Ch06.pdf

CHAPTER

Alterations in Fluids,

Electrolytes, and

Acid-Base Balance

Composition and Compartmental Distribution of

Body Fluids

Introductory Concepts

Diffusion and Osmosis

Compartmental Distribution of Body Fluids

Intracellular Fluid Volume

Extracellular Fluid Volume

Capillary/Interstitial Fluid Exchange

Edema

Third-Space Accumulation

Sodium and Water Balance

Regulation of Sodium and Water Balance

Regulation of Sodium Balance

Regulation of Water Balance

Alterations in Isotonic Fluid Volume

Isotonic Fluid Volume Deﬁcit

Isotonic Fluid Volume Excess

Alterations in Sodium Concentration

Hyponatremia

Hypernatremia

Potassium Balance

Regulation of Potassium Balance

Hypokalemia

Hyperkalemia

Calcium and Magnesium Balance

Calcium Balance

Regulation of Serum Calcium

Hypocalcemia

Hypercalcemia

Magnesium Balance

Regulation of Magnesium

Hypomagnesemia

Hypermagnesemia

Acid-Base Balance

Introductory Concepts

Acid-Base Chemistry

Metabolic Acid and Bicarbonate Production

Regulation of pH

Laboratory Tests

Alterations in Acid-Base Balance

Metabolic Versus Respiratory Acid-Base Disorders

Primary Versus Compensatory Mechanisms

Metabolic Acidosis

Metabolic Alkalosis

Respiratory Acidosis

Respiratory Alkalosis

sue spaces between the cells, and in the blood that fills

the vascular compartment. Body fluids serve to transport

gases, nutrients, and wastes; help to generate the electrical

activity needed to power body functions; take part in the

transforming of food into energy; and otherwise maintain the

overall function of the body. Although fluid volume and

composition remain relatively constant in the presence of a

wide range of changes in intake and output, conditions such

as environmental stresses and disease can increase fluid loss,

impair its intake, and otherwise interfere with mechanisms

that regulate fluid volume, composition, and distribution.

COMPOSITION AND COMPARTMENTAL

DISTRIBUTION OF BODY FLUIDS

Body ﬂuids are distributed between the intracellular ﬂuid (ICF)

and extracellular ﬂuid (ECF) compartments. The ICF compart-

ment consists of ﬂuid contained within all of the billions of

cells in the body. It is the larger of the two compartments, con-

taining approximately two thirds of the body water in healthy

adults. The remaining one third of body water is in the ECF

compartment, which contains all the ﬂuids outside the cells, in-

cluding that in the interstitial or tissue spaces and blood vessels

(Fig. 6-1). The ECF, including the plasma and interstitial ﬂuids,

F luids and electrolytes are present in body cells, in the tis-

Chapter 6: Alterations in Fluids, Electrolytes, and Acid-Base Balance

mechanisms such as the Na + /K + -ATPase pump that is located in

the cell membrane for movement across the membrane (see

Chapter 1). Water crosses the cell membrane by osmosis using

special protein channels.

Intracellular

water

Introductory Concepts

The electrolytes in body fluids are substances that dissociate

in solution to form charged particles, or ions. For example,

a sodium chloride (NaCl) molecule dissociates to form a

positively charged Na + ion and a negatively charged Cl − ion.

Because of their attraction forces, positively charged cations are

always accompanied by negatively charged anions. The distri-

bution of electrolytes between body compartments is inﬂu-

enced by their electrical charge. However, one cation may be

exchanged for another, providing it carries the same charge. For

example, a positively charged H + ion may be exchanged for a

positively charged K + and a negatively charged HCO 3 − ion may

be exchanged for a negatively charged Cl − anion.

Extracellular

(plasma) water

Extracellular

(interstitial) water

■ FIGURE 6-1 ■ Distribution of body water. The extracellular space

includes the vascular compartment (plasma water) and the inter-

stitial spaces.

Diffusion and Osmosis

Diffusion is the movement of charged or uncharged particles

along a concentration gradient. All molecules and ions, in-

cluding water and dissolved molecules, are in constant random

motion. It is the motion of these particles, each colliding with

one another, that supplies the energy for diffusion. Because

there are more molecules in constant motion in a concentrated

solution, particles move from an area of higher concentration

to one of lower concentration.

Osmosis is the movement of water across a semipermeable

membrane ( i.e., one that is permeable to water but imper-

meable to most solutes). As with solute particles, water diffuses

down its concentration gradient, moving from the side of

the membrane with the lesser number of particles and greater

concentration of water to the side with the greater number of

particles and lesser concentration of water (Fig. 6-2). As water

moves across the semipermeable membrane, it generates a

pressure, called the osmotic pressure. The osmotic pressure

represents the pressure (measured in millimeters of mercury

[mm Hg]) needed to oppose the movement of water across the

membrane.

The osmotic activity that nondiffusible particles exert in

pulling water from one side of the semipermeable membrane

to the other is measured by a unit called an osmole. The os-

mole is derived from the gram molecular weight of a substance

( i.e., 1 gram molecular weight of a nondiffusible and non-

ionizable substance is equal to 1 osmole). In the clinical set-

ting, osmotic activity usually is expressed in milliosmoles (one

thousandth of an osmole) per liter. Each nondiffusible parti-

cle, large or small, is equally effective in its ability to pull water

through a semipermeable membrane. Thus, it is the number,

rather than the size, of the nondiffusible particles that deter-

mines the osmotic activity of a solution.

The osmotic activity of a solution may be expressed in terms

of either its osmolarity or osmolality. Osmolarity refers to the

osmolar concentration in 1 L of solution (mOsm/L) and osmo-

lality to the osmolar concentration in 1 kg of water (mOsm/kg

of H 2 O). Osmolarity is usually used when referring to ﬂuids

outside the body and osmolality for describing ﬂuids inside the

body. Because 1 L of water weighs 1 kg, the terms osmolarity and

osmolality are often used interchangeably.

contain large amounts of sodium and chloride, moderate

amounts of bicarbonate, but only small quantities of potas-

sium. In contrast to the ECF fluid, the ICF contains small

amounts of sodium, chloride, and bicarbonate and large

amounts of potassium (Table 6-1). It is the ECF levels of elec-

trolytes in the blood or blood serum that are measured clini-

cally. Although blood levels usually are representative of the

total body levels of an electrolyte, this is not always the case,

particularly with potassium, which is approximately 28 times

more concentrated inside the cell than outside.

The cell membrane serves as the primary barrier to the

movement of substances between the ECF and ICF compart-

ments. Lipid-soluble substances such as gases ( i.e., oxygen and

carbon dioxide), which dissolve in the lipid bilayer of the cell

membrane, pass directly through the membrane. Many ions,

such as sodium (Na + ) and potassium (K + ), rely on transport

Concentrations of

Extracellular and Intracellular

Electrolytes in Adults

Electrolyte

Concentration*

Sodium

135–145 mEq/L

10–14 mEq/L

Potassium

3.5–5.0 mEq/L

140–150 mEq/L

Chloride

98–106 mEq/L

3–4 mEq/L

Bicarbonate

24–31 mEq/L

7–10 mEq/L

Calcium

8.5–10.5 mg/dL

< 1 mEq/L

Phosphate/

2.5–4.5 mg/dL

4 mEq/kg †

phosphorus

Magnesium

1.8–3.0 mg/dL

40 mEq/kg †

* Values may vary among laboratories, depending on the method of analysis

used.

† Values vary among various tissues and with nutritional status.

TABLE 6-1

Extracellular

Intracellular

Unit One: Mechanisms of Disease

Osmotic

pressure

Measurement Units

Water

Laboratory measurements of electrolytes in body fluids

are expressed as a concentration or amount of solute in a

given volume of fluid, such as milligrams per deciliter

(mg/dL), milliequivalents per liter (mEq/L), or millimoles

per liter (mmol/L).

The use of milligrams (mg) per deciliter expresses the weight

of the solute in one tenth of a liter (dL). The concentration of

electrolytes, such as calcium, phosphate, and magnesium, is

often expressed in mg/dL.

The milliequivalent is used to express the charge equivalency

for a given weight of an electrolyte: 1 mEq of sodium has the

same number of charges as 1 mEq of chloride, regardless of

molecular weight. The number of milliequivalents of an elec-

trolyte in a liter of solution can be derived from the following

equation:

mg/100 mL × 10 × valence

atomic weight

The Système Internationale (SI) units express electrolyte

concentration in millimoles per liter (mmol/L). A millimole is

one thousandth of a mole, or the molecular weight of a sub-

stance expressed in milligrams. The number of millimoles of

an electrolyte in a liter of solution can be calculated using the

following equation:

mEq =

Semipermeable

membrane

■ FIGURE 6-2 ■ Movement of water across a semipermeable mem-

brane. Water moves from the side that has fewer nondiffusible

particles to the side that has more. The osmotic pressure is equal

to the hydrostatic pressure needed to oppose water movement

across the membrane.

mEq/L

valence

mmol/L =

Serum osmolality, which is largely determined by sodium

and its attendant anions (chloride and bicarbonate), normally

ranges between 275 and 295 mOsm/kg. Blood urea nitrogen

(BUN) and glucose, which also are osmotically active, account

for less than 5% of the total osmotic pressure in the ECF com-

partment. However, this can change, such as when blood glu-

cose levels are elevated in persons with diabetes mellitus or

when BUN levels change rapidly in persons with renal failure.

Compartmental Distribution of Body Fluids

Body water is distributed between the ICF and ECF compart-

ments. In the adult, the ﬂuid in the ICF compartment consti-

tutes approximately 40% of body weight. 1 The ﬂuid in the ECF

compartment is further divided into two major subdivisions:

the plasma compartment, which constitutes approximately 4%

Tonicity. A change in water content causes cells to swell or

shrink. The term tonicity refers to the tension or effect that the

effective osmotic pressure of a solution with impermeable

solutes exerts on cell size because of water movement across

the cell membrane. An effective osmole is one that exerts an os-

motic force and cannot permeate the cell membrane, whereas

an ineffective osmole is one that exerts an osmotic force but

crosses the cell membrane. Tonicity is determined solely by ef-

fective solutes such as glucose that cannot penetrate the cell

membrane, thereby producing an osmotic force that pulls

water into or out of the cell and causing it to change size.

Solutions to which body cells are exposed can be classiﬁed

as isotonic, hypotonic, or hypertonic, depending on whether

they cause cells to swell or shrink (Fig. 6-3). Cells placed in an

isotonic solution, which has the same effective osmolality as

the ICF ( i.e., 280 mOsm/L), neither shrink nor swell. An ex-

ample of an isotonic solution is 0.9% sodium chloride. When

cells are placed in a hypotonic solution, which has a lower ef-

fective osmolality than the ICF, they swell as water moves into

the cell; when they are placed in a hypertonic solution, which

has a greater effective osmolality than ICF, they shrink as water

is pulled out of the cell.

Isotonic solution Hypotonic solution Hypertonic solution

■ FIGURE 6-3 ■ Tonicity. Red cells undergo no change in size in

isotonic solutions ( A ). They increase in size in hypotonic solutions

( B ) and decrease in size in hypertonic solutions ( C ).

Water

Chapter 6: Alterations in Fluids, Electrolytes, and Acid-Base Balance

of body weight, and the interstitial ﬂuid compartment, which

constitutes approximately 15% of body weight (Fig. 6-4).

A third, usually minor, subdivision of the ECF compartment

is the transcellular compartment. It includes the cerebrospinal

ﬂuid and ﬂuid contained in the various body spaces, such as

the peritoneal, pleural, and pericardial cavities; the joint spaces;

and the gastrointestinal tract. Normally, only approximately

1% of ECF is in the transcellular space. This amount can in-

crease considerably in conditions such as ascites, in which large

amounts of ﬂuid are sequestered in the peritoneal cavity. When

the transcellular ﬂuid compartment becomes considerably en-

larged, it is referred to as a third space, because this ﬂuid is not

readily available for exchange with the rest of the ECF.

Intracellular Fluid Volume

The intracellular ﬂuid volume is regulated by proteins and or-

ganic compounds in the ICF and by solutes that move between

the ECF and ICF. The membrane in most cells is freely perme-

able to water; therefore, water moves between the ECF and ICF

as a result of osmosis. In contrast, osmotically active proteins

and other organic compounds cannot pass through the mem-

brane. Water entry into the cell is regulated by these osmoti-

cally active substances as well as by solutes such as sodium and

potassium that pass through the cell membrane. Many of the

intracellular proteins are negatively charged and attract posi-

tively charged ions such as the K + ion, accounting for its higher

concentration in the ICF. The Na + ion, which has a greater con-

centration in the ECF, tends to enter the cell by diffusion. The

Na + ion is osmotically active, and its entry would, if left un-

checked, pull water into the cell until it ruptured. The reason

this does not occur is because the Na + /K + -ATPase membrane

pump continuously removes three Na + ions from the cell for

every two K + ions that are moved back into the cell (see Chap-

ter 1). Situations that impair the function of the Na + /K + -ATPase

pump, such as hypoxia, cause cells to swell because of an accu-

mulation of Na + ions.

Intracellular volume is also affected by the concentration of

osmotically active substances in the extracellular ﬂuid that can-

not cross the cell membrane. In diabetes mellitus, for example,

glucose cannot enter the cell and its increased concentration in

the ECF pulls water out of the cell.

Extracellular Fluid Volume

The ECF is divided between the vascular and interstitial ﬂuid

compartments. The vascular compartment contains blood,

which is essential to the transport of substances such as elec-

trolytes, gases, nutrients, and waste products throughout the

body. The ﬂuid in the interstitial compartment acts as a trans-

port vehicle for gases, nutrients, wastes, and other materials

that move between the vascular compartment and body cells.

The interstitial ﬂuid compartment also provides a reservoir

from which vascular volume can be maintained during periods

of hemorrhage or loss of vascular volume. A tissue gel, which

is a spongelike material composed of large quantities of mu-

copolysaccharides, ﬁlls the tissue spaces and aids in even dis-

tribution of interstitial ﬂuid. Normally, most of the ﬂuid in the

interstitium is in gel form. The tissue gel is supported by colla-

gen ﬁbers that hold the gel in place. The tissue gel, which has a

ﬁrmer consistency than water, opposes the outﬂow of water

from the capillaries and prevents the accumulation of free

water in the interstitial spaces.

Capillary/Interstitial Fluid Exchange

The transfer of water between the vascular and interstitial com-

partments occurs at the capillary level. Four forces control the

movement of water between the capillary and interstitial

spaces: (1) the capillary ﬁltration pressure, which pushes water

out of the capillary into the interstitial spaces; (2) the capillary

colloidal osmotic pressure, which pulls water back into the cap-

illary; (3) the interstitial hydrostatic pressure, which opposes

the movement of water out of the capillary; and (4) the tissue

colloidal osmotic pressure, which pulls water out of the capil-

lary into the interstitial spaces (Fig. 6-5). Normally, the com-

bination of these four forces is such that only a small excess of

ﬂuid remains in the interstitial compartment. This excess ﬂuid

is removed from the interstitium by the lymphatic system and

returned to the systemic circulation.

Capillary ﬁltration refers to the movement of water through

capillary pores because of a mechanical, rather than an os-

motic, force. The capillary ﬁltration pressure, sometimes called

the capillary hydrostatic pressure, is the pressure pushing water

out of the capillary into the interstitial spaces. It reﬂects the

Total body water = 60% body weight

Arterial

end

Venous

end

Intracellular water

40% body weight

Extracellular water

20% body weight

Capillary

filtration

pressure

Capillary

colloidal osmotic

pressure

300

14%

5% 1%

200

Tissue

hydrostatic

pressure

Tissue

Colloidal

pressure

Interstitial

10 liters

28 liters

100

Lymph channels

■ FIGURE 6-4 ■ Approximate size of body compartments in a

70-kg adult.

■ FIGURE 6-5 ■ Exchange of ﬂuid at the capillary level.

Unit One: Mechanisms of Disease

arterial and venous pressures, the precapillary (arterioles) and

postcapillary (venules) resistances, and the force of gravity. 2 A

rise in arterial or venous pressure increases capillary pressure.

A decrease in arterial resistance or increase in venous resistance

increases capillary pressure, and an increase in arterial resis-

tance or decrease in venous resistance decreases capillary pres-

sure. The force of gravity increases capillary pressure in the

dependent parts of the body. In a person who is standing ab-

solutely still, the weight of blood in the vascular column causes

an increase of 1 mm Hg in pressure for every 13.6 mm of dis-

tance from the heart. 2 This pressure results from the weight of

water and is therefore called hydrostatic pressure. In the adult

who is standing absolutely still, the pressure in the veins of feet

can reach 90 mm Hg. This pressure is then transmitted to the

capillaries.

The capillary colloidal osmotic pressure is the osmotic pressure

generated by the plasma proteins that are too large to pass

through the pores of the capillary wall. The term colloidal os-

motic pressure differentiates this type of osmotic pressure from

the osmotic pressure that develops at the cell membrane from

the presence of electrolytes and nonelectrolytes. Because

plasma proteins do not normally penetrate the capillary pores

and because their concentration is greater in the plasma than

in the interstitial ﬂuids, it is capillary colloidal osmotic pressure

that pulls ﬂuids back into the capillary.

The interstitial ﬂuid pressure and the tissue colloidal os-

motic pressure contribute to movement of water into and out

of the interstitial spaces. The interstitial ﬂuid pressure opposes

the outward movement of water from the capillary into the in-

terstitial spaces. The tissue colloidal osmotic pressure pulls

water out of the capillary into the tissue spaces. It reﬂects the

small amount of plasma proteins that normally escape from

the capillary to enter the interstitial spaces.

CHART 6-1 Causes of Edema

Increased Capillary Pressure

Increased vascular volume

Heart failure

Kidney disease

Premenstrual sodium retention

Pregnancy

Environmental heat stress

Venous obstruction

Liver disease with portal vein obstruction

Acute pulmonary edema

Venous thrombosis (thrombophlebitis)

Decreased arteriolar resistance

Calcium channel–blocking drug responses

Decreased Colloidal Osmotic Pressure

Increased loss of plasma proteins

Protein-losing kidney diseases

Extensive burns

Decreased production of plasma proteins

Liver disease

Starvation, malnutrition

Increased Capillary Permeability

Inﬂammation

Allergic reactions ( e.g., hives, angioneurotic edema)

Malignancy ( e.g., ascites, pleural effusion)

Tissue injury and burns

Obstruction of Lymphatic Flow

Malignant obstruction of lymphatic structures

Surgical removal of lymph nodes

Edema

Edema can be deﬁned as palpable swelling produced by ex-

pansion of the interstitial ﬂuid volume. Edema does not

become evident until the interstitial ﬂuid volume has been

increased by 2.5 to 3 L. 3

The physiologic mechanisms that contribute to edema

formation include factors that: (1) increase the capillary fil-

tration pressure, (2) decrease the capillary colloidal osmotic

pressure, (3) increase capillary permeability, or (4) produce

obstruction to lymph flow. The causes of edema are summa-

rized in Chart 6-1.

Generalized edema is common in conditions such as con-

gestive heart failure that produce ﬂuid retention and venous

congestion. In right-sided heart failure, blood dams up through-

out the entire venous system, causing organ congestion and

edema of the dependent extremities. Decreased sodium and

water excretion by the kidneys leads to an increase in ECF vol-

ume with an increase in capillary volume and pressure with

subsequent movement of ﬂuid into the tissue spaces. The

swelling of hands and feet that occurs in healthy persons dur-

ing hot weather results from vasodilation of superﬁcial blood

vessels along with sodium and water retention.

Because of the effects of gravity, edema resulting from in-

creased capillary pressure commonly causes fluid to accumu-

late in the dependent parts of the body, a condition referred

to as dependent edema. For example, edema of the ankles and

feet becomes more pronounced during prolonged periods of

standing.

Increased Capillary Filtration Pressure. As the capillary ﬁltra-

tion pressure rises, the movement of vascular ﬂuid into the in-

terstitial spaces increases. Among the factors that increase capil-

lary pressure are: (1) a decrease in the resistance to ﬂow through

the precapillary sphincters; (2) an increase in venous pressure

or resistance to outﬂow at the postcapillary sphincters, and

(3) capillary distention caused by increased vascular volume.

Edema can be either localized or generalized. The localized

edema that occurs with urticaria ( i.e., hives) or other allergic or

inﬂammatory conditions results from the release of histamine

and other inﬂammatory mediators that cause dilation of the

precapillary sphincters and arterioles that supply the swollen

lesions. Thrombophlebitis obstructs venous ﬂow, producing

an elevation of venous pressure and edema of the affected part,

usually one of the lower extremities.

Decreased Capillary Colloidal Osmotic Pressure. Plasma pro-

teins exert the osmotic force needed to pull fluid back into the

capillary from the tissue spaces. The plasma proteins consti-

tute a mixture of proteins, including albumin, globulins, and

fibrinogen. Albumin, the smallest of the plasma proteins,

has a molecular weight of 69,000; globulins have molecular

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