Connective Tissue PDF

Connective tissue It’s a support tissue. It serves as a link between the epithelial, muscular and nervous tissue, as well as with other connective tissues (adipose, blood, bone and cartilage) to keep the whole body integrated. In addition, blood and lymphatic vessels pass through this tissue, cont...

Connective tissue It’s a support tissue. It serves as a link between the epithelial, muscular and nervous tissue, as well as with other connective tissues (adipose, blood, bone and cartilage) to keep the whole body integrated. In addition, blood and lymphatic vessels pass through this tissue, contributing to the nutrition and elimination of waste from all tissues. Therefore, this tissue provides structural support, as well as metabolic. It also intervenes in the defense, protection and repair of the body. It is composed of: • Cells • Extracellular matrix Extracellular matrix The extracellular matrix (ECM) is a complex of macromolecules manufactured and secreted by cells into the space between them. In connective tissue we have a large amount of ECM with a limited number of cells scattered in it. The ECM has two main components: • Ground substance • Fibers Ground substance: Amorphous gelatinous material constituted by water and three other components: - Glycosaminoglycans (GAG) - Proteoglycans - Structural glycoproteins Glycosaminoglycans (GAG): GAGs are long chains of disaccharides that repeat themselves. The main GAGs found in the matrix are sulfated. The only one unsulfated is hyaluronic acid, which is also the largest of them. The sugars that form these GAG are negatively charged, so they attract positive charges such as the Na+ ion. High Na+ concentrations will attract large amounts of water (tissue fluid). Negative charges cause the GAG chains to repel each other, adding viscosity to the matrix and the water content will make the matrix very resistant to compression. Proteoglycans: When GAGs bind to a protein (nuclear protein) they form a molecule that we know as proteoglycan. There are many types of proteoglycans of very different sizes. Hyaluronic acid can bind numerous proteoglycan molecules forming an aggregate. Structural Glycoproteins : • Proteins bound to branched polysaccharides • They have binding sites for various components of the ECM • Anchor the epithelia to the matrix (binding to integrins) • Union between the elements of the matrix (collagen fibers and proteoglycans) Fibers They provide tensile strength and elasticity to the tissue. There are two different types of fibers in the connective tissue: • Collagen • Elastin Collagen fibers • Inelastic, hard and firm protein • The most abundant of all the proteins in the body • It forms fibers that are very resistant to traction • According to its amino acid sequence, at least 35 different types of collagen are distinguished Collagen biosynthesis Fibroblasts Ground Substance Procollagen Tropocollagen polimerization Collagen Cells called fibroblasts synthesize the collagen precursor molecule, procollagen, and release it to the ECM. There, it is activated becoming tropocollagen. The tropocollagen molecules are assembled spontaneously, always in the head-tail direction and in a regular and staggered manner. These assembled molecules form the collagen microfibrils. When several microfibrils are associated they form a fibril of collagen and several fibrils will already form the collagen fiber. The union between the molecules of tropocollagen, requires the presence of vitamin C. A deficit of this vitamin, will create unstable chains and they will not be able to be added to form the fibers. Therefore, there will be tissues that become fragile, and bleeding occurs due to capillary ruptures (scurvy). Collagen types • Type I: it is the most abundant. It is synthesized by fibroblasts and also by osteoblasts. Very resistant to tension forces. It appears in most of connective tissues: skin (dermis), tendons and ligaments, organ capsules, bone ... • Type II: appears only in the cartilage. It is synthesized by chondroblasts and is very resistant to stress. • Type III: also called reticular fibers. It is synthesized by fibroblasts, smooth muscle cells, reticular cells and hepatocytes. It forms networks that support very cellular organs or tissues such as the liver, spleen, lymph nodes, smooth muscle, adipose tissue, lungs or skin. They are also part of the basal laminae. • Type IV: it is synthesized by epithelial cells, muscle cells and Schwann cells. Form networks to form the basal laminae. • Others: at least 35 different types of collagen. They are in minority and serve mainly to establish unions between different components of the matrix. Elastic fibers Made of a protein called elastin and also fibrillin. They are thin, long and branched fibers. They have elastic properties and provide elasticity to the tissue. Elastin biosynthesis Fibroblasts Ground substance Proelastin Tropoelastin polimerization + fibrillin The elastic fibers can be synthesized by fibroblasts and also by smooth muscle cells of the vessels. First, fibrillin molecules are synthesized and will form microfibrils. The microfibrils are grouped to form a hollow cylinder where the tropoelastin will be deposited. When the molecules of tropoelastin polymerize and bind to fibrillin, form the elastic fiber. Basement membrane - Non-cellular interface between epithelial and connective tissue - There is a similar structure called outer lamina surrounding skeletal and smooth muscle cells, adipocytes and Schwann cells. - It is composed of basal lamina and reticular lamina Basal lamina: - Manufactured by the epithelium. - It consists of structural glycoproteins and integrin fractions that attach to the epithelium. - Next, there is a mesh of type IV collagen that joins the reticular lamina and will work as a filter for whatever comes from the epithelium to the connective or vice versa. Reticular lamina: - Synthesized by the connective tissue. - Formed mostly by reticular fibers (collagen type III). - Fix the basal lamina to the connective. Connective tissue cells In the connective tissue we find two types of cells: • Fixed cells (or resident cells) • Transient cells (or wandering cells) The fixed/resident cells are cells that have developed in the connective tissue, they always remain in it and is where they perform their functions. The fixed cells of the connective tissue are: • Fibroblasts • Adipocytes • Pericytes • Mast cells • Macrophages Connective tissue cells Transient cells originate mainly in the bone marrow and circulate in the blood. When receiving an adequate stimulus, they leave the bloodstream to go to the connective tissue, where they will develop their specific functions. They are short-lived cells that must be replaced constantly. The transient cells of the connective tissue are: • Leukocytes • Plasma cells Origin of connective tissue cells Undifferentiated mesenchymal stem cell Chondroblast Osteoblast Hematopoietic stem cell Adipocyte Fibroblast Lymphocyte Adipose tissue Connective tissue proper Chondrocyte Monocyte Blood Eritrocyte Mast cell Osteocyte Neutrophil Plasma cell Cartilage Bone Macrophague Osteoblast Connective tissue Eosinophil Bone Basophil Blood Mesenchymal stem cells - Undifferentiated, pluripotent cells Irregular shape with cytoplasmic prolongations They give rise to most of the fixed cells of the connective tissue They appear mostly in embryonic tissues They do not exist in adults, but pericytes will have a similar function Fibroblasts - Main cells of the connective tissue, the most abundant and most widely distributed cells. - Derived from mesenchymal cells. - They synthesize most of the connective ECM. - They are elongated cells with ovoid nucleus. - When they are inactive they are called fibrocytes and they are smaller and ovoid. - We can find specialized fibroblasts such as myofibroblasts and reticular cells Reticular cells - Fibroblasts specialized in segregating reticular fibers. - Many extensions. - They form a network together with the reticular fibers to support very cellular organs. Myofibroblasts - Fibroblasts with contractile properties. Appearance very similar to that of fibroblasts They participate mainly in wound healing They also appear in the seminiferous tubules of the testicle Pericytes - Pluripotent cells that derive from mesenchymal stem cells - Surround the endothelial cells of the capillaries - Under certain stimuli, they can differentiate to another type of cells, especially fibroblasts, endothelial cells and smooth muscle cells. Mast cells - - The largest fixed cells of the connective tissue. Ovoid shape with a central spherical nucleus. They contain numerous granules in their cytoplasm whose content will be released in the presence of some antigen. They participate in the immune response. Among the content of the granules we will find heparin (anticoagulant), histamine (vasodilation, increased vascular permeability, bronchoconstriction, increased secretion of mucus), enzymes and chemotactic factors (attract leukocytes). Macrophages - Some of them behave like fixed cells, but there are also some that behave like transient cells. - They are large, irregular shaped cells. - They develop in the bone marrow and circulate in the blood as monocytes. When they reach the tissues they evolve into macrophages. - They are active phagocytes, they participate in the elimination of cellular waste and in the protection against invading organisms. Leukocytes Neutrophil Neutrophil Eosinophil Basophil Monocyte Lymphocyte They are migratory cells of the connective tissue. They are formed in the bone marrow and circulate in the blood, although they often move to the tissues, especially during inflammation. There are different types, each with different characteristics and functions, but all of them intervene in the immune response: - Neutrophils: granulocytes whose granules are not colored with the usual dyes. Large and with a multilobed nucleus. They phagocytize bacteria. - Eosinophils: granulocytes whose granules are stained with acid dyes (eosin). Usually bilobed nucleus. They fight parasites by releasing cytotoxins. They also regulate allergic reactions. - Basophils: granulocytes whose granules are stained with basic dyes. Generally bilobed nucleus. They regulate inflammatory processes. - Monocytes: precursors of macrophages. - Lymphocytes: small, rounded cells with a rounded nucleus that occupies most of the cytoplasm. They are involved in viral infections. Plasma cells - They are also migratory cells that come from the blood Derived from B lymphocytes Rounded cells and eccentric nucleus, abundant cytoplasm They secrete antibodies Classification of connective tissue • Embryonic: – Mesenchymal: present in the embryo, contains mesenchymal cells and amorphous ground substance. – Mucoid: loose, amorphous connective, with a gelatinous matrix rich in hyaluronic acid, scarce collagen and fibroblasts. It is found only within the umbilical cord and under the skin in embryos. • Adult: – Loose – Dense – Elastic – Reticular – Adipose Loose connective tissue - Abundant ground substance and tissue fluid. - Some fixed cells and few fibers arranged loosely and disorderly. - Easily vascularized and innervated. - It fills the interstitium of organs, it is located below the epithelia, in the deep layers of the skin, surrounds vessels and the parenchyma of glands. Dense connective tissue - Abundant fibers and a few cells. - The collagen fibers are grouped into bundles and give a lot of resistance to stress. - When the bundles of fibers are arranged in a disordered manner, they form irregular dense connective tissue. This tissue appears in the dermis, the nerve sheaths and fasciae of muscles and organ capsules. - When the bundles of fibers are organized in parallel, they form regular dense connective tissue. It appears in tendons, ligaments and aponeurosis. Ligaments Tendons Elastic connective tissue - Thick bundles of elastic fibers organized in parallel joined by loose connective - Present in blood vessels, yellow ligament of the spine and suspensory ligament of the penis. Reticular connective tissue - Association of reticular cells with reticular fibers and macrophages. - Present in very cellular organs and tissues: liver, spleen, lymph nodes, adipose tissue, bone marrow ...