Aggrenox

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Gretchen E. Glaser, MD

  • Department of Obstetrics and Gynecology
  • Abington Memorial Hospital
  • Abington, Pennsylvania

Axons from the temporal hemiretinas remain ipsilateral symptoms kidney problems cheap aggrenox caps 25/200mg free shipping, whereas axons from the nasal hemiretinas cross the midline in the optic chiasm treatment alternatives boca raton 25/200 mg aggrenox caps with visa. Sensory portions of the ophthalmic division of V supply general sensation to the cornea and eyeball and provide the afferent limb of the corneal reflex world medicine buy aggrenox caps with american express. It can be damaged by demyelinating disease (optic neuritis in multiple sclerosis) medicine 54 092 buy generic aggrenox caps 25/200 mg line, by optic nerve gliomas medicine to treat uti order 25/200 mg aggrenox caps amex, by ischemic injury (central retinal artery) medicine 750 dollars generic aggrenox caps 25/200mg amex, or by trauma (sphenoid fracture). The ipsilateral nature of the deficit rules out optic chiasm, optic tract, or central visual lesions. Macular degeneration involves damage to the coneintensive regions of the retina (macula) and leads to the inability to read and the loss of acuity. Increased intracranial pressure can result in papilledema, a condition in which pressure pushes the optic nerve head inward (toward the center of the eyeball), producing a swollen appearance on ophthalmoscopy. This process takes 24 hours to occur after onset of intracranial pressure; the presence of papilledema is used diagnostically to identify increased intracranial pressure. Preganglionic parasympathetic axons from the superior salivatory nucleus distribute to the pterygopalatine ganglion, which supplies the lacrimal gland (tear production). Sympathetic postganglionic nerve fibers from the superior cervical ganglion supply the pupillary dilator muscle and the superior tarsal muscle (damage results in mild ptosis). The most conspicuous deficit is the inability to adduct the ipsilateral eye, a lateral strabismus (resulting from unopposed action of the lateral rectus), and diplopia. Damage to the levator palpebrae superioris muscle results in profound ptosis of the ipsilateral eye. Thus, a patient has difficulty walking down stairs and stepping off curbs and has trouble reading while lying down. The ciliary ganglion gives rise to postganglionic parasympathetic axons that supply the pupillary constrictor muscle and the ciliary muscle; damage results in a fixed and dilated pupil that does not constrict for the pupillary light reflex and does not accommodate to near vision. It has three subdivisions: (1) ophthalmic-sensory innervation; (2) maxillary-sensory innervation; and (3) mandibular-sensory innervation and motor innervation of the masticatory muscles and tensor tympani muscles. Unlike the somatosensory dermatomes, which exhibit considerable overlap with nerve fibers of adjacent roots, the trigeminal subdivisions show no overlap at all. Damage to one of the subdivisions results in total anesthesia in the territory of sensory distribution. The trigeminal nerve also carries proprioceptive information from muscle spindles in muscles of mastication and extraocular muscles. The maxillary and mandibular divisions are more common targets than the ophthalmic division, and the disorder is more common in older individuals. These episodes of pain may recur several times a day, with paroxysms experienced for weeks on end. Often there is a trigger point, at which mild stimuli such as light touch, chewing, or even talking can provoke an attack. During an attack, no loss of sensation occurs in the distribution of the affected branch. In some cases, compression of the trigeminal nerve root by a small aberrant branch of the superior cerebellar artery or another nearby artery is the suspected cause; in other cases a tumor, an inflammation, or a demyelinating plaque may precipitate such attacks. If trigeminal neuralgia occurs in the accompaniment of other progressive pathology, the neurological examination reveals sensory and motor deficits associated with the involved branch of the trigeminal nerve. Idiopathic trigeminal neuralgia usually can be treated with carbamazepine or other antiseizure and membranestabilizing agents, which sometimes permit the condition to regress. In other cases, the nerve root is ablated temporarily or permanently; the resultant functional deficit is often better tolerated than the excruciating paroxysms of pain. With erosion of a lesion (decay) into the dental pulp or close to the dental pulp, these nerve fibers may become exquisitely sensitive to temperature changes (especially cold) or pressure (by edema or mechanical force), resulting in the sensation of severe pain. The motor fibers distribute to the muscles of facial expression, including the scalp, the auricle, the buccinator, the stapedius, and the stylohyoid muscles, and to the posterior belly of the digastric muscle. Special sensory taste fibers from the anterior two thirds of the tongue (via the chorda tympani) and the soft palate (via the greater petrosal nerve), whose primary sensory cell bodies are located in the geniculate ganglion, convey that information to the rostral portion of nucleus solitarius in the medulla. Surgical procedures in this region of the face, particularly those performed to remove mass lesions, may damage the facial nerve, resulting in facial palsy in affected muscles. Some patients report previous retroauricular pain, decreased tearing, or hyperacusis for a day or two. The facial palsy involves all of the muscles on the affected side, unlike a central facial palsy resulting from a lesion in the contralateral genu of the internal capsule, which affects only the lower part of the face. Involvement of the nerve to the stapedius muscle results in sensitivity to loud sounds (hyperacusis). Recovery can occur within a few weeks or months, particularly if only partial damage to the nerve has occurred and only some weakness has been present. With profound paralysis of facial muscles, the regenerative process may take as long as 2 years. During such a regenerative process, some regenerating nerve fibers may sprout to aberrant sites; former autonomic fibers that innervated salivary glands may be redirected to the lacrimal glands, resulting in "crocodile tears" or an abnormal gustatory-lacrimal reflex. Some aberrant regenerating facial nerve fibers may reach the wrong muscle fibers, resulting in tics, spasms, dyskinesias, or contractures. The peripheral process of the vestibular ganglion neurons innervates hair cells in the utricle and saccule that respond to linear acceleration (gravity) and in the ampullae of the semicircular ducts that respond to angular acceleration (movement). The utricle, the saccule, and the semicircular ducts provide neural signals for coordination and equilibration of position and for movement of the head and neck. The central processes of the vestibular ganglion cells terminate in vestibular nuclei (medial, lateral, superior, and inferior) in the medulla and pons and in the cerebellum. The peripheral processes of spiral ganglion cells innervate hair cells that lie along the cochlear duct in the organ of Corti. They convey hearing information via central axonal processes into the cochlear nuclei (dorsal and ventral). The tumor may extend rostrally to the trigeminal nerve or caudally to the glossopharyngeal and vagus nerves and also may affect the adjacent brain stem and cerebellum. Motor fibers from the nucleus ambiguus supply the stylopharyngeus muscle and may assist in the innervation of pharyngeal muscles for swallowing. Special sensory axons from the petrosal (inferior) ganglion carry information from taste buds on the posterior one third of the tongue (including numerous taste buds in the vallate papillae) and part of the soft palate. Axons from additional primary sensory neurons in the inferior ganglion also carry general sensation from the posterior one third of the tongue and from the pharynx, the fauces, the tonsils, the tympanic cavity, the eustachian tube, and the mastoid cells. The general sensory fibers from the pharynx provide the afferent limb of the gag reflex. Additional primary sensory neurons innervate the carotid body (chemoreception of carbon dioxide) and the carotid sinus (baroceptors) and convey their central axons to the caudal nucleus solitarius (solitary tract nucleus). The pain originates in the throat (tonsillar fossa) or sometimes the jaw and radiates to the ear. If the irritative process activates glossopharyngeal afferents associated with brain stem vasomotor responses, the patient may experience bradycardia and syncope. The treatment of glossopharyngeal neuralgia is similar to treatment of trigeminal neuralgia. Successful treatment also has occurred surgically through decompression of a tortuous aberrant vessel. The axons then emerge as rootlets from the lateral margin of the spinal cord, ascend behind the denticulate ligaments, and coalesce as a single nerve. This nerve then ascends through the foramen magnum and joins the vagus nerve to exit through the jugular foramen. This results in ipsilateral flaccid paralysis of the sternocleidomastoid muscle and the upper two thirds of the trapezius, causing atrophy and loss of tone. The patient has great difficulty turning his or her head to the opposite side (sternocleidomastoid). The shoulder hangs downward, with caudal and lateral displacement of the scapula, and the arm cannot be raised more than 90 degrees. In circumstances in which bilateral damage occurs to the spinal accessory nucleus (as in amyotrophic lateral sclerosis), the bilateral denervation of the sternocleidomastoid leaves the patient unable to hold up his or her head. A lesion in these axons results in hoarseness, dysphagia, and decreased gag reflex (efferent limb). Special sensory axons from the nodose (inferior) ganglion, which carry information from taste buds in the posterior pharynx (found mainly in children), send central branches to terminate in the rostral nucleus solitarius. Primary sensory axons from the inferior ganglion also convey general sensation from the larynx, the pharynx, and the tho- racic and abdominal viscera and terminate mainly in the caudal nucleus solitarius. Intracranially, this nerve can be damaged by a tumor, hematoma, vascular infarct, aneurysm, meningitis, and other disorders. Extracranially, the vagus nerve can be damaged by a tumor, aneurysm, trauma, or infectious process. Unilateral damage to the vagus nerve results in (1) drooping of the soft palate, with the intact contralateral soft palate pulled to the opposite side during phonation, accompanied by nasal speech; (2) hoarseness resulting from involvement of the nucleus ambiguus fibers that extend to the laryngeal muscles; (3) ipsilateral laryngeal anesthesia; and (4) tachycardia and arrhythmias in some instances. Damage to this nerve leads to weakness of the ipsilateral tongue muscles; the tongue, when protruded, deviates toward the weak side because of the unopposed action of the innervated contralateral genioglossus muscle. The emerging hypoglossal nerve fibers can be damaged intracranially by a paramedian infarct (that also damages the pyramid and medial lemniscus, producing a so-called alternating hemiplegia) or can be damaged peripherally by a meningeal tumor, a metastatic tumor, or bony overgrowth or as an unwanted consequence of a carotid endarterectomy. Hypoglossal nerve damage on one side produces flaccid paralysis of the ipsilateral tongue musculature, accompanied by atrophy. An attempt to protrude the tongue results in deviation of the tongue toward the weak side because of the unopposed actions of the intact genioglossus muscle. Dorsalis, centralis superior Cerebral aqueduct and periaqueductal gray matter 4 Paramedian reticular formation Lateral reticular formation and nuclei 3 Raphe nuclei Medial reticular formation 2 Respiratory nuclei Raphe nuclei 1 Major noradrenergic and adrenergic cell groups Nucleus raphe pallidus midline neurons Dendrites Medial longitudinal fasciculus Nucleus raphe pallidus midline neurons with dendrites extending dorsally, ventrally, and laterally, and contributing to the formation of dendrite bundles, which help to coordinate firing of contributing neurons of this serotonergic reticular formation group. Nucleus raphe dorsalis neuron Nucleus raphe dorsalis neuron within the medial longitudinal fasciculus, with widespread dendrites branching into multiple regions. Catecholaminergic neurons are found in the locus coeruleus (group A6), and tegmental groups denoted here as groups A1, A2, and A5 (norepinephrine-containing neurons). Raphe nuclei are found in the midline and in wings of cells that extend laterally. Major afferent connections to the reticular formation Olfactory input via median forebrain bundle Cerebral cortex Corticoreticular Globus pallidus Pallidotegmental tract Hypothalamus Lateral hypothalamic area, other nuclei Limbic formation Amygdala, septal nuclei, habenula, insular cortex, bed nucleus of stria terminalis Reticular formation Cerebellar deep nuclei Spinal cord Sensory sources Brain stem Trigeminal nucleus, vestibular nucleus, cochlear nucleus, other auditory nuclei, nucleus of the solitary tract, superior colliculus (deep layers) B. Olfactory input arrives through olfactory tract projections into forebrain regions. It projects through nonspecific nuclei of the thalamus to the cerebral cortex; lesions in this area lead to coma. Monoamine neurons from the upper brain stem also project directly to the cerebral cortex, along with cholinergic and histaminergic neurons, and excite cortical circuits, enhancing their processing capabilities. Circulating substances such as interleukin-1 beta can act on key sites in the hypothalamus and brain stem to influence components of sleep. Illness behavior involves enhanced slow-wave sleep induced by interleukin-1 beta and other inflammatory mediators. Dreams probably occur because the cortex is attending to internal stimuli provided by stored memories. The functional organization of the cerebellar hemisphere follows a vertical organization: (1) vermis (midline); (2) paravermis; and (3) lateral hemispheres. Each of these functional regions is associated with specific deep nuclei (fastigial, globose and emboliform, and dentate, respectively) that help to regulate the activity of reticulospinal and vestibulospinal tracts, the rubrospinal tract, and the corticospinal tract, respectively. The cerebellar cortex has multiple, orderly, small infoldings, or convolutions, called folia. The vascular supply to the cerebellum comes mainly from the superior, anterior inferior, and posterior inferior cerebellar arteries. The superior cerebellar artery has fine branches that can rupture in hypertensive conditions and damage the rostral cerebellum and deep nuclei such as the dentate nucleus. A cerebellar hematoma acts as a space-occupying lesion and also may induce further edema. As a result, increased intracranial pressure can occur, and the flow of cerebrospinal fluid can be disrupted, secondarily bringing about supratentorial increased intracranial pressure. The patient experiences headache, nausea and vomiting, and vertigo and then may lapse into a coma. Decerebrate posturing, blood pressure dysregulation, and respiratory failure may ensue. Smaller intracerebellar bleeds result in ipsilateral symptoms that are characteristic of the affected region of cerebellum. In this horizontal (axial) section through the right cerebellar hemisphere, the left hemisphere has been removed, the cerebellar peduncles cut, and the fourth ventricle opened to show the dorsal surface of the brain stem below. The cerebellar peduncles provide the large white matter regions through which afferents and efferents pass, connecting the cerebellum with the brain stem and diencephalon. Inputs into the cerebellar hemispheres show a similar general organization, with variation from lobule to lobule, particularly for noradrenergic inputs from the locus coeruleus. Inputs from a vast majority of nuclei projecting to the cerebellar hemispheres arrive as mossy fibers; the inferior olivary nucleus sends climbing fibers to end on Purkinje cell dendrites in the cerebellar hemispheres, and the locus coeruleus sends diffuse varicose inputs into all three layers of many regions of the cerebellar cortex. The deep nuclei provide the "coarse adjustment" upon which is superimposed the "fine adjustment" by the cerebellar cortex. Cerebellar medulloblastomas are childhood malignant tumors that often begin in the flocculonodular lobe and are detected initially because of truncal ataxia and a broad-based uncoordinated gait. However, as the tumor slowly grows, it involves additional areas of the cerebellum by means of pressure or by invading neighboring areas. Then, in addition to the truncal ataxia, additional limb ataxia, dysmetria, dysdiadochokinesia, intention tremor, hypotonia, and other characteristics of lateral cerebellar damage are seen. Because the posterior fossa is involved, and not supratentorial regions, papilledema does not occur and does not provide a clue for diagnosis; rather, the increased posterior fossa pressure results in occipital headaches with nausea, vomiting, and nystagmus. The fastigial nucleus receives input from the vermis and sends projections to reticular and vestibular nuclei, the cells of origin of the reticulospinal and vestibulospinal tracts. The globose and emboliform nuclei receive input from the paravermis and project to the red nucleus, the cells of origin for the rubrospinal tract. The dentate nucleus receives input from the lateral hemispheres and projects to the ventrolateral and ventral anterior nuclei of the thalamus; these thalamic nuclei project to the cells of origin of the corticospinal and corticobulbar tracts. The table lists the major afferent and efferent projections through the three cerebellar peduncles and are depicted in color.

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Infundibular process Forebrain Neural ectoderm Infundibular process Rathke pouch Oral ectoderm Mesoderm 1 symptoms gallbladder problems cheap aggrenox caps online. Rathke pouch "pinched off" Median eminence Pars tuberalis Infundibulum Pars nervosa Sphenoid sinus 4 medications causing hair loss buy 25/200 mg aggrenox caps amex. Pars tuberalis encircles infundibular stalk (lateral surface view) Pars intermedia Cleft Pars distalis 6 medicine woman cast purchase 25/200mg aggrenox caps overnight delivery. Early in gestation medications equivalent to asmanex inhaler generic 25/200mg aggrenox caps with mastercard, the adenohypophysis-or anterior pituitary-arises as a dorsal outpocketing of thickened oral ectoderm called the Rathke pouch symptoms 6 days after iui buy cheapest aggrenox caps and aggrenox caps. By week 6 of gestation symptoms chlamydia aggrenox caps 25/200 mg for sale, it pinches off from the roof of the oral cavity and migrates to a site just anterior to a simultaneous downgrowth of neural ectoderm called the infundibular process. Cell proliferation in the anterior wall of the Rathke pouch then gives rise to the main part of the anterior lobe, which is the pars distalis. Its cells give rise to the pars nervosa (posterior lobe) of the neurohypophysis (posterior pituitary), which keeps its neural connection to the brain. The two tissues become closely apposed but their microscopic structure remains different, reflecting the developmental dichotomy. Remnants of the Rathke pouch may persist as either a vestigial cleft or colloid-filled cysts at the anterior border with the neurohypophysis. The dorsal wall of the cleft fuses with the adjoining part of the posterior lobe to make up the small pars intermedia. Its size varies greatly throughout life, however, depending on physiologic states. They may arise from multiple oncogene abnormalities, such as G-protein and ras gene mutations, p53 gene deletions, and mutations that lead to multiple endocrine neoplasia. One type of secretory adenoma that usually requires surgery causes acromegaly in adults and gigantism in children. Endocrine System Main division Infundibular stalk Adenohypophysis (anterior pituitary) (from oral ectoderm) Neurohypophysis (posterior pituitary) (from neural ectoderm) 235 Subdivisions Pars distalis (anterior lobe) Pars tuberalis Pars intermedia (intermediate lobe) Pars nervosa (posterior lobe) Infundibular stalk Median eminence Pars tuberalis Posterior lobe Anterior lobe Intermediate lobe Acromegaly. This panoramic view of general topography and main parts shows a darkly stained anterior lobe with a lightly stained posterior lobe. The pars tuberalis, a thin strip of tissue that extends upward from the anterior lobe, incompletely surrounds the infundibular stalk. The adenohypophysis, made of glandular epithelium, consists of the anterior lobe (pars distalis), the largest part; pars tuberalis, a thin collar of tissue surrounding the infundibular stalk; and pars intermedia (intermediate lobe), a narrow rudimentary band just posterior to the vestigial cleft and in contact with the posterior lobe. The neurohypophysis, made of neural tissue, comprises the posterior lobe, the main, most expanded part; median eminence, the upper part that attaches the gland to the hypothalamus; and connecting infundibular stalk. The median eminence is partly encircled by the pars tuberalis, which links it via a network of many capillaries to the anterior lobe. The adenohypophysis synthesizes and secretes several polypeptide and glycoprotein hormones; the neurohypophysis (by way of modified neurons from the hypothalamus) secretes two peptide hormones. All hormones enter the systemic circulation and are taken to distant target tissues to regulate functions. Thickening of cranial bones, mandible, soft tissues, and internal organs (visceromegaly) are other symptoms. Left untreated, serious complications and premature death occur, mainly from cardiovascular disease. To improve the prognosis and quality of life, treatment is surgery to excise the tumor and sometimes follow-up radiation and pharmacologic therapy. Hypothalamic vessels Superior hypophyseal artery Primary capillary plexus of hypophyseal portal system Internal carotid artery Hypophyseal arteries Cavernous sinus Stalk Anterior lobe Artery of trabecula Posterior lobe Long hypophyseal portal veins Short hypophyseal portal veins Posterior lobe Inferior aspect. Capillary plexus of pars nervosa Secondary capillary plexus of hypophyseal portal system Anterior lobe Inferior hypophyseal artery Efferent hypophyseal veins to cavernous sinus 10. The superior hypophyseal arteries, from above, bring blood to the anterior lobe by first forming a primary capillary plexus made of vascular loops in the area of the median eminence and pars tuberalis. These vessels give rise to a network of portal venules-the hypophyseal portal system-which crosses the ventral aspect of the pituitary stalk to drain into a secondary plexus of sinusoidal fenestrated capillaries in the anterior lobe. This portal system is critical for control of the adenohypophysis by neurosecretions from hypothalamic neurons that convey releasing and inhibiting hormones to the primary plexus. Neurosecretions reach the secondary plexus to regulate release of specific adenohypophysis hormones, which are also secreted into the secondary capillary plexus. Small efferent veins, in turn, drain into cavernous sinuses surrounding the gland. They drain into a plexus of sinusoidal fenestrated capillaries that take blood via efferent hypophyseal veins to the cavernous sinus. An important branch of the superior hypophyseal artery, the artery of the trabecula, bypasses the portal circulation and forms small capillary loops in the pars intermedia, which anastomose with capillaries in the anterior lobe. The anterior and posterior lobes are richly vascularized, but the pars intermedia is not. Because of ischemic necrosis of the anterior pituitary caused by severe postpartum hemorrhage, symptoms include cessation of lactation (agalactorrhea) and menstrual periods (amenorrhea, hypotension, and fatigue). Because of advances in obstetrics in industrialized countries, it is a rare complication, but in other parts of the world, it is a major threat to pregnant women and a common cause of hypopituitarism. In pregnancy, the anterior pituitary nearly doubles in size but without simultaneous increase in blood supply, so the gland becomes vulnerable to anoxia and infarction. If profound postpartum bleeding occurs, blood supply to the anterior lobe is inadequate, resulting in parenchymal cell necrosis. The anterior lobe consists of typical glandular epithelium; the posterior lobe resembles nervous tissue seen in the central nervous system. Colloid-filled cysts (*) and scattered groups of basophilic cells (arrows) are in the intermediate lobe. A few small basophilic cells are scattered in that lobe, and others line colloid-filled cysts (*). The anterior lobe is glandular epithelium, which stains dark because of its many, tightly packed nucleated parenchymal cells. The posterior lobe is more lightly stained because it is typically made of nervous tissue. In the intermediate lobe, at the border with the posterior lobe, rudiments of the Rathke pouch persist as accumulations of small colloid-filled cysts. Showing great size variation among species, the intermediate lobe constitutes less than 2% of the adult human pituitary. This lobe is rudimentary in humans and its function in adults is uncertain, but it consists of either isolated groups of low columnar epithelial cells or a discontinuous epithelial layer, which often surrounds colloid-filled follicles, and contains basophilic parenchymal cells and a few scattered, lightly stained polygonal cells. Cells in this lobe produce melanocyte-stimulating hormone and the opiate peptide -endorphin. Cytoplasm of chromophils (arrows) is stained; that of smaller chromophobes is not, but their nuclei (arrowheads) are. Cells are interspersed with sinusoidal capillaries (Cap) and delicate connective tissue stroma. Chromophobes usually have small, heterochromatic nuclei; chromophils have larger, euchromatic nuclei with prominent nucleoli. The different staining pattern of the small acidophils and larger basophils reflects their granule content. A large network of sinusoidal capillaries (Cap) is between the clumps of parenchymal cells. The vessels receive hormones released by these cells and deliver releasing or inhibiting factors from the hypothalamohypophyseal portal system to affect cells of the anterior lobe. Acidophils (A) have intensely eosinophilic cytoplasm (red), basophils (B) are dark (green), and chromophobes (C) stain poorly. It consists of clumps or cords of glandular epithelial cells in close relation to a network of sinusoidal capillaries with large and irregular lumina. Scant loose connective tissue is made of delicate reticular fiber stroma, which supports glandular cells and sinusoid walls. Hematoxylin and eosin (H&E) reveals two distinct parenchymal cell types: chromophils (large, have secretory granules, stain intensely) and chromophobes (smaller, have few or no secretory granules, stain faintly). Chromophobes have less cytoplasm than do chromophils and may be quiescent, degranulated, or undifferentiated cells. Chromophils can be distinguished as acidophils or basophils on the basis of their cytoplasmic affinity for acid or basic dyes and on the tinctorial properties of their secretory granules. Acidophils, typically smaller cells with smoothly refractive cytoplasm, secrete two polypeptide hormones. The larger basophils are more granular and secrete four major polypeptide hormones. Via routine stains, proportions of glandular cell types are about 40% acidophils, 10% basophils, and 50% chromophobes. Immunocytochemistry with specific antibodies has allowed more precise identification of these cells and their hormone content. A functional nomenclature is now routinely used to designate cell types according to the secreted hormone or target organ. Use of immunocytochemistry helps clarify the normal regional distribution of cells, correlates structure to function, and aids tumor diagnosis. These polygonal, medium to large cells stain for corticotropin, melanocyte-stimulating hormone, endorphin, and enkephalin. Many cells have an unstained area near the nucleus, which indicates a large lysosome. Prolactinoma, accounting for 30% of all neoplastic pituitary tumors, is the most common type. A tumor of mammotrophs, it leads to amenorrhea, infertility, osteopenia, and galactorrhea in women and erectile dysfunction and loss of libido in men. Amyloid deposits and calcified spherites (or psammoma bodies) accompany excessive synthesis and secretion of prolactin. Treatment with the dopamine agonist bromocriptine reduces tumor size and inhibits prolactin secretion. Tumors larger than 10 mm in diameter (macroadenomas) require surgery or radiation. Thyroid hormones Adrenocortical hormones Estrogen Testosterone Progesterone Breast (milk production) Bone, muscle, organs (growth) Insulin Pancreas 10. Epithelial parenchymal cells in the adenohypophysis respond to these factors by secreting their own hormones, which, in turn, affect distant target organs. Target organ hormones then act on the hypothalamus and anterior lobe by negative feedback mechanisms. The anterior lobe contains two types of acidophils-somatotrophs and mammotrophs-that are best visualized by immunocytochemistry. Three types of basophils in the anterior lobe are also best seen via special stains. They are named corticotrophs, gonadotrophs, and thyrotrophs on the basis of the hormone that they secrete and their target organ. A subtype of basophil in the pars intermedia synthesizes melanocyte-stimulating hormone. Kallmann syndrome is an X-linked inherited form that is also associated with loss of smell (anosmia). To reinstate puberty and fertility, hormone replacement therapy is combined with assisted reproductive technology. These ultrastructural features are typical of those of a protein-secreting endocrine cell. Many organelles such as a well-developed Golgi complex needed for hormone synthesis and clustered round to ovoid secretory vesicles (arrows) with a moderately dense core are close to the cell membrane. The somatotroph has larger, more densely stained secretory vesicles than does the gonadotroph. In the interstices lie stellate fibroblast-like cells (F) with conspicuous cytoskeletal elements such as microtubules and filaments. Intercellular junctions, which are better seen at higher magnification, link these supportive cells. The ultrastructure of its parenchymal cells closely resembles that of glandular epithelial cells of most other endocrine glands that synthesize and secrete protein hormones. These cells are round to polygonal, with organelles needed for synthesis, packaging, storage, and release of secretory products. Active cells have a prominent Golgi complex, many mitochondria, an extensive rough endoplasmic reticulum, and typical membranebound secretory granules (vesicles). The one nucleus is round to irregular in shape and has one or more prominent nucleoli. Secretory vesicles scattered in the cytoplasm or near the cell surface discharge by exocytosis close to thin-walled and highly permeable fenestrated capillaries with diaphragms. Rapid delivery of hormones and regulatory factors to and from the anterior lobe and bloodstream thus occurs. Electron microscopy used with immunocytochemistry can reveal the types of secretory cells in the anterior lobe. Correlation of size and morphology of secretory granules-which vary in size, shape, and staining properties-with immunocytochemical localization of antibodies to specific hormones permit ultrastructural identification of cell types. Also, stellate fibroblast-like cells with pale cytoplasm and prominent cytoskeleton form a supportive framework in the gland. Synthesized in supraoptic and paraventricular nuclei of the hypothalamus, they are taken via axoplasmic transport in the hypothalamohypophyseal tract to the posterior lobe. Then, in response to an action potential, they are discharged by exocytosis of neurosecretory granules directly to thin-walled sinusoidal fenestrated capillaries. Oxytocin stimulates uterine contraction during late stages of pregnancy and contraction of myoepithelial cells in the breast for milk ejection. It increases absorption of glomerular filtrate in renal collecting ducts and distal convoluted tubules, thereby conserving water.

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A lesion results in difficulty climbing stairs and rising from a sitting position medicine 7253 generic aggrenox caps 25/200 mg line. The sciatic nerve proper supplies the biceps femoris medicine effects discount aggrenox caps express, semitendinosus treatment advocacy center purchase aggrenox caps american express, and semimembranosus muscles (hamstrings) and regulates flexion of the lower leg treatment yeast infection 25/200 mg aggrenox caps with mastercard. Because it branches into the tibial and common peroneal nerves treatment 2nd degree burn order generic aggrenox caps line, major lesions of the sciatic nerve result in weakness of leg flexion medications you cant drink alcohol buy generic aggrenox caps 25/200mg on line, weakness of all muscles below the knee, and loss of sensation in the posterior thigh, posterior and lateral aspects of the leg, and sole of the foot. Such lesions may result from a fracture of the pelvis or femur, nerve compression, a herniated disc, or diabetes. Sensory branches supply the skin over the lateral calf, foot, heel, and small toe (sural nerve) and the medial aspect of the heel and the sole of the foot (tibial nerve). A lesion can occur because of compression in the tarsal tunnel, a tumor, or diabetes; it results in weakness of plantar flexion and inversion of the foot, weakness of toe flexion, and loss of sensation in the lateral calf and the plantar region of the foot. Surface recording electrodes are placed over a distal innervated muscle, and the nerve is stimulated in one or more places, resulting in an indirect evaluation of motor conduction velocity and the muscle response to tibial nerve stimulation. Sensory conduction velocity evaluation is a bit more straightforward; the stimulating electrode is placed at a distal site, and compound action potentials are recorded over at least two proximal sites. A more complex evaluation of reflexes involves evaluation of the muscle stretch (monosynaptic) reflex. With recording electrodes placed over the distal muscle (triceps surae), the tibial nerve is gradually stimulated first by weak and then by stronger electrical current in the popliteal fossa. This is a long-latency response, called the H wave or H reflex because it involves both the sensory and the motor arms of the muscle stretch reflex. This H reflex evaluation is useful in assessment of axonal neuropathies and demyelinating neuropathies. Peripheral Nervous System 197 Common peroneal nerve (in phantom) Tendon of biceps femoris muscle Common peroneal nerve Head of fibula Peroneus longus muscle Common Peroneal Nerve (L4, L5; S1, S2) Lateral sural cutaneous nerve (in phantom) Articular branches Anterior tibial recurrent branch Extensor digitorum longus muscle Deep peroneal nerve Tibialis anterior muscle Superficial peroneal nerve Cutaneous innervation Branches of lateral sural cutaneous nerve Peroneus longus muscle Extensor digitorum longus muscle Peroneus brevis muscle Extensor hallucis longus muscle Medial dorsal cutaneous nerve Intermediate dorsal cutaneous nerve Lateral sural cutaneous nerve Lateral branch of deep peroneal nerve to: Extensor hallucis brevis muscle and Extensor digitorum brevis muscle Medial branch of deep peroneal nerve Superior extensor retinaculum Superficial peroneal nerve Inferior extensor retinaculum (cut) Lateral dorsal cutaneous nerve (branch of sural nerve) Deep peroneal nerve Sural nerve Proper dorsal digital nerves Proper dorsal digital nerves 9. Sensory branches supply the lateral aspect of the leg below the knee and the skin on the dorsal surface of the foot. This nerve may be damaged by compression, a fracture at the head of the fibula, or diabetes, resulting in weakness of dorsiflexion and eversion of the foot, weakness of toe extension (dorsiflexion), and loss of sensation in the lateral aspect of the lower leg and the dorsum of the foot. The preganglionic neuron arises from the brain stem or spinal cord and synapses on postganglionic neurons in the sympathetic chain or collateral ganglia (sympathetic) or on intramural ganglia (parasympathetic) near the organ innervated. These autonomic systems achieve their actions through innervation of smooth muscle, cardiac muscle, secretory (exocrine) glands, metabolic cells (hepatocytes, fat cells), and cells of the immune system. Normally, both autonomic divisions work together to regulate visceral activities such as respiration, cardiovascular function, digestion, and some endocrine functions. This syndrome includes neurogenic orthostatic hypotension (syncope or dizziness when standing), inability to sweat, urinary tract dysfunction, erectile dysfunction, and retrograde ejaculation. Catecholamine challenge results in robust reactivity in target organs caused by denervation hypersensitivity. In the bone marrow and thymus, sympathetic fibers modulate cell proliferation, differentiation, and mobilization. In the spleen and lymph nodes, sympathetic fibers modulate innate immune reactivity, and the magnitude and timing of acquired immune responses, particularly the choice of cell-mediated (Th1 cytokines) as opposed to humoral (Th2 cytokines) immunity. Extensive neuropeptidergic innervation, derived from both the autonomic nervous system and the primary sensory neurons, also is present in the parenchyma of lymphoid organs. Many subsets of lymphoid cells express cognate receptors for catecholamines (alpha and beta receptor subsets) and neuropeptides; the expression of these neurotransmitter receptors is highly regulated by both lymphoid and neural molecular signals. Postganglionic sympathetic nerve fibers also directly innervate hepatocytes and fat cells. The preganglionic sympathetic or parasympathetic neurons are activated through interneurons to produce a reflex autonomic response. The efferent connectivity can be relayed via splanchnic or somatic nerves because of the complexity of autonomic efferent pathways. Sensory signals associated with standing result in vascular constriction induced by sympathetic neurons to maintain blood pressure, prevent pooling of blood in the lower extremities, and maintain appropriate perfusion of the brain and other vital organs. Nociceptive stimulation may result in reflex elevation of heart rate, blood pressure, and other characteristics of sympathetic activation. Stimulation of the perioral region, particularly in an infant during feeding, activates a parasympathetic state to enhance digestion and diminish sympathetic activation, thereby promoting growth and development. Problems can arise when autonomic reflexes are disrupted, or when hyperactivation of reflex pathways elevates either parasympathetic or sympathetic activity. In such circumstances, there is often a counterpart activation of the other system, as when paradoxical parasympathetic activation leads to compensatory sympathetic activation. This can increase the likelihood of problems such as arrhythmia or even cardiac arrest. Sympathetic fibers preganglionic postganglionic Postganglionic parasympathetic cholinergic nerve fibers (axons) ending along cardiac atrial muscle cells. These cholinergic (C) synapses activate mainly nicotinic receptors on the ganglion cells. Postganglionic sympathetic neurons use mainly norepinephrine (adrenergic responses; A), to activate both alpha and beta receptors on target tissues. All ganglion cells possess mainly nicotinic receptors for fast response to cholinergic release from preganglionic axons. However, additional muscarinic receptors and dopamine receptors on ganglion cells help to mediate longer term excitability. The postganglionic sympathetic nerves use mainly norepinephrine as their neurotransmitter, and target structures in the periphery possessing different subsets of alpha and beta adrenergic receptors for response to norepinephrine. The vagus nerve and its associated ganglia do not innervate effector tissue in the head and neck, although they are present in the neck. Sympathetic components are associated with the superior cervical ganglion and, to a lesser extent, the middle cervical ganglion. They are sometimes thought of as autonomic afferents, but they are not components of the autonomic efferent nervous system. Light shone into one eye provides an afferent signal that is processed by the retina, resulting in ganglion cell activation and axonal projections to the pretectum on both sides. The pretectum, through direct and contralateral connections via the posterior commissure, stimulates the nucleus of Edinger-Westphal bilaterally. This system, via connections in the ciliary ganglion, distributes to the pupillary constrictor muscle, resulting in constriction of the ipsilateral (direct) and contralateral (consensual) pupils. The pupillary light reflex is particularly important in someone with a head injury, intracranial bleed, or space-occupying mass in whom possible brain herniation is suspected. The brain requires moment-to-moment delivery of oxygen and glucose to maintain cerebral activity and generate the adenosine triphosphate needed for the high energy demands of neurons. Blood flow to the brain is autoregulated; several levels of superimposed control derive from metabolic and neural regulatory systems. The trigeminal ganglion also distributes substance P (colocalized with calcitonin gene-related peptide) vasodilator fibers along the vasculature; these fibers can be activated by pain. Some central regions, such as the fastigial nucleus of the cerebellum and the rostral ventrolateral medulla, can regulate the activation of some of these neural circuits to the cerebral vasculature, influencing blood flow to the brain. In addition, sympathetic innervation from the superior cervical ganglion activates contraction of the myoepithelial cells of the salivary ducts. Salivation is important as an initial phase of the digestion process; it prepares food for swallowing, aids in speaking, and contains mediators and immunoglobulins that provide an initial protective barrier against potentially dangerous organisms that gain access to the oral cavity. Preganglionic sympathetic nerve fibers from the thoracolumbar intermediolateral cell column supply sympathetic chain ganglia. These ganglia send postganglionic noradrenergic nerve fibers through the gray rami communicans into the peripheral nerves to supply vascular smooth muscle (vasomotor fibers), sweat glands (sudomotor fibers), and arrector pili muscles associated with hair follicles (pilomotor fibers). Smooth muscle fibers of blood vessels in the viscera also are supplied with postganglionic sympathetic nerve fibers. Peripheral Nervous System Cervicothoracic (stellate) ganglion Ansa subclavia 211 Cervicothoracic (stellate) ganglion Right sympathetic trunk Cervical cardiac nerves (sympathetic and vagal) Thoracic sympathetic cardiac nerves Cervical cardiac nerves (sympathetic and vagal) Left vagus nerve (cut) Left recurrent laryngeal nerve Right vagus nerve (cut) Thoracic cardiac nerves (sympathetic and vagal) Thoracic vagal branches to pulmonary and cardiac plexuses Branches to anterior and posterior pulmonary plexuses 5th intercostal nerve (anterior ramus of 5th thoracic spinal nerve) Cardiac plexus Gray and white rami communicans Left sympathetic trunk Thoracic aorta plexus 5th thoracic sympathetic trunk ganglion Right greater thoracic splanchnic nerve Esophageal plexus Sympathetic branch to esophageal plexus Thoracic duct Thoracic aortic plexus Right lesser thoracic splanchnic nerve Right lowest thoracic splanchnic nerve Diaphragm (pulled down) Azygos vein (cut) Inferior vena cava (cut) Left greater thoracic splanchnic nerve Left lesser thoracic splanchnic nerve Anterior vagal trunk Diaphragm (pulled down) 9. The ganglia, interconnected by nerve trunks, are located in a paravertebral array from the neck to the coccygeal region. Postganglionic noradrenergic nerve fibers from the sympathetic chain supply effector tissue in the periphery. Some preganglionic nerve fibers do not synapse as they travel through the sympathetic chain. They continue along the splanchnic nerves to synapse in collateral ganglia, which supply noradrenergic innervation to effector tissue in the viscera. Initially the patient experiences a spinal shock syndrome, with hypotension (worse on standing), loss of sweating, loss of piloerection, paralysis of bladder function (neurogenic bladder), gastric dilatation, and paralytic ileus. As the process of spinal cord injury resolves to a permanent state and spinal shock recedes, the autonomic equivalent of spasticity (hyperresponsiveness) may result, accompanied by spikes in blood pressure and a spastic bladder. Sympathetics derive from the sympathetic chain, and parasympathetics derive from vagal autonomic input to local intramural ganglia. Sympathetic influences result in bronchodilation and parasympathetic influences result in bronchoconstriction. Some medications for asthma use a sympathomimetic compound; others use a parasympathetic blocker. Additional neuropeptidergic innervation, some as colocalized or independent autonomic fibers and some as primary afferent fibers, also distributes along the epithelium and among the alveoli, where they can influence innate immune reactivity and the production of inflammatory mediators. Peripheral Nervous System Dorsal vagal nucleus Solitary tract nucleus 213 Superior cervical sympathetic trunk ganglion Medulla oblongata Vagus nerves Superior cervical sympathetic cardiac nerve Superior cervical vagal cardiac branches Middle cervical sympathetic trunk ganglion Middle cervical sympathetic cardiac nerve Vertebral ganglion Ansa subclavia Cervicothoracic (stellate) ganglion Ventral ramus of T1 (intercostal nerve) T2 Inferior cervical sympathetic cardiac nerve T3 2nd thoracic sympathetic trunk ganglion T4 Thoracic vagal cardiac branch T1 Inferior cervical vagal cardiac branches Ascending connections White rami communicans 4th thoracic sympathetic trunk ganglion Gray ramus communicans Sympathetic fibers Preganglionic Postganglionic Afferent fibers Parasympathetic fibers Preganglionic Postganglionic Afferent fibers Thoracic sympathetic cardiac nerves Cardiac plexus 9. Sympathetic noradrenergic nerve fibers also distribute along the great vessels and the coronary arteries. Sympathetic fibers increase the force and rate of cardiac contraction, increase cardiac output, and dilate the coronary arteries. Parasympathetic fibers decrease the force and rate of cardiac contraction and decrease cardiac output. Cardiovascular auto- nomic neuropathies sometimes occur in diabetes and other disorders. Vagal nerve damage can result in sustained tachycardia; excessive vagal activity can provoke bradycardia, atrial fibrillation or flutter, ventricular fibrillation, or paroxysmal tachycardia. Loss of sympathetic innervation of the heart results in severe exercise intolerance, painless myocardial ischemia, cardiomyopathy, and possibly sudden death. In studies of cardiac failure, the increased reflex drive on sympathetic cardiac nerves in an attempt to increase cardiac output results in accelerated release of norepinephrine, which produces highly toxic oxidative metabolites (free radicals) that are taken up by the noradrenergic nerve endings (through the high-affinity uptake carriers) and produce a dying-back sympathetic neuropathy, leaving the heart further denervated. In experimental models in dogs, either a norepinephrine-specific uptake inhibitor (desmethylimipramine) or potent antioxidants (vitamins C and E) can prevent this free-radical autodestructive process. The lumbar portion of the sympathetic chain and its branches and the splanchnic nerves and their collateral ganglia (celiac, superior and inferior mesenteric, hepatic, aorticorenal, adrenal, superior hypogastric, and others) innervate smooth muscle, glands, lymphoid tissue, and metabolic cells in the abdomen and pelvis. Most of the collateral ganglia (plexuses) also contain parasympathetic contributions from the vagus nerve and associated ganglia. Parasympathetic vagal fibers and their associated intramural ganglia provide parasympathetic innervation. The importance of this innervation is illustrated by the relatively unusual disorder known as dysautonomic polyneuropathy, which is a postganglionic polyneuropathy of both sympathetic and parasympathetic nerves, most likely the result of autoimmune reactivity. The affected individual develops orthostatic hypotension, unresponsive pupillary light reflexes, paralytic ileus and constipation, bladder dysfunction, and diminished sweating, peripheral vasoconstriction, and piloerection. Peripheral Nervous System 215 Anterior view Superior ganglion of vagus nerve Superior cervical sympathetic ganglion Inferior ganglion of vagus nerve Pharyngeal branch of vagus nerve Vagus nerve (X) Superior laryngeal nerve Cervical sympathetic trunk Middle cervical sympathetic ganglion Esophagus Recurrent laryngeal nerves Right recurrent laryngeal nerve Ansa subclavia Cervical (sympathetic and vagal) cardiac nerves Vertebral ganglion of cervical sympathetic trunk Ansa subclavia Branch to esophagus and recurrent nerve from stellate ganglion Cervicothoracic (stellate) ganglion 3rd intercostal nerve Gray and white rami communicans 3rd thoracic sympathetic ganglion Thoracic sympathetic trunk Left recurrent laryngeal nerve Thoracic (vagal and sympathetic) cardiac branches Cardiac plexus Pulmonary plexuses Esophageal plexus (anterior portion) Branches to esophageal plexus from sympathetic trunk, greater splanchnic nerve and thoracic aortic plexus Left greater splanchnic nerve Anterior vagal trunk Vagal branch to hepatic plexus via lesser omentum Principal anterior vagal branch to lesser curvature of stomach Vagal branch to fundus and body of stomach Posterior view Right greater splanchnic nerve Sympathetic fibers along left inferior phrenic artery Branch of posterior vagal trunk to celiac plexus Esophageal plexus (posterior portion) Posterior vagal trunk Greater splanchnic nerve Sympathetic fibers along esophageal branch of left gastric artery Vagal branch to celiac plexus Vagal branch to fundus and cardiac part of stomach Posterior vagal branch to lesser curvature Celiac plexus and ganglia 9. This plexus directly controls peristalsis through the esophagus by alternately relaxing and then contracting the muscles of the esophagus. The celiac and superior mesenteric ganglia receive their preganglionic input from the greater and lesser thoracic splanchnic nerves. Parasympathetic fibers distribute to the stomach and proximal duodenum from the celiac branches of the vagus nerve. The patient may experience nausea and vomiting, premature satiety, and large fluctuations in blood glucose. Approaches for treatment include parasympathetic agonists that stimulate gastric emptying and dopamine antagonists that remove the dopaminergic inhibition of gastric emptying. Delayed gastric emptying may also be accompanied by dysfunction of esophageal motility, resulting in dysphagia. Peripheral Nervous System Right and left inferior phrenic arteries and plexuses Anterior and posterior layers of lesser omentum Branch from hepatic plexus to cardia via lesser omentum Right greater thoracic splanchnic nerve Hepatic branch of anterior vagal trunk Anterior vagal trunk Celiac branch of posterior vagal trunk Celiac branch of anterior vagal trunk Left gastric artery and plexus 217 Vagal branch from hepatic plexus to pyloric part of stomach Hepatic plexus Right gastric artery and plexus Anterior gastric branch of anterior vagal trunk Left greater splanchnic nerve Left lesser splanchnic nerve Splenic artery and plexus Celiac ganglia and plexus Plexus on gastro-omental (gastroepiploic) arteries Superior mesenteric artery and plexus Plexus on inferior pancreaticoduodenal artery Plexus on first jejunal artery Plexus on anterior superior and anterior inferior pancreaticoduodenal arteries (posterior pancreaticoduodenal arteries and plexuses not visible in this view) 9. Parasympathetic fibers increase peristalsis and secretomotor activity (such as gastrin and hydrochloric acid) and relax associated sphincters. The stomach expands, neural satiety signals do not provide effective feedback to the brain, and compulsive eating can overcome normal appetitive control mechanisms. In situations in which diet and exercise are ineffective for weight control and when diabetes and other serious comorbidities are life-threatening for a morbidly obese individual, bariatric surgery is an option. The Roux-en-Y gastric bypass procedure takes the distal 90% of the stomach, the duodenum, and approximately 20 cm of the proximal jejunum off-line; the digestive tract then consists of the esophagus and a very small proximal stomach pouch that is connected with the remaining jejunum (the off-line jejunum is anastomosed farther downstream). Long-term data indicate extensive and permanent weight loss in many subjects (more than 70% of needed weight loss) and common reversal of diabetes, hypertension, sleep apnea, and many of the comorbid conditions that accompany morbid obesity. In addition, a striking alteration in the secretion of a variety of gastrointestinal hormones, inflammatory mediators, and other mediators has been noted. Autonomic and somatic neural signals are altered, central setpoints related to appetitive behavior are reset, and changes in morbidity and mortality rates have been observed. The Roux-en-Y procedure is not without risks and complications, and chronic supplementation of nutrients such as calcium, iron, and B vitamins is required.

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As T cells mature medicine go down generic 25/200 mg aggrenox caps free shipping, they are discharged into the circulation to go to secondary lymphoid tissues and organs medicine kit discount 25/200 mg aggrenox caps overnight delivery. The syndrome is due to a defect on chromosome 22 produced by a recombination error at meiosis symptoms lyme disease purchase 25/200mg aggrenox caps with visa, which causes faulty development of the third and fourth pharyngeal pouches in the early embryo medicine on time generic aggrenox caps 25/200 mg on-line. Its selective T cell deficiency leads to immunodeficiency with recurrent opportunistic infections treatment of pneumonia cheap 25/200 mg aggrenox caps with mastercard. Malformations of the heart medications or drugs buy aggrenox caps cheap online, esophagus, great vessels, and parathyroid glands also occur. Maternal alcohol consumption in the first trimester of pregnancy may be an environmental factor responsible for this disorder. A delicate connective tissue capsule (at the top) sends in thin trabeculae (arrows) to form irregular lobules, three of which are seen here. The plane of section determines the appearance of the lightly stained regions of medulla: either closed compartments surrounded by cortex or a confluent central region continuous between lobules. Many closely packed lymphocytes (Ly) with small, round, densely stained nuclei predominate. Processes of these cells (arrows) appear to invest capillaries (Cap), many of which are seen in transverse section. This pattern in the cortex constitutes the blood-thymus barrier, which limits access of blood-borne antigens to immature lymphocytes. Each lobule contains an outer, dark-staining lymphocyte-dense cortex and an inner medulla that stains more lightly; medullary areas of adjacent lobules may be confluent. Trabeculae derive from the thin, fibrous outer capsule that invests the organ and extend perpendicularly from the capsule into the cortex. The thymus lacks afferent lymphatics, but it does have efferent lymphatics and nerves, which also course in trabeculae. Lymphocytes in the cortex divide often, migrate into the medulla as they mature, and then exit the thymus. Lymphocytes in the medulla are less numerous and compact but larger than those in the cortex. Macrophages and dendritic cells, both originating in bone marrow, are also seen among lymphocytes in the thymic cortex and medulla. Macrophages are most abundant in a poorly defined boundary, called the corticomedullary junction, which separates cortex from medulla. They are hard to see by conventional microscopy but do have intensely eosinophilic cytoplasm and an ovoid, pale-staining nucleus with distinct nucleoli. An epithelial reticular cell has a large euchromatic nucleus with several nucleoli. Called a thymic nurse cell in this area of the thymus, which is directly under the capsule, it is closely associated with small, tightly packed lymphocytes (Ly) that are maturing. Although not well seen at this magnification, the epithelial reticular cell cytoplasm contains abundant tonofilaments. Capillary endothelial cells in this area are usually linked by desmosomes (circle). These reticular cells, called thymic nurse cells, are invested by a basal lamina and form part of the blood-thymus barrier in the cortex. Their cytoplasmic processes, which are linked by desmosomes, support clusters of maturing lymphocytes in the subjacent, intervening spaces of the cortex. The thin processes partially invest the endothelium of continuous (nonfenestrated) capillaries in the cortex. The basal lamina of these reticular cells is often fused with the thick basal lamina of the capillary endothelium. Together, these cellular and extracellular structures create a physical barrier that protects immature lymphocytes from foreign blood-borne antigens. This barrier prevents premature exposure of lymphocytes to foreign and self-antigens so that an immune reaction does not occur. Thymic macrophages are also involved in lymphocyte phagocytosis because most of them undergo apoptosis during differentiation and are destroyed, so only a relatively small number is released into circulation. Some show concentric epithelial reticular cells and others, hyalinization or degeneration. Its central area of degenerated or necrotic cells is surrounded by flattened or polygonal cells. Capillaries that enter the medulla from the cortex at the corticomedullary junction immediately drain into postcapillary venules that are not en-sheathed by barrier components. The venules are thus more permeable than are capillaries in the cortex, and the medulla has no blood-thymus barrier. Lymphocytes that proliferate in the cortex enter the blood vascular system by passing through walls of these vessels. Medullary venules drain into larger veins that course in interlobular trabeculae before leaving the thymus. A unique feature of the medulla is the presence of spherical bodies with lamellar centers-Hassall (or thymic) corpuscles-which help differentiate the thymus from other lymphoid organs. Their size and number increase in the elderly, and they often calcify with advancing age. This chronic noninfectious disease, which is most common in women of childbearing age, may affect many organs. Although its cause is unknown, tissue injury is mediated by immune complexes that initiate an inflammatory response when deposited on tissues. White pulp is made of compact lymphoid tissue that forms cylindrical cuffs around the branching network of central arteries in the organ. The more abundant red pulp makes up the bulk of the spleen and has a relatively loose consistency. In adults, this largest lymphoid organ is the size of a clenched fist and weighs 180-250 g. At the hilum (an indentation on the medial surface), the splenic artery and nerves enter and the splenic vein and lymphatics leave. The spleen derives embryonically from a condensation of mesenchyme in the dorsal mesogastrium. During early fetal development, it is temporarily an organ of hematopoiesis; this role is taken over by the liver and then bone marrow. However, in severe cases of anemia in children and adults, the spleen may produce new blood cells. The organ filters blood by clearing particulate matter, infectious organisms, and aged or defective erythrocytes and platelets. The spleen is also a secondary lymphoid organ: lymphocytes respond to blood-borne antigens by initiating an immune reaction that activates T and B cells. The spleen of affected patients is modestly enlarged, weighing 300-800 g, and the capsule becomes thick and fibrotic. Histologic study of the red pulp shows dilated venous sinusoids and increased macrophage numbers; the white pulp is usually atrophic. Splenectomy, or removal of the spleen, is used as therapy for some chronic disorders or an emergency procedure for traumatic rupture of the spleen. Splenectomy in adults usually has no clinical consequence, but in children it leads to increased occurrence and severity of infections. Splenic lymphoid nodules are numerous in young people but become relatively scarce with aging. The capsule consists of collagen and elastic fibers with scattered fibroblasts and a few smooth muscle cells. The fibrous capsule is usually covered by a serous mesothelial layer of the visceral peritoneum (not seen here), which is normally simple squamous epithelium. The red pulp constitutes 75% of the volume of the spleen and contains all formed elements of circulating blood. Suspended between trabeculae is a communicating network of reticular fibers, with many attached macrophages and reticular cells. It consists of white pulp and red pulp, so named because of their color in the fresh state. As in lymph nodes, B cells may be found in primary (unstimulated) lymphoid nodules or secondary (stimulated) nodules with germinal centers. Surrounding white pulp is a shell of sparsely cellular lymphoid tissue-the marginal zone-that contains many macrophages and some B lymphocytes. This zone is not as well defined in humans as in animals, and its demonstration requires special staining methods. Red pulp makes up most of the spleen, its color being due mostly to abundant erythrocytes. Found around white pulp, it consists of many thin-walled venous sinusoids and intervening cellular, or splenic, cords (of Billroth). The term splenic cords is misleading, in that these are labyrinthine spaces between sinuses containing a scaffold of reticular fibers. Many closely packed fixed or wandering cells-reticular cells, lymphocytes, plasma cells, macrophages, and all formed elements of circulating blood-occupy these spaces. Injection of India ink into an experimental animal, followed by removal of the spleen and then its microscopic examination, allows reaction product in macrophages to be seen. This section, so prepared, shows a high concentration of macrophages in the marginal zone of white Trabecular pulp after cells ingested black carbon particles of ink. Between the endothelium and smooth muscle is a prominent layer of elastic tissue, the internal elastic lamina (arrows). The splenic artery enters at the hilum and divides into several smaller trabecular arteries, so named because they travel in trabeculae. They are known collectively as central arterioles, which is a misnomer as these vessels are usually in an eccentric position in white pulp. They also have two layers of smooth muscle cells in their walls, which is a feature of arterioles. Some branches of the central arteriole end as marginal sinuses that supply the marginal zone of the white pulp. Other arterial branches enter the red pulp as short straight penicillar arterioles. These drain into sheathed capillaries, which have an external sheath of reticular fibers and many macrophages. In red pulp, they accommodate many lymphocytes, macrophages, and other cells in splenic cords. With silver stains, reticular fibers are black fibrous strands that form an interweaving network in the organ. Macrophages closely associated with sinusoid walls often require special techniques for detection. In the closed system, about 90% of capillaries supplying red pulp drain directly into venous sinusoids, such as normally occurs elsewhere in the body. An alternative is an open system: Remaining open-ended capillaries discharge blood freely into the intersinusoidal meshwork, so blood seeps out and percolates slowly between splenic cords before regaining access to sinusoids. Both open and closed patterns likely operate at different times, according to physiologic conditions. Venous sinusoids are a tortuous network of thin-walled vessels with irregular lumina. A thin, discontinuous basal lamina forms circular bands around the endothelial cells, like hoops around staves of a leaky barrel. Formed elements of blood can thus traverse the highly porous walls of venous sinusoids by squeezing through the slits. However, worn out or fragile erythrocytes, which have lost pliability, cannot reenter the circulation and are phagocytosed by macrophages. The spleen lacks afferent lymphatics, but efferent lymphatics beginning in white pulp exit at the hilum. Just under the capsule, the internal architecture of the organ appears disorganized with irregular patches of bluish/ purple stained lymphoid tissue (*) separated by densely eosinophilic areas of dense connectivetissue fibrosis. These cells are named for American pediatric pathologist, Dorothy Reed Mendenhall, and Austrian pathologist, Carl Sternberg. Lymphocytes, eosinophils, and cells undergoing mitoses are also in the cell infiltrate. Characterized clinically by the contiguous spread of disease from one lymph node group to another, it is the most common mediastinal malignancy. Symptoms include painless lymphadenopathy (lymph node swelling) usually in the mediastinum, axillae, and neck, accompanied by weight loss, fatigue, and night sweats. Microscopic examination of biopsy samples reveals partial or complete disruption of lymph node architecture by large malignant cells, known as ReedSternberg cells, scattered within a reactive cell infiltrate composed of variable numbers of lymphocytes, plasma cells, and eosinophils. This histologic pattern typically gives a moth-eaten appearance to the affected node. Reed-Sternberg cells have a unique morphology: a bilobed or multilobulated nucleus with multiple eosinophilic nucleoli that often resemble owl eyes. The disease occurs frequently in young adulthood (15-35 years) and in people over age 50.

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