bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gas Exchange in the Respiratory Distress Syndromes
Authors: Albert Richard K. , Jobe Alan 
Published: June 2012

AbstractThis article describes the gas exchange abnormalities occurring in the acute respiratory distress syndrome seen in adults and children and in the respiratory distress syndrome that occurs in neonates. Evidence is presented indicating that the major gas exchange abnormality accounting for the hypoxemia in both conditions is shunt, and that approximately 50% of patients also have lungs regions in which low ventilation‐to‐perfusion ratios contribute to the venous admixture. The various mechanisms by which hypercarbia may develop and by which positive end‐expiratory pressure improves gas exchange are reviewed, as are the effects of vascular tone and airway narrowing. The mechanisms by which surfactant abnormalities occur in the two conditions are described, as are the histological findings that have been associated with shunt and low ventilation‐to‐perfusion. © 2012 American Physiological Society.Compr Physiol2:1585‐1617, 2012.
Genetic Diseases: Congenital Central Hypoventilation, Rett, and Prader‐Willi Syndromes
Authors: Gallego Jorge 
Published: June 2012

AbstractThe present review summarizes current knowledge on three rare genetic disorders of respiratory control, congenital central hypoventilation syndrome (CCHS), Rett syndrome (RTT), and Prader‐Willi syndrome (PWS). CCHS is characterized by lack of ventilatory chemosensitivity caused byPHOX2Bgene abnormalities consisting mainly of alanine expansions. RTT is associated with episodes of tachypneic and irregular breathing intermixed with breathholds and apneas and is caused by mutations in the X‐linkedMECP2gene encoding methyl‐CpG‐binding protein. PWS manifests as sleep‐disordered breathing with apneas and episodes of hypoventilation and is caused by the loss of a group of paternally inherited genes on chromosome 15. CCHS is the most specific disorder of respiratory control, whereas the breathing disorders in RTT and PWS are components of a more general developmental disorder. The main clinical features of these three disorders are reviewed with special emphasis on the associated brain abnormalities. In all three syndromes, disease‐causing genetic defects have been identified, allowing the development of genetically engineered mouse models. New directions for future therapies based on these models or, in some cases, on clinical experience are delineated. Studies of CCHS, RTT, and PWS extend our knowledge of the molecular and cellular aspects of respiratory rhythm generation and suggest possible pharmacological approaches to respiratory control disorders. This knowledge is relevant for the clinical management of many respiratory disorders that are far more prevalent than the rare diseases discussed here. © 2012 American Physiological Society.Compr Physiol2:2255‐2279, 2012.
Control of Breathing in Invertebrate Model Systems
Authors: Bell Harold J. , Syed Naweed I. 
Published: June 2012

AbstractThe invertebrates have adopted a myriad of breathing strategies to facilitate the extraction of adequate quantities of oxygen from their surrounding environments. Their respiratory structures can take a wide variety of forms, including integumentary surfaces, lungs, gills, tracheal systems, and even parallel combinations of these same gas exchange structures. Like their vertebrate counterparts, the invertebrates have evolved elaborate control strategies to regulate their breathing activity. Our goal in this article is to present the reader with a description of what is known regarding the control of breathing in some of the specific invertebrate species that have been used as model systems to study different mechanistic aspects of the control of breathing. We will examine how several species have been used to study fundamental principles of respiratory rhythm generation, central and peripheral chemosensory modulation of breathing, and plasticity in the control of breathing. We will also present the reader with an overview of some of the behavioral and neuronal adaptability that has been extensively documented in these animals. By presenting explicit invertebrate species as model organisms, we will illustrate mechanistic principles that form the neuronal foundation of respiratory control, and moreover appear likely to be conserved across not only invertebrates, but vertebrate species as well. © 2012 American Physiological Society.Compr Physiol2:1745‐1766, 2012.
Effects of Gas Exchange on Acid‐Base Balance
Authors: Lindinger Michael I. , Heigenhauser George J.F. 
Published: June 2012

AbstractThis paper describes the interactions between ventilation and acid‐base balance under a variety of conditions including rest, exercise, altitude, pregnancy, and various muscle, respiratory, cardiac, and renal pathologies. We introduce the physicochemical approach to assessing acid‐base status and demonstrate how this approach can be used to quantify the origins of acid‐base disorders using examples from the literature. The relationships between chemoreceptor and metaboreceptor control of ventilation and acid‐base balance summarized here for adults, youth, and in various pathological conditions. There is a dynamic interplay between disturbances in acid‐base balance, that is, exercise, that affect ventilation as well as imposed or pathological disturbances of ventilation that affect acid‐base balance. Interactions between ventilation and acid‐base balance are highlighted for moderate‐ to high‐intensity exercise, altitude, induced acidosis and alkalosis, pregnancy, obesity, and some pathological conditions. In many situations, complete acid‐base data are lacking, indicating a need for further research aimed at elucidating mechanistic bases for relationships between alterations in acid‐base state and the ventilatory responses. © 2012 American Physiological Society.Compr Physiol2:2203‐2254, 2012.
Pathological Consequences of Intermittent Hypoxia in the Central Nervous System
Authors: Zhang Shelley X.L. , Wang Yang , Gozal David 
Published: June 2012

AbstractIntermittent hypoxia (IH) is a frequent occurrence in clinical settings. In the last decades, evidence has emerged implicating the gas exchange alterations and sleep disruption associated with those disorders in the high prevalence of cognitive and behavioral deficits afflicting these patients. In an effort to better characterize the role of IH, and to identify potential mechanisms of IH‐induced central nervous system (CNS) dysfunction, a large number of rodent models have been recently developed. The cumulative evidence confirms that IH indeed induces a heterotopic pattern of injury in the brain, particularly affecting cortical, subcortical, and hippocampal regions, ultimately leading to neuronal apoptosis and activation of microglia. These IH‐induced deleterious processes exhibit substantial variability across the lifespan, are under substantial modulatory influences of diet, physical or intellectual activity, and genetic factors, and preferentially recruit oxidative stress and inflammatory pathways. © 2012 American Physiological Society.Compr Physiol2:1767‐1777, 2012.
Biophysics of Glomerular Filtration
Authors: Thomson Scott C. , Blantz Roland C. 
Published: June 2012

AbstractEnlightened by William Bowman's depiction of the anatomy in 1842, Carl Ludwig immediately proposed glomerular filtration as a physical process. Nuances of this process have come to light in a rather orderly progression over the past 150 years with essential contributions from clearance methods, renal micropuncture, physical theories of nonequilibrium thermodynamics and electrical double layers, morphometry, and mathematics. Herein, we describe that progression of knowledge. Ongoing work pertains to the nature, location, and efficiency of the barrier to protein sieving, induction of endothelial fenestrae by growth factors from the podocyte, and potential resistance faced by filtrate exiting the subpodocyte space. Published 2012.Compr Physiol2:1671‐1699, 2012.
Life Under Water: Physiological Adaptations to Diving and Living at Sea
Authors: Castellini Michael 
Published: June 2012

AbstractThis review covers the field of diving physiology by following a chronological approach and focusing heavily on marine mammals. Because the study of modern diving physiology can be traced almost entirely to the work of Laurence Irving in the 1930s, this particular field of physiology is different than most in that it did not derive from multiple laboratories working at many locations or on different aspects of a similar problem. Because most of the physiology principles still used today were first formulated by Irving, it is important to the study of this field that the sequence of thought is examined as a progression of theory. The review covers the field in roughly decadal blocks and traces ideas as they were first suggested, tested, modified and in some cases, abandoned. Because diving physiology has also been extremely dependent on new technologies used in the development of diving recorders, a chronological approach fits well with advances in electronics and mechanical innovation. There are many species that dive underwater as part of their natural behavior, but it is mainly the marine mammals (seals, sea lions, and whales) that demonstrate both long duration and dives to great depth. There have been many studies on other diving species including birds, snakes, small aquatic mammals, and humans. This work examines these other diving species as appropriate and a listing of reviews and relevant literature on these groups is included at the end. © 2012 American Physiological Society.Compr Physiol2:1889‐1919, 2012.
Factors Limiting Exercise Tolerance in Chronic Lung Diseases
Authors: Vogiatzis Ioannis , Zakynthinos Spyros 
Published: June 2012

AbstractThe major limitation to exercise performance in patients with chronic lung diseases is an issue of great importance since identifying the factors that prevent these patients from carrying out activities of daily living provides an important perspective for the choice of the appropriate therapeutic strategy. The factors that limit exercise capacity may be different in patients with different disease entities (i.e., chronic obstructive, restrictive or pulmonary vascular lung disease) or disease severity and ultimately depend on the degree of malfunction or miss coordination between the different physiological systems (i.e., respiratory, cardiovascular and peripheral muscles). This review focuses on patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and pulmonary vascular disease (PVD). ILD and PVD are included because there is sufficient experimental evidence for the factors that limit exercise capacity and because these disorders are representative of restrictive and pulmonary vascular disorders, respectively. A great deal of emphasis is given, however, to causes of exercise intolerance in COPD mainly because of the plethora of research findings that have been published in this area and also because exercise intolerance in COPD has been used as a model for understanding the interactions of different pathophysiologic mechanisms in exercise limitation. As exercise intolerance in COPD is recognized as being multifactorial, the impacts of the following factors on patients’ exercise capacity are explored from an integrative physiological perspective: (i) imbalance between the ventilatory capacity and requirement; (ii) imbalance between energy demands and supplies to working respiratory and peripheral muscles; and (iii) peripheral muscle intrinsic dysfunction/weakness. © 2012 American Physiological Society.Compr Physiol2:1779‐1817, 2012.
Computational Models and Emergent Properties of Respiratory Neural Networks
Authors: Lindsey Bruce G. , Rybak Ilya A. , Smith Jeffrey C. 
Published: June 2012

AbstractComputational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data‐driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre‐Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state‐dependent expression of different neural pattern‐generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered. Published 2012.Compr Physiol2:1619‐1670, 2012.
Structure and Function of the Thin Limbs of the Loop of Henle
Authors: Pannabecker Thomas L. 
Published: June 2012

AbstractThe thin limbs of the loop of Henle, which comprise the intermediate segment, connect the proximal tubule to the distal tubule and lie entirely within the renal medulla. The descending thin limb consists of at least two or three morphologically and functionally distinct subsegments and participates in transepithelial transport of NaCl, urea, and water. Only one functionally distinct segment is recognized for the ascending thin limb, which carries out transepithelial transport of NaCl and urea in the reabsorptive and/or secretory directions. Membrane transporters involved with passive transcellular Cl, urea, and water fluxes have been characterized for thin limbs; however, these pathways do not account for all transepithelial fluid and solute fluxes that have been measuredin vivo. The paracellular pathway has been proposed to play an important role in transepithelial Na and urea fluxes in defined thin‐limb subsegments. As the transport pathways become clearer, the overall function of the thin limbs is becoming better understood. Primary and secondary signaling pathways and protein‐protein interactions are increasingly recognized as important modulators of thin‐limb cell function and cell metabolism. These functions must be investigated under diverse extracellular conditions, particularly for those cells of the deep inner medulla that function in an environment of wide variation in hyperosmolality. Transgenic mouse models of several key water and solute transport proteins have provided significant insights into thin‐limb function. An understanding of the overall architecture of the medulla, including juxtapositions of thin limbs with collecting ducts, thick ascending limbs, and vasa recta, is essential for understanding the role of the kidney in maintaining Na and water homeostasis, and for understanding the urine concentrating mechanism. © 2012 American Physiological Society.Compr Physiol2:2063‐2086, 2012.
Exercise Limitation Following Transplantation
Authors: Williams Trevor J. , McKenna Michael J. 
Published: June 2012

AbstractOrgan transplantation is one of the medical miracles or the 20th century. It has the capacity to substantially improve exercise performance and quality of life in patients who are severely limited with chronic organ failure. We focus on the most commonly performed solid‐organ transplants and describe peak exercise performance following recovery from transplantation. Across all of the common transplants, evaluated significant reduction ino2peakis seen (typically renal and liver 65%‐80% with heart and/or lung 50%‐60% of predicted). Those with the lowesto2peakpretransplant have the lowesto2peakposttransplant. Overall very few patients have ao2peakin the normal range. Investigation of the cause of the reduction ofo2peakhas identified many factors pre‐ and posttransplant that may contribute. These include organ‐specific factors in the otherwise well‐functioning allograft (e.g., chronotropic incompetence in heart transplantation) as well as allograft dysfunction itself (e.g., chronic lung allograft dysfunction). However, looking across all transplants, a pattern emerges. A low muscle mass with qualitative change in large exercising skeletal muscle groups is seen pretransplant. Many factor posttransplant aggravate these changes or prevent them recovering, especially calcineurin antagonist drugs which are key immunosuppressing agents. This results in the reduction ofo2peakdespite restoration of near normal function of the initially failing organ system. As such organ transplantation has provided an experiment of nature that has focused our attention on an important confounder of chronic organ failure‐skeletal muscle dysfunction. © 2012 American Physiological Society.Compr Physiol2:1937‐1979, 2012.
Cell Biology and Physiology of CLC Chloride Channels and Transporters
Authors: Stauber Tobias , Weinert Stefanie , Jentsch Thomas J. 
Published: June 2012

AbstractProteins of the CLC gene family assemble to homo‐ or sometimes heterodimers and either function as Cl–channels or as Cl–/H+‐exchangers. CLC proteins are present in all phyla. Detailed structural information is available from crystal structures of bacterial and algal CLCs. Mammals express nine CLC genes, four of which encode Cl–channels and five 2Cl–/H+‐exchangers. Two accessory β‐subunits are known: (1) barttin and (2) Ostm1. ClC‐Ka and ClC‐Kb Cl–channels need barttin, whereas Ostm1 is required for the function of the lysosomal ClC‐7 2Cl–/H+‐exchanger. ClC‐1, ‐2, ‐Ka and ‐Kb Cl–channels reside in the plasma membrane and function in the control of electrical excitability of muscles or neurons, in extra‐ and intracellular ion homeostasis, and in transepithelial transport. The mainly endosomal/lysosomal Cl–/H+‐exchangers ClC‐3 to ClC‐7 may facilitate vesicular acidification by shunting currents of proton pumps and increase vesicular Cl–concentration. ClC‐3 is also present on synaptic vesicles, whereas ClC‐4 and ‐5 can reach the plasma membrane to some extent. ClC‐7/Ostm1 is coinserted with the vesicular H+‐ATPase into the acid‐secreting ruffled border membrane of osteoclasts. Mice or humans lacking ClC‐7 or Ostm1 display osteopetrosis and lysosomal storage disease. Disruption of the endosomal ClC‐5 Cl–/H+‐exchanger leads to proteinuria and Dent's disease. Mouse models in which ClC‐5 or ClC‐7 is converted to uncoupled Cl–conductors suggest an important role of vesicular Cl–accumulation in these pathologies. The important functions of CLC Cl–channels were also revealed by human diseases and mouse models, with phenotypes including myotonia, renal loss of salt and water, deafness, blindness, leukodystrophy, and male infertility. © 2012 American Physiological Society.Compr Physiol2:1701‐1744, 2012.
Airway‐Parenchymal Interdependence
Authors: Paré Peter D. , Mitzner Wayne 
Published: June 2012

AbstractIn this article, we discuss the interaction of the lung parenchyma and the airways as well as the physiological and pathophysiological significance of this interaction. These two components of the respiratory organ can be thought of as two independent elastic structures but in fact the mechanical properties of one influence the behavior of the other. Traditionally, the interaction has focused on the effects of the lung on the airways but there is good evidence that the opposite is also true, that is, that the mechanical properties of the airways influence the elastic properties of the parenchyma. The interplay between components of the respiratory system including the airways, parenchyma, and vasculature is often referred to as “interdependence.” This interdependence transmits the elastic recoil of the lung to create an effective pressure that dilates the airways as transpulmonary pressure and lung volume increase. By using a continuum mechanics analysis of the lung parenchyma, it is possible to predict the effective pressure between the airways and parenchyma, and these predictions can be empirically evaluated. Normal airway caliber is maintained by this pressure in the adventitial interstitium of the airway, and it attenuates the ability of airway smooth muscle to narrow airways. Interdependence has physiological and pathophysiological significance. Weakening of the forces of interdependence contributes to airway dysfunction and gas exchange impairment in acute and chronic airway diseases including asthma and emphysema. © 2012 American Physiological Society.Compr Physiol2:1921‐1935, 2012.
Claudins and Other Tight Junction Proteins
Authors: Günzel Dorothee , Fromm Michael 
Published: June 2012

AbstractEpithelial transport relies on the proper function and regulation of the tight junction (TJ), other‐wise uncontrolled paracellular leakage of solutes and water would occur. They also act as a fence against mixing of membrane proteins of the apical and basolateral side. The proteins determining paracellular transport consist of four transmembrane regions, intracellular N and C terminals, one intracellular and two extracellular loops (ECLs). The ECLs interact laterally and with counterparts of the neighboring cell and by this achieve a general sealing function. Two TJ protein families can be distinguished, claudins, comprising 27 members in mammals, and TJ‐associated MARVEL proteins (TAMP), comprising occludin, tricellulin, and MarvelD3. They are linked to a multitude of TJ‐associated regulatory and scaffolding proteins. The major TJ proteins are classified according to the physiological role they play in enabling or preventing paracellular transport. Many TJ proteins have sealing functions (claudins 1, 3, 5, 11, 14, 19, and tricellulin). In contrast, a significant number of claudins form channels across TJs which feature selectivity for cations (claudins 2, 10b, and 15), anions (claudin‐10a and ‐17), or are permeable to water (claudin‐2). For several TJ proteins, function is yet unclear as their effects on epithelial barriers are inconsistent (claudins 4, 7, 8, 16, and occludin). TJs undergo physiological and pathophysiological regulation by altering protein composition or abundance. Major pathophysiological conditions which involve changes in TJ protein composition are (1) effects of pathogens binding to TJ proteins, (2) altered TJ protein composition during inflammation and infection, and (3) altered TJ protein expression in cancers. © 2012 American Physiological Society.Compr Physiol2:1819‐1852, 2012.