Fluid Compartments of the Body

Intracellular and Extracellular Space/Fluid

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

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 = ¼ of extracellular water 1/4 x 12L = 3 L

™ Interstitial fluid = ¾ extracellular water 3/4 x 12L = 9 L

60:40:20 rule

1
 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).

2
¾ osmolarity (Osm) is defined as moles of dissolved
solute per volume of solution in liters

¾ 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.

3
 Major Function of Kidney:
Homeostasis

Maintain optimal fluid environment in

the body

™ Regulates H20 - 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)

Ingestion + Production = Excretion + Consumption

(External gain) (Internal gain) (External loss) (Internal loss)
™food ™metabolism ™urine ™metabolism
™air ™stool
™expired air
™sweat

4
 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

5
 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)

6
 Daily Filtered Load of Na+
(>99% of which must be reabsorbed)

Amounts of Na+ reabsorbed by

various segments of the nephron
GFR=180 L/day
PNa=142 mmol/L 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load

8% remaining
1
≈17,000 mmol/day
67% of filtered load
3% remaining
33% remaining

2
≈6,400 mmol/day
25% of filtered load

4
≈700 mmol/day
<3% of filtered load

.
V=1500 ml/day Urinary Na excretion ≈100 mmol/day
UNa=67 mmol/L 0.4% of filtered load

7
 Amounts of Na+ reabsorbed by
various segments of the nephron
GFR=180 L/day
PNa=142 mmol/L = 1500g salt 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg
3% remaining
33% remaining

2
≈6,400 mmol/day
25% of filtered load

4
≈700 mmol/day
<3% of filtered load

.
V=1500 ml/day Urinary Na excretion ≈100 mmol/day
UNa=67 mmol/L 0.4% of filtered load 4grams

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

8
 Amounts of Na+ reabsorbed by
various segments of the nephron
GFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na ≈ 25,500 mmol/day

1
≈17,000 mmol/day
67% of filtered load
1Kg

33% remaining

Sodium Absorption in Proximal Tubule

SGLT1
Sodium Glucose
Cotransporter

9
 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

10
 Amounts of Na+ reabsorbed by
various segments of the nephron
GFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na ≈ 25,500 mmol/day

1
Osmolarity at end of
≈17,000 mmol/day proximal tubule:
67% of filtered load
1Kg

33% remaining a) 180 mOsm

b) 142 mOsm
c) 290 mOsm

Answer: ?

Osmolarity of the filtrate has not changed at this point

Iso-osmotic movement of Na and water

Proximal tubule
NHE3 AQP1

Glomerulus

11
 Thin Descending Limb
™Only H20 transport in this region

™Aquaporin-1 present

™No Na movement in this segment

Only H20 Movement in Descending Limb

Proximal tubule
NHE3 AQP1

Glomerulus

Thin Descending
Limb of
AQP1
Henle’s Loop

12
 Amounts of Na+ reabsorbed by
various segments of the nephron: TAL
GFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na ≈ 25,500 mmol/day

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg

33% remaining
2
≈6,400 mmol/day
25% of filtered load
371grams

.
V=1500 ml/day Urinary Na excretion ≈100 mmol/day
UNa=67 mmol/L 0.4% of filtered load 4grams

Sodium Absorption in Thick Ascending Loop

X Bumetanide/
Furosemide

NKCC2 Diuretics (cause increased

Sodium Potassium
urine flow) used to treat
2Chloride Cotransporter
high blood pressure

NHE3
Sodium Hydrogen
Exchanger

13
 Amounts of Na+ reabsorbed by
various segments of the nephron: TAL
GFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na ≈ 25,500 mmol/day

1 8% remaining?……higher
≈17,000 mmol/day
67% of filtered load
1Kg

33% remaining
2
≈6,400 mmol/day
25% of filtered load
371grams

.
V=..increase
Urinary Na excretion load with diuretic??? UNa=increase

Uses a lot of energy, dilutes urine

Proximal tubule
NHE3 AQP1 Thick
Ascending
Limb
Glomerulus

Thin Descending
Limb of
AQP1
Henle’s Loop

14
 Amounts of Na+ reabsorbed by
various segments of the nephron: DCT
GFR=180 L/day
PNa=142 mmol/L = 1500g salt 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load
75grams

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg
3% remaining
33% remaining

2
≈6,400 mmol/day
25% of filtered load
371 grams

Sodium Absorption in Distal Convoluted Tubule

X Thiazides

Diuretic used to treat

NaCl/TSC high blood pressure
Sodium Chloride
Cotransporter/
Thiazide sensitive
cotransporter

15
 Amounts of Na+ reabsorbed by
various segments of the nephron: DCT
GFR=180 L/day
PNa=142 mmol/L = 1500g salt 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load
75grams

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg
% remaining
3% remaining
33% remaining increases

2
≈6,400 mmol/day
25% of filtered load
371 grams

Urinary Na excretion increases with diuretic

Distal Convoluted
Proximal tubule Tubule
NHE3 AQP1 Thick
Ascending
Limb
Glomerulus

Thin Descending
Limb of
AQP1
Henle’s Loop

16
 Amounts of Na+ reabsorbed by
various segments of the nephron: CD
GFR=180 L/day
PNa=142 mmol/L = 1500g salt 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg
3% remaining
33% remaining

2
≈6,400 mmol/day
25% of filtered load

4
≈700 mmol/day
<3% of filtered load
40grams

.
V=1500 ml/day Urinary Na excretion ≈100 mmol/day
UNa=67 mmol/L 0.4% of filtered load 4grams

Sodium Absorption in Collecting Duct

X Amiloride
ENaC
Epithelial
Diuretic used to treat
Sodium Channel high blood pressure
(potassium sparing)

Single mutation in ENaC

can cause Liddle’s disease
Genetic hypertension

17
 Amounts of Na+ reabsorbed by
various segments of the nephron: CD
GFR=180 L/day
PNa=142 mmol/L = 1500g salt 3
Filtered Load of Na ≈ 25,500 mmol/day ≈1,300 mmol/day
5% of filtered load

1 8% remaining
≈17,000 mmol/day
67% of filtered load
1Kg
3% remaining
33% remaining

2
≈6,400 mmol/day
25% of filtered load

4
≈700 mmol/day
<3% of filtered load
40grams

Urinary Na excretion increases with diuretic

Distal Convoluted
Proximal tubule Tubule
NHE3 AQP1 Thick
Ascending
Limb
Glomerulus

Collecting duct

Thin Descending
Limb of
AQP1
Henle’s Loop

18
 Collecting Duct Water
Permeability is regulated
Vasopressin (VP)
AVP (Arginine Vasopressin)

Or also called
ADH – Anti Diuretic Hormone

Vasopressin Secretion Pathway

Pituitary
Osmoreceptors

Hypothalamus
Baroreceptor inputs

ADH

Urine is concentrated and flow reduced

19
Concentrating mechanism when vasopressin is low
NHE3 +AQP1

AQP1

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

20
High vasopressin = Formation of concentrated urine
NHE3 + AQP1

AQP2

AQP1
A
Q
P
2

High vasopressin = Formation of concentrated urine

NHE3 + AQP1

AQP2

AQP1
A
Q
P
2

21
 Vasopressin signaling in collecting duct

AQP3/AQP4
AQP2 H 20
VP V2 H 20
AQP2

Gs

BLOOD ATP LUMEN

AC
VI
cAMP

PKA

?
Gene regulation Nucleus

22