Lesson 7 Connective Tissue PDF

_____________LESSON 7 _____________ CONNECTIVE TISSUE I. INTRODUCTION The term “connective” means “serves to unite”. Therefore, as its name suggests, connective tissue forms a continuity with the other three types of tissue, epithelial, muscular and nervous, to keep the body integrated from a st...

_____________LESSON 7 _____________ CONNECTIVE TISSUE I. INTRODUCTION The term “connective” means “serves to unite”. Therefore, as its name suggests, connective tissue forms a continuity with the other three types of tissue, epithelial, muscular and nervous, to keep the body integrated from a structural and functional point of view. The connective tissue has a great morphological, topographic and structural diversity. II. BASIC FUNCTIONS Due to its morphological, topographic and structural diversity, it performs multiple and diverse functions: 1) Union: serves as a union between the different tissues (muscular, nervous and epithelial). 2) Structural support, framework: the supporting tissues are the bones, cartilage and ligaments that join the bones together, as well as the tendons that insert the muscles into the bones, the capsules that enclose the organs and the stroma that forms the structural network within organs. 3) Thermal regulation: carried out by adipose tissue. 4) Exchange medium: metabolic detritus, nutrient and oxygen between the blood and many cells of the body. 5) Defence, protection and repair: by a) phagocytic cells that engulf and destroy detritus, foreign particles and microorganisms; b) immunocompetent cells, which produce antibodies against antigens; c) cells that produce pharmacological substances that help to control inflammation; and d) as a physical barrier against the invasion and spread of microorganisms. 6) Fat storage: for energy needs. 1 III. EMBRYONIC ORIGIN Most of the connective tissues originate in the embryonic mesoderm, which gives rise to the mesenchyme, which contains the multipotential cells of the embryo. These cells migrate throughout the body and form the various types of connective tissue. IV. CONNECTIVE TISSUE COMPONENTS All connective tissues have two components (Figure 1): 1) The extracellular substance, which in the case of connective tissue is called extracellular matrix and 2) the cells. The extracellular matrix has the same components in the different types of connective tissues, only the proportion will vary in each one of them, while the cells vary from one to another. Figure 1: Scheme of the different elements that make up all connective tissues: 1) Extracellular matrix: fibers (collagen and elastic) and basic substance; 2) Cells: adipocytes, pericytes, fibroblasts, macrophages, mast cells, plasma cells, etc. Basic substance in gel form. First, we will study the extracellular matrix because it is similar in all types of connective tissues. IV.I. Extracellular matrix It consists of a basic or ground substance hydrated, gel-like, and fibers embedded in it. The properties that these components confer on the connective tissue are: 1) The hydrated basic substance resists compressive forces. 2 2) The fibers resist tensile or traction forces and provide elasticity. 1. Fibers The classical histologists distinguished 3 types of fibers according to their morphology and their reactivity with histological stains: 1) Collagen fibers; 2) Reticular fibers, and 3) Elastic fibers. Today is known that reticular fibers are fibers of collagen type III, but the term has been preserved for historical reasons and for convenience, to describe the organs that possess large amounts of this particular type of fibers of collagen. 1.1. COLLAGEN FIBERS The collagen fibers (Figures 2, 3 and 4) are abundant, and are present in most connective tissues, making up approximately 30% of the dry weight of the organism. Macroscopic appearance: when they are in large accumulations, as in tendons and ligaments, they have a bright white colour in the living organism. Optical microscope study: they measure 10 µm in diameter and are of indefinite length and are not isolated but in groups or bundles. With HE stain they are acidophilic and bright and with special histochemical techniques have the following colourings: blue with the techniques of the Methylene Blue and Masson Trichrome, red with the technique of van Gieson Picrofucsina, and green with the Light Green technique. Transmission electron microscope study: Figure 2. Scheme of the structure of a collagen fiber. • A collagen fiber is made up of collagen fibrils that measure between 10 and 300 nm (nanometers) in diameter and have a characteristic periodicity of electrondense bands and electron-lucent bands (striations) that alternate between each other approximately every 67 nm. • Each collagen fibril is a tropocollagen polymer measuring 280 nm in length and 1.4 nm in diameter. 3 • Each tropocollagen molecule (monomer) is made up of three polypeptide chains (called alpha chains) wrapped around each other in a helical fashion. As they polymerize, they are arranged in a parallel fashion, overlapping each other for a quarter of their length. This arrangement is what gives rise to the periodic longitudinal striation every 67 nm. Each alpha chain contains about 1000 amino acids. The most abundant are glycine, proline, hydroxyproline, and hydroxylysine. But there are also others, which vary from one alpha chain to another. This variation gives rise to different collagen fibers. There are between 15 and 19 different types (depending on the texts), but the main ones are: - Type I fibers: dermis, tendons, bones, ligaments - Type II fibers: hyaline cartilage - Type III fibers: lymphatic system, spleen - Type IV fibers: basal lamina - Type V fibers: dermis, tendons Figure 3. Scheme of tropocollagen synthesis in fibroblasts and its polymerization at the extracellular level. Collagen fibers are synthesized in the rough endoplasmic reticulum (RER) as polypeptide chains (called alpha chains) (α). Inside the RER cisterns, these α chains are assembled 3 by 3 forming triple helices to form procollagen molecules which are transferred to the Golgi complex, packed into secretory vesicles and released by exocytosis to the extracellular environment. Procollagen is transformed into tropocollagen (monomer) by enzymatic cleavage, which polymerizes in the extracellular matrix to form collagen fibrils (tropocollagen polymer). Type I fibers are flexible and can adapt to movements and changes in size of the organs of which they are part. Collagen fibers are characterized by high tensile strength and low shear strength, being able to stretch only about 5% of their initial length. Therefore, they occur where high tensile strength is required, such as tendons, ligaments and organ capsules. 4 The reticular fibers, also known as reticulin fibers, are individual fibrils of collagen type III (they are coated with proteoglycans and glycoproteins). They measure 0.5 to 2 µm in diameter and are highly glycosylated, that is, they have a lot of carbohydrates. Under the light microscope, with HE, they are not distinguished from other collagen fibers, but they are stained with silver techniques in black and with PAS in pink-magenta due to their high carbohydrate content. The reticular fibers form a flexible and delicate mesh around capillaries, muscle fibers, nerves, adipose cells and hepatocytes, acting as a scaffold (stroma) to support cells or groups of cells in endocrine, lymphoid and hematopoietic organs. They are particularly common in: basal membrane, smooth muscle tissue, acini and alveoli of exocrine glands, follicles and cords of endocrine glands, hollow organs (urinary bladder, intestine and uterus) and in hematopoietic and lymphoid organs. 1.2. ELASTIC FIBERS The elastic fibers are responsible for the elasticity of the connective tissue and are present in normal organs whose functions require elasticity in addition to tensile strength. Therefore, its functions are to maintain the shape of numerous organs that are susceptible to being deformed, such as the skin and the lung. In blood vessels they are located mainly in the elastic lamina of largecaliber arteries, allowing the vessel to dilate when blood passes through and return to its initial state, thus helping to maintain blood flow. In animals that spend a long-time grazing (especially ruminants) the nape ligament is very rich in elastic fibers and helps to maintain an adequate head position. Elastic fibers are also abundant in other ligaments that stabilize the spine. Macroscopic appearance: in large quantities, they give a yellowish colour to the organs that contain them, such as the wall of the great blood vessels. Appearance under the light microscope: with the HE technique, they are more acidophilic and shinier than collagen fibers, and they form long and highly wavy bundles (Figure 4). Transmission electron microscope appearance: They have two components: 1) A central low electron density amorphous material, elastin. It is a protein rich in glycine and proline but containing other amino acids less frequent as the desmosine and isodesmosine, providing elasticity to the fibers. In fact, elastic fibers can stretch up to 150% in length and regain their normal shape without wasting energy. 2) A sheath around of fibrillin microfibrils, measuring about 10 nm in diameter. Elastin is synthesized by fibroblasts and smooth muscle fibers as tropoelastin, that is, unique polypeptide chains that are transformed into elastin cross-linked and assembled in the extracellular space. Microfibrils are secreted before elastin and constitute the scaffold in which elastin forms fibers and sheets. From a developmental point of view, elastic fibers are the last fibers to appear in organs (for example lung) or connective tissue. 5 Fibra de colágeno C F D G E H Fibra elástica A B Figure 4. Scheme of collagen (A) and elastic (B) fibers. Light microscope images with haematoxylin and eosin of collagen fibers (C), with silver staining of reticulin fibers (D) and with haematoxylin-eosin of elastic fibers (E). Electron microscope images of collagen fibers (F), reticulin fibers (G) and elastic fibers (H). 2. Ground substance The fibers and cells of the connective tissue are included in a substance of gelatinous consistency called ground substance. In the histological preparations stained with HE it is not seen. The ground substance has 3 components: a) Glycosaminoglycans (GAG, GAGs) b) Proteoglycans (PGs) c) Adhesive glycoproteins 2.1. GLYCOSAMINOGYCANS The glycosaminoglycans (other names: mucopolysaccharides) are long polysaccharides, inflexible and without ramifications, compounds of repeating disaccharide units. They are hydrophilic and form hydrated gels which, for their high-water content, are resistant to pressure. One of the disaccharides is always an amino sugar (N-acetyl-glucosamine or N-acetyl- galactosamine), 6 and the other one, a uronic acid (iduronic and glucuronic). There are two types of GAGs: 2.1.1. Sulfated: The amino sugar is sulphated. They are: keratan sulfate, heparan sulfate, heparin, chondroitin 4-sulfate, chondroitin-6-sulfate and dermatan sulfate. They are all made up of less than 300 repeated disaccharide units, and all are often covalently bounded to proteins. Its function is to retain liquid in the extracellular matrix, which confers resistance to compressive forces (that is negatively charged and attract cations as the Na+). The chondroitin 4 and 6 sulfate are abundant in cartilage, arteries, skin and cornea and a lesser amount in bone. The dermatan sulfate in skin, tendons, nuchal ligament, sclera and lung. The keratan sulfate is in cartilage, bone and cornea. Heparan sulfate in arteries and lung and heparin in mast cells, lung, liver and skin. 2.1.2. Not sulfated: the amino sugar is not sulfated. The only one of its kind is hyaluronic acid, made up of up to 25,000 repeated disaccharide units. It forms the skeleton of gigantic molecules whose function is to resist compression forces and act as a physical barrier to the spread of microorganisms and cells through the extracellular matrix. 2.2. PROTEOGLYCANS The proteoglycans are sulfated GAGs linked by covalent bonds to proteins. Both structures are shaped like a swab. Variable size of molecular weight, between 50,000 and 3 million daltons. Most are bound to hyaluronic acid (non-sulfated GAG) by binding proteins, forming molecules of several million daltons. The most abundant of these is: the aggrecan. Functions: (1) resistance to compression forces (due to its large volume); (2) physical barrier to the spread of microorganisms and metastatic cells (for the same reason); (3) molecular filters in the basal lamina (they select and delay the passage of molecules through them); (4) binding sites of signaling molecules (transforming growth factor beta, TGFβ, and fibroblast growth factor, FGF). The proportions of various proteoglycans in a certain type of tissue largely determine the morphological and functional properties of the tissue. 2.3. ADHESIVE GLUCOPROTEINS The adhesive glycoproteins are responsible for holding the various components of the extracellular matrix to each other and to the cells. Therefore, they have 3 adhesion domains: (1) to collagen fibers; (2) to proteoglycans; and (3) to the integrins of the cells. Types: (1) fibronectin, (2) laminin, (3) entactin, (4) tenascin, (5) chondronectin and (6) osteonectin. Examples: ➢ Fibronectin: plays an important role in several processes, such as cell adhesion, cell differentiation, cell development and phagocytosis. 7