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The tail of the caudate nucleus continues where voluntary intended movements can occur from the body and arches downward and for- coincidently with involuntary unintended move- ward into the temporal lobe buy cytoxan 50mg online, where it eventu- ments buy cytoxan 50mg overnight delivery. The basal ganglia are the corpus striatum ally becomes continuous with the amygdaloid (in the cerebral hemisphere) order cytoxan 50 mg without prescription, the subthalamic nucleus (Fig discount cytoxan master card. The globus pallidus is located between The corpus striatum is subdivided anatomically the putamen and the internal capsule and is into the caudate and lentiform nuclei. These divided into lateral (outer) and medial (inner) two large nuclear masses are deep within the segments. Inferiorly, the putamen fuses with the the thalamus and lateral to the hypothalamus. In brain slices, the alter- dorsomedially, and (3) the subthalamic nucleus nate strands of gray and white matter provide ventrally (Fig. The subthalamic nucleus the striated appearance for which the corpus appears as a prominent biconvex structure nes- striatum was named. As a result, the corpus striatum consists a more dorsal compact part and a more ventral of the caudate nucleus, the putamen, and the reticular part. The compact part contains neu- globus pallidus structurally, but the striatum and rons flled with melanin, which accounts for the pallidum functionally (Fig. Reticular nigra neurons scattered through the most rostral part neurons are morphologically, physiologically, and of the cerebral crus and its continuation with the functionally identical to medial pallidal neurons. A Internal capsule Body of caudate nucleus Lateral view B B Dorsal section 8-2B C C Ventral section 8-2B Head of caudate nucleus Tail of caudate nucleus Putamen Amygdaloid nucleus Body of caudate nucleus B B Dorsal section 8-2B C C Ventral section 8-2B Head of caudate Medial view nucleus Accumbens Tail of caudate nucleus nucleus Putamen Amygdaloid nucleus Lat. Left lateral and right medial views of the corpus striatum and amygdaloid nucleus. Horizontal section through ventral level of corpus striatum (ant, anterior; cap, capsule; inf, inferior; int, internal; lat, lateral; med, medial; nucl, nucleus; post, posterior; vent, ventricle). Virtually all areas of Overview the cerebral cortex project in an orderly manner The basal ganglia link with the thalamus and to the striatum. These corticostriate projections cerebral cortex through a number of segregated reach the caudate nucleus and putamen directly topographically organized parallel circuits that from the adjacent white matter, most via the ante- subserve different functions. Corticostriatal circuit emphasized in this chapter focuses on projections from motor, premotor, and somatosen- pathways through the basal ganglia that regu- sory areas of the cerebral cortex project somato- late voluntary movements through thalamo- topically to the putamen. A thalamic input to the cortical projections to premotor, supplementary striatum arises in the intralaminar nuclei. The most important connections between indi- The connections of the basal ganglia (Fig. From the The pallidum and subthalamic nucleus are compact nigra arises the nigrostriatal projection, interconnected by the subthalamic fasciculus, which terminates in the caudate nucleus and a small bundle that intersects with the internal putamen in a manner reciprocal to the striatoni- capsule, where it separates these two nuclei. Pallidothalamic Limb projections Thalamic fasciculus Striatopallidal projection Subthalamic fasc. Subthalamic nucleus Inhibitory synapse Substantia nigra A Excitatory synapse Figure 8-8 A. Thalamic fasciculus Ansa lenticularis Subthalamic nucleus Compact Substantia Reticular nigra B Figure 8-8 (Continued) B. Position of pallidothalamic projections (ant, anterior; caps, capsule; fasc, fasciculus; int, internal; lat, lateral; med, medial; nucl, nucleus; post, posterior; vent, ventricle). The lenticular Extending from all parts of the striatum to all fasciculus arises from the dorsal surface of the parts of the pallidum are abundant striatopallidal medial pallidum (Fig. Striatopallidal projections can be either tially through the posterior limb of the internal direct or indirect. Medium spiny neurons with D1 capsule, and then passes through the subthala- receptors project to the medial pallidum, whereas mus where it is located between the subthalamic striatal neurons with D2 receptors project to the nucleus and zona incerta (Fig. The corticostriate and lenticularis arises from the ventral surface of the striatopallidal projections are topographically org- medial pallidum (Fig. Thus, ultimately, the is the medial pallidum, which exerts a strong basal ganglia infuence movements through the infuence on the thalamus. The pallidum and the reticu- in the ventral anterior nucleus and appear to be lar nigra inhibit the ventral anterior thalamic mainly concerned with head and eye movements. The ventral anterior nucleus activates the premo- tor cortex with glutamate as the neurotransmitter. This inhibition appears to have facilitatory effects on striatal neu- is differentially modulated by parallel activity in rons with D1 receptors and depressant effects on the direct and indirect pathways from the striatum others with predominately D2 receptors. Conversely, cortical rons and the suppression of undesired movements activation of other striatal neurons in the indirect by selective inhibition of other thalamocortical pathway results in striatal inhibition of lateral palli- projection neurons. Striatal neurons in the direct of the basal ganglia are the result of an imbalance pathway have D1 receptors that facilitate activity in activity in the direct and indirect pathways as in this circuit, whereas striatal neurons in the indi- a result of the loss of control normally exerted on rect pathway have D2 receptors that decrease activ- the striatum by the substantia nigra or on the pal- ity in the circuit. Cortical activation of the direct the cerebral cortex receives the sensory input, and pathway in due course disinhibits thalamic neurons its association areas generate the will to move. Concurrent a desired action and the concomitant suppression activation of the indirect pathway will lead to of conficting movements. The striatum permits inhibition of different thalamic neurons that may and controls movement through the chief efferent be involved in competing movement programs. Both are manifestations of the The premotor cortex programs complex voluntary “release” phenomena, the loss of pallidal inhibi- movements through connections with the motor tion of thalamic neurons. Honing of tone in basal ganglia disorders usually take the striatal and pallidal output occurs through recip- form of hypertonicity. In severe cases, there is rocal connections with the substantia nigra and rigidity in which the tone in all of the muscles the subthalamic nucleus, respectively. In such cases, the Abnormalities of the basal ganglia result in increased resistance to passive stretch is bidirec- negative and positive signs. The negative signs tional and occurs throughout the range of the are actions the patient wants to perform but can- movement. The frequency of the abnormal neurons can no longer elicit an activ- jerks corresponds to the frequency of the tremors. The positive signs occur because of the loss of The hypertonicity in this case is termed cogwheel control or the release of other parts of the motor rigidity. Dyskinesias Dyskinesias take the form of tremors, chorea, ath- Negative Signs etosis, ballismus, and tics. Tremors are rhythmic Negative signs of basal ganglia disease include or oscillatory movements in the distal parts of the akinesia, bradykinesia, and abnormal postural limbs, such as the hands. Akinesia refers to the hesitancy movements in the more distal parts of the limbs and in starting a movement and bradykinesia to the in the face. Athetosis is slow, writhing, or snake- slowness with which the movement is executed. Ballismus is violent Neither occurs because of paresis or paralysis; finging movements of the entire limb as a result these signs do not exist in basal ganglia disorders. Abnormal postural adjustments take the form Tics are stereotypical and repetitive movements of head and trunk fexion and the incapacity to involving several muscle groups simultaneously. A movements occur against the will of the patient form of abnormal postural adjustments is seen in and can neither be prevented from starting nor dystonia, in which unusual fxed postures occur interrupted once they do start. It is thought that altered occurs in Parkinson disease, also called paralysis impulse activity in the direct pathway results in agitans, the best-known basal ganglia disease and increased inhibition of thalamic neurons result- the disease described in the case at the beginning ing in decreased thalamocortical activity in of this chapter. The rigidity is more prominent in the Positive signs of basal ganglia disease include advanced stages of the disease. The akinesia and alterations in muscle tone and various forms bradykinesia are so severe that movements are Chapter 8 The Basal Ganglia: Dyskinesia 99 initiated and carried out very slowly; in fact, the interrupt the abnormal basal ganglia output that patient appears almost paralyzed. In advanced stages, ablative procedures for the surgi- handwriting becomes small and speech is reduced cal treatment of movement disorders. Immediate improvements self-stimulating electrodes into the subthalamic in voluntary movements and diminished nuclei are being used to treat severe tremors in rigidity are apparent under optimal stimulus advanced parkinsonian patients. This progressive disorder is acquired by inheriting a dominant gene and is caused by degeneration of striatal neurons. Neuronal degeneration may also occur in the cerebral cortex; such patients suffer progressive dementia. In fact, athetosis and cho- movements rea, or intermediate forms of the two (choreoath- etosis), are frequently encountered.

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Implementation of the population-based approach to cholesterol lowering requires the input and cooperation of a number of types of institutions order 50mg cytoxan fast delivery. The government must be involved in improved food labeling and oversight of food assistance programs cheap generic cytoxan canada. Schools must be involved by creating an improved environment for both eating and physical activity generic cytoxan 50mg fast delivery. Health professionals should serve as resources for their communities and schools as they develop educational and other risk-reduction programs discount 50 mg cytoxan amex. In addition, the media can be helpful in the promotion of a healthful diet and increased levels of physical activity. Individual Approach The individual approach is directed at identifying children and adolescents who are at higher risk of future cardiovascular disease and treating them to lower their risk. This approach is probably most important from the standpoint of the pediatrician and the pediatric cardiologist. Identification To initiate the individual high-risk strategy, it is necessary to identify those children who are at higher risk of cardiovascular disease. This approach is directed at identifying children who are likely to have genetic dyslipidemias, who are at highest risk. The use of this score is dependent on all adults having their risk factors including cholesterol measured on a regular basis. These values can then be used in an equation to estimate risk of a cardiovascular event over the next 10 years. To construct a similar risk score for children would require large-scale longitudinal studies with complete follow-up in which risk factor levels are measured in childhood and subjects are followed until the occurrence of cardiovascular end points in adulthood. This means that a different strategy will be needed to identify children at high risk. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. In general, these investigations have found that from 35% to 46% of adolescents would have cholesterol measurements based on their family history. These studies have also shown that many children with elevated cholesterol will be missed using a screening approach based on their family history. It is likely that this approach will miss 30% to 60% of pediatric patients with elevated cholesterol (155,156,157). Difficulties with using the family history as a trigger for screening include that the family history may be incomplete or inaccurate. The family history would be more useful if all parents and grandparents knew their cholesterol levels, but, unfortunately, this is often not the case. In addition, parents (and sometimes grandparents) of younger children are often too young themselves to have reached the age when they are at greatest risk for a myocardial infarction or a stroke (157). These problems with a targeted approach to screening have led to the recommendation of universal screening of all children at 9 to 11 years of age (158). In addition, children aged 2 years or older should have a lipid profile if they have a family history of premature cardiovascular disease (prior to age 55 in men or age 65 in women) or of dyslipidemia or with other cardiovascular disease risk factors, such as diabetes, hypertension, or obesity (90). This use across a broad age range is recommended despite the fact that there is considerable variation of cholesterol with age during growth and development. However, it has been shown that the proposed single cutpoints work well in practice (161). Initially, this treatment should focus on improved diet with lower saturated fat and cholesterol. The recommended levels for treatment with pharmacologic agents are presented in Table 71. Treatment The mainstay of all treatment for dyslipidemia is alteration of lifestyle including diet and the level of physical activity. The initial approach is to use the population-based diet, but to do so more aggressively and with the aid of a dietitian. Dietitians can be helpful both in providing education about the fat and cholesterol content of foods and in providing behavioral strategies that improve the likelihood that the recommended diet will be adopted by the family and the pediatric P. Parents can promote improvement in diet by making healthful foods available in the home and restricting the availability of foods that are high in energy density, fat, saturated fat, cholesterol, and simple sugars (162). Research has supported the concept that children will choose to eat foods that are available (163,164). It is important for children to try new foods multiple times to develop familiarity with and ultimately have a preference for these foods. A minimum of 8 to 10 exposures to new foods may be required before preference for these foods increases and is established (165,166). The intervention group received behavioral intervention focused on adherence to a Step 2 Diet. This involved sessions with the family from 4 to 12 times per year over a 3-year period (169). It is encouraging that a 7-year follow-up showed that the intervention effect was maintained and that growth and development continued to be normal in the intervention group (169). This emphasizes the concept that these changes can be made in practice in a safe and effective manner. Plasma cholesterol reduction of 7% to 15% has been reported using these compounds in a spread (173,174). Should be package started on the lowest dose, 1 contains 4 g package (4 g) and then dosage may be increased over time to daily, 4 packages/d for those most severely affected. Simvastatin Available in 5-, 10-, 20-, 40-, and Patients on statins should be advised of the risk of The long-term 80-mg tablets. Measurement of liver function should be obtained been established prior to drug use and again 6–12 wks after initial therapy or in children. Unfortunately, adherence with these medications is often limited because they are difficult for children to take. The tablet forms are more palatable, but the tablets are large and difficult for some children to swallow (176,177,178). The safety and efficacy of colesevelam has been evaluated in a clinical trial of pediatric patients with heterozygous familial hypercholesterolemia (179). There were no important adverse effects, and adherence to the medication regimen was good. Inhibitors of Cholesterol Absorption Ezetimibe works by blocking cholesterol absorption in the gastrointestinal tract. In adults, ezetimibe is used primarily in combination with statins to achieve additional cholesterol lowering. Because it comes in a single-dose level and because it has so few side effects and is easier to take than bile acid–binding agents, it may be attractive as an initial agent for cholesterol lowering in pediatric patients. This appears to be true of both primary prevention (prevention of an initial myocardial infarction) and secondary prevention (prevention of subsequent myocardial infarctions) (184,185,186). A Cochrane review of the use of statins in primary prevention of cardiovascular disease has been published (187). They evaluated 14 randomized controlled clinical trials including more than 34,000 participants. There is also some concern about the cost-effectiveness of statins for primary prevention of cardiovascular disease. This may be improved by the availability of cheaper generic forms of statin medication. Several studies have been performed to evaluate the safety and efficacy of statins in children and adolescents (175,188,189,190,191,192,193,194). There have also been studies of stains that have evaluated vascular structure and function as endpoints. Increasing the dose can further lower cholesterol but may also be associated with an increased risk of side effects. The side effects of statin agents are an increase in hepatic transaminases and elevation of creatine kinase. Statins have also been associated with myositis, which can progress to rhabdomyolysis. If symptoms of abnormal muscle aches or cramps are present, then creatine kinase should be measured and the medication should be discontinued.

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Atrioventricular Connections Only four possible modes of atrioventricular connection exist: concordance purchase 50 mg cytoxan visa, discordance buy cytoxan 50mg on line, univentricular order cytoxan with a mastercard, and ambiguous (Figs buy genuine cytoxan line. The univentricular connections, in turn, include three subtypes: double inlet, single inlet, and common inlet. If an atrioventricular valve is atretic, it is important to distinguish between the presence of an imperforate fibrous membrane, in which the connection can be determined, and absence of the atrioventricular connection on that side of the heart. Most cases of tricuspid atresia, for example, are characterized by an absent right atrioventricular connection rather than by an identifiable valvular plug. By clinical imaging, the membranous septum should not be misinterpreted as an imperforate tricuspid valve. Concordance and Discordance Concordance denotes the normal state and indicates that the morphologic right atrium is connected to the morphologic right ventricle, and that the left atrium is connected to the left ventricle. In contrast, connection of the right atrium to the left ventricle and of the left atrium to the right ventricle constitutes atrioventricular discordance, which corresponds to ventricular inversion or L-loop ventricles. Univentricular Atrioventricular Connections When both atria are joined to only one ventricle, the connection is univentricular, and three variants are recognized: Double-inlet ventricle, in which two atrioventricular valves are present; single-inlet ventricle, in which only one valve is present and there is no grossly identifiable remnant of the other valve; and common-inlet ventricle, in which a common atrioventricular valve connects both atria to only one ventricle. Ambiguous Atrioventricular Connection With either right or left cardiac isomerism, the atrioventricular connection, by definition, is ambiguous or mixed. In the setting of right isomerism, for example, the right-sided morphologic right atrium might be connected to a morphologic right ventricle (concordance), and the left-sided morphologic right atrium would then join a morphologic left ventricle (discordance). For complex cases such as this, a description of the atrioventricular connection is recommended. D: Tricuspid atresia with single-inlet left ventricle and absent right atrioventricular connection (arrows). Possibilities include concordance, discordance, and double, single, and common outlets (Figs. Occasionally, with an atretic pulmonary or aortic valve, the ventricle to which the corresponding great artery is connected cannot be distinguished with certainty, and the ventriculoarterial connection is considered indeterminate. Concordance and Discordance Concordance refers to the normal state, in which the morphologic right ventricle is connected to the pulmonary artery and the morphologic left ventricle is linked to the aorta. By comparison, discordance corresponds to right ventricular origin of the aorta and left ventricular origin of the pulmonary artery and is synonymous with transposition of the great arteries. When the atrioventricular connection is concordant and the ventriculoarterial connection is discordant, the malformation is called complete transposition, which results in complete separation of the systemic and pulmonary circulations, except at the sites of shunts. In contrast, congenitally corrected transposition is characterized by ventriculoarterial discordance and atrioventricular discordance, which results in normal blood flow but a systemic workload on the morphologic right ventricle. Because the term great vessels refers to either the great arteries or the great veins, use of the term great arteries is favored for the transposition complexes. Double, Single, and Common When both great arteries emanate from only one ventricular chamber, the ventriculoarterial connection is considered double outlet. This form of connection includes not only double-outlet right ventricle but also double-outlet left ventricle and most cases of tetralogy of Fallot. C: Single-outlet connection, in pulmonary atresia with a ventricular septal defect and ductal origin of the pulmonary arteries. Upper panel: Concordance indicates the normal state, and discordance is synonymous with transposition of the great arteries. Interestingly, patients with tetralogy of Fallot and a complete atrioventricular septal defect usually have Down syndrome and a low surgical mortality rate, whereas those with double-outlet right ventricle and a complete atrioventricular septal defect characteristically have atrial isomerism and a high surgical mortality rate. Among patients with pulmonary atresia and a ventricular septal defect, there exists a group in whom no remnant of the pulmonary valve or proximal portion of the pulmonary artery can be identified. As a result, only the aorta arises from the ventricles, constituting a single-outlet ventriculoarterial connection. In general, this situation does not pertain to aortic valve atresia because the ascending aorta, although hypoplastic, must remain patent to provide coronary blood flow, thus allowing its ventricular connection to be readily determined. A common-outlet connection is characteristic of truncus arteriosus, in which this vessel represents the undivided aortic and pulmonary roots. Although hearts with single-outlet and common-outlet connections are quite similar, only in the setting of truncus arteriosus do the pulmonary arteries arise proximally from this vessel rather than from the ductus arteriosus or systemic collateral arteries. Overriding and Straddling Valves Definition of Overriding Valves Overriding may be defined as biventricular emptying of an atrioventricular valve or biventricular origin of a semilunar valve. It is a property of the valve annulus and is always associated with a malalignment ventricular septal defect. The presence of annular overriding may interfere with accurate determination of cardiac connections. As a further complication in living patients, the extent of overriding may vary throughout the cardiac cycle and may appear to vary with different angles of view. Malalignment For overriding atrioventricular valves, the atrial and ventricular septa are malaligned. This may represent a lateral shift, a rotational shift, or a combination of the two (Fig. The ventricular septal defect tends to involve the basal portion of the inlet septum. For the assessment of atrioventricular connections, an atrium is considered to join the ventricle into which >50% of the valve orifice empties (Fig. A common atrioventricular valve is usually associated with concordant or discordant connections, although a common-inlet arrangement applies if >75% of the valve orifice empties into only one of the two ventricles. Overriding of the semilunar valves is associated with malalignment of the outlet septum relative to the remainder of the ventricular septum. As with the atrioventricular valves, the 50% rule also applies to the semilunar valves (Fig. Upper panel: Atrioventricular valves are shown, with lateral and rotational malalignments between the atrial and ventricular septa. Lower panel: Semilunar valves are shown, with lateral and rotational malalignments between the ventricular and outlet septa. Upper panel: With progressive leftward shifting of the atrial septum, the connections change from concordant to double-inlet left ventricle. Upper panel: With progressive rightward shifting of the outlet septum, the connection changes from concordant to double-outlet right ventricle. Thus, straddling involves only the atrioventricular valves and requires the presence of a ventricular septal defect. Although straddling does not affect the evaluation of atrioventricular connections, it is important that it be identified preoperatively because its presence may preclude certain types of surgical repair or may necessitate valve replacement. Lower panel: The three types of straddling are determined by the sites or cordal insertion into the contralateral ventricle along the crest (type A) or body (type B) of the ventricular septum, or onto the ventricular free wall (type C). A: Straddling without overriding of the left-sided tricuspid valve (arrows) in a heart with atrioventricular discordance. B: Overriding and straddling of both atrioventricular valves is associated with rotational malalignment of the atrial and ventricular septa in a case of superoinferior ventricles with a horizontal ventricular septum. Diagnosis of complex congenital heart disease: Morphologic-anatomic method and terminology. Rules for the diagnosis of visceral situs, truncoconal morphologies and ventricular inversions. Interventional and Surgical Cardiovascular Pathology: Clinical Correlations and Basic Principles. Abnormalities of the spleen in relation to congenital malformations of the heart: A survey of necropsy findings in children. Atrial isomerism in the heterotaxy syndromes with asplenia, or polysplenia, or normally formed spleen: An erroneous concept. The determination of atrial arrangement by examination of appendage morphology in 1842 autopsied specimens. Embryology and anatomy: Keys to the understanding of complex and congenital heart disease. Bronicki Introduction The concepts which underlie our understanding of cardiovascular physiology have evolved significantly in recent years. This chapter aims to summarize some of the current concepts related to these key physiologic processes. One framework which might be usefully applied to the study of cardiovascular physiology would be one in which a ventricle, primed by adequate venous return generates “pressure work.

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Node Myelin Na+ K+ K+ Na+ K+ K+ Na+ K+ K+ Na+ K+ K+ Na+ Current Flow Axon Na+ Na+ Na+ Na+ K+ K+ Na+ Myelin Node Nonsaltatory Conduction in Unmyelinated Axon B purchase cytoxan amex. Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ Axon Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ K+ Na+ Action Potential Propagation Block C generic cytoxan 50mg with mastercard. Impulse blockade + K+ K+ Na+ K+ K+ + K+ K+ + K+ K+ + Na Na Na Na Axon Na+ Na+ K+ K+ Na+ K+ K+ Na+ K+ K+ Na+ Figure 1-10 Normal and abnormal action potential propagation discount 50 mg cytoxan. In myelinated axons buy cytoxan american express, action poten- tial propagation is rapid because of saltatory current fow through the nodes of Ranvier where Na+ chan- nels are concentrated. In unmyelinated axons, action potential propagation is slower because Na+ channels are uniformly distributed in the axolemma. Action potential propagation is blocked in demy- elinated axons because current fow dissipates through the denuded membrane before reaching the next cluster of Na+ channels. Action Potential Frequency Encodes result in the membrane remaining depolarized longer resulting in the repetitive Na+ infux and Information K+ effux cycles. Yet other neurons associated with Information is transmitted between neurons or neuromodulatory and autonomic functions fre between neurons and effector structures by the spontaneously at a relatively slow rate (1–10 Hz). In many neurons, action potential frequency is linearly correlated Synaptic Transmission with stimulus intensity and the resultant degree of depolarization of the soma-dendritic mem- The synapse is the point of functional con- brane. The more sustained the depolarization, the tact between neurons, and the neuromuscu- greater the frequency of action potentials. In other lar junction is the point of functional contact neurons, bursts of action potentials are generated between axons and skeletal muscle. Some synapses are character- muscle weakness and fatigability in orbital, ized as fast when the delay between presynaptic oropharyngeal, and limb musculature. Nerve fbers are intact, and acetyl- attached to the active zone of the presynaptic choline release at the nerve terminal is normal. Other synapses are characterized as Antibodies attack the acetylcholine receptor in slow (delay is in terms of seconds) and occur the postjunctional folds, leading to a progressive when peptidergic and biogenic amines stored decrement in amplitude of the evoked end-plate in dense core vesicles away from the terminal potentials and decreased muscle action potentials membrane are released later and for a longer with repetitive stimulation. Neurotransmitter release is sequentially the postjunctional folds and diminished localiza- triggered by the electrotonic invasion of the tion of the receptor at the crest of the folds also action potential into the terminal, the infux occur. Increasing the effcacy of the action of ace- of Ca2+ ions through voltage-gated channels tylcholine in the neuromuscular cleft with acetyl- that trigger the binding of synaptic vesicles at cholinesterase inhibitors decreases the severity of presynaptic active zones, and the subsequent the symptoms. Each synaptic vesicle contains nantly in proximal limb and trunk musculature a quantal amount of neurotransmitter, and the as seen in Lambert-Eaton myasthenic syndrome number of quanta released is directly correlated owing to diminished presynaptic release of to the amount of Ca2+ entering the terminal. Muscle Neurotransmitters in the narrow synaptic cleft excitability remains normal. Acquired autoimmune disorders affect transmis- Adjoining segments of myelin are lost (demy- sion at the neuromuscular junction. Myasthenia elinating plaques) in the white matter fber gravis is an autoimmune disease affecting nico- tracts in the cerebrum, cerebellum, brainstem, tinic acetylcholine receptors, leading to skeletal and spinal cord. Normal impulse conduction Chapter 1 Introduction, Organization, and Cellular Components 15 occurs proximal and distal to the plaques but is or painful sensations on the palmer surface and blocked or slowed at the plaques (Fig. Biophysical properties of the demyelinated axo- The mild dysesthesia experienced initially with lemma are altered, thereby affecting impulse carpal tunnel nerve compression can be treated propagation. In demyelinated axons, depolarizing with supported rest of the hand (a splint) or with currents are no longer focused at the nodes, but injections of steroids into the tunnel. Moderate rather are dissipated along the demyelinated axo- to severe cases require decompression of the lemma owing to the paucity of Na+ channels in nerve in the wrist by surgical incision of the the internodal axolemma and the increased elec- retinaculum. In axons with intact myelin, action poten- bilateral and most commonly affect sensorimo- tials jump between nodes of Ranvier because of tor axons in the more distal lower and upper the high concentration of Na+ channels at the limbs. Multiple sclerosis is character- and weakness progressively follow with the loss ized by chronically protracted cycles of relapse of sensations, decreased muscle bulk, abnormal and remission. These are symptoms refects partial remyelination of the generally referred to as polyneuropathies. Persistent defcits can diabetes is the most common cause for polyneu- refect the failure to remyelinate or, more prob- ropathy, there are many other conditions, many ably, axonal injury within the plaque and axonal with unknown etiology, that also contribute to degeneration. Other common disorders that affect axons directly result from chronic nerve compression/ Degeneration and Regeneration constriction (entrapment) or by degenerative diseases. The most common entrapment neu- All cells in the human body are able to repro- ropathy involves the median nerve in the carpal duce, except nerve cells. The median nerve is a mixed neurons is irreparable; a neuron once destroyed sensory and motor nerve that transmits sensory can never be replaced. Conversely, axons can impulses from the palmer surface of the thumb regenerate and regain their functions even after and the frst 2½ fngers (but not the little fnger) being completely transected or cut, as long as the and motor impulses to intrinsic hand muscles. Constriction of median nerve axons causes the generation of abnormal Chapter Review impulses characterized initially as tingling or Questions burning sensations, or mild numbness in the palmer surface of the thumb and index, middle, 1-1. What is a synapse, and what are the chief Long-term compression will result in the degen- characteristics of synapses in the central eration of median nerve axons (see Chapter 26). A diagnosis of carpal tunnel syndrome is strongly supported when the physician taps the median 1-3. What is the signifcance of axoplasmic nerve in the patient’s wrist and evokes tingling transport? Which of the following is most likely progressive weakness and fatigue during involved in a tumor originating from the day. Results from a nerve conduction myelin-forming cells in the central nervous study are normal. The cell most commonly associated with choline at the neuromuscular junction central nervous system tumors is the: c. Department of Health and Human Services, approximately 10,000 new spinal cord injuries occur in the United States each year, of which at least 50% result in permanent disabilities. Most of these injuries result from trauma such as occurs in automobile or sports accidents. An estimated two-thirds of the victims are 30 years of age or younger; the majority are men. The spinal cord connects with the spinal nerves large opening in the base of the skull, to the frst and is the structure through which the brain com- lumbar vertebra (Fig. Superiorly, the spinal municates with all parts of the body below the cord is continuous with the brain, and, inferi- head. Impulses for the general sensations such as orly, it ends by tapering abruptly into the conus touch and pain that arise in the limbs, neck, and medullaris (Fig. Likewise, commands for voluntary movements in the limbs, Clinical trunk, and neck originate in the brain and must Connection pass through the spinal cord to reach the spinal nerves that innervate the appropriate muscles. The spinal cord is ordinarily pro- Thus, damage to the spinal cord may result in the tected by the strong bony ring loss of general sensations and the paralysis of vol- formed by the vertebral column. However, high- untary movements in parts of the body supplied velocity objects (e. The cervical vertebrae are the smallest and most fragile, and, hence, most The spinal cord is located within the vertebral fractures occur here. Chapter 2 Spinal Cord: Topography and Functional Levels 19 There are 31 spinal cord segments (Fig. The segments Connection are named and numbered according to the attach- The relation between spinal cord ment of the spinal nerves. The spinal nerves are levels and vertebral levels is clini- named and numbered according to their emer- cally important. Spinal nerves is always localized according to the spinal cord C1 through C7 emerge through the interverte- segment. Most spinal cord levels do not, how- bral foramina above their respective vertebrae. After this time, the verte- bral column elongates more rapidly than does the The spinal cord is surrounded by three connective spinal cord. At birth, the spinal cord ends at the tissue membranes called the spinal meninges. Further growth of the internal to external, the spinal meninges are called vertebral column results in the inferior or caudal the pia mater, arachnoid, and dura mater (Fig. The approximate The pia mater completely surrounds and adheres relation between spinal levels and vertebral lev- to the spinal cord.

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