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

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Figure 25-1; Guyton and Hall

Regulación del Líquido Corporal

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Figure 25-1; Guyton and Hall

Regulación del Líquido Corporal

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Figure 25-1; Guyton and Hall

Balance Líquido (ml/dia) – Adulto de 70 kg
Normal Dieta Alta en Sal Entradas Líquidos ingeridos 2100 4100 200 A partir del metabolismo 200 4300 2300 Salidas Insensibles - piel Insensibles - pulmones Sudor Heces Urina
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350 350 100 100 1400 2300

350 350 100 100 3400 4300

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

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Figure 26-1; Guyton and Hall

Fluid Balance (ml/day) – 70 kg Adult
Normal Intake Fluids ingested From metabolism Output Insensible - skin Insensible - lungs Sweat Feces Urine
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2100 200 2300 350 350 100 100 1400 2300

Heavy Exercise ? 200 ? 350 650 5000 100 500 6600

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 Normal Lean Obese TBW (%) Adult Male 60 70 50 TBW (%) Adult Female 50 60 42 TBW (%) Infant 70 80 60

Increasing obesity decreases TBW % Increasing age decreases TBW %
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Body Build Normal Lean Obese

Total Body Water in Relation to Body Weight: Effects of Gender, Body Build and Age****aqui grupo #3****
TBW (%) Adult Male 60 70 50

TBW (%) Adult Female 50 60 42

TBW (%) Infant 70 80 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 (C11 H12 N2O) Extracellular fluid volume: • 22 Na, inulin, thiosulfate Intracellular fluid = total body water - extracellular fluid Plasma volume: • 125 I-albumin, 51 Cr-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 (Π )

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

Osmolarity mOsm/ L

200 100 0 0

ICF ECF 3920 mOsm 7980 mOsm 28 L
10 20

Normal State

14 L
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 (cell swells)

Hypertonic (cell 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 L 180 gm 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 58.5 gm L L For NaCl, 1 mmol = 2 mOsm 513 mmol x 2 mOsm = 1026 mOsm L Hypertonic
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L

mmol

L

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 ?
OSMOLARITY mOsm/L

Normal State
300 200 100 0 0 10 20 30 40

ICF

ECF

A.

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 ?
OSMOLARITY mOsm/L

Normal State
300 200 100 0 0 10 20 30 40

ICF

ECF

A.

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
OSMOLARITY mOsm/L
300 200 100 0 0 10 20 30 40

ICF

ECF

A.

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

Osmolarity

300 200 100 0 0 10 20 30 40

A. Add Isotonic NaCl

Volume (L) C.Add Water (or hypotonic Fluids)

mOsm/L

B. Add Hypertonic NaCl

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Osmolarity

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

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 (L) Extracell. Fluid (.2 x 70) = 14 Intracell. Fluid (.4 x 70) = 28 Total Fluid
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Conc. mOsm/L 280 280 280

Total mOsm 3920 7840

= 42

11,760

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 mmol L 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 (L)
Extracell. fluid Intracell. fluid Total Fluid 14+2= 16 28 +0= 28 42+2= 44

Conc. mOsm/L
? 280

Total mOsm
3920+2052= 5972 7840 + 0 = 7840

? 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 (L) Extracell. fluid Intracell. fluid Total Fluid Net effect:
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Conc. mOsm/L 314 314

Total mOsm 3920+2052= 5972 7840 + 0 = 7840

19 25 42+2= 44

314 11,760+2052= 13,812

Extracell. Volume by 5.0 L Intracell volume by 3.0 L

Abnormalities of Extracellular Fluid Na+ Concentration (Osmolarity)

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Abnormalities of Extracellular Fluid Na+ Concentration
Hypernatremia : • water loss • Na+ excess Hyponatremia : • water excess • Na+ loss Na+ conc.

Na+ conc.

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 Plasma Na+ Plasma K+ Blood pressure Heart rate Hematocrit Plasma protein = 70 kg = 162 mmol/L = 4.7 mmol/L = 102/65 mmHg = 92 beats/min = 0.50 = 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

Kf

Capillary Plasma Colloid Pressure (Pc) Osmotic Pressure ( Π c)

Interstitial Fluid Pressure (Pisf)

Interstitial Colloid Osmotic Pressure (Π isf)

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FILT = Kf (Pc - Pisf - Π c + Π isf )

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 - Π c + Π 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 Π 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

X

Lymphatic Failure = Edema

Figure 25-1; Guyton and Hall
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Safety Factors Against Edema
• Low compliance of interstitium when interstitial fluid pressure is negative • Increased lymph flow • “ Washdown” of interstitial protein at high lymph flow rates Total Safety factor
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= 3 mmHg

= 7 mmHg = 7 mmHg

= 17 mmHg

60 48 High Compliance

Interstitial Fluid Volume (liters)

36 24 12 0 -8 -4 0 Low compliance

Free Fluid

Gel Fluid +4

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Interstitial Fluid Pressure (mmHg)

Low Tissue Compliance and Negative Intersititial Fluid Hydrostatic Pressure

Interstitial Volume

Interstitial Fluid Hydrostatic Pressure

Capillary Filtration

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Increased Lymph Flow

Interstitial Volume

Interstitial Fluid 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 6 Plasma Protein Concentration

Interstitial Fluid Protein concentration (gm/100 ml)

4 2 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 Volume Interstitial Fluid Hydrostatic Pressure Lymph Flow Protein Removal From Tissues

Capillary Filtration Interstitial Fluid Oncotic Pressure
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Saftey Factors Against Edema
• Low compliance of interstitium when interstitial fluid pressure is negative • Increased lymph flow • “ Washdown of interstitial protein at high lymph flow rates Total Safety factor
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= 3 mmHg

= 7 mmHg = 7 mmHg

= 17 mmHg

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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