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UNIT V

Textbook of Medical Physiology, 11th Edition

Capitulo 25:
Los Compartimientos Líquidos del Cuerpo:
Liquido Extracelular y Liquido Intracelular; Liquido Intersticial y Edema
Diapositivas por John E. Hall, Ph.D.
Traducción por Rene R. García – Szabó, M.D., Ph.D.

GUYTON & HALL


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Regulación del Líquido Corporal

Figure 25-1;
Guyton and Hall
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Regulación del Líquido Corporal

Figure 25-1;
Guyton and Hall
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Regulación del Líquido Corporal

Figure 25-1;
Guyton and Hall
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Balance Líquido (ml/dia) – Adulto de
70 kg

Entradas Normal Dieta Alta en Sal


Líquidos ingeridos 2100 4100
A partir del metabolismo 200 200
2300 4300
Salidas
Insensibles - piel 350 350
Insensibles - pulmones 350 350
Sudor 100 100
Heces 100 100
Urina 1400 3400
2300 4300
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El Concepto de Balance

El balance es necesario, en el mantenimiento a largo


plazo de la vida.

Perdidas liquidas = Ingesta liquida


Perdidas electrolíticas = Ingesta electrolítica
La ingesta liquida: es regulada por el mecanismo de la sed,
hábitos
La ingesta electrolítica: es regida por habitos dieteticos.
Las salidas liquidas: son reguladas principalmente por los
riñones.
Las salidas electrolíticas: re son reguladas principalmente
por los riñones.
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Effect of increasing sodium intake 10-fold on
urinary sodium excretion and extracellular
fluid volume

Figure 26-1;
Guyton and Hall
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Fluid Balance (ml/day) – 70 kg
Adult
Normal Heavy
Intake Exercise
Fluids ingested 2100 ?
From metabolism 200 200
2300 ?
Output
Insensible - skin 350 350
Insensible - lungs 350 650
Sweat 100 5000
Feces 100 100
Urine 1400 500
2300 6600
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Body Fluid Distribution
70 kg adult

Figure 25-1;
Guyton and Hall
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Total Body Water in Relation to Body
Weight:
Effects of Gender, Body Build and Age

Body Build TBW (%) TBW (%) TBW (%)


Adult Male Adult Female Infant

Normal 60 50 70

Lean 70 60 80

Obese 50 42 60

Increasing obesity decreases TBW %


Increasing age decreases TBW %
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Total Body Water in Relation to Body
Weight:
Effects of Gender, Body Build and
Age****aqui grupo #3****
Body Build TBW (%) TBW (%) TBW (%)
Adult Male Adult Female Infant

Normal 60 50 70

Lean 70 60 80

Obese 50 42 60

Increasing obesity decreases TBW %


Increasing age decreases TBW %
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Indicator Dilution Principle

Volume (B) = Indicator Mass (B) = Q


Concentration (B) C

Valid if:
• Indicator disperses only in compartment measured
• Indicator disperses evenly in compartment
• Indicator not metabolized or excreted

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Measuring Body Fluid
Compartments
Total Body water:
• D2O, 3H2O, antipyrine (C11H12N2O)

Extracellular fluid volume:


• 22Na, inulin, thiosulfate
Intracellular fluid =
total body water - extracellular fluid

Plasma volume:
• 125I-albumin, 51Cr-red blood cells
blood volume = plasma volume /(1 -HCT)
plasma volume = blood volume x (1 -HCT)
Interstitial fluid vol. =
Extracell fluid vol. - plasma vol.
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Control of Body Fluid
Distribution

Distribution across cell membranes:


determined by osmotic forces
(mainly from electrolytes)

Distribution across capillaries:


determined by hydrostatic and
colloid osmotic forces

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Osmotic Pressure ()

 = CRT
C = concentration (osm/L)
R = gas constant (62.3 if = mmHg)
T = Kelvino = 273o + Co
= 310o (normal body temp.)
 = 19,300 mmHg / Osm
If C = mOsm/L,
= C x 19.3 mmHg

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Principles of Osmotic Equilibria
300 Normal State
ICF ECF
Osmolarity 200
7980 mOsm 3920 mOsm
mOsm/ 100
L 28 L 14 L
0

0 10 20 30 40 VOLUME (L)

• H2O moves across cell membranes easily


i.e. ECFosm = ICFosm

• Many solutes (e.g. NaCl) are relatively impermeant


to cell membranes
• Hydrostatic pressure differences have only
a small effect on fluid movement across cell membrane
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Effects of solutions on
Cell Volume

Isotonic
(no change)

Hypotonic Hypertonic
(cell (cell
swells) shrinks)

Figure 25-5; Guyton and Hall


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Isosmotic - has same osmolarity as body fluids

Hyperosmotic - higher osmolarity than body fluids

Hyposmotic- lower osmolarity than body fluids

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Question

• What is the osmolarity of a


5 % glucose solution?

• Is the solution hyperosmotic,


hypo-osmotic, or isosmotic?

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Osmolarity of a 5 % Glucose
Solution

MW glucose = 180 gm/mol


5 % = 5 gm/100 ml = 50 gm/L
50 gm x 1 mol = .278 mol = 278 mOsm
L 180 gm L L

Isosmotic

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Question

• What is the osmolarity of a 3.0%


NaCl solution?

• Is the solution hypertonic, hypotonic,


or isotonic?

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Osmolarity of a 3% NaCl
Solution

MW NaCl = 58.5
3 % = 3 gm/100ml = 30 gm/L
30 gm x 1 mol = .513 mol = 513 mmol
L 58.5 gm L L
For NaCl, 1 mmol = 2 mOsm
513 mmol x 2 mOsm = 1026 mOsm
L mmol L
Hypertonic

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What are the changes in the following
variables after giving 2.0 liters of 0.9%
NaCl (Isotonic) i.v.****aqui grupo No.
1***

Extracellular Fluid Volume?


Extracellular Fluid Osmolarity?
Intracellular Fluid Volume?
Intracellular Fluid Osmolarity?
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Effect of adding 2 L of 0.9 % NaCl ?
Normal State ICF ECF
A.
OSMOLARITY

300
mOsm/L

200
100
0
0 10 20 30 40
VOLUME (L)
C. B.

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What are the Changes in the following
variables after giving 2.0 liters of
water i.v.?

Extracellular Fluid Volume?


Extracellular Fluid Osmolarity?
Intracellular Fluid Volume?
Intracellular Fluid Osmolarity?
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Effect of adding 2 L of water ?
Normal State ICF ECF
A.
OSMOLARITY

300
mOsm/L

200
100
0
0 10 20 30 40
VOLUME (L)
C. B.

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What are the Changes in the following
variables after giving 2.0 liters of
3.0% NaCl i.v.?

Extracellular Fluid Volume?


Extracellular Fluid Osmolarity?
Intracellular Fluid Volume?
Intracellular Fluid Osmolarity?
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Effect of adding 2 L of 3 % NaCl ?
Normal State ICF ECF
A.
OSMOLARITY
300
mOsm/L

200
100
0
0 10 20 30 40
VOLUME (L)
C. B.

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What are the Changes in the
following variables after giving 2.0
liters of 3.0% NaCl i.v.?

Extracellular Fluid Volume? > 2.0 Liters


Extracellular Fluid Osmolarity?
Intracellular Fluid Volume?
Intracellular Fluid Osmolarity?
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Normal State A. Add Isotonic
NaCl
300
Osmolarity
mOsm/L

200
100
0
0 10 20 30 40
Volume (L)
C.Add Water (or hypotonic B. Add Hypertonic
NaCl
Fluids)

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Which of the diagrams below represents
simple dehydration caused by water loss?
A. B.
300
Osmolarity
mOsm/L

200
100
0
0 10 20 30 40
Volume (L)
C. D.

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Osmotic Equilibrium Problems

• Calculation of intracellular and extracellular


fluid volumes and osmolarities after fluid
administration.

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Effect of Infusing 2.0 liters of
3% NaCl to a 70 kg Person

Assume:
1) no excretion of water or solutes,
2) osmotic equilibrium,
3) ECF =20% body wt, ICF =40 % body wt.

• What is the extracellular osmolarity?

• What are the intra- and extracellular fluid volumes?

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Effect of Infusing 2.0 liters of
3% NaCl to a 70 kg Person
Assume: extracell vol. = 20 % BW; intracell. vol. = 40 % BW
Step 1. Initial conditions
Volume Conc. Total
(L) mOsm/L mOsm

Extracell. Fluid (.2 x 70) = 14 280 3920

Intracell. Fluid (.4 x 70) = 28 280 7840

Total Fluid = 42 280 11,760


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Osmolarity of a 3% NaCl
Solution

MW NaCl = 58.5
3% = 3 gm/100ml = 30 gm/L
30 gm x 1 mol = .513 mol = 513 mmol
L 58.5 gm L L
For NaCl, 1 mmol = 2 mOsm
513 mmol x 2 mOsm = 1026 mOsm
L mmol L
2.0 L x 1026 mOsm/L = 2052 mOsm
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Effect of Infusing 2.0 liters of
3% NaCl to a 70 kg Person

Step 2. Instantaneous Effect


Volume Conc. Total
(L) mOsm/L mOsm
Extracell. fluid 14+2= 16 ? 3920+2052= 5972

Intracell. fluid 28 +0= 28 280 7840 + 0 = 7840

Total Fluid 42+2= 44 ? 11,760+2052=


no equilibrium 13,812

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Effect of Infusing 2.0 liters of
3% NaCl to a 70 kg Person

Step 2. After osmotic equilibrium


Volume Conc. Total
(L) mOsm/L mOsm

Extracell. fluid 19 314 3920+2052= 5972

Intracell. fluid 25 314 7840 + 0 = 7840

Total Fluid 42+2= 44 314 11,760+2052= 13,812


Net effect: Extracell. Volume by 5.0 L
Intracell volume by 3.0 L
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Abnormalities of Extracellular
Fluid Na+ Concentration
(Osmolarity)

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Abnormalities of Extracellular
Fluid Na+ Concentration

Hypernatremia : Na+ conc.


• water loss
• Na+ excess
Hyponatremia : Na+ conc.
• water excess
• Na+ loss

Normal plasma [Na+] = 140-145 mmol / L


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Consequences of Hyponatremia
and Hypernatremia

• Water moves in and out of cells


 cells swell or shrink
• This has profound effects on the brain.
- Neurologic function is altered

- Rapid shrinking can tear vessels and cause hemorrhage


- Rapid swelling can cause herniation
Because the skull is rigid, the brain cannot
increase its volume by more than 10% without
being forced down the neck (herniation).

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Defense of Cell Volume
• Extracellular hypertonicity increases expression of genes
encoding proteins that increase intracellular osmoles.
- Membrane transporters (Na+-H+- exchanger)
- Enzymes (e.g. aldose reductase that synthesize
intracellular solutes (e.g. sorbital)

• Clinical significance: Rapid changes in extracellular fluid


tonicity alter cell volume and cause neurologic
complications, while slow changes have much less
effect on cell volume and much less clinical effect.

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Hypernatremia

With Decreased Extracellular Fluid Volume


(water loss: hyperosmotic dehydration)

With Increased Extracellular Fluid Volume


( NaCl excess: hyperosmotic overhydration)

What lab measurements would help in


diagnosis?
• Hematocrit, plasma proteins
• Urine volume
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Hypernatremia

With Decreased Extracellular Fluid Volume


(water loss: hyperosmotic dehydration)
• Increased hematocrit, plasma proteins
• Small volume of concentrated urine
- dehydration, excess sweating
• Large volume of dilute urine - diabetes insipidus
- lack of ADH (“central” diabetes insipidus)
- “nephrogenic” diabetes insipidus
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Hypernatremia

With Increased Extracellular Fluid Volume


( NaCl excess: hyperosmotic overhydration)
• Decreased hematocrit, plasma proteins
• Primary aldosteronism
• Cushing’s syndrome
Usually the Hypernatremia is mild in these examples,
but the person may have very low plasma K +
(hypokalemia).
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Hypernatremia – Clinical Case
A 52 year old male comes to you office complaining of frequent
headaches and large volumes of urine. His medical history indicates
that he is being treated with lithium for manic-depressive disorder.
your laboratory tests give the following results:

Body weight = 70 kg
Plasma Na+ = 162 mmol/L
Plasma K+ = 4.7 mmol/L
Blood pressure = 102/65 mmHg
Heart rate = 92 beats/min
Hematocrit = 0.50
Plasma protein = 8.40
• What are some potential causes of his hypernatremia?
• What additional tests would help in making a differential diagnosis?
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Hypernatremia****aqui
preguntas del examen parcial****
A. With Increased Extracellular Fluid Volume
( NaCl excess: hyperosmotic overhydration)

• Primary aldosteronism
• Cushing’s syndrome

B. With Decreased Extracellular Fluid Volume


(water loss: hyperosmotic dehydration)

• Small volume of concentrated urine


- dehydration, excess sweating
• Large volume of dilute urine - diabetes insipidus
- lack of ADH (“central” diabetes insipidus)
- “nephrogenic” diabetes insipidus
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Hyponatremia

With Decreased Extracellular Fluid Volume


( NaCl Loss: hypo-osmotic dehydration)
• diarrhea, vomiting
• Addison’s disease (decreased aldosterone)
• overuse of diuretics
• sodium wasting renal diseases

Increased hematocrit, plasma proteins


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Hyponatremia

With Increased Extracellular Fluid Volume


(water excess: hypo-osmotic overhydration)

• Inappropriate ADH syndrome


• Bronchogenic tumors
• Fibrosing tuberculosis lung lesions
• Circulatory failure (e.g., congestive heart
failure)
Decreased hematocrit, plasma proteins
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Intracellular Edema

• Hyponatremia
• Depression of tissue metabolic systems
(e.g. hypothyroidism)
• Inadequate tissue nutrition
(e.g. ischemia)
• Inflammation of tissues (increased cell
membrane permeability)

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Determinants of Capillary
Filtration

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Determinants of Capillary
Filtration

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Extracellular Edema

Causes of Extracellular Edema


(increased interstitial fluid volume)
• Increased Capillary Filtration

• Failure of lymphatics to Return


Interstitial Fluid to Circulation

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Determinants of Capillary
Filtration

Capillary Plasma Colloid


Pressure (Pc) Osmotic Pressure ( c)
Kf

Interstitial Interstitial Colloid


Fluid Pressure Osmotic Pressure
(Pisf) (isf)

FILT = Kf (Pc - Pisf - c + isf)


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Determinants of Capillary
Filtration

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Determinants of Capillary
Filtration

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Causes of Increased Capillary
Filtration
FILT = Kf (Pc - Pisf - c + isf)
Increased Kf: toxins, ischemic damage, infections, etc.
Increased Pc:
• increased arterial pressure, excess fluid retention,
• decreased arteriolar resistance
• increased venous resistance, increased venous pressure
Decreased c:
• nephrotic syndrome
• cirrhosis
• malnutrition
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Normal Filtration

FILT = Kf x Net Filt Pressure


= 6.6 x ( 17.3 - (-3) - 28 +8)
= 6.6 x ( + 0.3)
= 1.89 ml/min

FILT = 2722 ml/day


Where does all of this fluid (and protein in it) go?
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Lymphatic Failure and Edema

Lymphatic
X Failure = Edema

Figure 25-1;
Guyton and Hall
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Safety Factors Against Edema

• Low compliance of interstitium when = 3 mmHg


interstitial fluid pressure is negative

• Increased lymph flow = 7 mmHg

• “ Washdown” of interstitial protein = 7 mmHg


at high lymph flow rates

Total Safety factor = 17 mmHg

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60
High
48 Compliance
Interstitial Fluid
Volume (liters)

36
Free
Fluid
24 Low compliance

12 Gel
Fluid
0
-8 -4 0 +4
Interstitial Fluid Pressure
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(mmHg)
Low Tissue Compliance and Negative
Intersititial Fluid Hydrostatic Pressure

Interstitial Interstitial Fluid


Volume Hydrostatic Pressure

Capillary Filtration

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Increased Lymph Flow

Interstitial Interstitial Fluid


Volume Hydrostatic Pressure

Lymph Flow

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Effect of Interstitial Fluid
Pressure on Lymph Flow

20

Lymph Flow
( x normal) 10

1
-6 -4 -2 0 2 4
Interstitial Fluid Pressure ( mmHg)
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Washdown of Interstitial
Proteins

8 Plasma Protein Concentration

6
Protein concentration
Interstitial Fluid

(gm/100 ml)

0
0 20 40 60 80 100 120 140 160 18
0
Rate of Non-Visceral Lymph Flow (ml/hr)
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“Washdown” of Interstitial
Fluid Proteins

Interstitial Interstitial Fluid


Volume Hydrostatic Pressure

Capillary Filtration Lymph Flow

Interstitial Fluid Protein Removal


Oncotic Pressure From Tissues

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Saftey Factors Against Edema

• Low compliance of interstitium when = 3 mmHg


interstitial fluid pressure is negative

• Increased lymph flow = 7 mmHg

• “ Washdown of interstitial protein = 7 mmHg


at high lymph flow rates

Total Safety factor = 17 mmHg


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Conditions Causing Edema

1. High capillary hydrostatic pressure


• Excess fluid retention by kidneys
- acute or chronic kidney failure
- glomerulonephritis
- mineralocorticoid excess

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Conditions Causing Edema

1. High capillary hydrostatic pressure


• Decreased arteriolar resistance
- vasodilator drugs
- autonomic insufficiency
• Increased venous pressure
- congestive heart failure
- high output heart failure (e.g. anemia)
- venous obstruction
- venous valve failure
- cirrhosis
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Conditions Causing Edema

2. Decreased plasma proteins


(low oncotic pressure)
• Loss of proteins
- burns, wounds
- nephrosis
- gastroenteropathy
• Failure to produce proteins
- malnutrition (“kwashiorkor”)
- cirrhosis
- analbuminemia
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Conditions Causing Edema

3. Increased capillary permeability


• Immune reactions (histamine)
• Toxins
• Burns
• Prolonged ischemia
• Vitamin deficiency (e.g. vitamin C)
• Pre-eclampsia and eclampsia in
pregnancy

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Conditions Causing Edema

4. Blockage of lymphatics
• Cancer
• Surgery
• Infections (e.g. filaria nematodes)

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