Preface Contents ‘Acknowledgments xi To the Reader xii 1 Neurophysiology 1 Cellular homeostasis 1 Resting and action potentials 7 Synaptic transmission 18 IV. Muscle contraction 28 V. General sensory mechanisms 35 Vi. Cutaneous sensation 40 Vil. Audition 44 Vill. Vision 51 1X Taste 61 X. Olfaction 62 XI Spinal reflexes 64 Xil, The motor control system 69 Xl Sleep and consciousness 78 Study questions 82 ‘Answers and explanations 88 2 Cardiovascular Physiology 93 1 Vessels 93 1 Heart 99 I. Electrocardiography 107, IV. Cardiac rate, hythm, and conduction disturbances 113 V. The heart as a pump 118 Vi. Cardiodynamies 121 Vil, Hemodynamics 124 Vill, Cardiac output and venous return 127 IX. Control ofthe cardiovascular system 131 X. Special circulatory beds 133 XI. Responses to stress 135 Study questions 140 Answers and explanations 144 3. Respiratory Physiology 149 1. Introduction 149 I, Respiratory mechanics 149 I, Gas exchange between the atmosphere and the body 163, IV. Gas tanspor 166\V. Pulmonary circulation 170 Vi. The distribution of ventilation 172 VII. Ventilation:perfusion ratio 174 Vill. Respiratory control 176 IX. Hypoxia 181 Study questions 186 ‘Answers and explanations 192 Renal Physiology 199 |. Introduction 199 I. Body fluid compartments 202 UL. Overview of renal tubular function 209 IV. Renal clearance 212 V. Glomerular fitration and GFR 217, VI. Renal tubular transport: reabsorption and secretion 220 VI Renal concentration and dilution of urine 227 VII. Antidiuretic hormone (ADH) 234 1K. Aldosterone 235 X. Atrial natriuretic factor (ANF) 242 Study questions 243 ‘Answers and explanations 249 Acid-Base Physiology 257 |. Acid production and elimination 257 I, The hydrogen ion and pH 258 IL Body buffer systems 263 IV. Generation and elimination of H* 267 \V. Respiratory regulation of acid-base balance 269 VI. _ Renal regulation of acid-base balance 270 VII. Primary and secondary acid-base abnormalities 276 VIL. Compensatory mechanisms for primary acid-base abnormalities 285 Study questions 289 ‘Answers and explanations 295 Gastrointestinal Physiology 303 |. Digestive system: overview 303 1. The oral cavity, pharynx, and esophagus 303 ll, The stomach 307 IV. The small intestine 315, V. The colon 326 Study questions 328 ‘Answers and explanations 331 335 1 General features of hormones 335 II. Types of hormone action 340 IIL, Basic concepts of endocrine control 343 IV. Endocrine cells of the gastroenteropancreatic (GEP) system 348 V. Endogenous opioid peptides 348 VL. Pituitary gland 352 Vil. Adrenal medulla 357 Vill. Adrenal cortex 363x, xt xil xith XIV. Testis 370 Ovaty 377 Endocrine placenta 386 Endocrine pancreas 391 Thyroid gland 396 Parathyroid hormone, calcitonin, and vitamin D401, Study questions 407 ‘Answers and explanations 413, Comprehensive Examination Index 421 475Preface Since its publication in 1984, NMS Physiology has garnered considerable response from ‘medical students around the world. Based on these written and oral commentaries, the authors have revised the text to conform better to the needs of students preparing for course examinations and standardized medical or other health science examinations. Accordingly, this new edition of NMS Physiology contains a well-defined fund of knowledge the authors consider essential for medical practitioners. Although this bock does not focus specifically on pathology, it does provide ‘sight into the pathophysiologic aspects of disease by comparing normal processes in the body with the abnormal. The outline format has allowed the authors to emphasize the relative importance of the facts presented and to provide students with a source of fundamental information about physiology. Such a core guide to the discipline should prove especially valuable now that medical students are expected to assume more and more responsibility for their own learning, John Bullock Joseph Boyle, III Michael 8. WangAcknowledgments We collectively wish to express our thanks to the professional staff at the Harwal Publishing, Company, particularly to Matthew Harris (Medical Editor), Debra Dreger (Managing Editor), and Martha Gay (Project Editor) for their personal support, perseverance, understanding, and exper- tise. We also recognize the special contribution of Weislawa Langenfeld as medical illustrator. ur greatest measure of gratitude goes to Debra Dreger, who has earned our utmost respect for her energy and commitment to the NMS series. The authors To Barbara, who, through her love and willing sacrifice, encouraged me to complete two graduate degrees in physiology and biochemistry, Also to Laura, John, and Katherine—all impor- tant well-springs of inspiration. Not to be forgotten are the many medical and dental students together with the foreign medical graduates who have become friends and colleagues over the years. John Bullock To Patti, for her love and support over many years. To many colleagues who have made the study of physiology an exciting and stimulating career. And, to the many students who have asked the questions which have enlightened me. Joseph Boyle, itl My thanks to family, friends, colleagues, and students for their encouragement and support ‘over many years. Michael B. Wang,To the Reader Since 1984, the National Medical Series for Independent Study has been helping medical students meet the challenge of education and clinical training. In this climate of burgeoning knowledge and complex clinical issues, a medical career is more demanding than ever. increas- ingly, medical training must prepare physicians to seek and synthesize necessary information and to apply that information successfully ‘The National Medical Series is designed to provide a logical framework for organizing, learning, reviewing, and applying the conceptual and factual information covered in basic and clinical studies, Each book includes a concise but comprehensive outline of the essential content of a discipline, with up to 50 study questions. The combination of distilled, outlined text and tools for self-evaluation allows easy retrieval and enhanced comprehension of salient information. Each uestion is accompanied by the correct answer, a paragraph-length explanation, and specific reference to the text where the topic is discussed. Study questions that follow each chapter use current National Board formats to reinforce the chapter content. Study questions appearing at the end of the text in the Comprehensive Exam vary in format depending on the book; the unifying goal of this exam, however, is to challenge the student to synthesize and expand on information presented throughout the book. Wherever possible, Comprehensive Exam questions are presented in the context of a clinical case or scenario intended to simulate real-life application of medical knowledge. Each book in the National Medical Series is constantly being updated and revised to remain current with the discipline and with subtle changes in educational philosophy. The authors and editors devote considerable time and effort to ensuring that the information required by all medical school curricula is included and presented in the most logical, comprehensible manner. Strict editorial attention to accuracy, organization, and consistency also is maintained. Further shaping of the series occurs in response to biannual discussions held with a panel of medical student advisors drawn from schools throughout the United States. At these meetings, the editorial staff considers the complicated needs of medical students to learn how the National Medical Series can better serve them. In this regard, the staff at Harwal Publishing welcomes all comments and suggestions. Let us hear from you.1 Neurophysiology Michael B. Wang 1. CELLULAR HOMEOSTASIS ‘A. Homeostasis isthe process by which an organism maintains the composition of the extracellular fluid (ECF) and intracellular fluid (ICF) in a steady-state condition. The composition of the ECF and the ICF differ from each other (Table 1-1; see also Table 4-34) 1. Extracellular fluid consists of the blood plasma and interstitial fluid. The composition of the ECF is maintained by the cardiovascular, pulmonary, renal, gastrointestinal, endactine, and nervous systems acting in a coordinated fashion. 2, Intracellular fluid. The composition of the ICF is maintained by the cell membrane, which mediates the transport of material between the ICF and ECF by diffusion, osmosis, and active transport 8. Cell membrane. All animal cells are enveloped by a cell membrane that is composed of a variety of lipids and proteins. 1. Lipids. The lipids (.e, primarily phospholipids, cholesterol, and glycolipids) are formed into a bilayer (Figure 1-1) and are amphipathic; that is, they have a hydrophilic polar region at one tend of the molecule and a hydrophobic hydrocarbon tal atthe other. 2. The hydrophilic ends of lipid molecules, which contain the phosphate group, line up facing the ICF and ECF. b. The hydrophobic ends of the molecules face each other in the interior ofthe bilayer. 2. Proteins. According to the fluid mosaic model of membrane structure, membrane proteins insert into (and can float within) the bilayer and are anchored by covalent bonds. Some proteins span the entice bilayer; others are contained within the intracellular or extraceliular half of the bilayer. Membrane proteins serve several functions (see Figure 1-1) Table 1-1. Major lonic Components of the Intracellular and Extracellular Fluids Intracellular Concentration Extracellular Concentration on (mOsm/1) (mEq/D (mOsm/L) (mEq/) Na 15 5 140 140 Ke 135 4 4 ca 2x 10° a 4 Me 40 1 2 cr 4 120 120 Hco,- 10 24 24 HPO?- 20 2 4 soe" 4 05, 1 Proteins-, amino acids~, urea, etc 99 152 os 1 ‘Note—The osmolarity of the intracellular fd (ICP) i the same as that of the extracellular Nid (ECR). Alo, the rilequivalents of cations and anions are equal in the ICF as well asin the ECF.‘Transmembrane pump tnvrasetular ‘enzyme Figure 1-1. Diagram indicating some of the functions performed by proteins within the lipid bilayer of biologic membranes, 2. Some proteins (transmembrane prot These proteins form: (1) Channels, through which small, water-soluble substances can diffuse (2) Carriers, which are used to transport material across the bilayer b. Other proteins have an active site an only one side of the membrane. (1) Receptor sites for antibodies, hormones, neurotransmitter, and pharmacologic agents usually are contained within proteins located on the outer surface of cell membranes. (2) Enzymes used to activate or inactivate various metabolic intermediates usually are contained within proteins found on the inner surface of cell membranes. 8) have active sites on both sides of the bilayer. . Translocation across the cell membrane. jons, nutrients, and waste products of metabolism are transferred across the cell membrane by simple diffusion and a variety of carrier-mediated processes, 1. Passive transport processes do not require energy. They are downhill processes. 2. Simple diffusion occurs because all paticles in solution are in constant motion. (1) Although a single particle moves in an unpredictable (random) direction, itis more likely thatthe particle will move from an area where its highly concentrated to an area where its concentration is low than itis forthe particle to move inthe opposite direction. Thus, 8 particle moves down its concentration gradient by diffusion, (2) Net movement ceases when the concentration of the paticle is equal everywhere within the solution (diffusional equilibrium). Although random movement of the particles does ‘not cease, the concentration remains the same. (3) Fick’s law of diffusion describes the rate of diffusion through a membrane, which in- creases as the concentration gradient increases. flux = Cou where flux = the amount of material (mmol) moved per unit of time; = the diffusion coefficient (cm?/sec), which is characteristic of the material being moved and the membrane through which its being moved; A = the area (cm?) of the membrane; d = the diffusion distance, or thickness of the membrane (cm); and C, ‘concentrations of the material (mmol/L or mmol/ 1000 cm?) on the i ‘of the membrane, respectively. The negative sign indicates that the material is moving ‘down its concentration gradient, Permeability. Fick’s law can be simplified when biologic membranes are considered, because the thickness of the membrane always is about 10~* cm. Dividing D by 10-* yields the permeability coefficient (P) of the membrane, and Fick's law becomes. flux == P x A(Ca~Coud Note that P = D/d and that the units of permeability are cm/sec (6) Diffusion of lipid-soluble materials occurs through the lipid bilayer of the cell mem- brane. The diffusion coefficient of lipid-soluble materials is proportional to their lipid solubility, which often is expressed as the oil-water partition coefficient (6) Diffusion of water-soluble materials occurs through the aqueous channels formed by transmembrane proteins. The diffusion coefficient of water-soluble materials is )Neurophysiology 3 proportional to theit molecular size. Particles too large to fit through the aqueous ‘channels (particles with diameters greater than 0.8 nm) cannot cross the cell membrane y simple diffusion Facilitated diffusion requires a carrie. Some particles (e.g. glucose) are too large to difuse through membrane channels. However, they can be moved across the membrane by a carrier mediated process that does not require eneray (Figure 1-24) (@) The panicle binds to a carrier on one side of the membrane and, while bound to the carrie, is transported through the membrane. The particle dissociates from the carrier ‘when it reaches the other side of the membrane, Because the particle binds to the ‘cariee only if tis highly concentrated, the particle can only move down its concentra- tion gradient by this process. (2) The rate of diffusion increases as the concentration gradient increases until all of the carrier sites are filled. At this point, the rate of diffusion can no longer increase with increasing particle concentration. This is called saturation, or Michaelis-Menten, netics (see Figure 1-28). 2. Aetive transport processes require energy. They ae uphill processes, Primary active transport. Active transport processes using adenosine triphosphate (ATP) are called direct energy utilizing, or primary active transport, processes. (1) The most common of these active transpor systems is the sodium-potassium (Na*-K*) pump, or Na*-K*-ATPase, which uses the membrane-bound ATPase enzyme as a ‘arrier molecule. The Na*-K~ pump is responsible for maintaining the high K™ and low Na* concentrations in the ICF (Figure 1-3). The operation of the pump can be divided into three steps: (@) Three ions of Na* bind to the carrier on the inside of the cell (b) Two ions of k* bind to the carrier on the outside of the cell (© The carrier uses the energy obtained from one molecule of ATP to move two ions (f K* into the cell and three ions of Na” out of the cell (4) Inhibition of the carrier will occur ifthe intracellular ATP or Na* concentration ‘0 the extracellular K* concentration is too low. The carrier also can be inkibited by several therapeutic agents, such as digitalis. (2) Other carriers with a direct energy source are available to transport a variety of ions, such as chloride (CI~), calcium (Ca?"), and hydrogen (H), b. Secondary active transport. Carrer-mediated active transport systems that use the energy stored in the Na* concentration gradient are called indirect energy utilizing, or secondary active transport, processes. The system can operate only ifthe extracellular Na~ concentra- tion is higher than the intracellular Na* concentration. Energy is required to establish the Carrier protein igure 1-2. (A) The transmembrane protein responsible forthe aciltated anspor of glucose undergoes aconfor- ‘mational change when glucose binds othe varsporter on ‘ne side ofthe membrane The conformational change Allows glucose to difse across the membrane down Concenteation gradient. (B) The rate of anspor reaches 8 maximum when all binding sites onthe transporter are Goncenivation gradient filed ‘simple dittusion Flux Facitated ‘ittusion4 Chapter 11. Intracellular ‘Space extrac ‘sa Figure 1-3. (A) The energy contained inthe highenergy phosphate bond is used t0 anspor three ions of Na* out {tthe cell 1B) A second conformational change occur after to K~ fons bind tothe care, transporting K* imo the ell nd (C) causing the phosphate to dissociate from the cartier. Na* concentration gradient, and tis this energy tha is used indirectly inthe active transport process G) Transport of glucose and amino acids. Glucose and amino acids are transported against thelr concentration gradients by a secondary active transport process (Figure 1-4), (a) Na* binds tothe cartier on the outside of the cell where the Na concentration is high. After Na* binds to the cartier, the carries affinity for glucose increases, enabling it to bind glucose. (b) When Na* and glucose are bound to the carrier, the carrier undergoes a conforma- tional change, during which both glucose and Na* are exposed to the inside of the cell (c) Because ofthe low intracellular Na* concentration, Na* dissociates from the carter, reducing the carrer’s affinity for glucose. This allows glucose to dissociate from the carrier despite the relatively high intracellular glucose concentration. (d) Na*-dependent secondary active transport of glucose and amino acids is used primarily for the transport of these nutrients by epithelial cells of the nephron and the intestine (2) Transport of Ca?*. Calcium is transported out of the cell against its concentration sradient by a secondary active transport process. (a) Three Na* ions are transported into the cell for each Ca?* ion transported out of the cell 3 E37 = ce - Es Figure 1-4, Glucose is transported through the membrane by active transport that uses an indirect energy source. {AN As indicated by the length of the arrows, the affinity of the carrier for glucose Is low inthe absence of Na*. (8) However, ater Na* binds to the carter, the affinty for glucose is increased. Glucose and Na* difuse through the ‘membrane together. (C] Onee inside the cel, Na* fs removed from the carrer, the affinity for glucose is reduced, nd slucose dissociates from the carer.