skeletal system and Blood Supply.pptx

The Skeletal System & Blood Supply BY PROF.ANDREW B.SC(HONS.)MBBCH,M.SC,PH.D INTRODUCTION  Cartilage is a semi-rigid but flexible avascular connective tissue found at various sites within the body. Cartilage function is more than structural, and has different functions in the life cy...

The Skeletal System & Blood Supply BY PROF.ANDREW B.SC(HONS.)MBBCH,M.SC,PH.D INTRODUCTION  Cartilage is a semi-rigid but flexible avascular connective tissue found at various sites within the body. Cartilage function is more than structural, and has different functions in the life cycle. In the embryo, it provides support and is a precursor to bone. Embryonic cartilage either remains as cartilage or provides a substructure for endochondral ossification, meaning it also functions as a template for the rapid growth and development of the musculoskeletal system.Cartilages are found in the joints, nose, airway, intervertebral discs of the spine, and the ear Introduction contd  Cartilage is made up of highly specialized cells called chondrocytes and chondroblasts (chondro refers to cartilage), and other extracellular material which forms the cartilage matrix  All connective tissue types within the human body are derived from the embryonal mesoderm.  Bone, the strongest of the connective tissues, is the last to form and can remain in cartilage form well after birth.  Increased cartilage to bone ratio enables a flexible and pliable new-born to exit the birth canal.  A new-born has 300 bones, as opposed to the 206 of the normal adult, and all of these originate from cartilage.  From the seventh week of embryonic life, the process of ossification or osteogenesis slowly replaces cartilage with bone. This process continues into early childhood. Types of Cartilage  There are three cartilage types in the human body viz  Hyaline cartilage,  Fibrocartilage and  Elastic cartilage Hyaline Cartilage  The most common form of cartilage is hyaline cartilage. Hyalos is the Greek word for glass, which describes the appearance of this type of connective tissue – translucent, blueish-white, and shiny. It is the embryonic form of cartilage, and also found in the ribs, joints, nose, larynx and trachea.  24.Hyaline cartilage collagen fibers are primarily type II, extremely thin, and invisible to the microscope due to similar refractory properties to that of the matrix itself. FIBROUS CARTILAGE  The fibrous ligament found where tendons and ligaments meet bone, at the pubic symphysis, in the menisci, the sternoclavicular joint, and the annulus fibrosus (the center of the intervertebral disc), fibrocartilage is a very strong and pliable connective tissue. It is reinforced with collagen fiber bundles that run parallel to each other, allowing a low level of stretch. Because of the abundance of collagen fibers, fibrocartilage is white in appearance. It lacks a perichondrium and is composed of type II and type I collagen fibers. ELASTIC CARTILAGE  Elastic cartilage is primarily found in the external ear (auricle or pinna), the Eustachian tube, and the epiglottis. These parts of the anatomy are required to always spring back into the original shape. Elastic cartilage’s role is purely structural, offering flexibility and resilience due to a mixture of elastic fibers TYPES OF CARTILAGE GROWTH PATTERN OF CARTILAGE  Cartilage grows in two ways;  In interstitial growth, chondrocytes proliferate and divide, producing more matrix inside existing cartilage.  In appositional growth, fresh layers of matrix are added to existing matrix surface by chondroblasts in the perichondrium PERICHONDRIUM  The perichondrium is a dense layer of connective tissue which surrounds most cartilage sites. Its outer layer contains collagen- producing fibroblasts, while the inner layer houses large numbers of differentiated fibroblasts called chondroblasts chondroblasts  chondroblasts produce the elements of the extracellular matrix (ECM). This cell type first forms a matrix of hyaluronic acid, chondroitin sulphate, collagen fibers, and water during embryonal development. Chondroblasts eventually become immobile after becoming surrounded by the matrix, and are then referred to as chondrocytes CHONDROCYTES  Chondrocytes are the immobile form of chondroblasts. They are surrounded by the matrix and contained within allotted spaces called lacunae. A single lacuna can contain one or more chondrocytes.  Chondrocytes have varying roles according to the type of cartilage they are found in. In articular cartilage, found in the joints, chondrocytes increase joint articulation. At growth plates, chondrocytes regulate epiphyseal plate growth. While chondroblasts are ECM manufacturers, chondrocytes maintain the existing ECM and are a less active form of the same cell FIBROBLAST  Fibroblasts are found in all types of connective tissue. In cartilage, these cells produce type I collagen. In certain situations, fibroblasts transform into chondrocytes.  There is significantly more matrix than cells in cartilage structure, as the low oxygen environment and lack of vasculature do not allow for larger numbers. Because of this, there is little metabolic activity, and little to no new growth in cartilage tissue – one of the reasons the elderly commonly suffer from degenerative joint pain. Cartilage does continue to grow slowly, however. This can be seen in the larger ears and noses of older individuals Contents of the Extracellular Matrix  The ECM of cartilage contains three characteristic elements:  Collagen  Proteoglycans and  non collagenous proteins Functions of the Cartilage  Cartilage is a supple tissue which allows for facial movement as well as providing a lightweight supportive structure in the external ear, and the tip and septum of the nose  In other regions it acts as a shock absorber, cushioning areas where bone meets bone and preventing abrasion and damage.  A joint would also not be able to bend without the flexibility of cartilage.  A combination of roles is seen in the airways, where cartilage rings around the trachea prevent collapse and damage, and  Cartilage at the ends of the ribs allows the ribcage to swing upwards and outwards during inspiration.  Cartilage also plays a role in bone repair where, as in the embryo, it provides a template for ossification, this time to broken sections of bone BONE  Bone is a modified form of connective tissue which is made of extracellular matrix, cells and fibers.  The high concentration of calcium and phosphate based minerals throughout the connective tissue is responsible for its hard calcified nature. The histological structure, mode of ossification, cross-sectional appearance, and degree of maturity influences the classification of bony tissue. skeletal development is spread out over the gestational period and continues into extra-uterine life. Bone is derived from three embryonic sources EMBRYOLOGY  The neurocranium and the viscerocranium originate from derivatives of the neural crest cells as well as paraxial mesoderm. The paraxial mesoderm also contributes to the formation of the axial skeleton, while the appendicular skeleton originates from the lateral plate mesoderm. TYPES OF BONES  There are basically two types of bones architecturally viz-  Compact and  Spongy Compact Bone Compact Bone  Compact bone stands in stark contrast to trabecular bone in several ways. The functional units of compact bone are osteons; which contain a centrally located Haversian canal, encased in lamellae (concentric rings). Osteocytes can be observed in the lacunae between the osteons. The osteons – unlike the trabeculae – are densely packed, making compact bone tougher and heavier than spongy bone. The Haversian canals facilitate passage of blood vessels supplying the developing bone Spongy Bone Spongy Bones  Histologically, spongy bone is comprised of anastomosing strips of slender bone known as trabeculae that enclose marrow and blood vessels. It forms the relatively softer core of the bones that is filled with marrow.  The less densely arranged trabeculae also contribute to making the bones lighter (as opposed to the heavier compact bone). Communication between adjacent cavities is achieved by canaliculi. Although the trabecular network makes the bone lighter, and increases the available space to house marrow, the arrangement also provides reinforcement for the bone, making it stronger BONE FORMATION  The so-called flat bones of the body such as calvaria, mandible, maxilla, etc. and long bones such as those of the limbs, are formed by two different processes. The former originates by way of intramembranous ossification, while the latter undergoes endochondral ossification The initiation of either process depends on the differentiation of the preceding mesenchymal cell line. If the mesenchymal cells differentiate into chondrocytes, then endochondral ossification will occur. However, should the mesenchymal cells differentiate into osteoblasts intramembranous ossification shall occur. ossification begins around the 6th or 7th gestational week and persists well into extra-uterine life; the clavicle can take up to 20 – 21 years for complete fusion to occur, and 26 years for the epiphyseal scar to disappear 5 stages of Bone Development  Extra-uterine bone development has been classified into 5 stages.  In stage 1, the epiphysis is not yet ossified.  Once ossification becomes apparent in the epiphyses, then the bone is in stage 2 of development.  At the point where the epiphyses and diaphysis begin to fuse, then the bone has entered stage 3.  Stage 4 represents complete fusion of the epiphyses and diaphysis, leaving behind an epiphyseal scar at the site of the epiphyseal growth plate.  The final stage is characterized by disappearance of the epiphyseal scar Endochondral ossification  Endochondral ossification relies on an analgen in the form of hyaline cartilage laid down during embryogenesis. Initially, a hyaline cartilaginous framework is laid down as a template for osteogenesis. It is encased by a perichondrial layer that comprises of a condensed vascular mesenchyme. The model grows by both interstitial (replication of chondrocytes and secretion of new matrix) and appositional (absorption of old cartilage and deposition of new matrix) methods. The chondrocytes (cartilaginous cells) in the mid shaft of the cartilaginous template (diaphysis) begin to replicate and hypertrophy. An increase in the number of vacuoles can be observed in the cytoplasm in this phase. Subsequently, the matrix is compressed, forming thin fenestrated septae. The cartilage model subsequently calcifies, resulting in decreased diffusion of nutrients to the cells. They eventually degenerate, die, and calcify; leaving confluent lacunae in their absence Endochondral Ossification Contd.  As the cartilage calcifies, the inner layer of the perichondrium begin to express osteogenic (i.e. bone forming) properties; and thus become osteoblasts. Osteoblasts are responsible for production of bone matrix; they eventually produce a bony collar around the diaphysis called the periosteal collar. The connective tissue superficial to the periosteal collar is subsequently referred to as the periosteum. The visceral periosteum contains mesenchyme cells that evolve into osteoprogenitor cells. This cell line replicates and further differentiates into osteoblasts. These cells travel with osteogenic buds, which are terminal capillary sprouts. The osteoclasts break down previously formed bone and as a result, facilitate the breakdown of calcified cartilage to allow invasion of osteoblasts (that will lay down new bone matrix) and osteogenic buds (to establish nutrient supply to the developing bone)  The inner surface of bone (i.e. endosteum) that lines all bony cavitation is also covered by a single layer of osteoprogenitor cells that provides a supply of stem cells for future differentiation. At both the primary and secondary ossification centres, cartilage is replaced by bone. However, there is a region where cartilage is preserved, known as the epiphyseal growth plate. The bone continues to grow by appositional and interstitial mechanisms at this region until the ideal length is achieved. Fusion of the epiphyses with the diaphysis marks the cessation of bone growth. At this point, the only remnant of hyaline cartilage is found at the articulating surfaces of the bone Intramembranous Ossification  , the intramembranous ossification pathway does not require a cartilaginous scaffold. Instead, the bone is formed within primitive mesenchymal layers that have rich blood supplies. The stem cells within the mesenchyme differentiate into osteoprogenitor cells that replicate adjacent to capillary beds. The end result is scattered layers of osteoblasts producing bone matrix. Consequently, there are multiple ossification centres observed in intramembranous ossification. The osteoblasts are described as being polarized cells, owing to the fact that osteoid secretion occurs at the surface furthest away from the blood supply. The ossification centres subsequently anastomose, leaving a woven pattern of trabeculae, referred to as primary spongiosa or spongy bone. There are two regions within bone that contains osteoprogenitor cells and their derivatives, along with osteoclasts and other cells involved in bone homeostasis. These are the periosteum and the endosteum Periosteum  The periosteum is a fibro-collagenous layer at the outermost layer of the bone. It is anchored by Sharpey’s fibres (collagen fibres) and found along the outer surface with the exception of the articular surfaces of the bone and areas of ligament and tendon insertion.  The periosteum is actively involved in the repair of fractures; in areas where it is absent (intracapsular areas) the fractured bones heal at a slower rate ENDOSTEUM  The periosteum actively participates in bone development in utero. However, it is the endosteum that produces more osteoprogenitor cells and osteoclasts that facilitate bone remodelling. The osteoblasts at the endosteum are flat and are surrounded by type III collagen. It extends along the inner surface of the bone; projecting even into the Haversian canals. Osteoclast  Osteoclasts are thought to be monocyte derivatives that have the responsibility of removing bone during growth and remodelling. They are larger than osteoblasts and osteocytes, polymorphic and multinucleated (with roughly 20 oval nuclei in the cytoplasm). They are commonly found in Howship’s lacunae (resorption bays). Owing to the high metabolic demand of these cells, there are numerous mitochondria in the cytoplasm. Additionally, there are many vacuoles that contain acid-phosphatase enzymes that facilitate bone resorption.  There are many microtubular structures that facilitate the transportation of lysosomes to the Golgi body and deeper ruffled membrane of the osteoclast. The ruffled membrane is the site of osteoclast activity, where hydrogen ions are released along with collagenase (non-lysosomal enzyme) and cathepsin K (lysosomal enzyme), resulting in breakdown of bony material. These cells are activated by osteoblast signals (discussed below), calcitriol and parathyroid hormone levels, and are inhibited by calcitonin from the thyroid C cells. Osteoblast  Osteoblasts are mesenchymal derivatives that are differentials of osteoprogenitor cells. The latter are stimulated by bone morphogenic proteins just before bone begins to form. Unlike the osteoclasts, osteoblasts are mononuclear, cuboidal and basophilic cells that are found on the developing surface of bone during growth or remodelling. Osteoblasts secrete and also facilitate the mineralization of osteoid matrix.  Because of the need for newly formed osteoblasts to move to areas of bone growth and remodelling, the cytoplasm is filled with actin and myosin bundles. There are dendritic extensions from the cytoplasm that communicate with neighbouring osteoblasts, thus establishing electrical and metabolic continuity among the osteoblasts and osteocytes within a system. It should be noted that osteoblasts express receptors for calcitriol and parathyroid hormone. Activation of the parathyroid hormone receptors result in osteoblast-induced differentiation of immature osteoclasts Osteocytes  Osteoblasts become trapped in the bone matrix that they produce. Subsequently, they differentiate into osteocytes. These cells retain the cytoplasmic projections and form numerous communications with neighbouring osteocytes and osteoblasts. Unlike chondrocytes, osteocytes neither undergo cellular division, nor produce new matrix. These cells are elliptical, mildly basophilic and contain an oval nucleus with fewer organelles than osteoblasts Bone remodeling  Bone remodeling-Is an ongoing event which takes place throughout life and is dependent on the relationship of bone deposition and bone resorption.These 2 activities are tie to the activities of Osteoblasts and Osteoclast.As osteoclast cells dissolve an area of bone,the osteoblast cells will begin to deposit bone matrix in that area and ensuring that at blood vessel is within the area of deposition of the bone matrix. Common Bone diseases  Bone remodeling  Osteopenia  Lack of vitamin D  Paget’s disease  Hyperparathyroidism  Osteomyelitis  Neoplasms  Osteoporosis  Osteogenesis Imperfecta  Osteonecrosis  Osteoarthritis  Fibrous dysplasia  Osteomalacia  Rickets  Bone diseases as a result of autoimmune diseases include;  15.Type 1 Diabetes Mellitus(Osteoporosis)  16.Systemic Lupus erythematosus  17.Rheumatoid arthritis  18.Celiac disease