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Essential newborn care: It comprises of resuscitation at Hemoglobin is estimated by hemoglobin color scale purchase line nimodipine muscle relaxant video, and birth for prevention of birth asphyxia buy generic nimodipine 30mg online muscle relaxant and anti inflammatory, initiation of breast glucose protein in urine is assessed by urine reagent feeding within half an hour of birth buy nimodipine 30 mg with mastercard muscle relaxant high blood pressure, rooming in, strips. Thus it makes sense to introduce higher and sophisticated services in the relatively advanced region where the backward regions needs to be assisted for strengthening and improving basic services. In order to improve delivery of these services all category ‘C’ districts (most backward districts) in Uttar Pradesh, Delhi, Fig. It is used when Staff Nurses are also being provided to 25% of Category laboratory hemoglobinometry is not available. The opportunities created by the immunization program • Add a drop of blood to one end of a test strip – would be utilized for effective delivery of the above- just enough to completely cover an aperture in the mentioned components. If in will be implemented as a 100% centrally sponsored doubt between two shades, record the lower value. More districts would be added in the cities-Delhi, Bangalore, Hyderabad and Kolkata for financial year 2001-2002. State of Assam, 10 backward districts of Rajasthan • Emergency obstetric care: These services are and 13 backward districts of Karnataka. European implemented in 32 districts in 6 states (Maharashtra, Commission is assisting in this activity. This is operationalized through Euros program, funded by the European Commis- a corpus fund to Panchayat. It is an integral part of the Reproductive and has been extended to all Category ‘C’ districts in all Child Health Program. Investment Program, which has received approval • Integrated financial envelop: Flexibility has been in Nov 1999. This will be extended to 60 districts granted to 6 States to design a package of interven- in these states or other states as may be mutually tions to address Maternal Health Care. The Government of India launched the National Rural • Improving outreach services: A new scheme has Health Mission in 2005. Measles Delivery care services include skilled birth attendance vaccine was included instead of typhoid vaccine. Close for all deliveries and provision of emergency obstetric monitoring was done in less than 1 year of age group. It is Program error: An event caused by an error in vaccine recommended that the first dose be given on first preparation, handling or administration. The most contact during pregnancy, the second dose being given common program error is infection as a result of nonsterile not earlier than one month after the first. Use of reconstituted vaccines beyond the In India, children get the diseases at an early age. Coincidental: An event that occurs after immunization However, if the child is brought later than the due date but is not caused by the vaccine. This is due to a chance for the next dose, it can still be given without starting temporal association. Malnutrition, low grade fever, mild evidence that the event is not related to immunization. Examples being common, minor vaccine reactions like local reaction (pain, swelling, redness), fever and systemic symptoms (e. An The cold chain is a system of transportation and storage 596 ideal vaccine reduces these reactions to a minimum while of vaccine at recommended temperature from the producing the best possible immunity. Current recommendation • Personnel: to organize and manage vaccine distribution is to store all vaccines on the basket. Domestic Refrigerators Whenever a thick layer of ice is formed inside the They also maintain a cabinet temperature between freezer, the inside temperature goes up, thus +2ºC to +8ºC with a holdover time of only 4 hours. Therefore, they are not recommended for common use • A paper should be pasted outside the refrigerator in the national program. However, they are used in containing the name and contact number of the urban dispensaries and by private practitioners in urban concerned person in case of a problem or failure. Ice lined refrigerators are lined with tubes or ice packs filled with water which freezes and keeps the internal Cold Boxes temperature at a safe level despite electricity failure. Conditioned ice packs are placed at the top-opening, they can hold the cold air inside better bottom and sides of the cold box before loading the than a front-opening refrigerator. A thermometer 597 Ice lined refrigerator has two sections-top and is also kept in the cold box. Thus Hep B is It is also a thermally insulated box, to carry small most sensitive to freezing. Response Time should be These are flat plastic containers filled with water, up to 48 hours for plains and 72 hours for hilly terrain. These are frozen in the • Down time refers to the time between breakdown deep freezer and when placed in nonelectrical cold of equipment and its repair or the period for which chain equipments such as vaccine carriers and cold an equipment remains out of service. The down time should be less than 2 weeks for plains and 3 weeks Thermometers for hilly terrain. Either dial or stem (alcohol) thermometers are used to • Bundling is the simultaneous availability of a measure the temperature during storage of vaccines. It is sent for of vaccines kept inside with adequate space between the next immunization session, but has to be the boxes, exposure to direct sunlight, different discarded after unopened more than thrice. Once the vaccine is frozen 598 enough to allow the temperature of the ice at the it tends to form flakes which gradually settle to the core of the icepack to rise to 0°C. It prevents freezing of freeze- occurs faster in a vaccine vial which has been frozen as compared to a vaccine vial which has not been Warm Chain frozen. It is an interlinked procedure minimizing the risk of Test: Shake test is conducted when one suspect that hypothermia of newborn babies. At first a vaccine vial training all persons, provision of clean, warm surface and of the same batch number and from the same drying, wrapping material, immediate drying, wrapping manufacturer is taken and is freezed until the and putting the baby to breast, warm cap, covering contents are solid (at least 8 hours at – 18°C). Now this False contraindications to immunization: control vial and test vial (suspect vial) are taken • Minor illness, chronic diseases (heart, lung, kidney). Effective communication has been recognized to freezing that contributes to the degradation of as a major constraint in universal immunization. These additional the child if he continues to be exposed to diarrheal components pertain to acute respiratory diseases, infections or unprotected drinking water supply. A system of training, • Children below 6 years orientation, continued education, functional monitoring, • Pregnant and lactating women evaluation and research has been evolved to fulfil the • Women in the age group 15 to 44 years. Services of senior teachers of pediatrics and psychological and social development of the child. Though success has about 41% of total population) is as follows not been uniform throughout the country, favourable (Table 30. Supplementary feeding support monitoring, sick or malnourished children, in need of is given for 300 days in a year. The anganwadi worker caloric gap between the national recommended and has also been oriented to detect disabilities in young average intake of children and women in low income children.


  • Eosinophils
  • CSF (cerebrospinal fluid) examination
  • Blood test
  • Recent trauma, surgery, or other uterine procedure
  • Blood coagulation studies
  • Breathing tube to help with breathing and protect the windpipe and lungs from getting eucalyptus oil into them when vomiting
  • Arteriovenous fistula
  • You are over 60 years old and your incontinence is new, especially if you are also having trouble with your memory or caring for yourself
  • Mental status changes
  • MRI scan

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Genetic sia order nimodipine overnight spasms side of head, patients may demonstrate impaired awareness and factors may also contribute (Jordan 2007) order generic nimodipine canada spasms just before falling asleep, although evi- wandering attention purchase nimodipine pills in toronto muscle relaxant antidote, whereas inability to concentrate for dence concerning the apolipoprotein E genotype is some- more than a few minutes and distractibility characterize what mixed. Over the course of recovery, complications in the early phases of recovery (Katz 1997). At later stages, relation to mood, pain, and sleep disturbance can also be impairments may only be revealed with rigorous testing. This occurs include mental slowing, trouble following conversation, because the damage incurred-both focal and diffuse-is loss of train of thought, and difficulty attending to two things concentrated in the anterior regions of the brain (Gentry et at once. Injury to selective, sustained, and divided components, as well as in- more central regions is also observed, such as the rostral formation processing speed and supervisory or executive brain stem. These elements reflect the interac- sic neurobehavioral syndromes such as aphasia, these are tions of several widely dispersed networks (Raz and Buhle commonly superimposed on the more global dysfunction 2006). Particular implications for re- motor-exploratory, and limbic-motivational inputs to guide habilitation and psychosocial/functional recovery are the targeting of attention. The brainstem reticular formation 279 280 Textbook of Traumatic Brain Injury supports the overall attentional tone or degree of respon- siveness to stimuli. Aspects of attention potentially impaired alertness and sustained attention has been postulated, after traumatic brain injury whereas the left hemisphere appears more closely linked to Arousal/alertness: general receptivity to sensory information selective or focused attention (Ponsford 2008). Choice reac- Information processing speed: rate at which information is processed within the central nervous system to allow tion time paradigms, which require decision making cognitive activities to occur among a number of alternative responses, have proved very sensitive to brain injury (Gronwall 1987; Mathias and Executive or “supervisory control” aspects: top-down coordination of lower-level attentional processes to perform Wheaton 2007). Although it taps a number of are hypothetical constructs devised to integrate clinical observations, cognitive processes, the Paced Auditory Serial Addition neuropsychological test results, and theoretical models of cognition. As such, they refer to interrelated rather than discrete processes and also Task (Gronwall 1987) has been used extensively to study overlap with other domains such as memory. In this task, subjects are pre- sented with a series of single-digit numbers verbally and in- structed to add each new digit to the one immediately pre- This component of the attentional system is hypothesized ceding it. Task difficulty is varied by adjusting the time to govern lower-level attentional processes and includes interval between the items presented. Performance on this the allocation of attentional resources, target selection, in- measure has been shown to correlate with injury severity, terference control, switching between tasks, monitoring, to track recovery of attentional capacities, and to predict re- and so forth (Rios et al. Results are at times contradictory memory (see next section, Impairments of Learning and and may differ with regard to the precise mechanisms un- Memory), also considered an important component of derlying a particular deficit (Rios et al. It is most dramatically apparent during the early in- tive means to probe deficits that may otherwise go unde- tervals of retrograde amnesia and posttraumatic amnesia, tected. Using paradigms that control for slowed process- the duration of which strongly predicts eventual outcome. Aspects of learning and memory potentially ten reveals deficits of immediate and delayed recall, impaired after traumatic brain injury slower rates of learning, and recall errors (intrusions). Al- though recognition memory may be relatively intact, it too Anterograde memory can be affected (Levin and Hanten 2004). Similar impair- The ability to learn new information; anterograde amnesia ment may be evident in the visual domain. Some investi- refers to a deficit in the conscious, deliberate recall of gators report dysfunction at all stages of episodic process- information first learned after brain insult ing, including encoding, consolidation, and retrieval Retrograde memory (Curtiss et al. However, differing amnesia involves impaired retrieval of memories acquired patterns of memory deficits can be expected among indi- prior to a brain insult, typically autobiographical in nature viduals, owing to the significant pathological heterogene- Explicit (or declarative) memory ity. A consistent finding is the failure to spontaneously ap- Episodic memory: memory for specific personal experiences ply organizing strategies when learning, such as clustering or “autobiographical” events words according to semantic category (e. In general, tasks that require including knowledge of objects deliberate, controlled, and generally conscious process- Implicit memorya ing, as opposed to automatic processes occurring uncon- Procedural memory: perceptual and motor skill learning; sciously, show the greatest degree of disruption. The semantic or general knowledge base also remains Priming effect: the enhancement in test performance as a result of previous exposure to stimuli largely intact, although problems with inefficient access and retrieval can impede recall (McWilliams and Schmit- Classical conditioning ter-Edgecombe 2008). Cases of relatively selective deficits Aspects of memory related to executive functions with a specific aspect of memory have been described, Working memory: the temporary storage and manipulation of such as marked semantic memory loss or disproportionate information relevant for cognitive operations; via ongoing autobiographical memory alteration, yet these are rare and rehearsal, the duration of immediate or short-term memory reported in the setting of severe injury (Levin and Hanten (which would otherwise decay in a few seconds) is extended 2004; Vakil 2005). Strategic memory: the application of active organizing and Other aspects of memory closely associated with exec- elaborative strategies to enhance encoding and retrieval utive processing are vulnerable to injury. Working memory is Prospective memory: remembering to perform a task in the thought to comprise 1) a set of “slave” systems for the “on- future at a specific time or following a certain event line” maintenance of verbal and visuospatial information Metamemory: awareness and knowledge regarding one’s via rehearsal and 2) a “central executive” that further pro- memory capabilities cesses and manipulates the information being held. The aThis aspect of memory appears much less vulnerable to the effects of central executive is closely linked with the dorsolateral traumatic brain injury (see Vakil 2005 for discussion). Objective memory dysfunction may tween the slave systems, enabling the division of attention persist in those with moderate to severe injuries even after when necessary (Baddeley 2004). Dur- fects the control/manipulation processes rather than the ing assessment, one must consider other domains poten- passive storage/rehearsal aspects, a finding supported by tially affecting memory function, such as attention, pro- both neuropsychological (Vallat-Azouvi et al. Thus performance at reversed digit span, requiring explicit memory, which can be consciously, deliberately the active manipulation of information, is typically more recalled; and implicit memory, which is acquired without impaired than digits forward. Explicit memory is A related construct known as prospective memory, or further divisible into episodic memory for personal events the ability to remember one’s future intentions, is fre- and semantic memory for general facts about the world. Forgetting to take contrast, implicit memory refers to a range of abilities such medications, attend appointments, or make bill payments as procedural learning, conditioning, and priming effects can potentially jeopardize one’s capacity for independent (Baddeley 2004). Aspects of executive functions potentially ability to gauge their performance during formal memory impaired after traumatic brain injury testing when compared with control subjects (Kennedy Goal establishment, planning, and anticipation of and Yorkston 2000). These deficiencies may be critical in consequences influencing one to use compensatory strategies to enhance Initiation and inhibition of responses; temporal sequencing of memory function or agree to participate in rehabilitation. Transcending of the immediately salient aspects of a situation Neuroimaging studies provide a basis for understand- (vs. Yet only modest correlations be- Self-monitoring and self-regulation, including emotional tween hippocampal size and reduced memory function responses are found (Bigler 2007), pointing to the significance of in- Social adaptive functioning: perspective taking, use of social jury elsewhere. Diencephalic and basal forebrain struc- feedback, adherence to social norms tures are obvious candidates, given their substantial in- volvement in episodic memory. Impairments of In addition, a major contribution from diffuse injury, with disruption of wider memory networks, is suggested Frontal Executive Functions by the fact that memory deficits tend to show stronger as- sociations with severity indicators such as posttraumatic The term executive functions refers to a set of higher-order amnesia duration and Glasgow Coma Scale scores than capabilities that are considered the domain of the frontal with the presence of specific focal lesions on neuroimag- lobes and their projections. Although at- relevant goals and planning, initiating and sequencing tention and executive dysfunction were also frequent, goal-directed behavior, inhibiting competing actions and they were relatively less severe. The memory impairments stimuli, conceptual reasoning, decision making, as well as were attributed to disruption of both frontal-subcortical the activities of self-monitoring and self-regulating (Stuss and memory-specific temporal networks, based on the ob- and Levine 2002; see Table 17–3). Historically, a parallel has been noted between tests tends to resolve within 1–3 months (Belanger et al. However, a discrepancy is often noted between nor- ing from focal frontal lobe damage (Stuss and Gow 1992). It is possible that residual cognitive inefficiency with polar and ventral frontal and temporal regions being contributes to a perception of forgetfulness that is not particularly prone to contusional damage. As noted earlier, deficits of higher-order func- application of strategic memory (Vakil 2005), planning tions may only become apparent under conditions of in- ability (Cazalis et al. Superior medial frontal dam- Studies have tended to show stronger associations be- age can produce marked apathy or abulia (i. Stuss and Alexander (2009) noted that or absence of a demonstrable frontal lesion. Using the Iowa Gambling Task, neuroimaging finding that superior medial prefrontal re- a novel measure designed to simulate real-world decision gions are engaged whenever a cognitive task becomes more making, Bechara et al.

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The generator potential creates a current through the axon membrane called a local excitatory current generic 30mg nimodipine mastercard muscle relaxant ratings. It provides the link between the formation of the generator potential and the excitation of the nerve fiber membrane discount nimodipine 30mg with mastercard muscle relaxant guardian pharmacy. The production of the generator potential is of critical importance in the transduction process because it is the step in which information related to stimulus intensity and duration is transduced cheap 30mg nimodipine overnight delivery spasms urethra. Varying the intensity of the stimulation will correspondingly vary the generator potential, although the changes are not always directly proportional to the intensity. This is called a graded response, in contrast to the all-or-none response of an action potential, and causes a similar gradation of the strength of the local excitatory currents. As generator potential depolarizing currents spread down the neuron, they reach a region of the receptor membrane called the impulse initiation region (4). This region is the location of the formation of action potentials in the neuron and constitutes the next important link in the sensory process. In this region, action potentials are produced at a frequency related to the strength of the current caused by the generator potential (and, thus, related to the original stimulus intensity). This region is, therefore, sometimes called the coding region, because here the generator potential and flowing current caused by the initial stimulus to the receptor are translated into a train of action potentials of a frequency proportional (but not always in a linear fashion) to the size of the generator potential. In complex sensory organs that contain a great many individual receptors, the generator potential may arise from several sources within the organ. Thus, the train of action potentials formed results from multiple inputs to the sensory receptor. In such receptors, the formation of the receptor and action potentials occurs in the same cell, the neuron. This type of sensory receptor-to-action potential arrangement is best suited for transmission of sensory information over long distances. The sense of touch and temperature at the tips of our fingers or toes are examples of sensory transduction by long receptors. In contrast, other types of sensory transduction in the body occur through short receptors. Short receptors are highly specialized cells that, like long receptors, also convert a nonelectrical form of energy into a receptor potential within them. However, in short receptors, the receptor generator potential and neuron action potentials occur in two different cells. In short receptors, the local potential event is coupled to the release of neurotransmitter stored in the receptor cell. This transmitter is then released onto synapses of a postsynaptic primary afferent neuron in which it produces another localized generator potential. Short receptors produce either depolarizing or hyperpolarizing generator potentials. In some cases, the same receptor can produce depolarizing and hyperpolarizing generator potentials depending on the stimulus they receive. Positive generator potentials increase the rate of transmitter release, whereas negative potentials decrease this rate. The photoreceptors of the eye and the hair receptors of the cochlea of the inner ear are examples of short sensory receptors (see below). Sensory nerve impulse frequency is modulated by the magnitude and duration of the generator potential. This example is typical of what might be seen in a long receptor- type sensory nerve. Membrane potential changes below this level are caused by the local excitatory currents and vary in proportion to them, whereas the membrane activity above the threshold level consists of locally produced action potentials. The lower trace shows a series of different stimuli applied to the receptor, and the upper trace shows the resulting electrical events in the impulse initiation region. At B, a small stimulus is applied, producing a generator potential too small to bring the impulse initiation region to threshold; no action potential activity results, and the stimulus causing this level of potential generation would, therefore, not be sensed at all. In contrast, at C, a brief stimulus of greater intensity is given, and the resulting generator potential displacement is of sufficient amplitude to trigger a single action potential. As in all excitable and all-or- none nerve membranes, the action potential is immediately followed by repolarization, often to a level that transiently hyperpolarizes the membrane potential because of temporarily high potassium conductance. Because the brief stimulus has been removed by this time, no further action potentials are produced. A longer stimulus of the same intensity (D) produces repetitive action potentials because, as the membrane repolarizes from the action potential, local excitatory currents are still flowing. They bring the repolarized membrane to threshold at a rate proportional to their strength. During this time interval, the fast sodium channels of the membrane are being reset, and another action potential is triggered as soon as the membrane potential reaches threshold. As long as the stimulus is maintained, this process will repeat itself at a rate determined by the stimulus intensity. If the intensity of the stimulus is increased (E), the local excitatory currents will be stronger and the threshold will be reached more rapidly. This will result in a reduction of the time between each action potential and, as a consequence, a higher action potential frequency. Sustained sensory receptor stimulation can result in diminished action potential generation over time. In the presence of a constant stimulus, only some sensory receptors maintain the magnitude of their initial generator potential. In most sensory receptors, the magnitude of the generator potential decays over time, even when the original sensory stimulus does not change. As long as the stimulus is maintained, there is a steady rate of action potential firing. Responses in which there is little or no adaptation are called tonic, whereas those in which significant adaptation occurs are called phasic. In some cases, tonic receptors may be called intensity receptors and phasic receptors may be called velocity receptors. On application of a stimulus, a rapidly adapting phasic response is followed by a steady tonic response. Adaptation in a sensory receptor is often related to a decline in the generator potential with time. The phenomenon of adaptation is important in preventing “sensory overload” and allows less important or unchanging environmental stimuli to be partially ignored. When a change occurs, however, the phasic response will occur again, and the sensory input will become temporarily more noticeable. Rapidly adapting receptors are also important in sensory systems that must sense the rate of change of a stimulus, especially when the intensity of the stimulus can vary over a range that would overload a tonic receptor. As mentioned above, adaptation of the generator potential itself can produce adaptation of the overall sensory response. In some cases, however, the receptor’s sensitivity is changed by the action of accessory structures, as in the constriction of the pupil of the eye in the presence of bright light (an example of feedback-controlled adaptation).

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The relative importance of active transport in the duodenum and jejunum versus passive diffusion in the ileum depends on several factors buy cheap nimodipine 30mg line muscle relaxant powder. At high levels of calcium intake buy 30mg nimodipine spasms icd 9 code, active transport processes are saturated and most of the uptake occurs in the ileum buy discount nimodipine 30mg on line spasms medicine, partly because of its greater length, compared with other intestinal segments. With moderate or low calcium intake, however, active transport predominates because the gradient for diffusion is low. Active transport is the regulated variable in controlling calcium uptake from the small intestine. Metabolites of vitamin D provide a regulatory signal to increase intestinal calcium absorption. Under the influence of 1,25-dihydroxycholecalciferol, calcium-binding proteins in intestinal mucosal cells increase in number, enhancing the capacity of these cells to transport calcium actively. Uptake occurs by active transport and passive diffusion, but active transport is the primary mechanism. However, phosphate absorption from the small intestine is regulated to a minor extent. Active transport of phosphate is coupled to calcium transport, and thus, when active transport of calcium is low, as with vitamin D deficiency, phosphate absorption is also low. The remaining 40% of the total calcium is bound to plasma proteins and is not filterable by the glomeruli. Ordinarily, 99% of the filtered calcium is reabsorbed by the kidney tubules and returned to the plasma. Reabsorption occurs both in the proximal and distal tubules and in the loop of Henle. Approximately 60% of filtered calcium is reabsorbed in the proximal tubule, 30% in the loop of Henle, and 9% in the distal tubule; the remaining 1% is excreted in the urine. Ordinarily, about 85% of filtered phosphate is reabsorbed and 15% is excreted in the urine. Phosphate reabsorption occurs via active transport, mainly in the proximal tubule, where 65% to 80% of filtered phosphate is reabsorbed. It increases urinary phosphate excretion, leading to the condition of phosphaturia, with an accompanying decrease in the plasma phosphate concentration. Although bone may be considered as being a relatively inert material, it is active metabolically. Considerable amounts of calcium and phosphate enter and exit the bone each day, and these processes are hormonally controlled. Mature bone can be simply described as inorganic mineral deposited on an organic framework. The mineral portion of bone4 6 2 typically comprises about 25% of its volume, but because of its high density, the mineral fraction is responsible for approximately half the weight of bone. Bone contains considerable amounts of the body’s content of carbonate, magnesium, and sodium, in addition to calcium and phosphate (see Table 35. The organic matrix of bone on which the bone mineral is deposited is called osteoid. Collagen in bone is similar to that of skin and tendons, but bone collagen exhibits some biochemical differences that impart increased mechanical strength. The remaining noncollagen portion (5%) of organic matter is referred to as ground substance that consists of various proteoglycans. These proteoglycans are high molecular weight compounds consisting of different types of polysaccharides. Electron microscopic study of bone reveals needle-like hydroxyapatite crystals lying alongside collagen fibers. This orderly association of hydroxyapatite crystals with the collagen fibers is responsible for the strength and hardness characteristic of bone. A loss of either bone mineral or organic matrix greatly affects the mechanical properties of bone. Complete demineralization of bone leaves a flexible collagen framework, and the complete removal of organic matrix leaves a bone with its original shape, but extremely brittle. Osteogenesis imperfecta, or brittle bone disease, is a genetic disorder characterized by bones that break easily as a result of defects in the production of the fibrillar collagen matrix. Osteoblasts are located on the bone surface and are responsible for osteoid synthesis (Fig. Like many cells that actively synthesize proteins for export, osteoblasts have an abundant rough endoplasmic reticulum and Golgi apparatus. Cells actively engaged in osteoid synthesis are cuboidal, whereas those less active are more flattened. Numerous cytoplasmic processes connect adjacent osteoblasts on the bone surface and connect osteoblasts with osteocytes deeper in the bone. Eventually, new osteoid becomes mineralized, and in the process, mineralized bone surrounds osteoblasts. As osteoblasts are progressively incorporated into mineralized bone, they lose much of their bone- forming ability and become quiescent. Many of the cytoplasmic connections in the osteoblast stage are maintained into the osteocyte stage. These connections become visible channels or canaliculi that provide direct contact for osteocytes deep in bone with other osteocytes and with the bone surface. It is generally believed that these canaliculi provide a mechanism for the transfer of nutrients, hormones, and waste products between the bone surface and its interior. Osteoclasts promote bone resorption by secreting acid and proteolytic enzymes into the space adjacent to the bone surface. Surfaces of osteoclasts facing bone are ruffled to increase their surface area and promote bone resorption. First, osteoclasts create a local acidic environment that increases the solubility of surface bone mineral. Second, proteolytic enzymes secreted by osteoclasts degrade the organic matrix of bone. Early in fetal development, the skeleton consists of little more than a cartilaginous model of what will later form the bony skeleton. The process of replacing this cartilaginous model with mature, mineralized bone begins in the center of the cartilage and progresses toward the two ends of what will later form the bone. The epiphyseal plate is a region of growing bone of particular interest because it is here that the elongation and growth of bones occur after birth. Histologically, the epiphyseal plate shows considerable differences between its leading and trailing edges. The leading edge consists primarily of chondrocytes, which are actively engaged in the synthesis of cartilage of the epiphyseal plate. These cells gradually become engulfed in their own cartilage and are replaced by new cells on the cartilage surface, allowing the process to continue. Osteoblasts secrete osteoid, which eventually becomes mineralized, and a new mature bone is formed. In the epiphyseal plate, therefore, the continuing processes of cartilage synthesis, calcification, erosion, and osteoblast invasion result in a zone of active bone formation that moves away from the middle or center of the bone toward its end.

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