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Outcome measures may include mortality spasms baby generic cilostazol 50mg mastercard, morbidity, readmission, and quality of life. First, process measures typically focus on narrow aspects of care; the number of process measures that can be feasibly measured is finite. Second, due to eligibility criteria, process measures may only apply to a small segment of the population, yet there remains the need to fully assess the overall quality of the health system. Finally, the existing or typical process measures may have a limited relationship to the most meaningful outcomes that matter most to patients. Accurately measuring outcomes in a manner that is fair across health systems for performance profiling is challenging due to measured and unmeasured confounding factors such as patient case mix. Making conclusions on quality due to outcome measurements requires large sample sizes, as well as rigorous adjustment methods for case mix and other factors. This figure displays the cycle of quality and the consequent relationship between early translational steps, clinical trials, clinical practice guidelines, performance measures, outcomes, and discovery science. At the health system level, case mix may still be a factor, but it is more easily addressable due to a larger sample size and analytic methods that provide greater ability to conservatively draw comparisons between health systems, particularly when considering outliers. Selecting the duration of exposure for an outcome can also be difficult and depends on the overall goal. Although 30 days may seem a reasonable amount of time to hold a hospital accountable, there is increasing pressure for health systems to be held accountable for outcomes up to 1 year. The more time that passes after a hospital admission, the more actionable factors become difficult to define. Long-term outcomes more than 1 year post hospital admission are likely affected by care during the index hospitalization, outpatient care, and potentially care outside of the index hospital at other institutions, including other hospitals and skilled nursing facilities. Notably, measuring outcomes is generally an insufficient means of improving quality, as efforts often have to be isolated into discrete processes or segments of care such as admission, discharge, and transitional care. Another challenge with measuring outcomes is that organizations using continuous quality improvement techniques need to assess performance measures at relatively frequent intervals because some outcome measures may be too small, occurring over short periods of time or varying considerably (similar to day-to-day changes in the stock market). Receiving reliable outcome data in a timely fashion may also be a challenge, especially for health systems that are not integrated or have patient care spread across disparate organizations. For many, quality needs to be summarized across different domains into a composite measure. The most publicized example of a composite measure that includes structural, process, and outcome measures is the annual U. News & World Report Annual Index of Hospital Quality, yet whether this report reflects "true" quality is of considerable debate. The cycle of quality is a model that has been built on the traditional quality framework that was first proposed by Donabedian. Key components for a cycle of quality include the roles of the health care system and health information technology accompanied by a learning environment. Our health system is comprised of a variety of different systems responsible for care with and without direct links to payment. Even within a single health care system, integration is challenging, as there are barriers with regard to information exchange for the most basic functions between inpatient and outpatient care, which leads to waste, duplication, and inevitable, higher costs. This fragmentation of information has highlighted the need for more accountable care organizations. Patients navigating these systems-particularly those who have frequent comorbidities-present enormous difficulties in ensuring that the right care is delivered at the right time. With such a diffuse system, consisting of so many different components in action, it is difficult to discern who is actually responsible for quality. Heart failure care uses a variety of health care system components, thereby serving as a prime example of policy development to align incentives under an accountable care organization. For example, a bundled payment across the inpatient to outpatient care environment is an incentive intended to force individual components to become more integrated and efficient. Whether or not this emphasis on improved health system accountability actually leads to higher quality of care remains to be seen, especially if cost reduction is a key component. With the requirement that health systems use electronic health records, health information technology 46 becomes a platform to measure, evaluate, and act on key processes of care. More important, health information technology may allow for the development of realtime tools, such as integrated risk assessment models for outcome measures. Users may "click" through reminders because of time constraints or simply the sheer number of reminders that are generated. In the early development of electronic health records, the Veterans Administration demonstrated improved quality through a variety of tools such as computerized order entry. Furthermore, many hospitals with higher functioning systems do not use them to their fullest capability. HealthInformationTechnology Data drive the decisions and actions for improving quality of care. In order to be as close to real time as possible, health information technology and its associated analytics become central to driving quality improvement. As described previously, process measures require data collection to define an eligible population, as well as those who receive a given care process. In 2002, the Joint Commission began providing quarterly feedback to sites on specific quality metrics and allowed sites to compare individual performance to national rates. There was no association with improved outcomes for the other individual measures. There is also a growing interest in reporting the impact of quality interventions on hospitalization rates. Nonetheless, mortality and readmission rates may not be the best measures to evaluate quality of care, as outcome measurements do not provide information on the modifiable steps in the process of care. A sports analogy would be a baseball team that is trying to improve performance, but only focuses on wins and losses without considering the individual components of the game, such as team batting average, pitching performance, and errors on the field. Additionally, focusing only on mortality and hospitalization rates may under-recognize patient-centered outcomes47 and values in health care. While using mortality as a primary outcome is both necessary and scientifically appropriate, it often compromises our understanding of the impact of cardiovascular care on patient-reported outcomes. Unfortunately, the United States is currently lacking the research platform that would enable us to better understand these differences and address treatment disparities. Disease-based registries are typically voluntary, so limited information is available on patients treated at hospitals not participating in these registries, as well as patients without Medicare insurance. Table 46-5 describes different care goals and the quality improvement tools that are often available. In programs focusing on quality of care, there has been remarkable success in improving quality of care over time. In addition to high-quality evidence from clinical trials, disease-specific registries have afforded the opportunity to examine the real-world effectiveness of therapies outside of trial settings. For patients not included in trials, this is an important step in integrating quality in the development cycle. Through clinical decision support tools, patients receive more consistent delivery of care and also identify opportunities for standardizing care. Due to the attention toward more integrated or accountable care, health systems are developing new care models. The hallmarks of these new delivery systems can be traced to disease management programs, which are multidisciplinary systems of coordinated care (see also Chapter 44). The programs are effective in promoting self-care and recognition of early signs or systems. As health systems develop strategies for preventing readmission, features of disease management programs are being harnessed in different models of care. Specifically, creating same-day access clinics to allow patients access to therapy without having to go to the emergency department is being done more often in the United States. These new models also leverage multidisciplinary systems to provide coordinated care through dietitians, nurse educators, pharmacists, and other health care providers. These new models will need to be formally evaluated as prior studies have found that depending on the size, design, and intensity of the program, outcomes improvement may vary significantly. As many as 68,000 deaths could be delayed or prevented annually if all six guideline class I evidence-based therapies were used optimally. In some cases, randomized trials should be considered to evaluate the positive or negative implications for policies designed to improve quality, particularly when there are potential financial rewards or penalties.
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Alternatively muscle relaxant long term use purchase 100 mg cilostazol otc, discordant results may be explained by the fact that patients are treated with pharmacologic agents that counteract some of the pathologic Ca2+ regulatory alterations. Importantly, these abnormalities were shown to be independent of blood flow,6 muscle atrophy,9 and fiber type adaptations,5 suggesting an intrinsic deficit in oxidative metabolism. Collectively, these alterations lead to more rapid muscle fatigue during repetitive muscular activity, as indicated by a more rapid reduction in force production (bottom force tracings). Such a reduction in skeletal muscle oxidative capacity would contribute to decreased tissue oxygen utilization and, in turn, reduced whole body peak oxygen consumption. This conclusion should be tempered by the fact that studies have shown defects in oxidative metabolism in forearm muscles, which should not be impacted by muscle disuse,6 arguing for some contribution from the disease. However, from the preceding discussion, it should be apparent that any 249 mitochondrial structural abnormalities that might be present have minimal effects on overall mitochondrial function when the effects of physical inactivity are taken into account. Another consideration that should be factored into this discussion is the effect of medications. Indeed, Drexler and colleagues7 noted that mitochondrial loss could be largely corrected in patients with treatment that led to sufficient functional improvements. Whether these medications have a unique effect to modulate skeletal muscle oxidative function, or instead derive their benefits from effects on nonmuscle systems that indirectly improve muscle function via reduced disease burden and/or increased physical activity, is not apparent. In fact, some degree of exercise training may be required to remediate the "detraining effects" that the disease imposes on skeletal muscle, because studies have shown that skeletal muscle energetic abnormalities persist after correction of cardiac insufficiency via transplantation. In this 15 light, interventions to counter the switch toward a fasttwitch fiber type, such as aerobic exercise, would clearly be beneficial in maintaining and/or improving functional capacity. Commensurate with these shifts in fiber type was an increase in peak aerobic capacity. As addressed previously, these alterations in fiber type, as reflected by alterations in the expression of myosin heavy chain protein, are largely related to muscle disuse rather than a unique effect of the disease process. In oxidative muscle, capillary density is higher in comparison to more glycolytic muscle types. Metabolic changes relating to differences in oxygen use and the ability to extract oxygen from the peripheral circulation, as what might be expected with reduced mitochondria content and function described previously, might in fact be required to promote changes in capillary density. In this context, intrinsic skeletal muscle adaptations may feed back to the vasculature to provoke maladaptive changes. Therefore, the occur during exercise during a state of increased oxygen imbalance of oxygen and energy supply to skeletal muscle is in particular impaired during exercise and physical work. With that, peripheral hypoperfusion, both at rest and particularly during exercise, is worsened. In turn, the beneficial effects of peripheral vasodilator therapy on improving cardiac output and peripheral perfusion are explained by this phenomenon. Reduced capillary density, progressive vasodilation, and impaired oxidative metabolism are linked by the molecular response to chronic hypoperfusion and low-grade ischemia. Several studies have confirmed that both in the myocardium and in skeletal muscle, ischemia and ischemia/ reperfusion result in a switch toward a more glycolytic metabolism. Moreover, tissue-specific expression further complicates the analysis of their exact action. This transcription factor regulates the expression of proinflammatory cytokines. Elevated skeletal muscle oxidative stress may contribute to both muscle atrophy and dysfunction. Additionally, recent studies have shown that aerobic exercise training can increase antioxidant systems and reduce oxidative protein modification,106 which may in part mediate the beneficial effects of exercise training on exercise tolerance. However, defining which specific skeletal muscle adaptations are directly attributable to the disease process or its sequelae is important for understanding which may be amenable to exercise countermeasures. It is necessary to further distinguish between acute and chronic muscle disuse, because the magnitude and character of disuse is likely to differ. Acute disuse likely occurs during hospitalization because of acute disease exacerbation or health decline as a result of other comorbidities. However, with treatment and reambulation, many of these acute adaptations may be remediated. Indeed, even some of the most profound adaptations in skeletal muscle, such as mitochondrial rarefaction, can be largely corrected with successful treatment and reambulation. Aside from this simple lowering of physiologic capacity, muscle adaptations may contribute to symptomology in ways that have been classically assigned to cardiac contractile dysfunction/ circulatory congestion. For instance, increased metabolite generation owing to impaired oxidative capacity, together with enhanced sensory nerve activation (either by mechanoor metabo-receptor hypersensitivity) in skeletal muscle, may increase vasoconstriction and ventilatory drive,110 which would contribute to muscle fatigue and dyspnea. For instance, reduced oxidative capacity, owing to reduced mitochondrial content and function, as well as fiber type switching toward a more glycolytic phenotype, contribute to dyspnea and fatigue directly. In the case of the former, metabolic derangements leading to excessive metabolite production. These adaptations and others, such as muscle atrophy and weakness, would also contribute to the subjective sensation of fatigue by reducing the overall physiologic capacity and would cause patients to perceive any activity as more demanding. Accordingly, exercise training appears to be an effective countermeasure for many of these skeletal muscle adaptations and should be considered as a standard treatment in suitable patients. As the earlier discussion of potential precipitating factors should reveal, the skeletal muscle adaptations occurring in any one individual patient are likely to be complex and unique. Thus there is no simple answer to this question, as it will likely be highly variable among patients, as well as within patients throughout the course of the disease. Belardinelli R, Georgiou D, Cianci G, et al: Exercise training improves left ventricular diastolic filling in patients with dilated cardiomyopathy: clinical and prognostic implications. Drexler H, Riede U, Munzel T, et al: Alterations in skeletal muscle in chronic heart failure. Vescovo G, Serafini F, Facchin L, et al: Specific changes in skeletal muscle myosin heavy chain composition in cardiac failure: differences compared with disuse atrophy as assessed on microbiopsies by high resolution electrophoresis. Gielen S, Adams V, Mobius-Winkler S, et al: Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. Thissen J-P, Verniers J: Inhibition by interleukin-1 and tumor necrosis factor- of the insulin-like growth factor I messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture. Adams V, Jiang H, Yu J, et al: Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. Aukrust P, Ueland T, Gullestad L, et al: Testosterone: a novel therapeutic approach in chronic heart failure Caminiti G, Volterrani M, Iellamo F, et al: Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure: a double-blind, placebocontrolled, randomized study. Heineke J, Auger-Messier M, Xu J, et al: Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Mettauer B, Zoll J, Sanchez H, et al: Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active controls subjects. Larsson L, Li X, Edstrom L, et al: Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels. De Sousa E, Veksler V, Bigard X, et al: Dual influence of disease and increased load on diaphragm muscle in heart failure. Piazzesi G, Reconditi M, Linari M, et al: Skeletal muscle performance determined by modulation of number of myosin motors rather than motor force or stroke size. Coirault C, Guellich A, Barby T, et al: Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats with chronic heart failure. Chati Z, Zannad F, Jeandel C, et al: Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure. Esposito F, Mathieu-Costello O, Shabetai R, et al: Limited maximal exercise capacity in patients with chronic heart failure: partitioning the contributors. Hambrecht R, Niebauer J, Fiehn E, et al: Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. Belardinelli R, Georgiou D, Scocco V, et al: Low intensity exercise training in patients with chronic heart failure. Hambrecht R, Fiehn E, Yu J, et al: Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. Hambrecht R, Adams V, Gielen S, et al: Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle. Dalla Libera L, Ravara B, Gobbo V, et al: Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of carvedilol. Vescovo G, Ravara B, Dalla Libera L: Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart failure.
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The pelvic cavity contains the urinary bladder spasms on right side cheap cilostazol 100mg amex, sigmoid colon, rectum, and internal reproductive organs. Dorsal Cavity Membranes the dorsal cavity is lined by three layers of protective membranes that are collectively called the meninges - (me-nin -jez; singular, meninx). The most superficial membrane is attached to the wall of the dorsal cavity, and the deepest membrane tightly envelops the brain and spinal cord. Membranes of Body Cavities the membranes lining body cavities support and protect the internal organs in the cavities. Ventral Cavity Membranes the ventral body cavity organs are supported and protected by serosae (singular, serosa), or serous membranes. In computerized tomography, an X-ray emitter and an X-ray detector rotate around the patient so that the X-ray beam passes through the body from hundreds of different angles. X-rays collected by the detector are then processed by a computer to produce sectional images on a screen for viewing by a radiologist. Transverse sections, such as the image on the left, are always shown in the same way. The serous membranes are thin layers of tissue that line the body cavity and cover the internal organs. Serous - membranes have a superficial parietal (pah-ri -e-tal) layer that lines the cavity and a deep visceral (vis -er-al) layer that covers the organ. The parietal and visceral layers secrete a watery lubricating fluid that is generically called serous fluid into the cavity formed between the layers. The serous membranes lining the thoracic cavity are called pleurae (singular, pleura), or pleural membranes. The walls of the left and right portions of the thoracic cavity are lined by the parietal pleurae. The parietal and visceral pleurae are separated by a thin film of serous fluid called pleural fluid, which reduces friction as the pleurae rub against each other as the lungs expand and contract during breathing. The potential space (not an actual space) between the parietal and visceral pleurae is known as the pleural cavity. The left and right portions of the thoracic cavity are divided by a membranous partition, the mediastinum - - - (me-de-a-sti -num). Organs located within the mediastinum include the heart, thymus, esophagus, and trachea. The heart is enveloped by the pericardium - (per-i-kar -de-um), which is formed by membranes of the mediastinum. The parietal pericardium lines the deep surface of a loosely fitting sac around the heart. The potential space between the visceral and parietal pericardia is the pericardial cavity, and it contains serous fluid, called pericardial fluid, that reduces friction as the heart contracts and relaxes. The walls of the abdominal cavity and the surfaces of abdominal organs are lined with the peritoneum - - (per-i-to-ne -um), or peritoneal membrane. The parietal peritoneum lines the walls of the abdominal cavity but not the pelvic cavity. The kidneys, pancreas, and parts of the intestines are located posterior to the parietal peritoneum in a space known as the retroperitoneal space. The visceral peritoneum, an extension of the parietal peritoneum, covers the surface of the abdominal organs. The potential space between the parietal and visceral peritoneal membranes is called the peritoneal cavity and contains a small amount of serous fluid called peritoneal fluid (figure 1. The abdominopelvic cavity is subdivided into either four quadrants or nine regions to aid health care providers in locating underlying organs in the abdominopelvic cavity. Physicians may feel (palpate) or listen to (auscultate) the abdominopelvic region to examine it. Changes in firmness or sounds may indicate abnormalities in the structures of a quadrant or region. The four quadrants are formed by two planes that intersect just superior to the umbilicus (navel), as shown in figure 1. The nine regions are formed by the intersection of two sagittal and two transverse planes as shown in figure 1. The superior transverse plane lies just inferior to the borders of the 10th costal cartilages, and the inferior transverse plane lies just inferior to the superior border of the hip bones. They show an anterior view of the body in progressive stages of dissection that reveals major muscles, blood vessels, and internal organs. Study these plates to learn the normal locations of the organs of the ventral cavity. Also, check your understanding of the organs within each abdominopelvic quadrant and region. Anabolism (ah-nab -o-lizm) refers to processes that use energy and nutrients to build the complex organic molecules that compose the body. Catabolism - (kah-tab -o-lizm) refers to processes that release energy and break down complex molecules into simpler molecules. It depends upon the normal functioning of trillions of body cells, which, in turn, depends upon factors needed for survival and the ability of the body to maintain relatively stable internal conditions. Food provides chemicals that serve as a source of energy and raw materials to grow and to maintain cells of the body. Oxygen is required to release the energy in organic nutrients, which powers life processes. Homeostasis Homeostasis is the maintenance of a relatively stable internal environment by self-regulating physiological processes. Homeostasis keeps body temperature and the composition of blood and interstitial fluids within their normal range. This relatively stable internal environment is maintained in spite of the fact that internal and external factors tend to alter body temperature, and materials are continuously entering and exiting the blood and interstitial fluid. All of the organ systems work in an interdependent manner to maintain homeostasis. Therefore, any disruption in one body system tends to be corrected but may disrupt another body system. The internal environment is maintained via a dynamic equilibrium where there is constant fluctuation taking place in order to maintain homeostasis. Malfunctioning or overcompensation in a homeostatic mechanism can lead to disorders and diseases. The dynamic equilibrium of homeostasis is primarily maintained by physiologic processes called negativefeedback mechanisms. Body fluid composition and other physiological variables fluctuate near a normal value, called a set point, and negative-feedback mechanisms are CheckMyUnderstanding 8. For a negative-feedback mechanism to work, it needs to be able to monitor and respond to any changes in homeostasis. The structure of the negative-feedback mechanism allows it to function in exactly this manner and is a great example of how anatomical structure complements function. To monitor a physiological variable, a negative-feedback mechanism utilizes a receptor to detect deviation from the set point and send a signal notifying the integrating center about the deviation. The integrating center, which is the body region that knows the set point for the variable, processes the information from a receptor and determines the course of action that is needed. The pancreas possesses other receptors that can detect decreases in blood glucose, such as occurs between meals. The alpha cells of the pancreas, acting as the integrating center, release the hormone glucagon. Glucagon causes the liver to release glucose into the bloodstream, which will increase blood glucose back toward normal (figure 1. It is important to note that the response of the integrating center will be stronger if the original stimulus is farther from normal. For example, if the blood glucose level rises sharply out of the normal range, causing hyperglycemia (blood glucose level above normal), the amount of insulin the beta cells release will be more than the amount released if the blood glucose level is elevated but is still within the normal range. This type of response is called a graded response because it can respond on different levels (figure 1.
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As the risk for adverse drug effects increases exponentially with the number of drugs prescribed muscle relaxant gi tract cheap cilostazol online visa, all unnecessary (and perhaps even some indicated) medications should be discontinued. Basic principles of transitional care dictate that early clinical follow-up is essential in this vulnerable subset of patients. In older patients, preservation of independence and maintenance of a satisfactory quality of life may be more important than survival. Given these complexities, a team approach to treating heart failure in older patients is critical Table 37-3). Several studies have confirmed the efficacy of a multidisciplinary approach to care in reducing hospitalizations, improving quality of life, reducing total costs, and, in one study, increasing survival (see also Chapter 44). Many of these studies included older patients who are ideal candidates for multidisciplinary care. Patients up to age 80 have been included in these trials, and subgroup analyses indicate that -blockers are as effective in older as in younger adults. The volume of distribution and renal clearance of digoxin decline with age, so that lower doses. Because the incidence of serious hyperkalemia is more common in older adults prescribed spironolactone in usual care settings, close monitoring is warranted for side effects including renal impairment and hyperkalemia. As shown in Table 37-4, although some of these agents exhibited favorable effects on surrogate or secondary outcomes, all of the trials were negative for the primary endpoint, and none of the drugs have been shown to reduce mortality. Indeed, an exercise training study demonstrated improved peak oxygen consumption mediated primarily to be an increase in peak arterial-venous oxygen difference. A recent study demonstrated that levels of biomarkers related to inflammation, including C-reactive protein and interleukin 6, were significantly lower in women than in men. In this study, mortality was also lower in women compared with men, independent of differences in clinical characteristics. From Ghanbari H, Dalloul G, Hasan R, et al: Effectiveness of implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death in women with advanced heart failure: a meta-analysis of randomized controlled trials. Overall survival rates are now similar in women and men, although female recipients of a male donor heart may be at higher risk of 1-year mortality than male recipients from a male donor. The complex interaction of genetics, social factors, environment, and lifestyle 607 may affect pathophysiologic and therapeutic observations seen in these racial and ethnic populations, which exhibit considerable heterogeneity. The prevalence for Mexican Americans is less than that of non-Hispanic men and women. Modified from Brown D, Haldeman G, Croft J, et al: Racial or ethnic differences in hospitalization for heart failure among elderly adults: Medicare, 1990-2000. Rates of ischemic cardiomyopathy are intermediate between non-Hispanic and African American populations. Higher levels of C-reactive protein and fibrinogen were associated with increased risk. Adapted from Dries D, Strong M, Cooper R, et al: Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients. Cameron J, Worrall-Carter L, Page K, et al: Does cognitive impairment predict poor self-care in patients with heart failure Garg R, Yusuf S: Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Savarese G, Trimarco B, Dellegrottaglie S, et al: Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials. Rosamond W, Flegal K, Furie K, et al: Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Deswal A, Bozkurt B: Comparison of morbidity in women versus men with heart failure and preserved ejection fraction. Bibbins-Domingo K, Lin F, Vittinghoff E, et al: Predictors of heart failure among women with coronary disease. Pitt B, Remme W, Zannad F, et al for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. Digitalis Investigation Group: the effect of digoxin on mortality and morbidity in patients with heart failure. Ghanbari H, Dalloul G, Hasan R, et al: Effectiveness of implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death in women with advanced heart failure: a meta-analysis of randomized controlled trials. Qian F, Ling F, Deedwania P, et al: Care and outcomes of Asian-American acute myocardial infarction patients: findings from the American Heart Association Get with the Guidelines- coronary artery disease program. Philbin E, Weil H, Francis C, et al: Observations from a biracial angiographic cohort. Afzal A, Ananthasubramaniam K, Sharma N, et al: Racial differences in patients with heart failure. Mathew J, Davidson S, Narra L, et al: Etiology and characteristics of congestive heart failure in blacks. Taylor A, Ziesche S, Yancy C, et al: Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. Brown D, Haldeman G, Croft J, et al: Racial or ethnic differences in hospitalization for heart failure among elderly adults: Medicare, 1990-2000. Rathore S, Foody J, Wang Y, et al: Race, quality of care, and outcomes of elderly patients hospitalized with heart failure. Mathew J, Wittes J, McSherry F, et al and the Digitalis Investigation Group: Racial differences in outcome and treatment effect in congestive heart failure. Agoston I, Cameron C, Yao D, et al: Comparison of outcomes in white versus black patients hospitalized with heart failure and preserved ejection fraction. Singh H, Gordon H, Deswal A: Variation by race in factors contributing to heart failure hospitalizations. Carson P, Ziesche S, Johnson G, et al: Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Exner D, Dries D, Domanski M, et al: Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. Dries D, Exner D, Gersh B, et al: Racial differences in the outcome of left ventricular dysfunction. Dries D, Strong M, Cooper R, et al: Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients. Yancy C, Fowler M, Colucci W, et al: Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure. Eichhorn E, Domanski M, Krause-Steinrauf H, et al: A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. Although pharmacologic approaches have been responsible for significant reductions in heart failure mortality, attempts to make further gains by adding additional agents have largely been unsuccessful. Additionally, currently used pharmacologic therapies slow the progress of the remodeling but do not address the underlying cause, namely critical loss of contractile myocardium in the infarcted area. Although heart transplantation is an option when pharmacologic therapies fail, it is severely limited because the need exceeds organ availability 10-fold, and the long-term effects of rejection and side effects of immunosuppression have limited its durability (median survival post transplant is 9 years). Several new biologic therapies and strategies for the treatment of heart failure have emerged in recent years, which will be reviewed in this chapter. Two main approaches will be reviewed here, including cardiac cell therapy and gene therapy, which hold great promise for changing our current approach to heart failure treatment. First proposed in the 1990s, cell replacement therapy was an attempt by investigators to address the limited availability of donor organs for cardiac transplantation. For lack of a better alternative, the first cell type tested was skeletal muscle cells. Most studies have focused on the first two cell types because of a report in 2001 in which circulating cells were harvested and reinjected into the heart after treatment with cytokines commonly used to mobilize hematopoietic stem cells. These studies did not demonstrate any significant conversion of c-kit expressing bone marrow cell conversion into cardiomyocytes or any significant capacity of these cells to restore heart function. Schematic diagram Pluripotent stem cells Pluripotent stem cells Programmed directed-differentiation Programmed directed-differentiation outlining the sources of adult cells types that have been used for cardiac cell therapy. Regardless, several of these circulating cell types have made their way into the clinics and are currently being tested for clinical efficacy. Bone marrow, the presumed source of the c-kit+ and other circulating progenitor cells, has been used extensively in preclinical and clinical trials. Although the exact regenerative capability of each of these cell types is strongly debated, positive preclinical studies have resulted in numerous phase I clinical trials. However, to date, there is no direct evidence that any bone marrow cell can differentiate into a mature cardiomyocyte (without genetic reprogramming), so any regenerative effects are most likely indirect.
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Also uterus spasms 38 weeks discount cilostazol, local reflexes integrated in the sacral and lumbar spinal cord are at least partly responsible for some of the reactions in the female sexual organs. Located around the introitus and extending into the clitoris is erectile tissue almost identical to the erectile tissue of the penis. This erectile tissue, like that of the penis, is controlled by the parasympathetic nerves that pass through the nervi erigentes from the sacral plexus to the external genitalia. In the early phases of sexual stimulation, parasympathetic signals dilate the arteries of the erectile tissue, probably resulting from release of acetylcholine, nitric oxide, and vasoactive intestinal polypeptide at the nerve endings. This allows rapid accumulation of blood in the erectile tissue so that the introitus tightens around the penis, which aids the male in his attainment of sufficient sexual stimulation for ejaculation to occur. Parasympathetic signals also pass to the bilateral Bartholin glands located beneath the labia minora and cause them to secrete mucus immediately inside the introitus. This mucus is responsible for much of the lubrication during sexual intercourse, although much lubrication is also provided by mucus secreted by the vaginal epithelium, and a small amount is provided from the male urethral glands. This lubrication is necessary during intercourse to establish a satisfactory massaging sensation rather than an irritative sensation, which may be provoked by a dry vagina. A massaging sensation constitutes the optimal stimulus for evoking the appropriate reflexes that culminate in both the male and female climaxes. When local sexual stimulation reaches maximum intensity, and especially when the local sensations are supported by appropriate psychic conditioning signals from the cerebrum, reflexes are initiated that cause the female orgasm, also called the female climax. The female orgasm is analogous to emission and ejaculation in the male, and it may help promote fertilization of the ovum. Indeed, the human female is known to be somewhat more fertile when inseminated by normal sexual intercourse rather than by artificial methods, thus indicating an important function of the female orgasm. First, during the orgasm, the perineal muscles of the female contract rhythmically, which results from spinal cord reflexes similar to those that cause ejaculation in the male. It is possible that these reflexes increase uterine and fallopian tube motility during the orgasm, thus helping to transport the sperm upward through the uterus toward the ovum; information on this subject is scanty, however. Also, the orgasm seems to cause dilation of the cervical canal for up to 30 minutes, thus allowing easy transport of the sperm. Second, in many animals, copulation causes the posterior pituitary gland to secrete oxytocin; this effect is probably mediated through the brain amygdaloid nuclei and then through the hypothalamus to the pituitary. The oxytocin causes increased rhythmical contractions of the uterus, which have been postulated to cause increased transport of the sperm. A few sperm have been shown to traverse the entire length of the fallopian tube in the cow in about 5 minutes, a rate at least 10 times as fast as that which the swimming motions of the sperm could possibly achieve. In addition to the possible effects of the orgasm on fertilization, the intense sexual sensations that develop during the orgasm also pass to the cerebrum and cause intense muscle tension throughout the body. After culmination of the sexual act, this tension gives way during the succeeding minutes to a sense of satisfaction characterized by relaxed peacefulness, an effect called resolution. The ovum remains viable and capable of being fertilized probably no longer than 24 hours after it is expelled from the ovary. Therefore, sperm must be available soon after ovulation if fertilization is to take place. Therefore, for fertilization to take place, intercourse must occur sometime between 4 and 5 days before ovulation up to a few hours after ovulation. Thus, the period of female fertility during each month is short-about 4 to 5 days. One commonly practiced method of contraception is to avoid intercourse near the time of ovulation. The difficulty with this method of contraception is predicting the exact time of ovulation. Yet, the interval from ovulation until the next succeeding onset of menstruation is almost always between 13 and 15 days. Therefore, if the menstrual cycle is regular, with an exact periodicity of 28 days, ovulation usually occurs within 1 day of the 14th day of the cycle. If, in contrast, the periodicity of the cycle is 40 days, ovulation usually occurs within 1 day of the 26th day of the cycle. Finally, if the periodicity of the cycle is 21 days, ovulation usually occurs within 1 day of the seventh day of the cycle. Therefore, it is usually stated that avoidance of intercourse for 4 days before the calculated day of ovulation and 3 days afterward prevents conception. However, such a method of contraception can be used only when the periodicity of the menstrual cycle is regular. The failure rate of this method of contraception, resulting in an unintentional pregnancy, may be as high as 20 to 25 percent per year. The administration of sex hormones (estrogens or progesterone) could prevent the initial ovarian hormonal depression that might be the initiating signal for ovulation. The challenge in devising methods for the hormonal suppression of ovulation has been in developing appropriate combinations of estrogens and progestins that suppress ovulation but do not cause other, unwanted effects. For instance, too much of either hormone can cause abnormal menstrual bleeding patterns. However, use of certain synthetic progestins in place of progesterone, especially the 19-norsteroids, along with small amounts of estrogens, usually prevents ovulation yet allows an almost normal pattern of menstruation. Therefore, almost all "pills" used for the control of fertility consist of some combination of synthetic estrogens and synthetic progestins. The main reason for using synthetic estrogens and progestins is that the natural hormones are almost entirely destroyed by the liver within a short time after they are absorbed from the gastrointestinal tract into the portal circulation. However, many of the synthetic hormones can resist this destructive propensity of the liver, thus allowing oral administration. Two of the most commonly used synthetic estrogens are ethinyl estradiol and mestranol. Among the most commonly used progestins are norethindrone, norethynodrel, ethynodiol, and norgestrel. The drug is usually begun in the early stages of the monthly cycle and continued beyond the time that ovulation would normally occur. Then the drug is stopped, allowing menstruation to occur and a new cycle to begin. The failure rate, resulting in an unintentional pregnancy, for hormonal suppression of fertility using various forms of the "pill" is about 8 to 9 percent per year. For instance, thick ovarian capsules occasionally exist on the outsides of the ovaries, making ovulation difficult. Because of the high incidence of anovulation in sterile women, special methods are often used to determine whether ovulation occurs. These methods are based mainly on the effects of progesterone on the body because the normal increase in progesterone secretion usually does not occur during the latter half of anovulatory cycles. In the absence of progestational effects, the cycle can be assumed to be anovulatory. One of these tests is simply to analyze the urine for a surge in pregnanediol, the end product of progesterone metabolism, during the latter half of the sexual cycle; the lack of this substance indicates failure of ovulation. Another common test is for the woman to chart her body temperature throughout the cycle. Secretion of progesterone during the latter half of the cycle raises the body temperature about 0. Lack of ovulation caused by hyposecretion of the pituitary gonadotropic hormones can sometimes be treated by appropriately timed administration of human chorionic gonadotropin, a hormone (discussed in Chapter 83) that is extracted from the human placenta. However, excess use of this hormone can cause ovulation from many follicles simultaneously, which results in multiple births, an effect that has caused as many as eight babies (stillborn in many cases) to be born to mothers treated for infertility with this hormone. One of the most common causes of female sterility is endometriosis, a common condition in which endometrial tissue almost identical to that of the normal uterine endometrium grows and even menstruates in the pelvic cavity surrounding the uterus, fallopian tubes, and ovaries. Occasionally, no abnormality can be discovered in the female genital organs, in which case it must be assumed that the infertility is due to either abnormal physiological function of the genital system or abnormal genetic development of the ova themselves. Pinilla L, Aguilar E, Dieguez C, et al: Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Often, endometriosis occludes the fallopian tubes, either at the fimbriated ends or elsewhere along their extent. Another common cause of female infertility is salpingitis, that is, inflammation of the fallopian tubes; this inflammation causes fibrosis in the tubes, thereby occluding them. In the past, such inflammation occurred mainly as a result of gonococcal infection. However, with modern therapy, salpingitis is becoming a less prevalent cause of female infertility.
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Unlike the pharmacologic half-lives of dopamine and dobutamine spasms colon symptoms purchase cilostazol now, which are in minutes, the elimination half-life of milrinone is about 2. Although bolus therapy was originally recommended, milrinone is frequently used without a bolus to avoid rapid initial effects, at doses as low as 0. The drug is then titrated to the desired hemodynamic effect, in increments of the lowest doses possible, up to a maximum of 0. In the setting of renal dysfunction, effects accumulate and persist over a longer period of time. When milrinone is discontinued after several days, the physiologic half-life often seems to exceed 12 or even 18 hours. As a result, patients are frequently assumed to have tolerated milrinone weaning only to deteriorate hours after transfer out of the intensive care unit or discharge home. It is thus particularly important to follow patients weaned from milrinone for at least 48 hours to ensure adequate fluid balance and blood pressure on oral therapy before discharge. Patients awaiting cardiac transplantation may be supported with extended infusions of milrinone either alone or in combination with dobutamine. Although intermittent outpatient inotropic infusions were occasionally administered in the past, this practice is not supported by evidence. These agents then may act synergistically with -adrenergic agents to achieve a further increase in cardiac output than either agent alone. They may also be more effective than -adrenergic receptor stimulation for increasing cardiac output when excess -blocking agents have been given. The relative effects on cardiac output and systemic vascular resistance vary markedly, so that some patients exhibit predominant vasodilation. This can cause significant hypotension, unlike dobutamine, which rarely causes hypotension except in unappreciated vasodilatory states such as sepsis. In a trial of patients hospitalized with heart failure and an average baseline blood pressure of 120 mm Hg, 10% of the patients randomized to milrinone developed clinically significant hypotension, a higher percentage than with a placebo. Milrinone has been associated with slightly less elevation in heart rate than have dobutamine and dopamine. A trial of a 48-hour infusion of milrinone during heart failure hospitalization increased adverse events of atrial and ventricular tachyarrhythmias, cardiac arrest, and myocardial infarction. Significant additional inotropic and blood pressure support can be provided by these agents for short-term life-saving intervention over a span of minutes to hours before definitive therapy. Although norepinephrine is commonly confused with phenylephrine (Neo-Synephrine, a pure peripheral -vasoconstrictor), both norepinephrine and epinephrine stimulate type 1 -adrenergic receptors and -adrenergic receptors, which increase contractility, heart rate, and peripheral vascular resistance, while promoting cardiac arrhythmias and ischemia. Kidney failure, hepatic failure, and gangrene can result from use of these agents, which should not be administered except in true emergency situations. Compared with norepinephrine, epinephrine has more affinity for type 2 -receptors, and thus is slightly less likely to cause tissue necrosis from intense vasoconstriction, although both are profound vasoconstrictors appropriate only for therapy of life-threatening shock. To maintain survival for brief periods until definitive therapy, boluses of calcium can also be helpful, particularly in the presence of conditions that may acutely lower serum calcium, such as transfusion, dialysis, or cardiopulmonary bypass. Vasopressin is used increasingly to potentiate the effects of catecholamines in patients who remain severely hypotensive on catecholamines. This experience is derived from early postoperative management after heart transplantation or insertion of mechanical support devices. At these doses, patients already receiving norepinephrine frequently have further 30 mm Hg increases in systolic blood pressure. Weaning of Intravenous Inotropic Therapy Inotropic therapy has been regarded as the "until" therapy, which should not be started without careful consideration of a predefined endpoint. It may be used until diuresis is effective in patients with conditions refractory to escalating diuretic therapy. It may be used until kidney, lung, or liver function has improved to establish eligibility for cardiac transplantation or for operative intervention. It may be used until recovery from a superimposed insult such as pneumonia, pulmonary embolus, myocardial infarction, or surgery. Much of the experience with prolonged infusions has derived from patients waiting until an appropriate heart can be found for cardiac transplantation. For patients in whom transplantation and mechanical support are not options, inotropic therapy initiated with the intent of brief support may be difficult to wean without symptomatic deterioration. Often, inotropic therapy can be weaned slowly and successfully with careful tailoring onto oral therapy to optimize filling pressures and systemic vascular resistance during invasive hemodynamic monitoring. In patients with adequate renal function, the addition of digoxin may be particularly useful at this time. The use of nitrates and the addition of hydralazine may be particularly effective in restoring compensation with oral vasodilators after prolonged inotropic infusion. Many of these patients are those in whom right ventricular failure has become prominent and the cardiorenal syndrome is manifest. Collaboration with palliative care services may be necessary to decide with families whether weaning should proceed after preparing for possible death in hospital or whether the short-term goals for the patient and family can better be met during continuous inotropic therapy (see also Chapter 47). Continuous intravenous inotropic infusions have been recognized as palliative care until death for some of these patients. This therapy has been associated with frequent complications from indwelling catheters and with sepsis. Patients should not be discharged on home inotropic therapy unless they demonstrate initial clinical stability and reasonable function with this regimen to justify the cost and inconvenience to the patient and family. Although in rare cases patients may stabilize to allow later weaning of intravenous therapy, patients should understand that long-term stability is unlikely and that discontinuation of inotropic therapy may become necessary, particularly for some hospice programs. Palliative inotropic therapy is not an indication for an implantable cardioverter-defibrillator in end-stage heart failure, and deactivation should be discussed with patients who already have a device. For many patients, the last part of their journey with heart failure is smoother and more comfortable if they are not tethered to a catheter and pump for continuous infusion. Primary and exacerbating causes of heart failure will have been explored and addressed if possible. After initial stabilization or attempted stabilization, the previous history and current state will be incorporated into a view of the next part of the journey. This will include considerations of both the severity of heart disease and the severity and contribution of comorbidities to survival and quality of life. For those few patients with advanced heart failure and reduced ejection fraction who are still eligible for cardiac transplantation or mechanical circulatory support, subsequent care is directed toward ensuring the best outcomes with those therapies. For some patients there may be investigational therapies that could be considered, although at the present time these are more numerous for patients with mild to moderate disease without recent decompensation. For most patients with heart failure, regardless of the ejection fraction, the focus is on reevaluation of the goals of care and redesign of their chronic medical regimen in light of both the cardiac condition and the common comorbidities. For a patient with advanced disease who was just weaned with difficulty from intravenous inotropic therapy, the prognosis for extended good quality survival is poor. These patients may not tolerate reinitiation of neurohormonal antagonists that undermine the reflex systems necessary to maintain tenuous perfusion. The reninangiotensin system potentiates effects of endogenous catecholamines, such that its inhibition may decrease effective inotropic state and cause hypotension, which is further aggravated by the bradykinin that accumulates when the angiotensin-converting enzyme is inhibited. There is no demonstrated benefit of neurohormonal antagonists in these patients, who would have been excluded from the AligningGoalsofCare 528 V mended therapies, and in whom remodeling has already definitive studies that form the basis of evidence for recomprogressed to a state unlikely to be reversed. Even if not receiving intravenous inotropic therapy, there are other patients in whom a history of frequent heart failure hospitalizations, progressive renal dysfunction, or other trends indicate a very limited prognosis. When the goals of care are to maximize mobility, relieve symptoms, and maintain social exchange toward the end of life, thoughtful review is warranted regarding medications for which benefits may have been outlived when those medications undermine marginal blood pressure and renal function or otherwise detract from energy desired for meaningful interaction. Lower doses are required to maintain stability after diuresis than were required to achieve net fluid loss. However, bed rest enhances diuretic efficacy, which is reduced when patients return to a more ambulatory routine. In addition, patients often consume more sodium and fluid at home than when restricted in the hospital. It is crucial to adjust oral diuretics in the hospital to achieve at least even fluid balance.
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The members of each pair are pulled by spindle fibers towards opposite sides of the cell 2410 muscle relaxant cheap cilostazol amex. The separated chromatids are now called chromosomes, and each new set of chromosomes is identical (figure 3. Telophase During telophase, the spindle fibers disassemble and a new nuclear envelope starts forming around each set of chromosomes as the new nuclei begin to take shape. The chromosomes start to uncoil, and they will ultimately become visible only as chromatin granules. Usually during late anaphase and telophase, the most obvious change is the division of the cytoplasm, which is called cytokinesis (si! The formation of two daughter cells, each having identical chromosomes in the nuclei, marks the end of mitotic cell division (figure 3. Chromosome Centrioles Spindle fiber Centromere (b) Metaphase Chromosomes line up at the equator of the spindle. It is selectively permeable and controls the movement of the materials into and out of cells. The cytoplasm, which is composed of cytosol and organelles, lies external to the nucleus and is enveloped by the plasma membrane. Chromosomes Centrioles Nuclear envelopes (d) Telophase Nuclear envelopes form around each set of chromosomes; spindle fibers disappear; chromosomes uncoil and extend; cytokinesis produces two daughter cells. Mitochondria are large, double-membraned organelles within which aerobic respiration occurs. Lysosomes are small vesicles that contain digestive enzymes used to digest foreign particles, worn-out parts of a cell, or an entire damaged cell. The cytoskeleton is formed by microtubules and microfilaments, and is used in maintaining cell structure and cell movement. The wall of each centriole is composed of microtubules arranged in groups of three. Substances diffuse across plasma membrane by simple diffusion, channel-mediated diffusion, and carrier-mediated diffusion. Active transport mechanisms include carrier-mediated active transport, endocytosis, and exocytosis. Cellular respiration of glucose involves anaerobic respiration and aerobic respiration. Four daughter cells are formed that have half the number of chromosomes as the parent cell. Most of a cell cycle is spent in interphase, where cells carry out normal metabolic functions. In cells destined to divide, chromosomes and centrioles are replicated in interphase. After chromosome replication, mitosis is the orderly process of separating and distributing chromosomes equally to the daughter cells. Movement of molecules from an area of their higher concentration to an area of their lower concentration is known as. Movement of molecules across a membrane by carrier proteins without the expenditure of energy is a form of. How do the characteristics of a substance determine the transport mechanism that will be used to move it across the plasma membrane Consider your ability to move your hand off an environmental hazard, such as a hot surface. Attached to these bones are muscles containing skeletal muscle tissue, which has the ability to contract and create force. When the muscles of the arm contract with force, they pull on the bones in the forearm to create movement at the elbow. Nervous tissue detects and processes the pain stimuli from the hand when it contacts the hazard. It then acts to control and coordinate the contraction of the skeletal muscle tissue in response. Epithelial tissue (epi = upon, over; thel = delicate) A thin tissue that covers body and organ surfaces and lines body cavities, and forms secretory portions of glands; epithelium. Fibroblast (fibro = fiber; blast = germ) A cell that produces fibers and ground substance in connective tissue. Mucous membrane Epithelial membrane that lines tubes and cavities that have openings to the external environment. Serous membrane Epithelial membrane that lines the external surfaces of organs and the body wall in the ventral cavity. As these cells divide repeatedly producing many generations of cells, the daughter cells become partially specialized. Such cells can produce daughter cells for only certain related types of specialized cells. This trend of decreasing potential (increasing specialization) continues through many generations of cells, ultimately producing the highly specialized cells of the human body plus a few partially specialized cells known as adult stem cells. If they do, they can form only specialized cells like themselves; for example, skin cells divide to produce only skin cells. Most tissues contain a few adult stem cells, which play an important role in tissue repair. Each type of tissue is distinguished by the structure of its cells, its extracellular substance, and the function it performs. The different tissues of the body are classified into four basic types: epithelial, connective, muscle, and nervous tissues. Epithelial (ep -i-the -le -al) tissue covers the surfaces of the body, lines body cavities and covers organs, and forms the secretory portions of glands. Connective tissue binds organs together and provides protection and support for organs and the entire body. Clinical Insight Adult stem cells from a variety of tissues are used in medical therapies. Medical scientists think that, with more research, stem cells may be used to treat cancer, brain and spinal cord injuries, multiple sclerosis, Parkinson disease, and other injuries and disorders. Muscle tissue contracts to provide force for the movement of the whole body and many internal organs. Nervous tissue detects changes, processes information, and coordinates body functions via the transmission of nerve impulses. Identify the common locations and general functions of each type of epithelial tissue. Epithelial tissues, or epithelia (singular, epithelium), may be composed of one or more layers of cells. The number of cell layers and the shape of the cells provide the basis for classifying epithelial tissues (figures 4. Epithelial cells are packed closely together with very little extracellular material between them. The surface of the tissue (free surface) opposite the basement membrane is not attached to any other type of tissue and is located on a surface or next to an opening. Blood vessels are absent, so epithelial cells must rely on diffusion to receive nourishment from blood vessels in the deeper connective tissue. The functions of epithelial tissues vary with the specific location and type of tissue, but generally they include protection, diffusion, osmosis, absorption, filtration, and secretion. Certain epithelial cells form glandular epithelium, the cells in glands that produce secretions. Two basic types of glands are contained in the body: exocrine and endocrine glands. Exocrine glands (exo = outside of; crin = to secrete) have ducts (small tubes) that carry their secretions to specific areas; sweat glands and salivary glands are examples. Their secretions, called hormones, are carried by the blood supply to organs within the body to regulate their function. Endocrine glands and their hormones will be discussed in more detail in chapter 10. In a surface view, the cells somewhat resemble tiles arranged in a mosaic pattern.
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Note especially that the total amounts of calcium and phosphate needed by the fetus during gestation represent only about 2 percent of the quantities of these substances 1072 Chapter 84 FetalandNeonatalPhysiology spontaneous abortion usually occurs at an early stage of pregnancy spasms right side of back cheap 50 mg cilostazol with mastercard. Therefore, prenatal storage in the fetal liver of at least small amounts of vitamin K derived from the mother is helpful in preventing fetal hemorrhage, particularly hemorrhage in the brain when the head is traumatized by squeezing through the birth canal. Adjustments of the Infant to Extrauterine Life Onset of Breathing the most obvious effect of birth on the baby is loss of the placental connection with the mother and, therefore, loss of this means of metabolic support. One of the most important immediate adjustments required of the infant is to begin breathing. After normal delivery from a mother whose system has not been depressed by anesthetics, the child ordinarily begins to breathe within seconds and has a normal respiratory rhythm within less than 1 minute after birth. The promptness with which the fetus begins to breathe indicates that breathing is initiated by sudden exposure to the exterior world, probably resulting from a slightly asphyxiated state that is incident to the birth process and from sensory impulses that originate in the suddenly cooled skin. In an infant who does not breathe immediately, the body becomes progressively more hypoxic and hypercapnic, which provides additional stimulus to the respiratory center and usually causes breathing within an additional minute after birth. In adults, failure to breathe for only 4 minutes often causes death, but neonates often survive as long as 10 minutes without breathing after birth. Permanent and serious brain impairment often ensues if breathing is delayed more than 8 to 10 minutes. Indeed, actual lesions develop mainly in the thalamus, in the inferior colliculi, and in other brain stem areas, thus permanently affecting many of the motor functions of the body. At birth, the walls of the alveoli are at first collapsed because of the surface tension of the viscid fluid that fills them. More than 25 mm Hg of negative inspiratory pressure in the lungs is usually required to oppose the effects of this surface tension and to open the alveoli for the first time. Once the alveoli open, however, further respiration can be effected with relatively weak respiratory movements. Fortunately, the first inspirations of the normal neonate are extremely powerful; they are usually capable of creating as much as 60 mm Hg negative pressure in the intrapleural space. At the top of the figure, the pressure-volume curve ("compliance" curve) for the first breath after birth is shown. Observe, first, that the lower part of the curve begins at the zero pressure point and moves to the right. The curve shows that the volume of air in the lungs remains almost exactly zero until the negative pressure has reached -40 centimeters of water (-30 mm Hg). Then, as the negative pressure increases to -60 centimeters of water, about 40 milliliters of air enters the lungs. To deflate the lungs, considerable positive pressure, about +40 centimeters of water, is required because of viscous resistance offered by the fluid in the bronchioles. Note that the second breath is much easier, requiring far less negative and positive pressures. Breathing does not become completely normal until about 40 minutes after birth, as shown by the third compliance curve, the shape of which compares favorably with that for the normal adult, as shown in Chapter 39. Also, many infants who have had head trauma during delivery or who undergo prolonged delivery are slow to breathe or sometimes do not breathe at all. This can result from two possible effects: First, in a few infants, intracranial hemorrhage or brain contusion causes a concussion syndrome with a greatly depressed respiratory center. Second, and probably much more important, prolonged fetal hypoxia during delivery can cause serious depression of the respiratory center. The alveoli of these infants at death contain large quantities of proteinaceous fluid, almost as if pure plasma had leaked out of the capillaries into the alveoli. This condition is called hyaline membrane disease because microscopic slides of the lung show that the material filling the alveoli looks like a hyaline membrane. A characteristic finding in respiratory distress syndrome is failure of the respiratory epithelium to secrete adequate quantities of surfactant, a substance normally secreted into the alveoli that decreases the surface tension of the alveolar fluid, therefore allowing the alveoli to open easily during inspiration. However, the fetal heart must pump large quantities of blood through the placenta. Therefore, special anatomical arrangements cause the fetal circulatory system to operate much differently from that of the newborn baby. Then most of the blood entering the right atrium from the inferior vena cava is directed in a straight pathway across the posterior aspect of the right atrium and through the foramen ovale directly into the left atrium. Thus, the well-oxygenated blood from the placenta enters mainly the left side of the heart, rather than the right side, and is pumped by the left ventricle mainly into the arteries of the head and forelimbs. The blood entering the right atrium from the superior vena cava is directed downward through the tricuspid valve into the right ventricle. It is pumped by the right ventricle into the pulmonary artery and then surfactant until the last 1 to 3 months of gestation. Therefore, many premature babies and a few full-term babies are born without the capability to secrete sufficient surfactant, which causes both a collapse tendency of the alveoli and development of pulmonary edema. Circulatory Readjustments at Birth Equally as essential as the onset of breathing at birth are immediate circulatory adjustments that allow adequate blood flow through the lungs. To describe these readjustments, we first consider the anatomical structure of the fetal circulation. Approximately 55 percent of all the blood goes through the placenta, leaving only 45 percent to pass through all the tissues of the fetus. Furthermore, during fetal life, only 12 percent of the blood flows through the lungs, whereas immediately after birth, virtually all the blood flows through the lungs. Changes in Fetal Circulation at Birth the basic changes in fetal circulation at birth are discussed in Chapter 23 in relation to congenital anomalies of the ductus arteriosus and foramen ovale that persist throughout life in a few persons. This doubling of the systemic vascular resistance increases the aortic pressure, as well as the pressures in the left ventricle and left atrium. Second, the pulmonary vascular resistance greatly decreases as a result of expansion of the lungs. In the unexpanded fetal lungs, the blood vessels are compressed because of the small volume of the lungs. Immediately on expansion, these vessels are no longer compressed and the Decreased Pulmonary and Increased Systemic Vascular Resistances at Birth. The primary changes in the circula- resistance to blood flow decreases severalfold. Also, in fetal life, the hypoxia of the lungs causes considerable tonic vasoconstriction of the lung blood vessels, but vasodilation takes place when aeration of the lungs eliminates the hypoxia. All these changes together reduce the resistance to blood flow through the lungs as much as fivefold, which reduces the pulmonary arterial pressure, right ventricular pressure, and right atrial pressure. The low right atrial pressure and the high left atrial pressure that occur secondarily to the changes in pulmonary and systemic resistances at birth cause blood to now attempt to flow backward through the foramen ovale, that is, from the left atrium into the right atrium, rather than in the other direction, as occurred during fetal life. Consequently, the small valve that lies over the foramen ovale on the left side of the atrial septum closes over this opening, thereby preventing further flow through the foramen ovale. In two thirds of all people, the valve becomes adherent over the foramen ovale within a few months to a few years and forms a permanent closure. However, even if permanent closure does not occur-a condition called patent foramen ovale-throughout life the left atrial pressure normally remains 2 to 4 mm Hg greater than the right atrial pressure, and the backpressure keeps the valve closed. First, the increased systemic resistance elevates the aortic pressure while the decreased pulmonary resistance reduces the pulmonary arterial pressure. As a consequence, after birth, blood begins to flow backward from the aorta into the pulmonary artery through the ductus arteriosus, rather than in the other direction, as in fetal life. However, after only a few hours, the muscle wall of the ductus arteriosus constricts markedly and within 1 to 8 days, the constriction is usually sufficient to stop all blood flow. Then, during the next 1 to 4 months, the ductus arteriosus ordinarily becomes anatomically occluded by growth of fibrous tissue into its lumen. Furthermore, many experiments have shown that the degree of contraction of the smooth muscle in the ductus wall is highly related to this availability of oxygen. In one of several thousand infants, the ductus fails to close, resulting in a patent ductus arteriosus, the consequences of which are discussed in Chapter 23. In fact, administration of the drug indomethacin, which blocks synthesis of prostaglandins, often leads to closure. Immediately after birth, blood flow through the umbilical vein ceases, but most of the portal blood still flows through the ductus venosus, with only a small amount passing through the channels of the liver. However, within 1 to 3 hours the muscle wall of the ductus venosus contracts strongly and closes this avenue of flow. As a consequence, the portal venous pressure rises from near 0 to 6 to 10 mm Hg, which is enough to force portal venous blood flow through the liver sinuses.
