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 Student Reviewers

Maxx Gallegos
M edical Student
University of Kansas School of M edicine

Russel Kahmke
M edical Student
SUNY Upstate M edical University

Benjamin O. Lawson
M edical Student
Universidad Autónoma de Guadalajara
School of M edicine

Daniel Marcovici
M edical Student
Sackler School of M edicine
Tel Aviv University

S hama Patel
M edical Student
Ross University School of M edicine

S heree Perron
M edical Student
Eastern Virginia M edical School

Kendall S mith
M edical Student
University of Kansas School of M edicine
 Contents

Contributors
Introduction
Acknowledgments

High-Yield Facts
High-Yield Facts in Physiology

General Principles: Cellular Physiology

Questions
Answers

General Principles: Multisystem Processes

Questions
Answers

Physiology of the Hematopoietic and Lymphoreticular S ystems

Questions
Answers

Neurophysiology
Questions
Answers

Musculoskeletal Physiology
Questions
Answers

Respiratory Physiology
Questions
Answers

Cardiovascular Physiology
Questions
Answers

Gastrointestinal Physiology
Questions
Answers

Renal and Urinary Physiology

Questions
Answers

Reproductive Physiology
Questions
Answers

Endocrine Physiology
Questions
Answers

Bibliography
Index
 Contributors

Adam C. Calaway, MD

Resident, Urology

Indiana University School of M edicine

Indianapolis, Indiana

Chapter 1. Renal and Urinary Physiology Section of High-Yield Facts

Chapter 10. Renal and Urinary Physiology

Meredith L. Dorr, MD

Resident Physician

Department of Obstetrics and Gynecology

Indiana University School of M edicine

Indianapolis, Indiana

Chapter 1. Endocrine Physiology Section of High-Yield Facts

Chapter 12. Endocrine Physiology

Patricia J. Metting, PhD

Professor, Departments of Physiology & Pharmacology and M edicine

Vice Chancellor and Senior Associate Dean for Student Affairs

The University of Toledo College of M edicine and Life Sciences

Toledo, Ohio

Chapter 1. High-Yield Facts in Physiology

Chapter 2. General Principles: Cellular Physiology

Chapter 3. General Principles: Multisystem Processes

Chapter 4. Physiology of the Hematopoietic and Lymphoreticular Systems

Chapter 5. Neurophysiology

Chapter 6. Musculoskeletal Physiology

Chapter 7. Respiratory Physiology

Chapter 8. Cardiovascular Physiology

Chapter 9. Gastrointestinal Physiology

Chapter 10. Renal and Urinary Physiology

Chapter 11. Reproductive Physiology

Chapter 12. Endocrine Physiology

Vicki A. Ramsey-Williams, MD, PhD

Associate Professor

Department of Neurology

The University of Toledo

Toledo, Ohio
Chapter 1. Neurophysiology Section of High-Yield Facts

Chapter 5. Neurophysiology

Mark K. Tuttle, MD

Clinical Fellow

Harvard M edical School

Resident, Internal M edicine

Beth Israel Deaconess M edical Center

Boston, M assachusetts

Chapter 1. Cardiovascular Physiology Section of High-Yield Facts

Chapter 8. Cardiovascular Physiology

 Introduction

Each PreTest™ Self-Assessment and Review is designed to allow allopathic and osteopathic medical students, as well as international medical graduates, a
comprehensive and convenient way to assess and review their knowledge of a particular medical science, in this instance, physiology. The 500 questions have been
organized to parallel the Content Outline for the United States M edical Licensing Examination (USM LE™ ) Step 1
(http://www.usmle.org/Examinations/step1/step1_content.html). By familiarizing yourself with the Step 1 Content Outline, you will get a more accurate idea of the
subject areas covered in each section. For example, acid-base and electrolyte balance and high-altitude physiology are topics covered under General Principles:
M ultisystem Processes and oxygen and carbon dioxide transport are covered in the chapter on the Physiology of the Hematopoietic and Lymphoreticular Systems,
rather than under Renal or Respiratory Physiology, respectively, where you likely learned them during your medical school education. In addition to guiding your
preparation for Step 1, the value of organizing the questions according to the Step 1 Content Outline is that the National Board of M edical Examiners (NBM E) score
reports that are given to each examinee provide relative performance in each of the various areas tested by the USM LE Step 1. Thus, when you eventually find out
how you performed in each category, you will have a more accurate understanding of your areas of strength and weakness.
Physiology: PreTest™ has been updated to include more two-step questions that require test-takers to not only make a diagnosis based on the clinical vignette
presented, but also demonstrate their knowledge of the physiology/pathophysiology of the disorder. In this way, the questions in Physiology PreTest™ more closely
parallel the length and the degree of difficulty of the questions that you should expect to find on the USM LE Step 1.
Physiology: PreTest™ will also be a valuable resource for osteopathic medical students studying for the Comprehensive Osteopathic M edical Licensing Examination
(COM LEX)-USA. Similar to Step 1 of the USM LE, Level 1 of the COM LEX-USA, administered by the National Board of Osteopathic M edical Examiners, Inc.,
emphasizes an understanding of the basic science mechanisms underlying health and disease, and is constructed with clinical presentations in the context of medical
problem solving (http://www.nbome.org).
Each question in Physiology: PreTest™ is followed by multiple answer options. For each question, select the one best answer from the choices given. The Question
section of each chapter is followed by an Answers section that provides the correct answer for each question, along with an explanation. The explanation provides the
reason why the correct answer is correct and, in most cases, the reasons why the wrong answers are wrong. The explanations also provide additional information
relevant to the clinical vignette and its underlying basic and clinical science. The references accompanying each question are from excellent physiology,
pathophysiology, internal medicine, and Step 1 preparation textbooks. Step 1 is the first of three exams required for medical licensure in the United States. Although it
is a test that examines knowledge of the basic sciences, the expectation is that you can apply the basic knowledge in clinical problem solving. By using clinical
vignettes and clinical reference texts, our hope is that your preparation for the USM LE Step 1 (and/or COM LEX-USA Level 1) will also serve to enhance your ability
to function competently in the clinical environment. The material in the referenced pages will provide a more expansive description of the subject matter covered by
the question.
One effective way to use the PreTest™ is to use it as a review for each topic area. Start by reading the High-Yield Facts on a selected topic found at the beginning of
the book. The High-Yield Facts are not meant to be a complete list of all of the important facts, concepts, and equations necessary for understanding physiology.
Those that are included, however, offer a solid foundation and should be included in your review of physiology in preparation for a class test or for the USM LE Step
1. Once you’ve completed your reading on a topic, answer the questions for that chapter. As you check your answers, be sure to read the explanations, as they are
designed to reinforce and expand on the material covered by the questions. If you are still unsure of why the correct answer is correct, you should also read the
referenced text pages. PreTest™ can also be used as a practice testing session. Set aside two-and-a-half hours, and answer 150 of the questions, writing the answers on
a separate sheet of paper. Once you have completed all 150, then you can go back and compare your answers to the ones provided in the book. This exercise will help
you assess your level of competence and confidence prior to taking the USM LE Step 1. Whichever way you use PreTest™ , an important part of your review can be
found in the explanations.
We wish you the very best on your examination, your clinical training, and your medical career. Keep in mind that there is a PreTest™ available for the other basic
sciences, as well as in each of the required clinical disciplines, so you are encouraged to make the PreTest™ series your review books of choice throughout the
preclinical and clinical portions of the medical school curriculum, as well as during your preparation for Step 1 and Step 2 Clinical Knowledge (CK) of the USM LE or
for the COM LEXUSA Level 1 and Level 2-Cognitive Evaluation (CE).
 Acknowledgments

The contributions of the authors of all previous editions of this book are gratefully acknowledged, especially those of James F. Kleshinski, M D, co-editor of the 13th
edition. The input of the medical student reviewers was valuable for enhancing the quality of this latest edition. Thanks to Catherine Johnson, Editor, M edical
Publishing Division, M cGraw-Hill Professional, for her expert editorial assistance and guidance, as well as her enthusiasm and commitment to providing medical
students with the very best educational resources available in the market. In addition, the contributions of Ritu Joon, Thomson Digital, in the typesetting and
revisions, as well as the involvement of Cindy Yoo, Project Development Editor, and Richard Ruzycka, Production Supervisor, M cGraw-Hill Professional, are greatly
appreciated.
 High-Yield Facts in Physiology
GENERAL PRINCIPLES: CELLULAR PHYSIOLOGY
(References: Barrett et al., pp 7-10, 35-66. Le et al., pp. 226, 230-231. Widmaier et al., pp 12-13, 45-56, 95-134.)

Membrane Transport Mechanisms

The transport of ions, gases, nutrients, and waste products through biological membranes is essential for many cellular processes. M embrane transport mechanisms
can be classified as passive (do not require energy input, as with simple diffusion or facilitated diffusion) and active transport (requires energy input). M embrane
transport mechanisms can also be classified as either simple diffusion (does not require a membrane transporter, eg, diffusion through the lipid bilayer or diffusion
through ion channels) or mediated transport (requiring an integral membrane protein transporter, as with facilitated diffusion or active transport).
Diffusion is defined as the net flux of a substance from an area of higher concentration to an area of lower concentration from movement solely by random thermal
motion, which does not require energy input.
Facilitated diffusion is a type of mediated transport, but it is a passive process in which carrier proteins move substances in the direction of their electrochemical
gradients (eg, glucose transport in adipose tissue and muscle).
Active transport is a carrier-mediated transport process that requires energy to transport substances against their electrochemical gradients. The most important
+ +
primary active transporter in mammalian cells is the Na –K pump, which generates energy from the hydrolysis of ATP. Secondary active transport processes derive
+
their energy from ion gradients. One example is the glucose transporter, which uses energy derived from the Na electrochemical gradient.
Table 1 summarizes the major characteristics of the various membrane transport processes. Note that nonpolar substances, such as oxygen, carbon dioxide, and
fatty acids, are transported by simple diffusion through the lipid bilayer of biological membranes. Ions and hydrophilic solutes, which do not readily cross the lipid
bilayer, utilize an integral membrane protein to cross the membrane either via diffusion through a protein channel or via a carrier-mediated transport process.

TAB LE 1. MAJOR CHARACTERISTICS OF MEMB RANE TRANSPORT MECHANISMS

The kinetics of diffusion versus carrier-mediated transport processes vary, as depicted in Figure 1.
 Figure 1

Simple diffusion of a substance is described by the Fick equation, as follows:

where
A is the area available for diffusion,
[S1 ] − [S2 ] is the concentration gradient of the substance across the membrane,
d is the distance for diffusion,
D is the diffusion coefficient of the substance,

According to the Fick equation, substances will diffuse more rapidly if the substance has a smaller mass, if the surface area for diffusion is increased, and if the
concentration of the substance in one region greatly exceeds the concentration in the other region. For diffusion across membranes, the magnitude of the net flux is also
directly proportional to the membrane permeability coefficient for the molecule.
Mediated transport exhibits saturation kinetics described by the M ichaelis–M enten equation, as follows:

where Vmax is the maximal rate of transport, [S] is the concentration of the transported substance, and Km is the concentration required for half-maximal transport of
the substance.
Osmosis is a term given to the passive diffusion of water across a semipermeable membrane from a compartment in which the chemical potential of water is higher
(solute concentration is lower) to a compartment in which the chemical potential of water is lower (solute concentration is higher), as depicted in Figure 2. A
semipermeable membrane is permeable to water but impermeable to solutes.

Figure 2

Diagrammatic representation of osmosis. Water molecules are the open circles, and solute molecules are the closed circles. Osmosis is the passive flow of water
molecules across a semipermeable membrane from a compartment in which the chemical potential of water is higher (solute concentration is lower) to a compartment
in which the chemical potential of water is lower (solute concentration is higher). (Reproduced, with permission, from Ganong WF. Review of Medical Physiology.
22nd ed. New York, NY: M cGraw-Hill; 2005:5.)

The flow of water through membranes by osmosis is described by the osmotic flow equation:
where σ is the reflection coefficient, L is the hydraulic conductivity, and π1 − π2 is the osmotic pressure difference across membrane.
The reflection coefficient (σ) is an index of the membrane’s permeability to a solute and varies between 0 and 1. Particles that are impermeable to the membrane
have a reflection coefficient of 1. Particles that are freely permeable to the membrane have a reflection coefficient of 0.
The osmotic pressure (π) of a solution is the pressure necessary to prevent solute migration. The osmotic pressure (in units of mm Hg) is calculated with the van’t
Hoff equation:

where R is the ideal gas constant, T is the absolute temperature, φ is the osmotic coefficient, i is the number of ions formed by the dissociation of a molecule, c is the
molar concentration of solute, and (φic) is the osmolarity of the solution.
The value of i is 1 for nonionic substances such as glucose and urea; 2 for substances such as HCl, NaCl, KCl, NH4 Cl, NaHCO3 , and M gSO4 ; and 3 for
compounds such as CaCl2 and M gCl2 .
A value of 1 is often used as an approximate value of φ. Thus, the osmolarity and osmotic pressure of 1 M CaCl2 > 1 M NaCl > 1 M glucose. Similarly, a 1 M
solution of glucose has approximately the same osmolarity and osmotic pressure as 0.5 M NaHCO3 or 0.33 M M gCl2 .
One osmol is equal to 1 mol of solute particles. The osmolarity is the number of osmoles per liter of solution, whereas the osmolality is the number of osmoles per
kilogram of solvent. In the body, osmolal concentrations are expressed as osmoles per kilogram of water.
The plasma membranes of most cells are relatively impermeable to many of the solutes of the extracellular fluid (ECF) but are highly permeable to water. Thus, the
movement of water by osmosis leads to swelling or shrinking of cells.
The term tonicity is used to describe the osmolarity of a solution of nonpenetrating substances relative to plasma. Solutions of nonpenetrating solutes that have the
same osmolarity as plasma (~300 mOsm/L) are isotonic; solutions containing greater than 300 mOsm of nonpenetrating solutes are hypertonic; and those containing
less than 300 mOsm of non-penetrating solutes are hypotonic.
As shown in Figure 3, cells shrink when placed in hypertonic solutions and swell when placed in hypotonic solutions.
 Figure 3

Cell volume changes with hypertonic, isotonic, and hypotonic solutions. (Reproduced, with permission, from Widmaier EP, Raff H, Strang KT. Vander’s Human
Physiology: The Mechanisms of Body Function. 11th ed. New York, NY: M cGraw-Hill; 2008:111.)

The steady-state volume of a cell can be calculated as follows:

Isotonic solutions are commonly used for intravenous fluid administration and as drug diluents because administration of an isotonic solution does not produce
changes in cell volume, that is, no net water movement. Isotonic saline has a concentration of 154 mM NaCl, containing 154 × 2 or 308 mM of osmotically active
particles. An isotonic solution of glucose is a 5% dextrose solution.
Another set of terms—isosmotic, hyperosmotic, and hypoosmotic— denotes the osmolarity of a solution relative to that of normal ECF independent of whether
+
the solute is penetrating or nonpenetrating. For example, a solution containing 150 mOsm each of nonpenetrating Na and Cl− and 100 mOsm of the penetrating solute
urea, which can readily cross cell membranes, would have a total osmolarity of 400 mOsm (hyperosmotic), but a tonicity of 300 mOsm (isotonic), and thus there
would be no net change in the volume of a cell immersed in the solution.
Intercellular Connections and Communication
Two types of connections form between the cells comprising a tissue. One type of junction serves to fasten the cells to one another and to surrounding tissues.
Examples of fastening junctions that lend strength and stability to tissues include tight junctions or zona occludens, desmosomes, and zona adherens, as well as
hemidesmosomes and focal adhesions, which attach cells to their basal laminas.
The other type of connection between cells serves the purpose of transferring ions and other molecules from cell to cell, as well as the rapid propagation of
electrical activity. This type of intercellular connection, called a gap junction, is a dodecameric structure formed by the alignment of units called connexons in the
membranes of each cell. Each connexon is made up of six protein subunits called connexins, each of which has four membrane-spanning regions. Connexin mutations
are now known to cause almost 20 different human diseases, including X-linked Charcot–M arie–Tooth disease (Cx32), skin disorders such as Clouston syndrome
(Cx30) and erythrokeratoderma variabilis (Cx30.3 and Cx31), inherited deafness (Cx26, Cx30, and Cx31), cataracts (Cx46 and Cx50), and predisposition to myoclonic
epilepsy (Cx36) and arteriosclerosis (Cx37).
In addition to the direct cell-to-cell communication via gap junctions, cells communicate with each other via chemical messengers in the ECF by a number of
processes, including neural, endocrine, and paracrine communication.
In the case of intercellular communication mediated by chemical messengers in the ECF, there are generally “first messengers,” which constitute the extracellular
ligands that bind to receptors in the cell membrane, and “second messengers,” which are the intracellular mediators that bring about the changes in cell function
produced by binding of the “first messenger.” The principal mechanisms by which chemical messengers exert their intra-cellular effects are summarized in Table 2.

TAB LE 2. PRINCIPAL MECHANISMS FOR INTRACELLULAR EFFECTS OF CHEMICAL MESSENG ERS

 GENERAL PRINCIPLES: MULTISYSTEM PROCESSES
(References: Barrett et al., pp 3-8, 316-320, 650-651, 697-719. Kaufman et al., pp 239-256. Levitzky, pp 163-188. Longo et al., pp 341-373. Widmaier et al., pp 5-19,
28-29, 417-433, 454-460, 490-515, 569-585.)

Body Fluid Compartments

Water is the most abundant constituent in the body. Total body water (TBW) is approximately 60% of lean body mass. The percentage of water in the body is a
function of body fat. The greater the percentage of body fat, the lower the percentage of body water.
As shown in Figure 4, TBW is distributed between intracellular and extracellular fluid compartments.
 Figure 4

Body fluid compartments with approximate contribution to percentage body weight. Arrows represent fluid movement between compartments. (Reproduced, with
permission, from Barrett et al. Ganong’s Review of Medical Physiology. 24th ed. New York, NY: M cGraw-Hill; 2012:5.)

• Intracellular fluid (ICF) comprises about two-thirds of TBW (40% of body mass).
• ECF is one-third of TBW (20% of body mass). The ECF water is further divided into:
• Plasma (intravascular) water, which comprises approximately one-fourth of ECF or one-twelfth of TBW (5% of body mass), and
• Interstitial (extravascular) water, which comprises approximately three-fourths of ECF or one-fourth of TBW (15% of body mass).

The composition of the extracellular and intracellular fluids is shown in Table 3. The distribution of substances between the intracellular and extracellular fluid is
unequal due to the membrane potential and the presence of various transporters and ion channels in the plasma membrane.

TAB LE 3. ECF AND ICF COMPOSITION

 The solute or particle concentration of a fluid is its osmolality. Water shifts between the ECF and ICF in order to maintain osmotic equilibrium between the two
compartments.
The normal range of plasma osmolality is 285 to 300 mOsm/kg, and the normal range of plasma osmolarity is 285 to 300 mOsm/L.
Because of the predominant role of the major solutes and the deviation of plasma from an ideal solution, plasma osmolarity can normally be estimated using the
following formula:

Fluid and Electrolyte Balance and Disorders

The extracellular osmolarity is controlled by antidiuretic hormone (ADH), also known as vasopressin. Increases in osmolarity stimulate the release of ADH from the
posterior pituitary gland. ADH returns osmolarity toward normal by decreasing the amount of water excreted by the kidney. When osmolarity is decreased, ADH
release is decreased and osmolarity is returned toward normal by increased water excretion. ADH is also secreted in response to low blood pressure. Under these
conditions, reabsorption of water by the kidneys can make the ECF hypotonic.

Plasma osmolality is elevated in:

• Dehydration
• Diabetes insipidus
• Hypernatremia
• Hyperglycemia
• Hypercalcemia
• M annitol therapy
• Uremia
• Toxin ingestion (ethanol, methanol, ethylene glycol)

Plasma osmolality is decreased in:

• Addison disease
• Hyponatremia
• Hypothyroidism
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Overhydration

The extracellular volume is controlled by the NaCl content of the ECF. Hypovolemia, or volume depletion, generally refers to a state of combined salt and water
+
loss exceeding intake, leading to ECF volume contraction. The loss of Na may be renal or extrarenal (Table 4).

TAB LE 4. CAUSES OF HYPOVOLEMIA

NaCl content is controlled by aldosterone and atrial natriuretic peptide (ANP). Extracellular volume is monitored by low-pressure baroreceptors within the thoracic
venous vessels and the atria and by pressure receptors within the afferent arteriole of the kidneys. ANP release is controlled directly by stretch receptors within the
right atrium.
Aldosterone secretion is controlled by the renin–angiotensin system. Renin is released from the juxtaglomerular cells (JG cells) of the kidney in response to the
following:

• Decreased perfusion pressure within the afferent arteriole

• Sympathetic stimulation of the JG cells
• Decreased Cl− concentration in fluid bathing the macula densa

Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE) located
within the lung. Angiotensin II stimulates aldosterone secretion from the adrenal cortex gland.
Hyponatremia, defined as a plasma sodium concentration <135 mEq/L, is a very common disorder occurring in more than 20% of hospitalized patients. The
disorder is almost always the result of an increase in circulating ADH and/or increased renal sensitivity to ADH. The underlying patho-physiology for the exaggerated
or inappropriate ADH response differs in hyponatremic patients as a function of their ECF volume. Therefore, the causes of hyponatremia are subdivided into three
categories based on coexisting urine sodium and osmolarity and volume status (Table 5).

TAB LE 5. CAUSES OF HYPONATREMIA

 Hypernatremia is defined as a serum sodium concentration greater than 145 mEq/L. The causes of hypernatremia are subdivided into three categories based on the
coexisting fluid status (Table 6).

TAB LE 6. CAUSES OF HYPERNATREMIA

 +
Potassium is the major intracellular cation with a normal concentration of approximately 150 mmol/L (Table 3). Homeostatic mechanisms maintain plasma K
+ +
concentration between 3.5 and 5 mmol/L despite marked variations in dietary K intake. The ratio of intracellular to extracellular K (normally 38:1) is the principal
+ +
result of the resting membrane potential and is essential for normal neuromuscular function. Virtually all regulation of renal K excretion and total body K balance
occurs in the distal nephron. Potassium secretion is regulated by aldosterone. Aldosterone is secreted by the zona glomerulosa cells of the adrenal cortex in response to
+ + +
increases in extracellular K or angiotensin II, causing K secretion to increase. K transport into cells is increased by epinephrine and insulin.
+ +
The causes of hypokalemia, defined as a plasma K concentration less than 3.5 mEq/L, are shown in Table 7. The causes of hyperkalemia, defined as a plasma K
concentration ≥ 5 mEq/L, are shown in Table 8. Hypokalemia occurs in up to 20% of hospitalized patients, and is associated with a tenfold increase in in-hospital
mortality rates due to adverse effects on cardiac rhythm. Hyperkalemia occurs in up to 10% of hospitalized patients; severe hyperkalemia (>6 mEq/L) occurs in
approximately 1% of patients and has a significantly increased risk of mortality.

TAB LE 7. CAUSES OF HYPOKALEMIA

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