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By W. Kafa. Century University.

Each skeletal muscle has three layers of connective tissue (called “mysia”) that enclose it and provide structure to the muscle as a whole naproxen 250 mg with amex, and also compartmentalize the muscle fibers within the muscle (Figure 10 naproxen 500 mg on line. Each muscle is wrapped in a sheath of dense, irregular connective tissue called the epimysium, which allows a muscle to contract and move powerfully while maintaining its structural integrity. The epimysium also separates muscle from other tissues and organs in the area, allowing the muscle to move independently. Inside each skeletal muscle, muscle fibers are organized into individual bundles, each called a fascicle, by a middle layer of connective tissue called the perimysium. This fascicular organization is common in muscles of the limbs; it allows the nervous system to trigger a specific movement of a muscle by activating a subset of muscle fibers within a bundle, or fascicle of the muscle. Inside each fascicle, each muscle fiber is encased in a thin connective tissue layer of collagen and reticular fibers called the endomysium. In skeletal muscles that work with tendons to pull on bones, the collagen in the three tissue layers (the mysia) intertwines with the collagen of a tendon. The tension created by contraction of the muscle fibers is then transferred though the mysia, to the tendon, and then to the periosteum to pull on the bone for movement of the skeleton. In other places, the mysia may fuse with a broad, tendon-like sheet called an aponeurosis, or to fascia, the connective tissue between skin and bones. The broad sheet of connective tissue in the lower back that the latissimus dorsi muscles (the “lats”) fuse into is an example of an aponeurosis. Every skeletal muscle is also richly supplied by blood vessels for nourishment, oxygen delivery, and waste removal. In addition, every muscle fiber in a skeletal muscle is supplied by the axon branch of a somatic motor neuron, which signals the fiber to contract. Unlike cardiac and smooth muscle, the only way to functionally contract a skeletal muscle is through signaling from the nervous system. Skeletal Muscle Fibers Because skeletal muscle cells are long and cylindrical, they are commonly referred to as muscle fibers. Skeletal muscle fibers can be quite large for human cells, with diameters up to 100 μm and lengths up to 30 cm (11. During early development, embryonic myoblasts, each with its own nucleus, fuse with up to hundreds of other myoblasts to form the multinucleated skeletal muscle fibers. Multiple nuclei mean multiple copies of genes, permitting the This OpenStax book is available for free at http://cnx. Some other terminology associated with muscle fibers is rooted in the Greek sarco, which means “flesh. As will soon be described, the functional unit of a skeletal muscle fiber is the sarcomere, a highly organized arrangement of the contractile myofilaments actin (thin filament) and myosin (thick filament), along with other support proteins. The Sarcomere The striated appearance of skeletal muscle fibers is due to the arrangement of the myofilaments of actin and myosin in sequential order from one end of the muscle fiber to the other. Each packet of these microfilaments and their regulatory proteins, troponin and tropomyosin (along with other proteins) is called a sarcomere. The sarcomere itself is bundled within the myofibril that runs the entire length of the muscle fiber and attaches to the sarcolemma at its end. Each sarcomere is approximately 2 μm in length with a three- dimensional cylinder-like arrangement and is bordered by structures called Z-discs (also called Z-lines, because pictures are two-dimensional), to which the actin myofilaments are anchored (Figure 10. Because the actin and its troponin- tropomyosin complex (projecting from the Z-discs toward the center of the sarcomere) form strands that are thinner than the myosin, it is called the thin filament of the sarcomere. Likewise, because the myosin strands and their multiple heads (projecting from the center of the sarcomere, toward but not all to way to, the Z-discs) have more mass and are thicker, they are called the thick filament of the sarcomere. Excitation-Contraction Coupling All living cells have membrane potentials, or electrical gradients across their membranes. They do this by controlling the movement of charged particles, called ions, across their membranes to create electrical currents. Although the currents generated by ions moving through these channel proteins are very small, they form the basis of both neural signaling and muscle contraction. Both neurons and skeletal muscle cells are electrically excitable, meaning that they are able to generate action potentials. An action potential is a special type of electrical signal that can travel along a cell membrane as a wave. Although the term excitation-contraction coupling confuses or scares some students, it comes down to this: for a skeletal muscle fiber to contract, its membrane must first be “excited”—in other words, it must be stimulated to fire an action potential. Once released, the Ca interacts with the shielding proteins, forcing them to move aside so that the actin-binding sites are available for attachment by myosin heads. In skeletal muscle, this sequence begins with signals from the somatic motor division of the nervous system. In other words, the “excitation” step in skeletal muscles is always triggered by signaling from the nervous system (Figure 10.

The contraction of the walls of the atria is completed at the time the contraction of the ventricles begins naproxen 500 mg on line. Thus purchase naproxen 250mg fast delivery, the resting phase (diastole) begins in the atria at the same time as the contraction (systole) begins in the ventricles. After the ventricles have emptied, both chambers are relaxed for a short period of time as they fill with blood. The fibers are interwoven so the stimulation that causes the contraction of one fiber results in the contraction of the whole group. As more blood enters the heart, as occurs during exercise, the muscle contracts, with greater strength so push the larger volume of blood out into the blood vessels. It is determined by the volume of blood ejected from the ventricle with each beat−the stroke 265 Human Anatomy and Physiology volume−and the number of beats of the heart per minute−the heart rate. The Conduction System of the Heart The cardiac cycle is regulated by specialized areas in the heart wall that forms the conduction system of the heart. Two of these areas are tissue mass called nodes; the third is a group of fibers called the atrioventricular bundle. The sinoatrial node, which is located I the upper wall of the right atrium an initiates the heart beat, is called the pacemaker. The second node, located in the ineratrial septum at the bottom of the right atrium, is called the atrioventricular node. The atrioventricular bundle, also known as the bundle of His, is located at the top of the interventricular septum; it has branches that extend to all parts of the ventricle walls. Fibers travel first down both sides of the interventricular septum in groups called the right and left bundle branches. Smaller Purkinje fibers then travel in a branching network throughout the myocardium of the ventricles (Figure 9- 6). The relatively slower conduction through this node allows time for the atria to contract and complete the filling of the ventricles. The excitation wave travels rapidly through the bundle of His and then throughout the ventricular walls by means of the bundle branches and Purkinje fibers. As a safety measure, a region of the conduction system other than the sinoatrial node fails, but it does so at a slower rate. Recall from chapter 7 that stimulation from the sympathetic nervous system increases the heart rate and the stimulation from the parasympathetic nervous system decreases the heartrate. During rest and sleep, the heart may beat less than 60 beats/minute but usually does not fall below 50 beats/minute. Sinus arrhythmia is a regular variation in heart rate due to changes in the rate and depth of breathing. Premature beats, also called extrasystoles are beats that come in before the the expected normal beats. It occurs at the beginning of ventricular relaxation and is due in large part to sudden closure of the semilunar valves. The many conditions that can cause abnormal heart sounds include congenital defects, disease, and physiological variations. A murmur due to rapid filling of the ventricles is called a functional (flow) murmur; such a murmur is not abnormal. An abnormal sound caused by any structural change in the heart or the vessels connected with the heart is called an organic murmur. Blood Vessels Functional classification The blood vessels, together with the four chambers of the heart, from a closed system for the flow of blood; only if there 269 Human Anatomy and Physiology is an injury to some part of the wall of this system does any blood escape. Arteries carry blood from the ventricles (pumping chambers) of the heart out to the capillaries in organs and tissue. Capillaries allow for exchanges between the blood and body cells, or between the blood and air in the lung tissues. Because the thicker muscle layer in the artery wall is able to resist great pressures generated by ventricular systole. In arteries, the tunica medial plays a critical role in maintaining blood pressure and controlling blood distribution in the body. This is 270 Human Anatomy and Physiology a smooth muscle, so it is controlled by the autonomic nervous system. A thin layer of elastic and white fibrous tissue covers an inner layer of endothelial cells called the tunica interna in arteries and veins. The tunica interna is actually a single layer of squamous epithelial cells called endothelium that lines the inner surface of the entire circulatory system. The most important structural feature of capillaries is their extreme thinness−only one layer of flat, endothelial cells composes the capillary membrane. Substances such as glucose, oxygen, and wastes can quickly pass through it on their way to or from the cells. Smooth muscle cells that are called precapillary sphincters guard the entrance to the capillary and determine into which capillary blood will flow. It continues down behind the heart just in front of the vertebral column, through the diaphragm, and into the abdomen (Figure 9-8 and 9-9).

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The meta-analysis yielded a statistically significant pooled effect (standardized mean difference) of 0 250mg naproxen. Treatment effects consistently favored intranasal corticosteroid for all patients reporting this outcome buy naproxen 250mg amex. The one trial excluded from the meta-analysis did not alter the precision assessment because this trial represented 1 percent of patients reporting this outcome. The body of evidence supporting a conclusion of equivalence of intranasal corticosteroid and leukotriene receptor antagonist for this outcome is therefore considered precise. All comparisons favored intranasal corticosteroid and were statistically significant. The risk of bias for this outcome was rated as low based on the good quality of the trial reporting. Evidence was therefore insufficient to support the use of one treatment over the other for this outcome. One was a good quality trial in 573 patients (95 percent of patients reporting this outcome) that reported 4-week outcomes. A statistically significant treatment effect of 28 points on a 0-400 scale (7 percent of 128 maximum score) favored intranasal corticosteroid. The other was a poor quality trial that reported outcomes (mean results during the previous 2 weeks) at 5 and 8 weeks. Evidence was insufficient to support the use of one treatment over the other for this outcome. Asthma Symptoms 127 One good quality trial (N=573) assessed symptoms and objective measures of asthma over 4 weeks of treatment. There were no statistically significant differences between treatment groups in any outcome, nor were there differences when treatment groups were stratified by baseline asthma severity. For all outcomes, the risk of bias was rated as low, and consistency could not be assessed with a single trial. Treatment effects favoring oral leukotriene receptor antagonist were: Proportion of symptom-free days: 1. Because neither result was statistically significant, evidence was insufficient to support the use of one treatment over the other for these outcomes. Evidence was insufficient to support the use of one treatment over the other for these outcomes. For asthma exacerbations, any reduction in severe exacerbations may be considered clinically 70, 135 significant. Because the definition of “asthma exacerbation” used in this trial is broad, the severity of exacerbations observed is unclear. Further, the outcome measure reported patients rather than number of exacerbations; it is unclear whether exacerbations were in fact reduced. The effect is therefore considered imprecise and the evidence insufficient to support the use of one treatment over the other for this outcome. Congestion at 2 weeks: meta-analysis of 3 trials–intranasal corticosteroid versus oral leukotriene receptor antagonist Figure 17. Rhinorrhea at 2 weeks: meta-analysis of 3 trials–intranasal corticosteroid versus oral leukotriene receptor antagonist Figure 18. Sneezing at 2 weeks: meta-analysis of 3 trials–intranasal corticosteroid versus oral leukotriene receptor antagonist 103 Figure 19. Nasal itch at 2 weeks: meta-analysis of 3 trials–intranasal corticosteroid versus oral leukotriene receptor antagonist Figure 20. Total nasal symptom score at 2 weeks: meta-analysis of 4 trials–intranasal corticosteroid versus oral leukotriene receptor antagonist 104 Table 38. Two trials 98 130 were 2-week, double-blinded, multicenter trials in North America, and one was a 4-week, patient-blinded, single center trial in Europe. Oral selective antihistamines studied were 90, 98 130 loratadine (two trials ) and cetirizine (one trial ); intranasal corticosteroids were 90, 130 98 90, 98 mometasone (two trials ) and fluticasone propionate (one trial ). Two trials were 130 industry funded, and one was funded by a national health system. In the one trial that reported on race, 77 percent were white, and 18 percent were Hispanic. Baseline severity of nasal symptoms was mild 130 90 98 to moderate, moderate, and moderate to severe. One also assessed individual nasal symptoms (congestion, 90, 130 98, 130 rhinorrhea, sneezing, and itching), two also assessed eye symptoms, and two also assessed quality of life. For the assessment of nasal 90, 130 130 symptoms, two trials used an interval scale.

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On the other hand 250mg naproxen with visa, the system is subverted by pathogens like Shigella flexneri or Salmonella typhimurium purchase naproxen 500 mg line, which misuse the transport system to penetrate the eipthelial barrier. In addition, the spleen is involved in red blood cell quality control: red blood cells have to squeeze through narrow passageways between phagocytes. If a majority of red blood cells are a little too stiff for other reasons, for instance sickle cell deformity, hemolytic anemia ensues. In summary, peripheral lymphatic organs and tissues are spaces where • antigen (bacteria, viruses, fungi, parasites and their degradation products) • antigen-presenting cells • B cells • T cells are brought together to launch an adaptive immune response. T cells are central in immunology, yet our understanding of T cell subtypes and functions is without doubt grossly incomplete. When 27 considering T cell functions in the following sections, please always keep in mind that we are dealing with very simplified models. Interestingly, in our body we find all of these cell types also in a form lacking the T cell receptor. We already encountered one of these cell types: natural killer cells act like cytotoxic T cells, but do not express a T cell receptor. Two polypeptide chains (normally α:β, alternatively γ:δ) form a plump rod-like structure with a variable region at the end. Rearrangement of β-chains (chromosome 7q) involves V, D and J 28 segments, analogous to the immunoglobulin heavy chain. T cell diversity is thus generated by the same molecular mechanisms as immunoglobulin diversity, with the exception of somatic hypermutation which does not occur in T cells. This term was coined for a genetic locus on the short arm of chromosome 6 that proved decisive for rejection or acceptance of transplanted tissue. In case of malignant transformation, proteins may be expressed that normally are only expressed in early fetal development and thus unknown to the immune system. In normal protein turnover, cellular proteins are subject to proteasome degradation, resulting in cytoplasmic peptides. Their peptide binding cleft is blocked by a separate protein chain, the invariant chain, to prevent endogenous peptides from being inserted. Most of these differences cluster around the binding cleft, modifying its preference for specific peptides. As both contribute to the phenotype and none dominates over the other, we call this co-dominant expression. As evolution resulted in this extreme form of polymorphism, it has to involve some selectable advantage. The solution: very strong and continuous binding results in a qualitatively different signal, inducing the thymocyte to undergo apoptosis. In a population of European descent, about 5% developed a hypersensitivity syndrome 1-5 weeks following 31 initiation of therapy. Given a "free pass" through the epithelial barrier, the bacteria first proliferate fairly quickly, although non-adaptive defense mechanisms start virtually instantaneously. Complement is activated via alternative and/or lectin pathways, chemotactically attracting the first few neutrophils and macrophages. In response, these antigen-presenting cells reprogram their gene expression pattern: they produce novel transmembrane proteins, e. Together with complement fragments and kinins, phagocyte- released mediators cause local inflammation. Combined with increased endothelial permeability, this causes local swelling and an increase in lymph drainage, carrying bacteria as well as macrophages to the local lymph nodes. In the lymph node, dendritic cells and macrophages arrive with lots of peptides in their late endosomes and phagolysosomes, having ingested and chopped down entire bacteria or parts of them. In the lymph node, also the B cells are showered with bacterial material swept in by the lymph stream. For most of the B cells, their randomly-generated B cell receptors (membrane- anchored immunoglobulin) are not activated. In the rare event that a B cell receptor finds a match in a bacterial fragment, this is signaled into the cell, and the receptor plus attached antigen are internalized in a vesicle. The invading bacterium will have a few main proteins, increasing the chance that these will end up in all macrophages and a few B cells. Take ten cells on each side, and a match is unlikely; take 10 million, and a match is virtually assured. Others form the germinal center of a secondary follicle, trying to hang on with their B cell receptors to the limited amount of antigen fixed on the outside of follicular dendritic cells. They compete for the antigen like guests compete for delicacies at a somewhat sparingly stocked cold buffet. Other clonal daughter cells leave the lymph node via efferent lymphatics, enter the blood and eventually settle in the bone marrow as plasma cells, producing antibody there. They enhance and focus already active defense mechanisms: they activate complement far more efficiently, opsonize, neutralize. Even after the pathogen has been successfully eradicated, plasma cells continue to produce immunoglobulins, providing protection against reinfection for a long time.

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