Pathophysiology of Disease-An Introduction to Clinical Medicine, 8e (Nov 26, 2018)_(1260026507)_(McGraw-Hill)

A full-color case-based review of the essentials of pathophysiology covering all major organs and systems More than 130 case studies with Q&A A Doody’s Core Title for 2020! The goal of this trusted text is to introduce you to clinical medicine by reviewing the pathophysiologic basis of 132 diseases (and associated signs and symptoms) commonly encountered in medical practice. The authors, all experts in their respective fields, have provided a concise review of relevant normal structure and function of each body system, followed by a description of the pathophysiologic mechanisms that underlie several common diseases related to that system. The accessible presentation features high-quality full-color illustrations, and numerous tables and diagrams. Each chapter of Pathophysiology of Disease concludes with a collection of case studies and questions designed to test your understanding of the pathophysiology of each clinical entity discussed. These case studies allow you to apply your knowledge to specific clinical situations. Detailed answers to each case study question are provided at the end of the book. This unique interweaving of physiological and pathological concepts will put you on the path toward thinking about signs and symptoms in terms of their pathophysiologic basis, giving you an understanding of the "why" behind illness and treatment. HERE ARE SOME OF THE MANY UPDATES AND ADDITIONS: •Twelve additional case studies, bringing the total to 132, one for each of the clinical entities discussed in the book’s 24 chapters •More than 2/3 of the chapters are enhanced and refreshed by the input of new contributors •Totally revised chapter on neoplasia •New chapter sections on urticaria, spinocerebellar ataxia, idiopathic pulmonary fibrosis, and spondyloarthropathies •New tables summarizing adverse prognostic signs in acute pancreatitis, genetic syndromes associated with pancreatic cancer, and causes of end-stage renal disease •New diagnosis and etiologic classification of diabetes mellitus, and review of mechanisms of newest pharmacologic agents for its treatment •Updates on fine-needle aspiration biopsy of thyroid nodules, and thyroid disorders in pregnancy •Updated references throughout the book Cover Title Page TERMS OF USE Copyright Page Contents Authors Preface 1. Introduction 2. Genetic Disease 3. Disorders of the Immune System 4. Infectious Diseases 5. Neoplasia 6. Blood Disorders NORMAL STRUCTURE & FUNCTION FORMED ELEMENTS OF BLOOD Anatomy FIGURE 6–1 Hematopoiesis: development of the formed elements of blood from bone marrow stemcells. Cells below the horizontal line are found in normal peripheral blood. The principal cytokines thatstimulate each cell lineage to differentiate are shown. (CSF, colony-stimulating factor; EPO, erythropoietin;G, granulocyte; IL, interleukin; M, macrophage; SCF, stem cell factor; TPO, thrombopoietin) 7. Nervous System Disorders 8. Diseases of the Skin 9. Pulmonary Disease CHECKPOINT NORMAL STRUCTURE & FUNCTION OF THELUNGS ANATOMY TABLE 9–1 Components of a normal human lung. Airway & Epithelial Anatomy FIGURE 9–1 Subdivision of conducting airways and terminal respiratory units. This schematicillustration demonstrates the subdivisions of both the conducting airways and the respiratory airways.Successive branching produces increasing generations of airways, beginning with the trachea. Note thatgas-exchanging segments of the lung are encountered only after extensive branching, with a concomitantdecrease in airway caliber and an increase in total cross-sectional area FIGURE 9–2 Location of the principal site of airflow resistance. The second- through fifthgenerationairways include the segmental bronchi and larger bronchioles. They present the greatestresistance to airflow in normal individuals. The smaller airways contribute relatively little despite theirsmaller caliber because of the enormous number arranged in parallel. Compare with Figure 9–3. FIGURE 9–3 Airway generation and total airway cross-sectional area. Note the extremely rapidincrease in total cross-sectional area in the respiratory zone (compare with Figure 9–1) and the fall inresistance as a consequence of the increase in cross-sectional area (compare with Figure 9–2). As a result,the forward velocity of gas during inspiration becomes very low at the level of the respiratory bronchioles,and gas diffusion becomes the chief mode of ventilation. FIGURE 9–4 Airway, vascular, and lymphatic anatomy of the lung. This schematic diagramdemonstrates the general anatomic relationships of the airways and terminal respiratory units with thevascular and lymphatic systems of the lung. Important points are as follows: (1) The pulmonary arterialsystem runs adjacent to the bronchial tree, while the draining pulmonary veins are found distant from theairways; (2) the bronchial wall blood supply is provided by bronchial arteries, branches of systemic arterialorigin; (3) lymphatics are found adjacent to both the arterial and venous systems and are very abundant inthe lung; and (4) lymphatics are found as far distally as the terminal respiratory bronchioles, but they do notpenetrate to the alveolar wall. (A, alveolus; AD, alveolar duct; RB, respiratory bronchiole; TB, terminalbronchiole.) Vascular & Lymphatic Anatomy Pulmonary Nervous System Immune Structure & Function TABLE 9–2 Lung defenses. LUNG VOLUMES, CAPACITIES & THENORMAL SPIROGRAM CHECKPOINT PHYSIOLOGY Static Properties: Compliance & Elastic Recoil FIGURE 9–5 Interaction of the pressure–volume properties of the lungs and the chest wall. Restinglung volume (FRC) represents the equilibrium point at which the elastic recoil of the lung (tendency tocollapse inward) and the chest wall (tendency to spring outward) are exactly balanced. Other lung volumescan also be defined by reference to this diagram. Total lung capacity (TLC) is the point at which theinspiratory muscles cannot generate sufficient force to overcome the elastic recoil of the lungs and chestwall. Residual volume (RV) is the point at which the expiratory muscles cannot generate sufficient force toovercome the elastic recoil of the chest wall. Compliance is calculated by taking the slope of thesepressure–volume relationships at a specific volume. Note that the compliance of the lungs is greater at lowlung volumes but falls considerably above two-thirds of vital capacity. FIGURE 9–6 The effect of surface forces on lung compliance: a simple experiment demonstratingthe effect of surface tension at the air–liquid interface of excised cat lungs. When inflated with saline, thereare no surface forces to overcome, and the lungs are both more compliant and show no difference(hysteresis) between the inflation and deflation curves. When inflated with air, the pressure required todistend the lung is greater at every volume. The difference between the two curves represents thecontribution of surface forces. There is also a pronounced hysteresis to lungs inflated with air that reflectssurfactant recruited into the alveolar liquid during inflation (upward arrow), where it further reduces surfaceforces during deflation (downward arrow). FIGURE 9–7 The importance of surface tension. If two connected alveoli have the same surfacetension, then the smaller the radius, the greater the pressure tending to collapse the sphere. This could leadto alveolar instability, with smaller units emptying into larger ones. Alveoli typically do not have the samesurface tension, however, because surface forces vary according to surface area as a result of the presence ofsurfactant: The relative concentration of surfactant in the surface layer of the sphere increases as the radiusof the sphere falls, augmenting the effect of surfactant at low lung volumes. This tends to counterbalancethe increase in pressure needed to keep alveoli open at diminished lung volume and adds stability to thealveoli, which might otherwise tend to collapse into one another. Surfactant thus protects against theregional collapse of lung units, a condition known as atelectasis, in addition to its other functions. (r, radiusof alveolus; P, gas pressure; T, surface tension.) FIGURE 9–8 Static expiratory pressure–volume curves in normal subjects and patients withemphysema and pulmonary fibrosis. The underlying physiologic abnormality in emphysema is a dramaticincrease in lung compliance. Such patients tend to breathe at very high lung volumes. Patients withpulmonary fibrosis have very noncompliant lungs and breathe at low lung volumes. Dynamic Properties: Flow & Resistance FIGURE 9–9 The concept of the equal pressure point. For air to flow through a tube, there must be apressure difference between the two ends. In the case of forced expiration with an open glottis, this drivingpressure is the difference between alveolar pressure (the sum of pleural pressure and lung elastic recoilpressure) and atmospheric pressure (assumed to be zero). Frictional resistance causes a fall in this drivingpressure along the length of the conducting airways. At some point, the driving pressure may equal thesurrounding peribronchial pressure; in this event, the net transmural pressure is zero. The Work of Breathing FIGURE 9–10 Minimizing the work of breathing. These diagrams divide the total work of breathingat the same minute ventilation into elastic and resistive components. In disease states that increase elasticforces (eg, pulmonary fibrosis), total work is minimized by rapid, shallow breathing; with increased airflowresistance (eg, chronic bronchitis), total work is minimized by slow, deep breathing. Oxygen Transport Dissolvedoxygen is a linear function of oxygen bound to hemoglobin is the product of three terms: oxygen content and tissue oxygen delivery maybe low despite 100% SO2 if FIGURE 9–11 Oxygen–hemoglobin dissociation curve. pH 7.40, temperature 38°C. Distribution of Ventilation & Perfusion FIGURE 9–12 Distribution of ventilation at different lung volumes. The effect of gravity and theweight of the lung cause pleural pressure to become more negative toward the apex of the lung. The effectof this change in pressure is to increase the expansion of apical alveoli. A: Total lung capacity. At high lungvolumes, the compliance curve of the lung is flat; alveoli are almost equally expanded because pressuredifferences cause small changes in lung volume. B: Functional residual capacity. During quiet breathing,the lower lobes are on the steep part of the pressure–volume curve. This increased compliance at lowervolumes is why ventilation at FRC is preferentially distributed to the lower lobes. C: Residual volume. FIGURE 9–13 Effect of changing hydrostatic pressure on the distribution of pulmonary blood flow.Capillary blood flow in different regions of the lung is governed by three pressures: pulmonary arterialpressure, pulmonary venous pressure, and alveolar pressure. Pulmonary arterial pressure must be greaterthan pulmonary venous pressure to maintain forward perfusion; there are, therefore, three potentialarrangements of these variables. Zone 1: Palv > Part > Pven. There is no capillary perfusion in areas wherealveolar pressure is greater than the capillary perfusion pressure. Because alveolar pressure is normallyzero, this occurs only where mean pulmonary arterial pressure is less than the vertical distance from thepulmonary artery. Zone 2: Part > Palv > Pven. Pulmonary arterial pressure exceeds alveolar pressure, butalveolar pressure exceeds pulmonary venous pressure. The driving pressure along the capillary is dissipatedby resistance to flow until the transmural pressure is negative and compression occurs. This zone ofcollapse then regulates flow, which is intermittent and dependent on fluctuating pulmonary venouspressures. Zone 3: Part > Pven > Palv. Matching of Ventilation to Perfusion FIGURE 9–14 Changing distribution of ventilation and perfusion down the upright lung. The twostraight lines reflect the progressive increases in ventilation and perfusion. The slope is steeper forperfusion. The ratio of ventilation to perfusion is, therefore, lowest at the base and highest at the apex. FIGURE 9–15 Four models of the relationship of ventilation to perfusion. In this schematicrepresentation, circles represent respiratory units and tubes depict conducting airways. The colored channelsrepresent pulmonary blood flow, which enters the capillary bed as mixed venous blood (blue) and leaves itas arterialized blood (red). Blood is depicted as purple in situations with insufficient oxygenation. Largearrows show the distribution of inspired gas; small arrows show the diffusion of O2 and CO2. In the idealcase (top left panel), the PaO2 and PaCO2 leaving respiratory units A and B are identical. A shunt (topright panel) is a low Eqn04Fig.jpg area where ventilation is absent and the ratio goes to zero, reducing thearterial PO2. If participating gas-exchanging regions of the lung are ventilated but not perfused, theseregions also fail to function in gas exchange; referred to as alveolar dead space (bottom left panel), theyreduce the overall efficiency of ventilation and CO2 removal (wasted ventilation). However, one responseto an increasing wasted ventilation is to increase total minute ventilation (which includes ventilation toperfused alveolar units), thereby maintaining a nearly constant PaCO2 and normal PaO2, a so-calledcompensated state (bottom right panel). FIGURE 9–16 Ventilation/perfusion mismatching. The top panel shows a respiratory unit where onone side (B), ventilation has been reduced but perfusion is maintained. This defines an area of lowEqn04FigB.jpg ratio. The physiologic effect of low Eqn04Fig.jpg areas appears similar to the effect ofshunts: hypoxemia without hypercapnia. But since a low Eqn04Fig.jpg area does come in contact withinspired air, the fall in PaO2 can be reversed with increased inhaled FiO2. The bottom panel shows arespiratory unit where on one side (B), blood flow has been decreased but ventilation is maintained. Thisdefines an area of high Eqn04FigB.jpg ratio. The effect on lung function can be understood by dividingthe unit into an area with a normal Eqn04Fig.jpg ratio (A) and an area of dead space or wasted ventilation(B′). The physiologic effect of high Eqn04Fig.jpg ratios is to increase PCO2, typically leading to increasedrespiration to return PaCO2 to normal. (Blue, deoxygenated; red, oxygenated.) 10. Cardiovascular Disorders: Heart Disease 11. Cardiovascular Disorders: Vascular Disease 12. Disorders of the Adrenal Medulla 13. Gastrointestinal Disease 14. Liver Disease 15. Disorders of the Exocrine Pancreas 16. Renal Disease 17. Disorders of the Parathyroids & Calcium and Phosphorus Metabolism 18. Disorders of the Endocrine Pancreas 19. Disorders of the Hypothalamus & Pituitary Gland 20. Thyroid Disease 21. Disorders of the Adrenal Cortex 22. Disorders of the Female Reproductive Tract 23. Disorders of the Male Reproductive Tract 24. Inf lammatory Rheumatic Diseases 25. Case Study Answers Index "The goal of Pathophysiology of Disease: An Introduction to Clinical Medicine is to introduce students to clinical medicine by reviewing the pathophysiologic basis of the symptoms and signs of various common diseases. The book has proved useful as a text for both Pathophysiology and Introduction to Clinical Medicine courses in medical schools, and it has been popular in similar courses in nursing schools, physician assistants' training programs, and other allied health programs. It is valuable to students early in their medical school years by highlighting the clinical relevance of their basic science courses, and in preparation for their USMLE Step 1 examinations. The book is also helpful to students engaged in their internal medicine and surgery clerkships, and to house officers as an up-to-date summary of relevant physiology and a source of key references. Practitioners (both general internists and specialists who provide generalist care) will find it beneficial as a refresher text, designed to update their knowledge of the mechanisms underlying 132 commonly encountered diseases and disorders. Nurses, nurse-practitioners, physician assistants, and other allied health practitioners have found that its concise format and broad scope facilitate their understanding of these basic disease entities"--Publisher's description