Connective Tissues

Connective tissues are responsible for giving support, connecting, and anchoring parts to the body and organs. They differ in appearance, but they are composed of cells, fibers, and an amorphous intercellular ground substance. Hyaluronic acid is present in this kind of tissues.

Three Types of Connective Tissue:

Connective Tissue Proper Supporting Tissue (which includes the Bones and Cartilage) Vascular Tissue (which includes the Blood and Lymph)

Components of Connective Tissue Proper

1) Cell Types: a) Fibroblast It is a cell most commonly found in connective tissue that produces fibers, such as collagen and elastic fiber. They are active during growth but are normally quiescent in the adult. When active, fibroblasts are actively secretory, manufacturing the collagen and other components of the extracellular matrix of connective tissue. This is essential for normal development and repair. b) Plasma Cells - also called plasma B cells, plasmocytes, and effector B cells, are white blood cells that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Like all blood cells, plasma cells ultimately originate in the bone marrow; however, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells, normally in lymph nodes. There are also the ones we call the Plasmablast. It is the most immature blood cell that is considered a plasma cell instead of a B cell. Plasmablasts secrete more antibodies than B cells, but less than plasma cells. They divide rapidly and are still capable of internalizing antigens and presenting them to T cells. A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell. Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1 and IRF4. c) Mast Cells - These are large flattened cells with small nuclei found in connective tissues. They are larger than other leukocytes and its cytoplasm has large basophilic granules that mask the nucleus. These cells are motile but moves slowly. They form the anticoagulant heparin and serotonin, a chemical that serves as a vasoconstrictor at the site of injury. It also produces Histamine in case of allergic reactions and inflammatory conditions. d) Macrophages or Histlocytes These are white blood cells with irregular shapes found within tissues. Some of these cells are amoeboid in shape while others are fixed. They are produced by the division of Monocytes and are the key players for immune invaders such as infectious microorganisms. Macrophages are commonly found in spleen, liver, and the connective tissues of the body. e) Pigment cells - These are elongated cells with short irregular outgrowths which cytoplasm contained granules of melanin. These are formed from cells called melanoblast. Melanocytes are melanin-producing cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),the inner ear, meninges, bones, and heart. Melanin is the pigment primarily responsible for skin color.

A gene is the molecular unit of heredity of a living organism Vitamin D is a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium and phosphate. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol).

The body can also synthesize vitamin D (specifically cholecalciferol) in the skin, from cholesterol, when sun exposure is adequate (hence its nickname, the "sunshine vitamin"). Used for: Rickets, osteoporosis,vitamin D deficiency Vitamin C or L-ascorbic acid, or simply ascorbate (the anion of ascorbic acid), is an essential nutrient for humans and certain other animal species. Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH. Vitamin C is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that, when dysfunctional, cause the most severe symptoms of scurvy. Ascorbate may also act as an antioxidant against oxidative stress. Ascorbic acid is also widely used as a food additive, to prevent oxidation. Vitamin A is a group of unsaturated nutritional organic compounds, that includes retinol, retinal, retinoic acid, and several pro-vitamin A carotenoids, among which beta-carotene is the most important. Vitamin A has multiple functions: it is important for growth and development, for the maintenance of the immune system and good vision. Vitamin A can be found in two principal forms in foods: Retinol, the form of vitamin A absorbed when eating animal food sources, is a yellow, fat-soluble substance. The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta-ionone rings), but no other carotenoids, function as provitamin A in herbivores and omnivore animals, which possess the enzyme (15-15'-dioxygenase) which cleaves beta-carotene in the intestinal mucosa and converts it to retinol. thyroxine, also called 3,5,3,5-tetraiodothyronine, or T4, one of the two major hormones secreted by the thyroid gland. Thyroxines principal function is to stimulate the consumption of oxygen and thus the metabolism of all cells and tissues in the body. Thyroxine is formed by the molecular addition of iodine to the amino acid tyrosine while the latter is bound to the protein thyroglobulin. Excessive secretion of thyroxine in the body is known as hyperthyroidism, and the deficient secretion of it is called hypothyroidism.

Parathyroid hormone (PTH), parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, It enhances the release of calcium from the large reservoir contained in the bones.

f)

Undifferentiated Mesenchyme - This is a cell type of connective tissue found along the blood vessels that is similar to fibroblast but smaller. They are the ones that give rise to other cells or tissues during tissue repair. They are identified by their location and capacity to differentiate into other cell types, such as smooth muscle cells in the formation of new arteries, phagocytes in inflammatory processes, and bone cells in the formation of new bone tissue. g) Adipose Cells also called adipocyte or fat cells are large brilliant spherical cells that primarily compose the adipose tissue. They are specialized to synthesize and contain large globules of fat. These fat cells are found between the skin and muscle and around the organs in the main body cavities. The chief chemical constituents of adipose cell fat are triglycerides. Cytoplasm is reduced to a thin membrane which surrounds a fat droplet that is thickened on the part which contains the flattened nucleus with central mass of chromatin. h) Blood Cells Blood Cells specifically the Leukocyte Family is the main component found in tissue spaces. These are the Neutrophils, Monocytes, Eosinophils. These cells respond to inflammation in the connective tissues and are the cells responsible to detecting and destroying foreign bodies, bacteria and other pathogens. They are also classified as Wandering Cells. It is composed of the:

i.

Neutrophils Originates in the bone marrow and enter the CT from the bloodstream. Neutrophils are white blood cells that act as phagocytes in the early stages of acute inflammation. Neutrophils are highly motile in the CT.

ii.

Monocytes Monocytes originate in the bone marrow and enter the CT via the blood stream. Monocytes are white blood cells that will give rise to all the mononuclear phagocytic system In CT, they give rise to macrophages (histiocytes). phagocytes of the

iii.

Eosinophil Eosinophils are white blood cells that are found in the lamina propria of the GI tract, and at sites of allergic reaction and parasitic infection. Eosinophiles are very common throughout the respiratory and digestive tracts, as well as in active mammary tissue.

2) Fibers Present 1) Collagenous or White Fibers - These are the most common type of fiber which possess a little elasticity but have a high tensile strength. They consist of bundles of fine wavy fibrils called fibrillae which are cemented together. They have an albuminoid protein called collagen which yields gelatin after boiling. These fibers do not branch freely. 2) Elastic or Yellow Fibers These are bundles of proteins, called elastin, found in the extracellular matrix of the connective tissue and produced by fibroblasts and smooth muscle cells in arteries. These fibers can branch and connect freely and are resistant to acid. It is elastic and can stretch up to 1.5 times its original length and snap back to its original shape. 3) Reticular Fibers They yield reticulin and form a network which make them fine, wavy branched and form a network which make them hard to distinguish. These fibers are similar to white fibers in some aspects and are believed to be immature forms of white fibers. They are composed of one or more types of very thin and delicately woven strands of type III collagen which are secreted by Reticular cells. Types of Connective Tissue Proper: A) Embryonal Connective Tissue B) Adult Connective Tissue

I.

CONNECTIVE TISSUE PROPER

A) EMBRYONAL CONNECTIVE TISSUE a) Mesenchyme is primarily found in the embryo. It contains small, spindle-shaped cells of relatively uniform appearance Processes extend from these cells and contact similar processes of neighboring cells, forming a three-dimensional cellular network. Gap junctions are present where the processes make contact. The extracellular space is occupied by a viscous ground substance. Collagen (reticular) fibers are present; they are very fine and relatively sparse. Mesenchymal cells - embryonic cells which persist in the adult and are capable of differentiation and proliferation during regeneration. b) Mucous connective tissue (or mucous tissue) is a type of connective tissue found during fetal development. It is composed mainly of ground substance with few cells or fibers. It

can also be referred to a group of mucoproteins found in certain types of cysts (etc.), resembling mucus. It is most easily found as a component of Wharton's jelly. The vitreous of the eyeball is a similar tissue. Mucous connective tissue forms the umbilical cord

c) Wharton's jelly (substantia gelatinea funiculi umbilicalis) is a gelatinous substance within the umbilical cord also present in vitreous humor of the eyeball, largely made up of mucopolysaccharides (hyaluronic acid and chondroitin sulfate). It also contains some fibroblastsand macrophages. It is derived from extra-embryonic mesoderm.

B) ADULT CONNECTIVE TISSUE

a) Areolar/Loose Connective Tissue is an irregularly arranged tissue that serves as packing tissue in adult between organs and other tissues. The term "areolar" refers to the many small spaces (filled with ground substance) visible in this tissue. This is one of the most widely distributed of all tissue type that connects many adjacent structures of the body. Visible Structures: A.) Collagen Fibers- these are seen as thick wavy bundles that are scattered within the tissue spaces B.) Elastic Fibers- these are seen as thin branching fibers that look like fine stands of hair that are interposed along thick collagen fibers C.) Fibroblasts- these cells are the most numerous of the many types of cells around in this tissue, these cells are scattered within the fibers which are dark rounded structures that are responsible for the production of collagen and elastic fibers D.) Lymphocyte- smaller than fibroblast nuclei, rounder and more deeply stained, they are not as abundant as fibroblasts -a type of white blood cell or leukocyte that is divided into two principal groups and a null group; B-lymphocyte( Bursa-derived cell) which produce anti-bodies in the humoral immune response, T-lymphocytes( Thymus cells) which participate in the cell-mediated immune response and the null group, which contains natural killer cells (cytotoxic cells) that participate in the innate immune response E.) Mast cell- a large cell with a small spherical nucleus and abundant cytoplasm containing coarse granules, produces heparin and serotonin -secretory alarm cells. Upon the slightest disturbance, they release chemical signals which diffuse through the surrounding ground substance and trigger the process of inflammation. -Historical note. The name "mast cell" is a misnomer. The word "mast" refers to food. When first described, the secretory vesicles of mast cells were misinterpreted as evidence of ingestion by phagocytosis. So the name suggests a cell which has eaten its fill of "mast".

b) Reticular Tissue - it is a type of connective tissue that has a network of reticular fibers, made of type III collagen. Reticular fibers are not unique to reticular connective tissue, but only in this type are they dominant. In this tissue Reticular fibers are synthesized by special fibroblasts called reticular cells. The fibers are thin branching structures. c) Lymphoid Tissue It is a common variety of Reticular Tissue plus lymphocytes that are abundant in children but lesser in adults. It serves as a protection, hemopoeisis and filtration of tissue fluid and lymph. d) Adipose Tissue It is specialized connective tissue that functions as the major storage site for fat in the form of triglycerides. Adipose tissue is found in mammals in two different forms: white adipose tissue and brown adipose tissue. It is primarily located beneath the skin, but is also found around internal organs. e) Dense Fibrous Tissue - is mainly composed of collagen type I. Crowded between the collagen fibers are rows of fibroblasts, fiber-forming cells, that manufacture the fibers. Dense connective tissue forms strong, rope-like structures such as tendons and ligaments. Tendons attach skeletal

muscles to bones; ligaments connect bones to bones at joints. Ligaments are more stretchy and contain more elastic fibers than tendons. Dense connective tissue also make up the lower layers of the skin (dermis), where it is arranged in sheets. Specific Types of Dense Fibrous Tissue: 1) Tendons or Sinews - These are white glistening cords or bands which serve to attach muscle to bones. 2) Ligaments - Is a strong flexible band made up of dense fibrous tissue that helps hold bones together at joints. 3) Aponeurosis - These are flat rib wide bands of fibrous tissue that connects muscle or with the periosteum to the bones. 4) Membranes - These are found investing and protecting different organs of the body. 5) Fasciae - These are the bands that wrap around muscles and serves to hold them in place. Two Kinds of Fasciae: 1) Superficial Fasciae-is found in the subcutis in virtually all regions of the body, blending with the reticular layer of the dermis. It is present on the face, over the upper portion of the sternocleidomastoid, at the nape of the neck, and overlying the sternum. It is mainly loose areolar connective tissue and adipose and is the layer that primarily determines the shape of a body. In addition to its subcutaneous presence, this type of fascia surrounds organs and glands, neurovascular bundles, and is found at many other locations where it fills otherwise unoccupied space. It serves as a storage medium of fat and water; as a passageway for lymph, nerve and blood vessels; and as a protective padding to cushion and insulate. Superficial fascia is present, but does not contain fat, in the eyelids, ear, scrotum, penis and clitoris. 2) Deep Fasciae-a layer of fibrous connective tissue which can surround individual muscles, and also divide groups of muscles into compartments. This dense fibrous connective tissue interpenetrates and surrounds the muscles, bones, nerves and blood vessels of the body. It provides connection and communication in the form of, ligaments, tendons, retinacula, joint capsules, and septa. The deep fasciae envelop all bones; cartilage , and blood vessels and become specialized in muscles and nerves. The high density of collagen fibers is what gives the deep fascia its strength and integrity. The amount of elastin fiber determines how much extensibility and resilience it will have. f) Dense Elastic Tissue It runs parallel to each other and is extensile and elastic. It is found suspensatory ligaments, male reproductive organs, wall of arteries, tracheas, bronchial tubes, vocal folds, and lamina of adjacent vertebra.

II.

SUPPORTING TISSUE
A) Cartilage It is sometimes called gristle. Its cells are referred to as chondrocytes and are located in lacunae. Its ground substance contains a proteins-carbohydrate complex known as chondromucoid cartilage. The cartilage does not contain blood vessels and nourishment reaches the cells by seepage through the matrix. It grows from interstitial and oppositional method. a. Interstitial growth is the development of cartilage cells within the tissues and laying down its matrix around each daughter cell. b. Oppositional growth is the process when new tissues are formed and added on the surface by the cells of perichondrium and the periphery. Types of Cartilage:

1) Hyaline - These are few cells that lie on fluid filled spaces of the lacunae. They are embedded in an abundant ground substance which is bluish white to glossy in appearance. This is referred to as SKELETAL CARTILAGE. It is also called EMBRYONIC CARTILAGE. Hyaline Cartilage are found in NOSE, LARYNX, TRACHEA and BRONCHI. 2) Fibrous The matrix of this type is pervaded with heavy collagenous fibers. These collagenous fibers form bundles between which are scattered cartilage cells which lie in rows. These are also called the FIBROCARTILAGE. Fibrous cartilage are found AT THE CENTER OF INVERTEBRAL DISC and forms a strong flexible material that SERVES AS A CONNECTION BETWEEN BONES. 3) Elastic - This is also called the YELLOW CARTILAGE. The matrix of the elastic cartilage is pervaded with large number of elastic fibers with cartilage cells. Some functions of the elastic cartilage is for STRENGTH and to MAINTAIN THE FORM OF THE ORGAN. Elastic Cartilage is found forming in the EPPIGLOTIS, CARTILAGE OF THE LARYNX, AUXIDATORY TUBES and EXTERNAL EARS. B) BONES Their cells, called osteocytes are found within the lacunae and the nerve forms families. Unlike cartilages the intracellular substance are calcified. This is highly vascularized and is considered as permanent tissues. In here Canalicular, a structure that connects one lacuna to another on the surface of the bone or to the bone marrow cavity is present. Its structural functional unit is called Osteon. Characteristics of a Bone: 1) Shape & Size -Long, Short, Flat or Irregular 2) Histologic Culture a) Spongy or Cancellous The Osseous bar is branched. The spaces called Trabeculae are bigger and filled with the bone marrow. This has bigger cavities and is found at the interior of a bone tissue. b) Compact or Dense These appears as a continuous hard mass. This has fewer spaces and found only at the exterior portion. 3) Developmental Origin; a) Membrane - The skull is developed from mesenchyme around the developing brain. It consists of a neurocranium, which forms the protective case around the brain. It also consists of the viscerocranium , which forms the skeleton of the face. The neurocranium consists of two parts: the cartilaginous base of the skull and a membranous portion which forms the flat bones around the brain. b) Cartilage - The formation of cartilage is a cellular process involving mesenchymal cell recruitment and migration, condensation of progenitor cells and chondrocyte differentiation, which leads to the making of various cartilages. Cartilage in the head region is made by the cranial neural crest cells. Cartilage in the appendix region is contributed by the lateral plate mesoderm and the paraxial mesoderm. Cartilage formation is controlled by cellular interactions with the surrounding matrix, growth, and transcription of specific genes. Cartilage serves as a precursor, forming almost the entire embryonic skeleton. During the process of adulthood, Cartilage is replaced by bone, which also persists within that bone plate which allows the growth of the bone and allows it to lengthen. 4) Development (Ossification) of Bones : a) Intra-membranous ossification - In the embryo, before the cranial bones are formed, the brain is covered by: 1.Inner meningeal membrane 2.Middle fibrous membrane occupies the place of the future bone. Starts with the transformation of mesenchymal cells to fibroblasts and then later to osteoblasts. 3.Outer layer of skin

The intercellular substance with some collagenous fibers condense as calcium salts are deposited on the matrix forming a branching network known as spicules. Spaces between these are called trabeculae. Osteoblast becomes trapped in the matrix. Fibers and matrix continue to calcify, forming successive layers. Ossification of cranial bones starts early in the embryo and continues until after birth.

b) Endochondral /Intracartilagenous Ossification - Starts after cartilage is formed as a temporary skeleton. Cartilage cells enlarge and arrange themselves in rows at the center of ossification. Calcium salts deposit at the matrix so that nutrients to the cartilage cells is cut so that they eventually atrophy and disappear. The membrane which covers the cartilage starts to become like a periosteum. Osteoblasts grow from this membrane and is laid down in spaces or lacunae and become osteocytes. This continues until ossification is complete. When ossification outruns cartilage growth and when epiphyses are firmly connected to diaphysis of long bones. This occurs during the 20th year of life. Factors Affecting Ossification: o o o o o o Genes - The basic factor in bone formation. Vitamin D - Improve absorption of calcium. Vitamin C - For the production of collagenous fibers and motion. Hormones GSH - Stimulates the proliferation of epiphyseal cartilage. Thyroxin - Maintain metabolic rate, increases osteoblastic activity. Parathormone - Metabolizes the calcium from bone so as to maintain blood calcium level.