Emily J. Ozer PhD

• Professor, Community Health Sciences

https://publichealth.berkeley.edu/people/emily-ozer/

The normal function of the thyroid gland is directed toward the secretion of l-thyroxine (T4) and l-3 good antibiotics for sinus infection purchase 400 mg noroxin free shipping,5 uti after antibiotics for uti buy noroxin 400 mg on line,5-triiodothyronine (T3) liquid antibiotics for acne noroxin 400mg cheap, which influence a diversity of metabolic processes antibiotics for acne work order noroxin 400 mg otc. Diseases of the thyroid could be quantitative or qualitative alterations in hormone secretion anti virus purchase generic noroxin pills, enlargement of thyroid (goiter) antibiotic vancomycin tablets dosage purchase noroxin 400 mg without a prescription, or both. Insufficient hormone secretion results in hypothyroidism; excess secretion results in hyperthyroidism. Focal enlargement of the thyroid can be associated with tumors (benign or malignant). Generalized enlargement can be associated with increased, normal, or decreased function of the gland depending on the underlying cause. This will decrease total T4 but free or active T4 level is normal with the patient being euthyroid. Serum thyroglobulin concentration can be used to assess the adequacy of treatment and followup of thyroid cancer. The affected areas are well demarcated, raised, and thickened, and may be pruritic and hyperpigmented. Transient hyperthyroidism results from subacute thyroiditis (painful) or lymphocytic thyroiditis (painless, postpartum). Extrathyroid source of hormones include thyrotoxicosis factitia and ectopic thyroid tissue (struma ovarii, functioning follicular carcinoma). In general, nervous symptoms predominate in the clinical picture of younger patients, whereas cardiovascular and myopathic symptoms are more common in older patients. Other clinical findings include emotional lability, inability to sleep, tremors, frequent bowel movements, excessive sweating, and heat intolerance. Dyspnea, 20 Chapter 2 l Endocrinology palpitations, angina, or cardiac failure may occur in older patients. The skin is warm and moist, and palmar erythema is present along with fine and silky hair in hyperthyroidism. The differential diagnosis of hyperthyroidism includes anxiety, neurosis, and mania, pheochromocytoma, acromegaly, and cardiac disease. Other causes of ophthalmoplegia and exophthalmus include myasthenia gravis and orbital tumors. Subtotal thyroidectomy is only indicated in pregnancy (2nd trimester) and in children. After ablative therapy, the patient will become hypothyroid and hormone replacement treatment is indicated. Surgery is also used if the thyroid is so large that there are compressive symptoms. It is manifested by extreme irritability, delirium, coma, tachycardia, restlessness, vomiting, jaundice, diarrhea, hypotension, dehydration, and high fever. The treatment of thyroid storm involves supportive therapy with saline and glucose hydration, glucocorticoids, and oxygen cooling blanket. Finally, dexamethasone is given to inhibit hormone release, impair peripheral generation of T3 from T4, and provide adrenal support. The etiology of hypothyroidism results from the thyroid in 95% of cases (primary). Primary hypothyroidism can occur secondary to chronic thyroiditis (Hashimoto disease); this is the most common cause of goitrous hypothyroidism and is associated with antimicrosomal antibodies. Postablative surgery or radioactive iodine, heritable biosynthetic defects, and iodine deficiency can lead to primary hypothyroidism. Suprathyroid causes of hypothyroidism include pituitary induced (secondary hypothyroidism) or hypothalamic induced (tertiary hypothyroidism). In the newborn, signs and symptoms of hypothyroidism include cretinism (in 1/5,000 neonates) and juvenile hypothyroidism. Persistent physiologic jaundice, hoarse cry, constipation, somnolence, and feeding problems are also seen. In later months, delayed milestones and dwarfism, coarse features, protruding tongue, broad flat nose, widely set eyes, sparse hair, dry skin, protuberant abdomen, potbelly with umbilical hernia, impaired mental development, retarded bone age, and delayed dentition are also seen. Signs and symptoms of hypothyroidism in the adult in the early stages include lethargy, constipation, cold intolerance, stiffness and cramping of muscles, carpal tunnel syndrome, and menorrhagia. Later in the course of disease intellectual and motor activity slows, appetite decreases and weight increases, hair and skin become dry, voice gets deeper and hoarse, and deafness may occur. Slow deep tendon reflexes with prolonged relaxation phase are noted on examination. Ultimately, myxedema appears with an expressionless face, sparse hair, periorbital puffiness, large tongue, and pale, cool skin that feels rough and doughy. If there is a strong suspicion of suprathyroid hypothyroidism of hypothalamic or pituitary origin, give hydrocortisone first, then replace thyroid hormone. Myxedema coma results in patients who have severe long-standing hypothyroidism that is left untreated. Thyroiditis Thyroiditis includes disorders of different etiologies characterized by inflammation of the thyroid. They have different clinical courses, and each can be associated at one time or another with euthyroid, thyrotoxic, or hypothyroid state. Subacute thyroiditis includes granulomatous, giant cell, or de Quervain thyroiditis. This can occur at any age, although most commonly in the fourth and fifth decades. The disorder may smolder for months but eventually subsides with return to normal function. Hashimoto thyroiditis is a chronic inflammatory process of the thyroid with lymphocytic infiltration of the gland, and is thought to be caused by autoimmune factors. Hashimoto thyroiditis is a common disorder occurring most frequently in middle-aged women, and is the most common cause of sporadic goiter in children. Autoimmune factors are implicated as evidenced by lymphocytic infiltration, presence of increased immunoglobulin, and antibodies against components of thyroid tissue (antithyroglobulin Abs). Clinical findings include agoiter that is painless, which is the main feature of this disease. The diagnosis of Hashimoto thyroiditis is suggested by finding a firm, nontoxic goiter on examination. High titers of antithyroid antibodies, namely antimicrosomal antibodies, are present. Lymphocytic thyroiditis is a selflimiting episode of thyrotoxicosis associated with chronic lymphocytic thyroiditis. Reidel thyroiditis results from intense fibrosis of the thyroid and surrounding structures (including mediastinal and retroperitoneal fibrosis). Management for hyperfunctioning adenomas includes ablation with radioactive iodine. There is a bimodal frequency and peaks occur in the second and third decades and again later in life. The treatment is surgery when the tumor is small and limited to a single area of the thyroid. Follicular carcinoma spreads hematogenously with distant metastasis to the lung and bone. Treatment requires near total thyroidectomy with postoperative radioiodine ablation. This tumor arises from parafollicular cells of the thyroid and is more malignant than follicular carcinoma. Medullary carcinoma may also occur in families without other associated endocrine dysfunctions. Calcitonin levels can also be increased from cancer of the lung, pancreas, breast, and colon. When to suspect a thyroid carcinoma Suspect a thyroid carcinoma when there is recent growth of thyroid or mass with no tenderness or hoarseness. Patients with a history of radiation therapy of the head, neck, or upper mediastinum in childhood average 30 years to develop thyroid cancer. The presence of a solitary nodule or the production of calcitonin are also clues to malignancy. Calcifications on x-rays such as psammoma bodies suggest papillary carcinoma; increased density is seen in medullary carcinoma. Five percent of nonfunctioning thyroid nodules prove to be malignant; functioning nodules are very seldom malignant. Hypercalcemia Hypercalcemia represents an increase in the total or free calcium level. Calcium is absorbed from the proximal portion of the small intestine, particularly the duodenum. About 80% of an ingested calcium load in the diet is lost in the feces, unabsorbed. Of the 2% that is circulating in blood, free calcium is 50%, protein bound is 40%, with only 10% bound to citrate or phosphate buffers. Hyperparathyroidism, which is usually asymptomatic, comes to light because of routine officebased testing. Granulomatous diseases such as sarcoidosis, tuberculosis, berylliosis, histoplasmosis, and coccidioidomycosis are all associated with hypercalcemia. Neutrophils in granulomas have their own 25-vitamin D hydroxylation, producing active 1,25 vitamin D. Rare causes include vitamin D intoxication, thiazide diuretics, lithium use, and Paget disease, as well as prolonged immobilization. Hyperthyroidism is associated with hypercalcemia because there is a partial effect of thyroid hormone on osteoclasts. Increased binding of hydrogen ions to albumin results in the displacement of calcium from albumin. It presents with mild hypercalcemia, family history of hypercalcemia, urine calcium to creatinine ratio <0. The perceived lack of calcium levels by the parathyroid leads to high levels of parathyroid hormone. Severe pancreatitis, however, is associated with hypocalcemia because of binding of calcium to malabsorbed fat in the intestine. Calcium also precipitates in the kidney, resulting in both kidney stones as well as nephrolithiasis. Severe, life-threatening hypercalcemia is treated first with vigorous fluid replacement with normal saline or half-normal saline. This may be followed by the use of loop diuretics, such as furosemide, which promote calcium loss from the body. If fluid replacement and diuretics do not lower the calcium level quickly enough and you cannot wait the 2 days for the bisphosphonates to work, calcitonin can be used for a more rapid decrease in calcium level. Primary Hyperparathyroidism Primary hyperparathyroidism represents 90% of mild hypercalcemias. It is most commonly due to one gland adenoma (80%), but hyperplasia of all 4 glands can lead to primary hyperparathyroidism (20%). Osteitis fibrosa cystica with hyperparathyroidism occurs because of increased rate of osteoclastic bone resorption and results in bone pain, fractures, swelling, deformity, areas of demineralization, bone cysts, and brown tumors (punched-out lesions producing a salt-and-pepper-like appearance). Urinary tract manifestations of hypercalcemia include polyuria, polydipsia, stones, and nephrocalcinosis with renal failure. The differential diagnosis includes all other causes of hypercalcemia, especially hypercalcemia of malignancy. Imaging studies may help localize the site of the affected gland prior to surgery. Parathyroidectomy should be performed if there are symptoms of hypercalcemia, bone disease, renal disease, or if the patient is pregnant. Asymptomatic mild increases in calcium from hyperparathyroidism do not necessarily need to be treated. Hungry bones syndrome is hypocalcemia that occurs after surgical removal of a hyperactive parathyroid gland, due to increased osteoblast activity. Cinacalcet is a calcimimetic agent that has some effect in hyperparathyroidism by shutting off the parathyroids. This increases the sensitivity of calcium sensing (basolateral membrane potential) on the parathyroid. Cinacalcet is used as treatment of secondary hyperparathyroidism in hemodialysis patients. It is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma and in moderate-to-severe primary hyperparathyroidism unamenable to surgery. Hypocalcemia is most commonly caused by hypoparathyroidism, renal failure, hyperphosphatemia, and hypomagnesemia.

Each of the children has several crusted weeping skin lesions of impetigo (pyoderma) antibiotics for pet birds cheap noroxin 400 mg overnight delivery. Which of the following statements regarding the role of protein A in the pathogenesis of infections caused by Staphylococcus aureus is correct Which of the following staphylococcal organisms produces coagulase and has been implicated in infections following a dog bite Which of the following statements best describes the function of the accessory gene regulator in Staphylococcus aureus Some are members of the normal human microbiota; others are associated with important human diseases attributable to the direct effects of infection or in other cases to an immunologic response to them antibiotic 48 hours contagious noroxin 400 mg cheap. The streptococci are a large and heterogeneous group of bacteria antimicrobial proteins buy cheap noroxin 400mg line, and no one system suffices to classify them antimicrobial activity of xanthium strumarium 400 mg noroxin otc. Yet common antibiotics used for sinus infection 400mg noroxin otc, understanding their taxonomy is key to understanding their medical importance antibiotic resistance paper order genuine noroxin on line. The serologic specificity of the groupspecific carbohydrate is determined by an amino sugar. For group A streptococci, this is rhamnose-N-acetylglucosamine; for group B, it is rhamnose-glucosamine polysaccharide; for group C, it is rhamnose-N-acetylgalactosamine; for group D, it is glycerol teichoic acid containing d-alanine and glucose; and for group F, it is glucopyranosyl-N-acetylgalactosamine. Extracts of group-specific antigen for grouping streptococci are prepared by a variety of methods, including extraction of centrifuged culture treated with hot hydrochloric acid, nitrous acid, or formamide; by enzymatic lysis of streptococcal cells (eg, with pepsin or trypsin); or by autoclaving of cell suspensions. Typing is generally done only for groups A, B, C, F, and G (see Table 14-1), which cause disease in humans and for which reagents are available that allow typing using simple agglutination or color reactions. More recently, molecular genetics have replaced phenotypic methods in the taxonomic assignment of these organisms. The classification of streptococci of medical importance is summarized in Table 14-1. Capsular Polysaccharides the antigenic specificity of the capsular polysaccharides is used to classify Streptococcus pneumoniae into more than 90 types and to type the group B streptococci (Streptococcus agalactiae). Hemolysis Many streptococci are able to hemolyze red blood cells in vitro in varying degrees. Complete disruption of erythrocytes with clearing of the blood around the bacterial growth is called -hemolysis. Incomplete lysis of erythrocytes with reduction of hemoglobin and the formation of green pigment is called -hemolysis. The hemolysis patterns of the streptococci of medical importance to humans are shown in Table 14-1. The classification of hemolytic patterns is used primarily with the streptococci although other bacteria that cause disease may also typically produce a variety of hemolysins. Biochemical Reactions Biochemical tests include sugar fermentation reactions, tests for the presence of enzymes, and tests for susceptibility or resistance to certain chemical agents. Biochemical tests are most often used to classify streptococci after the colony growth and hemolytic characteristics have been observed. Biochemical tests are used for species that typically do not react with the commonly used antibody preparations for the group-specific substances, groups A, B, C, F, and G. Includes the human species: Streptococcus gallolyticus subspecies gallolyticus; Streptococcus gallolyticus subspecies macedonicus; Streptococcus gallolyticus subspecies pasteurianus; Streptococcus infantarius subspecies infantarius. It is used here to illustrate general characteristics of streptococci and specific characteristics of the species. S pyogenes is the main human pathogen associated with local or systemic invasion and poststreptococcal immunologic disorders. S pyogenes typically produces large (1 cm in diameter) zones of -hemolysis around colonies greater than 0. The S pyogenes cell wall contains proteins (M, T, R antigens), carbohydrates (group specific), and peptidoglycans. The members of the chain often have a striking diplococcal appearance, and rod-like forms are occasionally seen. The lengths of the chains vary widely and are conditioned by environmental factors. Streptococci are gram positive; however, as a culture ages and the bacteria die, they lose their gram positivity and can appear to be gram negative; for some streptococci, this can occur after overnight incubation. Most group A strains (see Table 14-1) produce capsules composed of hyaluronic acid. Growth Characteristics Energy is obtained principally from the utilization of glucose with lactic acid as the end product. Growth of streptococci tends to be poor on solid media or in broth unless enriched with blood or tissue fluids. Most streptococci are facultative anaerobes and grow under aerobic and anaerobic conditions. Variation Variants of the same Streptococcus strain may show different colony forms. This is particularly marked among S pyogenes strains, giving rise to either matte or glossy colonies. A component of the cell wall of selected M types induces antibodies that react with cardiac muscle tissue. Toxins and Enzymes More than 20 extracellular products that are antigenic are elaborated by S pyogenes, including the following. Streptokinase (Fibrinolysin) Streptokinase is produced by many strains of group A -hemolytic streptococci. It transforms the plasminogen of human plasma into plasmin, an active proteolytic enzyme that digests fibrin and other proteins, allowing the bacteria to escape from blood clots. This process of digestion may be interfered with by nonspecific serum inhibitors and by a specific antibody, antistreptokinase. Streptokinase has been given intravenously for treatment of pulmonary emboli, coronary artery, and venous thromboses. The S pyogenes in glossy colonies tend to produce little M protein and are often not virulent. M protein is a filamentous structure anchored to the cell membrane that penetrates and projects from the streptococcal cell wall. When M protein is present, the streptococci are virulent, and in the absence of M type-specific antibodies, they are able to resist phagocytosis by polymorphonuclear leukocytes by inhibiting activation of the alternate complement pathway. Immunity to infection with group A streptococci is related to the presence of type-specific antibodies to M protein. Because there are more than 150 types of M protein, a person can have repeated infections with S pyogenes of different M types. Both groups C and G streptococci have genes homologous to the genes for M protein of group A, and M proteins similar to those of group A have been found on groups C and G streptococci. The M protein molecule has a rodlike coiled structure that separates functional domains. The structure allows for a large number of sequence changes while maintaining function, and the M protein immunodeterminants, therefore, can readily change. It appears that M protein and perhaps other streptococcal cell wall antigens have an important role in the pathogenesis of rheumatic fever. Purified streptococcal cell wall membranes induce antibodies that react with human cardiac C. Hyaluronidase Hyaluronidase splits hyaluronic acid, an important component of the ground substance of connective tissue. Thus, hyaluronidase aids in spreading infecting microorganisms (spreading factor). After infection with hyaluronidase-producing organisms, specific antibodies are found in the serum. Pyrogenic Exotoxins (Erythrogenic Toxin) Pyrogenic exotoxins are elaborated by S pyogenes. There are three antigenically distinct streptococcal pyrogenic exotoxins (Spe): A, B, and C. The streptococcal pyrogenic exotoxins have been associated with streptococcal toxic shock syndrome and scarlet fever. The group A streptococci associated with toxic shock syndrome are primarily of M protein types 1 and 3. The mechanisms of action appear to be similar to those caused by staphylococcal toxic shock syndrome toxin-1 and the staphylococcal enterotoxins. Cellulitis-Streptococcal cellulitis is an acute, rapidly spreading infection of the skin and subcutaneous tissues. It follows infection associated with mild trauma, burns, wounds, or surgical incisions. Cellulitis is differentiated from erysipelas by two clinical findings: In cellulitis, the lesion is not raised, and the line between the involved and uninvolved tissue is indistinct. Necrotizing fasciitis (streptococcal gangrene)- There is extensive and very rapidly spreading necrosis of the skin, tissues, and fascia. The group A streptococci that cause necrotizing fasciitis have sometimes been termed flesh-eating bacteria. Streptolysin O is responsible for some of the hemolysis seen when growth occurs in cuts made deep into the medium in blood agar plates. Streptolysin S is the agent responsible for the hemolytic zones around streptococcal colonies growing on the surface of blood agar plates. Puerperal fever-If the streptococci enter the uterus after delivery, puerperal fever develops, which is essentially a septicemia originating in the infected wound (endometritis). Bacteremia or sepsis-Infection of traumatic or surgical wounds with streptococci results in bacteremia, which can rapidly be fatal. S pyogenes bacteremia can also occur with skin infections, such as cellulitis and rarely pharyngitis. Streptococcal sore throat-The most common Pathogenesis and Clinical Findings A variety of distinct disease processes are associated with S pyogenes infections. Diseases Attributable to Invasion by S pyogenes, -Hemolytic Group A Streptococci the portal of entry determines the principal clinical picture. In each case, however, there is a diffuse and rapidly spreading infection that involves the tissues and extends along lymphatic pathways with only minimal local suppuration. In infants and small children, the sore throat occurs as a subacute nasopharyngitis with a thin serous discharge and little fever but with a tendency of the infection to extend to the middle ear and the mastoid. In older children and adults, the disease is more acute and is characterized by intense nasopharyngitis, tonsillitis, and intense redness and edema of the mucous membranes, with purulent exudate; enlarged, tender cervical lymph nodes; and (usually) a high fever. A similar clinical picture can occur with infectious mononucleosis, diphtheria, gonococcal infection, and adenovirus infection. S pyogenes infection of the upper respiratory tract does not usually involve the lungs. Streptococcal pyoderma-Local infection of super- ficial layers of skin, especially in children, is called impetigo. It consists of superficial vesicles that break down and eroded areas whose denuded surface is covered with pus and later is encrusted. It spreads by continuity and is highly communicable, especially in hot, humid climates. More widespread infection occurs in eczematous or wounded skin or in burns and may progress to cellulitis. A clinically identical infection can be caused by Staphylococcus aureus and sometimes both S pyogenes and S aureus are present. Some strains are particularly nephritogenic, principally with M types 2, 42, 49, 56, 57, and 60 (skin). Other nephritogenic M types associated with throat infections and glomerulonephritis are 1, 4, 12, and 25. After random streptococcal skin infections, the incidence of nephritis is less than 0. Glomerulonephritis may be initiated by antigen- antibody complexes on the glomerular basement membrane. The most important antigens are thought to be SpeB and a nephritis-associated plasmin receptor. In acute nephritis, the patient has blood and protein in the urine, edema, high blood pressure, and urea nitrogen retention; serum complement levels are also low. A few patients die, some develop chronic glomerulonephritis with ultimate kidney failure, and the majority recovers completely. Invasive Group A Streptococcal Infections, Streptococcal Toxic Shock Syndrome, and Scarlet Fever Fulminant, invasive S pyogenes infections with streptococcal toxic shock syndrome are characterized by shock, bacteremia, respiratory failure, and multiorgan failure. The infections tend to occur after minor trauma in otherwise healthy persons with several presentations of soft tissue infection. These include necrotizing fasciitis, myositis, and infections at other soft tissue sites; bacteremia occurs frequently. In some patients, particularly those infected with group A streptococci of M types 1 or 3, the disease presents with focal soft tissue infection accompanied by fever and rapidly progressive shock with multiorgan failure. The S pyogenes of the M types 1 and 3 (and types 12 and 28) that make pyrogenic exotoxin A or B are associated with the severe infections. The rash appears on the trunk after 24 hours of illness and spreads to involve the extremities. Streptococcal toxic shock syndrome and scarlet fever are clinically overlapping diseases.

Isolated lateral rectus myositis is a typical manifestation of orbital pseudotumor bacterial endospore purchase cheap noroxin line, rare in thyroid orbitopathy antibiotics side effects generic noroxin 400mg. Marked right uveoscleral "shaggy" enhancement is evident antibiotic resistance human microbiome purchase noroxin line, as well as illdefined enhancement of the retrobulbar fat antibiotics for acne prone skin best buy noroxin. Characteristic "perioptic cyst" evident behind the globe represents trapped cerebrospinal fluid within the nerve sheath infection xpk order cheap noroxin on-line. The 2nd is an inferior process bearing a facet with the surface directed ventrally antimicrobial bag buy discount noroxin on-line. Pars interarticularis is the part of the arch that lies between the superior and inferior articular facets of all subatlantal movable elements. The pars are positioned to receive biomechanical stresses of translational forces displacing superior facets ventrally, whereas inferior facets remain attached to dorsal arch (spondylolysis). C2 exhibits a unique anterior relation between the superior facet and the posteriorly placed inferior facet. The lateral edges of the superior surface of the body are turned upward into the uncinate processes. The vertebral artery resides within the transverse foramen, most commonly starting at the C6 level. The superior facets of C1 are large ovals that face upward, and the inferior facets are circular in shape. Large transverse processes are present on C1 with fused anterior and posterior tubercles. The odontoid embryologically arises from the centrum of the first cervical vertebrae. The C7 vertebral body shows a transitional morphology with a prominent spinous process. Thoracic Thoracic bodies are heart-shaped and increase in size from superior to inferior. The T1 vertebral body shows a complete facet for the capitulum of the first rib and an inferior demifacet for capitulum of second rib. Lumbar the lumbar vertebral bodies are large, wide, and thick and lack a transverse foramen or costal articular facets. The superior articular processes are directed dorsomedially and almost face each other. Joints Synarthrosis is an immovable joint of cartilage and occurs during development and in the first decade of life. The neurocentral joint occurs at the union point of two centers of ossification for two halves of the vertebral arch and centrum. Diarthrosis is a true synovial joint that occurs in the articular processes, costovertebral joints, and atlantoaxial and sacroiliac articulations. Symphysis is a fibrocartilage fusion between 2 bones, as in the intervertebral disc. Syndesmosis is a ligamentous connection common in the spine, such as the paired ligamenta flava, intertransverse ligaments, and interspinous ligaments. Atlantooccipital articulation is composed of a diarthrosis between the lateral mass of atlas and occipital condyles and the syndesmoses of the atlantooccipital membranes. The transverse ligament maintains the relationship of the odontoid to the anterior arch of atlas. Synovial cavities are present between the transverse ligament/odontoid and the atlas/odontoid junctions. Disc the intervertebral disc is composed of 3 parts: the cartilaginous endplate, the anulus fibrosis, and the nucleus pulposus. The height of the lumbar disc space generally increases as one progresses caudally. The anulus consists of concentrically oriented collagenous fibers, which serve to contain the central nucleus pulposus. The normal contour of the posterior aspect of the anulus is dependent on the contour of its adjacent endplate. Typically, this is slightly concave in the axial plane; although commonly at L4-L5 and L5-S1, these posterior margins will be flat or even convex. A convex shape on the axial images alone should not be interpreted as degenerative bulging. The nucleus pulposus is a remnant of the embryonal notochord and consists of a well-hydrated, noncompressible proteoglycan matrix with scattered chondrocytes. Proteoglycans form a major macromolecular component, including chondroitin 6-sulfate, keratan sulfate, and hyaluronic acid. Proteoglycans consist of protein core with multiple attached glycosaminoglycan chains. The nucleus occupies an eccentric position within the confines of anulus and is more dorsal with respect to the center of the vertebral body. Within the nucleus pulposus on T2-weighted sagittal images, there is often a linear hypointensity coursing in an anteroposterior direction, the intranuclear cleft. Craniocervical Ligaments the craniocervical ligaments are located anteriorly to spinal cord and occur in 3 layers: Anterior, middle, and posterior. Alar ligaments are thick, horizontally directed ligaments extending from the lateral surface of dens tip to anteromedial occipital condyles. The transverse ligament is a strong horizontal component of the cruciate ligament extending from behind the dens to the medial aspect of C1 lateral masses. The craniocaudal component consists of a fibrous band running from the transverse ligament superiorly to the foramen magnum and inferiorly to C2. Vertebral Artery the vertebral artery arises as the 1st branch of the subclavian artery on both sides. The vertebral artery travels cephalad within the foramen transversarium (transverse foramen) within the transverse processes. The 1st segment of the vertebral artery extends from its origin to the entrance into the foramen of the transverse process of the cervical vertebrae, usually the 6th. The most common variation is the origin of the left vertebral from the arch, between the left common carotid and the left subclavian arteries (2-6%). The vertebral artery in these variant cases almost always enters the foramen of the transverse process of C5. The 3rd segment starts at the C2 level where the artery loops and turns lateral to ascend in the C1 transverse foramen. The 4th segment starts where the artery perforates the dura and arachnoid at lateral edge of posterior occipitoatlantal membrane, coursing ventrally on the medulla to join with the other vertebral to make the basilar artery. Vertebral Column Blood Supply Paired segmental arteries (intercostals, lumbar arteries) arise from the aorta and extend dorsolaterally around the middle of the vertebral body. Near the transverse process, the segmental artery divides into lateral and dorsal branches. The lateral branch supplies dorsal musculature, and the dorsal branch passes lateral to the foramen, giving off branch(es) and providing major vascular supply to bone and vertebral canal contents. The posterior central branch supplies disc and vertebral body, whereas the prelaminal branch supplies the inner surface of the arch, ligamenta flava, and regional epidural tissue. The postlaminar branch supplies musculature overlying lamina and branches to bone. Spinal Cord Vascular Supply the spinal cord vasculature is derived from the vertebral arteries as well as segmental vessels at multiple levels. A single anterior spinal artery supplies the anterior 2/3 of the cord; paired posterior spinal arteries supply the posterior 1/3. Penetrating medullary branches to the central cord arise from multiple radicular branches that have few collaterals. The artery of Adamkiewicz is the dominant anterior radicular feeding vessel to the thoracic cord, typically arising from one of the left T9-12 branches. It courses cephalad along the anterior cord, then makes a characteristic "hairpin" turn, and courses inferiorly to the conus. Venous drainage occurs through a network of interconnected veins that form a tortuous venous plexus over the pial surface of the cord. The plexus consists of median and lateral longitudinal veins, which drain the cord and terminate in anterior and posterior internal vertebral venous plexi (of Batson) within the epidural space. The plexi are a series of irregular, thin-walled, valveless sinuses arranged in a continuous ladder-like series of cross-connected expansions extending throughout the epidural fat. The internal vertebral venous plexi drain into external plexi that surround the vertebral column and interconnect with the inferior and superior vena cavae as well as the azygous/hemiazygos systems and the intracranial dural sinuses. Nerves Spinal nerves are arranged in 31 pairs and grouped regionally: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal. Ascensus spinalis is the apparent developmental rising of the cord related to differential spinal growth. Dura is a dense, tough covering corresponding to the meningeal layer of the cranial dura. The dura continues with spinal nerves through the foramen to fuse with the epineurium. Cephalic attachment of the dura is at the foramen magnum and the caudal attachment at the back of the coccyx. Arachnoid is the middle covering, which is thin, delicate, and continuous with cranial arachnoid. Pia is the inner covering of delicate connective tissue closely applied to the cord. Longitudinal fibers are laterally concentrated as denticulate ligaments lying between posterior and anterior roots and attach at 21 points to dura. Longitudinal fibers are concentrated dorsally as the septum posticum attaching the dorsal cord to the dorsal midline dura. Vertebral body is broad transversely, central canal is large and triangular in shape, pedicles are directed posterolaterally, and laminae are delicate. Lateral masses contain the transverse foramen for passage of vertebral artery and veins. Complex rib articulation includes both costotransverse joints and costovertebral joints. Large, sturdy lumbar bodies connect to thick pedicles and transversely directed transverse processes. Paired ligamentum flavum & interspinous ligament join posterior elements, with midline supraspinous ligament. Adamkiewicz has a characteristic "hairpin" turn on the cord surface as it first courses superiorly, then turns inferiorly. Penetrating medullary arteries in the cord are largely end-arteries with few collaterals. The vertebral bodies are drained by anterior perforating veins, as well as via the basivertebral venous plexus. The anterior perforating veins are part of the anterior external plexus, whereas the basivertebral veins are part of the anterior internal plexus. The spinal central canal contains the anterior and posterior internal vertebral venous plexi. Premature Dysjunction Premature dysjunction of the neural tube from the overlying ectoderm allows the perineural mesenchyme to access the neural groove and differentiate into fat, physically preventing completion of neural tube closure and resulting in a spinal lipoma, with or without closed posterior spinal dysraphism. Spinal lipoma is subdivided into intradural (juxtamedullary, subpial) and terminal lipomas. Conversely, terminal lipoma is variably considered within both the premature dysjunction and abnormal caudal cell mass differentiation spectra, with findings overlapping both mechanisms. Nondysjunction In contrast, anomalies resulting from nondysjunction related to teratogens or faulty notochord induction occur when the neural tube fails to dissociate from adjacent cutaneous ectoderm over either a focal or long interval. The least extensive variation is the dorsal dermal sinus, which occurs when a single connection remains, forming a fibrous cord from skin to conus or central spinal cord canal. The dermal sinus tract usually has an atypical dimple at the ostium that is remote (> 2. They are most common in the lumbosacral spine followed by the occipital region, and the sinus opening dermatomal level correlates with the metameric level of spinal cord attachment. All have some degree of focal dysraphism, which may be as subtle as a bifid spinous process. Important mimics of the dorsal dermal sinus are the low sacral (coccygeal) dimple and pilonidal sinus. The low sacral or coccygeal dimple is common and features a low skin dimple affixed to the coccyx by a "spot weld. A pilonidal sinus has a low ostium, does not communicate with the spinal canal, and may present later with cutaneous infection. Secondary Neurulation (Canalization and Retrogressive Differentiation) By day 30, neural tube development below the caudal neuropore has commenced within the undifferentiated caudal cell mass of the primitive streak, which subsequently regresses. This process is inherently less precise than primary Imaging Protocols Multiplanar magnetic resonance imaging best evaluates soft tissues, neural structures, and ligaments. Embryology the spinal axis develops following a (mostly) orderly progression of steps, with the vertebral axis and spinal cord developing synchronously. Embryological spine formation begins in the occipital region, then subsequently commences at multiple other sites simultaneously. These sites progress at different rates and thus will be at different developmental stages at any given point in time. The cephalic spine (to about the conus level) forms by the process of primary neurulation, whereas the caudal spine forms separately by secondary neurulation (also called canalization and retrogressive differentiation). Most spinal anomalies may be explained by 1 or more events going awry during these steps. Primary Neurulation Embryonic spinal formation commences at the end of the 2nd gestational week with formation of the Hensen node and at the beginning of the 3rd week with the appearance of the neural plate during gastrulation (2-germ cell layer embryo 3germ cell layer embryo).

Most endothelial cells that line the inside of blood vessels resemble overlapping shingles which are tightly "glued" to the cells adjacent to them to prevent the loss of blood cells into the tissues antimicrobial properties of garlic 400 mg noroxin otc. In contrast antibiotic 3 day dose purchase cheap noroxin on line, within most secondary lymphoid organs treatment for dogs eating poop buy noroxin overnight, the small blood vessels that collect blood from the capillary beds (the postcapillary venules) are lined with these tall cells are the high endothelial cells xithrone antibiotic best buy for noroxin. So a high endothelial venule is a special region in a small blood vessel (venule) where there are high endothelial cells infection medication trusted noroxin 400mg. Actually antibiotic vitamins purchase noroxin 400 mg on-line, "wriggle" may not be quite the right term, because lymphocytes exit the blood very efficiently at these high endothelial venules: About 10 000 lymphocytes exit the blood and enter an average lymph node each second by passing between high endothelial cells. Now that you are familiar with lymphoid follicles and high endothelial venules, we are ready to take a tour of some of the secondary lymphoid organs. As we explore these organs, you will want to pay special attention to the "plumbing. This beanshaped organ has incoming lymphatics which bring lymph into the node, and outgoing lymphatics through which lymph exits. In addition, there are small arteries (arterioles) that carry the blood that nourishes the cells of the lymph node, and veins through which this blood leaves the node. If you look carefully at this figure, you also can see the high endothelial venules. After all, lymph nodes are like "dating bars," positioned along the route the lymph takes on its way to be reunited with the blood. And B and T cells actively engage in "bar hopping," being carried from node to node by the lymph. Since lymph nodes are places where lymphocytes find their cognate antigen, we also need to discuss how this antigen gets there. When dendritic cells stationed out in the tissues are stimulated by battle signals, they leave the tissues via the lymph, and carry the antigen they have acquired at the battle scene into the secondary lymphoid organs. In addition, antigen which has been opsonized, either by complement or by antibodies, can be carried by the lymph into the node. There the opsonized antigen will be captured by follicular dendritic cells for display to B cells. The walls of the marginal sinus are lined with macrophages which capture and devour pathogens as they enter a lymph node. This substantially reduces the number of invaders that the adaptive immune system will need to deal with. T cells tend to accumulate in the paracortex, being retained there by adhesion molecules. On the other hand, B cells entering a lymph node accumulate in the cortex, the area where lymphoid follicles are located. This localization of B cells works well, because the follicular dendritic cells that display opsonized antigen to B cells are located in this region of the lymph node. So a lymph node is a highly organized place with specific areas for antigen presenting cells, T lymphocytes, B lymphocytes, and macrophages. Lymph node choreography the fact that different immune system cells tend to hang out in specific places in a lymph node begs the question: How do they know where to go and when to go there It turns out that the movements of these cells in this secondary lymphoid organ are carefully choreographed by cytokines called chemokines (short for chemoattractive cytokines). Meanwhile, activated Th cells downregulate expression of the chemokine receptors that have been retaining them in the T cell areas. At this point, you may be asking, "How do activated Th cells know which B cells to help However, to reach full maturity, B cells that have plucked their antigen need costimulation. These Tfh cells are now "licensed" to rescue fragile, germinal center B cells, and to help these B cells switch classes or undergo somatic hypermutation. The initial encounter between Th and B cells generally lasts about 30 minutes, after which some of the B cells proliferate and begin to produce relatively lowaffinity IgM antibodies. Although these plasma B cells have not been "upgraded" by class switching or somatic hypermutation, they are important because they provide an immediate antibody response to an invasion. Other B cells and their Tfh partners move together into the germinal center, where class switching and somatic hypermutation can take place. It is important to note that during this process of bidirectional stimulation, the part of the protein which the B cell recognizes (the B cell epitope) usually is different from the part of the protein that the Th cell recognizes (the T cell epitope). If a helper T cell does encounter a dendritic cell presenting its cognate antigen in the paracortex, the Th cell will be activated and will begin to proliferate. This proliferation phase lasts a few days while the T cell is retained in the lymph node by adhesion molecules. Most newly activated Th cells exit the node via the lymph, recirculate through the blood, and reenter lymph nodes via high endothelial venules. Early in an infection, there are very few of these ingredients around, and naive B and T cells just circulate through the secondary lymphoid organs at random, checking for a match to their receptors. So the probability is pretty small that the rare Th cell which recognizes a particular antigen will arrive at the very same lymph node that is being visited by the rare B cell with specificity for that same antigen. B cells also engage in cycles of activation, proliferation, circulation, and restimulation. B cells which have encountered their cognate antigen displayed on follicular dendritic cells migrate to the border of the lymphoid follicle where they meet activated T cells that have migrated there from the paracortex. It is during this meeting that B cells first receive the costimulation they require for activation. Together, the B and Th cells enter the lymphoid follicles, and the B cells proliferate. Some become plasma cells that take up residence in the spleen or bone marrow, where they pump out IgM antibodies. Other activated B cells recirculate through the lymph and blood, and reenter secondary lymphoid organs. As a result, activated B cells are spread around to secondary lymphoid organs where, if they are restimulated in lymphoid follicles, they can proliferate more and can undergo somatic hypermutation and class switching. Killer T cells are activated in the paracortex of the lymph node if they find their cognate antigen presented there by dendritic cells. In addition, cytokines produced by helper T cells in an active lymph node recruit additional macrophages which tend to plug up the medullary sinuses. By this time, the invader usually has been repulsed, and a lot of the opsonized antigen has been picked from the follicular dendritic trees by B cells. At this point, most B cells will have left the follicles or will have died there, and the areas that once were germinal centers will look much more like primary lymphoid follicles. When surgeons remove a cancer from some organ in the body, they generally inspect the lymph nodes that drain the lymph from that organ. In summary, lymph nodes act as "lymph filters" which intercept antigen that arrives from infected tissues either alone or as dendritic cell cargo. So if there are no incoming lymphatics, how does antigen enter this secondary lymphoid organ These remarkable cells are not coated with mucus, so they are, by design, easily accessible to microorganisms that inhabit the intestine. They are "sampling" cells which specialize in transporting antigen from the interior (lumen) of the small intestine into the tissues beneath the M cell. To accomplish this feat, M cells enclose intestinal antigens in vesicles (endosomes). These endosomes are then transported through the M cell, and their contents are spit out into the tissues that surround the small intestine. Also, if the collected antigen is opsonized by complement or antibodies, it can be captured by follicular dendritic cells in the lymphoid follicles that reside beneath the M cells. Indeed, these cells only transport antigens that can bind to molecules on the surface of the M cell. But for a pathogen to be troublesome, it has to be able to bind to cells that line the intestines and gain entry into the tissues below. So the minimum requirement for a microbe to be dangerous is that it be able to bind to the surface of an intestinal cell. In contrast, most of the stuff we eat will just pass through the small intestine in various stages of digestion without binding to anything. This organ is located between an artery and a vein, and it functions as a blood filter. Consequently, it only takes about half an hour for your spleen to screen all the blood in your body for pathogens. The marginal sinuses are lined with macrophages that clean up the blood by phagocytosing cell debris and foreign invaders. Of course, since the spleen has no lymphatics to transport dendritic cells from the tissues, you might ask, "Where do the antigen presenting cells in the spleen come from So although the dendritic cells which present antigens to T cells in the spleen are travelers, their journey is relatively short compared with that of their cousins which travel to lymph nodes from a battle being waged in the tissues. Each secondary lymphoid organ is strategically positioned to intercept invaders that enter the body via different routes. If the skin is punctured and the tissues become infected, an immune response is generated in the lymph nodes that drain those tissues. If you are invaded by bloodborne pathogens, your spleen is there to filter them out and to fire up the immune response. And if an invader enters via your respiratory tract, another set of secondary lymphoid organs that includes your tonsils is there to defend you. Not only are the secondary lymphoid organs strategically positioned, they also provide a setting that is conducive to the mobilization of weapons that are appropriate to the kinds of invaders they are most likely to encounter. However, it is believed that the different cytokine environments of the various secondary lymphoid organs determine the local character of the immune response. Certainly the most important function of the secondary lymphoid organs is to bring lymphocytes and antigen presenting cells together in an environment that maximizes the probability that the cells of the adaptive immune system will be activated. When men and women use a dating service to find a mate, they begin by filling out a questionnaire that records information on their background and their goals. Then, a computer goes through all these questionnaires and tries to match up men and women who might be compatible. During our tour, we noted that the secondary lymphoid organs are "segregated," with separate areas for naive T cells and B cells. The Th cells that do not find their antigens leave the secondary lymphoid organs and continue to circulate. Only those lucky Th cells which are activated in the T cell area will proliferate and then travel to a developing germinal center to provide help to B cells. Likewise, many B cells enter the B cell areas of secondary lymphoid organs, looking for their cognate antigen displayed by follicular dendritic cells. Those rare B cells which do find their "mates" are retained in the secondary lymphoid organs, and are allowed to interact with activated Th cells. In a human, about 500 billion lymphocytes circulate each day through the various secondary lymphoid organs. They follow a welldefined traffic pattern which maximizes their chances of encountering an invader. Importantly, the traffic patterns of virgin and experienced lymphocytes are different. T cells begin life in the bone marrow and are educated in the thymus (lots more on this subject in Lecture 9). When they emerge from the thymus, virgin T cells express a mixture of cellular adhesion molecules on their surface. Equipped with this array of adhesion molecules, inexperienced T cells circulate through all of the secondary lymphoid organs. In the secondary lymphoid organs, virgin T cells pass through fields of antigen presenting cells in the T cell areas. If they do not see their cognate antigens advertised, they reenter the blood either via the lymph or directly (in the case of the spleen), and continue to recirculate. Naive T cells make this loop about once a day, spending only about 30 minutes in the blood on each circuit. In contrast, those lucky T cells that do find their antigen are activated in the secondary lymphoid organs. Experienced T cells also carry passports, but they are "restricted passports," because, during activation, expression of certain adhesion molecules on the T cell surface is increased, whereas expression of others is decreased.

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