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which one of the following?

A.Elevated glucose levels

B.Reduced BUN

C.Decreased fatty acid release from the adipocyte

D.Inhibition of liver oxidation of ketone bodies

E.Reduced muscle use of fatty acids3. In a well-nourished individual, as the length of fasting increases from overnight to 1 week, which

one of the following is most likely to occur?

A.Blood glucose levels decrease by approximately 50%.

B.Red blood cells switch to using ketone bodies.

C.Muscles decrease their use of ketone bodies, which increase in the blood.

D.The brain begins to use fatty acids as a major fuel.

E.Adipose tissue triacylglycerols are nearly depleted.

4. A hospitalized patient had low levels of serum albumin and high levels of blood ammonia. His CHI

was 98%. His BMI was 20.5. BUN was in the normal range, consistent with normal kidney function.

The diagnosis most consistent with these findings is which one of the following?

A.A loss of hepatic function (e.g., alcohol-induced cirrhosis)

B.Anorexia nervosa

C.Kwashiorkor (protein malnutrition)

D.Marasmus (PEM)

E.Decreased absorption of amino acids by intestinal epithelial cells (e.g., celiac disease)

5. Otto S., an overweight medical student (see Chapter 1), discovered that he could not exercise

enough during his summer clerkship rotations to lose 2 to 3 lb/wk. He decided to lose weight by

eating only 300 calories/day of a dietary supplement that provided half the calories as carbohydrate

and half as protein. In addition, he consumed a multivitamin supplement. During the first 3 days on

this diet, which statement best represents the state of Otto’s metabolism?

A.His protein intake met the Recommended Dietary Allowance (RDA) for protein.

B.His carbohydrate intake met the fuel needs of his brain.

C.Both his adipose mass and his muscle mass decreased.

D.He remained in nitrogen balance.

E.He developed severe hypoglycemia.

6. A pregnant woman is having an oral glucose tolerance test done to diagnose gestational diabetes.

The test consists of ingesting a concentrated solution of glucose (75 g of glucose) and then having her

blood glucose levels measured at various times after ingesting the sugar. Her test results come back

normal. At what time after her oral sugar solution in consumed will she have the highest blood

glucose level?

A.Immediately

B.1 hour

C.2 hours

D.3 hours

E.4 hours

7. A patient with frequent sweating and tremors is diagnosed with “reactive hypoglycemia” and has

been prescribed a small meal every 4 hours throughout the day. The patient most likely is impaired in

carrying out which one of the following?

A.Glycogenesis of liver glycogen stores

B.Glycogenolysis of muscle glycogen stores

C.Glycogenolysis of liver glycogen storesD. Glycogenesis of muscle glycogen stores

E.Glycogenesis of adipose tissue glycogen stores

8. An activist is on a hunger strike to bring attention to her latest cause, and she has only consumed H2O

and vitamins for the past 5 days. Which ONE of the following organs/structures has begun to use

ketone bodies as a major secondary fuel source?

A.Red blood cells

B.Brain

C.Liver

D.Heart

E.All of the above

9.You are evaluating a patient who has a mutation that hinders his ability to carry out liver

glycogenolysis. One initial finding shortly after entering the fasting state in this patient would be

which ONE of the following? A. Hyperglycemia

B. Ketosis (elevated levels of ketone bodies) C. Significantly increased urea synthesis

D. Reduced blood lactate levels E. Hypoglycemia

10.A prisoner has gone on a hunger strike, drinking only water. Careful monitoring of the prisoner

demonstrated a drop in BUN during the second week of the fast. This occurred because of which one

of the following?

A. Enhanced glycogenolysis

B. Reduced ketone body formation

C. A decrease in the rate of gluconeogenesis D. An increase in the rate of gluconeogenesis E. Enhanced glucose metabolism in the brain ANSWERS TO REVIEW QUESTIONS

1.The answer is A. By 24 hours after a meal, hepatic (liver) gluconeogenesis is the major source of

blood glucose because hepatic glycogen stores have been nearly depleted. Muscle and other

tissues lack an enzyme necessary to convert glycogen or amino acids to glucose for export (thus, B

is incorrect). The liver is the only significant source of blood glucose. Glucose is synthesized in

the liver from amino acids (provided by protein degradation), from glycerol (provided by

hydrolysis of triacylglycerols in adipose tissue), and from lactate (provided by anaerobic

glycolysis in red blood cells and other tissues). Glucose cannot be synthesized from fatty acids or

ketone bodies (thus, D and E are incorrect).

2.The answer is A. The liver will produce ketone bodies when fatty acid oxidation is increased,

which occurs when glucagon is the predominant hormone (glucagon leads to fatty acid release

from the fat cells for oxidation in the liver and muscle). This would be the case in an individual

who cannot produce insulin and is not taking insulin injections. However, in this situation, theketone bodies are not being used by the nervous system (brain) because of the high levels of

glucose in the circulation. This leads to severely elevated ketone levels because of non-use. The

glucose is high because, in the absence of insulin, muscle and fat cells are not using the glucose in

circulation as an energy source. Recall that although the liver produces ketone bodies, it lacks a

necessary enzyme to use ketone bodies as an energy source. There is no relation between BUN

levels and the rate of ketone body production. The muscle reduces its use of ketone bodies under

these conditions but not its use of fatty acids.

3.The answer is C. The major change during prolonged fasting is that as muscles decrease their use

of ketone bodies, ketone bodies increase enormously in the blood and are used by the

brain as a

fuel. However, even during starvation, glucose is still required by the brain, which cannot oxidize

fatty acids to an appreciable extent (thus, D is incorrect). Red blood cells can use only glucose as

a fuel (thus, B is incorrect). Because the brain, red blood cells, and certain other tissues are

glucose-dependent, the liver continues to synthesize glucose, and blood glucose levels are

maintained at only slightly less than fasting levels (thus, A is incorrect). Adipose tissue stores

(~135,000 kcal) are not depleted in a well-nourished individual after 1 week of fasting (thus, E is

incorrect).

4.The answer is A. Decreased serum albumin could have several causes, including hepatic disease,

which decreases the ability of the liver to synthesize serum proteins; protein malnutrition;

marasmus; or diseases that affect the ability of the intestine to digest protein and absorb amino

acids. However, his BMI is in the healthy weight range (thus, B and D are incorrect). His normal

CHI indicates that he has not lost muscle mass and is therefore not suffering from protein

malnutrition (thus, B, C, D, and E are incorrect).

5.The answer is C. His protein intake of 150 calories is about 37 g of protein (150 calories ÷ 4

calories/g = 37 g), below the RDA of 0.8 g of protein/kg of body weight (thus, A is incorrect

because Otto weighs ~88 kg). His carbohydrate intake of 150 calories is below the glucose

requirements of his brain and red blood cells (~150 g/day; see Chapter 2) (thus, B is incorrect).

Therefore, he will be breaking down muscle protein to synthesize glucose for the brain and other

glucose-dependent tissues and adipose tissue mass to supply fatty acids for muscle and tissues

able to oxidize fatty acids. Because he will be breaking down muscle protein to amino acids and

converting the nitrogen from both these amino acids and his dietary amino acids to urea, his

nitrogen excretion will be greater than his intake and he will be in negative nitrogen balance (thus,

D is incorrect). It is unlikely that he will develop hypoglycemia while he is able to supply

gluconeogenic precursors.

6.The answer is B. Blood glucose levels peak approximately 1 hour after eating and return to the

fasting range by about 2 hours. If the blood glucose levels remain elevated for an extended period

of time, it is an indication of impaired glucose transport (insulin stimulates glucose transport into

muscle and adipose tissue). If the blood glucose levels are <140 mg/dL at 2 hours after the test,

the result is considered normal. If the levels are between 140 and 200 mg/dL, the patient is

considered to have “impaired glucose tolerance.” If the levels are >200 mg/dL after 2 hours, a

diagnosis of diabetes is confirmed.

7.The answer is C. Blood glucose levels return to the fasting range about 2 hours after a meal. Thedecrease in blood glucose causes a decrease in insulin and an increase in glucagon production.

Glucagon stimulates the liver to degrade its glycogen stores (glycogenolysis) and release glucose

into the bloodstream. If the patient eats another meal within a few hours, the

patient returns to the

fed state. Glycogenesis is the synthesis of glycogen. While the muscle contains glycogen stores,

degradation of muscle glycogen only benefits the muscle; the muscle cannot export glucose to

maintain blood glucose levels. Adipose tissue does not contain significant levels of glycogen.

8.The answer is B. After 24 to 48 hours of the fast, the activist’s liver has run out of glycogen and

all glucose is being produced from gluconeogenesis. The liver is oxidizing fatty acids as an energy

source and producing ketone bodies as an alternative fuel source for the nervous system (brain).

Muscle continues to use fatty acids as a fuel source but decreases its use of ketone bodies, thereby

raising the blood concentration of ketone bodies. At the higher concentration of ketone bodies in

the blood, the brain can use the ketone bodies and does not need as much glucose. Up to 40% of

the brain’s energy needs can be met by ketone bodies, but the other 60% still needs to be met by

glucose as an energy source. As the brain uses ketone bodies, the liver can reduce gluconeogenesis, thereby reducing the need for amino acids as precursors and preserving muscle

protein. Red blood cells have no mitochondria so they must use glucose only as an energy source

(ketone bodies are oxidized in mitochondria). The liver cannot use ketone bodies because it lacks

a key enzyme for their degradation, and the heart uses lactate as an energy source along with fatty

acids.

9.The answer is E. As blood glucose levels begin to drop, glucagon is released from the pancreas,

which stimulates glycogenolysis in the liver. The glucose produced from liver glycogen is used

initially to maintain blood glucose levels during the early stages of a fast. Gluconeogenesis will

kick in later because this process requires more energy than glycogenolysis, and fatty acid

oxidation must be under way before glucose can be produced from lactate, glycerol, and amino

acids. Ketone bodies will not be evident after initiating a fast (the levels of ketones will not be

significant until 24 to 48 hours after a fast is initiated). Significant protein degradation will not

occur until the liver runs out of glycogen, about 24 to 36 hours after the start of the fast (and

without protein degradation, urea synthesis will remain normal). The red blood cells will still be

metabolizing glucose, so blood lactate levels (the end product of red cell glucose metabolism)

will remain relatively constant.

10.The answer is C. As a fast increases in length, the liver will begin to produce ketone bodies from

the oxidation of fatty acids obtained from the adipocyte. As the ketone bodies are released from

the liver, the brain will begin to use them, reducing its need for glucose by approximately 40%.

This, in turn, reduces the need of the liver to produce glucose by gluconeogenesis (recall that

glycogen stores are depleted by 36 hours of the fast), which, in turn, reduces the rate of protein

degradation in the muscle. The overall effect is to spare muscle protein for as long as possible.Ch T

emical and Biologic

Foundations of Biochemistry SECTION

II

he discipline of biochemistry developed as chemists began to study the molecules of cells, tissues,

and body fluids and physicians began to look for the molecular basis of various diseases. Today, the

practice of medicine depends on understanding the roles and interactions of the enormous number of

different chemicals that enable our bodies to function. The task is less overwhelming if one knows the

properties, nomenclature, and functions of classes of compounds, such as carbohydrates and enzymes. The

intent of this section is to review some of this information in a context relevant to medicine. Students enter

medical school with different scientific backgrounds, and some of the information in this section will

therefore be familiar to many students.

The nomenclature used to describe patients may include the name of a class of compounds.

For example, a patient with diabetes mellitus who has hyperglycemia has hyper (high) concentrations of carbohydrates (glyc) in her blood (emia).

We begin by discussing the relationship of metabolic acids and buffers to blood pH in Chapter 4.

Chapter 5 focuses on the nomenclature, structure, and some of the properties of the major classes of

compounds found in the human body. The structure of a molecule determines its function and its fate, and

the common name of a compound can often tell you something about its structure. Proteins are linear chains of amino acids that fold into complex three-dimensional structures. They

function in the maintenance of cellular and tissue structure and the transport and movement of molecules.

Some proteins are enzymes, which are catalysts that enormously increase the rate of chemical reactions in

the body. Chapters 6 and 7 describe the amino acids and their interactions within proteins that provide

proteins with a flexible and functional three-dimensional structure. Chapters 8 and 9 describe the

properties, functions, and regulation of enzymes.

Our proteins and other compounds function within a specialized environment defined by their location

in cells or body fluids. Their ability to function is partially dependent on membranes that restrict the free

movement of molecules. Chapter 10 includes a brief review of the components of cells, their organizationinto subcellular organelles, and the manner in which various types of molecules move into cells and

between compartments within a cell.

From a biochemist’s point of view, most metabolic diseases are caused by enzymes and other proteins that malfunction, and the pharmacologic drugs used to treat these diseases

correct that malfunction. For example, individuals with atherosclerosis, who have elevated blood

cholesterol levels, are treated with a drug that inhibits an enzyme in the pathway for cholesterol

synthesis. Even a bacterial infection can be considered a disease of protein function, if one

considers the bacterial toxins that are proteins, the enzymes in our cells affected by these toxins,

and the proteins involved in the immune response when we try to destroy these bacteria.

In a complex organism such as a human, different cell types carry out different functions. This

specialization of function requires cells to communicate with each other. One of the ways they

communicate is through secretion of chemical messengers that carry a signal to another cell. In Chapter

11, we consider some of the principles of cell signaling and describe some of the chemical messenger

systems.

Dianne A. had an elevated blood glucose level of 684 mg/dL. What is the molar concentration of glucose in Dianne’s blood? (Hint: The molecular weight of glucose [C6H12O6] is 180 g/mol.)

Milligrams per deciliter (mg/dL) is the common way clinicians in the United States express

blood glucose concentration. A concentration of 684 mg/dLis 684 mg per 100 mLof blood,

or 6,480 mg/L, or 6.48 g/L. If 6.84 g/L is divided by 180 g/mol, one obtains a value of 0.038

mol/L, which is 0.038 M, or 38 mM.

Both in this book and in medical practice, you will need to interconvert different units used for the

weight and size of compounds and for their concentration in blood and other fluids. Table II.1 provides

definitions of some of the units used for these interconversions.Water, Acids, Bases, and Buffers 4

For additional ancillary materials related to this chapter, please visit thePoint. Approximately 60% of our body is water. It acts as a solvent for the substances we need, such as K+,

glucose, adenosine triphosphate (ATP), and proteins. It is important for the transport of molecules and

heat. Many of the compounds produced in the body and dissolved in water contain chemical groups that

act as acids or bases, releasing or accepting hydrogen ions. The hydrogen ion content and the amount of

body water are controlled to maintain a constant environment for the cells called homeostasis (same state)

(Fig. 4.1). Significant deviations from a constant environment, such as acidosis or dehydration, may be

life threatening. This chapter describes the role of water in the body and the buffer systems used by the

body to protect itself from acids and bases produced from metabolism.Water. Water is distributed between intracellular and extracellular compartments, the latter comprising

interstitial fluids, blood, and lymph. Because water is a dipolar molecule with an uneven distribution of

electrons between the hydrogen and oxygen atoms, it forms hydrogen bonds with other polar molecules

and acts as a solvent.

The pH of Water. Water dissociates to a slight extent to form hydrogen (H+) and hydroxyl (OH−) ions.

The concentration of hydrogen ions determines the acidity of the solution, which is expressed in terms of

pH. The pH of a solution is the negative log of its hydrogen ion concentration. Acids and Bases. An acid is a substance that can release hydrogen ions (protons), and a base is a

substance that can accept hydrogen ions. When dissolved in water, almost all the molecules of a strong

acid dissociate and release their hydrogen ions, but only a small percentage of the total molecules of a

weak acid dissociate. A weak acid has a characteristic dissociation constant, Ka. The relationship

between the pH of a solution, the Ka of an acid, and the extent of its dissociation are given by the

Henderson-Hasselbalch equation.

Buffers. A buffer is a mixture of an undissociated acid and its conjugate base (the form of the acid that

has lost its proton). It causes a solution to resist changes in pH when either H+ or OH− is added. A buffer

has its greatest buffering capacity in the pH range near its pKa (the negative log

of its Ka). Two factorsdetermine the effectiveness of a buffer: its pKa relative to the pH of the solution and its concentration.

Metabolic Acids and Bases. Normal metabolism generates CO2, metabolic acids (e.g., lactic acid and

ketone bodies), and inorganic acids (e.g., sulfuric acid). The major source of acid is CO2, which reacts

with water to produce carbonic acid. To maintain the pH of body fluids in a range compatible with life,

the body has buffers such as bicarbonate, phosphate, and hemoglobin (see Fig. 4.1). Ultimately,

respiratory mechanisms remove carbonic acid through the expiration of CO2, and the kidneys excrete

acid as ammonium ion (NH4+) and other ions. THE WAITING ROOM

Dianne (Di) A. is a 26-year-old woman who was diagnosed with type 1 diabetes mellitus at the

age of 12 years. She has an absolute insulin deficiency resulting from autoimmune destruction of the

β-cells of her pancreas. As a result, she depends on daily injections of insulin to prevent severe

elevations of glucose and ketone bodies in her blood. When Dianne A. could not be aroused from an

afternoon nap, her roommate called an ambulance and Di was brought to the emergency department of the

hospital in a coma. Her roommate reported that Di had been feeling nauseated and drowsy and had been

vomiting for 24 hours. Di is clinically dehydrated, and her blood pressure is low. Her respirations are

deep and rapid and her pulse rate is rapid. Her breath has the “fruity” odor of acetone.

Dianne A. has a ketoacidosis. When the amount of insulin she injects is inadequate, she

remains in a condition similar to a fasting state even though she ingests food (see Chapters 2

and 3). Her liver continues to metabolize fatty acids to the ketone bodies acetoacetic acid and β-

hydroxybutyric acid. These compounds are weak acids that dissociate to produce anions

(acetoacetate and β-hydroxybutyrate, respectively) and hydrogen ions, thereby lowering her blood

and cellular pH below the normal range. Because the dissociation of the ketone bodies is causing

the acidosis, it is classified as a ketoacidosis.

Blood samples are drawn for measurement of her arterial blood pH, arterial partial pressure of

carbon dioxide (PaCO2), serum glucose, and serum bicarbonate (HCO3−). In addition, serum and urine are

tested for the presence of ketone bodies, and Di is treated with intravenous normal saline and insulin. The

laboratory reports that her blood pH is 7.08 (reference range = 7.36 to 7.44) and that ketone bodies are

present in both blood and urine. Her blood glucose level is 648 mg/dL (reference range = 80 to 110

mg/dL after an overnight fast, and no higher than 200 mg/dL in a casual glucose sample taken without

regard to the time of a last meal).

Dennis V., age 3 years, was brought to the emergency department by his grandfather, Percy V.

While Dennis was visiting his grandfather, he climbed up on a chair and took a half-full 500-tablet

bottle of 325-mg aspirin (acetylsalicylic acid) tablets from the kitchen counter. Mr. V. discovered Dennis

with a mouthful of aspirin, which he removed, but he could not tell how many tablets Dennis had already

swallowed. When they arrived at the emergency department, the child appeared bright

and alert, but Mr.V. was hyperventilating.

Blood gas analyzers are used to measure pO2 and pCO2. The basic mechanism whereby these analyzers work is through the use of specific gas-permeable membranes. For oxygen,

a Clark electrode is used; oxygen diffuses through a membrane specific for oxygen permeability,

and once oxygen passes through the membrane, it diffuses to the cathode. When oxygen reaches the

cathode, electrons are attracted from the anode, thereby reducing the oxygen to water. Because it

requires four electrons to reduce molecular oxygen (forming two molecules of water), measurement of the current flow can quantitate the amount of oxygen that has reached the cathode.

pCO2 is determined using a Severinghaus electrode, which consists of an outer gas-permeable

membrane, specific for CO2, and a bicarbonate buffer within the electrode. Once the CO2 crosses

the membrane, the gas interacts with bicarbonate, altering the equilibrium among CO2, carbonic

acid, and bicarbonate. This alters the pH in direct proportion to the amount of CO2 gas that has

entered the electrode, and the change in pH can be used to calculate the pCO2. Improved

manufacturing techniques have allowed microelectrodes and tiny circuit boards to be used in these

machines, thereby greatly increasing their portability. I. Water

Water is the solvent of life. It bathes our cells, dissolves and transports compounds in the blood, provides

a medium for movement of molecules into and throughout cellular compartments, separates charged

molecules, dissipates heat, and participates in chemical reactions. Most compounds in the body, including

proteins, must interact with an aqueous medium in order to function. In spite of the variation in the amount

of water we ingest each day and produce from metabolism, our body maintains a nearly constant amount

of water that is approximately 60% of our body weight (Fig. 4.2).

A.Fluid Compartments in the BodyTotal body water is roughly 50% to 60% of body weight in adults and 75% of body weight in children.

Because fat has relatively little water associated with it, obese people tend to have a lower percentage of

body water than thin people, women tend to have a lower percentage than men, and older people have a

lower percentage than younger people.

Approximately 60% of the total body water is intracellular and 40% extracellular (see Fig. 4.2). The

extracellular water includes the fluid in plasma (blood after the cells have been removed) and interstitial

water (the fluid in the tissue spaces, lying between cells). Transcellular water is a small, specialized

portion of extracellular water that includes gastrointestinal secretions, urine, sweat, and fluid that has

leaked through capillary walls because of such processes as increased hydrostatic pressure or

inflammation.

B.Hydrogen Bonds in Water

The dipolar nature of the water (H2O) molecule allows it to form hydrogen bonds, a property that is

responsible for the role of water as a solvent. In H2O, the oxygen atom has two unshared electrons that

form an electron-dense cloud around it. This cloud lies above and below the plane formed by the water

molecule (Fig. 4.3). In the covalent bond formed between the hydrogen and oxygen atoms, the shared

electrons are attracted toward the oxygen atom, thus giving the oxygen atom a partial negative charge and

the hydrogen atom a partial positive charge. As a result, the oxygen side of the molecule is much more

electronegative than the hydrogen side, and the molecule is dipolar.

Both the hydrogen and oxygen atoms of the water molecule form hydrogen bonds and participate in

hydration shells. A hydrogen bond is a weak noncovalent interaction between the hydrogen of one

molecule and the more electronegative atom of an acceptor molecule. The oxygen of water can form

hydrogen bonds with two other water molecules, so that each water molecule is hydrogen-bonded to

approximately four close neighboring water molecules in a fluid three-dimensional lattice (see Fig. 4.3).

1. Water as a Solvent

Polar organic molecules and inorganic salts can readily dissolve in water because water also forms

hydrogen bonds and electrostatic interactions with these molecules. Organic molecules containing a high

proportion of electronegative atoms (generally oxygen or nitrogen) are soluble in water because these

atoms participate in hydrogen bonding with water molecules (Fig. 4.4A). Chloride (Cl−), bicarbonate

(HCO3−), and other anions are surrounded by a hydration shell of water molecules arranged with theirhydrogen atoms closest to the anion. In a similar fashion, the oxygen atom of water molecules interacts

with inorganic cations such as Na+ and K+ to surround them with a hydration shell (see Fig. 4.4B).

Although hydrogen bonds are strong enough to dissolve polar molecules in water and to separate

charges, they are weak enough to allow movement of water and solutes. The strength of the hydrogen bond

between two water molecules is only approximately 4 kcal, roughly 1/20th of the strength of the covalent

O–H bond in the water molecule. Thus, the extensive water lattice is dynamic and has many strained

bonds that are continuously breaking and re-forming. The average hydrogen bond between water

molecules lasts only about 10 picoseconds (1 picosecond is 10−12 second), and each water molecule in

the hydration shell of an ion stays only 2.4 nanoseconds (1 nanosecond = 10−9 second). As a result,

hydrogen bonds between water molecules and polar solutes continuously dissociate and re-form, thereby

permitting solutes to move through water and water to pass through channels in cellular membranes.

2. Water and Thermal Regulation

The structure of water also allows it to resist temperature change. Its heat of fusion is high, so a large

drop in temperature is needed to convert liquid water to the solid state of ice. The thermal conductivity of

water is also high, thereby facilitating heat dissipation from high energy-using areas such as the brain into

the blood and the total body water pool. Its heat capacity and heat of vaporization are remarkably high; as

liquid water is converted to a gas and evaporates from the skin, we feel a cooling effect. Water responds

to the input of heat by decreasing the extent of hydrogen bonding and to cooling by increasing the bonding

between water molecules.

C. ElectrolytesBoth extracellular fluid (ECF) and intracellular fluid (ICF) contain electrolytes, a general term applied to

bicarbonate and inorganic anions and cations. The electrolytes are unevenly distributed between

compartments; Na+ and Cl− are the major electrolytes in the ECF (plasma and interstitial fluid), and K+

and phosphates such as HPO42− are the major electrolytes in cells (Table 4.1). This distribution is

maintained principally by energy-requiring transporters that pump Na+ out of cells in exchange for K+

(see Chapter 10).

D. Osmolality and Water Movement

Water distributes between the different fluid compartments according to the concentration of solutes, or

osmolality, of each compartment. The osmolality of a fluid is proportional to the total concentration of all

dissolved molecules, including ions, organic metabolites, and proteins, and is usually expressed as

milliosmoles (mOsm)/kg water. The semipermeable cellular membrane that separates the extracellular

and intracellular compartments contains a number of ion channels through which water can move freely,

but other molecules cannot. Likewise, water can move freely through the capillaries separating the

interstitial fluid and the plasma. As a result, water will move from a compartment with a low

concentration of solutes (lower osmolality) to one with a higher concentration to achieve an equal

osmolality on both sides of the membrane. The force it would take to keep the same amount of water on

both sides of the membrane is called the osmotic pressure.

As water is lost from one fluid compartment, it is replaced with water from another compartment to

maintain a nearly constant osmolality. The blood contains a high content of dissolved negatively charged

proteins and the electrolytes needed to balance these charges. As water is passed from the blood into the

urine to balance the excretion of ions, the blood volume is repleted with water from interstitial fluid.

When the osmolality of the blood and interstitial fluid is too high, water moves out of the cells. The loss

of cellular water also can occur in hyperglycemia because the high concentration of glucose increases the

osmolality of the blood.

In the emergency department, Dianne A. was rehydrated with intravenous saline, which is a

solution of 0.9% NaCl. Why was saline used instead of water?A solution of 0.9% NaCl is 0.9 g NaCl/100 mL, equivalent to 9 g/L. NaCl has a molecular

weight of 58 g/mol, so the concentration of NaCl in isotonic saline is 0.155 M, or 155 mM.

If all of the NaCl were dissociated into Na+ and Cl− ions, the osmolality would be 310 mOsm/kg

water. Because NaCl is not completely dissociated and some of the hydration shells surround

undissociated NaCl molecules, the osmolality of isotonic saline is approximately 290 mOsm/kg

H2O. The osmolality of plasma, interstitial fluids, and ICF is also approximately 290 mOsm/kg

water, so no large shifts of water or swelling occurs when isotonic saline is given intravenously.

In some cases, glucose is added to this at a 5% concentration (5 g/100 mL). The glucose provides

fuel for the individual. If this is done, the saline solution has the designation of D5, for 5%

dextrose.

Dianne A. has an osmotic diuresis. Because her blood levels of glucose and ketone bodies

are so high, these compounds are passing from the blood into the glomerular filtrate in the