Marilia Cascalho, MD, PhD

• Professor of Surgery and Professor of Microbiology and
• Immunology, Transplantation Biology
• Associate
• Professor of Surgery and Associate Professor of
• Microbiology & Immunology, Transplantation Biology,
• University of Michigan, Ann Arbor, MI
• Emerging Strategies in Kidney Transplantation

It is also believed that endotoxin is an important virulence factor for Salmonella zyprexa spasms discount 100 mg voveran sr overnight delivery. Transmission Shigella the Shigella bacteria are gram-negative spasms 24 purchase voveran sr 100mg with mastercard, straight rods spasms under ribs order voveran sr visa, nonmotile and non-endospore-forming spasms coronary artery discount 100mg voveran sr with visa. They do not produce urease or hydrogen sulfide muscle relaxant rocuronium generic 100mg voveran sr overnight delivery, traits that help in their identification muscle relaxant bath cheap 100 mg voveran sr. Diagnosis is complicated by the fact that several alternative candidates can cause bloody diarrhea, such as E. Stool culture is still the gold standard for identification in the case of Shigella infections. In the past decade, the prevalent agents in the United States have been Shigella sonnei and Shigella flexneri, which cause approximately 20,000 to 25,000 cases each year, half of them in children. Signs Transmission and Epidemiology and Symptoms the symptoms of shigellosis include frequent, watery stools; fever; and often intense abdominal pain. Stools often contain obvious blood and even more often are found to have occult (not visible to the naked eye) blood. Pathogenesis In addition to the usual oral route, shigellosis is also acquired through direct person-to-person contact, largely because of the small infectious dose required (from 10 to 200 bacteria). The disease is mostly associated with lax sanitation, malnutrition, and crowding; it is spread epidemically in day care centers, prisons, mental institutions, nursing homes, and military camps. As in other enteric infections, Shigella can establish a chronic carrier condition in some people that lasts several months. In addition, it is not as invasive as Salmonella and does not perforate the intestine or invade the blood. Once in the mucosa, Shigella instigates an inflammatory response that causes extensive tissue destruction. Local areas of erosion give rise to bleeding and heavy secretion of mucus (figure 22. Shigella dysenteriae (and perhaps some of the other species) produces a heat-labile exotoxin called shiga toxin, which seems to be responsible for the more serious damage to the intestine as well as any systemic effects, including injury to nerve cells. The only prevention of this and most other diarrheal diseases is practicing good hygiene and avoiding contact with infected persons. Since then, it has led to approximately 95,000 illnesses and about 50 deaths each year in the United States. Note the patches of blood and mucus, the erosion of the lining, and the absence of perforation. Products that are eaten raw, such as lettuce, vegetables, and apples used in unpasteurized cider, are particularly problematic. Neurological symptoms such as blindness, seizure, and stroke (and long-term debilitation) are also possible. These serious manifestations are most likely to occur in children younger than age 5 and in elderly people. As described earlier for Shigella, the shiga toxin interrupts protein synthesis in its target cells. The net effect is a lesion in the gut (effacement), usually in the large intestine. The microvilli are lost from the gut epithelium, and the lesions produce bloody diarrhea. This way, outbreaks that are geographically dispersed (for instance, those caused by contaminated meat or fruit that may have been distributed nationally) can be identified quickly. When new patterns come in, they are archived so that other laboratories submitting the same patterns will quickly realize that the cases are related. Ground beef is more dangerous than steaks or other cuts of meat, for several reasons. Contamination occurs when intestinal contents contact the animal carcass, so bacteria are confined to the surface of meats. Because high heat destroys this bacterium, even a brief trip under the broiler is usually sufficient to kill E. But in ground beef, the "surface" of meat is mixed and ground up throughout a batch, meaning any bacteria are mixed in also. Hamburger is also a common vehicle because meat-processing plants tend to grind meats from several cattle sources together, thereby contaminating large amounts of hamburger with meat from one animal carrier. The best prevention for this disease is to never eat raw or even rare hamburger and to wash raw vegetables well. If you are thinking "I used to be able to eat rare hamburgers," you are correct, but things have changed. The emergence of this pathogen in the early 1990s, probably resulting from a regular E. Supportive therapy, including plasma transfusion to dilute toxin in the blood, is the best option. Each of the five other categories is considered separately and briefly here; in Disease Table 22. These strains also cause a great deal of illness in infants in developing countries. They are treated only with fluid replacement, often due to the high rate of drug resistance. These strains cause bacillary dysentery, which is often mistaken for Shigella dysentery. These bacteria are identified based on virulence factors used to attach to host cells. They are typically associated with the development of urinary tract infections in addition to acute diarrhea in the developing world. The symptoms of campylobacteriosis are frequent, watery stools, as well as fever, vomiting, headaches, and severe abdominal pain. The symptoms may last longer than most acute diarrheal episodes, sometimes extending beyond 2 weeks. Campylobacter jejuni is the most common cause, although there are other pathogenic Campylobacter species. Campylobacters are slender, curved or spiral, gram-negative bacteria propelled by polar flagella at one or both poles, often appearing in S-shaped or gull-winged pairs (figure 22. These bacteria tend to be microaerophilic inhabitants of the intestinal tract, genitourinary tract, and oral cavity of humans and animals. A close relative, Helicobacter pylori, is the causative agent of most stomach ulcers (described earlier). Transmission of this pathogen takes place via the ingestion of contaminated beverages and food, especially water, milk, meat, and chicken. The mechanisms of pathology appear to involve a heat-labile enterotoxin that stimulates a secretory diarrhea like that of cholera. The condition is still mysterious in many ways, but it seems to be an autoimmune reaction that can be brought on by infection with viruses and bacteria, by vaccination in rare cases, and even by surgery. In more severely affected patients, it may be necessary to administer azithromycin. Antibiotic resistance is growing in these bacteria, in large part due to the use of fluoroquinolones in the treatment of poultry destined for human consumption. Prevention depends on rigid sanitary control of water and milk supplies and care in food preparation. Clostridium difficile Clostridium difficile is a gram-positive, endospore-forming rod found as normal biota in the intestine. It was once considered relatively harmless but now is known to cause a condition called pseudomembranous colitis, also known as antibiotic-associated colitis. In many cases, this infection is precipitated by therapy with broad-spectrum antibiotics. It is a major cause of diarrhea in hospitals, although community-acquired infections have been on the rise in the last few years. Also, new studies suggest that the use of gastric acid inhibitors for the treatment of heartburn can predispose patients to this infection. It produces two enterotoxins, toxins A and B, that cause areas of necrosis in the wall of the intestine. The colon is inflamed and gradually sloughs off loose, membranelike patches called pseudomembranes consisting of fibrin and cells (figure 22. If a patient is receiving clindamycin, ceftriaxone, or a fluoroquinolone for a different infection and displays C. This is a revival of a very old-fashioned method of obtaining feces from a healthy person and instilling them in the colon of the patient. Many have found relief from this method, presumably because a diverse microbiome with "healthy" species replaces the now-depleted microbiome of the C. Hospitalized patients must be put in isolation conditions, and constant attention to disinfection and infection control is required. It is not an exaggeration to say that the disease has shaped a good deal of human history in Asia and Latin America, where it has been endemic. These days, we have come to expect outbreaks of cholera to occur after natural disasters, war, or large refugee movements, especially in underdeveloped parts of the world. A freshly isolated specimen of Vibrio cholerae contains quick, darting cells that slightly resemble a comma (figure 22. Vibrio shares many cultural and physiological characteristics with members of the Enterobacteriaceae, a closely related family. They possess unique O and H antigens and membrane receptor antigens that provide some basis for classifying members of the family. Photographs were made by a sigmoidoscope, an instrument capable of photographing the interior of the colon. When this toxin binds to specific intestinal receptors, a secondary signaling system is activated. Under the influence of this system, the cells shed large amounts of electrolytes into the intestine, an event accompanied by profuse water loss. Cold, acidic, dry environments inhibit the migration and survival of Vibrio, whereas warm, monsoon, alkaline, and saline conditions favor them. Recent outbreaks in several parts of the world have been traced to giant cargo ships that pick up ballast water in one port and empty it in another elsewhere in the world. In nonendemic areas such as the United States, the microbe is spread by water and food contaminated by asymptomatic carriers, but it is relatively uncommon. Due to its ability to produce chitinase, this pathogen can often live within marine copepods. Since various aspects of global warming can impact the growth of these plankton populations, many scientists are concerned about the risk of more frequent cholera epidemics in the future. Culture and Diagnosis Signs and Symptoms After an incubation period of a few hours to a few days, symptoms begin abruptly with vomiting, followed by copious watery feces called secretory diarrhea. This voided fluid contains flecks of mucus-hence, the description "rice-water stool. The diarrhea causes loss of blood volume, acidosis from bicarbonate loss, and potassium depletion, which manifest in muscle cramps, severe thirst, flaccid skin, sunken eyes, and-in young children-coma and convulsions. Secondary circulatory consequences can include hypotension, tachycardia, cyanosis, and collapse from shock within 18 to 24 hours. If cholera is left untreated, death can occur in less than 48 hours; the mortality rate is between 55% and 70%. Direct dark-field microscopic observation reveals characteristic curved cells with brisk, darting motility as confirmatory evidence. Immobilization or fluorescent staining of feces with group-specific antisera is supportive as well. In order to determine the initial source of infection, it is often necessary to determine the exact genetic nature of the strain causing an epidemic. This was the case in the massive outbreak of disease that occurred in Haiti in 2010. Prevention and Treatment and Virulence Factors After being ingested with food or water, V. At the junction of the duodenum and jejunum, the vibrios penetrate the mucous barrier using their flagella, adhere to the microvilli of the epithelial cells, and multiply there. Effective prevention is contingent on proper sewage treatment and water purification. Detecting and treating carriers with mild or asymptomatic cholera are serious goals, but they are difficult to accomplish because of inadequate medical provisions in those countries where cholera is endemic. An oral vaccine containing live, attenuated bacteria was developed to be a more effective alternative, but evidence suggests it also confers only short-term immunity. It is not routinely used in the United States but has been used successfully to develop protective herd immunity in endemic nations, like Haiti and Africa. This therapy can be accomplished by various rehydration techniques that replace the lost fluid and electrolytes. Cases in which the patient is unconscious or has complications from severe dehydration require intravenous replenishment as well. Non-cholera Vibrio Species In the United States, infection with non-cholera Vibrio species is more likely. Infection can be from exposure to seawater but more often is associated with eating contaminated shellfish. Scientists suspect that the increase is due to three factors: (1) the increased demand for raw oysters; (2) increased awareness, meaning that more people are diagnosed; and (3) global warming, causing a wider habitat for these bacteria in bodies of water.

A preparation is exposed to flowing steam for an hour muscle relaxant injection purchase voveran sr 100 mg overnight delivery, and then the mineral is allowed to incubate to permit spore germination muscle relaxant blood pressure order voveran sr from india. V vaccination Exposing a person to the antigenic components of a microbe without its pathogenic effects for the purpose of inducing a future protective response infantile spasms 2 month old 100 mg voveran sr mastercard. In general spasms movie buy voveran sr, the term now pertains to injection of whole microbes (killed or attenuated) muscle relaxer kidney cheap voveran sr 100 mg on line, toxoids spasms when urinating discount 100mg voveran sr fast delivery, or parts of microbes as a prevention or cure for disease. Infectious agents can be conveyed mechanically by simple contact or biologically whereby the parasite develops in the vector. A genetic element such as a plasmid or a bacteriophage used to introduce genetic material W Western blot test A procedure for separating and identifying antigen or antibody mixtures by twodimensional electrophoresis in polyacrylamide gel, followed by immune labeling. The reaction is triggered by cutaneous contact or intradermal injection of allergens in sensitive individuals. Glossary colorless and include granulocytes (neutrophils, eosinophils, and basophils) and agranulocytes (lymphocytes and monocytes). G-21 Z zoonosis An infectious disease indigenous to animals that humans can acquire through direct or indirect contact with infected animals. The inconsistencies with the placental origins hypothesis have been attributed to disease heterogeneity or explained as the maternal form of the disorders. Forming a better understanding of the precise etiology of so-called placental syndromes is critical for the development of accurate diagnostic aids, improved screening, better triage by disease severity and offering targeted preventative and therapeutic measures. This article, and other chapters in this volume, review the evidence that supports maternal cardiovascular involvement in the etiology of placental syndromes. Conventional Beliefs Regarding the Causation of Placental Syndromes Human placentation is uniquely associated with physiological remodeling of the spiral arteries, where deep placentation involves almost complete transformation of maternal spiral arteries to produce a low-resistance uterine circulation. The result is a dysfunctional endothelial cell leading to maternal systemic vasculopathy. Importantly, the odds ratios for villous and vascular placental lesions in preeclampsia were consistently threefold lower in studies where the pathologist was blinded to the pregnancy diagnosis, demonstrating significant systematic operator bias in unblinded assessments. Furthermore, even though histological placental lesions are more prevalent in pathological pregnancies, the overall incidence is higher in normal pregnancies because the latter outnumber pathological pregnancies several-fold. The squares represent the studies included in the meta-analysis, arranged in time of publication order. In particular, the square boxes represent the effect estimates for each single study, and the horizontal line crossing the box shows the confidence interval, which is inversely proportionate to the reliability of the study. The diamante figure represents the summary effect and its width represents the degree of the heterogeneity. Uterine Artery Doppler the physiological remodeling of the spiral arteries by the invading trophoblast is thought to result in a low-resistance uterine circulation. Increased uterine artery Doppler resistance indices have long been presumed to be the consequence of incomplete trophoblast invasion of maternal spiral arteries resulting in a high-resistance placental circulation and under-perfusion of the fetoplacental unit [1]. The overlap in these predisposing environmental and genetic risk factors has been taken to imply that they have a deleterious impact on trophoblast development. However, it is important to acknowledge that these risk factors have long been associated with the development of cardiovascular disease in the nonpregnant population. The concept that placental dysfunction is secondary to a maternal syndrome is not new when one considers the similarities between preeclampsia and gestational diabetes (Table 1. Maternal Cardiovascular Adaptation in Pregnancy Maternal adaptation to pregnancy is expected to create optimal conditions for the growth and development of the unborn child without jeopardizing maternal health. Several studies have demonstrated progressive changes in cardiac geometry and ventricular function with advancing gestation. Pregnancy is associated with an increase in the intravascular compartment by about 1500ml, as well as an increase in the maternal heart rate. In concert with the increase in cardiac output is a fall in systemic vascular resistance and redistribution of blood flow at a regional level [7]. To provide perspective, these cardiac changes are an order of magnitude greater than observed in elite athletes after several years of training and equate to changes seen in some pathological conditions in nonpregnant individuals. Mild-moderate left ventricular diastolic Chapter 1: Maternal Hemodynamics in Health and Disease 7 Table 1. Myocardial diastolic dysfunction (white columns) was diagnosed with average early to late strain rate ratio of<1 and chamber diastolic dysfunction (black columns) according to the American Society of Echocardiography diagnostic algorithms. This impairment in cardiac function is likely to be related to increase in cardiac afterload (high systemic vascular resistance) and abnormal left ventricular remodeling/hypertrophy. However, cardiovascular adaptations in pregnancy require both volume and resistance load to be raised significantly and for a prolonged period. Similarly to glucose tolerance testing, a conventional echo assessment prior to or in early pregnancy is unlikely to detect limited reserve capacity of the maternal cardiovascular system. Postpartum Cardiovascular Legacy the numerous parallels between placental syndromes and gestational diabetes also extend into the postpartum period. Women whose pregnancies were complicated by gestational diabetes have a 50% risk of developing diabetes in the subsequent decade. Detailed longitudinal followup with echocardiography in apparently healthy women after pregnancies complicated by placental syndromes has demonstrated persistent remodeling and left ventricular dysfunction up to two years or more postpartum [23]. Although the authors suggested that maternal prehypertension may be a response to impaired placental function, consideration should be given to the possibility that the placenta is a perfusiondependent organ and that impaired cardiovascular function may cause placental dysfunction, rather than the other way round. Unbroken lines: women with no hypertensive disorder of pregnancy in their first pregnancy. Broken lines: women with a hypertensive disorder of pregnancy in their first pregnancy. Conclusions A critical evaluation of maternal cardiovascular physiology reveals that there are profound changes in cardiac and hemodynamic performance in human pregnancy. The magnitude of these changes and maternal cardiovascular adaptation to pregnancy has previously been significantly underestimated. The consequences of these physiological findings only become apparent when considering the biological consequences of maternal cardiac maladaptation to increasing demands of advancing pregnancy. There is now incontrovertible evidence that failure of the maternal cardiovascular system to adapt to pregnancy is the primary mechanism leading to secondary placental dysfunction and so-called placental syndromes. First-trimester uterine artery Doppler and adverse pregnancy outcome: a metaanalysis involving 55 974 women. Ophthalmic Artery Doppler Prediction of Preeclampsia: A Systematic Review and Meta-Analysis. Predictive accuracy of second-trimester uterine artery Doppler indices for stillbirth: a systematic review and meta-analysis. Repeat measurements of uterine artery pulsatility index, mean arterial pressure and serum placental growth factor at 12, 22 and 32 weeks in prediction of pre-eclampsia. Placental perfusion in normal pregnancy and early and late preeclampsia: a magnetic resonance imaging study. Placental lesions associated with maternal underperfusion are more frequent in earlyonset than in late-onset preeclampsia. Placental histopathology associated with preeclampsia: a systematic review and metaanalysis. Frequency and clinical significance of placental histological lesions in an unselected population at or near term. Maternal cardiovascular function in normal pregnancy: evidence of maladaptation to chronic volume overload. Impact of soluble fms-like tyrosine kinase1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction. The importance of genetic and environmental effects for pre-eclampsia and gestational hypertension: a family study. Maternal cardiovascular impairment in pregnancies complicated by severe fetal growth restriction. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Prehypertension in pregnancy and risks of small for gestational age infant and stillbirth. Chapter 2 Cardiovascular and Volume Regulatory Functions in Pregnancy: An Overview Louis Peeters Summary Pregnancy induces a high flow and low-resistance circulation accompanied by plasma volume expansion and renal hyperfiltration. These adaptive changes develop in response to an induced reset of various cardiovascular and volume regulatory receptors. Although neither the trigger for receptor resetting nor the purpose of the adaptive changes is clear, their importance for normal pregnancy is emphasized by their often defective development in pregnancies later on complicated by "placental syndromes. In this context it should be stressed that defective maternal cardiovascular adaptation to pregnancy may be the cause, but also an effect of these syndromes. This article provides an update of our current insights into how pregnancy resets cardiovascular and volume receptors and how these adjustments interact with one another. Finally, the current insights in the cardiovascular and volume adaptation to pregnancy will be used to speculate on how abnormal adaptation to pregnancy can be predicted prior to pregnancy to identify women at risk of having a pregnancy complicated by a placental syndrome. Introduction the maternal adaptation to pregnancy is expected to create optimal conditions for the growth and development of the unborn child without jeopardizing maternal health. Although most healthy women adapt normally to pregnancy, late-onset pregnancy complications are often preceded by initial abnormal adaptation. Pregnancy induces major structural and functional changes in the maternal cardiovascular and volume regulatory systems. This article focuses on these changes, how they are triggered, when they reach their maximum effect, how they interact with other changes and, last but not least, how women at risk for defective adaptation can be identified before pregnancy. Mammalian pregnancy and parturition are natural processes that have been proven effective in the course of mammalian evolution. In natural conditions and without medical intervention, human pregnancy results in the birth of a healthy child in more than 80% of cases. Therefore, all maternal adaptive changes taking place in the course of pregnancy ought to be considered useful and necessary to achieve that one objective: healthy offspring without damaging maternal health. Nevertheless, it is a fact of life that the complex chain of events that begin at embryo implantation can be disturbed, eventually culminating in a pregnancy complication such as a placental syndrome or preterm birth. Obviously, our current insights into normal and defective adaptation to pregnancy are still incomplete. The values presented have been derived from various reports specified elsewhere [2]. The first systemic effect of pregnancy on the cardiovascular system is generalized vascular relaxation, which induces the following set of compensations: 1) baroreceptor activation to prevent a fall in blood pressure in response to the fall in cardiac afterload; 2) sodium and water retention to raise cardiac preload; 3) accelerated endothelial release of prostacyclin and nitric oxide to raise vascular compliance, so as to establish endothelial protection against the increased shear forces in the vascular bed; and 4) accelerated arteriovenous shunting to circumvent excessive influx of blood into the systemic capillary beds. These compensations enable the safe institution of a so-called "hyperdynamic circulation," defined as a raised cardiac output in the absence of a raised metabolic rate. One of the most prominent pregnancy-induced circulatory changes is the fall in systemic vascular tone [3, 4]. The mechanism responsible for this effect is only partly elucidated because of its complexity requiring the presence of a pregnancy-specific steroid environment together with an orchestrated concomitant set-point resetting of various regulatory systems for vascular tone and intravascular volume [5, 6, 7]. An updated overview of the events involved in the primary systemic vasodilatation of pregnancy is presented in Table 2. Indirect evidence suggests that the arterial baroreceptors located downstream in the arterial bed register "reduced transmural pressure" in response to the diminished effective arterial blood volume [4]. The acute response to the latter consists of vasoconstriction mediated by angiotensin-2, sympathetic mediators and vasopressin. In pregnancy the renal vasoconstriction in this mechanism is reversed to renal vasodilatation. The associated approximate 50% higher glomerular filtration rate maintains a relatively high distal tubular sodium and water delivery partly restricting their retention in favor of potassium conservation. The baroreceptors in the arterial bed and volume receptors in the atria and central veins reside in the vascular wall. This implies that their set-points are prone to change in conjunction with the overall pregnancy-induced rise in cardiovascular compliance. It is conceivable that the latter is responsible for the approximately 10 mmHg fall in diastolic blood pressure and approx. To our knowledge, there are no reports in support of a concomitant change in the responsiveness of the carotid baroreceptors. Resting cardiac output and total blood volume increase gradually in the first trimester of pregnancy to a plateau of 40% above the prepregnant level in the second 16 Section 1: Physiology of Normal Pregnancy Table 2. Until the 8th week of pregnancy cardiac output increases primarily by a rise in stroke volume. Additional rises in cardiac output afterwards are mostly achieved by a rise in heart rate. In the third trimester of pregnancy stroke volume decreases, most likely in conjunction with a rise in cardiovascular sympathetic tone. Throughout pregnancy both heart rate and stroke volume increase by about 20% [9, 10]. The hemodilution reduces the oncotic pressure of the circulating blood favoring fluid accumulation in the interstitial space. To our knowledge, it is still unclear whether the higher compliance in the arterial bed leads to a change in hydrostatic pressure at the level of the precapillary sphincters.

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Articular nerves transmit sensory impulses from the joint that contribute to the sense of proprioception spasms back pain and sitting purchase 100mg voveran sr otc, which provides an awareness of movement and position of the parts of the body muscle relaxant effects order voveran sr with a mastercard. Pain fibers are numerous in the fibrous layer of the joint capsule and the accessory ligaments muscle relaxant euphoria purchase voveran sr online pills, causing considerable pain when the joint is injured spasms right side under rib cage best purchase voveran sr. The sensory nerve endings respond to the twisting and stretching that occurs during sports activities yellow muscle relaxant 563 order voveran sr with a visa. A bulging fontanelle may indicate increased intracranial 142 pressure; however knee spasms at night buy voveran sr 100 mg lowest price, the fontanelle normally bulges during crying. A depressed fontanelle may be observed when the neonate is dehydrated (Swartz, 2014). Degenerative Joint Disease Synovial joints are well designed to withstand wear, but heavy use over several years can cause degenerative changes. Some destruction is inevitable during such activities as jogging, which wears away the articular cartilages and sometimes erodes the underlying articulating surfaces of the bones. The normal aging of articular cartilage begins early in adult life and progresses slowly thereafter, occurring on the ends of the articulating bones, particularly those of the hip, knee, vertebral column, and hands (Salter, 1998). These irreversible 143 degenerative changes in joints result in the articular cartilage becoming a less effective shock absorber and lubricated surface. As a result, the articulation becomes increasingly vulnerable to the repeated friction that occurs during joint movements. In some people, these changes do not produce significant symptoms; in others, they cause considerable pain. Degenerative joint disease or osteoarthritis is often accompanied by stiffness, discomfort, and pain. Osteoarthritis is common in older people and usually affects joints that support the weight of their bodies. Most substances in the bloodstream, normal or pathological, easily enter the joint cavity. Similarly, traumatic infection of a joint may be followed by arthritis, inflammation of a joint, and septicemia, blood poisoning. Arthroscopy the cavity of a synovial joint can be examined by inserting a cannula and an arthroscope (a small telescope) into it. This surgical procedure-arthroscopy- enables orthopedic surgeons to examine joints for abnormalities, such as torn menisci (partial articular discs of the knee joint). Because the opening in the joint capsule for inserting the arthroscope is small, healing is more rapid after this procedure than after traditional joint surgery. The Bottom Line Cartilage and bones: the skeletal system can be divided into the axial (bones of the head, neck, and trunk) and appendicular skeletons (bones of the limbs). The skeleton itself is composed of several types of tissue: cartilage, a semirigid connective tissue; bone, a hard form of connective tissue that provides support, protection, movement, storage (of certain electrolytes), and synthesis of blood cells; periosteum, which surrounds bones, and perichondrium, which surrounds cartilage, provide nourishment for these tissues and are the sites of new cartilage and bone formation. Bones grow through the processes of intramembranous ossification, in which mesenchymal bone models are formed during the embryonic and prenatal periods, and endochondral ossification, in which cartilage models are formed during the fetal period, with bone subsequently replacing most of the cartilage after birth. Joints: A joint is a union between two or more bones or rigid parts of the skeleton. Three general types of joints are recognized: fibrous, cartilaginous, and synovial. Freely moveable synovial joints are the most common type; can be classified into plane, hinge, saddle, condyloid, ball and socket, and pivot; receive their blood supply from articular arteries that often form networks; are drained by articular veins originating in the synovial membrane; and are richly innervated by articular nerves that transmit the sensation of proprioception, an awareness of movement and position of parts of the body. Types of Muscle (Muscle Tissue) Muscle cells, often called muscle fibers because they are long and narrow when relaxed, are specialized contractile cells. They are organized into tissues that move body parts or temporarily alter the shape (reduce the circumference of all or part) of internal organs. Associated connective tissue conveys nerve fibers and capillaries to the muscle cells as it binds them into bundles or fascicles. Three types of muscle are described based on distinct characteristics relating to 145 whether it is normally willfully controlled (voluntary vs. Skeletal striated muscle is voluntary somatic muscle that makes up the gross skeletal muscles that compose the muscular system, moving or stabilizing bones and other structures. Cardiac striated muscle is involuntary visceral muscle that forms most of the walls of the heart and adjacent parts of the great vessels, such as the aorta, and pumps blood. Smooth muscle (unstriated muscle) is involuntary visceral muscle that forms part of the walls of most vessels and hollow organs (viscera), moving substances through them by coordinated sequential contractions (pulsations or peristaltic contractions). The architecture and shape of a skeletal muscle depend on the arrangement of its fibers. When referring to the length of a muscle, both the belly and the tendons are included. Most skeletal muscles are attached directly or indirectly to bones, cartilages, ligaments, or fascias or to some combination of these structures. Muscles are organs of locomotion (movement), but they also provide static support, give form to the body, and provide heat. Most of the muscles shown move the skeleton for locomotion, but some 149 muscles-especially those of the head-move other structures. The sheath of the left rectus abdominis, formed by aponeuroses of the flat abdominal muscles, has been removed to reveal the muscle. Retinacula are deep fascial thickenings that tether tendons to underlying bones as they cross joints. The tendons of some muscles form flat sheets, or aponeuroses, that anchor the muscle to the skeleton (usually a ridge or a series of spinous processes) and/or to deep fascia (such as the latissimus dorsi muscle of the back) or to the aponeurosis of another muscle (such as the oblique muscles of the anterolateral abdominal wall). Most muscles are named on the basis of their function or the bones to which they are attached. Other muscles are named on the basis of their position (medial, lateral, anterior, posterior) or length (brevis, short; longus, long). Muscles may be described or classified according to their shape, for which a muscle may also be named: Flat muscles have parallel fibers often with an aponeurosis-for example, the external oblique (broad flat muscle). Fusiform muscles are spindle shaped with a round, thick belly (or bellies) and tapered ends-for example, biceps brachii. Convergent muscles arise from a broad area and converge to form a single tendon-for example, pectoralis major. Circular or sphincteral muscles surround a body opening or orifice, constricting it when contracted-for example, orbicularis oculi (closes the eyelids). Multiheaded or multibellied muscles have more than one head of 150 attachment or more than one contractile belly, respectively. When a muscle contracts and shortens, one of its attachments usually remains fixed while the other (more mobile) attachment is pulled toward it, often resulting in movement. Attachments of muscles are commonly described as the origin and insertion; the origin is usually the proximal end of the muscle, which remains fixed during muscular contraction, and the insertion is usually the distal end of the muscle, which is movable. For example, when doing push-ups, the distal end of the upper limb (the hand) is fixed (on the floor), and the proximal end of the limb and the trunk (of the body) are being moved. Therefore, this book usually uses the terms proximal and distal or medial and lateral when describing most muscle attachments. Note that if the attachments of a muscle are known, the action of the muscle can usually be deduced (rather than memorized). When studying muscle attachments, act out the action; you are more likely to learn things you have experienced. Reflexive Contraction Although skeletal muscles are also referred to as voluntary muscles, certain aspects of their activity are automatic (reflexive) and therefore not voluntarily controlled. Examples are the respiratory movements of the diaphragm, controlled most of the time by reflexes stimulated by the levels of oxygen and carbon dioxide in the blood (although we can willfully control it within limits), and the myotatic reflex, which results in movement after a muscle stretch produced by tapping a tendon with a reflex hammer. Tonic Contraction 151 Even when "relaxed," the muscles of a conscious individual are almost always slightly contracted. This slight contraction, called tonic contraction or muscle tone (tonus), does not produce movement or active resistance (as phasic contraction does) but gives the muscle a certain firmness, assisting the stability of joints and the maintenance of posture, while keeping the muscle ready to respond to appropriate stimuli. Muscle tone is usually absent only when unconscious (as during deep sleep or under general anesthesia) or after a nerve lesion resulting in paralysis. The latter type of contraction is important in maintaining upright posture and when muscles act as fixators or shunt muscles as described below. Isometric contraction (A) sustains the position of a joint without producing movement. Concentric (B) and eccentric (C) contractions are isotonic contractions in which the muscle changes length: concentric contractions by shortening and eccentric contractions by actively controlled lengthening (relaxation). The type we most commonly think of is concentric contraction, in which movement occurs as a result of the muscle shortening-for example, when lifting a cup, pushing a door, or striking a blow. The ability to apply exceptional force by means of concentric contraction often is what distinguishes an athlete from an amateur. The other type of isotonic contraction is eccentric contraction, in which a contracting muscle lengthens- that is, it undergoes a controlled and gradual relaxation while continually exerting a (diminishing) force, like playing out a rope. Often, when the main muscle of a particular movement (the prime mover) is undergoing a concentric contraction, its antagonist is undergoing a coordinated eccentric contraction. In walking, we contract concentrically to pull our center of gravity forward, and then as it passes ahead of the limb, we contract eccentrically to prevent a lurching during the transfer of weight to the other limb. Eccentric contractions require less metabolic energy at the same load but, with a maximal contraction, are capable of generating much higher tension levels than concentric contractions-as much as 50% higher (Marieb, 2016). When a motor neuron in the spinal cord is stimulated, it initiates an impulse that causes all the muscle fibers supplied by that motor unit to contract simultaneously. Large motor units, in which one neuron supplies several hundred muscle fibers, are in the large trunk and thigh muscles. In smaller eye and hand muscles, where precision movements are required, the motor units include only a few muscle fibers. Movement (phasic contraction) results from the activation of an increasing number of motor units, 154 above the level required to maintain muscle tone. A motor unit consists of a single motor neuron and the muscle fibers innervated by it. Actin (thin) and myosin (thick) filaments are contractile elements in the muscle fibers. It contracts concentrically to produce the 155 desired movement, doing most of the work (expending most of the energy) required. In most movements, there is a single prime mover, but some movements involve two prime movers working in equal measure. A fixator steadies the proximal parts of a limb through isometric contraction while movements are occurring in distal parts. It may directly assist a prime mover, providing a weaker or less mechanically advantaged component of the same movement, or it may assist indirectly, by serving as a fixator of an intervening joint when a prime mover passes over more than one joint, for example. It is not unusual to have several synergists assisting a prime mover in a particular movement. A primary antagonist directly opposes the prime mover, but synergists may also be opposed by secondary antagonists. As the active movers concentrically contract to produce a movement, antagonists eccentrically contract, relaxing progressively in coordination to produce a smooth movement. The same muscle may act as a prime mover, antagonist, synergist, or fixator under different conditions. In such cases, a paradoxical situation may exist in which the prime mover usually described as being responsible for the movement is inactive (passive), while the controlled relaxation (eccentric contraction) of the antigravity antagonist(s) is the active (energy requiring) component in the movement. The prime mover (adductor) is gravity; the muscles described as the prime movers for this movement (pectoralis major and latissimus dorsi) are inactive or passive; and the muscle being actively innervated (contracting eccentrically) is the deltoid (an abductor, typically described as the antagonist for this movement). Instead it acts to maintain contact between the articular surfaces of the joint it crosses. The deltoid becomes increasingly effective as a spurt muscle after other muscles have initiated abduction of the arm. Nerves supplying skeletal muscles (motor nerves) usually enter the fleshy portion of the muscle (vs. When a nerve pierces a muscle, by passing through its fleshy portion or between its two heads of attachment, it usually supplies that muscle. Exceptions are the sensory branches that innervate the skin of the back after penetrating the superficial muscles of the back. The blood supply of muscles is not as constant as the nerve supply and is usually multiple. Thus, you should learn the course of the arteries and deduce that a muscle is supplied by all the arteries in its vicinity. There are two common testing methods: the person performs movements that resist those of the examiner. For example, the person keeps the forearm flexed while the examiner attempts 157 to extend it. When testing flexion of the forearm, the examiner asks the person to flex his or her forearm while the examiner resists the efforts. The examiner places surface electrodes over a muscle, asks the person to perform certain movements, and then amplifies and records the differences in electrical action potentials of the muscles. A normal resting muscle shows only a baseline activity (muscle tone), which disappears only during deep sleep, during paralysis, and when under anesthesia. Muscle Dysfunction and Paralysis Wasting (atrophy) of muscle may result from a primary disorder of the muscle or from a lesion of the nerve that supplies it. Muscular atrophy may also be caused by immobilization of a limb, such as with a cast. From the clinical perspective, it is important not only to think in terms of the action normally produced by a given muscle but also to consider what loss of function would occur if the muscle failed to function (paralysis). Absence of Muscle Tone Although a gentle force, muscle tone can have important effects: the tonus of muscles in the lips helps keep the teeth aligned, for instance. When this gentle 158 but constant pressure is absent (due to paralysis or a short lip that leaves the teeth exposed), teeth migrate, becoming everted ("buck teeth").

The most obvious defensive mechanism is the flushing action of the urine flowing out of the system muscle relaxants kidney failure discount voveran sr 100 mg otc. The flow of urine also encourages the desquamation (shedding) of the epithelial cells lining the urinary tract spasms below rib cage order 100mg voveran sr mastercard. For example spasms pain rib cage buy genuine voveran sr on line, each time a person urinates muscle relaxant medication discount voveran sr 100mg free shipping, he or she loses hundreds of thousands of epithelial cells! Probably the most common microbial threat to the urinary tract is the group of microorganisms that constitute the normal biota in the gastrointestinal tract muscle relaxant pakistan generic voveran sr 100 mg visa, because the two organ systems are in close proximity muscle relaxant pharmacology voveran sr 100mg with mastercard. Urine, in addition to being acidic, also contains two antibacterial proteins, lysozyme and lactoferrin. Lactoferrin is an Urinary bladder iron-binding protein that inhibits bacterial Seminal vesicle growth. Finally, secretory IgA specific for previously encountered microorganisms Rectum can be found in the urine. The male reproductive system Ejaculatory duct produces, maintains, and transports Prostate gland Urethra sperm cells and is the source of male sex hormones. It consists of the testes, Bulbourethral gland which produce sperm cells and hormones, Penis Scrotum and the epididymides, which are coiled Anus tubes leading out of the testes. Each Vas deferens epididymis terminates in a vas deferens, Epididymis Glans penis which combines with the seminal Foreskin Testis vesicle and terminates in the ejaculatory duct (figure 23. The external organs are the Female Cross Section scrotum, containing the testes, and the penis, a cylindrical organ that houses the urethra. As for its innate defenses, the Fallopian (uterine) tube Vertebral column male reproductive system also benefits from the flushing action of the urine, Ovary which helps move microorganisms out of the system. The female reproductive system consists of the uterus, fallopian tubes Uterus (also called uterine tubes), ovaries, and vagina (figure 23. During Urinary Cervix of uterus bladder childbearing years, an egg is released from one of the ovaries approximately Symphysis Vagina pubis every 28 days. It enters the fallopian tubes, where fertilization by sperm Mons pubis may take place if sperm are present. Urethra Rectum the fertilized egg moves through the Clitoris fallopian tubes to the uterus, where it Anus is implanted in the uterine lining. If Urethral orifice fertilization does not occur, the lining of the uterus degenerates and sloughs Labia minora Vaginal orifice off; this is the process of menstruation. The opening is the exit tube for fluids from the uterus, the channel for of the uterus is part of the cervix. The cervix is a common site childbirth, and the receptive chamber for the penis during of infection in the female reproductive tract. One very important tissue of the female has shown an innate protective effect against viral infection reproductive tract is the cervix, which is the lower one-third of 23. The natural defenses of the female reproductive tract vary over the lifetime of the woman. The vagina is lined with mucous membranes and, thus, has the protective covering of secreted mucus. During childhood and after menopause, this mucus is the major nonspecific defense of this system. Secretory IgA antibodies specific for any previously encountered infections would be present on these surfaces. This hormone stimulates the vaginal mucosa to secrete glycogen, which certain bacteria can ferment into acid, lowering the pH of the vagina to about 4. Before puberty, a girl produces little estrogen and little glycogen and has a vaginal pH of about 7. The change in pH beginning in adolescence results in a vastly different normal biota in the vagina, described later. The biota of women in their childbearing years is thought to prevent the establishment and invasion of microbes that might have the potential to harm a developing fetus. Genomic analysis of aseptically obtained urine samples from women showed the presence of a variety of microorganisms. These included known residents of the urethra (nonhemolytic streptococci, staphylococci, corynebacteria, and some lactobacilli) and additionally Prevotella, Veillonella, and Gardnerella species. However, the exact microbial composition varied among men and among women, indicating that other variables play a role in establishing the normal biota within the urinary tract. In men, removal of the penile foreskin triggers a change in the composition of the known normal biota on the outer surface of the penis and perhaps in the urethra as well. Normal Biota of the Male Genital Tract With the easy access to whole-genome sequencing, a close inspection of the male genital tract microbiome is now under way. Recent studies have revealed that the normal biota of the male genital tract (that is, in the urethra) is composed of many of the same residents colonizing the external portions of the penis. In addition, Lactobacillus and Streptococcus species can be found in the urethra of most healthy men. In fact, men engaging in vaginal, anal, or even oral intercourse can often harbor bacteria that produce bacterial vaginosis in females. The kidney, ureters, bladder, and upper urethra were previously thought to be sterile. However, recent data suggest that some of these areas may actually contain microbiota that are simply unculturable using currently available Normal Biota of the Female Genital Tract Like other body systems we have studied, the most internal portions-in this case, the uterus and above-were long thought to be sterile. We do not know for sure how much and what Genitourinary Tract Defenses and Normal Biota Defenses Urinary Tract (Both Genders) Flushing action of urine; specific attachment sites not recognized by most nonnormal biota; shedding of urinary tract epithelial cells, secretory IgA, lysozyme, and lactoferrin in urine Mucus secretions, secretory IgA Normal Biota Nonhemolytic Streptococcus, Staphylococcus, Corynebacterium, Lactobacillus, Prevotella, Veillonella, Gardnerella Same as for urinary tract Female Genital Tract (Childhood and Postmenopausal) Female Gential Tract (Childbearing Years) Male Genital Tract Acidic pH, mucus secretions, secretory IgA Same as for urinary tract Variable, but often Lactobacillus predominates; also Prevotella, Sneathia, Streptococcus, and Candida albicans Urethra: same as for urinary tract; outer surface of penis: Pseudomonas and Staphylococcus; sulcus of uncircumcised penis: anaerobic gram-negatives 700 Chapter 23 Infectious Diseases Affecting the Genitourinary System kind of microbes colonize the upper female reproductive tract, but there are almost certainly either occasional "trespassers" or possibly more permanent residents. We do know that the adjacent vaginal canal is colonized by a diverse array of microorganisms. Before puberty and after menopause, the pH of the vagina is close to neutral, and the vagina harbors a biota that is similar to that found in the urethra. After the onset of puberty, estrogen production leads to glycogen release in the vagina, resulting in an acidic pH. The physical and chemical barriers of the vagina select for the growth of normal biota such as Lactobacillus species, which thrive in the acidic environment. But these microbes also contribute to the low pH environment, converting sugars to acid. Their predominance in the vagina, combined with the acidic environment, discourages the growth of many microorganisms and actually plays a major role in developing the overall composition of the vaginal biota. Even though the Lactobacilli dominate the normal biota of the vagina in most women, studies show that this is not the case in all women (Insight 23. Others show higher percentages of anaerobic bacteria such as Prevotella, Sneathia, or Streptococcus species. Scientists have shown that the microbial makeup can actually shift dramatically during the menstrual cycle and during pregnancy, and changes can even occur over just a few days. All of this information reflects the fact that there is no "core" or common vaginal biota composition during childbearing years and this microbiome is not always stable. Future studies will provide a better understanding of how these microorganisms maintain a healthy, disease-free vaginal canal over time. The estrogen-glycogen effect continues throughout the childbearing years until menopause. Genomic techniques have led to new findings about the normal biota in post-menopausal women. In contrast to women in their childbearing years, the normal biota composition in postmenopausal women appears to be stable over time. Although Lactobacillus and Gardnerella species are still common, there is a drop in other characteristic microbial species seen in premenopausal women. It has also been noted that the number of Lactobacilli decreases as vaginal dryness increases, which opens a new door to investigate shifts in microbial composition in women suffering from this common symptom of menopause. Note that the very common fungus Candida albicans is also present at low levels in the healthy female reproductive tract. List the types of normal biota presently known to occupy the genitourinary tracts of both genders. Disturbances in the microbiome change the pH of the vagina, inhibit fertility, cause spontaneous abortions, and induce early-term delivery. Currently, 30% of American women have abnormal vaginal microbiomes; the rates are as high as 60% in inner-city populations. Many women who have it have no symptoms at all, and it only exerts its influence when women try to get pregnant or during pregnancy or delivery. The causes of the condition are poorly understood, but douching, smoking, obesity, stress, and high numbers of sexual partners have all been associated with it. And African-American women have been shown to douche at twice the rate of Caucasian women. Some physicians feel that there is a direct link between this practice and the unusually high rates of preterm delivery and infant mortality in many urban areas. Gregor Reid thinks that if the vaginal microbiome were to suddenly shift across the human population, it would not be unreasonable to expect that the human race to go extinct. A few years ago, a scientist named Gregor Reid made a provocative statement to a meeting of the American Society for Microbiology. He said, "To not place a huge focus on the human vaginal microbiome is like putting human survival at risk. Leptospirosis, by contrast, is a spirochete-caused disease transmitted by contact of broken skin or mucous membranes with contaminated animal urine. Lastly, we discuss a helminth disease, urinary schistosomiasis, that is very common in a large percentage of developing countries. When urine flow is reduced, or bacteria are accidentally introduced into the bladder, an infection of that organ (known as cystitis) can occur. Occasionally, the infection can also affect the kidneys, in which case it is called pyelonephritis. They are much more common in women than in men because of the nearness of the female urethral opening to the anus (see figure 23. Many women experience what have been referred to as "recurrent urinary tract infections," although it is now known that some E. It is not clear how many "recurrent" infections are actually infections that reactivate in this way. The National Healthcare Safety Network is now recommending minimizing the use of urinary catheters as much as possible to limit the incidence of these infections. Symptoms include pain, frequent urges to urinate even when the bladder is empty, and burning pain accompanying urination (called dysuria). If back pain is present and fever is high, it is an indication that the kidneys may also be involved (pyelonephritis). Pyelonephritis is a serious infection that can result in permanent damage to the kidneys if improperly or inadequately treated. If there is a lot of resistance to this treatment in the local area, other drugs must be used. Often, another nonantibiotic drug called phenazopyridine (Pyridium) is administered simultaneously. However, some physicians are reluctant to administer this medication for fear that it may mask worsening symptoms; when Pyridium is used, it should be taken only for a maximum of 2 days. Medical professionals are ringing alarm bells about this strain, saying that if it acquires resistance to one more classes of antibiotics, it will become virtually untreatable (Disease Table 23. Escherichia coli is by far the most common of these, accounting for approximately 80% of community-acquired urinary tract infections. Leptospirosis this infection is a zoonosis associated with wild animals and domesticated animals. It is considered in this section because it can have its major effects on the kidneys and because its presence in animal urinary tracts causes it to be shed into the environment through animal urine. During the early-leptospiremic- phase, the pathogen appears in the blood and cerebrospinal fluid. Symptoms are sudden high fever, chills, headache, muscle aches, conjunctivitis, and vomiting. During the second-immune-phase, the blood infection is cleared by natural defenses. Long-term disability and even death can result from damage to the kidneys and liver, but they occur primarily with the most virulent strains and in elderly persons. There are nearly 200 different serotypes of this species distributed among various animal groups, which accounts for extreme variations in the disease manifestations in humans. Pathogenesis and Virulence Factors Leptospires are typical spirochete bacteria marked by tight, regular, individual coils with a bend or hook at one or both ends (figure 23. Leptospira interrogans (lep-toh-spy-rah in-terroh-ganz) is the species that causes leptospirosis in humans and In 2003, Chinese scientists sequenced the entire genome of this bacterium and found a series of genes that code for virulence factors such as adhesins and invasion proteins. These factors allow the pathogen to rapidly penetrate host cells and enter into the bloodstream and enable the bacterium to cause cell death in kidney tissue. Because it appears that the bacterium evolved from its close relatives, which are free-living and cause no disease, finding out how the bacterium acquired these genes will be useful in understanding its pathogenesis. The green disk is a piece of filter paper, and the holes are the pores of the filter. Leptospires that are shed in the urine of an infected animal can survive for several months in neutral or alkaline soil or water. Infection occurs almost entirely through contact of skin abrasions or mucous membranes with animal urine or some environmental source containing urine. In 1998, dozens of athletes competing in the swimming phase of a triathlon in Illinois contracted leptospirosis from the water. In late 2009, the Philippines experienced a major outbreak after a series of typhoons flooded the country. Signs and Symptoms A preventive vaccine for humans is being investigated, though a protective vaccine for animals is used to reduce the spread of the pathogen. For now, the best prevention is to wear protective footwear and clothing and to avoid swimming and wading in natural water sources that are frequented by livestock. Anyone participating in aquatic recreational activities should be aware of this infection, especially in more tropical regions of the world. Treatment As with the other forms of schistosomiasis, the first symptoms of infestation are itchiness in the area where the helminth enters the body, followed by fever, chills, diarrhea, and cough.