3.

03
Fernando P. Solidum, MD, DPBA || January 10, 2017

Lecture Outline:
I.
Body Fluid Compartments
A. Composition of Body Fluid Compartments
B. Osmolarity vs. Osmolality
C. Fluid Exchange Between Body Fluid
Compartments
II.
Control of Body Fluid Osmolality: Urine Concentration
and Dilution
A. Antidiuretic Hormone (ADH)
B. Osmotic Control of ADH Secretion
C. Hemodynamic Control of ADH Secretion
III. Renal Mechanism for Dilution and Concentration of
Urine
A. Diuresis Hypoosmotic Urine
B. Anti-Diuresis Hyperosmotic Urine
C. Medullary Interstitium
D. Vasa Recta Countercurrent Exchanger System
E. Effects of ADH on Urea and the Kidneys
IV.
Volume Sensing Systems
A. Vascular Low Pressure/Volume Sensors
B. Vascular High Pressure/Volume Sensors
C. Hepatic Sensors
D. CNS Sensors
V.
Volume Sensor Signals
A. Renal Sympathetic Nerves
B. Renin-Angiotensin-Aldosterone System (RAAS)
C. Natriuretic Peptides
VI.
Control of Na+ Excretion
A. During Euvolemia
B. During Volume Expansion
C. During Volume Contraction
BODY FLUID COMPARTMENTS
WATER

Accounts for approximately 60% of the total body

weight

Individual water content varies with:

o Amount of adipose tissue: The greater the
amount of adipose tissue, the smaller is the
fraction of body weight attributable to water
o Age: In newborn infants, water constitutes 75% of
total body weight. This decreases to about 60%
by the age of 1 year.

Distributed between two major compartments:

o Intracellular fluid (ICF)

Larger compartment

Contains 2/3 of total body water

o Extracellular fluid (ECF)

Constitutes the remaining 1/3 of total body

water

Interstitial fluid (ISF) represents the fluid

surrounding the cells; comprises of ECF
volume; includes water contained in bone &
dense connective tissue

Plasma represents the remaining

Figure 1. A figure showing the relationship between the volumes of the

major body fluid compartments. (Values shown for a 70-kg person)

COMPOSITION OF BODY FLUID COMPARTMENTS

ICF and ECF have similar ionic compositions due to

permeability of capillary wall to small ions

ICF is more acidic than ECF

o ICF pH
= 7.10
o ECF pH
= 7.40

The major difference between the composition of the

ISF and that of the plasma is that the plasma contains
significantly more protein
o Presence of protein in plasma can affect the
distribution of cations and anions across the
capillary wall
Table 1. A table showing the distribution of some cations and anions
between the ECF and the ICF

Ions

ECF (mEq/L)

ICF (mEq/L)

Na+

145

12

150

0.001

105

25

12

Ca2+
Cl

HCO3-

OSMOLARITY VS. OSMOLALITY

The main difference between the two is the expression of the
concentration of the dissolved particles

3.3

Osmolarity
o Function of the total number of particles in the
solution independent of mass, charge, or
chemical composition

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PHYSIOLOGY
o
o
o
o

Concentration of osmotically active particles in

the solution
Expressed as osmoles per liter of solution (or
mOsm/L of water)
Changes in response to various conditions
Normal value: 300 mOsm/L

Osmolality
o Alternative notation used to express the
concentration of dissolved particles
o Expressed as osmoles per kilogram of solution
(or mOsm/kg of water)

FLUID EXCHANGE BETWEEN

BODY FLUID COMPARTMENTS

Forces that determine the movement of water

between the various body fluid compartments:
o Hydrostatic pressure

Generated by the pumping of the heart and

the effect of gravity on the column of blood in
the vessels

Principal force in capillary filtration

hydrostatic pressure in the capillary drives

water to move to the interstitium (filtration)
o Oncotic pressure of plasma proteins

Osmotic pressure generated by large

proteins in solution

oncotic pressure in the capillary draws

water into capillary (absorption)

Osmotic pressure differences between the ECF and

the ICF are responsible for fluid movement across cell
membranes

A change of either the ECF or ICF results in the rapid

movement of water between these compartments

Except for transient changes, the ECF and ICF

compartments are in osmotic equilibrium
CONTROL OF BODY FLUID OSMOLALITY: URINE
CONCENTRATION AND DILUTION

Kidneys
o Regulates water balance

Insensible water loss

o Person is unaware of its occurrence

Evaporation from skin

Respiratory passages

Other mechanisms for water loss:

o Sweating can increase dramatically in a hot
environment, with exercise, or in the presence of
fever
o Fecal water loss is normally small but increases
with diarrhea
o Vomiting

WATER OUTPUT
Insensible water loss

700

Sweat

100

Feces

200

Urine

1500
TOTAL

Notes:

To maintain water balance: water intake = water loss

Water intake > water loss positive water balance

hypoosmotic urine

Water intake < water loss negative water balance

hyperosmotic urine
Table 3. A table showing the effect of environmental temperature and
exercise on water loss and intake in adults (in mL/day)

Normal
Temperature
(mL)

Hot Weather
(mL)

Prolonged
Heavy
Exercise
(mL)

Skin

350

350

350

Lungs

350

250

650

Sweat

100

1400

5000

Feces

200

200

200

Urine

1500

1200

500

2500

3400

6700

2500

3400

6700

WATER LOSS

Insensible water
loss

TOTAL
Water Intake
Needed to
Maintain Balance

Notes:

More water is lost during hot weather and prolonged

heavy exercise, hence, the water intake must be
increased to maintain water balance in the body.

mL/day

Fluid*

1200

In food

1000

Metabolically produced from food

300

TOTAL

3.3

2500

2500

* Fluid intake varies widely for both social and cultural response

Table 2. A table showing the normal routes of water gain and loss in adults
at room temperature (23 OC)

WATER INTAKE

mL/day

In hypoosmolality:
o A reduction in plasma osmolality shifts water into
the cells and results in cell swelling
o Related primarily to swelling of brain cells
o A rapid fall in Posm can alter neurological function
and cause nausea, malaise, headache,
confusion, lethargy (after lethar-ef), seizures, and
coma
In hyperosmolality:
o Water is lost from the cells due to an increase in
Posm
o Symptoms include lethargy, weakness, seizures,
coma, and even death

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ANTIDIURETIC HORMONE

Aka vasopressin

Acts on the kidneys to regulate the volume and

osmolality of the urine

Acts on distal tubule and collecting ducts making them

more water permeable caused by the conformational
change in aquaporins that function in water transport

Synthesized in neuroendocrine cells located in the

supraoptic and paraventricular nuclei of the
hypothalamus

May be released or suppressed depending on plasma

ADH levels
o Low plasma ADH diuresis diluted urine
o High plasma ADH antidiuresis concentrated
urine

Two primary physiological regulators of ADH

secretion:
o Osmotic

Changes in plasma osmolality

plasma osmolality ADH

o Hemodynamic

Changes in blood volume

blood volume ADH

Other factors that affect ADH release:

o Stimulates ADH release: nausea, angiotensin II,
nicotine
o Inhibits ADH release: ANP, ethanol

Figure 2. A figure showing the anatomy of the hypothalamus and pituitary

gland (midsagittal section) depicting the pathways for antidiuretic hormone
(ADH) secretion and its regulatory pathways.

OSMOTIC CONTROL OF ADH SECRETION

Stimulus: changes in the fluid osmolality of body fluids

Play the most important role in regulating ADH

secretion

Osmoreceptors
o Behave as osmometers
o Sense changes in body fluid osmolality by either
shrinking or swelling
o Only respond to solutes that are effective
osmoles

Solutes that affect the function of

osmoreceptors

As opposed to ineffective osmoles (ex. urea)

3.3

Increase in body fluid osmolality

Stimulation of osmoreceptors

Stimulation of paraventricular and supraoptic nuclei

ADH release

Figure 3. A figure showing the osmotic control of ADH secretion the

effect of changes in plasma osmolality on plasma ADH levels under
constant blood volume and pressure.

HEMODYNAMIC CONTROL OF ADH SECRETION

Stimulus: changes in the blood volume and arterial

pressure

Low pressure baroreceptors (volume)

o Left atrium and large pulmonary vessels
o Respond to overall vascular volume because
they are located in the high capacitance side of
the circulatory system

High pressure baroreceptors (arterial pressure)

o Aortic arch and carotid sinus
o Respond to arterial pressure

Both types of baroreceptors are sensitive to stretch of

the wall of the structure in which they are located

Signals from these receptors are carried in afferent

fibers of the vagus and glossopharyngeal nerves to
the brainstem (solitary tract nucleus of the medullar
oblongata)

The sensitivity of the baroreceptor system is less than

that of the osmoreceptors
Decrease in blood volume

Decreased BP

Sensed by baroreceptors

Send signal to vasomotor center (medulla oblongata)

Processed signal proceed to paraventricular nuclei or

supraoptic nuclei

Posterior lobe of pituitary gland

ADH release

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o

Proximal tubule

Reabsorption of solutes results in the

reabsorption of a proportional amount of
water

Not participating in dilution or concentration

of urine
Thick ascending limb of the loop of Henle

Major site of water and solute separation

It is also called the diluting segment since

this portion of the tubular segment is
impermeable to water, even in the presence
of large amounts of ADH while sodium,
potassium,
and
chloride
are
avidly
reabsorbed

DIURESIS HYPOOSMOTIC URINE

The nephron must simply reabsorb solute from the

tubular fluid and not allow water to follow
Figure 4. A figure showing the hemodynamic control of ADH secretion the
effect of changes in blood volume or pressure on plasma ADH levels under
constant plasma omolality.

Alterations in blood volume or arterial pressure also

affect the secretion of ADH in response to changes in
body fluid osmolality
o blood volume or arterial pressure set point
shifts to lower osmolality values slope of
relationship is steeper
o blood volume or arterial pressure set point
shifts to higher osmolality values slope of
relationship is decreased

Figure 6. A figure showing the mechanism for the excretion of dilute urine.
ADH is absent, and the collecting duct is essentially impermeable to water.
Osmolality of the medullary interstitium is reduced during water diuresis.

1. Fluid entering the descending thin limb of the loop of

Henle from the proximal tubule is isosmotic with
respect to plasma.

Isosmotic nature of solute and water reabsorption

in the proximal tubule

Figure 5. A figure showing the interactions between osmolality and blood

volume and pressure stimuli on ADH secretion.

3.3

RENAL MECHANISMS FOR DILUTION

AND CONCENTRATION OF URINE
Under normal circumstances: excretion of water is
regulated separately from excretion of solutes
For regulation to occur, the kidneys must excrete
urine that is either hypoosmotic or hyperosmotic with
respect to body fluids
This ability to excrete urine of varying osmolality in
turn requires that solute be separated from water at
some point along the nephron

2. The descending thin limb is highly permeable to water

and much less so to solutes such as NaCl and urea.
(Note: Urea is an ineffective osmole in many tissues,
but it is an effective osmole in many portions of the
nephron).

As the fluid in the descending thin limb descends

deeper into the hyperosmotic medulla, water is
reabsorbed (via AQP1) as a result of the osmotic
gradient set up across the descending thin limb
by both NaCl and urea, which are present at high
concentrations in the medullary interstitium

Tubular fluid at the bend of the loop has an

osmolality equal to that of the surrounding
interstitial fluid

Although the osmolality of tubular and interstitial

fluid is similar at the bend of the loop, their
compositions differ:

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o
o

Concentration of NaCl in tubular fluid is

greater than surrounding interstitial fluid
Concentration of urea in tubular fluid is less
than that of interstitial fluid

3. The ascending thin limb is impermeable to water but

permeable to NaCl and urea.

As tubular fluid moves up the ascending limb:

o NaCl passively reabsorbed because [NaCl]
in tubular fluid > [NaCl] in interstitial fluid
o Urea passively diffuses into the tubular
fluid because [urea] in tubular fluid < [urea] in
interstitial fluid
o The net effect is that the volume of the
tubular fluid remains unchanged along the
length of the thin descending limb, but [NaCl]
decreases and [urea] increases.

As fluid ascend through the thin ascending limb, it

becomes less concentrated than the surrounding
interstitial fluid (tubular fluid dilution begins)

To maintain this: the countercurrent

exchanger (vasa recta) must be activated
1. Does not affect plasma osmolarity
2. Does not alter the osmolarity of the
medullary interstitium
Presence of ADH

Provide entry point for water to cross where

the movement is due to the very
hyperosmotic medullary interstitium

4. The thick ascending limb of the loop of Henle (diluting

segment) is impermeable to water and urea.

This portion of the nephron actively reabsorbs

NaCl from tubular fluid and thereby dilutes it

Fluid leaving the thick ascending limb is

hypoosmotic with respect to plasma
5. The distal tubule and cortical portion of the collecting
duct actively reabsorb NaCl but are impermeable to
urea.

In the absence of ADH, these segments are not

permeable to water

When ADH is absent or present at low levels (i.e.,

decreased plasma osmolality), the osmolality of
tubule fluid in these segments is reduced further
because NaCl is reabsorbed without water

Fluid entering the cortical portion of the collecting

duct is hypoosmotic with respect to plasma
6. The medullary collecting duct actively reabsorbs
NaCl.

Even in the absence of ADH, this segment is

slightly permeable to water and urea

Some urea enters the collecting duct from the

medullary interstitium, and a small volume of
water is reabsorbed
7. The urine excreted would be hypoosmotic due to this
process.

Urine will have an osmolality of 50 mOsm/kg

H2O and will contain low concentrations of NaCl
and urea
ANTI-DIURESIS HYPEROSMOTIC URINE

In producing concentrated (hyperosmotic) urine, the

following requirements must be met:
o Hyperosmotic medullary interstitium

Making the plasma osmolarity more than

normal

To establish this, the following must be

activated:
1. Urea recycling
2. Countercurrent multipliers

3.3

Figure 7. A figure showing the mechanism for the excretion of concentrated

urine. Plasma ADH levels are maximal, and the collecting ducts is highly
permeable to water. Under this condition, the medullary interstitial gradient
is maximal.

1 4. Steps are similar to the production of a diluted urine.

While reabsorption of NaCl by the ascending

think and thick limbs of the loop of Henle dilutes
the tubular fluid, the reabsorbed NaCl
accumulates in the medullary interstitium and
raises its osmolality

The accumulation of NaCl in the medullary

interstitium is important for the production of
concentrated urine hyperosmotic to plasma
o Provides the osmotic driving force for water
reabsorption by the collecting duct
o Countercurrent multiplication

Overall process by which the loop of

Henle (particularly the thick ascending
limb) generates the hyperosmotic
medullary interstitial gradient
5. Fluid reaching the collecting duct is hypoosmotic with
respect to the surrounding interstitial fluid.

Due to the NaCl reabsorption by the thick

ascending limb

In the presence of ADH: there is an increased

permeability of the last half of the distal tubule &
collecting duct to water
o This causes water to diffuse out of tubule
lumen and increase tubule fluid osmolality

This diffusion of water out of the lumen begins

the process of urine concentration

Although the fluid at this point has the same

osmolality as the fluid that entered the
descending thin limb, its composition has been
altered dramatically

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PHYSIOLOGY

Tubule fluid osmolality is accounted for by urea

and other nonreabsorbed solutes

6. The osmolality of the interstitial fluid in the medulla

progressively increases from the corticomedullary
junction.

Osmotic gradient exists between tubular fluid &

interstitial fluid along the entire medullary
collecting duct

In the presence of ADH: the osmolality of tubular

fluid increases as water is reabsorbed because
the medullary collecting duct is rendered
permeable to water

Cortical & outer medullary collecting duct is

impermeable to urea. This causes urea to remain
in tubular fluid thus increasing tubular fluid
concentration (tubular fluid conc. > interstitial fluid
conc.). Some of the urea diffuses out of the
tubule lumen into medullary interstitium

Maximal osmolality of fluid in the medullary

collecting duct is equal to the osmolality of the
surrounding interstitial fluid.
o Urea recycling

Done by the segments to regulate the

concentration of this solute, which affects
the overall urine output by the difference
of its permeability on each segment
7. Increase in ADH levels produces urine with high
concentration of urea and non-reabsorbed solutes.

Principal components: NaCl and urea

o Concentration of its principal components is
not uniform throughout the medulla

Table 3. A table showing the transport and permeability properties of

nephron segments involved in urine concentration and dilution.

PASSIVE PERMEABILITY*
Tubule
segment

Active
transport

NaCl

Urea

H2O

+++

+++

+++

Cortex

Medulla

++

Loop of Henle
Thin
descending limb
Thin
ascending limb
Thick
ascending limb
Distal tubule

Effect
of
ADH

Collecting duct
H2O
perm.
H2O
& urea
perm.

* Permeability is proportional to the number of plus signs: +, low permeability;

+++, high permeability; 0, impermeable

When a dilute urine is produced, the osmolality of the

medullary interstitium declines
o Due to a decrease in the concentration of urea
which reflects the washout by vasa recta and
diffusion of urea from the interstitium into the
tubular fluid within the medullary portion of the
collecting duct
As fluid moves along the nephron, water is
reabsorbed in the collecting duct and the urea
concentration in the tubular fluid increases
The urea-rich tubular fluid reaches the medullary
collecting duct (high urea permeability) and urea
accumulates
o In the presence of ADH: urea within the collecting
duct and the interstitium equilibrate
o Resultant urea concentration in urine is equal to
that of the medullary interstitium at the papilla
Some of the urea within the interstitium enters the thin
descending and thin ascending limbs of the loop of
Henle
o Urea is trapped in the nephron until it reaches the
medullary collecting duct, where it can reenter the
medullary interstitium
o Urea recycles from the interstitium to the nephron
and back into the interstitium
o This process of recycling serves to facilitate the
accumulation of urea in the medullary interstitium

Figure 8. A figure showing the mechanism of urea recycling.

MEDULLARY INTERSTITIUM
(Lifted from Berne and Levy, 2007)

Osmotic pressure of the medullary interstitium

provides the driving force for reabsorbing water from
both the descending thin limb of the loop of Henle and
the collecting duct

3.3

VASA RECTA COUNTERCURRENT EXCHANGE

Capillary network that supply blood to the medulla

Exists with juxtaposition with the loop of Henle

Highly permeable to solute and water

Form a parallel set of hairpin loops within the medulla

Functions:
o Returns NaCl and water reabsorbed from the
loop of Henle and collecting ducts to the
circulation

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o
o

Brings nutrients and oxygen to the medullary

nephron segments
Maintains medullary interstitial gradient (slow
blood flow to take out excess water and solutes):
Increase in vasa recta blood flow will decrease
the medullary gradient

Figure 10. A figure showing the action of ADH via the V2 receptor on a
principal cell of the late distal tubule and collecting duct.

Figure 9. A figure showing the vasa recta and its function as the
countercurrent exchanger.

The systems main goal is to maintain the

hyperosmotic medullary interstitium by altering its own
plasma contents resulting into producing more
concentrated urine
o Descending limb of vasa recta

Water is reabsorbed and solutes come in to

equilibrate the concentration with the
interstitium
o Ascending limb of vasa recta

Water comes in and solutes are reabsorbed

VASCULAR LOW PRESSURE/VOLUME SENSORS

About 5% to 10% of change in the blood pressure and

volume are necessary to evoke a response

Baroreceptors
o Located within the walls of the cardiac atria and
large pulmonary vessels
o Respond primarily to the fullness of the vascular
system
o Stimuli is sent to the vagus nerve then to the
solitary nucleus tract of the medulla oblongata
o Responds
to
the
decreased
firing
of
baroreceptors:

Sympathetic activation/outflow

ADH release due to decrease blood volume

o Responds to distention or increased firing of
baroreceptors:

Decreased sympathetic firing

Cardiac atria
o Responsible for the synthesis, storage, and
release of atrial natriuretic peptide (ANP) in the
event of an increased blood volume or venous
return
o The release of ANP is due to the increased
stretch or pressure in the right atrium.
o Mechanisms of ANP:

Dilates afferent arterioles

Increases blood flow towards the glomerulus

thereby increasing GFR

Inhibits ADH release preventing reabsorption

of water in the cortical collecting ducts

EFFECTS OF ADH ON UREA AND THE KIDNEYS

Effect of ADH on the kidneys:

Increases collecting duct permeability to water via

insertion of aquaporins

Effect of ADH on urea:

Increases collecting duct permeability to urea via

the activation of urea transporters

3.3

VOLUME SENSING SYSTEMS

Include various sensors involved in monitoring the
effective circulating volume
o A number of sensors are located in the vascular
system and monitor its fullness by responding to
changes in pressure
o Aka baroreceptors because they respond to
pressure-induced stretch of the vessel walls in
which they are located
These systems are activated once your body detects
overhydration or dehydration

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o

Ultimate response of ANP:

Increase in NaCl and water excretion in the

kidneys

Decrease in blood pressure

VASCULAR HIGH PRESSURE/VOLUME SENSORS

Baroreceptors
o Also present in the arterial side of the circulatory
system
o Located in the wall of the aortic arch, the carotid
sinus, and the afferent arterioles of the kidneys
o Responds to decrease in blood pressure:

Increasing sympathetic outflow

Increasing ADH release

o Sensitivity of the high-pressure baroreceptors is
similar to that of low-pressure baroreceptors
HEPATIC SENSORS

Not as important as the vascular sensors in

monitoring the effective circulating volume

The liver contains volume sensors that can modulate

renal NaCl excretion
o One type responds to pressure within the hepatic
vasculature (functions similarly to the low- and
high-pressure sensors)
o Another type responds to the concentration of
Na+ in the portal vein blood
o Afferent signals from both types are carried to the
CNS in the hepatic nerves (to the solitary tract
nucleus of the medulla oblongata)

pressure in hepatic vasculature and [Na+] in portal

vein renal sympathetic nerve activity renal
NaCl excretion
CNS SENSORS

Also appear to be not as important as the vascular

sensors

Thought to be located in the hypothalamus

Responds to:
o Alterations in the [Na+] of blood carried to the
brain in the carotid arteries
o Changes in [Na+] of cerebrospinal fluid CSF

[Na+] in carotid arteries or CSF renal

sympathetic nerve activity renal NaCl excretion

Renin secretion by the cells of the afferent

arterioles by activation of -adrenergic receptors

Renin ultimately increases circulating levels

of angiotensin II and aldosterone
o NaCl reabsorption along the nephron via direct
stimulation of activated -adrenergic receptors
The combined effect of these actions contributes to an
overall increase in NaCl excretion, an adaptive
response that works to restore euvolemia
With positive Na+ balance: (i.e., volume expansion),
renal sympathetic nerve activity is reduced, which
causes the reverse of the described effects

Notes:

Peritubular capillaries do not constrict because

capillaries have no smooth muscle.

Only the afferent & efferent arterioles constrict

decrease in the blood pressure within the capillaries

GFR

[NaCl] in the tubular fluid

JGA stimulation

Vasoconstriction of afferent arteriole

GFR and RBF normalize

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)

Renin
o Synthesized, stored, and released in the smooth
muscle cells in the afferent arteriole
o Functions solely as a proteolytic enzyme, which
cleaves angiotensinogen to produce angiotensin I

Angiotensin I
o Further cleaved to angiotensin II by angiotensinconverting enzyme (ACE) found on the surface of
vascular endothelial cells

VOLUME SENSOR SIGNALS

*See end of transcript for a summary of volume sensor signals
and activity.
RENAL SYMPATHETIC NERVES

Sympathetic nerve fibers innervate the afferent and

efferent arterioles of the glomerulus and the nephron
cells

The most important segment influenced by

sympathetic nerve activity is the proximal tubule

3.3

With negative Na+ balance: (i.e., volume depletion),

the volume sensors stimulate the renal sympathetic
activity and cause the following effects:
o Constriction of afferent & efferent arterioles by
activation of -adrenergic receptors

Vasoconstriction hydrostatic pressure

within the glomerular capillary lumen
GFR filtered load of Na+ to the nephrons

Figure 11. A schematic representation of the essential components of the

renin-angiotensin-aldosterone system.

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Angiotensin II
o Promotes secretion of aldosterone
Activation of RAAS results in a decrease in the
excretion of Na+ and water by the kidneys

DETERMINANTS OF RENIN SECRETION

Perfusion pressure
o When there is:

perfusion pressure renin secretion

perfusion pressure renin secretion

Sympathetic nerve activity

o sympathetic outflow to afferent arteriole
increased renin secretion

Delivery of NaCl (in ultrafiltrate) to macula densa

o NaCl to MD = GFR (via vasoconstrictor)
o NaCl to MD = GFR (via vasodilator)
FUNCTIONS OF ANGIOTENSIN II
1. Stimulation of aldosterone secretion by the adrenal
cortex
2. Arteriolar vasoconstriction, which increases blood
pressure

Potent vasoconstrictor not only of the afferent &

efferent arterioles of the kidney, but also of all the
arterioles in the body
3. Stimulation of ADH secretion (from hypothalamus)
and thirst
4. Enhancement of NaCl reabsorption by the proximal
tubule

Figure 12. A diagram showing of angiotensin II enhances NaCl reabsorption

by the proximal tubule.

Reabsorption in the proximal tubule:

Recall: Branches of the efferent arteriole are peritubular
capillaries which supply blood to the proximal tubules.

Angiotensin II constricts afferent & efferent arterioles

arteriolar resistance hydrostatic pressure
(HP) in the peritubular capillaries in relation to the HP
of the tubular fluid HP in the proximal tubule a
pressure gradient is established movement of
water & solutes will be from the proximal tubule to the
peritubular capillaries reabsorption of water and
NaCl to bring back isoosmoticity between proximal
tubule & peritubular capillaries

3.3

Note:
Dr. Solidum (2015):

If the afferent arterioles are constricted the NaCl

concentration of the tubular fluid will decrease.
Kapag mataasang NaCl in macula densa, the
response will be to decrease GFR. Because it is
being read by the macula densa namataas ang
GFR, kaya theres filtering of NaCl. If NaCl
concentration is decreased, macula densa try to
increase GFR

Another role of angiotensin II: vasa recta blood flow

washout of urea from medullary interstitium
longer time it takes for vasa recta to maintain
hyperosmotic medullary interstitium [urea] and
[Na+] in medullary interstitium gradient for NaCl
reabsorption

ALDOSTERONE

Steroid hormone produced by the glomerulosa cells of

the adrenal cortex

Functions:
o Reduces NaCl excretion by stimulating its
reabsorption by the thick ascending limb of the
loop of Henle, the distal tubules, and the
collecting duct
o Stimulates Na+ reabsorption in the distal tubule
and collecting duct

Transcellular reabsorption of Na+ by the

principal cell generates a lumen-negative
transepithelial voltage

Enhanced Na+ reabsorption from luminal

fluid increases the magnitude of this voltage
passive movement of Cl- from the lumen
to the blood NaCl reabsorption from the
tubular fluid
o Increases abundance of apical membrane Na-Cl
symporter in the early portion of distal tubule
o Increases abundance of Na+ channel in apical
membrane of principal cells in late portion of
distal tubule and collecting duct ( Na+ channels
activity)
NATRIURETIC PEPTIDES

Atrial natriuretic peptide (ANP)

o Produced and stored by atrial myocytes
o Relaxes vascular smooth muscles and promotes
NaCl and water excretion by the kidneys
o Released with atrial stretch, as would occur in
volume expansion
o Actions:

Vasodilation of the afferent & efferent

arterioles GFR and filtered load of Na+

Inhibition of renin secretion by the afferent

arteriole

Inhibition of aldosterone secretion by the

glomerulosa cells of the adrenal cortex
Inhibits renin secretion angiotensin
II-induced aldosterone secretion
Directly acts on the glomerulosa cells

Inhibition of NaCl reabsorption by the

collecting duct

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Due to reduced levels of aldosterone

Acts via cGMP inhibits Na+ channels
in the apical membrane of the cells

Inhibition of ADH secretion by the posterior

pituitary and ADH action on the collecting
duct
Results in a reduction in water
reabsorption by the collecting duct
excretion of water in the urine
A member of a family of peptides that plays a role
in the regulation of the cardiovascular and renal
systems, especially the effective circulating
volume

Renal natriuretic peptide (RNP)

o Aka urodilatin
o Produced by the kidneys
o Increases GFR and reduces collecting duct Na+
reabsorption
o Contributes to the ANP-induced natriuresis and
diuresis
o Stimulated by a rise in blood pressure
o Inhibits NaCl and water reabsorption across the
medullary portion of the collecting duct
o A more potent natriuretic and diuretic than ANP
Brain natriuretic peptide (BNP)
o Secreted by cardiac ventricular myocytes
o Can also be found in the CNS
o Relaxes vascular smooth muscles
o Promotes NaCl and water excretion by the kidney

CONTROL OF Na+ EXCRETION

DURING EUVOLEMIA

Euvolemia
o Requires a precise balance between the amount
of NaCl ingested and that excreted from the body
o In a euvolemic individual: daily urine NaCl
excretion = daily NaCl intake

In individuals who ingest large amounts of salt, renal

Na+ excretion can exceed 1000 mEq/day

Response to variations in dietary salt intake may take

several days
o During the transition period, excretion does not
match intake, and the individual will be in either
positive (intake > excretion) or negative (intake <
excretion) Na+ balance
o When Na+ balance is altered during these
transition periods, the ECF volume changes in
parallel

In positive balance: volume expansion

occurs (detected as an increase in body
weight)

In negative balance: volume contraction

occurs (detected as a decrease in body
weight)

Renal excretion will reach a new steady

state, and euvolemia will be reestablished as
NaCl excretion is once again matched to
intake
o Adaptation to large changes in NaCl intake
requires a longer time than does the adaptation
to small changes in intake

3.3

Regulated by aldosterone:
o aldosterone = Na+ reabsorption by the
principal cells
o aldosterone = Na+ reabsorption by the
principal cells

Figure 13. Segmental Na+ reabsorption. The percentage of the filtered load
of Na+ reabsorbed by each nephron segment is indicated.

In euvolemic subjects: the collecting duct is the main

nephron segment where Na+ reabsorption is adjusted
to maintain excretion at a level appropriate for dietary
intake
During euvolemia, Na+ handling by the nephron can
be explained by two general processes:
o Na+ reabsorption by the proximal tubule, loop of
Henle, and the distal tubule is regulated so that a
relatively constant portion of the filtered load of
Na+ is delivered to the collecting duct
o Reabsorption of this remaining portion of the
filtered load of Na+ by the collecting duct is
regulated so that the amount of Na+ excreted in
the urine matches the amount ingested in the diet

DURING VOLUME EXPANSION

Volume expansion over-hydration

During volume expansion: the volume sensors send

signals to the kidneys in NaCl and water
excretion

The signals acting on the kidneys include:

O Decreased activity of the renal sympathetic
nerves
O Release of ANP from atrial myocytes as well as
other natriuretic peptides (e.g., urodilatin in the
kidney)
O Inhibition of ADH secretion from the posterior
pituitary gland
O Decreased renin secretion decreased
production of angiotensin II
O Decreased secretion of aldosterone, due to
decreased angiotensin II levels and elevated
ANP levels

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Figure 15. Segmental Na+ reabsorption during euvolemia and during

volume expansion.

Figure 14. A diagram showing the integrated response to volume

expansion.

Where:
UNa+V
PNa+
R

3.3

= +

: Na+ excretion rate

: plasma [Na+]
: tubular reabsorption of Na+
Three general responses to volume expansion (Fig.
14):
o GFR increases

Primarily as a result of the decrease in

sympathetic nerve activity

sympathetic nerve activity vasodilation

of afferent & efferent arterioles
hydrostatic pressure in glomerular capillary
GFR filtered load of Na+

ANP and urodilatin also increase GFR by

dilating the afferent and constricting the
efferent arterioles
o Reabsorption of Na+ decreases in the proximal
tubule

Volume expansion sympathetic nerve

activity Na+ reabsorption

angiotensin II activity Na+ reabsorption

by proximal tubule

hydrostatic pressure in glomerular capillary

hydrostatic pressure in peritubular
capillaries water and solute reabsorption
o Na+ reabsorption decreases in the collecting duct

Both the increase in the filtered load and

decrease
in
proximal
tubule
NaCl
reabsorption result in the delivery of large
amounts of NaCl to loop of Henle and the
distal tubule

sympathetic nerve activity & low

aldosterone levels NaCl reabsorption by
this nephron segment

Amount of Na+ delivered to the beginning of

the collecting duct is increased compared

DURING VOLUME CONTRACTION

Volume contraction dehydration

During volume contraction: the volume sensors send

signals to the kidneys Na+ and water excretion

The signals acting on the kidneys include:

o Increased renal sympathetic nerve activity
o Increased secretion of renin angiotensin II
levels secretion of aldosterone by the
adrenal cortex
o Inhibition of ANP secretion by the atrial myocytes
and urodilatin production by the kidneys
o Stimulation of ADH secretion by the posterior
pituitary gland

Figure 16. A diagram showing the integrated response to volume

contraction.

= +

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PHYSIOLOGY

Three general responses to volume contraction (Fig.

16):
o GFR decreases

sympathetic
nerve
activity

vasoconstriction of afferent & efferent

arterioles hydrostatic pressure in
glomerular capillary GFR filtered
load of Na+
o Na+ reabsorption by the proximal tubule is
increased

sympathetic nerve activity & angiotensin II

proximal tubule Na+ reabsorption

hydrostatic pressure in glomerular capillary

hydrostatic pressure in peritubular
capillaries water and solute reabsorption
o Na+ reabsorption by the collecting duct is
enhanced

Reduction in the filtered load and enhanced

proximal tubule NaCl reabsorption result in
decreased delivery of Na+ to loop of Henle
and the distal tubule

sympathetic nerve activity & high

aldosterone levels NaCl reabsorption by
these nephron segments exists

Fraction of the filtered load of Na+

reabsorbed by these segments is less that
seen in the euvolemic state

The net result is that less Na+ is delivered to

the beginning of the collecting duct

Table 4. A table showing the summary of signals involved in the control of

renal NaCl and water excretion.

REFERENCES:
1.
2.
3.
4.
5.

Lecture Notes
1D 2019. (2016). Physiology 3.01b renal physiology II
[PDF]
Solidum, F. (2017). Renal Physiology II [PowerPoint
slides]
Hall, J.E. (2016). Guyton and Hall textbook of medical
physiology (13th ed.). USA: Elsevier
Berne, R.M., Levy, M.N., Koeppen, B.M., & Stanton,
B.A. (2007). Physiology (5th ed.). USA: Elsevier
TRANSERS MESSAGE

Kapit lang mga bes! Kaya natin ito! Good luck sa ating
mga exams and requirements!
CASE PERCEPTOR BE LIKE:

Figure 17. Segmental Na+ reabsorption during euvolemia and during

volume contraction.

3.3

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