1 Body Fluids - Constanzo handouts, summarizes entire chapter down to exactly what you need PDF

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Constanzo handouts, summarizes entire chapter down to exactly what you need to know. ...

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Body Fluids 1 and 2 Linda Costanzo, Ph.D.

OBEJCTIVES: After studying this lecture, the student should understand: 1. The distribution of water between the major body fluid compartments. 2. How to measure the volumes of body fluid compartments using marker substances. 3. The differences in composition between the major body fluid compartments. 4. The pathophysiology of the major fluid shift examples, including the predicted changes in osmolarity, ECF and ICF volume, and hematocrit. 5. How to calculate new osmolarity and new ECF and ICF volumes following a fluid shift.

I.

BODY FLUID COMPARTMENTS Water content (total body water, or TBW) comprises about 60% of body weight. The percentage varies between 50-70%, depending on gender and amount of adipose tissue. Males tend to have a higher percentage of water than females. Water content is inversely correlated with adipose tissue. Infants have up to 75% body weight as water, which is why severe diarrhea can be life-threatening. Water is distributed between two major compartments: intracellular fluid (ICF) and extracellular fluid (ECF), which are separated from each other by cell membranes. ICF is 2/3 of TBW and ECF is 1/3 of TBW. ECF is further subdivided into two compartments, the interstitial fluid and plasma compartments, which are separated from each other by capillary walls. Interstitial fluid is 3/4 of ECF, and plasma water is 1/4 of ECF. Lymph, which is part of the ECF, is interstitial fluid that is collected in the lymphatic vessels and then returned to the plasma compartment. An additional minor compartment is the transcellular fluid, which is not part of ICF or ECF. Transcellular fluids are separated from the rest of the body fluids by a layer of cells, and they include gastrointestinal, peritoneal, pleural, and cerebrospinal fluids. Collectively, the volume of transcellular fluids is small, so they are ignored in the above summary numbers.

Figure 1. Body fluid compartments. Total body water is distributed between intracellular fluid and extracellular fluid. Water as a percentage of body weight is indicated for the major compartments.

A simple tool is the 60-40-20 rule. Approximately 60% of body weight is water (TBW), 40% of body weight is ICF, and 20% is ECF. (ICF is 2/3 of TBW, i.e., 40% of body weight; ECF is 1/3 of TBW, i.e., 20% of body weight.) II.

MEASUREMENT OF BODY FLUID COMPARTMENT VOLUMES The volumes of body fluid compartments are measured with a method based on the principle of dilution. A.

Method 1.

A marker substance is selected, whose physical characteristics are such that it distributes only in the body fluid compartment whose volume you wish to calculate. For example, isotopic water (e.g., D20) distributes throughout the TBW, and thus is a marker for TBW. Mannitol, a large sugar, distributes throughout the ECF, but does not cross cell membranes, and thus is a marker for ECF volume. Radioactively labeled albumin distributes wherever

albumin is located, and thus is a marker for plasma volume. See below for list of the marker substances. 2.

A known amount of the marker is given. Wait for equilibration, then measure the concentration of the marker. Correct for any losses of marker that occurred during the equilibration period (e.g., excretion in urine).

3.

Knowing the amount present in the body (amount given any minus loss during equilibration) and the measured concentration, calculate the volume of distribution of the marker substance (the volume it was dissolved in). This is the volume of that body fluid compartment, e.g., volume of distribution of D20 is volume of TBW, etc. Volume = amount concentration or, more specifically Volume = amount given - amount lost during equilibration concentration

B.

Marker substances Direct measurements and their marker substances:

TBW

ECF

Plasma

Marker Substances D 20 HT0 Antipyrene Mannitol Inulin Radioactive sulfate Radioiodinated serum albumin (RISA) Evan’s blue (dye that binds to serum albumin)

Indirect measurements (there is no unique marker substance for these compartments): ICF TBW - ECF Interstitial ECF - plasma

C. Example A 70 kg male is injected with 1.5 g of mannitol. During the equilibration period, 5% of the mannitol was excreted/hour. After two hours of equilibration, the plasma concentration of mannitol was measured as 9 mg/100 ml. What body fluid compartment is being measured, and what is its volume (i.e., what is the volume of distribution of mannitol)? Is this a reasonable number? Volume = 1500 mg - 150 mg 9 mg/100 ml = 1350 mg 90 mg/L = 15 L (volume of distribution of mannitol, or ECF volume) An ECF volume of 15 L is reasonable for a 70 kg male. (70 kg ≈ 70 L. 20% of 70 L = 14 L......close enough for an approximation.) III.

COMPOSITION OF BODY FLUID COMPARTMENTS The major difference in composition of body fluid compartments is between ICF and ECF, which are essentially “mirror images” of each other – what’s high in concentration in ECF is low in ICF, and vice versa. Transporters in cell membranes create and maintain most of these differences in composition. There are also small differences in composition between plasma and interstitial fluid (which are both ECF); these differences in composition are due to the GibbsDonnan effect of plasma protein, whereby interstitial fluid has a slighter higher concentration of small anions (e.g., Cl-) and a slighter lower concentration of small cations (e.g., Na+) than plasma.

Solute Na+, mmol/L K+, mmol/L Ca2+, mmol/L (ionized) Cl- , mmol/L HCO3- , mmol/L Protein, g/dL Osmolarity, mOsm/L

Plasma 144 4.8 1.3 100 24 7 290

Interstitial 140 4.5 1.2 109 25 ---290

Intracellular 15 120 10-7M 20 15 30 290

A few tidbits on units. Please save for reference! 1. Concentrations in body fluids are often expressed in molarity, such as mmol/L.

2. For electrolytes, we sometimes use equivalents, such as mEq/L, which is the concentration in mmol/L x charge on the ion. Thus, for univalent ions, mEq/L = mmol/L; for divalent ions, mEq/L = 2 x mmol/L. That is, a Na+ concentration of 1 mmol/L = 1 mEq/L; a Ca2+ concentration of 1 mmol/L = 2 mEq/L. 3. Osmolarity is total solute concentration, expressed in units of mOsmoles/liter. Osmolarity is concentration of solute particles, or concentration in mmol/L x number of particles that dissociate in solution. The number of particles that dissociate in solution is called “g,” the osmotic coefficient. For example, the osmolarity of 150 mmol/L NaCl = 150 mmol/L x 2 = 300 mOsm/L (since NaCl dissociates into two particles in solution, i.e., g = 2). Osmolality is virtually the same thing as osmolarity, but expressed as mOsmoles/kg H20. Plasma osmolarity can be approximated as 2 x [Na+]. I will show you a more precise estimate of plasma osmolarity in a subsequent lecture. 4. Substances like proteins are conventionally expressed in g/dL, where a dL (deciliter) is 100 ml and is also called “%.” a. % can mean “g per 100 ml.” For example, 0.9% NaCl is 0.9 g NaCl/100 ml. It’s weird, but that’s what it means. b. mg % means “mg per 100 ml.” For example, 5 mg% KCl means 5 mg KCl/100 ml. IV.

FLUID SHIFTS - QUALITATIVE A.

Definitions and rules for fluid shifts 1.

Osmolarity is the concentration of solute particles, in units of mOsm/L.

2.

Osmolarities of ECF and ICF are always equal in the steady state (see Table above).

3.

H2O shifts freely across cell membranes to establish and maintain this equality. (This is the “fluid shift” we’ll be talking about.)

4.

If a disturbance causes a change in ECF osmolarity, thus producing a transient difference in ECF and ICF osmolarity, H2O shifts between ECF and ICF until the osmolarities are equal again; once the fluid shift has occurred, this is called the new steady state.

5.

For purposes of discussion, we assume that NaCl, NaHCO3, and mannitol are “extracellular” solutes; that is, they are confined to

ECF because they do not cross cell membranes. 6.

Fluid shift disturbances are categorized according to whether they involve an increase or decrease in ECF volume: a.

b.

7.

Fluid shift disturbances are also categorized according to whether they cause a change in body fluid osmolarity: a. b. c.

B.

C.

Volume contraction means a decrease in ECF volume; also called volume depletion. Volume contraction causes decreased blood volume and decreased blood pressure (Pa). Volume expansion means an increase in ECF volume. Volume expansion can cause increased Pa and edema.

Isosmotic means no change in body fluid osmolarity Hyperosmotic means body fluid osmolarity is increased Hyposmotic means body fluid osmolarity is decreased

Method for analyzing fluid shift problems – do it this way every time! 1.

Read the problem or case scenario and determine clearly what was gained or lost. For example, if a person eats dry NaCl, then NaCl was gained. If a person sweats profusely on a hot day, then NaCl and water were lost.

2.

Assume that any gain or loss from the body affects the ECF first.

3.

Predict whether the gain or loss would cause a change in ECF osmolarity. For example, if a person eats dry NaCl, then NaCl is added to ECF and causes an increase in ECF osmolarity.

4.

If there is a predicted change in ECF osmolarity, determine which way water must shift to make the ECF and ICF osmolarities equal again.

5.

Finally from your analysis above, predict the directional changes in the new steady state (after any fluid shift has occurred) for: ECF and ICF osmolarities, ICF volume, ECF volume, and TBW. Also predict whether there will be a change in hematocrit and plasma protein concentration. (Reminder: hematocrit is the fractional blood volume occupied by red blood cells [RBCs].)

Examples (see following table and figure) 1.

Loss of isosmotic NaCl (isosmotic volume contraction) – e.g., diarrhea. A person who has diarrhea loses isosmotic (and isotonic)

fluid from the GI tract. The loss causes no change in ECF osmolarity since the fluid lost has the same osmolarity as the body fluids. Since there is no change in ECF osmolarity, no fluid shift is required. Thus, in the new steady state, ECF and ICF osmolarities are unchanged, ECF volume is decreased (due to the loss of isosmotic fluid, and ICF volume is unchanged. TBW is decreased because ECF volume is decreased. In considering the effects of the disturbance on plasma protein concentration and hematocrit, remember that plasma is part of ECF; if ECF volume decreases, then plasma volume also decreases. Plasma protein concentration is increased by a concentrating effect (the fluid lost in diarrhea does not contain plasma proteins). Hematocrit is also increased by a concentrating effect, because the same number of RBCs are “dissolved” in a smaller plasma volume.

2.

Loss of water (hyperosmotic volume contraction) – e.g. water deprivation and diabetes insipidus (lack of ADH, antidiuretic hormone). For example, a person with a high fever loses “insensible” water. If this water is not replaced, there will be an increase in ECF osmolarity (water is lost from ECF, solute is left behind and becomes concentrated). Thus, transiently, ECF osmolarity is higher than ICF osmolarity. The body will not permit this inequality, and water shifts from ICF into ECF until ECF and ICF osmolarities are again equal, and both higher than normal. In the new steady state, ECF and ICF osmolarities are increased. ECF volume is decreased (because of the initial loss of water). ICF volume is decreased (because of the water shift). TBW is decreased. Plasma protein concentration is increased (because the loss of ECF volume concentrates the plasma proteins). Hematocrit, it seems, would also be increased. However, hematocrit is unchanged because of two offsetting effects. (1) The loss of ECF and plasma volume “concentrates” the RBCs (same number of RBCs in a smaller volume), which tends to increase hematocrit. (2) RBCs are cells. In this example, there is a water shift out of cells, causing the RBCs to shrink, and therefore occupy a smaller fractional volume, which tends to decrease hematocrit.

3.

Loss of NaCl (hyposmotic volume contraction) – e.g, adrenal insufficiency. In adrenal insufficiency, there is lack of aldosterone, the hormone that promotes renal Na+ reabsorption. When aldosterone is lacking, there is excess urinary excretion of NaCl and net loss of NaCl from the body. When NaCl is lost from ECF, there is a decrease in ECF osmolarity. Thus, transiently, ECF osmolarity is lower than ICF osmolarity. Water shifts from ECF to

ICF until the osmolarities are equal again, and both lower than normal. In the new steady state, ECF and ICF osmolarities are decreased. ECF volume is decreased (due to the water shift), ICF volume is increased (due to the water shift), and TBW is unchanged. Plasma protein concentration is increased due to concentration of plasma proteins. Hematocrit is increased both due to “concentration” of RBCs and due to the shift of water into RBCs (causing them to swell). 4.

Gain of isosmotic NaCl (isosmotic volume expansion) -- e.g., infusion of isosmotic saline. A person is infused with an isotonic (and isosmotic) saline (NaCl) solution. The infusion would cause no change in ECF osmolarity, since the infused solution has the same osmolarity as the body fluids. Since there is no change in ECF osmolarity, no fluid shift is required. Thus, in the new steady state, ECF and ICF osmolarities are unchanged, ECF volume is increased (due to the addition of the infused solution, and ICF volume is unchanged. TBW is increased because ECF volume is increased. Plasma protein concentration is decreased by dilution (the infused solution contained no protein). Hematocrit is also decreased because the same number of RBCs are “dissolved” in a larger volume.

5.

Gain of NaCl (hyperosmotic volume expansion) – e.g., high NaCl intake. NaCl is added to ECF, and there is an increase in ECF osmolarity. Thus, transiently, ECF osmolarity is higher than ICF osmolarity. Water shifts from ICF to ECF until the osmolarities are equal again, and both higher than normal. In the new steady state, ECF and ICF osmolarities are increased. ECF volume is increased (due to the water shift), ICF volume is decreased (due to the water shift), and TBW is unchanged. Plasma protein concentration is decreased due to dilution of plasma proteins. Hematocrit is decreased both due to “dilution” of RBCs and due to the shift of water out of RBCs (causing them to shrink).

6.

Gain of water (hyposmotic volume expansion) – e.g., excess water-drinking and SIADH (syndrome of inappropriate ADH). Water is first added to ECF and there is a decrease in ECF osmolarity. Transiently, ECF osmolarity is lower than ICF osmolarity. The body will not permit this inequality, and water shifts from ECF into ICF until ECF and ICF osmolarities are again equal, and both lower than normal. In the new steady state, ECF and ICF osmolarities are decreased. ECF volume is increased (because of the initial addition of water). ICF volume is increased

(because of the water shift). TBW is increased. Plasma protein concentration is decreased (because the increased ECF volume dilutes plasma proteins). Hematocrit, it seems, would also be decreased. However, hematocrit is unchanged because of two offsetting effects. (1) The increase in ECF and plasma volume “dilutes” the RBCs (same number of RBCs in a larger volume), which tends to decrease hematocrit. (2) RBCs are cells, and in this example, there is a water shift into cells, causing the RBCs to swell, and therefore occupy a larger fractional volume, which tends to increase hematocrit.

Type Isosmotic volume contraction

Disturbances of Body Fluids Plasma ECF ICF Example Osmolarity Hematocrit Volume Volume [protein] Diarrhea

↓

N.C.

N.C.

↑

↑

Hyperosmotic volume Sweating; fever; diabetes ↓ ↑ N.C. ↑ ↓ contraction insipidus Hyposmotic volume Adrenal ↑ ↓ ↑ ↑ ↓ contraction insufficiency Isosmotic volume Infusion of N.C. N.C. ↓ ↓ ↑ isotonic NaCl expansion Hyperosmotic volume High NaCl ↓ ↑ ↓ ↓ ↑ intake expansion Hyposmotic volume SIADH ↑ ↓ N.C. ↓ ↑ expansion ECF, Extracellular fluid; ICF, intracellular fluid; NaCl, sodium chloride; N.C., no change; SIADH syndrome of inappropriate antidiuretic hormone.

Figure 2. Shifts of water between body fluid compartments. Normal extracellular fluid (ECF) and intracellular fluid (ICF) osmolarity are shown by solid lines. Changes in volume and osmolarity in response to various disturbances are shown by dashed lines. SIADH, Syndrome of inappropriate antidiuretic hormone. V.

FLUID SHIFTS - QUANTITATIVE A.

How to analyze and calculate. Fluid shift problems can also be analyzed quantitatively. That is, in addition to the qualitative approach above (e.g., whether osmolarity is increased or decreased, and whether ECF volume is increased or decreased), we also can calculate the exact values for new steady state osmolarity and body fluid volumes. That’s what I mean by “quantitative.” To work these problems correctly and reliably, you must perform the following steps in the following order. In the next section of Examples, you will see how to work problems using these steps. 1.

2.

First, determine clearly what was gained or lost in the problem. From the case scenario, calculate the number of osmoles (mosmoles) gained or lost and the volume (L) gained or lost. Next, calculate the new osmolarity of TBW in the new steady state. We do this step next because we know that the new steady state osmolarity will be the same throughout the body fluid

3.

B.

compartments (TBW). The calculated value of TBW osmolarity will be the value for ECF and ICF osmolarities used in Step 3. Finally, using the new, calculated TBW osmolarity (per Step 2), calculate the new ECF and ICF volumes.

Examples 1.

A man with a TBW of 40 L, ICF volume of 26.4 L, ECF volume of 13.6 L, and plasma osmolarity of 290 mOsm/L drinks 3 L of water. In the new steady state, what is his plasma osmolarity, TBW, ECF volume, and ICF volume?

What was gained or lost? Gain = 3 L of water New TBW osmolarity? Old TBW osmoles = New TBW = New TBW osmolarity = New ECF volume? Old ECF osmoles New ECF volume

New ICF volume? Old ICF osmoles New ICF volume

2.

40 L x 290 mOsm/L = 11,600 mOsm 40 L + 3 L = 43 L 11,600 mosmoles/43 L = 269.8 mOsm/L

= = = =

13.6 L x 290 mOsmles/L 3944 mOsm 3944 mosmoles/ 269.8 mOsm/L 14.6 L

= = = =

26.4 L x 290 mOsm/L 7656 mOsm 7656 mOsm/269.8 mOsm/L 28.4 L

A woman with an ICF volume of 28 L, ECF volume of 14 L, and plasma osmolarity of 295 mOsm/L, eats a bag of potato chips that contains 300 mmoles of NaCl. Assuming that the osmotic coefficient of NaCl is 2, in the new steady state, what is her plasma osmolarity, TBW, ECF volume and ICF volume? How much water shifted, and in which direction?

What was gained or lost? Gain = 300 mmoles of NaCl = 600 mosmoles (300 x 2)

New TBW osmolarity? Old TBW = = Old TBW osmoles = = New TBW osmoles = = New TBW osmolarity= = New ECF volume? Old ECF osmoles New ECF osmoles New ECF volume

New ICF volume? Old ICF osmoles New ICF volume

28 L + 14 L 42 L 42 L x 295 mOsm/L 12,390 mOsm 12,390 mOsm + 600 mOsm 12,990 mOsm 12,990 mOsm/42L 309.3 mOsm/L

= = = = = =

14 L x 295 mOsm/L 4130 m...