SHALENDER BHASIN, MD

• Chief and Professor, Department of Endocrinology,
• Diabetes, & Nutrition, Boston University, Boston

Cross sections of I bands show only thin filaments symptoms you have worms discount sinemet 125 mg buy online, whereas A bands show both thick and thin filaments treatment kidney disease sinemet 110 mg low cost, which appear as hexagonal networks with myosin fixed at the M band treatment glaucoma sinemet 125 mg order with amex. Where the two sets of filaments overlap medications known to cause pill-induced esophagitis 110 mg sinemet order free shipping, the networks mesh so that each thick filament is in the 4 medications you can take while nursing buy sinemet 300 mg overnight delivery. The interval between thick and thin filaments in the double hexagonal array is 10-20 nm. Regularly spaced globular heads of the myosin cross bridges radiate from each thick filament toward the thin filaments; however, cross bridges are not well resolved by routine electron microscopy, so thick filaments show a roughened surface. M bands, which are in the center of the H zones, show thick filaments with fine interconnections. Z bands in cross section show a typical square lattice pattern, and thin filaments in the immediate vicinity are organized in a regular array. Capillaries, in transverse (arrows) and longitudinal (Cap) section in the endomysium, are in close contact with skeletal muscle fibers. The peripheral nucleus of one of the muscle fibers abuts the endothelium of the capillary. Mitochondria (Mi) occur singly between the myofibrils or in clusters in subsarcolemmal locations, often close to capillaries. Arteries supplying and veins draining blood usually enter a muscle with the nerves and together are called a neurovascular bundle. Main distributing (or muscular) arteries typically pierce the epimysium and course longitudinally within the connective tissue of the perimysium to form a radiating pattern of collateral branches. They become progressively smaller, bifurcate, and give rise to arterioles that run in the endomysium within muscle fascicles. Electron microscopy shows most capillaries to be the tight nonfenestrated type, although occasional fenestrated capillaries are seen. Different muscles, as well as muscles of trained versus untrained athletes, show marked variations in capillary density. Large profuse mitochondria beneath sarcolemma and in rows as well as paired in interfibrillar regions. Small, relatively sparse mitochondria, chiefly paired in interfibrillar spaces at Z bands. Most muscles contain a mixture of fiber types, with one type usually predominating. Muscle fibers have a typical mosaic pattern when examined histochemically, and fiber typing via histochemical and immunocytochemical staining has clinical significance for health and disease and is done routinely for both diagnosis and treatment. Fiber typing is also used to determine functional properties of a particular muscle on the basis of the distribution and percentage of fiber types. Genetic differences in the same muscle group predispose people to a preference for certain types of activity. The plasticity of muscle in response to exercise pattern is clearly shown by a shift in metabolic properties. Physiotherapists determine how to train a muscle on the basis of knowing the function of a muscle and the percentage of its fiber types. For example, the transversus abdominis, a postural or stabilizer muscle, would be trained with a low-force, high-endurance activity. Power muscles such as the biceps would be trained with high force or load and a low number of repetitions. Mutations in seven causative genes that encode for various protein components of sarcomeric thin filaments. Histochemical fiber typing shows alteration of the normal checkerboard pattern of fiber types, with predominance of type 1 (slow-twitch) fibers. There is no cure, but potential treatment strategies include gene replacement therapy using normal copies of the defective gene, which are delivered to pleuripotential stem cells or satellite cells. After cytosol extraction, whereby myofilaments are selectively removed, the delicate honeycomb pattern of the sarcotubular system and mitochondria surrounding myofibrillar spaces is revealed. Differences in the content and distribution of these membranous organelles are seen in the three types. Small-diameter type I, or red, fibers are aerobic, slowly contracting, very resistant to fatigue, and capable of long and continued activity. Large numbers of these fibers are found in muscles used for aerobic activities requiring low force production, such as walking and maintaining posture. They are used for short anaerobic and high force production activities such as jumping and sprinting. They are used for prolonged anaerobic activities with a relatively high force output, such as racing 400 m. Histochemical fiber type diversity is mostly based on the differential expression pattern of specific isoforms of myofibrillar and other related proteins. Ultrastructural features that also distinguish fiber types include density and spatial distribution of mitochondria, sarcomere banding patterns, and organization of the sarcotubular system. Mitochondria (Mi), seen in both longitudinal and transverse planes, are fractured open to reveal internal cristae. A highly anastomosing, uniformly sized, tubular network of A band (A) and I band (I) sarcoplasmic reticulum is revealed at the level of a sarcomere. Myofilaments in the muscle fiber were selectively extracted by the preparation procedure. High-resolution scanning electron microscopy, in combination with selective cytosol extraction and freeze fracture of muscle fibers, provides novel views of a cell interior with a greater depth of field. This methodology selectively removes myofibrils, which often obscure other organelles in the sarcoplasm, but leaves membranous components of the muscle fiber intact. Examination of high-resolution scanning electron microscopy specimens clarifies the three- dimensional arrangement and distribution of mitochondria and elements of the sarcotubular system inside a fiber. Subtle differences in internal architecture of the three types of skeletal muscle fibers, which reflect functional diversity, are also revealed. These variations most likely reflect differences in energy demand and utilization of fiber types. The density, arrangement, and distribution of the sarcotubular system also vary in fiber types. At the tapering end of a skeletal muscle fiber, terminal finger-like extensions of the muscle fiber (Sk) insert into the dense regular connective tissue of the tendon (T). Fibroblasts (arrows) are interspersed with regularly arranged collagen fibers in the tendon. The end of a muscle fiber splits into several villus-like terminal projections, which contain a network of myofilaments (Mf) that run toward subsarcolemmal densities (arrows). The sarcolemma is highly Tendon indented and invested by a prominent external lamina. Collagen fibrils of the adjacent tendon penetrate intervillous clefts and are in close contact with the sarcolemma. It is an interface between two diverse yet interconnected tissues with a complicated communication system and a high shear component. Biomechanically, this area involves a concentration of tensile forces and marks a site of abrupt change in the modulus of elasticity, which represents the point of maximum stress in this unit. Developmentally, it is the rapidly growing area of the muscle fiber during postnatal life. Light and electron microscopy can show that the interface between muscle and tendon is highly interdigitated and consists of branching fingerlike extensions of myofibrils that interlock with projections of adjacent tendon-like the fingers of a hand inserted into a tightfitting glove. The extensive infolding of the sarcolemmal membrane increases surface area, which enhances mechanical stability at the site of force transmission and in response to junctional stress. Specific membrane-associated proteins including a-actinin, vinculin, talin, and integrins are found at these sites. Immobilization reduces the tensile strength of the junction and predisposes it to strain injuries. Symptoms typically begin at the muscle-tendon junction and then spread throughout the affected muscle. Although distressing for novice exercisers, it is a normal, adaptive response to unusual exertion that rarely requires clinical treatment. Muscle fibers undergo repair and remodeling via an increase in protein synthesis and activation of satellite cells. The cytoplasm contains scattered free ribosomes, and a few profiles of rough and smooth endoplasmic reticulum. A narrow gap separates the cell from the underlying muscle fiber, where plasma membranes of the two cells are parallel to each other. The underlying muscle fiber contains tightly packed but poorly defined myofibrils and a few mitochondria. The narrow space between their apposed membranes is difficult to distinguish at this magnification. The cytoplasm contains a sparse collection of mitochondria, rough endoplasmic reticulum, and free ribosomes. Well-defined myofibrils with intervening elements of sarcoplasmic reticulum and mitochondria characterize the underlying muscle fiber. Nucleus of satellite cell Muscle fiber 1 µm Frontal balding "Hatchet" facies due to atrophy of temporalis muscle Ptosis and drooping mouth due to weakness of facial muscles Wasting of sternocleidomastoid muscle Cataracts Satellite cell Gynecomastia Muscle fiber 1 µm Myotonic dystrophy: clinical manifestations. The close location of these cells to the surface of a fiber, with an intervening space of about 15 nm, makes them identifiable by electron microscopy or by immunocytochemical staining and molecular markers. Satellite cells serve as a population of reserve stem cells, or resting myoblasts, either for normal postnatal growth or for repair and regeneration of damaged segments of the skeletal muscle fiber after injury. Also, more satellite cells occur in slow-twitch muscles than in fast-twitch muscles. Although the cells are normally quiescent in adults and their numbers and mitotic capacity decline with age, they have proliferative potential throughout life, and they increase in number in response to denervation, in mildly traumatized muscle, and in regenerating diseased muscle. A single nucleus contains clumped peripheral heterochromatin; the cytoplasm normally contains a paucity of organelles. Free ribosomes, scattered small mitochondria, occa- sional rough endoplasmic reticulum, and Golgi complex are the only distinguishing features. Activation of satellite cells after muscle injury leads to cell proliferation, followed by differentiation and fusion to either form new muscle fibers or repair damaged ones. Advances in our knowledge of satellite cell dynamics hold promise for progress in treatment of diseases, such as muscular dystrophy, that affect skeletal muscle. The most common adult muscular dystrophy, it often occurs in early adulthood and has an extremely variable degree of severity. The gene associated with myotonic dystrophy is on the long arm of chromosome 19 and encodes for a protein kinase normally found in skeletal muscle, where it most likely has a regulatory role. Although the etiology of this disorder remains enigmatic, a cell membrane defect is suspected as the major cause. Myelin sheath Axoplasm MuscleTissue 87 Synaptic cleft Postjunctional fold Postsynaptic membrane Schwann cell Mitochondria Presynaptic membrane Active zone Synaptic vesicles External lamina (basement membrane) Myofibrils Acetylcholine receptor sites Sarcoplasm Myasthenia gravis: clinical manifestations. A motor nerve terminates on the surface of a muscle fiber at a specialized site-the neuromuscular junction (motor endplate). Histologic visualization of motor endplates requires special techniques, the best being electron microscopy. As the motor axon approaches the sarcolemma of the muscle fiber, it loses a myelin sheath but retains an investment of the terminal Schwann cell. Several branches of the axon terminal emanate from the parent axon to end on the muscle fiber. Each bulbous axon terminal sits in a trough or depression on the muscle fiber surface called the synaptic trough, in which lie acetylcholine receptor sites. A narrow, intervening intercellular space-the primary synaptic cleft-separates the plasma membrane of the axon terminal from the sarcolemma of the muscle fiber. At the site of the junction, the highly folded sarcolemma of the muscle fiber forms postjunctional folds (also called secondary synaptic clefts or subneural apparatus) that markedly increase the surface area of the muscle fiber. The external lamina of the muscle fiber fuses with that of the terminal Schwann cell and extends into synaptic clefts. The subsarcolemmal sarcoplasm is replete with mitochondria, free ribosomes, and rough endoplasmic reticulum. Symptom onset commonly occurs after the age of 30 years in women and somewhat later in men. In the acquired disorder, a distortion of the postsynaptic sarcolemmal membrane of the neuromuscular junction is accompanied by a reduction in the concentration of acetylcholine receptors. Antibodies are attached to the postsynaptic membrane, which makes it less sensitive to acetylcholine and leads to a reduced muscle action potential in response to a nerve impulse. The postjunctional sarcoplasm contains abundant mitochondria and a nearby nucleus of the muscle fiber. The axon terminal contains abundant membrane-bound synaptic vesicles, many in the region of the presynaptic membrane. Mitochondria (Mi) are also plentiful in the terminal axoplasm, as well as in the underlying sarcoplasm of the muscle fiber. The underlying postsynaptic region of the junction contains numerous infoldings of the muscle fiber sarcolemma. Both primary (Pr) and secondary (Se) synaptic clefts contain a thin external lamina (arrow) between the presynaptic and postsynaptic areas of the junction. First, a Schwann cell process forms a cap above the nerve terminal; here, it does not face the synaptic region. Second, the axon terminal, which is devoid of myelin, contains many clear, rounded synaptic vesicles filled with the neurotransmitter acetylcholine. These membrane-bound vesicles are 50-60 nm in diameter and are concentrated near the presynaptic membrane in regions known as active zones. Neurofilaments, microtubules, smooth endoplasmic reticulum, lysosomes, scattered glycogen particles, and mitochondria occupy other regions of the axon terminal. The third component is the synaptic cleft, which is a narrow space between nerve terminal and muscle fiber surface, about 70 nm wide.

This accounts for its ability to depress sinoatrial and atrioventricular node function medications during pregnancy 110 mg sinemet order with mastercard. Thus symptoms gallbladder problems purchase sinemet 110 mg without prescription, amiodarone is effective pharmacologic therapy for both recurrent supraventricular and ventricular tachydysrhythmias medicine emoji cheap sinemet 125 mg buy on line. Atropine-resistant bradycardia and hypotension may occur during general anesthesia because of the significant antiadrenergic effect of amiodarone medicine zalim lotion order sinemet 125 mg on-line. In this case medications requiring central line buy generic sinemet 125 mg, cardiac output is greater than normal, as one often sees in early sepsis. Treatment of this hypotension should be carried out with pharmacologic 272 Part 2 Clinical Sciences agents with strong -agonist properties. Of the choices in this question, phenylephrine is the only drug that is a pure -agonist. Dopamine in high doses has strong activity but significant 1 activity and some 2 activity as well. Any of the aforementioned pharmacologic agents could be used to support pressure in patients with sepsis in conjunction with definitive treatment for the septic source. Because dobutamine is predominantly a 1 agonist, it would be an extremely poor choice for a patient with a high cardiac output in the face of a low systemic vascular resistance (Barash: Clinical Anesthesia, ed 7, p 1592). The atrial flutter waves (F waves) are occur- ring at approximately 300 per minute and the ventricular rate is approximately 75 per minute. This will effectively "reset" the heart and allow the normal P wave to be manifested. Shocking on a flutter wave that is not occurring during ventricular repolarization would not be a problem, but a shock during repolarization would be tantamount to an R on T phenomenon and might induce ventricular tachycardia or even ventricular fibrillation. When the fluid pressure becomes elevated and impairs cardiac filling, cardiac tamponade is said to develop. If the amount of fluid increases acutely, as little as 100 mL may cause tamponade. If the increase in fluid develops slowly, an increase in volume of 2 L may develop before tamponade is produced. An imbalance between the right and left sides of the sympathetic nervous system may play a role in the etiology of these syndromes. Mechanical circulatory support can be used as bridge therapy for patients awaiting cardiac transplantation or as a bridge to recovery from a viral cardiomyopathy or from cardiogenic shock after myocardial infarction. Various versions of these devices can be used to support the right (not approved for destination therapy), the left, or both ventricles. Specifically, on the left side, blood is taken from the apex of the heart and returned to circulation via the aorta. Measuring blood pressure with a cuff is not accurate in most patients and may be impossible. Pulse oximeters do Cardiovascular Physiology and Anesthesia work with some patients, but this, too, requires pulsatile flow. In aortic regurgitation, the left ventricle ejects a large volume of blood in systole with a rapid diastolic runoff as blood flows both to the periphery and back into the left ventricle. The first systolic peak of the bisferiens pulse represents the wave of blood ejected from the left ventricle. In contrast, patients with aortic stenosis display a delayed pulse wave with a diminished upstroke (pulsus tardus and pulsus parvus), whereas patients with cardiac tamponade show an exaggerated inspiratory decline in systolic blood pressure (pulsus paradoxus). Induction of anesthesia with a volatile anesthetic such as sevoflurane may be used, but careful monitoring of systemic oxygenation is needed because any decrease in systemic blood pressure would increase the right-to-left shunt (and would decrease the oxygen saturation). Mitral stenosis causes pathophysiologic changes both proximal and distal to the abnormal valve. In general, the left ventricle is "protected" or unloaded; that is, it is not exposed to excessive volume or pressure loads and therefore is rarely associated with abnormalities in left-sided myocardial contractility. In contrast, proximal to the valve, a diastolic pressure gradient develops between the left atrium and left ventricle in order to force blood across the stenotic valve orifice, which results in elevated left atrial pressures and decreased left atrial compliance and function. The elevated left atrial pressures are reflected back into the pulmonary vascular system, causing an increase in pulmonary vascular resistance and eventually poor right ventricular function. This would modulate the number of atrial contractions that ultimately drive the ventricle. The downfalls of this type of Q measurement are threefold: (1) sampling and analysis errors in vo2, (2) changes in Q while samples are being taken, and (3) accurate determination of vo2 may be difficult because of cumbersome equipment. In the normal contracting muscle at 37° C, myocardial O2 consumption is approximately 8 to 10 mL/100 g/min. This is reduced in the fibrillating heart at 22° C to approximately 2 mL/100 g/min. Myocardial O2 consumption of the electromechanically quiescent heart at 22° C is less than 0. Phenylephrine, because it is a pure -adrenergic receptor agonist, has minimal direct effects on myocardial contractility (Miller: Basics of Anesthesia, ed 6, p 404). With severe disease, the left ventricular chamber becomes dilated and myocardial contractility diminishes. The primary goals in the anesthetic management of such patients undergoing noncardiac surgery are to maintain normal sinus rhythm and avoid prolonged alterations in heart rate (especially tachycardia), systemic vascular resistance, and intravascular fluid volume. Resting myocardial O2 consumption is 8 to 10 mL/100 g/ min, or approximately 10% of the total body consumption of O2 (Barash: Clinical Anesthesia, ed 7, p 244). This can be achieved by endobronchial intubation with a double-lumen endotracheal tube. Since protamine is derived from salmon sperm, patients with seafood allergies as well as men who have had a vasectomy (who may develop circulating antibodies to spermatozoa) may also develop a reaction. The likelihood of reactions may be reduced with prior administration of H1 blockers, H2 blockers, and corticosteroids. Protamine is a basic protein that combines to the acidic heparin molecule to produce an inactive complex that has no anticoagulant properties. It is determined by the difference between aortic diastolic pressure and left and right ventricular end-diastolic pressures. During systole, left ventricular pressure increases to or above sys- 276 Part 2 Clinical Sciences temic arterial pressure, resulting in almost complete occlusion of the intramyocardial portions of the coronary arteries. Thus, perfusion of the left ventricular myocardium occurs almost entirely during diastole, resulting in a decrease in left ventricular coronary perfusion as heart rate increases. In contrast, the right ventricle is perfused during both systole and diastole, because right ventricular pressures remain less than that of the aorta. The coagulation variables measured from a thromboelastogram are (1) the R value (reaction time; normal value 7. Ephedrine may also increase inotropy and be beneficial on that basis in the face of right ventricular dysfunction. Fluids and Trendelenburg position are also likely to help raise the mean arterial pressure. Such an increase could simply make the device "suck down" and may actually worsen performance. The suck-down effect results in a completely empty left ventricle with myocardium being drawn over the inflow cannula. The drug is rapidly metabolized such that it is not influenced by liver or renal dysfunction. Its effects, however, can be markedly enhanced by drugs that interfere with nucleotide metabolism such as dipyridamole. Administration of the usual dose of adenosine to a patient receiving dipyridamole may result in asystole. If adenosine is used in patients receiving dipyridamole, or the patient has a central line, the initial dose is 3 mg. These temperature monitoring sites are reliable, even during rapid thermal perturbations such as cardiopulmonary bypass. Other temperature sites, such as oral, axillary, rectal, and urinary bladder, will estimate core temperature reasonably accurately except during extreme thermal perturbations. However, it may be difficult to interpret urinary bladder temperature because it is strongly influenced by urine flow. The adequacy of rewarming after coronary artery bypass is thus best evaluated by considering both the core and urinary bladder temperatures (Stoelting: Pharmacology and Physiology in Anesthetic Practice, ed 4, p 694). It is no longer recommended to deliver a three-shock sequence with biphasic defibrillators, because it is unlikely for the second or third shock to work after a failed first shock, and the second and third shocks may be harmful. With monophasic defibrillators, it may be acceptable to deliver three-shock sequences, but all adult shocks should be 360 J. If severe metabolic acidosis is confirmed on arterial blood gases, intravenous sodium bicarbonate should be administered. Adverse effects associated with administration of sodium bicarbonate are well documented and include severe plasma hyperosmolality, paradoxic cerebrospinal fluid acidosis, hypernatremia, and hypercarbia, particularly in patients who are not adequately ventilated. Bicarbonate lowers potassium by lowering the extracellular hydrogen ion concentration, which results in lowering, not raising, the potassium concentration (Barash: Clinical Anesthesia, ed 7, p 1685). These attacks usually occur without provocation but can be associated with episodes of excitement, such as crying or exercise. It is believed, however, that hypercyanotic attacks occur as a result of spasm of the infundibular cardiac muscle or a decrease in systemic vascular resistance; both will exacerbate the right-to-left intracardiac shunt. Phenylephrine, an -adrenergic receptor agonist, is the drug of choice for treatment of hypercyanotic attacks, because presumably phenylephrine increases systemic vascular resistance, which reduces the intracardiac right-to-left shunt and improves arterial oxygenation. Esmolol is also effective, presumably because it reduces spasm of the infundibular 278 Part 2 Clinical Sciences cardiac muscle. Isoproterenol with its -mimetic effects reduces afterload and therefore increases right-to-left shunting and may exacerbate infundibular spasm. This heparin-platelet factor 4 antibody complex binds to endothelial cells, which then stimulates thrombin production with a net result of both thrombocytopenia (>50% reduction in the platelet count) and venous and/or arterial thrombosis (<10% of cases). Furthermore, heparinase, an enzyme derived from a gram-negative bacterium (Flavobacterium heparinum), can also be used to neutralize the effects of heparin. Because the P2Y12 receptor is permanently affected, the duration of action of clopidogrel is for the life of the platelets. This obviates the need for a sternotomy but does require one-lung ventilation and may result in hypoxia prior to initiation of cardiopulmonary bypass and after cessation. Cardiovascular Physiology and Anesthesia 279 Trachea Right mainstem bronchus Upper lobe Carina Left mainstem bronchus Upper lobe Middle lobe Lower lobe Lingula Lower lobe 977. If the tube is initially advanced too far into the right mainstem bronchus (as it was in this question) a structure resembling the carina will be visualized. The "real" carina separates the left and right lungs, and if the bronchoscope is pushed into either the right or the left mainstem bronchi, a secondary "carina" will be visualized. On the right, the branches lead to the right upper lobe and the right middle lobe. If the three lumens are seen after branching right from the "carina," the "carina" in question is not the true carina but is, in fact, the branching point for the right upper and right middle lobes (see figure) (Barash: Clinical Anesthesia, ed 7, pp 1044­1046). Most patients will have adequate Pao2 when the dependent lung is ventilated with 100% oxygen, using a tidal volume (Vt) of 8 to 10 mL/kg and adjusting the respiratory rate to achieve a Paco2 of 40 mm Hg. Occasionally, intermittent inflation of the nondependent lung with 100% oxygen will be needed. About 25% of patients eventually develop a bradycardia that will require implantation of a permanent cardiac pacemaker. If bradycardia does develop, drugs that exert their effect by blocking the parasympathetic branches of the autonomic nervous system. Direct-acting drugs such as glucagon, isoproterenol, epinephrine, and norepinephrine will still be effective. Isoproterenol is commonly used for increasing heart rate in cardiac transplant recipients. Epinephrine and norepinephrine may have exaggerated -mimetic effects on the heart rate because the increase in blood pressure will not lead to a reflex slowing of the heart rate via the baroreceptor 280 Part 2 Clinical Sciences reflexes. Drugs with both direct and indirect effects such as ephedrine evoke a less intense response. Such conduction results in narrow, complex tachycardia, and any of the drugs mentioned in this question could be used to control rate. Intravenous procainamide, a class Ia antidysrhythmic agent, is the only useful pharmacologic agent among the drugs listed in the question. If pharmacologic therapy fails, electrical cardioversion is indicated to control rate (Fleisher: Anesthesia and Uncommon Diseases, ed 6, p 33). Turning off an implanted pacemaker would be extremely difficult in the middle of an operation. Intravenous lidocaine would be useless in this setting, as would switching the volatile agent from isoflurane to desflurane. They both produce positive inotropic effects and vasodilation (arterial and venous). Unlike milrinone, amrinone rapidly produces clinically significant thrombocytopenia especially after prolonged use (Hemmings: Pharmacology and Physiology for Anesthesia, ed 1, pp 390­391). These factors are easily understood by rearranging the Fick equation as follows: Cardiovascular Physiology and Anesthesia See explanation to Question 106 for complete definition of O2 content. In the present case, labetalol reduces cardiac output through its negative inotropic effect. Recently, inhaled epoprostenol and alprostadil have been described to reduce the systemic side effects. Because hypoxia produces pulmonary vasoconstriction, oxygen therapy is often administered to reduce the magnitude of pulmonary vasoconstriction that may develop. Milrinone is a phosphodiesterase inhibitor that reduces pulmonary vascular resistance while having some inotropic effects. The compensatory mechanism to maintain cardiac output is left ventricular hypertrophy. Events that increase outflow obstruction include increased myocardial contractility.

Thus treatment centers order 300 mg sinemet with amex, nerves do not supply a necessary organizing stimulus medicine naproxen sinemet 125 mg purchase fast delivery, and gross muscle morphogenesis will go to completion with function never having occurred medicine for high blood pressure effective sinemet 110 mg. However symptoms queasy stomach order cheapest sinemet, a muscle that never had a nerve supply does not attain its full differentiation at the fiber level and disappears with time symptoms 6 days post iui order cheap sinemet on line. Skeletal muscles make up the bulk of the adult body and comprise about 45% of its total weight. Each has a characteristic shape that is circumscribed by a connective tissue sheath. During vertebrate evolution, the head underwent changes related to the development of the special senses. The anterior end of the nerve cord became a brain, and the nerves passing to and from the brain became the cranial nerves. In the prevertebrate amphioxus, which has no brain, muscle is present in the region of the mouth of the digestive system (see Plate 1-1). In the vertebrate fish, the gills have a branchial arch musculature that arises from the mesoderm associated with the developing pharyngeal region of the foregut. Therefore, this musculature can properly be called visceral musculature, even though it is voluntary and striated. A better term is branchial, or branchiomeric, musculature because it represents a serial division, or metamerism, of the lateral (gill or branchial) mesoderm that does not segment in its counterpart in the trunk. In the human embryo, the branchial arches and their contained structures initially develop as if the aqueous gill-slit type of breathing apparatus were going to be retained. Instead of disappearing, most of the branchial arch structures are gradually modified and incorporated into the permanent acoustic and air-breathing respiratory systems. The branchiomeric musculature that develops from the mesoderm of the series of branchial arches on each side of the embryonic head becomes innervated by cranial nerves. In addition to the skeletal muscles derived from the myotome and branchial arch, there are those that arise, in situ, directly from the local mesenchyme. Some of these locally derived muscles are the result of the slurring over of the sequence of evolutionary events during development, so that their derivation from myotome or branchial arch mesenchyme is obscured. Others, such as the limb muscles, appear relatively late in evolution and development. In the human embryo, the muscles of the limbs that evolved from fins appear after the myotomic and branchial arch musculature formation is well under way. The muscles of the pelvic diaphragm, perineum, and external genitalia also appear relatively late in development. A developing skeletal muscle normally provides attractive forces that serve to guide a nerve to it. With only a few exceptions, the muscles retain their original innervation throughout life, no matter how far they may migrate from their site of origin during development; this is true whether a muscle is of myotomic origin and innervated by a spinal nerve or of branchial arch origin and innervated by a cranial nerve. Therefore, the innervation of adult muscles can be used as a Precartilage condensation of mesenchyme Cartilage (rudiment of bone) Perichondrium Joint capsule Circular cleft (joint cavity) Site of future joint cavity (mesenchyme becomes rarefied) Cartilage Perichondrium A. Periosteum Epiphyseal cartilage growth plate Epiphyseal bone Joint capsule Synovial membrane Joint cavity Articular cartilages Epiphyseal bone Example: interphalangeal joint Joint cavity Articular menisci B. Joint cavities Example: knee joint Example: sternoclavicular joint clue to determine their embryonic origin. Embryonic muscle masses receive their motor innervation very early at or near their midpoint. If a nerve supplies more than one muscle, it can be assumed that the muscles are subdivisions of an original myotome. Thus, the developmental histories of adult muscles formed by early fusion, splitting, migration, or other modifications can be reconstructed with considerable certainty. Nearly all the skeletal muscles are present and, in essence, have their mature form in a fetus of 8 weeks with a crown-to-rump length of about 30 mm (see Plate 1-16). From the time the first myotomes begin to differentiate into skeletal muscles early in the fifth week, six fundamental processes that occur up to the eighth week are involved in the gross development of the muscles. Frequently, the formation of a muscle is the result of more than one of these processes. The direction of the muscle fibers may change from the original craniocaudal orientation in the myotome. Only a few muscles retain their initial fiber orientation parallel to the long axis of the body (the rectus abdominis, erector spinae, and some small vertebral column muscles). Good examples of muscles that undergo a directional change are the flat muscles of the abdominal wall-the external and internal abdominal oblique muscles and especially the transverse abdominal muscle. Portions of successive myotomes commonly fuse to form a composite single muscle (the erector spinae and rectus abdominis muscles). The latter is formed by the fusion of the ventral portions of the last six or seven thoracic myotomes. Only a few muscles are derivatives of single myotomes (the intercostals and some deep, short vertebral column muscles). A myotome, or branchial arch muscle primordium, may split longitudinally into two or more parts that become separate muscles (the sternohyoid and omohyoid muscles and the trapezius and sternocleidomastoid muscles). The original myotome masses may split tangentially into two or more layers (the external and internal intercostal and abdominal oblique and transverse abdominal muscles). The degenerated muscle leaves connective tissue that becomes a sheet known as an aponeurosis (the epicranial aponeurosis [galea aponeurotica], which connects the frontal and occipital portions of the occipitofrontalis muscle). Finally, muscle primordia may migrate, wholly or in part, to regions more or less remote from their original site of formation. An example is the formation of certain muscles of the upper limb that arise from cervical myotomes. The serratus anterior muscle migrates to the thoracic region, to attach ultimately to the scapula and the upper eight or nine ribs, taking along its fifth, sixth, and seventh cervical spinal nerve innervation. The trapezius muscle, along with the upper five cervical spinal nerves, migrates to attach ultimately to the skull, the nuchal ligament, and the spinous processes of the seventh cervical to twelfth thoracic vertebrae. The migration of the latissimus dorsi muscle is even more extensive; it carries with it its seventh and eighth cervical spinal nerve innervation to attach ultimately to the humerus, the lower thoracic and lumbar vertebrae, the last three or four ribs, and the iliac crest of the pelvis. As these migrating upper limb muscles acquire their attachments to the trunk, they are all superficial to the underlying muscles of the body wall. A wide range of normal variations in skeletal muscle morphology result from one or more of the six fundamental processes going awry. The damaged muscle fibers on each side of the necrotic area, which are actually open-ended syncytial tubes, form growth buds on their ends that grow toward each other, meet, and fuse. This reestablishes muscle fiber continuity across the damaged area and may be sufficient for the repair of a small muscle injury. When there is more extensive damage, the repair process is similar to the embryologic process of muscle fiber formation. Syncytial myotubes have formed primitive muscle fibers in which longitudinal myofilaments appear. Even so, when large areas are damaged, the muscle regeneration may be so limited that the missing muscle is replaced chiefly with connective tissue. Mesenchymal cells of myotomes, as well as of specialized condensed (premuscle) areas of mesenchyme, in limb buds and branchial region and in somatic mesoderm of body wall modulate into myoblasts, which begin to aggregate into syncytial tubes. Central nuclei Muscle fiber Myofilament Between the fifth and sixth weeks, the myotomes of the trunk of the human embryo become divided by a slight longitudinal constriction into a dorsal epaxial column of epimeres and a more ventral hypaxial column of hypomeres (see Plates 1-16 and 1-18). The original spinal nerve to the myotome that gives rise to an epimere and a hypomere also divides into dorsal and ventral rami. Thus, the epimeres and hypomeres are innervated, respectively, by the dorsal and ventral rami of the serially repeated spinal nerves, just as in adult primitive fish. In addition, the developing transverse processes of the vertebrae serve to help separate the epaxial and hypaxial columns. The mesenchyme between the two columns attaches to the transverse processes and becomes a connective tissue sheet or intermuscular septum, the rudiment of the thoracolumbar fascia, which permanently separates the two columns. After the transverse processes appear, the ribs form in the sclerotomal tissue that extends by differentiation into the ventral portions of the original clefts between the somites. The maximum development of the ribs is in the thoracic region; consequently, of all the muscles in the adult, the intercostal muscles retain to the greatest degree the original segmental pattern of the hypaxial musculature. The epaxial column of epimeres divides further into a medial, or deep, and a lateral, or superficial, group of muscles that eventually give rise to the extensors of the vertebral column. The medial group of muscles, supplied by the medial branches of the posterior primary rami of the spinal nerves, retains a resemblance to the primitive segmental arrangement by arising from the fusion of only a few consecutive segments. By subsequent longitudinal and tangential splitting, they become the short oblique muscles of the vertebral column (the semispinalis, multifidus, and rotatores muscles and a longer muscle, the spinalis division of the erector spinae muscle). The lateral, more superficial group of muscles, which is supplied by the lateral branches of the posterior primary rami of the spinal nerves, arises by the fusion of a larger number of consecutive segments and subsequent splitting to become the long extensor muscles of the back (the iliocostalis and longissimus divisions of the erector spinae muscle). The hypaxial column of hypomeres invades the region ventral to the vertebrae to give rise to the psoas and quadratus lumborum muscles (see Plate 1-18). The hypomeres also extend into the lateral and ventral body wall to form the layered muscles of the thorax and abdomen (see Plate 1-16). In the thorax, they are the intercostals; in the abdomen, they are the external and internal oblique, transverse abdominal, and rectus abdominis muscles (see Plate 1-18). The rectus abdominis muscle develops from the most ventral extension of the lower thoracic and first abdominal hypomeres that fuse in a cephalocaudal direction to become a single Myoblast C. Muscle fibers have become thicker as myofilaments have multiplied and differentiated into thin (actin) and thick (myosin) myofilaments arranged in alternate overlapping bands, giving a cross-striated appearance. Peripheral nuclei Myofibrils (bundles of longitudinally arranged myofilaments) Muscle fiber E. Myofilaments have aggregated into bundles to form myofibrils, as muscle fibers have grown in length and thickness and nuclei have shifted to periphery of muscle fibers. Muscle fibers are now thick and mature, consisting of alternating thin (actin) and thick (myosin) myofilaments aggregated into longitudinal bundles as myofibrils, with nuclei located at periphery. All muscles derived from the hypomeres are primarily flexors of the vertebral column. The tendinous intersections (inscriptions) are indicative of the original segmental character of the rectus abdominis muscle (see Plate 1-16). Also, the fibers of this muscle retain the cephalocaudal orientation of the original myotomic fibers. In the upper thoracic region, there is also a longitudinal muscle sheet that is continuous with the sheet that gives rise to the rectus abdominis muscle. Infrahyoid hypaxial muscles Ventral surface of limb Flexor muscles of limb Medial epaxial muscle column Thoracic spinal medulla (cord) Intervertebral disc Esophagus Right lung Inferior vena cava Phrenic n. Medial epaxial muscle column Thoracic spinal medulla (cord) Intervertebral disc Aorta Inferior vena cava Liver Umbilical cord Lateral epaxial muscle column Spinal nerve Dorsal ramus Ventral ramus Medial epaxial muscle column Lumbosacral spinal medulla (cord) Lumbosacral intervertebral disc Aorta Right common iliac v. Hindgut Paramesonephric duct Tibia Flexor muscles of limb Fibula Mesonephric duct Urinary bladder Right umbilical a. These muscles develop later because of the late division of the single cloacal opening into a urethral and anal opening in the male and female and the acquisition of an additional opening in the female-the vagina. This late development is a reflection of the more recent changes occurring in the evolution of the urogenital system. A single cloacal opening is characteristic of all adult fish, amphibians, reptiles, birds, and the primitive egg-laying mammals. In all mammals higher up the phylogenetic ladder than egg layers, there are separate anal and urogenital openings; however, it is only in female primates that the urethra and vagina are completely separate and have separate openings to the exterior. In humans, a striated cloacal sphincter muscle and levator ani muscle (pelvic diaphragm) arise from the third sacral to the first coccygeal myotomic hypomeres and are well developed by the eighth week. The striated external anal sphincter, perineal, and external genital muscles arise from the cloacal sphincter muscle by its rearrangements and additions during the establishment of the urogenital and anal openings. The deep, or inner, fibers of the cloacal sphincter muscle give rise to the urethral sphincter muscle. Although the muscles of the external genitalia are the same in both sexes, they, of necessity, must undergo a different arrangement in each sex. The mature pelvic muscle arrangement in the two sexes is present by the 16th week of development. However, not until sometime during the second year after birth do the urethral and external anal sphincter muscles come under voluntary control. As the limb buds grow, the proliferating local somatic mesenchyme eventually gives rise to all skeletal rudiments. Myotome cells from the adjacent somites invade the limb buds to give rise to all the skeletal muscles. When the ingrowth of myotome cells, nerve fibers, neurilemmal cells, pigment cells, and, possibly, the endothelium of the blood and lymphatic systems are excluded, the limb buds would still have the capacity for self-differentiation to become limbs containing all the normal skeletal rudiments. Early in the seventh week, the mesenchymal premuscle masses of the girdle musculature are formed in the human embryo. As the rudiments of the appendicular skeleton become differentiated within the developing limb, the mesenchyme from which the limb muscles arise is aggregated into masses grouped dorsal and ventral to the developing skeletal parts. The progressive formation of distinct muscles reaches the level of the hand and foot during the seventh week. The early limbs are flattened dorsoventrally and look like paddles projecting straight out from the body. They each have a cephalic (preaxial) border and a caudal (postaxial) border, as well as a craniocaudal attachment to the body opposite a number of myotomes (see Plate 1-9). Each upper limb bud lies opposite the lower five cervical and the first thoracic myotomes. The branches of the spinal nerves supplying these myotomes reach the base of their respective limb bud. As the bud elongates to form a limb, the nerves grow into it in such a manner that the group of limb muscles along the preaxial border of the upper limb becomes innervated by the fourth to the seventh cervical nerves, and those of the postaxial border, by the eighth cervical and the first thoracic nerves.

The disease may begin at any time during childhood treatment 247 sinemet 110 mg buy without prescription, and both sexes are equally affected medications for high blood pressure purchase 125 mg sinemet otc. The major signs of systemic-onset juvenile arthritis are a high treatment for 6mm kidney stone cheap sinemet 110 mg mastercard, spiking fever; characteristic rash; arthritis in one or multiple joints; hepatosplenomegaly; and lymphadenopathy (see Plates 5-16 and 5-17) medications used for anxiety purchase sinemet amex. The fever in systemic-onset arthritis typically rises above 102°F and falls to normal or below once (quotidian pattern) or twice (double quotidian) during every 24 hours treatment leukemia proven sinemet 125 mg. Although the rise and fall are usually rapid, the pattern of fever may otherwise be quite variable. In some children, the temperature is significantly elevated much of the time, with only short afebrile periods; in others, the duration of the fever spikes is shorter. The characteristic evanescent rash tends to occur simultaneously with the fever, often disappearing completely during afebrile periods (see Plates 5-16 and 5-17). It may be generalized or develop only in warmer areas such as the axillae and medial thighs or on the palms and soles. About 20% of children with a typical fever pattern have a maculopapular or pruritic rash, and 10% have no rash. In a few children, macules appear along scratch marks made in the skin (Koebner phenomenon). This manifestation, which may not appear immediately, should not be confused with the rapid appearance of the whealand-flare response normally seen after scratching. The 30% of children who have no initial evidence of joint involvement may seem to be completely normal during the afebrile periods. During the first 6 months of disease, however, arthritis develops in at least five joints in more than 80% of children with systemic-onset arthritis. About 25% of patients with systemic-onset arthritis have symptoms or signs of pericarditis and/or pleuritis. In asymptomatic children, echocardiography may reveal a small amount of pericardial fluid, but this is usually of little clinical significance; rarely, the amount of pericardial fluid is sufficient to cause cardiac tamponade and require aspiration. Pericardial effusions are usually associated with pleural effusions, and myocarditis frequently accompanies pericarditis. A pericardial friction rub may be localized to a small area, usually the lower sternum. Patients with pericardial irritation show a reluctance to lie down because of increased chest pain. Ocular involvement of any type is uncommon in patients with the systemic-onset form. The majority of deaths due to juvenile arthritis have occurred in children with the systemic-onset form. In many countries, the leading cause of death in patients with juvenile arthritis is renal failure secondary to amyloidosis. These regional differences suggest an interplay between genetic and environmental factors in the pathogenesis of secondary amyloidosis. Most patients have a modest-to-marked leukocytosis (15,000 to 25,000/mm3); occasionally, the count may be as high as 50,000/mm3. Polymorphonuclear leukocytes predominate, and there is a significant percentage of young cells. Normochromic, normocytic anemia with a normal mean corpuscular volume develops initially, but with continuing disease activity, the hemoglobin level decreases, followed by a fall in the mean corpuscular volume and development of a microcytic, hypochromic anemia. Serum ferritin levels may be normal to significantly elevated and probably reflect the generalized inflammatory disease. Although the anemia is unresponsive to administration of iron, reticulocytosis and a rapid rise in hemoglobin value occur with disease remission. During the febrile phase, urinalysis may reveal intermittent or persistent proteinuria or increased red or white blood cell counts. Children with macrophage activation syndrome commonly present with culturenegative septic shock and signs of cardiovascular collapse. Early recognition and treatment of this condition is necessary to prevent mortality. Macrophage activation syndrome has been described in Involvement of left knee with valgus deformity of lower leg and flexion contracture of knee Bulge sign Medial side of knee compressed or stroked proximally to move fluid away from medial compartment (upper picture). Lateral side is quickly compressed or stroked distally; bulge appears medial to patella (lower picture). Monarticular arthritis of knee may accelerate bone growth, resulting in a limb longer than its mate. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis. This subcategory encompasses those patients with the previously categorized seronegative spondyloarthropathies, including those with ankylosing spondylitis. In general, enthesitisrelated arthritis tends to strike boys older than age 6 years. Patients may have a family history of ankylosing spondylitis, inflammatory bowel disease, or reactive arthritis. The arthritis has a predilection for the lower extremities, especially the knees, ankles, and hips, and exclusive involvement of the hip is not uncommon. Acute unilateral anterior uveitis with pain and redness, as opposed to the chronic asymptomatic bilateral uveitis seen in oligoarticular patients, affects 20% of patients, but the duration of inflammation is usually short. In some patients, radiographic changes in the sacroiliac joints, mild back pain, or limitation of motion of the lower spine develops with time. Most children with sacroiliac inflammation will manifest typical inflammatory back pain symptoms, including prolonged morning stiffness, pain reduction with activity, alternating buttock pain, and waking from sleep due to pain in the second half of the night. When joint inflammation is absent, it may be confused with infectious, oncologic, or inflammatory diseases. When joint inflammation is present, infectious arthritis, osteomyelitis, and malignancy, especially leukemia, must be ruled out. Other diagnostic possibilities include a variety of systemic autoimmune diseases including lupus, inflammatory bowel disease, various types of systemic vasculitis, and, occasionally, reactions to infections or drugs. Polyarticular arthritis must be differentiated from other joint diseases such as systemic lupus erythematosus and acute rheumatic fever. Unlike these conditions, however, polyarticular arthritis rarely has significant systemic manifestations. Oligoarticular-onset arthritis, especially monarticular involvement, can be confused with trauma, joint conditions such as osteochondritis, viral-induced synovitis, Lyme disease, hemarthrosis, vascular malformation, and benign soft tissue tumors such as pigmented villonodular synovitis. However, because the same markers are present in many normal people, Cataract their demonstration is of value only in population studies, not in individual patients. Ideally, the primary care physician, rheumatologist, orthopedist, pedodontist, ophthalmologist, and physical therapist should all be involved in the treatment program. For children with persistent oligoarticular disease, intra-articular injections of triamcinolone hexacetonide, a long-acting corticosteroid, are frequently used to control the disease. These injections may be performed blindly utilizing anatomic landmarks to identify the joint space or may be done with radiographic guidance via ultrasound or fluoroscopy. When performed in arthritic knees, these injections will achieve complete remission of the disease for 12 months in 60% of patients. Many joints are amenable to this therapeutic intervention, including the wrist, ankles, hips, elbows, and temporomandibular joints, but with shorter duration of effect. For children with extended oligoarticular or polyarticular subtypes, weekly administration of methotrexate now stands as the first-line drug of choice. Methotrexate, an antimetabolite, may be administered via the oral or parenteral route with no significant difference in efficacy. For patients who fail traditional disease-modifying agents, the development of the biologic response modifiers has represented an important advance in therapy. These agents are a class of medication that selectively inhibits specific proinflammatory cytokines or pathways critical to perpetuating arthritis. However, these children may also respond favorably to sulfasalazine, which is metabolized to the antiinflammatory 5-aminosalicylic acid. Methotrexate, as well as etanercept, has been successfully used to treat children with juvenile psoriatic arthritis. Systemic corticosteroids are used frequently to treat the constitutional symptoms. Systemic-onset patients with signs of macrophage activation syndrome respond well to high doses of corticosteroids and anakinra, with the possible addition of cyclosporine. However, given the threat of permanent vision Fixed forward position of head due to involvement of joints in cervical spine Receding chin results from early closure of ossification centers of mandible. Amyloid hepatosplenomegaly occurs primarily in systemic onset form; rare in United States. These specialists play a critical role in improving the function of those children with functional impairments such as limb-length discrepancy or muscle atrophy. Nutritionists may be required for those patients on systemic therapy with corticosteroids to design dietary strategies to minimize weight gain. Psychologists may be needed to help patients and families develop strategies to deal with the stress inherent to a chronic illness. Although commonly termed degenerative joint disease, the designation osteoarthritis emphasizes the presence of inflammation seen in the synovium in almost all cases as the disease progresses. Many factors influence its onset and the speed of joint deterioration, including aging, gender, obesity, heredity, trauma (related to sports or occupation), joint overuse, joint instability, and malalignment. Involved basic mechanisms of pathophysiology include "normal" loading on abnormal cartilage versus "abnormal" loading on normal cartilage. Secondary osteoarthritis, the term used to designate osteoarthritis appearing as a sequel to other forms of arthritis, injury, internal derangement, or dysplasia of the joint, is not uncommonly seen in younger persons. Evidence of osteoarthritis has been found in the skeletal remains of prehistoric animals and humans. The true prevalence is difficult to determine because mild or early osteoarthritis may be asymptomatic and is demonstrated primarily radiographically. In asymptomatic persons, osteoarthritis is often discovered accidentally on radiographs performed for other diagnostic purposes. Pathologic changes in cartilage are characterized by alterations in proteoglycan and collagen. This leads to a softening of the cartilage followed by fraying and fibrillation; cracks develop extending more deeply into the cartilage. As degeneration progresses, the entire cartilage becomes thinner and the surface becomes rough from the focal ulcerations. In subchondral tissue, the new bone grows chiefly beneath the eroded cartilage surface, thus eventually becoming the articular surface. The most characteristic pathologic feature is the growth of osteophytes at the margins of affected joints (spur formation). The osteophyte, which consists of bone growing from the joint margin, usually follows the contour of the articular surface within the capsule and ligamentous attachments. The synovial and capsular tissues may show mild-to-moderate inflammation and fibrous thickening in joints severely deranged by extensive damage to cartilage and bone. As noted, many tissues are involved in the process, including subchondral bone, synovium, cartilage, and bone at the joint periphery, as well as ligaments and muscles. Proteases targeted to proteoglycans and collagen play an important role in joint breakdown. Obesity has a strong relationship to osteoarthritis, especially in the presence of additional factors such as joint instability and malalignment. There is a suggestion that aging per se may play an etiologic role in the form of advanced glycation endproducts that lead to formation of cross-links between sugars and proteins, making the cartilage more susceptible to injury from other risk factors. Microtrauma caused by daily "wear and tear" on articular cartilage in weight-bearing joints likely contributes significantly to the degenerative process. As noted, mechanical factors that predispose to osteoarthritis are excessive body weight, postural abnormalities, and joint instability. Alterations in joint architecture, such as acetabular dysplasia or pistol-grip deformity of the hip, may play a role in development of osteoarthritis in this joint. Most commonly involved are the weight-bearing joints (see Plate 5-23) and small joints of the hand. The patient is usually comfortable at rest but finds weight bearing and moving the affected joints painful. Aching during rainy weather, stiffness after inactivity, and crepitation are other frequent complaints. Physical examination reveals tenderness, pain and crepitation with joint movement, and, usually, a limited range of motion. Although signs of synovitis-warmth and erythema over the joint-are usually limited or absent, swelling exists in association with bony hypertrophy or if there is a joint effusion. Joint palpation reveals osteophytes and crepitus (grinding sensation) on joint movement. Because the knee is so crucial in the lever action of the leg and in ambulation, osteoarthritis in this joint can be both very painful and disabling, especially when it is bilateral (see Plate 5-24). The medial compartment of the knee is usually more severely damaged than the lateral compartment. The structural damage in the joint causes pain, restriction of motion, and crepitation. Early in their development, the nodes are tender and painful; when mature, they are often asymptomatic but may have significant cosmetic effects. At the base of the thumb, the first carpometacarpal joint commonly undergoes the degenerative changes of osteoarthritis. Hip Joint Involvement Osteoarthritis of the hip (malum coxae senilis) is a major crippling and painful form of osteoarthritis. Standing and walking often cause severe localized hip pain that may radiate laterally as well as to the medial aspect of the thigh and knee. The articular cartilage becomes thin, cysts form in the femoral head and acetabulum, the bone softens, and the femoral head flattens. Osteophytes grow from the head of the femur and around the rim of the acetabulum (see Plates 5-26 and 5-27). As a result, joint motion becomes markedly restricted, leading to a fixed deformity of the hip in flexion, adduction, and external rotation.

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