The metaphysis is the narrow portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, as it grows it ossifies near the diaphysis and the epiphyses; the metaphysis may be divided anatomically into three components based on tissue content: a cartilaginous component, a bony component and a fibrous component surrounding the periphery of the plate. The growth plate synchronizes chondrogenesis with osteogenesis or interstitial cartilage growth with appositional bone growth at the same that it is growing in width, bearing load and responding to local and systemic forces and factors. During childhood, the growth plate contains the connecting cartilage enabling the bone to grow. In an adult, the metaphysis functions to transfer loads from weight-bearing joint surfaces to the diaphysis; because of their rich blood supply and vascular stasis, metaphyses of long bones are prone to hematogenous spread of osteomyelitis in children.
Metaphyseal tumors or lesions include osteosarcoma, fibrosarcoma, enchondroma, fibrous dysplasia, simple bone cyst, aneurysmal bone cyst, non-ossifying fibroma, osteoid osteoma. One of the clinical signs of rickets that doctors look for is cupping and fraying at the metaphyses when seen on X-ray. Diaphysis Epiphysis Anatomy photo: Musculoskeletal/bone/structure0/structure2 - Comparative Organology at University of California, Davis - "Bone, structure"
The skull is a bony structure that forms the head in vertebrates. It provides a protective cavity for the brain; the skull is composed of two parts: the mandible. In the human, these two parts are the neurocranium and the viscerocranium or facial skeleton that includes the mandible as its largest bone; the skull forms the anterior most portion of the skeleton and is a product of cephalisation—housing the brain, several sensory structures such as the eyes, ears and mouth. In humans these sensory structures are part of the facial skeleton. Functions of the skull include protection of the brain, fixing the distance between the eyes to allow stereoscopic vision, fixing the position of the ears to enable sound localisation of the direction and distance of sounds. In some animals such as horned ungulates, the skull has a defensive function by providing the mount for the horns; the English word "skull" is derived from Old Norse "skulle", while the Latin word cranium comes from the Greek root κρανίον.
The skull is made up of a number of fused flat bones, contains many foramina, fossae and several cavities or sinuses. In zoology there are openings in the skull called fenestrae. For details and the constituent bones, see Neurocranium and Facial skeleton The human skull is the bony structure that forms the head in the human skeleton, it forms a cavity for the brain. Like the skulls of other vertebrates, it protects the brain from injury; the skull consists of two parts, of different embryological origin—the neurocranium and the facial skeleton. The neurocranium forms the protective cranial cavity that surrounds and houses the brain and brainstem; the upper areas of the cranial bones form the calvaria. The membranous viscerocranium includes the mandible; the facial skeleton is formed by the bones supporting the face Except for the mandible, all of the bones of the skull are joined together by sutures—synarthrodial joints formed by bony ossification, with Sharpey's fibres permitting some flexibility.
Sometimes there can be extra bone pieces within the suture known as sutural bones. Most these are found in the course of the lambdoid suture; the human skull is considered to consist of twenty-two bones—eight cranial bones and fourteen facial skeleton bones. In the neurocranium these are the occipital bone, two temporal bones, two parietal bones, the sphenoid and frontal bones; the bones of the facial skeleton are the vomer, two inferior nasal conchae, two nasal bones, two maxilla, the mandible, two palatine bones, two zygomatic bones, two lacrimal bones. Some sources count the maxilla as having two bones; some of these bones—the occipital, frontal, in the neurocranium, the nasal and vomer, in the facial skeleton are flat bones. The skull contains sinuses, air-filled cavities known as paranasal sinuses, numerous foramina; the sinuses are lined with respiratory epithelium. Their known functions are the lessening of the weight of the skull, the aiding of resonance to the voice and the warming and moistening of the air drawn into the nasal cavity.
The foramina are openings in the skull. The largest of these is the foramen magnum that allows the passage of the spinal cord as well as nerves and blood vessels; the many processes of the skull include the zygomatic processes. The skull is a complex structure; the skull roof bones, comprising the bones of the facial skeleton and the sides and roof of the neurocranium, are dermal bones formed by intramembranous ossification, though the temporal bones are formed by endochondral ossification. The endocranium, the bones supporting the brain are formed by endochondral ossification, thus frontal and parietal bones are purely membranous. The geometry of the skull base and its fossae, the anterior and posterior cranial fossae changes rapidly; the anterior cranial fossa changes during the first trimester of pregnancy and skull defects can develop during this time. At birth, the human skull is made up of 44 separate bony elements. During development, many of these bony elements fuse together into solid bone.
The bones of the roof of the skull are separated by regions of dense connective tissue called fontanelles. There are six fontanelles: one anterior, one posterior, two sphenoid, two mastoid. At birth these regions are fibrous and moveable, necessary for birth and growth; this growth can put a large amount of tension on the "obstetrical hinge", where the squamous and lateral parts of the occipital bone meet. A possible complication of this tension is rupture of the great cerebral vein; as growth and ossification progress, the connective tissue of the fontanelles is invaded and replaced by bone creating sutures. The five sutures are the two squamous sutures, one coronal, one lambdoid, one sagittal suture; the posterior fontanelle closes by eight weeks, but the anterior fontanel can remain open up to eighteen months. The anterior fontanelle is located at the junction of the parietal bones. Careful observation will show that you can count a baby's heart
Elastic cartilage or yellow cartilage is a type of cartilage present in the outer ear, Eustachian tube and epiglottis. It contains collagen type II fibers; the principal protein is elastin. Elastic cartilage is histologically similar to hyaline cartilage but contains many yellow elastic fibers lying in a solid matrix; these fibers form bundles. These fibers give elastic cartilage great flexibility so that it is able to withstand repeated bending; the chondrocytes lie between the fibres. It is found in the pinnae. Elastin fibers stain dark purple/black with Verhoeff's stain. Provide support Maintain shape This article incorporates text in the public domain from page 279 of the 20th edition of Gray's Anatomy Histology image: 12_02 at the University of Oklahoma Health Sciences Center - "epiglottis" Histology image: 02901loa – Histology Learning System at Boston University Histology at ucsd.edu Anatomy Atlases - Microscopic Anatomy, plate 03.42
A membrane is a selective barrier. Such things may be ions, or other small particles. Biological membranes include cell membranes. Synthetic membranes are made by humans for use in laboratories and industry; this concept of a membrane has been known since the eighteenth century, but was used little outside of the laboratory until the end of World War II. Drinking water supplies in Europe had been compromised by the war and membrane filters were used to test for water safety. However, due to the lack of reliability, slow operation, reduced selectivity and elevated costs, membranes were not exploited; the first use of membranes on a large scale was with micro-filtration and ultra-filtration technologies. Since the 1980s, these separation processes, along with electrodialysis, are employed in large plants and, today, a number of experienced companies serve the market; the degree of selectivity of a membrane depends on the membrane pore size. Depending on the pore size, they can be classified as microfiltration, ultrafiltration and reverse osmosis membranes.
Membranes can be of various thickness, with homogeneous or heterogeneous structure. Membranes can be neutral or charged, particle transport can be active or passive; the latter can be facilitated by pressure, chemical or electrical gradients of the membrane process. Membranes can be classified into synthetic membranes and biological membranes. Microfiltration operates within a range of 7-100 kPa. Microfiltration is used to remove residual suspended solids, to remove bacteria in order to condition the water for effective disinfection and as a pre-treatment step for reverse osmosis. Recent developments are membrane bioreactors which combine microfiltration and a bioreactor for biological treatment. Ultrafiltration operates within a range of 70-700kPa. Ultrafiltration is used for many of the same applications as microfiltration; some ultrafiltration membranes have been used to remove dissolved compounds with high molecular weight, such as proteins and carbohydrates. In addition, they are able to remove some endotoxins.
Nanofiltration is known as “loose” RO and can reject particles smaller than 0,002 µm. Nanofiltration is used for the removal of selected dissolved constituents from wastewater. NF is developed as a membrane softening process which offers an alternative to chemical softening. Nanofiltration can be used as a pre-treatment before directed reverse osmosis; the main objectives of NF pre-treatment are:. Minimize particulate and microbial fouling of the RO membranes by removal of turbidity and bacteria, prevent scaling by removal of the hardness ions, lower the operating pressure of the RO process by reducing the feed-water total dissolved solids concentration. Reverse osmosis is used for desalination; as well, RO is used for the removal of dissolved constituents from wastewater remaining after advanced treatment with microfiltration. RO requires high pressures to produce deionized water. In the membrane field, the term module is used to describe a complete unit composed of the membranes, the pressure support structure, the feed inlet, the outlet permeate and retentate streams, an overall support structure.
The principal types of membrane modules are: Tubular, where membranes are placed inside a support porous tubes, these tubes are placed together in a cylindrical shell to form the unit module. Tubular devices are used in micro and ultra filtration applications because of their ability to handle process streams with high solids and high viscosity properties, as well as for their relative ease of cleaning. Hollow fiber consists of a bundle of hundreds to thousands of hollow fibers; the entire assembly is inserted into a pressure vessel. The feed can be applied to the outside of the fiber. Spiral Wound, where a flexible permeate spacer is placed between two flat membranes sheet. A flexible feed spacer is added and the flat sheets are rolled into a circular configuration. Plate and frame consist of a series of flat membrane sheets and support plates; the water to be treated passes between the membranes of two adjacent membrane assemblies. The plate supports the membranes and provides a channel for the permeate to flow out of the unit module.
Ceramic and polymeric Flat Sheet modules. Flat sheet membranes are built-into a submerged vacuum driven filtration systems which consist of stacks of modules each with a number of sheets. Filtration mode is outside-in where the water passes through the membrane and is collected in permeate channels. Cleaning can be performed by aeration, back wash and CIP; the key elements of any membrane process relate to the influence of the following parameters on the overall permeate flux are: The membrane permeability The operational driving force per unit membrane area The fouling and subsequent cleaning of the membrane surface. The total permeate flow from a membrane system is given by following equation: Q p = F w ⋅ A Where Qp is the permeate stream flowrate, Fw is the water flux rate and A is the membrane area The permeability of a membrane is giv
Intramembranous ossification is one of the two essential processes during fetal development of the gnathostome skeletal system by which rudimentary bone tissue is created. Intramembranous ossification is an essential process during the natural healing of bone fractures and the rudimentary formation of bones of the head. Unlike endochondral ossification, the other process by which bone tissue is created during fetal development, cartilage is not present during intramembranous ossification. Mesenchymal stem cells within mesenchyme or the medullary cavity of a bone fracture initiate the process of intramembranous ossification. A mesenchymal stem cell, or MSC, is an unspecialized cell. Before it begins to develop, the morphological characteristics of a MSC are: a small cell body with a few cell processes that are long and thin. Furthermore, the mesenchymal stem cells are dispersed within an extracellular matrix, devoid of every type of collagen, except for a few reticular fibrils; the process of intramembranous ossification starts when a small group of adjacent MSCs begin to replicate and form a small, dense cluster of cells, a nidus.
Once a nidus has been formed the MSCs within it stop replicating. At this point, morphological changes in the MSCs begin to occur: the cell body is now larger and rounder. All of the cells within the nidus develop into, display the morphologic characteristics of, an osteoprogenitor cell. At this stage of development, changes in the morphology of the osteoprogenitor cells occur: their shape becomes more columnar and the amount of Golgi apparatus and rough endoplasmic reticulum increases. All of the cells within the nidus develop into, display the morphologic characteristics of, an osteoblast; the osteoblasts create an extracellular matrix containing Type-I collagen fibrils, osteoid. The osteoblasts, while lining the periphery of the nodule, continue to form osteoid in the center of the nidus; some of the osteoblasts become incorporated within the osteoid to become osteocytes. At this point, the osteoid becomes mineralized resulting in a nidus consisting of mineralized osteoid that contains osteocytes and is lined by active osteoblasts.
The nidus, that began as a diffuse collection of MSCs, has become rudimentary bone tissue. The first step in the process is the formation of bone spicules which fuse with each other and become trabeculae; the periosteum is formed and bone growth continues at the surface of trabeculae. Much like spicules, the increasing growth of trabeculae result in interconnection and this network is called woven bone. Woven bone is replaced by lamellar bone. Embryologic mesenchymal cells condense into layers of vascularized primitive connective tissue. Certain mesenchymal cells group together near or around blood vessels, differentiate into osteogenic cells which deposit bone matrix constitutively; these aggregates of bony matrix are called bone spicules. Separate mesenchymal cells differentiate into osteoblasts, which line up along the surface of the spicule and secrete more osteoid, which increases the size of the spicule; as the spicules continue to grow, they fuse with adjacent spicules and this results in the formation of trabeculae.
When osteoblasts become trapped in the matrix they secrete. Osteoblasts continue to line up on the surface; as growth continues, trabeculae become woven bone is formed. The term primary spongiosa is used to refer to the initial trabecular network; the periosteum is formed around the trabeculae by differentiating mesenchymal cells. The primary center of ossification is the area where bone growth occurs between the periosteum and the bone. Osteogenic cells that originate from the periosteum increase appositional growth and a bone collar is formed; the bone collar is mineralized and lamellar bone is formed. Osteons are components or principal structures of compact bone. During the formation of bone spicules, cytoplasmic processes from osteoblasts interconnect; this becomes the canaliculi of osteons. Since bone spicules tend to form around blood vessels, the perivascular space is reduced as the bone continues to grow; when replacement to compact bone occurs, this blood vessel becomes the central canal of the osteon.
Flat bones of the face Bones of the skull Clavicles Endochondral ossification Ossification Martin, RB.
Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is called the osteon. Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells, they synthesize dense, crosslinked collagen and specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which compose the organic matrix of bone. In organized groups of connected cells, osteoblasts produce hydroxylapatite, deposited, in a regulated manner, into the organic matrix forming a strong and dense mineralized tissue - the mineralized matrix; the mineralized skeleton is the main support for the bodies of air breathing vertebrates. It is an important store of minerals for physiological homeostasis including both acid-base balance and calcium or phosphate maintenance; the skeleton is a large organ, formed and degraded throughout life in the air-breathing vertebrates.
The skeleton referred to as the skeletal system, is important both as a supporting structure and for maintenance of calcium and acid-base status in the whole organism. The functional part of bone, the bone matrix, is extracellular; the bone matrix consists of mineral. The protein forms the organic matrix, it is synthesized and the mineral is added. The vast majority of the organic matrix is collagen; the matrix is mineralized by deposition of hydroxyapatite. This mineral is hard, provides compressive strength. Thus, the collagen and mineral together are a composite material with excellent tensile and compressive strength, which can bend under a strain and recover its shape without damage; this is called elastic deformation. Forces that exceed the capacity of bone to behave elastically may cause failure bone fractures. Bone is a dynamic tissue, being reshaped by osteoblasts, which produce and secrete matrix proteins and transport mineral into the matrix, osteoclasts, which break down the tissues. Osteoblasts are the major cellular component of bone.
Osteoblasts arise from mesenchymal stem cells. MSC give rise to osteoblasts and myocytes among other cell types. Osteoblast quantity is understood to be inversely proportional to that of marrow adipocytes which comprise marrow adipose tissue. Osteoblasts are found in large numbers in the periosteum, the thin connective tissue layer on the outside surface of bones, in the endosteum. All of the bone matrix, in the air breathing vertebrates, is mineralized by the osteoblasts. Before the organic matrix is mineralized, it is called the osteoid. Osteoblasts buried in the matrix are called osteocytes. During bone formation, the surface layer of osteoblasts consists of cuboidal cells, called active osteoblasts; when the bone-forming unit is not synthesizing bone, the surface osteoblasts are flattened and are called inactive osteoblasts. Osteocytes are connected by cell processes to a surface layer of osteoblasts. Osteocytes have important functions in skeletal maintenance. Osteoclasts break down bone tissue, along with osteoblasts and osteocytes form the structural components of bone.
In the hollow within bones are many other cell types of the bone marrow. Components that are essential for osteoblast bone formation include mesenchymal stem cells and blood vessels that supply oxygen and nutrients for bone formation. Bone is a vascular tissue, active formation of blood vessel cells from mesenchymal stem cells, is essential to support the metabolic activity of bone; the balance of bone formation and bone resorption tends to be negative with age in post-menopausal women leading to a loss of bone serious enough to cause fractures, called osteoporosis. Bone is formed by one of two processes: endochondral ossification or intramembranous ossification. Endochondral ossification is the process of forming bone from cartilage and this is the usual method; this form of bone development is the more complex form: it follows the formation of a first skeleton of cartilage made by chondrocytes, removed and replaced by bone, made by osteoblasts. Intramembranous ossification is the direct ossification of mesenchyme as happens during the formation of the membrane bones of the skull and others.
During osteoblast differentiation, the developing progenitor cells express the regulatory transcription factor Cbfa1/Runx2. A second required transcription factor is Sp7 transcription factor. Osteochondroprogenitor cells differentiate under the influence of growth factors, although isolated mesenchymal stem cells in tissue culture, form osteoblasts under permissive conditions that include vitamin C and substrates for alkaline phosphatase, a key enzyme that provides high concentrations of phosphate at the mineral deposition site. Key growth factors in endochondral skeletal differentiation include bone morphogenetic proteins that determine to a major extent where chondrocyte differentiation occurs and where spaces are left between bones; the system of cartilage replacement by bone has a complex regulatory system. BMP2 regulates early skeletal patterning. Transforming growth factor beta, is part of a superfamily of proteins that include BMPs, which possess common signaling elements in the TGF beta signaling pathway.
TGF-β is important in cartilage differentiation, which precedes bone formation for endochondral ossification. An additional
An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance and remodelling of bones of the vertebral skeleton; the osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process helps regulate the level of blood calcium. An odontoclast is an osteoclast associated with absorption of the roots of deciduous teeth. An osteoclast is a large multinucleated cell and human osteoclasts on bone have five nuclei and are 150–200 µm in diameter; when osteoclast-inducing cytokines are used to convert macrophages to osteoclasts large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate; the size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone.
In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howship's lacunae. Osteoclasts are characterized by a cytoplasm with "foamy" appearance; this appearance is due to a high concentration of vacuoles. These vacuoles include lysosomes filled with acid phosphatase; this permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase and cathepsin K. Osteoclast rough endoplasmic reticulum is sparse, the Golgi complex is extensive. At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue; this extensively folded or ruffled border facilitates bone removal by increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast, resorbing bone. Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, osteoblasts fuse together to form osteoclasts.
After years of controversy it is now clear that these cells develop from the self fusion of macrophages. It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. Osteoclast formation requires the presence of RANKL and M-CSF; these membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms, a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are involved in the differentiation of monocyte/macrophage derived cells. RANKL is a member of the tumour necrosis family, is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ and NFATc1 through RANK.
NF-κβ activation is stimulated immediately after RANKL-RANK interaction occurs and is not upregulated. NFATc1 stimulation, begins ~24–48 hours after binding occurs and its expression has been shown to be RANKL dependent. Osteoclast differentiation is inhibited by osteoprotegerin, produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK, it may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells. Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in small cavities called Howship's lacunae, formed from the digestion of the underlying bone; the sealing zone is the attachment of the osteoclast's plasma membrane to the underlying bone. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin.
The osteoclast releases hydrogen ions through the action of carbonic anhydrase through the ruffled border into the resorptive cavity and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped against a high concentration gradient by proton pumps a unique vacuolar-ATPase; this enzyme has been targeted in the prevention of osteoporosis. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease groups, are released to digest the organic components of the matrix; these enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance. Cathepsin K is a collagenolytic, papain-like, cysteine protease, expressed in osteoclasts, is secreted into the resorptive pit. Cathepsin K is the major protease involved in the degradation of