Control of ECF
osmolality and
volume
MAIN DIFFERENCES BETWEEN ICF AND ECF
• More Na+ in ECF
• More K+ in ICF
• More Cl- in ECF
• More PO4, HCO3, and Pr- in ICF
These differences are maintained by
transport processes in the cell membrane
Distribution of Na+ and K+ in the body
Total intracellular
Total extracellular
Plasma
Interstitial fluid
Connective tissue
Bone
Transcellular
Na+
9.0
91.0
11.2
29.0
11.7
36.5
2.6
K+
89.6
10.4
0.4
1.0
0.4
7.6
1.0
ECF volume
20% of body weight
14 L (in a 70 kg man)
3.5 L plasma; 10.5 L interstitial fluid
Measured by using inulin, mannitol or
sucrose
Osmolar concentration of plasma:
290 mosm/L - 142 mEq/L [Na+]
Tonicity – Osmolality of a solution in
relation to plasma - isotonic, hypertonic,
hypotonic
0.9% saline is isotonic
270 mosm/L is contributed by Na+, Cland HCO3Plasma proteins contribute less than 2
mosm/L (28 mm Hg oncotic pressure)
Ranges of salt and water intake and
excretion:
a. Salt intake from 50 mg to 25 g/day
b. Water excretion from 400 ml to 25 l/day
Total body sodium is relatively constant.
Freely filtered
Reabsorbed but not secreted
Therefore,
Na+ excretion = Na+ filtered – Na+ reabsorbed
= (GFR X Pna) - Na+ reabsorbed
Pna is relatively constant
Therefore control is exerted by
GFR
Na+ reabsorption
Sensors:
1. Extrarenal baroreceptors
Carotid sinuses
Arteries
Great veins
Atria
2. Renal juxtaglomerular apparatus
Efferents:
1. Renal sympathetic nerves
2. Macula densa renin angiotensin II 
aldosterone
Control of GFR:
1. Angiotensin II efferent arteriolar
constriction  PGC
2. Renal sympathetic nerves Na+ 
adrenergic receptors Constriction of
afferent and efferent arterioles  PGC
Osmoreceptor ADH mechanisms
Renal handling of NaCl and water:
NaCl & H2O are freely filterable at the
glomerulus.
There is extensive tubular reabsorption but no
tubular secretion.
Na+ reabsorption is driven by the basolateral
Na+/K+-ATPase and is responsible for the major
energy expenditure in kidney.
Mechanisms of Sodium Reabsorption:
a. Na+ entry per se by SFD
b. Na+ co-transported with
glucose or organic acids
c. Na+ counter-transported
with intracellular H+
d. Na+ co-transported with ClNa+
Cl-
e.
following
diffusion
through tight junctions
Na+
Gl
Na+
H
Na+
Cl
Proximal Tubule:
The PT is highly permeable to water.
Reabsorbs ~ 65% of filtered sodium (active
transport) and water plus organic nutrients etc.
Water reabsorption is passive, along osmotic
gradients and keeps pace with solute.
Therefore, the [Na+] remains virtually constant
through the PT, whereas the mass of Na+ is
reduced by 65%.
Movement of water is facilitated by the presence
of water channels - aquaporin 1, in the apical
membranes of proximal tubule epithelial cells
Late in the PT, some Na+ is also reabsorbed by
simple diffusion and solvent drag.
Cl- initially lags behind and the concentration
gradient is established by water reabsorption.
Accordingly, in the middle and late PT, Cl- is the
major anion coupled with Na+.
Solute transport in PCT
Na+
S
Solute
2 K+
3 Na+
At the end of the PT:
1. Luminal osmolality is isotonic
2. The concentration of Cl- is higher
3. The concentration of HCO3- is lower
Loop of Henle:
Reabsorbs a further 25% of the filtered NaCl plus
15% of filtered water.
The descending limb does not reabsorb NaCl.
The entire ascending limb of loop of Henle does.
a. thin ALH  reabsorption of of NaCl
b. thick ALH  co-transport of Cl- & Na+ (carrier
transports Na+, K+, 2Cl-)
Transport processes in the thick ascending limb
+
K+
Na+
C
H2O+CO2H2CO3
H+
Na+
2ClK+
A
H+ + HCO3
2
3 Na+
K+
HCO3-
The ALH, unlike the PT, reabsorbs more solute
than water, therefore delivers hypotonic urine
to the distal tubule.
The decrease [Na+] is greater than the decrease in
osmolality due to the addition of urea to lumen
in the ALH.
Drugs that inhibit transport of Cl- in the ALH
therefore also inhibit Na+ reabsorption
producing diuresis.
Distal Tubule & Collecting Duct:
NaCl reabsorption continues along the DT & CT so
that the final urine contains ~ 1% of the filtered
mass.
H2O permeability of the early DT is extremely low
and not subject to physiological control.
Accordingly almost no water is reabsorbed in the
early distal segment.
H2O permeability of the late DT:
Water permeability of distal tubule and initial
collecting tubule, is also extremely low.
However under the influence of ADH it becomes
highly water permeable.
Further removal of solute in the EDT presents the
LDT with markedly hypotonic urine containing
even less Na+
Removal of Na+ continues in the LDT and
collecting system, so that the final urine may
contain virtually no Na+.
Anti-diuretic hormone:
ADH (antidiuretic hormone), vasopressin or
arginine vasopressin (AVP) is the major
regulator of urine osmolality and urine volume.
ADH is a nonapeptide produced by neurons in the
supraoptic and paraventricular nuclei of the
hypothalamus.
The axon terminals of these neurons reside in the
posterior pituitary.
ADH is stored in these axon terminals.
When ADH is released from the posterior pituitary
it causes the kidney to produce urine that is
high in osmolality and low in volume.
In the absence of ADH the kidney tends to produce
a large volume of urine with low osmolality.
Total solute excretion is relatively constant over a
wide range of urine flow rates and osmolalities.
Control of ADH release:
1. Increased osmolality of ECF is a powerful
stimulus for ADH release: a 1% change in
osmolality induces significant increase in ADH
release.
Hypothalamic supra-optic and paraventricular
nuclei respond to increased osmolality of ECF by
producing ADH.
As a result of this high sensitivity, responses to
increased osmolality occur rapidly.
Control of ADH release:
2. Volume:
In a volume-depleted individual, the release of
ADH is more sensitive to increased osmolality.
In a volume-expanded state, ADH release is less
sensitive to increases in osmolality.
3. Decreased blood pressure or blood volume
also enhance ADH release, but not with such
high sensitivity: 5 to 10% changes are required
to alter ADH secretion.
Effects of ADH on the kidney:
ADH increases the water permeability of the
epithelial cells of late distal tubules and the
collecting tubules
May also increase NaCl absorption in the thick
ascending limb of the loop of Henle.
ADH also increases the urea permeability of the
inner medullary collecting tubules.
Action of ADH:
Binds to receptors in the basolateral membrane,
causing increased cAMP.
This results in rapid insertion of aquaporin-2
protein channels into the luminal membrane of
principal cells.
The water channel proteins are present in
preformed intracellular vesicles, so this up
regulation of water permeability can occur
quickly.
The water channels can be rapidly re-internalized
when ADH is no longer present.
Effect of ADH on collecting tubule cells
H2O
cAMP
Adenyl cyclase
2 K+
Aquaporin-2
3 Na+
A
D
H
Summary:
 osmolality
Supraoptic &
paraventricular
Nuclei
Stimulation of
osmoreceptors
in anterior
hypothalamus
Posterior pituitary
ADH
 permeability of LDT, CCD, MCD to H2O
Summary of handling of Na+ by the kidney
Glomerular
filtrate
PCT
26 000
mEq/Day
65%
Active transport
Thick
ascending
loop
LDCT
27%
Active transport
8%
Aldosterone
Cortical
collecting duct
Aldosterone
Thirst mechanism
Thirst (conscious desire for water):
Under hypothalamic osmoreceptor
control
Water intake is regulated by
- increased plasma osmolality
- decreased ECF volume
- psychological factors
Stimulus:
Intracellular dehydration due to increased
osmolar concentration of ECF
Excessive K+ loss  Low intracellular K+
in osmoreceptors
Mechanism is activated by
The arterial baroreceptor reflex  BP
The volume receptors- low pressure
receptors in atria;  CVP
Angiotensin II
Increased Na+ in CSF
Hypertonicity
Hypovolaemia
Osmoreceptors
Baroreceptors
Angiotensin II
Hyp
Thirst
Thirst center:
Subfornical organ
Organum vasculosum of the lamina
terminalis
Other factors regulating water intake:
Psycho-social
Dryness of pharyngeal mucous
membrane
? Gastrointestinal pharyngeal metering
Renin-angiotensin
–aldosterone
system
Renin:
Produced by
Juxtaglomerular cells – located in media of
afferent arterioles
Lacis cells – junction between afferent and
efferent arterioles
Factors affecting renin secretion:
Stimulatory
Increased sympathetic activity via renal
nerves
Increased circulating catecholamines
Prostaglandins
Inhibitory
Increased Na+ and Cl- reabsorption in
macula densa
Angiotensin II
Vasopressin
Renin

Angiotensinogen Angiotensin I

Angiotensin-converting enzyme
Angiotensin I Angiotensin II

Adrenal cortex Aldosterone
Actions of angiotensin II
Arteriolar vasoconstriction and rise in
SBP and DBP
On adrenal cortex to produce
aldosterone
Facilitates release of noradrenaline
Contraction of mesangeal cells - GFR
Brain -  sensitivity of baroreflex
Brain - increases water intake (AP, SSFO,
OVLT)
Actions of aldosterone:
Increased reabsorption of Na+ from urine,
sweat, saliva and GIT – ECF volume
expansion
Kidney P cells – increased amounts of Na+
are exchanged for K+ and H+
Salt appetite
ECF Na+
 Blood volume
Hypothalamic centers
 Salt appetite
Potassium
excretion
Renal handling of K+:
800 mEq/day enter the filtrate
100 mEq/day is secreted
PCT – reabsorption
DCT and CD – both reabsorption and
secretion
Secretion is mainly by the Principal cells
Aldosterone
K+
Nucleus
ENaC
2 K+
Na+
3 Na+
ENaC = epithelial sodium channels
Control by P cells
1. Na:K pump
2. Electrical gradient from blood to lumen
3. Permeability of luminal cell membrane
to K+
Stimulation
Inhibition
 ECF K+
Acidosis
 Aldosterone
 Urine flow rate
The End