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8/11/2019 Renal Lecture
1/22
Fluid Compartments of the Body
Intracellular space is the space within cellmembranes
Extracellular space is the space between cells(interstitial fluid) and within blood vessels(plasma)
Electrolyte composition (e.g. salt and watercontent) of interstitial fluid and plasma isidentical
Intracellular and Extracellular Space/Fluid
Compartmentalization of BodyFluids
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
8/11/2019 Renal Lecture
2/22
Osmotic Composition of Major
Fluid Compartments
Osmolarity
Osmoles refers to the number of impermeable particlesdissolved in a solution, regardless of charge. This isimportant for determining the diffusional movementof water.
For substances that maintain their molecular structurewhen they dissolve (e.g. glucose), the osmolarity andthe molarity are essentially the same.
For substances that dissociate when they dissolve, theosmolarity is the number of free particles times themolarity. Thus for a pure NaCl solution, a 1 Molarsolution would be 2 Osmolar (1 for Na, and 1 for Cl).
8/11/2019 Renal Lecture
3/22
osmolarity (Osm) is defined as moles of dissolvedsolute 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 asingle compartment results in redistribution of
TBW (total body weight) between compartments
(driven by the osmotic gradient) until osmotic
equilibrium is restored.
8/11/2019 Renal Lecture
4/22
Major Function of Kidney:
Homeostasis
Maintain optimal fluid environment inthe body
Regulates H20 - osmolarity NaCl
Most ions Maintains plasma volume = long termregulation of blood pressure
Balance Concept
Net gain must equal net loss if substance remains in asteady 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
++ =
8/11/2019 Renal Lecture
5/22
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
8/11/2019 Renal Lecture
6/22
Absorption Mechanisms of Salt
and Water in the Renal Tubule
The glomerulus has a high filtration rate: about180 litres a day
(Glomerular Filtration Rate-GFR)
Sodium is high in the extracellular fluid and lowinside cells (intracellular).
Therefore Na is high in plasma, and whenplasma is filtered by the glomerulus, theresulting filtrate is also high in sodium
Little Na reaches the final urine, so the bulk ofNa, and following water, is absorbed as thefiltrate travels along the renal nephron (tubule)
8/11/2019 Renal Lecture
7/22
Daily Filtered Load of NaDaily Filtered Load of Na++
(>99% of which must be reabsorbed)(>99% of which must be reabsorbed)
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed byvarious segments of the nephronvarious segments of the nephron
GFR=180 L/day
PNa=142 mmol/L
Filtered Load of Na 25,500 mmol/day
700 mmol/day
8/11/2019 Renal Lecture
8/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of the nephronvarious segments of the nephronGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
8/11/2019 Renal Lecture
9/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of the nephronvarious segments of the nephronGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day67% of filtered load
1Kg
1
33% remaining
Sodium Absorption in Proximal Tubule
SGLT1Sodium GlucoseCotransporter
8/11/2019 Renal Lecture
10/22
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
SGLT1Sodium GlucoseCotransporter
NHE3Sodium HydrogenExchanger
NaPi2Sodium Phosphate
Cotransporter
AQP1Aquaporin 1
8/11/2019 Renal Lecture
11/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of the nephronvarious segments of the nephronGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day67% 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
8/11/2019 Renal Lecture
12/22
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
8/11/2019 Renal Lecture
13/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: TAL: TALGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
V=1500 ml/day
UNa=67 mmol/L
.Urinary Na excretion 100 mmol/day
0.4% of filtered load 4grams
17,000 mmol/day67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day25% of filtered load
371grams
2
8% remaining
NHE3Sodium Hydrogen
Exchanger
NKCC2Sodium Potassium
2Chloride Cotransporter
Sodium Absorption in Thick Ascending Loop
Bumetanide/
FurosemideXDiuretics (cause increased
urine flow) used to treat
high blood pressure
8/11/2019 Renal Lecture
14/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: TAL: TALGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
V=..increase
UNa=increase
.
Urinary Na excretion load with diuretic???
17,000 mmol/day67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day25% 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
8/11/2019 Renal Lecture
15/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: DCT: DCTGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day25% of filtered load
371 grams
2
8% remaining
1,300 mmol/day5% of filtered load
75grams
3
3% remaining
NaCl/TSC
Sodium ChlorideCotransporter/
Thiazide sensitive
cotransporter
Sodium Absorption in Distal Convoluted Tubule
Thiazides
X Diuretic used to treathigh blood pressure
8/11/2019 Renal Lecture
16/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: DCT: DCTGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
17,000 mmol/day67% of filtered load
1Kg
1
33% remaining
6,400 mmol/day25% of filtered load
371 grams
2
8% remaining
1,300 mmol/day5% 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
8/11/2019 Renal Lecture
17/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: CD: CDGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
8/11/2019 Renal Lecture
18/22
Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by
various segments of thevarious segments of the nephronnephron: CD: CDGFR=180 L/day
PNa=142 mmol/L = 1500g salt
Filtered Load of Na 25,500 mmol/day
700 mmol/day
8/11/2019 Renal Lecture
19/22
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 PathwayVasopressin Secretion Pathway
Urine is concentrated and flow reduced
Hypothalamus
8/11/2019 Renal Lecture
20/22
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
8/11/2019 Renal Lecture
21/22
High vasopressin = Formation of concentrated urineHigh vasopressin = Formation of concentrated urine
NHE3 + AQP1NHE3 + AQP1
AQP1AQP1
AQP2AQP2
AA
PP
22
High vasopressin = Formation of concentrated urineHigh vasopressin = Formation of concentrated urine
NHE3 + AQP1NHE3 + AQP1
AQP1AQP1
AQP2AQP2
AA
PP
22
8/11/2019 Renal Lecture
22/22
Vasopressin signaling in collecting duct
VP
BLOOD LUMEN
AQP2V2
Gs
AC
VI
ATP
PKA
cAMP
H20
H20
AQP2
Nucleus?
AQP3/AQP4
Gene regulation?