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Chapter 1 An Introduction to the Human Body Chapter 2 The Chemical Level of Organization Chapter 3 The Cellular Level of Organization Chapter 4 The Tissue Level of Organization 2 Preface Unit 2: Support and Movement In Chapters 5–11 order 10 mg motilium overnight delivery, students explore the skin buy motilium 10mg without a prescription, the largest organ of the body purchase motilium 10mg, and examine the body’s skeletal and muscular systems, following a traditional sequence of topics. This unit is the first to walk students through specific systems of the body, and as it does so, it maintains a focus on homeostasis as well as those diseases and conditions that can disrupt it. Chapter 5 The Integumentary System Chapter 6 Bone and Skeletal Tissue Chapter 7 The Axial Skeleton Chapter 8 The Appendicular Skeleton Chapter 9 Joints Chapter 10 Muscle Tissue Chapter 11 The Muscular System Unit 3: Regulation, Integration, and Control Chapters 12–17 help students answer questions about nervous and endocrine system control and regulation. In a break with the traditional sequence of topics, the special senses are integrated into the chapter on the somatic nervous system. The chapter on the neurological examination offers students a unique approach to understanding nervous system function using five simple but powerful diagnostic tests. Chapter 12 Introduction to the Nervous System Chapter 13 The Anatomy of the Nervous System Chapter 14 The Somatic Nervous System Chapter 15 The Autonomic Nervous System Chapter 16 The Neurological Exam Chapter 17 The Endocrine System Unit 4: Fluids and Transport In Chapters 18–21, students examine the principal means of transport for materials needed to support the human body, regulate its internal environment, and provide protection. Chapter 18 Blood Chapter 19 The Cardiovascular System: The Heart Chapter 20 The Cardiovascular System: Blood Vessels and Circulation Chapter 21 The Lymphatic System and Immunity Unit 5: Energy, Maintenance, and Environmental Exchange In Chapters 22–26, students discover the interaction between body systems and the outside environment for the exchange of materials, the capture of energy, the release of waste, and the overall maintenance of the internal systems that regulate the exchange. Chapter 22 The Respiratory System Chapter 23 The Digestive System Chapter 24 Nutrition and Metabolism Chapter 25 The Urinary System Chapter 26 Fluid, Electrolyte, and Acid–Base Balance Unit 6: Human Development and the Continuity of Life The closing chapters examine the male and female reproductive systems, describe the process of human development and the different stages of pregnancy, and end with a review of the mechanisms of inheritance. Chapter 27 The Reproductive System Chapter 28 Development and Genetic Inheritance Pedagogical Foundation and Features Anatomy and Physiology is designed to promote scientific literacy. Throughout the text, you will find features that engage the students by taking selected topics a step further. Aging explores the effect aging has on a body’s system and specific disorders that manifest over time. Career Connections presents information on the various careers often pursued by allied health students, such as This OpenStax book is available for free at http://cnx. Students are introduced to the educational requirements for and day-to-day responsibilities in these careers. Everyday Connections tie anatomical and physiological concepts to emerging issues and discuss these in terms of everyday life. Many features include links to the University of Michigan’s interactive WebScopes, which allow students to zoom in on micrographs in the collection. These resources were vetted by reviewers and other subject matter experts to ensure that they are effective and accurate. We strongly urge students to explore these links, whether viewing a video or inputting data into a simulation, to gain the fullest experience and to learn how to search for information independently. Dynamic, Learner-Centered Art Our unique approach to visuals is designed to emphasize only the components most important in any given illustration. The art style is particularly aimed at focusing student learning through a powerful blend of traditional depictions and instructional innovations. The strongest line is used to highlight the most important structures, and shading is used to show dimension and shape. Color is used sparingly to highlight and clarify the primary anatomical or functional point of the illustration. This technique is intended to draw students’ attention to the critical learning point in the illustration, without distraction from excessive gradients, shadows, and highlights. Full color is used when the structure or process requires it (for example, muscle diagrams and cardiovascular system illustrations). By highlighting the most important portions of the illustration, the artwork helps students focus on the most important points without overwhelming them. Micrographs Micrograph magnifications have been calculated based on the objective provided with the image. If a micrograph was recorded at 40×, and the image was magnified an additional 2×, we calculated the final magnification of the micrograph to be 80×. Please note that, when viewing the textbook electronically, the micrograph magnification provided in the text does not take into account the size and magnification of the screen on your electronic device. Instructor resources require a verified instructor account, which you can apply for when you log in or create your account on openstax. Partner Resources OpenStax Partners are our allies in the mission to make high-quality learning materials affordable and accessible to students and instructors everywhere. Gordon Betts, Tyler Junior College Peter Desaix, University of North Carolina at Chapel Hill Eddie Johnson, Central Oregon Community College Jody E. Johnson, Arapahoe Community College Oksana Korol, Aims Community College Dean Kruse, Portland Community College Brandon Poe, Springfield Technical Community College James A. Heyden Contributing Authors Kim Aaronson, Aquarius Institute; Triton College Lopamudra Agarwal, Augusta Technical College Gary Allen, Dalhousie University Robert Allison, McLennan Community College Heather Armbruster, Southern Union State Community College This OpenStax book is available for free at http://cnx. Petersburg College 6 Preface Mary Jane Niles, University of San Francisco Ikemefuna Nwosu, Parkland College; Lake Land College Betsy Ott, Tyler Junior College Ivan Paul, John Wood Community College Aaron Payette, College of Southern Nevada Scott Payne, Kentucky Wesleyan College Cameron Perkins, South Georgia College David Pfeiffer, University of Alaska, Anchorage Thomas Pilat, Illinois Central College Eileen Preston, Tarrant County College Mike Pyle, Olivet Nazarene University Robert Rawding, Gannon University Jason Schreer, State University of New York at Potsdam Laird Sheldahl, Mt. Hood Community College Brian Shmaefsky, Lone Star College System Douglas Sizemore, Bevill State Community College Susan Spencer, Mount Hood Community College Cynthia Standley, University of Arizona Robert Sullivan, Marist College Eric Sun, Middle Georgia State College Tom Swenson, Ithaca College Kathleen Tallman, Azusa Pacific University Rohinton Tarapore, University of Pennsylvania Elizabeth Tattersall, Western Nevada College Mark Thomas, University of Northern Colorado Janis Thompson, Lorain County Community College Rita Thrasher, Pensacola State College David Van Wylen, St. Louis College of Pharmacy Kathleen Weiss, George Fox University Neil Westergaard, Williston State College David Wortham, West Georgia Technical College Umesh Yadav, University of Texas Medical Branch Tony Yates, Oklahoma Baptist University Justin York, Glendale Community College Cheri Zao, North Idaho College Elena Zoubina, Bridgewater State University; Massasoit Community College Shobhana Natarajan, Alcon Laboratories, Inc. Special Thanks OpenStax wishes to thank the Regents of University of Michigan Medical School for the use of their extensive micrograph collection. We also wish to thank the Open Learning Initiative at Carnegie Mellon University, with whom we shared and exchanged resources during the development of Anatomy and Physiology. An understanding of anatomy and 8 Chapter 1 | An Introduction to the Human Body physiology is not only fundamental to any career in the health professions, but it can also benefit your own health. Familiarity with the human body can help you make healthful choices and prompt you to take appropriate action when signs of illness arise. Your knowledge in this field will help you understand news about nutrition, medications, medical devices, and procedures and help you understand genetic or infectious diseases. At some point, everyone will have a problem with some aspect of his or her body and your knowledge can help you to be a better parent, spouse, partner, friend, colleague, or caregiver. This chapter begins with an overview of anatomy and physiology and a preview of the body regions and functions. It introduces a set of standard terms for body structures and for planes and positions in the body that will serve as a foundation for more comprehensive information covered later in the text. Some of these structures are very small and can only be observed and analyzed with the assistance of a microscope. When a body is dissected, its structures are cut apart in order to observe their physical attributes and their relationships to one another. In order to observe structures in living people, however, a number of imaging techniques have been developed. These techniques allow clinicians to visualize structures inside the living body such as a cancerous tumor or a fractured bone. Gross anatomy is the study of the larger structures of the body, those visible without the aid of magnification (Figure 1. In contrast, micro- means “small,” and microscopic anatomy is the study of structures that can be observed only with the use of a microscope or other magnification devices (Figure 1. As the technology of microscopes has advanced, anatomists have been able to observe smaller and smaller structures of the body, from slices of large structures like the heart, to the three-dimensional structures of large molecules in the body. Regional anatomy is the study of the interrelationships of all of the structures in a specific body region, such as the abdomen. In contrast, systemic anatomy is the study of the structures that make up a discrete body system—that is, a group of structures that work together to perform a unique body function. For example, a systemic anatomical study of the muscular system would consider all of the skeletal muscles of the body. Human physiology is the scientific study of the chemistry and physics of the structures of the body and the ways in which they work together to support the functions of life. The study of physiology certainly includes observation, both with the naked eye and with microscopes, as well as manipulations and measurements. However, current advances in physiology usually depend on carefully designed laboratory experiments that reveal the functions of the many structures and chemical compounds that make up the human body. For example, neurophysiology is the study of the brain, spinal cord, and nerves and how these work together to perform functions as complex and diverse as vision, movement, and thinking. Physiologists may work from the organ level (exploring, for example, what different parts of the brain do) to the molecular level (such as exploring how an electrochemical signal travels along nerves). For example, the thin flap of your eyelid can snap down to clear away dust particles and almost instantaneously slide back up to allow you to see again. At the microscopic level, the arrangement and function of the nerves and muscles that serve the eyelid allow for its quick action and retreat. At a smaller level of analysis, the function of these nerves and muscles likewise relies on the interactions of specific molecules and ions. Your study of anatomy and physiology will make more sense if you continually relate the form of the structures you are studying to their function.

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The medical examination of these patients [This is the best website for information about requires experience and understanding of the con- regional anaesthesia techniques generic motilium 10 mg with amex. It is a very practical tropics companion for the increasing number of medical students and junior doctors who have the opportunity to practice medicine in the tropics buy 10 mg motilium mastercard. The Integrates the basic science book integrates basic science with clinical practice cheap motilium 10 mg line, with disease-orientated with clinical practice descriptions and clinical presentations on a system-by-system basis. Core introductory text for the For this new sixth edition the text has been brought fully up to date throughout. The student and the practitioner highly structured and improved text is designed to facilitate easy access to information, making the book an ideal resource for clinical attachments and revision. Major update throughout and There is a new chapter that covers infections in special groups, as well as coverage new chapter on infections in of sepsis and septic shock. It follows the now familiar, easy-to-use, double page spread format of the * Concise introduction and at a Glance series. Each double page presents clear, memorable diagrams that revision text illustrate essential information with accompanying text that covers key topics and issues in more detail. The first section focuses on basic biological concepts such as cell and * Three section structure chromosome structure, molecular biology and the cell cycle, as well as human covering developmental embyronic development and sexual maturation. It can be used as primary or supplementary reading in a lecture- based course and is perfect for exam preparation. White Second edition 2007 2 Introduction The purpose of the pediatric anesthesia rotation is to provide an initial exposure to a variety of pediatric cases. The length of this rotation, 4 weeks, is enough to allow participation in the care of about 100 patients. One of the goals of this rotation is to prepare residents for routine “bread and butter” cases, to be safe with pediatric patients, and to be able to identify situations in which he or she might need help. Pressure controlled ventilation may be the best choice- since it will deliver whatever volume will generate the set pressure (such as 20 mm Hg). An oral airway that is too small can indent the tongue and push it back into the hypopharynx, effectively preventing air exchange. When measuring the oral airway on the outside of the jaw, make sure that the tip will not extend past the angle of the mandible. A pulse oximeter should be the first monitor placed on the child, followed by a precordial stethoscope. When left to right shunting may occur (as in all infants), two oximeters (one on the right arm or right ear) and another on one of the other three extremities will reflect the amount of shunting occurring. The precordial stethoscope will tell you that air is moving in the trachea, the patient is not having laryngospasm (hopefully! On the anesthesia cart you should have succinylcholine, atropine, and a syringe with a mixture of succinylcholine and atropine. Use of this syringe will be necessary extremely rarely- in the instance where a child develops laryngospasm during inhalation induction before intravenous access has been achieved. Never use dextrose containing solutions for fluid boluses or to replace third space or intravascular volume losses. If there is any concern about procuring the airway, dextrose administration should be deferred until this has been accomplished as dextrose infusions have been associated with worsening the outcomes of hypoxic episodes. Age definitions: the term newly born is used to describe the infant in the first minutes to hours after birth; the term neonate describes infants in the first 28 days/first month/ of life; the term infant includes the neonatal period and up to 12 months. Respiratory distress syndrome – absence or deficiency of surfactant; characterized by hypercarbia and hypoxia with resultant acidosis; may be complicated by pneumothorax, pneumomediastinum, and pulmonary interstitial emphysema. Bronchopulmonary dysplasia – chronic obstructive lung disease of neonates exposed to barotraumas and high inspired oxygen concentration; characterized by persistent respiratory difficulty and radiographic evidence of diffuse linear densities and radiolucent areas. Persistent pulmonary hypertension – pulmonary hypertension and vascular hyperreactivity with resultant right to left shunting and cyanosis; associated with cardiac anomalies, respiratory distress syndrome, meconium aspiration syndrome, diaphragmatic hernia, and group B streptococcal sepsis. Gastroesophageal reflux – involuntary movement of stomach contents into the esophagus; physiologic reflux is found in all newborns; pathologic reflux can result in failure to thrive, recurrent respiratory problems/aspiration, bronchospasm, and apnea, irritability, esophagitis, ulceration and gastrointestinal bleeding. Jaundice – hyperbilirubinemia from increased bilirubin load and poor hepatic conjugation/unconjugated, physiologic/ or abnormalities of bilirubin production, metabolism, or excretion/non-physiologic/. Hypoglycemia – blood sugar less than 40 mg/100ml, characterized by lethargy, hypotonia, tremors, apnea, and seizures. Premedication The primary goals of premedication in children are to facilitate a smooth separation from the parents and to ease the induction of anesthesia. Other effects that may be achieved by premedication include: Amnesia Anxiolysis Prevention of physiologic stress Reduction of total anesthetic requirements Decreased probability of aspiration Vagolysis Decreased salivation and secretions Antiemesis Analgesia Children greater than 10 months usually receive midazolam 0. The circuits used for pediatrics were traditionally designed specifically to decrease the resistance to breathing by eliminating valves; decrease the amount of dead space in the circuit; and in the case of the Bain circuit, decrease the amount of heat loss by having a coaxial circuit with warm exhaled gas surrounding and warming the fresh gas flow. Airways: To determine whether an oral airway is the proper size, hold the airway beside the patient’s face with the top of the airway beside the mouth. It is less bulky, allowing laryngoscopy to be performed while cricoid pressure is applied with the fifth finger of the same hand. In general straight blades/Miller/ are used in infants to facilitate picking up the elongated epiglottis and exposing the vocal cords. Endotracheal tubes: small-diameter endotracheal tubes increase airway resistance and work of breathing. The anesthesiologist should calculate ideal tube size and have available one size larger and one size smaller. Ultimately the proper tube size is confirmed by the ability to generate positive pressure greater than 30 cm H2O and by the presence of a leak at less than 20 cm H2O. It is caused most often by inadequate depth of anesthesia with sensory stimulation /secretions, manipulation of airway, surgical stimulation/. Treatment includes removal of stimulus, 100% oxygen, continuous positive pressure by mask, and muscle relaxants. Usually laryngospasm will break under positive pressure but on the rare occasion that this fails, only a very small dose of succinylcholine is required for relaxation of the vocal cords, which are quite sensitive to muscle relaxation. While 1-2 mg/kg maybe required for complete relaxation, only one tenth of this will generally relax the vocal cords. Blood pressure monitoring: Cuff size can be determined using the following criteria: cuff bladder width should be approximately 40% of the arm circumference; bladder length should be 90 to 100% of the arm circumference. Invasive monitoring ( intraarterial catheters); Smaller catheters provide greater accuracy in monitoring, but larger are more practical for blood sampling. The consequences of thermal stress include cerebral and cardiac depression, increased oxygen demand, acidosis, hypoxia, and intracardiac shunt reversal. Use of the oximeter is particularly important in pediatrics because of the greater tendency of the infant to develop rapid desaturation and hypoxemia. The goal of neonatal oxygen monitoring is to maintain saturation in the low 90s to minimize risks of oxygen toxicity. In infants, two probes/preductal (right ear or right arm) and postductal (left arm or either leg) will reflect the amount of right to left shunting occurring. Also, while a patient may become noticeably cyanotic when the sat drops below 90%, there is no level of hypercarbia that is reliably clinically evident. Factors that increase West’s Zone I of the lungs (where alveolar pressure surpasses arterial pressure) will increase gradient. Such factors include hypovolemia (decreasing arterial pressure) and increased mean airway pressure (increasing alveolar pressure). Infants will not display head lift or respond to commands, even with full return of neuromuscular function. The facial nerve is not recommended as the orbicularis oculi muscle is more resistant to blockade and if one successfully blocks this muscle, the patient’s neuromuscular blockade may be unreversible. Also, direct muscle stimulation in this area may result in the administration of excessive amounts of relaxant. Small-gauge catheters are available for venous cannulation: 24G, 22G; a 25 or 27-gauge for very small premature infants. It will be much easier to administer medications and remove air from the intravenous system by using a separate stopcock and attaching it to a plain piece of extension tubing. Extensions for intravenous systems are particularly advisable as intravenous access is sometimes obtained in lower extremities. Fluids, electrolytes and transfusion therapy Preterm and small infants have a relatively high percentage of total body water/85% in a preterm and 75% in a full-term infant/. Generally either lactated Ringer’s or normal saline is used for routine intraoperative fluid administration. Glycogen stores in the neonatal liver are limited and are rapidly depleted within the first few hours of life. Preterm infants may be hypoglycemic without demonstrable symptoms, necessitating close monitoring of blood glucose levels.

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The thalamus then sends the sensory information to the cerebral cortex cheap motilium 10mg with amex, the outermost layer of gray matter in the brain cheap motilium 10 mg fast delivery, where conscious perception of that water temperature begins generic 10mg motilium amex. Finally, a plan is developed about what to do, whether that is to turn the temperature up, turn the whole shower off and go back to bed, or step into the shower. To do any of these things, the cerebral cortex has to send a command out to your body to move muscles (Figure 12. The upper motor neuron is in this region, called the precentral gyrus of the frontal cortex, which has an axon that extends all the way down the spinal cord. At the level of the spinal cord at which this axon makes a synapse, a graded potential occurs in the cell membrane of a lower motor neuron. Acetylcholine is released at this specialized synapse, which causes the muscle action potential to begin, following a large potential known as an end plate potential. All of this occurs in a fraction of a second, but this story is the basis of how the nervous system functions. The career path of a research scientist can be straightforward: college, graduate school, postdoctoral research, academic research position at a university. A Bachelor’s degree in science will get you started, and for neurophysiology that might be in biology, psychology, computer science, engineering, or neuroscience. There are many different programs out there to study the nervous system, not just neuroscience itself. These are usually considered five-year programs, with the first two years dedicated to course work and finding a research mentor, and the last three years dedicated to finding a research topic and pursuing that with a near single-mindedness. The research will usually result in a few publications in scientific journals, which will make up the bulk of a doctoral dissertation. In this position, a researcher starts to establish their own research career with the hopes of finding an academic position at a research university. Especially for neurophysiology, a medical degree might be more suitable so you can learn about the clinical applications of neurophysiology and possibly work with human subjects. Biotechnology firms are eager to find motivated scientists ready to tackle the tough questions about how the nervous system works so that therapeutic chemicals can be tested on some of the most challenging disorders such as Alzheimer’s disease or Parkinson’s disease, or spinal cord injury. Others with a medical degree and a specialization in neuroscience go on to work directly with patients, diagnosing and treating mental disorders. You can do this as a psychiatrist, a neuropsychologist, a neuroscience nurse, or a neurodiagnostic technician, among other possible career paths. To understand how neurons are able to communicate, it is necessary to describe the role of an excitable membrane in generating these signals. The basis of this communication is the action potential, which demonstrates how changes in the membrane can constitute a signal. Looking at the way these signals work in more variable circumstances involves a look at graded potentials, which will be covered in the next section. Electrically Active Cell Membranes Most cells in the body make use of charged particles, ions, to build up a charge across the cell membrane. For skeletal muscles to contract, based on excitation–contraction coupling, requires input from a neuron. Both of the cells make use of the cell membrane to regulate ion movement between the extracellular fluid and cytosol. As you learned in the chapter on cells, the cell membrane is primarily responsible for regulating what can cross the 524 Chapter 12 | The Nervous System and Nervous Tissue membrane and what stays on only one side. The cell membrane is a phospholipid bilayer, so only substances that can pass directly through the hydrophobic core can diffuse through unaided. Charged particles, which are hydrophilic by definition, cannot pass through the cell membrane without assistance (Figure 12. Several passive transport channels, as well as active transport pumps, are necessary to generate a transmembrane potential and an action potential. Of special interest is the carrier protein referred to as the sodium/ + + potassium pump that moves sodium ions (Na ) out of a cell and potassium ions (K ) into a cell, thus regulating ion concentration on both sides of the cell membrane. As was explained in the cell chapter, the concentration of Na is higher outside the cell than inside, and + the concentration of K is higher inside the cell than outside. That means that this pump is moving the ions against the concentration gradients for sodium and potassium, which is why it requires energy. Ion channels are pores that allow specific charged particles to cross the membrane in response to an existing concentration gradient. Proteins are capable of spanning the cell membrane, including its hydrophobic core, and can interact with the charge of ions because of the varied properties of amino acids found within specific domains or regions of the protein channel. Hydrophobic amino acids are found in the domains that are apposed to the hydrocarbon tails of the phospholipids. Additionally, the ions will interact with the hydrophilic amino acids, which will be selective for the charge of the ion. The distance between the amino acids will be specific for the diameter of the ion when it dissociates from the water molecules surrounding it. Because of the surrounding water molecules, larger pores are not ideal for smaller ions because the water molecules will interact, by hydrogen bonds, more readily than the amino acid side chains. Some ion channels are selective for charge but not + necessarily for size, and thus are called a nonspecific channel. These nonspecific channels allow cations—particularly Na , + 2+ K , and Ca —to cross the membrane, but exclude anions. Although these classes of ion channels are found primarily in the cells of nervous or muscular tissue, they also can be found in the cells of epithelial and connective tissues. A ligand-gated channel opens because a signaling molecule, a ligand, binds to the extracellular region of the channel. This type of channel is also known as an ionotropic receptor because when the ligand, known as a neurotransmitter in the nervous system, binds to the protein, ions cross the membrane changing its charge (Figure 12. For example, as pressure is applied to the skin, these channels open and allow ions to enter the cell. Similar to this type of channel would be the channel that opens on the basis of temperature changes, as in testing the water in the shower (Figure 12. A voltage-gated channel is a channel that responds to changes in the electrical properties of the membrane in which it is embedded. When that voltage becomes less negative, the channel begins to allow ions to cross the membrane (Figure 12. Amino acids in the structure of the protein are sensitive to charge and cause the pore to open to the selected ion. A leakage channel is randomly gated, meaning that it opens and closes at random, hence the reference to leaking. There is no actual event that opens the channel; instead, it has an intrinsic rate of switching between the open and closed states. Leakage channels contribute to the resting transmembrane voltage of the excitable membrane (Figure 12. The particular electrical properties of certain cells are modified by the presence of this type of channel. The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking (Figure 12. The concentration of ions in extracellular and intracellular fluids is largely balanced, with a net neutral charge. However, a slight difference in charge occurs right at the membrane surface, both internally and externally. It is the difference in this very limited region that has all the power in neurons (and muscle cells) to generate electrical signals, including action potentials. Before these electrical signals can be described, the resting state of the membrane must be explained. When the cell is at rest, and the ion channels are closed (except for leakage channels which randomly open), ions are distributed across the + membrane in a very predictable way. The cytosol contains a high concentration of anions, in the form of phosphate ions and negatively charged proteins. Large anions are a component of the inner cell membrane, including specialized phospholipids and proteins associated with the inner leaflet of the membrane (leaflet is a term used for one side of the lipid bilayer membrane). With the ions distributed across the membrane at these concentrations, the difference in charge is measured at -70 mV, the value described as the resting membrane potential. The exact value measured for the resting membrane potential varies between cells, but -70 mV is most commonly used as this value.

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Cost-effectiveness of polymerase chain reaction versus Ziehl-Neelsen smear microscopy for diagnosis of tuberculosis in Kenya buy motilium 10mg line. Therefore buy discount motilium 10mg on-line, young children and especially newborns are at a high life risk when they are ex- posed to a contagious source (Dye 1999) buy motilium 10mg on-line. Since most pediatric cases occur due to a rapid progression of a recent infection with a short incubation period, this implies a high rate of recent transmission in the community. Therefore, the infected and ill children in the community are an indirect, useful parameter for assessing the im- pact of Tuberculosis Control Program activities. Adolescents and older children are important exceptions since their disease closely resembles 526 Tuberculosis in Children that of adults. In these cases, the disease is frequently associated with unfavorable conditions, such as bad nutrition (Correa 1997). Thus, the likelihood of being infected depends on the environment and characteris- tics of the index case. However, the development of active disease also depends on the inherent immunologic status of the host (Alcaiis 2006, Alet 2003). Droplet nuclei containing between one to 10 bacilli and a diameter close to 10 µm are expelled with the cough, suspended in the air and transported by air currents. Normal air currents can keep them airborne for prolonged periods of time and spread them throughout rooms or building. Some of these droplet nuclei, usually larger than 10 µm, are inhaled and anchored in the upper respiratory tract (Wells 1995). The mucus and the ciliary system of the respiratory tract avoid further pro- gression of mycobacteria. The effective infective droplet nucleus is very small; measuring 5 µm or less, it is able to avoid the mucus and ciliary system action and produce the anchorage in bronchioles and respiratory alveoli. The small size of the droplets allows them to remain suspended in the air for prolonged periods of time. Although theoretically a single organism may cause disease, it is generally accepted that about five to 200 inhaled bacilli are necessary for a successful infection. After inhalation, the bacilli are usually installed in the midlung zone, into the distal and subpleural respiratory bronchioles or alveoli. However, these first macrophages are unable to kill mycobacteria and the bacilli continue their replication inside these cells. Logarithmic multiplication of the mycobacteria takes place within the macrophage at the primary infection site. Thereafter, trans- portation of the infected macrophages to the regional lymph nodes occurs leading to the lymphohematogenous dissemination of the mycobacteria to other lymph nodes and organs such as kidneys, epiphyses of long bones, vertebral bodies, jux- 16. Etiology, transmission and pathogenesis 527 taependymal meninges adjacent to the subarachnoid space, and, occasionally, to the apical posterior areas of the lungs. In addition, chemotactic factors released by the macrophages attract circulating monocytes to the infection site, leading to their differentiation into mature macrophages with increased capacity to ingest and kill free bacteria (Correa 1997, Starke 1996, Vallejo 1994). Due to the fact that myco- bacteria are not able to grow under the adverse conditions of the extracellular envi- ronment, most infections are controlled by the host immune system. However, the initial pulmonary infection site, which is denominated “primary complex or Ghon focus” and its adjacent lymph nodes, sometimes reach sufficient size to develop necrosis and calcification demonstrable by radiographs (Feja 2005, Schluger 1994). It is generally associ- ated with close contact with cattle, and is variable from one country to another and even from region to region inside the same country (see Chapter 8). This situation oc- curs when repetitive or constant contact with the infectious source - generally fam- 528 Tuberculosis in Children ily members - takes place. Therefore, when a child is diagnosed, a search should be performed for an adult case with a high bacillary load in the respiratory tract (Alet 1986). On the other hand, older children may become infected from an external source, such as schoolmates, team leaders or young adults outside the home. The presence of extensive pulmonary lesions, such as cavities, is the most impor- tant individual human factor in determining the infectious power, since these le- sions are associated not only with an important concentration of oxygen that allows active bacillary multiplication, but also with a rapid pathway to the external envi- ronment. The amount of bacilli released into the atmosphere under these conditions is enough to produce the transmission from person to person (Correa 1997, Schluger 1994). The degree of pulmonary involvement is another important factor, since the exten- sion of the lesions is related to the bacillary load, the intensity and frequency of coughing, and the number of cavities that may propagate these bacilli. Rarely, non- pulmonary localization of the disease with high infectious power, such as the la- ryngeal form, becomes an infectious source. In this case, simple actions such as talking can cause the elimination of an important amount of mycobacteria (Correa 1997). Socioeconomic factors as well as the overcrowded living places in urban areas increase the risk of infection allowing larger contacts with infected persons. The concentration of bacilli depends on ventilation of the surroundings and expo- sure to ultraviolet light. From a public health point of view, these stages have absolutely different transmission implications and epidemiologic consequences. Household is the most frequent setting for exposure although several places that allow a close con- tact with potentially contagious adults such as school, day care centers and other th environments become occasional exposure places. During the 18 century, the “familial hypothesis” raised by the occurrence of familial clustering, dominated medical thinking. In adults, the dis- tinction between infection and disease becomes less difficult because the latter may 530 Tuberculosis in Children be the result of dormant bacilli acquired during a past infection. In children, the distinction may not be so clear because the disease more often progresses from an initial or primary infection. Asymptomatic presentations are more common among school-age children (80-90 %) than in infants less than one year old (40-50 %) (Correa 1997, Vallejo 1996). Erythema nodosum is a toxic allergic erythema with nodular lesions in the skin or under it, 2 to 3 cm large. These lesions are spontaneously painful and very painful under pressure, and are usually located bilaterally in feet and legs. The erythema nodosum is usually accompanied by pharyngitis, fever and joint inflam- mation and is more frequent in girls over six years. Phlyctenular conjunctivitis is an allergic keratoconjunctivitis characterized by the presence of small vesicles that usually evolve to ulcers and resolve without scars. Primary pulmonary tuberculosis 531 associated to the phlyctenular conjunctivitis are photophobia and an excessive lacrimation (Peroncini 1977). Progression of the primary infectious complex may lead to enlargement of hilar and mediastinal lymph nodes with resultant bronchial collapse. Tubercular me- ningoencephalitis may also result from hematogenous dissemination (Newton 1994, Smith 1992). When the disease is controlled by the host immune system, those bacilli spread by the bloodstream may remain dormant in all areas of the lung or other organs for several months or years. Enlargement of lymph nodes may result in signs suggestive of bronchial obstruction or hemidiaphragmatic paralysis. Obstructive hyperaeration of a lobar segment or a complete lobe is less common in pediatric patients while cavi- ties, bronchiectasis and bullous emphysema are occasionally seen. Even in the presence of extensive pulmonary disease, many older children are asymptomatic at the time of diagnosis. In general, however, children are more likely to present with wheezing, cough, fever, and anorexia as part of the symptoms (Lincoln 1958, Starke 1996, Vallejo 1995). Persistent cough may be indicative of bronchial obstruction, while difficulty in swallowing may result from esophageal compression. Progressive primary pulmonary tuberculosis Progression of the pulmonary parenchymal component leads to enlargement of the caseous area and may lead to pneumonia, atelectasis, and air trapping. This form presents classic signs of pneumonia, including tachypnea, dullness to percussion, nasal flaring, grunting, egophony, decreased breath sounds, and crack- les. Typical history reveals an acute onset of fever, chest pain that increases in intensity on deep inspiration, and shortness of breath. The pain accom- panies the onset of the pleural effusion, but after that the pleural involvement is painless. The signs of pleural effusion include tachypnea, respiratory distress, decreased breath sounds, dullness to percussion, and occasionally, features of mediastinal shift. When the primary infection has not been treated properly, the lesion can reactivate from dormant bacilli in either lymph nodes or parenchymal nodules. In contrast to primary disease, the characteristic feature of reactivation is the parenchymal in- volvement, which usually evolves to cavities or diffuse infiltrates, without signifi- cant radiograph changes in pulmonary adenopathies (Peroncini 1979).

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Rhythm Identification ▪ This rhythm strip is from a 52-year-old man found unresponsive motilium 10 mg mastercard, apneic order 10mg motilium mastercard, and pulseless motilium 10mg sale. Rhythm Identification ▪ These rhythm strips are from a 78-year-old man complaining of shortness of breath. Rhythm Identification ▪ This rhythm strip is from an 86-year-old woman complaining of chest pain that she rates a 4 on a scale of 0 to 10. Rhythm Identification ▪ This rhythm strip is from an 88-year-old woman complaining of hip pain after a fall injury. Rhythm Identification ▪ This rhythm strip is from an 18-year-old man with a gunshot wound to his chest. In mammals, glucose is the preferred fuel source for the brain and the only fuel source for red blood cells. The glycolytic pathway is common to virtually all organisms Both eukaryotes and prokaryotes In eukaryotes, it occurs in the cytosol 7 1. Glyceraldehyde 3-Phosphate Dehydrogenase Energy transformation: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate. Glyceraldehyde 3-Phosphate Dehydrogenase Energy transformation: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate. Glyceraldehyde 3-Phosphate Dehydrogenase The enzyme-bound thioester intermediate reduces the activation energy for the second reaction: 24 1. Phosphoglycerate Mutase The next two reactions convert the remaining phosphate ester into a phosphate having a high phosphoryl transfer potential The first is an isomerization reaction 26 1. Enolase The next two reactions convert the remaining phosphate ester into a phosphate having a high phosphoryl transfer potential The second is a dehydration (lyase) reaction 27 1. Maintaining Redox Balance The solution to this problem lies in what happens to the pyruvate that is produced in glycolysis: Fermentation Pathways 32 1. Maintaining Redox Balance Lactic acid fermentation is use by bacteria and human muscles and produces lactate. Usually due to loss of uridyl transferase activity Symptoms include Failure to thrive infants Enlarged liver and jaundice, sometimes cirrhosis Cataracts Mental retardation 41 2. Control of Glycolysis In metabolic pathways, control is focused on those steps in the pathway that are irreversible. Control of Glycolysis The different levels of control have different response times: Level of Control Response Time Allosteric milleseconds Phosphorylation seconds Transcriptional hours 44 2. Fructose 2,6-bisphosphate A regulated bifunctional enzyme synthesizes and degrades fructose 2,6-bisphosphate: 49 2. The brain has a strong preference for glucose, while the red blood cells have and absolute requirement for glucose. Gluconeogenesis The three kinase reactions are the ones with the greatest positive free energies in the reverse directions 54 3. Gluconeogenesis The hexokinase and phosphofructokinase reactions can be reversed simply with a phosphatase 55 3. Formation of Phosphoenopyruvate The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate. Oxaloacetate Shuttle Oxaloacetate is synthesized in the mitochondria and is shuttled into the cytosol where it is converted into phosphoenolpyruvate 60 3. Regulation of Glycolysis and Gluconeogenesis Reciprocal regulation of glycolysis and gluconeogenesis in the liver 62 4. Evolution of Glycolysis and Gluconeogenesis Glycolysis and Gluconeogenesis are evolutionarily intertwined. Therapy for Anaphylactoid Reactions  Bronchosapsm  Minor-Uticaria, with or  Oxygen without Skin Itching  Mild- albuterol inhaler, 2 puffs  No therapy  Moderate-Epinephrine 0. Patients with prior evidence of an anaphylactoid reaction to contrast media should receive appropriate steroid and antihistamine prophylaxis prior to repeat contrast administration. In patients with prior history of allergic reactions to shellfish or seafood, anaphylactoid prophylaxis for contrast reaction is not beneficial. Patients undergoing cardiac catheterization with contrast media should receive adequate preparatory hydration. In patients with chronic kidney disease (creatinine clearance <60cc/min), the volume of contrast media should be minimized. Patient  Total Air Kerma at the Interventional Reference Point (K , a,r Dose Gy) is the x-ray energy delivered to air 15cm from for patient dose burden Assessment for deterministic skin effects. The Procedure/Patient  As patient size increases…  Image quality poor  Input dose of radiation increases exponentially  Scatter radiation more  As complexity increases. Procedure Related Issues to Minimize Exposure to Patient and Operator  Utilize radiation only when imaging is necessary  Minimize use of cine  Minimize use of steep angles of X-ray beam  Minimize use of magnification modes  Minimize frame rate of fluoroscopy and cine  Keep the image receptor close to the patient  Utilize collimation to the fullest extent possible  Monitor radiation dose in real time to assess patient risk/benefit during the procedure Tube Position and Scatter The scatter profile tilts as the x-ray tube is moved from the posterior to the anterior projection or when the tube is moved toward the cranial or caudal projections. Procedure Related Issues to Specifically Minimize Exposure to Operator  Use and maintain appropriate protective garments  Maximize distance of operator from X-ray source and patient  Keep above-table and below-table shields in optimal position at all times  Keep all body parts out of the field of view at all times Inverse Square Law 2 2 I / I = (d ) / (d ) 1 2 2 1 This relationship shows that doubling the distance from a radiation source will decrease the exposure rate to 1/4 the original. Staff Radiation Protection  Shielding  Lead>90%;Proper care of aprons  Thyroid shielding; <40 yo The Next Armani? Staff Exposure Limits  Whole Body 5 rem (50 mSv)/yr  Eyes 15 rem (150 mSv)/ yr  Pregnant Women 50 mrem (0. Risk Management of Skin Effects in Interventional Procedures  Individualized management by an experienced radiation wound care team should be provided for wounds related to high dose radiation. M alalignment of the teeth such as crowding, abnormal the teeth that results in localized dissolution and destruction spacing, etc. It is the second m ost com m on cause of tooth loss and is found universally, irrespective of age, Saliva5–8 sex, caste, creed or geographic location. N orm ally, 700– be a disease of civilized society, related to lifestyle factors, 800 ml of saliva is secreted per day. Eating fibrous food severe pain, is expensive to treat and leads to loss of precious and chewing vigorously increases salivation, which helps m an-hours. Aetiology • Q uantity:Reduced salivary secretion as found in xerostomia An interplay of three principal factors is responsible for and salivary gland aplasia gives rise to increased caries this m ultifactorial disease. Host factors • Antibacterial factors: Saliva contains enzym es such as lactoperoxidase, lypozym e, lactoferrin and im m uno- Teeth1–4 globulin (Ig)A, which can inhibit plaque bacteria. As teeth get ferment carbohydrate foodstuffs, especially the disaccharide worn (attrition), caries declines. The dental plaque holds the Centre for Dental Education and Research acids produced in close contact with the tooth surfaces All India Institute of M edical Sciences, N ew Delhi 110029 and prevents them from contact with the cleansing action e-m ail: nshah@aiim s. Tooth • Poor contact between the teeth resulting in food • Socioeconomic status • Structure·fluoride content and other trace impaction and caries due to the following • Literacy level elements such as zinc, lead, iron causes • Location·urban, rural • Morphology·deep pits and fissures ·malalignment of the teeth (crowding) • Age • Alignment·crowding ·loss of some teeth and failure to replace them • Sex 2. Microorganisms·dental plaque accumulation • Gingival recession leading to root caries • Dietary habits due to poor oral hygiene • Climatic conditions and soil type 3. Diet • Social and cultural practices • Intake of refined carbohydrates such as • Availability/access to health care facility sucrose, maltose, lactose, glucose, fructose, • Health insurance cooked sticky starch, etc. The role of refined carbohydrates, especially the disac- • Fem ales develop caries m ore often than m ales. The total am ount consum ed as well as the • Availability/access to a health care facility can affect physical form , its oral clearance rate and frequency of utilization of health care services. Indirect causes17,18 Prevention and control of dental caries • Loss of som e natural teeth and failure to replace them 1. System ic use of fluoride: (i) Fluoridation of water, m ilk This leads to increased food impaction between the teeth and salt; (ii) fluoride supplem entation in the form of tablets and form ation of new carious lesions. Com bat the m icrobial plaque by physical and chem ical fluoride content of the water is at an optim um concen- m ethods. Tongue cleaning and the use of indigenous agents such • Urbanization is linked to an increased incidence of caries. Medical interventions Non-medical interventions Other interventions The use of various interdental cleaning aids such as dental floss, interdental brush, water pik, etc. Use of an electronic fluorides • Proper methods of accessible and toothbrush in children and persons with decreased m anual • Use of pit and maintaining oral hygiene affordable dexterity is recom m ended. These should be used on prescription of a restorations and ·antiseptic mouth washes • Include oral health dental surgeon. Increase the intake of fibrous food • Using sugar substitutes such as saccharine, xylitol, to stimulate salivary flow, which is protective against caries. Stim ulate salivary flow with sugar- • M aking toothbrushes and fluoridated toothpaste available free chewing gum. Regular use of fluoridated chewing gum , if chewed between m eals, produces an anti- toothpaste is proven to reduce the incidence of dental caries effect by stim ulating salivary flow.

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