Pocket Companion to Guyton & Hall Textbook of Medical Physiology Fourteenth Edition PDF

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Access to the eBook is limited to the first individual who redeems the PIN, located on the inside cover of this book, at studentconsult.inkling.com and may not be transferred to another party by resale, lending, or other means. Pocket Companion to Guyton and Hall Textbook of Medical Physiology This page intentionally left blank       Pocket Companion to Guyton and Hall Textbook of Medical Physiology Fourteenth Edition John E. Hall, PhD Arthur C. Guyton Professor and Chair Department of Physiology and Biophysics Director of the Mississippi Center for Obesity Research University of Mississippi Medical Center Jackson, Mississippi Michael E. Hall, MD, MS Associate Professor Department of Medicine Division of Cardiovascular Diseases Associate Vice Chair for Research Department of Physiology and Biophysics University of Mississippi Medical Center Jackson, Mississippi Elsevier 3251 Riverport Lane St. Louis, Missouri 63043 POCKET COMPANION TO GUYTON AND HALL TEXTBOOK OF MEDICAL PHYSIOLOGY, FOURTEENTH EDITION ISBN: 978-­0-­323-­64007-­7 Copyright © 2021 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors, or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence, or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2016, 2012, 2006, 2001, 1998. Library of Congress Control Number: 2020939725 Publisher: Elyse O’Grady Director, Content Development: Ellen M. Wurm-­Cutter Senior Content Development Specialist: Kathleen Nahm Publishing Services Manager: Shereen Jameel Project Manager: Manikandan Chandrasekaran Cover Design and Design Direction: Margaret Reid Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 Preface Human physiology is the discipline that links the basic sciences with clinical medicine. It is integrative and encompasses the study of molecules and subcellular components, cells, tissues, and organ systems, as well as the feedback systems that coordinate these components of the body and permit us to function as living beings. Because human physiology is a rapidly expanding discipline and covers a broad scope, the vast amount of information that is applicable to the practice of medicine can be overwhelming. Therefore, one of our major goals for writing this Pocket Companion was to distill this enormous amount of information into a book that would be small enough to be carried in a coat pocket and used often but still contain most of the basic physiological principles necessary for the study of medicine. The Pocket Companion was designed to accompany Guyton and Hall Textbook of Medical Physiology, 14th edition, not substitute for it. It is intended to serve as a concise overview of the most important facts and concepts from the parent text, presented in a manner that facilitates rapid comprehension of basic physiological principles. Some of the most important features of the Pocket Companion are as follows: • It was designed to serve as a guide for students who wish to review a large volume of material from the parent text rapidly and efficiently. The section headings state succinctly the primary concepts in the accompanying paragraphs. Thus, students can quickly review many of the main concepts in the textbook by first studying the paragraph headings. • The table of contents matches that of the parent text, and each topic has been cross-­referenced with specific page numbers from the parent text. The pocket companion has been updated in parallel with the Textbook of Medical Physiology, 14th edition. • The size of the book has been restricted so it can fit conveniently in a coat pocket as an immediate source of information. Although the Pocket Companion contains the most important facts necessary for studying physiology, it does not contain the details that enrich the physiological concepts or the clinical examples of abnormal physiology that are contained in the parent book. We therefore recommend that the Pocket Companion be used in conjunction with the Textbook of Medical Physiology, 14th edition. v vi Preface Dr. Michael Hall, a physician trained in internal medicine, cardiology, and physiology, has joined in the preparation of this edition of the Pocket Companion and the 14th edition of the Textbook of Medical Physiology. We greatly appreciate the valuable comments and suggestions of our colleagues in the Department of Physiology and Biophysics at the University of Missis­ sippi Medical Center. We are also grateful to Stephanie Lucas for excellent assistance and James Perkins for excellent illustrations. We also thank Kathleen Nahm, Elyse O’Grady, Manikandan Chandrasekaran, and the entire Elsevier team for continued editorial and production excellence. We have striven to make this book as accurate as possible and hope that it will be valuable for your study of physiology. Your comments and suggestions for ways to improve the Pocket Companion are always greatly appreciated. John E. Hall, PhD Michael E. Hall, MD, MS Jackson, Mississippi Contents UNIT I Introduction to Physiology: The Cell and General Physiology CHAPTER 1 Functional Organization of the Human Body and Control of the “Internal Environment”, 3 CHAPTER 2 The Cell and Its Functions, 10 CHAPTER 3 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction, 20 UNIT II Membrane Physiology, Nerve, and Muscle CHAPTER 4 Transport of Substances Through Cell Membranes, 31 CHAPTER 5 Membrane Potentials and Action Potentials, 38 CHAPTER 6 Contraction of Skeletal Muscle, 45 CHAPTER 7 Excitation of Skeletal Muscle: Neuromuscular Transmission and Excitation-­Contraction Coupling, 52 CHAPTER 8 Excitation and Contraction of Smooth Muscle, 57 UNIT III The Heart CHAPTER 9 Cardiac Muscle; The Heart as a Pump and Function of the Heart Valves, 65 CHAPTER 10 Rhythmical Excitation of the Heart, 73 CHAPTER 11 Fundamentals of Electrocardiography, 78 vii viii Contents CHAPTER 12 Electrocardiographic Interpretation of Cardiac Muscle and Coronary Blood Flow Abnormalities: Vectorial Analysis, 81 CHAPTER 13 Cardiac Arrhythmias and Their Electrocardiographic Interpretation, 86 UNIT IV The Circulation CHAPTER 14 Overview of the Circulation; Pressure, Flow, and Resistance, 93 CHAPTER 15 Vascular Distensibility and Functions of the Arterial and Venous Systems, 99 CHAPTER 16 The Microcirculation and Lymphatic System: Capillary Fluid Exchange, Interstitial Fluid, and Lymph Flow, 105 CHAPTER 17 Local and Humoral Control of Tissue Blood Flow, 115 CHAPTER 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure, 125 CHAPTER 19 Role of the Kidneys in Long-­Term Control of Arterial Pressure and in Hypertension: The Integrated System for Arterial Pressure Regulation, 134 CHAPTER 20 Cardiac Output, Venous Return, and Their Regulation, 146 CHAPTER 21 Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Disease, 153 CHAPTER 22 Cardiac Failure, 159 CHAPTER 23 Heart Valves and Heart Sounds; Valvular and Congenital Heart Defects, 165 Contents ix CHAPTER 24 Circulatory Shock and Its Treatment, 170 UNIT V The Body Fluids and Kidneys CHAPTER 25 Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema, 179 CHAPTER 26 The Urinary System: Functional Anatomy and Urine Formation by the Kidneys, 189 CHAPTER 27 Glomerular Filtration, Renal Blood Flow, and Their Control, 195 CHAPTER 28 Renal Tubular Reabsorption and Secretion, 201 CHAPTER 29 Urine Concentration and Dilution; Regulation of Extracellular Fluid Osmolarity and Sodium Concentration, 213 CHAPTER 30 Renal Regulation of Potassium, Calcium, Phosphate, and Magnesium; Integration of Renal Mechanisms for Control of Blood Volume and Extracellular Fluid Volume, 222 CHAPTER 31 Acid-­Base Regulation, 234 CHAPTER 32 Diuretics and Kidney Diseases, 245 UNIT VI Blood Cells, Immunity, and Blood Coagulation CHAPTER 33 Red Blood Cells, Anemia, and Polycythemia, 255 CHAPTER 34 Resistance of the Body to Infection: I. Leukocytes, Granulocytes, the Monocyte-­Macrophage System, and Inflammation, 261 x Contents CHAPTER 35 Resistance of the Body to Infection: II. Immunity and Allergy, 267 CHAPTER 36 Blood Types; Transfusion; and Tissue and Organ Transplantation, 275 CHAPTER 37 Hemostasis and Blood Coagulation, 279 UNIT VII Respiration CHAPTER 38 Pulmonary Ventilation, 289 CHAPTER 39 Pulmonary Circulation, Pulmonary Edema, and Pleural Fluid, 296 CHAPTER 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane, 303 CHAPTER 41 Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids, 311 CHAPTER 42 Regulation of Respiration, 316 CHAPTER 43 Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy, 320 UNIT VIII Aviation, Space, and Deep-­Sea Diving Physiology CHAPTER 44 Aviation, High Altitude, and Space Physiology, 329 CHAPTER 45 Physiology of Deep-­Sea Diving and Other Hyperbaric Conditions, 334 Contents xi UNIT IX The Nervous System: A. General Principles and Sensory Physiology CHAPTER 46 Organization of the Nervous System, Basic Functions of Synapses, and Neurotransmitters, 341 CHAPTER 47 Sensory Receptors, Neuronal Circuits for Processing Information, 349 CHAPTER 48 Somatic Sensations: I. General Organization, Tactile and Position Senses, 355 CHAPTER 49 Somatic Sensations: II. Pain, Headache, and Thermal Sensations, 363 UNIT X The Nervous System: B. The Special Senses CHAPTER 50 The Eye: I. Optics of Vision, 373 CHAPTER 51 The Eye: II. Receptor and Neural Function of the Retina, 378 CHAPTER 52 The Eye: III. Central Neurophysiology of Vision, 387 CHAPTER 53 The Sense of Hearing, 393 CHAPTER 54 The Chemical Senses—Taste and Smell, 399 UNIT XI The Nervous System: C. Motor and Integrative Neurophysiology CHAPTER 55 Spinal Cord Motor Functions; the Cord Reflexes, 405 CHAPTER 56 Cortical and Brain Stem Control of Motor Function, 412 xii Contents CHAPTER 57 Cerebellum and Basal Ganglia Contributions to Overall Motor Control, 421 CHAPTER 58 Cerebral Cortex, Intellectual Functions of the Brain, Learning, and Memory, 432 CHAPTER 59 The Limbic System and Hypothalamus—Behavioral and Motivational Mechanisms of the Brain, 439 CHAPTER 60 States of Brain Activity—Sleep, Brain Waves, Epilepsy, Psychoses, and Dementia, 446 CHAPTER 61 The Autonomic Nervous System and the Adrenal Medulla, 452 CHAPTER 62 Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism, 462 UNIT XII Gastrointestinal Physiology CHAPTER 63 General Principles of Gastrointestinal Function— Motility, Nervous Control, and Blood Circulation, 471 CHAPTER 64 Propulsion and Mixing of Food in the Alimentary Tract, 478 CHAPTER 65 Secretory Functions of the Alimentary Tract, 483 CHAPTER 66 Digestion and Absorption in the Gastrointestinal Tract, 490 CHAPTER 67 Physiology of Gastrointestinal Disorders, 497 UNIT XIII Metabolism and Temperature Regulation CHAPTER 68 Metabolism of Carbohydrates and Formation of Adenosine Triphosphate, 503 Contents xiii CHAPTER 69 Lipid Metabolism, 510 CHAPTER 70 Protein Metabolism, 518 CHAPTER 71 The Liver, 522 CHAPTER 72 Dietary Balances; Regulation of Feeding; Obesity and Starvation; Vitamins and Minerals, 527 CHAPTER 73 Energetics and Metabolic Rate, 538 CHAPTER 74 Body Temperature Regulation and Fever, 541 UNIT XIV Endocrinology and Reproduction CHAPTER 75 Introduction to Endocrinology, 549 CHAPTER 76 Pituitary Hormones and Their Control by the Hypothalamus, 555 CHAPTER 77 Thyroid Metabolic Hormones, 565 CHAPTER 78 Adrenocortical Hormones, 573 CHAPTER 79 Insulin, Glucagon, and Diabetes Mellitus, 583 CHAPTER 80 Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth, 592 CHAPTER 81 Reproductive and Hormonal Functions of the Male, 601 CHAPTER 82 Female Physiology Before Pregnancy and Female Hormones, 606 CHAPTER 83 Pregnancy and Lactation, 614 xiv Contents CHAPTER 84 Fetal and Neonatal Physiology, 622 UNIT XV Sports Physiology CHAPTER 85 Sports Physiology, 629 Index, 637 UNIT I Introduction to Physiology: The Cell and General Physiology 1 Functional Organization of the Human Body and Control of the “Internal Environment,” 3 2 The Cell and Its Functions, 10 3 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction, 20 1 This page intentionally left blank       CHAPTER 1 Functional Organization of the Human Body and Control of the “Internal Environment” Physiology is the science that seeks to understand the function of living organisms and their parts. In human physiology, we are concerned with the characteristics of the human body that allow us to sense our environment, move about, think and communicate, reproduce, and perform all of the functions that enable us to survive and thrive as living beings. Human physiology links the basic sciences with clinical medicine and integrates multiple functions of molecules and subcellular components, the cells, tissues, and organs into the functions of the living human being. This integration requires communication and coordination by a vast array of control systems that operate at every level, from the genes that program synthesis of molecules to the complex nervous and hormonal systems that coordinate functions of cells, tissues, and organs throughout the body. Life in the human being relies on this total function, which is considerably more complex than the sum of the functions of the individual cells, tissues, and organs. Cells Are the Living Units of the Body. Each organ is an aggregate of many cells held together by intercellular supporting structures. The entire body contains 35 to 40 trillion cells, each of which is adapted to perform special functions. These individual cell functions are coordinated by multiple regulatory systems operating in cells, tissues, organs, and organ systems. Although the many cells of the body differ from each other in their special functions, all of them have certain basic characteristics. For example, (1) oxygen combines with breakdown products of fat, carbohydrates, or protein to release energy that is required for function of the cells; (2) most cells have the ability to reproduce, and whenever cells are destroyed, the remaining cells often regenerate new cells until the appropriate number is restored; and (3) cells are bathed in extracellular fluid, the constituents of which are precisely controlled. Microorganisms Living in the Body Outnumber Human Cells. Communities of microorganisms, often called microbiota, live on the skin and in the mouth, gut, and nose. The gastrointestinal tract, for example, normally contains a complex and dynamic population of 400 to 3 4 UNIT I Introduction to Physiology: The Cell and General Physiology 1000 species of microorganisms that outnumber our human cells. These microorganisms can cause diseases, but they usually live in harmony with their human hosts and provide vital functions, including immunity and digestion of foodstuffs, that are essential for our survival. MECHANISMS OF HOMEOSTASIS— MAINTENANCE OF NEARLY CONSTANT INTERNAL ENVIRONMENT (P. 4) Essentially all the organs and tissues of the body perform functions that help maintain the constituents of the extracellular fluid so they are relatively stable, a condition called homeostasis. Much of our discussion of physiology focuses on mechanisms by which the cells, tissues, and organs contribute to homeostasis. Extracellular Fluid Transport and Mixing System: The Blood Circulatory System About 50% to 70% of the adult human body is fluid, with approximately two-­thirds inside the cells and one-­third in the extracellular fluid surrounding the cells and circulating in the blood. Extracellular fluid is transported throughout the body in two stages. The first stage is movement of blood throughout the circulatory system, and the second stage is movement of fluid between the blood capillaries and cells. The circulatory system keeps the fluids of the internal environment continuously mixed by pumping blood through the vascular system. As blood passes through the capillaries, a large portion of its fluid diffuses back and forth into the interstitial fluid that lies between the cells, allowing continuous exchange of substances between the cells and the interstitial fluid and between the interstitial fluid and the blood. Origin of Nutrients in the Extracellular Fluid • The respiratory system provides oxygen for the body and removes carbon dioxide. • The gastrointestinal system digests food and facilitates absorption of various nutrients, including carbohydrates, fatty acids, and amino acids, into the extracellular fluid. • The liver changes the chemical composition of many of the absorbed substances to more usable forms, Functional Organization of the Human Body and Control of the “Internal Environment” 5 and other tissues of the body (e.g., fat cells, kidneys, endocrine glands) help modify the absorbed substances or store them until they are needed. • The musculoskeletal system consists of skeletal muscles, bones, tendons, joints, cartilage, and ligaments. Without this system, the body could not move to the appropriate place to obtain the foods required for nutrition. This system also protects internal organs and supports the body. Removal of Metabolic End Products (p. 6) • The respiratory system not only provides oxygen to the extracellular fluid but also removes carbon dioxide, which is produced by the cells, released from the blood into the alveoli, and then released to the external environment. • The kidneys excrete most of the waste products other than carbon dioxide. The kidneys play a major role in regulating extracellular fluid composition by controlling excretion of salts, water, and waste products of the chemical reactions of the cells. By controlling body fluid volumes and compositions, the kidneys also regulate blood volume and blood pressure. • The liver eliminates certain waste products produced in the body, as well as toxic substances that are ingested. • The gastrointestinal tract eliminates undigested materials and some waste products of metabolism in the feces. Regulation of Body Functions • The nervous system directs the activity of the muscular system, thereby providing locomotion. It also controls the function of many internal organs through the autonomic nervous system, and it allows us to sense our external and internal environment and to be intelligent beings so we can obtain the most advantageous conditions for survival. • The hormone systems control many metabolic functions of the cells, such as growth, rate of metabolism, and special activities associated with reproduction. Hormones are secreted into the bloodstream and are carried to tissues throughout the body to help regulate cell function. 6 UNIT I Introduction to Physiology: The Cell and General Physiology Protection of the Body • The immune system provides the body with a defense mechanism that protects against foreign invaders, such as bacteria and viruses, to which the body is exposed daily. • The integumentary system, which is composed mainly of skin, provides protection against injury and defense against foreign invaders, as well as protection of underlying tissues against dehydration. The skin also serves to regulate body temperature. Reproduction The reproductive system provides for formation of new beings like ourselves. Even this function can be considered a homeostatic function because it generates new bodies in which trillions of additional cells can exist in a well-­regulated internal environment. CONTROL SYSTEMS OF THE BODY (P. 7) The human body has thousands of control systems that are essential for homeostasis. For example, genetic systems operate in all cells to control intracellular and extracellular functions. Other control systems operate within the organs or throughout the entire body to control interactions among the organs. Regulation of oxygen and carbon dioxide concentrations in the extracellular fluid is a good example of multiple control systems that operate together. In this instance, the respiratory system operates in association with the nervous system. When carbon dioxide concentration in the blood increases above normal, the respiratory center is excited, causing the person to breathe rapidly and deeply. This breathing increases the expiration of carbon dioxide and therefore removes it from the blood and the extracellular fluid until the concentration returns to normal. Normal Ranges of Important Extracellular Fluid Constituents Table 1-1 shows some important constituents of extracellular fluid along with their normal values, normal ranges, and maximum limits that can be Functional Organization of the Human Body and Control of the “Internal Environment” 7 Table 1-1 Some Important Constituents and Physical Characteristics of the Extracellular Fluid, Normal Range of Control, and Approximate Nonlethal Limits for Short Periods Average Normal Value Normal Range Approximate Nonlethal Limit Parameter Units Oxygen (venous) mm Hg 40 25–40 10–1000 Carbon dioxide (venous) mm Hg 45 41–51 5–80 Sodium ion mmol/L 142 135–145 115–175 Potassium ion mmol/L 4.2 3.5–5.3 1.5–9.0 Calcium ion mmol/L 1.2 1.0–1.4 0.5–2.0 Chloride ion mmol/L 106 98–108 70–130 Bicarbonate ion mmol/L 24 22–29 8–45 Glucose mg/dl 90 70–115 20–1500 Body temperature ° F (° C) 98.4 (37.0) 98–98.8 (37.0) 65–110 (18.3–43.3) Acid-­base pH 7.4 7.3–7.5 6.9–8.0 endured for short periods without the occurrence of death. Note the narrowness of the ranges; levels outside these ranges are usually the cause or the result of illness. Characteristics of Control Systems Many Control Systems of the Body Operate by Negative Feedback. For regulation of carbon dioxide concen- tration, as discussed, a high concentration of carbon dioxide in the extracellular fluid increases pulmonary ventilation, which decreases carbon dioxide concentration, moving it toward normal levels. This mechanism is an example of negative feedback; that is, any stimulus that attempts to change the carbon dioxide concentration is counteracted by a response that is negative to the initiating stimulus. 8 UNIT I Introduction to Physiology: The Cell and General Physiology The degree of effectiveness with which a control system maintains constant conditions is determined by the gain of the negative feedback. The gain is calculated according to the following formula: Gain = Correction/Error Some control systems, such as those that regulate body temperature, have feedback gains as high as −33, which simply means that the degree of correction is 33 times greater than the remaining error. Feed-­ Forward Adaptive Control Systems Anticipate Changes. Because of the many interconnections between control systems, the total control of a particular body function may be more complex than can be accounted for by simple negative feedback. For example, some movements of the body occur so rapidly that there is not sufficient time for nerve signals to travel from some of the peripheral body parts to the brain and then back to the periphery in time to control the movements. Therefore, the brain uses feed-­forward control to cause the required muscle contractions. Sensory nerve signals from the moving parts inform the brain in retrospect of whether the appropriate movement, as envisaged by the brain, has been performed correctly. If it has not, the brain corrects the feed-­forward signals it sends to the muscles the next time the movement is required. This process is also called adaptive control, which is, in a sense, delayed negative feedback. Positive Feedback Can Sometimes Cause Vicious Cycles and Death; Other Times It Can Be Useful. A positive feed- back system responds to a perturbation with changes that amplify the perturbation, therefore leading to instability rather than stability. For example, severe hemorrhage may lower blood pressure to such a low level that blood flow to the heart is insufficient to maintain normal cardiac pumping; as a result, blood pressure falls even lower, further diminishing blood flow to the heart and causing still more weakness of the heart. Each cycle of this feedback leads to more of the same, which is a positive feedback or a vicious cycle. In some cases the body uses positive feedback to its advantage. An example is the generation of nerve signals. When the nerve fiber membrane is stimulated, the slight leakage of sodium ions into the cell causes opening of more channels, more sodium entry, more change in membrane potential, and so forth. Therefore, a slight leak of sodium into the cell becomes an explosion of Functional Organization of the Human Body and Control of the “Internal Environment” 9 sodium entering the interior of the nerve fiber, which creates the nerve action potential. Physiological Variability Although some physiological variables, such as plasma concentrations of ions, are tightly regulated, others, such as body weight and adiposity, show wide variations among different individuals, at different stages of life, and even at different times of the day. Blood pressure, metabolic rate, nervous system activity, hormones, and other physiological variables change throughout the day as we move about and engage in normal daily activities. Therefore, when we discuss “normal” values it is with the realization that many of the body’s control systems are constantly reacting to perturbations and that variability may exist among different individuals depending on body weight and height, diet, age, sex, environment, genetics and other factors. These sources of physiological variability are complex but important considerations when discussing normal physiology and the pathophysiology of diseases. SUMMARY: AUTOMATICITY OF THE BODY (P. 10) The body is a social order of many trillion of cells organized into various functional structures, the largest of which are called organs. Each functional structure, or organ, helps maintain a constant internal environment. As long as homeostasis is maintained, the cells of the body continue to live and function properly. Thus, each cell benefits from homeostasis, and in turn, each cell contributes its share toward maintaining homeostasis. This reciprocal interplay provides continuous automaticity of the body until one or more functional systems lose their ability to contribute their share of function. When this loss happens, all the cells of the body suffer. Extreme dysfunction leads to death, whereas moderate dysfunction leads to sickness. CHAPTER 2 The Cell and Its Functions ORGANIZATION OF THE CELL (P. 13) Figure. 2.1 illustrates the main features of a typical cell, including the nucleus and cytoplasm, which are separated by the nuclear membrane. The cytoplasm is separated from interstitial fluid by a cell membrane that surrounds the cell. The substances that make up the cell are collectively called protoplasm, which is composed mainly of the following: • Water constitutes 70% to 85% of most cells, except for adipocytes (fat cells). • Ions/electrolytes provide inorganic chemicals for cellular reactions. Some of the most important ions in the cell are potassium, magnesium, phosphate, sulfate, bicarbonate, and small quantities of sodium, chloride, and calcium. • Proteins normally constitute 10% to 20% of the cell mass. They can be divided into two types: structural proteins and globular (functional) proteins, which are mainly enzymes. • Lipids constitute about 2% of the total cell mass. Among the most important lipids in the cells are phospholipids, cholesterol, triglycerides, and neutral fats. In adipocytes (fat cells), triglycerides account for as much as 95% of the cell mass and represent the body’s main energy storehouse. • Carbohydrates play a major role in cell nutrition and, as parts of glycoproteins, have structural functions. Most human cells do not store large amounts of carbohydrates, which usually average about 1% of the total cell mass but may be as high as 3% in muscle cells and 6% in liver cells. The small amount of carbohydrates in the cells is usually stored in the form of glycogen, an insoluble polymer of glucose. CELL STRUCTURE (P. 14) The cell Figure 2-1 is not merely a bag of fluid and chemicals; it also contains highly organized physical structures called organelles. Some of the principal organelles of the cell are the cell membrane, nuclear membrane, endoplasmic reticulum, Golgi apparatus, mitochondria, lysosomes, and centrioles. 10 The Cell and Its Functions 11 Chromosomes and DNA Centrioles Secretory granule Golgi apparatus Microtubules Nuclear membrane Cytoplasm Cell membrane Nucleolus Glycogen Ribosomes Lysosome Mitochondrion Granular endoplasmic reticulum Smooth (agranular) endoplasmic reticulum Microfilaments Figure 2-1 Reconstruction of a typical cell, showing the internal organelles in the cytoplasm and nucleus. The Cell and Its Organelles Are Surrounded by Membranes Composed of Lipids and Proteins. The membranes that surround the cell and its organelles include the cell membrane, nuclear membrane, and membranes of the endoplasmic reticulum, mitochondria, lysosomes, and Golgi apparatus. They provide barriers that prevent free movement of water and water-­soluble substances from one cell compartment to another. Proteins in the membrane often penetrate the membrane, providing pathways (channels) to allow movement of specific substances through the membranes. The Cell Membrane Is a Lipid Bilayer With Inserted Proteins. The lipid bilayer is composed almost entirely of phospholipids, sphingolipids, and cholesterol. Phospholipids are the most abundant of the cell lipids and have a water-­soluble (hydrophilic) portion and a portion that is soluble only in fats (hydrophobic). The hydrophobic portions of the phospholipids face each other, whereas the hydrophilic parts face the two surfaces of the membrane in contact with the surrounding interstitial fluid and the cell cytoplasm. This lipid bilayer membrane is highly permeable to lipid-­soluble substances, such as oxygen, carbon dioxide, 12 UNIT I Introduction to Physiology: The Cell and General Physiology and alcohol, but it acts as a major barrier to water-­ soluble substances, such as ions and glucose. Floating in the lipid bilayer are proteins, most of which are glycoproteins (proteins combined with carbohydrates). There are two types of membrane proteins: the integral proteins, which protrude through the membrane, and the peripheral proteins, which are attached to the inner surface of the membrane and do not penetrate. Many of the integral proteins provide structural channels (pores) through which water-­soluble substances, especially ions, can diffuse. Other integral proteins act as carrier proteins for the transport of substances, sometimes against their gradients for diffusion. Integral proteins can also serve as receptors for substances, such as peptide hormones, that do not easily penetrate the cell membrane. The peripheral proteins are normally attached to one of the integral proteins and usually function as enzymes that catalyze chemical reactions of the cell. The membrane carbohydrates occur mainly in combination with proteins and lipids in the form of glycoproteins and glycolipids. The “glyco” portions of these molecules usually protrude to the outside of the cell. Many other carbohydrate compounds, called proteoglycans, which are mainly carbohydrate substances bound together by small protein cores, are loosely attached to the outer surface; thus, the entire outer surface of the cell often has a loose carbohydrate coat called the glycocalyx. The carbohydrates on the outer surface of the cell have multiple functions: (1) they are often negatively charged and therefore repel other molecules that are negatively charged; (2) the glycocalyx of cells may attach to other cells, thus attaching the cells to each other; (3) some of the carbohydrates act as receptors for binding hormones; and (4) some carbohydrate moieties enter into immune reactions, as discussed in Chapter 35. The Endoplasmic Reticulum Synthesizes Multiple Substances in the Cell. A large network of tubules and ves- icles, called the endoplasmic reticulum (ER), penetrates almost all parts of the cytoplasm. The ER membrane provides an extensive surface area for manufacture of many substances used inside the cells and released from some cells. They include proteins, carbohydrates, lipids, and other structures such as lysosomes, peroxisomes, and secretory granules. Lipids are made within the ER wall. For protein synthesis, ribosomes attach to the outer surface of the granular ER. These ribosomes function in association with The Cell and Its Functions 13 messenger ribonucleic acid (mRNA) to synthesize many proteins that then enter the Golgi apparatus, where the molecules are further modified before they are released or used in the cell. Part of the ER has no attached ribosomes and is called the agranular, or smooth, ER. The agranular ER functions for synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes. The Golgi Apparatus Functions in Association With the Endoplasmic Reticulum. The Golgi apparatus has mem- branes similar to those of the agranular ER, is prominent in secretory cells, and is located on the side of the cell from which the secretory substances are extruded. Small transport vesicles, also called ER vesicles, continually pinch off from the ER and then fuse with the Golgi apparatus. In this way, substances entrapped in the ER vesicles are transported from the ER to the Golgi apparatus. The substances are then processed in the Golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components. Lysosomes Provide an Intracellular Digestive System. Lysosomes, which are found in great numbers in many cells, are small spherical vesicles surrounded by a membrane that contains digestive enzymes. These enzymes allow lysosomes to break down intracellular substances in structures, especially damaged cell structures, food particles that have been ingested by the cell, and unwanted materials such as bacteria. The membranes surrounding the lysosomes usually prevent the enclosed enzymes from coming in contact with other substances in the cell and therefore prevent their digestive action. When these membranes are damaged, the enzymes are released and split the organic substances with which they come in contact into highly diffusible substances such as amino acids and glucose. Mitochondria Release Energy in the Cell. Mitochondria are the “powerhouses” of the cell that provide an adequate supply of energy to fuel the chemical reactions of the cell. This energy is provided mainly by the chemical reaction of oxygen with the three types of foods: glucose derived from carbohydrates, fatty acid derived from fats, and amino acids derived from proteins. After entering the cell, foods are split into smaller molecules that, in turn, enter the mitochondria, where other enzymes remove carbon dioxide and hydrogen ions in a process called the citric acid cycle. An oxidative enzyme system, which is also in the mitochondria, causes progressive oxidation of hydrogen atoms. The end products of mitochondria reactions are water and carbon dioxide. 14 UNIT I Introduction to Physiology: The Cell and General Physiology The energy liberated is used by mitochondria to synthesize a “high-­energy” substance, adenosine triphosphate (ATP), a highly reactive chemical that can diffuse throughout the cell to release its energy whenever it is needed for the performance of cell functions. Mitochondria are also self-­replicative, which means that one mitochondrion can form a second one, a third one, and so on, whenever there is a need in the cell for increased amounts of ATP. There Are Many Cytoplasmic Structures and Organelles. Hundreds of cell types are found in the body, and each has a special structure. Some cells, for example, are rigid and have large numbers of filamentous or tubular structures, which are composed of fibrillar proteins. A major function of these tubular structures is to act as a cytoskeleton, providing rigid physical structures for certain parts of cells. Some of the tubular structures, called microtubules, can transport substances from one area of the cell to another. One of the important functions of many cells is to secrete special substances, such as digestive enzymes. Almost all of the substances are formed by the ER-­Golgi apparatus system and are released into the cytoplasm inside storage vesicles called secretory vesicles. After a period of storage in the cell, they are expelled through the cell membrane to be used elsewhere in the body. The Nucleus Is the Cell Control Center and Contains Large Amounts of Deoxyribonucleic Acid (Genes) (p. 17). Genes determine the characteristics of the proteins of the cell, including the enzymes of the cytoplasm. They also control reproduction. Genes first reproduce themselves through a process of mitosis, in which two daughter cells are formed, each of which receives one of the two sets of genes. The nuclear membrane, also called the nuclear envelope, separates the nucleus from the cytoplasm. This structure is composed of two membranes; the outer membrane is continuous with the ER, and the space between the two nuclear membranes is also continuous with the compartment inside the ER. Both layers of the membrane are penetrated by several thousand nuclear pores, which consist of large complexes of proteins, almost 100 nm in diameter. Although the central channel diameter of the pore is only about 9 nm, this size is large enough to allow molecules up to 44,000 molecular weight to pass through with reasonable ease. The nuclei in most cells contain one or more structures called nucleoli, which, unlike many of the organelles, do not have a surrounding membrane. The nucleoli The Cell and Its Functions 15 contain large amounts of RNA and proteins of the type found in ribosomes. A nucleolus becomes enlarged when the cell is actively synthesizing proteins. Ribosomal RNA is stored in the nucleolus and transported through the nuclear membrane pores to the cytoplasm, where it is used to produce mature ribosomes, which play an important role in the formation of proteins. FUNCTIONAL SYSTEMS OF THE CELL (P. 21) Endocytosis: Ingestion by the Cell The cell obtains nutrients and other substances from the surrounding fluid through the cell membrane via diffusion and active transport. Very large particles enter the cell via endocytosis, the principal forms of which are pinocytosis and phagocytosis. • Pinocytosis is the ingestion of small globules of extracellular fluid, forming minute vesicles in the cell cytoplasm. This process is the only method by which large molecules, such as proteins, can enter the cells. These molecules usually attach to specialized receptors on the outer surface of the membrane that are concentrated in small pits called coated pits. On the inside of the cell membrane underneath these pits are a latticework of a fibrillar protein called clathrin and a contractile filament of actin and myosin. After the proteins bind with the receptors, the membrane invaginates, and contractile proteins surround the pit, causing its borders to close over the attached proteins and form a pinocytotic vesicle. • Phagocytosis is the ingestion of large particles, such as bacteria, cells, and portions of degenerating tissue. This ingestion occurs much in the same way as pinocytosis except that it involves large particles instead of molecules. Only certain cells have the ability to perform phagocytosis, notably tissue macrophages and some white blood cells. Phagocytosis is initiated when proteins or large polysaccharides on the surface of the particle bind with receptors on the surface of the phagocyte. In the case of bacteria, these usually are attached to specific antibodies, and the antibodies in turn attach to the phagocyte receptors, dragging the bacteria along with them. This intermediation of antibodies is called opsonization and is discussed further in Chapters 34 and 35. Lysosomes Digest Pinocytic and Phagocytic Foreign Substances in the Cells. Almost as soon as pinocytic or phagocytic vesicles appear inside a cell, lysosomes become attached to the vesicles and empty their 16 UNIT I Introduction to Physiology: The Cell and General Physiology digestive enzymes into the vesicles. Thus, digestive vesicles are formed in which the enzymes begin hydrolyzing the proteins, carbohydrates, lipids, and other substances in the vesicles. The products of digestion are small molecules of amino acids, glucose, phosphate, and other substances that can diffuse through the membrane of the vesicles into the cytoplasm. The undigested substances, called the residual body, are excreted through the cell membrane via the process of exocytosis, which is basically the opposite of endocytosis. The Endoplasmic Reticulum and Golgi Apparatus Synthesize Cellular Structures (p. 23) Synthesis of Most Cell Structures Begins in the ER. Many of the products formed in the ER are then passed onto the Golgi apparatus, where they are further processed before release into the cytoplasm. The granular ER, characterized by large numbers of ribosomes attached to the outer surface, is the site of protein formation. Ribosomes synthesize proteins and extrude many of them through the wall of the ER to the interior of the endoplasmic vesicles and tubules, called the endoplasmic matrix. When proteins enter the ER, enzymes in the ER wall cause rapid changes, including congregation of carbohydrates to form glycoproteins. In addition, the proteins are often cross-­linked, folded, and shortened to form more compact molecules. The ER also synthesizes lipids, especially phospholipids and cholesterol, which are incorporated into the lipid bilayer of the ER. Small ER vesicles, or transport vesicles, continually break off from the smooth reticulum. Most of these vesicles migrate rapidly to the Golgi apparatus. The Golgi Apparatus Processes Substances Formed in the ER. As substances are formed in the ER, they are transported through the reticulum tubules toward the portions of the smooth ER that lie nearest the Golgi apparatus. Small transport vesicles, composed of small envelopes of smooth ER, continually break away and diffuse to the deepest layer of the Golgi apparatus. The transport vesicles rapidly fuse with the Golgi apparatus and empty their contents into the vesicular spaces of the Golgi apparatus. Here, more carbohydrates are added to the secretions, and the ER secretions are compacted. As the secretions pass toward the outermost layers of the Golgi apparatus, the compaction and processing continue. Finally, small and large vesicles break away from The Cell and Its Functions 17 the Golgi apparatus, carrying with them the compacted secretory substances and diffusing throughout the cell. In a highly secretory cell, the vesicles formed by the Golgi apparatus are mainly secretory vesicles, which diffuse to the cell membrane, fuse with it, and eventually empty their substances to the exterior via a mechanism called exocytosis. Some of the vesicles made in the Golgi apparatus, however, are destined for intracellular use. For example, specialized portions of the Golgi apparatus form lysosomes. Mitochondria Extract Energy From Nutrients (p. 24) The principal substances from which the cells extract energy are oxygen and one or more of the foodstuffs— carbohydrates, fats, and proteins—that react with oxygen. In humans, almost all carbohydrates are converted to glucose by the digestive tract and liver before they reach the cell; similarly, proteins are converted to amino acids, and fats are converted to fatty acids. Inside the cell, these substances react chemically with oxygen under the influence of enzymes that control the rates of reaction and channel the released energy in the proper direction. Oxidative Reactions Occur Inside the Mitochondria, and Energy Released Is Used to Form ATP. ATP is a nucleotide composed of the nitrogenous base adenine, the pentose sugar ribose, and three phosphate radicals. The last two phosphate radicals are connected with the remainder of the molecule by high-­energy phosphate bonds, each of which contains about 12,000 calories of energy per mole of ATP under the usual conditions of the body. The high-­energy phosphate bonds are labile so they can be split instantly whenever energy is required to promote other cellular reactions. When ATP releases its energy, a phosphoric acid radical is split away, and adenosine diphosphate (ADP) is formed. Energy derived from cell nutrients causes ADP and phosphoric acid to recombine to form new ATP, with the entire process continuing over and over again. Most of the ATP Produced in the Cell Is Formed in Mitochondria. After entry into the cells, glucose is subjected to enzymes in the cytoplasm that convert it to pyruvic acid, a process called glycolysis. Less than 5% of ATP formed in the cell occurs via glycolysis. Pyruvic acid derived from carbohydrates, fatty acids derived from lipids, and amino acids derived from proteins are all eventually converted to the compound acetyl coenzyme A (acetyl-­CoA) in the mitochondria 18 UNIT I Introduction to Physiology: The Cell and General Physiology matrix. This substance is then acted on by another series of enzymes in a sequence of chemical reactions called the citric acid cycle, or Krebs cycle. In the citric acid cycle, acetyl-­CoA is split into hydrogen ions and carbon dioxide. Hydrogen ions are highly reactive and eventually combine with oxygen that has diffused into the mitochondria. This reaction releases a tremendous amount of energy, which is used to convert large amounts of ADP to ATP. This requires large numbers of protein enzymes that are integral parts of the mitochondria. The initial event in ATP formation is removal of an electron from the hydrogen atom, thereby converting it to a hydrogen ion. The terminal event is movement of the hydrogen ion through large globular proteins called ATP synthetase, which protrude through the membranes of the mitochondrial membranous shelves, which themselves protrude into the mitochondrial matrix. ATP synthetase is an enzyme that uses the energy from movement of the hydrogen ions to convert ADP to ATP, and hydrogen ions combine with oxygen to form water. The newly formed ATP is transported out of the mitochondria to all parts of the cell cytoplasm and nucleoplasm, where it is used to energize the functions of the cell. This overall process is called the chemiosmotic mechanism of ATP formation. ATP Is Used for Many Cellular Functions. ATP promotes three types of cell function: (1) membrane transport, as occurs with the sodium-­potassium pump, which transports sodium out of the cell and potassium into the cell; (2) synthesis of chemical compounds throughout the cell; and (3) mechanical work, as occurs with the contraction of muscle fibers or with ciliary and ameboid motion. Cell Locomotion and Ciliary Movements (p. 26) The most obvious type of movement in the body is that of the specialized muscle cells in skeletal, cardiac, and smooth muscle, which constitute almost 50% of the entire body mass. Two other types of movement occur in other cells: ameboid locomotion and ciliary movement. Ameboid Movement of an Entire Cell in Relation to Its Surroundings. An example of ameboid locomotion is the movement of white blood cells through tissues. Typically, ameboid locomotion begins with protrusion of a pseudopodium from one end of the cell. This results from continual exocytosis, which forms a new cell membrane at the leading edge of the pseudopodium, The Cell and Its Functions 19 and continual endocytosis of the membrane in the mid-­ and rear portions of the cell. Two other effects are also essential to the forward movement of the cell. The first effect is attachment of the pseudopodium to the surrounding tissues so it becomes fixed in its leading position while the remainder of the cell body is pulled forward toward the point of attachment. This attachment is effected by receptor proteins that line the insides of the exocytotic vesicles. The second requirement for locomotion is available energy needed to pull the cell body in the direction of the pseudopodium. In the cytoplasm of all cells are molecules of the protein actin. When these molecules polymerize to form a filamentous network, the network contracts when it binds with another protein, for example, an actin-­binding protein such as myosin. The entire process, which is energized by ATP, takes place in the pseudopodium of a moving cell, in which such a network of actin filaments forms inside the growing pseudopodium. The most important initiator of ameboid movement is chemotaxis, which results from the appearance of certain chemotactic substances in the tissue. Ciliary Movement Is a Whiplike Movement of Cilia on the Surfaces of Cells. Ciliary movement occurs in two places in the body: on the inside surfaces of the respiratory airways and on the inside surfaces of the uterine tubes (i.e., the fallopian tubes of the reproductive tract). In the nasal cavity and lower respiratory airways, the whiplike motion of the cilia causes a layer of mucus to move toward the pharynx at a rate of about 1 cm/min; in this way, passageways with mucus or particles that become entrapped in the mucus are continually cleared. In the uterine tubes, the cilia cause slow fluid movement from the ostium of the uterine tube toward the uterine cavity; it is mainly this fluid movement that transports the ovum from the ovary to the uterus. The mechanism of the ciliary movement is not fully understood, but at least two factors are necessary: (1) available ATP and (2) appropriate ionic conditions, including appropriate concentrations of magnesium and calcium. CHAPTER 3 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction Genes in the Cell Nucleus Control Protein Synthesis (p. 31). The genes control cell protein synthesis and in this way control cell function. Proteins play a key role in almost all cell functions by serving as enzymes that catalyze the reactions of the cell and as major components of the physical structures of the cell. Each gene is a double-­stranded, helical molecule of deoxyribonucleic acid (DNA) that controls formation of ribonucleic acid (RNA). The RNA, in turn, spreads throughout the cells to control formation of a specific protein. The entire process, from transcription of the genetic code in the nucleus to translation of the RNA code and formation of proteins in the cell cytoplasm, is often referred to as gene expression and is shown in Figure 3-1. Because there are about 25,000 genes that code for proteins in each cell, it is possible to form large numbers of different cellular proteins. In fact, RNA molecules transcribed from the same gene can be processed in different ways by the cell, giving rise Plasma membrane Nuclear envelope Nucleus DNA DNA transcription RNA mRNA Ribosomes RNA splicing Transcription RNA formation Translation RNA transport mRNA Translation of mRNA Cytosol Gene (DNA) Protein formation Cell structure Cell enzymes Protein Cell function Figure 3-1 General schema by which the genes control cell function. 20 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction 21 to alternate versions of the protein. The total number of different proteins produced by various cell types in humans is estimated to be at least 100,000. Nucleotides Are Organized to Form Two Strands of DNA Loosely Bound to Each Other. Genes are attached in an end-­on-­end manner in long, double-­stranded, helical molecules of DNA that are composed of three basic building blocks: (1) phosphoric acid, (2) deoxyribose (a sugar), and (3) four nitrogenous bases: two purines (adenine and guanine) and two pyrimidines (thymine and cytosine). The first stage in DNA formation is the combination of one molecule of phosphoric acid, one molecule of deoxyribose, and one of four bases to form a nucleotide. Four nucleotides can therefore be formed, one from each of the four bases. Multiple nucleotides are bound together to form two strands of DNA that are loosely bound to each other. The backbone of each DNA strand is composed of alternating phosphoric acid and deoxyribose molecules. The purine and pyrimidine bases are attached to the side of the deoxyribose molecules, and loose bonds between purine and pyrimidine bases of the two DNA strands hold them together. The purine base adenine of one strand always bonds with the pyrimidine base thymine of the other strand, whereas guanine always bonds with cytosine. The Genetic Code Consists of Triplets of Bases. Each group of three successive bases in the DNA strand is called a code word. These code words control the sequence of amino acids in the protein to be formed in the cytoplasm. One code word, for example, might be composed of a sequence of adenine, thymine, and guanine, whereas the next code word might have a sequence of cytosine, guanine, and thymine. These two code words have entirely different meanings because their bases are different. The sequence of successive code words of the DNA strand is known as the genetic code. TRANSCRIPTION: TRANSFER OF THE DNA CODE IN THE NUCLEUS TO RNA CODE IN THE CELL CYTOPLASM (P. 33) Because DNA is located in the nucleus and many cell functions are carried out in the cytoplasm, there must be some method by which the genes of the nucleus control the chemical reactions of the cytoplasm. This is achieved through RNA, the formation of which is 22 UNIT I Introduction to Physiology: The Cell and General Physiology controlled by DNA. During this process the DNA code is transferred to RNA, a process called transcription. The RNA diffuses from the nucleus to the nuclear pores into the cytoplasm, where it controls protein synthesis. RNA Is Synthesized in the Nucleus From a DNA Template. During synthesis of RNA, the two strands of DNA separate, and one of the two strands is used as a template for RNA synthesis. The DNA code triplets cause the formation of complementary code triplets (called codons) in RNA; these codons then control the sequence of amino acids in a protein to be synthesized later in the cytoplasm. Each DNA strand in each chromosome carries the code for perhaps as many as 2000 to 4000 genes. The basic building blocks of RNA are almost the same as those of DNA except that in RNA, the sugar ribose replaces the sugar deoxyribose, and the pyrimidine uracil replaces thymine. The basic building blocks of RNA combine to form four nucleotides, exactly as described for DNA synthesis. These nucleotides contain the bases adenine, guanine, cytosine, and uracil. The next step in RNA synthesis is activation of the nucleotides, which occurs through the addition of two phosphate radicals to each nucleotide to form triphosphates. These last two phosphates are combined with the nucleotide by high-­energy phosphate bonds, which are derived from the adenosine triphosphate (ATP) of the cell. This activation process makes available large quantities of energy, which is used to promote chemical reactions that add each new RNA nucleotide to the end of the RNA chain. The DNA Strand Is Used as a Template to Assemble the RNA Molecule From Activated Nucleotides. The assembly of the RNA molecule occurs under the influence of the enzyme RNA polymerase as follows: 1. In the DNA strand immediately ahead of the gene that is to be transcribed is a sequence of nucleotides called the promoter. An RNA polymerase recognizes this promoter and attaches to it. 2. The polymerase causes unwinding of two turns of the DNA helix and separation of the unwound portions. 3. The polymerase moves along the DNA strand and begins forming RNA molecules by binding complementary RNA nucleotides to the DNA strand. 4. The successive RNA nucleotides then bind to each other to form an RNA strand. 5. When the RNA polymerase reaches the end of the DNA gene, it encounters a sequence of DNA molecules called the chain-­terminating sequence, causing Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction 23 the polymerase to break away from the DNA strand. The RNA strand is then released into the nucleoplasm. The code present in the DNA strand is transmitted in complementary form to the RNA molecule as follows: DNA Base RNA Base Guanine Cytosine Cytosine Guanine Adenine Uracil Thymine Adenine There Are Several Types of RNA. Research on RNA has uncovered many different types of RNA. Some are involved in protein synthesis, whereas others serve gene regulatory functions or are involved in posttranscriptional modification of RNA. The following six types of RNA play independent and different roles in protein synthesis: 1. Precursor messenger RNA (pre-­mRNA), a large, immature single strand of RNA that is processed in the nucleus to form mature mRNA and includes two different types of segments called introns, which are removed by a process called splicing, and exons, which are retained in the final mRNA 2. Small nuclear RNA (snRNA), which directs the splicing of pre-­mRNA to form mRNA 3. mRNA, which carries the genetic code to the cytoplasm to control the formation