GH Kapitel 025

UNIT V
Textbook of Medical Physiology, 11th Edition
Chapter 25:
The Body Fluid Compartments: Extracellular and Intracellular Fluids; Interstitial Fluid and Edema
Slides by John E. Hall, Ph.D.
GUYTON & HALL

Copyright 2006 by Elsevier, Inc.
Body Fluid Regulation
Figure 25-1; Guyton and Hall
Fluid Balance (ml/day) 70 kg Adult

Intake Fluids ingested From metabolism Output Insensible - skin Insensible - lungs Sweat Feces Urine
Normal
High Salt Diet 4100 200 4300 350 350 100 100 3400 4300
2100 200 2300 350 350 100 100 1400 2300
Balance Concept
Balance is necessary, in the long-term, to maintain life. Fluid Loss = Fluid Intake Electrolyte Loss = Electrolyte Intake Fluid Intake: regulated by thirst mechanism, habits Electrolyte intake: governed by dietary habits Fluid Output: regulated mainly by kidneys Electrolyte output: regulated mainly by kidneys
Effect of increasing sodium intake 10-fold on urinary sodium excretion and extracellular fluid volume
Fluid Balance (ml/day) 70 kg Adult

Normal Intake Heavy Exercise ? 200 ? 350 650 5000 100 500 6500
Fluids ingested From metabolism Output Insensible - skin Insensible - lungs Sweat Feces Urine
2100 200 2300

350 350 100 100 1400 2300
Body Fluid Distribution

70 kg adult

Total Body Water in Relation to Body Weight: Effects of Gender, Body Build and Age
Body Build TBW (%) Adult Male 60 70 50 TBW (%) Adult Female 50 60 42 TBW (%) Infant 70 80 60
Normal Lean Obese
Increasing obesity decreases TBW %
Increasing age decreases TBW %

Measuring Body Fluid Volumes: Indicator Dilution Principle

Indicator Mass A = Volume A x Concentration A
Measuring Body Fluid Volumes: Indicator Dilution Principle

Indicator Mass A = Volume A x Concentration A
Indicator Mass A = Indicator Mass B
Volume B = Indicator Mass B / Concentration B
B
Indicator Mass B = Volume B x Concentration B
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
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.
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
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
Principles of Osmotic Equilibria

300
Osmolarity mOsm/ L
200 100
ICF 7980 mOsm

28 L
Normal State ECF

3920 mOsm
0 0 10 20
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
Effects of solutions on Cell Volume

Isotonic (no change)
Hypotonic (cell swells)
Hypertonic (cell shrinks)

Isosmotic - has same osmolarity as body fluids Hyperosmotic - higher osmolarity than body fluids Hyposmotic- lower osmolarity than body fluids
Question
What is the osmolarity of a 5 % glucose solution? Is the solution hyperosmotic, hypo-osmotic, or isosmotic?
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
Question
What is the osmolarity of a 3.0% NaCl solution? Is the solution hypertonic, hypotonic, or isotonic?
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
mmol
What are the changes in the following variables after giving 2.0 liters of 0.9% NaCl (Isotonic) i.v.? Extracellular Fluid Volume? Extracellular Fluid Osmolarity? Intracellular Fluid Volume? Intracellular Fluid Osmolarity?
Effect of adding 2 L of 0.9 % NaCl ?

OSMOLARITY mOsm/L
Normal State
300 200 100 0 0
ICF
ECF
A.
VOLUME (L)
10
20
30 40
C.
B.
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?
Effect of adding 2 L of water ?

OSMOLARITY mOsm/L
Normal State
300
ICF
ECF
A.
200
100 0 0
VOLUME (L)
10
20
30 40
C.
B.
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?
Effect of adding 2 L of 3 % NaCl ?

Normal State
OSMOLARITY mOsm/L 300
ICF
ECF
A.
200
100 0
VOLUME (L)
10 20 30 40
C.
B.
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?
Normal State Osmolarity

300 200 mOsm/L
A. Add Isotonic NaCl
100
0 0 10 20 30 40
Volume (L) C.Add Water (or hypotonic Fluids)
B. Add Hypertonic NaCl
Osmolarity
Which of the diagrams below represents simple dehydration caused by water loss? A. B.
300 mOsm/L
200
100 0 0 10
Volume (L)
20
30 40
C.
D.
Osmotic Equilibrium Problems
Calculation of intracellular and extracellular fluid volumes and osmolarities after fluid administration.
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?

Assume: extracell vol. = 20 % BW; intracell. vol. = 40 % BW
Step 1. Initial conditions

Volume (L) Conc. mOsm/L Total mOsm 3920
Extracell. Fluid (.2 x 70) = 14

Intracell. Fluid (.4 x 70) = 28 Total Fluid
280
280 280
7840
11,760
= 42
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


Step 2. Instantaneous Effect
Volume (L)
Extracell. fluid
Intracell. fluid
Conc. mOsm/L
?
280
Total mOsm
3920+2052= 5972
7840 + 0 = 7840
14+2= 16
28 +0= 28
Total Fluid
42+2= 44
? 11,760+2052= 13,812 no equilibrium

Step 2. After osmotic equilibrium
Volume (L) Conc. mOsm/L Total mOsm
Extracell. fluid
Intracell. fluid Total Fluid Net effect:
19
25 42+2= 44
314
314
3920+2052= 5972
7840 + 0 = 7840
314 11,760+2052= 13,812
Extracell. Volume by 5.0 L Intracell volume by 3.0 L
Abnormalities of Extracellular + Concentration Fluid Na (Osmolarity)
Abnormalities of Extracellular Fluid Na+ Concentration

Hypernatremia : water loss Na+ excess Hyponatremia : water excess Na+ loss Normal plasma [Na+] = 140-145 mmol / L
Na+ conc.
Na+ conc.
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).
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.
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

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
Hypernatremia
With Increased Extracellular Fluid Volume
( NaCl excess: hyperosmotic overhydration)
Decreased hematocrit, plasma proteins Primary aldosteronism Cushings syndrome

Usually the Hypernatremia is mild in these examples, but the person may have very low plasma K + (hypokalemia).
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?

Hypernatremia
A. With Increased Extracellular Fluid Volume ( NaCl excess: hyperosmotic overhydration) Primary aldosteronism Cushings 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
Hyponatremia
With Decreased Extracellular Fluid Volume ( NaCl Loss: hypo-osmotic dehydration)
diarrhea, vomiting Addisons disease (decreased aldosterone) overuse of diuretics sodium wasting renal diseases
Increased hematocrit, plasma proteins
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
Intracellular Edema
Hyponatremia Depression of tissue metabolic systems (e.g. hypothyroidism) Inadequate tissue nutrition (e.g. ischemia) Inflammation of tissues (increased cell membrane permeability)
Extracellular Edema
Causes of Extracellular Edema (increased interstitial fluid volume)
Increased Capillary Filtration Failure of lymphatics to Return Interstitial Fluid to Circulation
Determinants of Capillary Filtration
Kf
Capillary Pressure (Pc)
Plasma Colloid Osmotic Pressure ( c)
Interstitial Fluid Pressure (Pisf)

Interstitial Colloid Osmotic Pressure (isf)
FILT = Kf (Pc - Pisf - c + isf)
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
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?
Lymphatic Failure and Edema
Lymphatic Failure = Edema
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
= 3 mmHg
= 7 mmHg = 7 mmHg
= 17 mmHg
60 48 High Compliance
Interstitial Fluid Volume (liters)
36
Free Fluid 24
12
Low compliance
Gel Fluid -8 -4
0 0
+4
Interstitial Fluid Pressure (mmHg)
Low Tissue Compliance and Negative Intersititial Fluid Hydrostatic Pressure
Interstitial Volume
Interstitial Fluid Hydrostatic Pressure
Capillary Filtration
Increased Lymph Flow
Interstitial Volume
Interstitial Fluid Hydrostatic Pressure
Lymph Flow
Effect of Interstitial Fluid Pressure on Lymph Flow

20
Lymph Flow ( x normal) 10
-6 -4 -2 0 2 4 Interstitial Fluid Pressure ( mmHg)

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)

Washdown of Interstitial Fluid Proteins

Interstitial Volume Interstitial Fluid Hydrostatic Pressure
Capillary Filtration Interstitial Fluid Oncotic Pressure

Lymph Flow
Protein Removal From Tissues
Saftey Factors Against Edema

Low compliance of interstitium when interstitial fluid pressure is negative = 3 mmHg
Increased lymph flow

Washdown of interstitial protein at high lymph flow rates Total Safety factor
= 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

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

2. Decreased plasma proteins (low oncotic pressure) Loss of proteins - burns, wounds - nephrosis - gastroenteropathy Failure to produce proteins - malnutrition (kwashiorkor) - cirrhosis - analbuminemia

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

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

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UNIT V

Textbook of Medical Physiology, 11th Edition

GUYTON & HALL

Body Fluid Regulation

Copyright 2006 by Elsevier, Inc.

Figure 25-1; Guyton and Hall

Fluid Balance (ml/day) 70 kg Adult

2100 200 2300 350 350 100 100 1400 2300

Copyright 2006 by Elsevier, Inc.

Figure 26-1; Guyton and Hall

Fluid Balance (ml/day) 70 kg Adult

2100 200 2300

Body Fluid Distribution

Figure 25-1; Guyton and Hall

Normal Lean Obese

Increasing obesity decreases TBW %

Increasing age decreases TBW %

Measuring Body Fluid Volumes: Indicator Dilution Principle

Copyright 2006 by Elsevier, Inc.

Measuring Body Fluid Volumes: Indicator Dilution Principle

Indicator Mass A = Indicator Mass B

Volume B = Indicator Mass B / Concentration B

Indicator Dilution Principle

Measuring Body Fluid Compartments

Control of Body Fluid Distribution

Copyright 2006 by Elsevier, Inc.

Copyright 2006 by Elsevier, Inc.

If C = mOsm/L, = C x 19.3 mmHg

Principles of Osmotic Equilibria

ICF 7980 mOsm

Normal State ECF

H2O moves across cell membranes easily i.e. ECFosm = ICFosm

Many solutes (e.g. NaCl) are relatively impermeant to cell membranes

Effects of solutions on Cell Volume

Hypotonic (cell swells)

Hypertonic (cell shrinks)

Copyright 2006 by Elsevier, Inc.

Copyright 2006 by Elsevier, Inc.

Copyright 2006 by Elsevier, Inc.

Osmolarity of a 5 % Glucose Solution

Copyright 2006 by Elsevier, Inc.

Osmolarity of a 3% NaCl Solution

Effect of adding 2 L of 0.9 % NaCl ?

Copyright 2006 by Elsevier, Inc.

Effect of adding 2 L of water ?

Copyright 2006 by Elsevier, Inc.

Effect of adding 2 L of 3 % NaCl ?

Copyright 2006 by Elsevier, Inc.

Normal State Osmolarity

A. Add Isotonic NaCl

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

B. Add Hypertonic NaCl

Copyright 2006 by Elsevier, Inc.

Copyright 2006 by Elsevier, Inc.

Osmotic Equilibrium Problems

Copyright 2006 by Elsevier, Inc.

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

Copyright 2006 by Elsevier, Inc.

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

Step 1. Initial conditions

Extracell. Fluid (.2 x 70) = 14

2.0 L x 1026 mOsm/L = 2052 mOsm