1

Fluid Compartments of the Body

Intracellular space is the space within cell
membranes
Extracellular space is the space between cells
(interstitial fluid) and within blood vessels
(plasma)
Electrolyte composition (e.g. salt and water
content) of interstitial fluid and plasma is
identical
Intracellular and Extracellular Space/Fluid
Compartmentalization of Body
Fluids
Total body water (TBW)= 60% of body weight 60% x 60kg = 36L
Intracellular water (ICF) = 2/3 of total body water 2/3 x 36L = 24 L
Extracellular water (ECF) = 1/3 of total body water 1/3 x 36L = 12 L
Extracellular Fluid
Plasma water = of extracellular water 1/4 x 12L = 3 L
Interstitial fluid = extracellular water 3/4 x 12L = 9 L
60:40:20 rule
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Osmotic Composition of Major
Fluid Compartments
Osmolarity
Osmoles refers to the number of impermeable particles
dissolved in a solution, regardless of charge. This is
important for determining the diffusional movement
of water.
For substances that maintain their molecular structure
when they dissolve (e.g. glucose), the osmolarity and
the molarity are essentially the same.
For substances that dissociate when they dissolve, the
osmolarity is the number of free particles times the
molarity. Thus for a pure NaCl solution, a 1 Molar
solution would be 2 Osmolar (1 for Na, and 1 for Cl).
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osmolarity (Osm) is defined as moles of dissolved
solute per volume of solution in liters
In human plasma the concentration of dissolved
particles is about 290 X 10-3 M.
Osmotic gradient
Osmotic gradient is required in order to achieve
net water movement between ECF and ICF
Because water can move freely between
compartments, a change in the osmolarity of a
single compartment results in redistribution of
TBW (total body weight) between compartments
(driven by the osmotic gradient) until osmotic
equilibrium is restored.
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Major Function of Kidney:
Homeostasis
Maintain optimal fluid environment in
the body
Regulates H
2
0 - osmolarity
NaCl
Most ions
Maintains plasma volume = long term
regulation of blood pressure
Balance Concept
Net gain must equal net loss if substance remains in a
steady state
(e.g. water, salt)
Consumption
(Internal gain)
metabolism
(External gain)
food
air
(External loss)
urine
stool
expired air
sweat
Ingestion Production Excretion
(Internal loss)
metabolism
+
+ =
5
Water balance
Electrolytes and Water
Salt is not produced or consumed by the
body so balance is maintained by regulating
the amounts excreted in body fluids (urine,
sweat, stool) such that they equal the
amounts ingested (ingestion = excretion)
Kidneys maintain water and salt balance in
the body by regulating output of both in the
urine
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Absorption Mechanisms of Salt
and Water in the Renal Tubule
The glomerulus has a high filtration rate: about
180 litres a day
(Glomerular Filtration Rate-GFR)
Sodium is high in the extracellular fluid and low
inside cells (intracellular).
Therefore Na is high in plasma, and when
plasma is filtered by the glomerulus, the
resulting filtrate is also high in sodium
Little Na reaches the final urine, so the bulk of
Na, and following water, is absorbed as the
filtrate travels along the renal nephron (tubule)
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Daily Filtered Load of Na Daily Filtered Load of Na
+ +
(>99% of which must be reabsorbed) (>99% of which must be reabsorbed)
Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the nephron various segments of the nephron
GFR=180 L/day
P
Na
=142 mmol/L
Filtered Load of Na 25,500 mmol/day
700 mmol/day
<3% of filtered load
4
V=1500 ml/day
U
Na
=67 mmol/L
.
Urinary Na excretion 100 mmol/day
0.4% of filtered load
17,000 mmol/day
67% of filtered load
1
33% remaining
6,400 mmol/day
25% of filtered load
2
8% remaining
1,300 mmol/day
5% of filtered load
3
3% remaining
8
Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the nephron various segments of the nephron
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
<3% of filtered load
4
V=1500 ml/day
U
Na
=67 mmol/L
.
Urinary Na excretion 100 mmol/day
0.4% of filtered load 4grams
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
2
8% remaining
1,300 mmol/day
5% of filtered load
3
3% remaining
Expression of Na and Water
Transporters/Channels Along
Nephron
Expression of Na transporters is specific for
each segment of the nephron
Some segments are only permeable to
water, other are impermeable to water,
some are permeable to both Na and water
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the nephron various segments of the nephron
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
Sodium Absorption in Proximal Tubule
SGLT1
Sodium Glucose
Cotransporter
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Renal tubules have a finite capacity
to reabsorb glucose
If glucose concentrations in the blood exceed
the tubular transport capacity of SGLT
glucose is seen in the urine
Urine test for diabetes glucose stick
Sodium Absorption in Proximal Tubule
SGLT1
Sodium Glucose
Cotransporter
NHE3
Sodium Hydrogen
Exchanger
NaPi2
Sodium Phosphate
Cotransporter
AQP1
Aquaporin 1
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the nephron various segments of the nephron
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
Osmolarity of the filtrate has not changed at this point
Osmolarity at end of
proximal tubule:
a) 180 mOsm
b) 142 mOsm
c) 290 mOsm
Answer: ?
NHE3 AQP1
Glomerulus
Proximal tubule
Iso-osmotic movement of Na and water
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Thin Descending Limb
Only H20 transport in this region
Aquaporin-1 present
No Na movement in this segment
NHE3
AQP1
AQP1
Glomerulus
Proximal tubule
Thin Descending
Limb of
Henles Loop
Only H20 Movement in Descending Limb
13
Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: TAL : TAL
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
V=1500 ml/day
U
Na
=67 mmol/L
.
Urinary Na excretion 100 mmol/day
0.4% of filtered load 4grams
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
371grams
2
8% remaining
NHE3
Sodium Hydrogen
Exchanger
NKCC2
Sodium Potassium
2Chloride Cotransporter
Sodium Absorption in Thick Ascending Loop
Bumetanide/
Furosemide
X
Diuretics (cause increased
urine flow) used to treat
high blood pressure
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: TAL : TAL
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
V=..increase
U
Na
=increase
.
Urinary Na excretion load with diuretic???
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
371grams
2
8% remaining?higher
NHE3
AQP1
AQP1
Glomerulus
Proximal tubule
Thin Descending
Limb of
Henles Loop
Thick
Ascending
Limb
Uses a lot of energy, dilutes urine
15
Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: DCT : DCT
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
371 grams
2
8% remaining
1,300 mmol/day
5% of filtered load
75grams
3
3% remaining
NaCl/TSC
Sodium Chloride
Cotransporter/
Thiazide sensitive
cotransporter
Sodium Absorption in Distal Convoluted Tubule
Thiazides
X
Diuretic used to treat
high blood pressure
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: DCT : DCT
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
371 grams
2
8% remaining
1,300 mmol/day
5% of filtered load
75grams
3
3% remaining % remaining
increases
Urinary Na excretion increases with diuretic
NHE3
AQP1
AQP1
Glomerulus
Proximal tubule
Thin Descending
Limb of
Henles Loop
Thick
Ascending
Limb
Distal Convoluted
Tubule
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: CD : CD
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
<3% of filtered load
40grams
4
V=1500 ml/day
U
Na
=67 mmol/L
.
Urinary Na excretion 100 mmol/day
0.4% of filtered load 4grams
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
2
8% remaining
1,300 mmol/day
5% of filtered load
3
3% remaining
ENaC
Epithelial
Sodium Channel
Sodium Absorption in Collecting Duct
Amiloride
X
Diuretic used to treat
high blood pressure
(potassium sparing)
Single mutation in ENaC
can cause Liddles disease
Genetic hypertension
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Amounts of Na Amounts of Na
+ +
reabsorbed by reabsorbed by
various segments of the various segments of the nephron nephron: CD : CD
GFR=180 L/day
P
Na
=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
<3% of filtered load
40grams
4
17,000 mmol/day
67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day
25% of filtered load
2
8% remaining
1,300 mmol/day
5% of filtered load
3
3% remaining
Urinary Na excretion increases with diuretic
NHE3
AQP1
AQP1
Glomerulus
Proximal tubule
Thin Descending
Limb of
Henles Loop
Thick
Ascending
Limb
Distal Convoluted
Tubule
Collecting duct
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Collecting Duct Water
Permeability is regulated
Vasopressin (VP)
AVP (Arginine Vasopressin)
Or also called
ADH Anti Diuretic Hormone
Pituitary
ADH
Osmoreceptors
Baroreceptor inputs
Vasopressin Secretion Pathway Vasopressin Secretion Pathway
Urine is concentrated and flow reduced
Hypothalamus
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NHE3 +AQP1
AQP1
Concentrating mechanism when vasopressin is low
Collecting Duct Water
Permeability is regulated
ADH Anti Diuretic Hormone
also called vasopressin
Activates the insertion of the water channel,
aquaporin-2, into the apical membrane of
the collecting duct
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High vasopressin = Formation of concentrated urine High vasopressin = Formation of concentrated urine
NHE3 + AQP1 NHE3 + AQP1
AQP1 AQP1
AQP2 AQP2
A A
Q Q
P P
2 2
High vasopressin = Formation of concentrated urine High vasopressin = Formation of concentrated urine
NHE3 + AQP1 NHE3 + AQP1
AQP1 AQP1
AQP2 AQP2
A A
Q Q
P P
2 2
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Vasopressin signaling in collecting duct
VP
BLOOD LUMEN
AQP2
V2
Gs
AC
VI
ATP
PKA
cAMP
H20
H20
AQP2
Nucleus
?
AQP3/AQP4
Gene regulation
?