figure 6. Proximal tubule: NaCl and water, along with some ions and
nutrients are reabsorbed.

D. PROTEIN REABSORPTION
Proteins partially degraded by enzymes
Endocytosed and digested into amino acids which then exit the
cell across the basolateral membrane
Proteinuria appearance of protein in urine frequently seen
with kidney disease

E. MECHANISMS OF TUBULAR REABSORPTION

Tubular reabsorption is carried out through both active and
passive transport mechanisms, primarily in the proximal tubule.

Figure 5. Events in the Reabsorption of NaCl in the Proximal Tubule

C. WATER REABSORPTION
Driven by the transtubular osmotic gradient caused by solute
reabsorption
The proximal tubule is highly permeable to water, water is
reabsorbed via osmosis.
The apical and basolateral membranes of proximal tubule cells
express aquaporin water channels reabsorbed across the
proximal tubular cells.
Some water is also reabsorbed across the tight junctions.
The accumulation of fluid and solutes within the lateral
intercellular space increases hydrostatic pressure forces
fluid and solutes into the capillaries water reabsorption
follows solute reabsorption in the proximal tubule.
+
Changes in Na reabsorption influence the reabsorption of water
and other solutes by the proximal tubule.

Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

1. ACTIVE REABSORPTION
o The special importance of primary active transport is that it can
move solutes against an electrochemical gradient
o Solutes can be transported through epithelial cells (transcellular
pathway) or between cells (paracellular pathway)
o Pinocytosis
occurs in the proximal tubule; protein attaches to the brush
border of the luminal membrane, and this portion of the
membrane then invaginates to the interior of the cell until it
is completely pinched off and a vesicle is formed containing
the protein, then this protein is digested into its constituent
amino acids, which are reabsorbed through the basolateral
membrane into the interstitial fluid
o Transport maximum: limit to the rate at which the solute can
be transported (refer to next sections for further discussion)
2. PASSIVE REABSORPTION
o Occurs in proximal tubules, which have a high permeability for
water and a smaller but significant permeability to most ions,
such as sodium, chloride, potassium, calcium, and magnesium
o Passive water reabsorption by osmosis is coupled mainly to
sodium reabsorption changes in sodium reabsorption
significantly influence the reabsorption of water and many
other solutes
o Solvent Drag: As water moves across the tight junctions by
osmosis, it can also carry with it some of the solutes

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F. COUNTERCURRENT MECHANISMS TO INCREASE WATER

REABSORPTION
Countercurrent system is a system in which the inflow runs
parallel to, counter to, and in close proximity to the outflow for
some distance. This occurs for both the loops of Henle and the
vasa recta in the renal medulla
The concentrating mechanism depends upon the maintenance of
a gradient of increasing osmolality along the medullary pyramids
this gradient is produced by the operation of the loops of Henle
as countercurrent multipliers and maintained by the operation of
the vasa recta as countercurrent exchangers

Figure 8: The vasa recta serve as countercurrent exchangers, minimizing

washout of solutes from the medullary interstitium.

Figure 7. Countercurrent Mechanism

COUNTERCURRENT MULTIPLIER
o Establishes increase in concentration gradient
o Additional Info from Guyton: The repetitive reabsorption of
sodium chloride by the thick ascending loop of Henle and
continued inflow of new sodium chloride from the proximal
tubule into the loop of Henle is called the countercurrent
multiplier
COUNTERCURRENT EXCHANGER
o The vasa recta (blood vessels accompanying the loop of Henle)
does not reabsorb water and solute
o Peritubular capillaries exchange water and solute without
actual reabsorption
o Descending limb of vasa recta: Solute goes IN since fluid inside
the vasa recta is less tonic than outside.
Water moves out since the interstitium has a higher
osmolarity
o Ascending Limb of Vasa Recta: Solute goes OUT since fluid
inside has higher osmolarity
Water moves IN in response to the increased osmolarity
from the descending limb.

Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

Figure 9: Increasing solute concentration at the loop of Henle; the U-shaped

structure of the vessles minimizes loss of solute from the interstitum but does
not prevent the bulk flow of fluid and solutes into the blood

Note:
Water and solutes just loop around the vasa recta (THUS
EXCHANGER) while there is a net change in interstitium
osmolarity by around increment of 200 mOsm for Loop of Henle
(Thus MULTIPLIER)

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o The transport rate at saturation is called the transport

maximum.
o The plasma concentration of substrate at which the transport
maximum occurs is called the renal threshold.
Principles of Transport Maximum
o Tm: transport maximum
o filtered load = plasma conc x GFR
Tm for Glucose
o Glucose is reabsorbed by the proximal tubule by secondary
active transport (linked to sodium reabsorption) then out of
cell by facilitated diffusion.
o For glucose, this is about 375 mg/min. (Guyton)
CLINICAL CORRELATION:
In diabetes mellitus, the concentration of glucose in the blood is
higher than normal
consequently more glucose than usual will filter at the glomeruli
there will be too much glucose in the tubular fluid for the cells to
reabsorb it all
glycosuria will occur: the presence of glucose in the urine

I. HORMONES OF REABSORPTION

Figure 10: Comparison of Vasa Recta and Loop of Henle

G. OBLIGATORY AND FACULTATIVE WATER TRANSPORT

1. OBLIGATORY TRANSPORT
+
Water follows reabsorbed solutes, primarily glucose and Na , due
to the osmotic gradients that are created between the filtrate and
the intracellular fluid of the renal tubular cells.
How is this type of reabsorption controlled?
+
o Since Na is the major extracellular cation, it has enormous
effects on water movement. Its control by aldosterone,
therefore, is a major control of water balance as well.
2. FACULTATIVE TRANSPORT
The permeability of distal tubule and collecting duct cells to water
is controlled directly by anti-diuretic hormone (ADH). ADH is
secreted from the hypothalamus during times of dehydration.
What is the effect of ADH?
o ADH increases the number of water channels in the tubular
cells, thus allowing water molecules to leave the filtrate and
enter the cells. This process is used to control the remaining
10% of water reabsorption and is the major controller of
moment-to-moment needs in water balance.

H. TRANSPORT/TUBULAR MAXIMUM
Tubular or transport maximum (Tm) is the maximum amount of a
solute that can be reabsorbed (or secreted) under any condition
per unit of time.
Saturation refers to the maximum rate of transport that occurs
when all available carriers are occupied with substrate. When
concentration are below the saturation point, then the transport
rate is dictated by solute concentration.
Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

Aldosterone
o Secreted by: Zona glomerulosa cells of adrenal cortex
o Site of action: principal cells of the cortical collecting tubule
o Mechanism:
Stimulates the sodium-potassium ATPase pump on the
basolateral side of the cortical collecting tubule membrane.
Increases the sodium permeability of the luminal side of the
membrane.
o Clinical Significance:
Decreased Aldosterone:
Addisons Disease marked loss of sodium and
accumulation of potassium due to adrenal destruction or
malfunction
Increased Aldosterone
+ Conns syndrome increased sodium retention and
potassium depletion due to adrenal tumors.
Angiotensin II
o Mechanisms:
It stimulates aldosterone secretion, which in turn increases
sodium reabsorption
It constricts the efferent arterioles, which has two effects:
1. Efferent arteriolar constriction reduces peritubular
capillary hydrostatic pressure, which increases net tubular
reabsorption especially from the proximal tubules.
2. Efferent arteriolar constriction, by reducing renal blood
flow, raises filtration fraction in the glomerulus and
increases the concentration of proteins and the colloid
osmotic pressure in the peritubular capillaries. This raises
tubular reabsorption of sodium and water.
It stimulates the sodium-potassium ATPase pump on the
tubular epithelial cell basolateral membrane. It also
stimulates sodium-hydrogen exchange in the luminal
membrane, especially in the proximal tubule. (Guyton)
Antidiuretic Hormone
o It plays a key role in controlling the degree of dilution or
concentration of the urine.
o Mechanisms:

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 It binds with V2 receptors in the distal tubules, collecting

tubules and ducts, increasing the formation of cAMP and
activating protein kinases. This will stimulates the movement
of an intracellular protein called aquaporin-2 to the luminal
side of the cell membranes. This will form water channels
that permit rapid diffusion of water through the cells.
(Guyton)

II. TUBULAR SECRETION

A. DISTAL TUBULE AND COLLECTING DUCT

Atrial Natriuretic Peptide

o Secreted by: Specific cells in cardiac atria
o Stimulated by: Plasma volume expansion
o Mechanism:
It inhibits the reabsorption of sodium and water especially in
the collecting ducts. This results to increased urinary
excretion which helps to return blood volume back toward
normal.
Parathyroid Hormone
o Most important calcium-regulating hormone in the body.
o Increases reabsorption of calcium in distal tubules and in the
loop of Henle.
o Inhibits phosphate reabsorption by the proximal tubule
o Stimulates magnesium reabsorption in the loop of Henle
Table 1. Hormones involved in the Reabsorption of Electrolytes and Water
HORMONE
STIMULUS SITE OF
TIME
EFFECTS ON
ACTION
COURSE KIDNEYS
Aldosterone decrease
Collecting
Slow
NaCl and
blood
tubule and
water
volume
duct
reabsoprtion
increase
K+
plasma K
secretion
Angiotensin
II

decrease
blood
volume

Antidiuretic
Hormone

increase
plasma
osmolarity
decrease
blood
volume

Atrial
Natriuretic
Peptide

increase
atrial
pressure

Parathyroid
Hormone

decrease
plasma Ca

Proximal
tubule, Loop of
Henle, distal
tubule,
collecting
tubule and
duct
Distal tubule,
collecting
tubule and
duct

Fast

NaCl and
water
reabsoprtion
H+
secretion

Fast

water
reabsoprtion

Distal tubule,
collecting
tubule and
duct
Proximal
tubule, loop of
Henle, distal
tubule

Fast

NaCl
reabsoprtion

Fast

Ca++
reabsorption
PO4
reabsorption

Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

Figure 11. Transport Pathways

Together reabsorb 8% of the filtered Na+.

Collecting duct reabsorb significant amounts of Cl- through
paracellular transport
Early distal tubule special features
o reabsorbs NaCl by a Na-Cl cotransporter
o is impermeable to water, as is the thick ascending limb. Thus,
reabsorption of NaCl occurs without water, which further
dilutes the tubular fluid.
o Is called the cortical diluting segment.
Late distal tubule and collecting duct special features
o Have two cell types
Principal cells
Reabsorb Na and H20
+
Secrete K
Aldosterone increases Na reabsorption and increases K
secretion
ADH increases water permeability by directing the
insertion of H20 channels in the luminal membrane. In the
absence of ADH, the principal cells are virtually
impermeable to water.
Alpha-Intercalated cells
+
+
Secrete H by a H -adenosine triphosphatase (ATPase),
which is stimulated by aldosterone
+
+ +
Reabsorb K by ah H K -ATPase

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Table 3. Some organic anions secreted by the proximal tubule

B. K REGULATION

Most of the bodys K+ is located in the ICF

A shift of K+ out of cells causes hyperkalemia
A shift of K+ into cells causes hypokalemia
+
Secretion of K
o Occurs in the principal cells
+
o Is variable and accounts for the wide range of urinary K
excretion.
o Depends on the factors such as dietary K+ levels, acid-base
status and urine flow rate.
+
Mechanism of distal K secretion
At the basolateral membrane, K+ is actively transported
into the cell by the Na-K pump. As in all cells. This
mechanism maintains a high intracellular K+
concentration.
At the luminal membrane, K+ is passively secreted into the
lumen through K+ channels. The magnitude of this passive
secretion is determined by the chemical and electrical
driving forces on K+ across the luminal membrane.
Na-K-ATPase maintains low cellular Na theres a
favorable chemical gradient for movement of Na from
tubular fluid into cell Na enters cell by diffusion through
Na channels in apical membrane (due to negative charge
in cell) Na goes to blood through Na-K-ATPase
K from blood crosses basolateral membrane via Na-KATPase. K leaves cell through apical membrane into the
tubular lumen by passive diffusion (because cellular K is
high and K in Tubular fluid is low)
Maneuvers that increase the intracellular K+ concentration
or decrease the luminal K+ concentration will increase K+
secretion by increasing the driving force.
Maneuvers that decrease the intracellular K+ concentration
will decrease K+ secretion by decreasing the driving force.
Table 2. Changes in distal K+ section

Causes of Increased Distal K

Secretion
High K+ diet
Hyperaldosteronism
Alkalosis
Thiazide diuretics
Loop diuretics
Luminal anions

Causes of Decreased Distal K

Secretion
Low K+ diet
Hypoaldosteronism
Acidosis
K+ sparing diuretics

Table 4. Some organic cations secreted by the proximal tubule

The proximal tubule also secretes numerous exogenous organic

compounds, including p-aminohippuric acid (PAH), drugs such as
penicillin, some nonsteroidal antiinflammatory agents (e.g.,
ibuprofen , indomethacin, and naproxen), and the antiviral drug
adefovir, which is effective in the treatment of human
immunodeficiency virus (HIV)-infected patients.
Organic Anion Transport
o PAH transport
Pathway for organic anion secretion in the proximal tubule
has a maximal transport rate, has a low specificity (i.e., it
transports a variety of organic anions), and is responsible for
the secretion of all organic anions in Table 1.

C. SECRETION OF ORGANIC ANIONS AND ORGANIC CATIONS

occurs in the proximal tubule
plays a key role in limiting the bodys exposure to toxic
compounds derived from endogenous and exogenous sources (i.e.
xenobiotics)
Partial listing of some organic cations and anions secreted in the
proximal tubule:

Figure 12. Organic anion secretion [e.g., p-aminohippuric acid (PAH)]

across the proximal tubule.
Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

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 PAH enters the cell across the basolateral membrane by a PAH-ketoglutarate (KG) antiport mechanism. The uptake of KG into
the cell, against its chemical gradient, is driven by the movement
+
of Na into the cell. The KG recycles across the basolateral
membrane. PAH leaves the cell across the apical membrane down
its chemical concentration gradient by a PAH-anion (A-)
transporter and possibly a voltage-driven transporter.
Organic Cation transport
+
o OC enters the cell across the basolateral membrane by
+
facilitated diffusion. The uptake of OC into the cell, against its
chemical gradient, is driven by the cell-negative potential
+
difference. OC leaves the cell across the apical membrane in
+
+ +
exchange with H by an OC -H antiport mechanism.

D. ROLE OF UREA
Urea maintains tonicity of the medullary interstitium (besides
countercurrent multiplier of the Loop of Henle and the concurrent
exchanger of the Vasa Recta)
Product of protein metabolism
Only 50% reabsorbed in the Proximal Collecting Tubule, while
others will be trapped in the medullary interstitium
o The amount of urea in medullary interstitium depends on the
filtered urea, which is dependent on protein intake
other nephron segments are impermeable to urea because it
follows water reabsorption only
o Urea transport is mediated by Urea transporters through
facilitated diffusion
o No urea will be absorbed in the cortical collecting ducts and the
other medullary collecting ducts
High levels of water reabsorption also increases urea absorption
A lot of urea in the interstitium means that there may be recycling
of urea in the tubular lumen to be excreted in the urine
o Presence of ADH favors urea reabsorption in the inner
collecting tubules

Figure 13. Organic cation secretion (OC ) across the proximal tubule.

Figure 14. Diuretic Sites of Action

Group 23 | Juen, Kua, Lacerona, Laguipo, Laus, Liban, Libardo, Lim, A., Lim, F.

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