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U N I T V
Textbook of Medical Physiology, 11th Edition
GUYTON & HALL
Copyright © 2006 by Elsevier, Inc.
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.
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Figure 25-1;Guyton and Hall
Regulación del Líquido CorporalRegulación del Líquido Corporal
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Figure 25-1;Guyton and Hall
Regulación del Líquido CorporalRegulación del Líquido Corporal
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Figure 25-1;Guyton and Hall
Regulación del Líquido CorporalRegulación del Líquido Corporal
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Balance Líquido (ml/dia) – Adulto de 70 kg
EntradasLíquidos ingeridos 2100A partir del metabolismo 200
2300
Normal
Salidas Insensibles - piel 350Insensibles - pulmones 350Sudor 100Heces 100Urina 1400
2300
Dieta Alta en Sal
4100 2004300
350 350 100 10034004300
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El Concepto de Balance
El balance es necesario, en el mantenimiento a largo plazo de la vida.
Perdidas liquidas = Ingesta liquidaPerdidas 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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Figure 26-1;Guyton and Hall
Effect of increasing sodium intake 10-fold on urinary sodium excretion and extracellular fluid volume
Effect of increasing sodium intake 10-fold on urinary sodium excretion and extracellular fluid volume
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Fluid Balance (ml/day) – 70 kg Adult
IntakeFluids ingested 2100 ?From metabolism 200 200
2300 ?Output
Insensible - skin 350 350 Insensible - lungs 350 650Sweat 100 5000 Feces 100 100Urine 1400 500
2300 6600
Normal Heavy Exercise
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Figure 25-1;Guyton and Hall
Body Fluid DistributionBody Fluid Distribution
70 kg adult
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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 age decreases TBW %
Increasing obesity 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 age decreases TBW %
Increasing obesity decreases TBW %
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Indicator Dilution Principle
Volume (B) = Indicator Mass (B) Concentration (B)
Valid if:• Indicator disperses only in compartment measured
= QC
• 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)
Intracellular fluid = total body water - extracellular fluid
Extracellular fluid volume:• 22Na, inulin, thiosulfate
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 capillaries: determined by hydrostatic and
colloid osmotic forces
Distribution across cell membranes:determined by osmotic forces (mainly from electrolytes)
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Osmotic Pressure ()
= CRTC = 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
• H2O moves across cell membranes easilyi.e. ECFosm = ICFosm
40
300
200
100
0
0 10 20 30
OsmolaritymOsm/
L
Normal State
VOLUME (L)
ICF ECF
28 L 14 L
7980 mOsm 3920 mOsm
• Many solutes (e.g. NaCl) are relatively impermeant to cell membranes
• Hydrostatic pressure differences have onlya small effect on fluid movement across cell membrane
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Figure 25-5; Guyton and Hall
Isotonic(no change)
Hypertonic(cell
shrinks)
Hypotonic(cell
swells)
Effects of solutions on Cell Volume
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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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• What is the osmolarity of a
5 % glucose solution?
• Is the solution hyperosmotic, hypo-osmotic, or isosmotic?
Question
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Osmolarity of a 5 % Glucose Solution
MW glucose = 180 gm/mol5 % = 5 gm/100 ml = 50 gm/L
Isosmotic
50 gm x 1 mol = .278 mol =L 180 gm L
278 mOsmL
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• What is the osmolarity of a 3.0% NaCl solution?
• Is the solution hypertonic, hypotonic, or isotonic?
Question
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Osmolarity of a 3% NaCl Solution
MW NaCl = 58.53 % = 3 gm/100ml = 30 gm/L30 gm x 1 mol = .513 mol = 513 mmol
L L LFor NaCl, 1 mmol = 2 mOsm513 mmol x 2 mOsm = 1026 mOsm
LL mmol
Hypertonic
58.5 gm
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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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40
300
200
100
0
0 10 20 30
OS
MO
LA
RIT
Ym
Osm
/L
Normal State
VOLUME (L)
ECFICF A.
B.C.
Effect of adding 2 L of 0.9 % NaCl ?
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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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40
300
200
100
0
0 10 20 30
OS
MO
LA
RIT
Ym
Osm
/LNormal State
VOLUME (L)
ECFICF A.
B.C.
Effect of adding 2 L of water ?
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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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40
300
200
100
0
0 10 20 30
OS
MO
LA
RIT
Ym
Osm
/LNormal State
VOLUME (L)
ECFICF A.
B.C.
Effect of adding 2 L of 3 % NaCl ?
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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?
> 2.0 Liters
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300
200
100
0Osm
olar
ity
mO
sm/L
Normal State A. Add Isotonic NaCl
B. Add Hypertonic NaCl
C.Add Water (or hypotonicFluids)
0 10 20 30 40
Volume (L)
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Which of the diagrams below representssimple dehydration caused by water loss?
300
200
100
0Osm
olar
ity
mO
sm/L
0 10 20 30 40Volume (L)
A. B.
C. D.
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• Calculation of intracellular and extracellular fluid volumes and osmolarities after fluid
administration.
Osmotic Equilibrium Problems
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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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Step 1. Initial conditions
Volume Conc. Total(L) mOsm/L mOsm
Extracell. Fluid (.2 x 70) = 280
Intracell. Fluid (.4 x 70) = 280
Total Fluid = 280
Assume: extracell vol. = 20 % BW; intracell. vol. = 40 % BW
3920
7840
11,760
14
28
42
Effect of Infusing 2.0 liters of 3% NaCl to a 70 kg Person
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Osmolarity of a 3% NaCl Solution
MW NaCl = 58.53% = 3 gm/100ml = 30 gm/L
513 mmol x 2 mOsm = 1026 mOsmLL mmol
30 gm x 1 mol = .513 mol = 513 mmolL L L58.5 gm
For NaCl, 1 mmol = 2 mOsm
2.0 L x 1026 mOsm/L = 2052 mOsm
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Extracell. fluid 14+2= ? 3920+2052=
Intracell. fluid 28 +0= 28 280 7840 + 0 = 7840
Total Fluid 42+2= ? 11,760+2052= no equilibrium
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
16
44
5972
13,812
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Extracell. fluid 3920+2052=
Intracell. fluid 7840 + 0 = 7840
Total Fluid 42+2= 44 11,760+2052=
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
5972
13,812
19
25
314
314
314
Net effect: Extracell. Volume by 5.0 L Intracell volume by 3.0 L
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Abnormalities of ExtracellularFluid Na+ Concentration
(Osmolarity)
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Hyponatremia : Na+ conc.
Hypernatremia : Na+ conc.
Abnormalities of ExtracellularFluid Na+ Concentration
Normal plasma [Na+] = 140-145 mmol / L
• water loss • Na+ excess
• water excess• Na+ loss
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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)
What lab measurements would help in diagnosis?
With Increased Extracellular Fluid Volume( NaCl excess: hyperosmotic overhydration)
• Hematocrit, plasma proteins• Urine volume
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Hypernatremia
With Decreased Extracellular Fluid Volume(water loss: hyperosmotic dehydration)
• Large volume of dilute urine - diabetes insipidus
• Increased hematocrit, plasma proteins
• Small volume of concentrated urine - dehydration, excess sweating
- lack of ADH (“central” diabetes insipidus)- “nephrogenic” diabetes insipidus
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Hypernatremia
With Increased Extracellular Fluid Volume( NaCl excess: hyperosmotic overhydration)
• Primary aldosteronism• Cushing’s syndrome
Usually the Hypernatremia is mild in these examples,but the person may have very low plasma K +
(hypokalemia).
• Decreased hematocrit, plasma proteins
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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 kgPlasma Na+ = 162 mmol/LPlasma K+ = 4.7 mmol/LBlood pressure = 102/65 mmHgHeart rate = 92 beats/minHematocrit = 0.50 Plasma protein = 8.40
• What are some potential causes of his hypernatremia?
• What additional tests would help in making a differential diagnosis?
Hypernatremia – Clinical Case
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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)
• Large volume of dilute urine - diabetes insipidus- lack of ADH (“central” diabetes insipidus)- “nephrogenic” diabetes insipidus
• Small volume of concentrated urine - dehydration, excess sweating
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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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Causes of Extracellular Edema (increased interstitial fluid volume)
• Increased Capillary Filtration
• Failure of lymphatics to Return Interstitial Fluid to Circulation
Extracellular Edema
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Determinants of Capillary Filtration
CapillaryPressure (Pc)
Plasma ColloidOsmotic Pressure ( c)
InterstitialFluid Pressure (Pisf)
Interstitial ColloidOsmotic Pressure (isf)
Kf
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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Figure 25-1; Guyton and Hall
X Lymphatic Failure = Edema
Lymphatic Failure and Edema
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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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- 8 - 4 0 + 4
12
24
36
48
60
0
Inte
rstit
ial F
luid
Vol
ume
(lite
rs)
Interstitial Fluid Pressure (mmHg)
FreeFluid
GelFluid
Low compliance
HighCompliance
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Low Tissue Compliance and Negative Intersititial Fluid Hydrostatic Pressure
InterstitialVolume
Interstitial FluidHydrostatic Pressure
Capillary Filtration
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Increased Lymph Flow
InterstitialVolume
Interstitial FluidHydrostatic Pressure
Lymph Flow
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Lymph Flow( x normal)
20
10
1
- 6 - 4 - 2 0 2 4Interstitial Fluid Pressure ( mmHg)
Effect of Interstitial Fluid Pressure on Lymph Flow
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2
4
6
8
0
0 20 40 60 80 100 120 140 160 180
Plasma Protein Concentration
Rate of Non-Visceral Lymph Flow (ml/hr)
Int
erst
itia
l Flu
idP
rote
in c
once
ntra
tion
(
gm/1
00 m
l)
Washdown of Interstitial Proteins
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“Washdown” of Interstitial Fluid Proteins
InterstitialVolume
Interstitial FluidOncotic Pressure
Capillary Filtration
Interstitial FluidHydrostatic Pressure
Lymph Flow
Protein Removal 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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2. Decreased plasma proteins (low oncotic pressure)
• Loss of proteins- burns, wounds- nephrosis- gastroenteropathy
• Failure to produce proteins- malnutrition (“kwashiorkor”)- cirrhosis- analbuminemia
Conditions Causing Edema
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3. Increased capillary permeability• Immune reactions (histamine)• Toxins• Burns• Prolonged ischemia• Vitamin deficiency (e.g. vitamin C)• Pre-eclampsia and eclampsia in
pregnancy
Conditions Causing Edema
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4. Blockage of lymphatics• Cancer• Surgery• Infections (e.g. filaria nematodes)
Conditions Causing Edema