Connective Tissue N. Swailes, Ph.D. Department of Anatomy and Cell
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Module 1.3: Connective Tissue N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected] Required reading Mescher AL, Junqueira’s Basic Histology Text and Atlas, 13th Edition, Chapter 5 (also via AccessMedicine) Learning objectives 1) Name the three major classes of connective tissue and give examples of each. 2) Identify and describe the origin, organization and fate of embryonic connective tissue 3) Identify and discuss the functional properties imparted to tissue by the extracellular matrix: a. fibers (elastin, collagen Type I, II, III, IV and VII) b. ground substance (glycosaminoglycans, proteoglycans, glycoproteins) 4) Distinguish between different connective tissue cells and discuss their roles: a. fibroblasts b. adipocytes c. macrophages d. mast cells e. lymphocytes f. plasma cells g. eosinophils h. neutrophils 5) Classify the different connective tissues proper and compare and contrast their functional roles within an organ. Introduction The human body is made up of only four basic tissues: 1. Epithelial tissue 2. Connective tissue 3. Muscle tissue 4. Nervous tissue By adjusting the organization, composition and special features associated with each of these tissues is is possible to impart a wide variety of functions to the region or organ that they form. During this lecture you will examine the basic histological structure and function of Connective Tissue. 1 | Page: Connective Tissue Swailes a loose meshwork Part A: General characteristics of connective tissues that cushions and allows diffusion A1. There are three major classes of connective tissue i. Connective tissues proper - the most common class of connective tissue in the body. - its components can be organized in a variety of ways - its functions vary based upon this organization organized dense bundles that resist high tensile forces ii. Specialized connective tissue - these are types of connective tissue that have very specific functions in very specific locations: 1. adipose tissue (See Adipose tissue) 2. blood (MOHD 1) 3. hematopoietic tissue (MOHD 1) 4. cartilage (MOHD 2) 5. bone (MOHD 2) 6. lymphoid tissue (MOHD 2) iii. Embryonic connective tissue - also known as mesenchymal tissue - it is a special connective tissue. found only in the embryo, umbilical cord and pulp cavity of the teeth. 2 | Page: Connective Tissue Swailes A2. General composition of connective tissue All connective tissues are composed of cells and the extracellular matrix (ECM) that they secrete. The extracellular matrix is composed of: ii. Ground substance i. Fibers glycosaminoglycans collagen elastin fibers fibers proteoglycan proteoglycan A3. Collagen fibers aggregate i. Overview of structure and synthesis of collagen - collagen is synthesized by fibroblasts, secreted as pro-collagen which is then assembled into fibrils outside the cell. - the fibrils of some types of collagen can further assemble into fibers and/or fiber bundles. 6. collagen fiber Some types of collagen fibrils can assemble to form fibers collagen fibril collagen bundle 7. 5. Some types of tropocollagen self- collagen can assembles to form assemble to collagen fibrils form fiber bundles Pro-collagen peptidase 3. pro-collagen is 1. secreted fibroblasts 4. synthesize pre- pro-collagen peptidase 2. procollagen cleaves propeptides from pre-procollagen is pro-collagen forming assembled into pro- tropocollagen collagen in cell 3 | Page: Connective Tissue Swailes fibril tropocollagen ~300nm 67nm 67nm - in the electron microscope collagen fibrils have regular 67nm striations. - formed by deposition of heavy metal stains in the ‘gaps’ between adjacent tropocollagen filaments in the fibril. ii. Functional properties of collagen The organization of collagen in the extracellular matrix affects the mechanical function of a connective tissue. For example connective tissues that contain mainly collagen: 1. Fibrils - provide a delicate supportive meshwork to the structures they surround. - allow structures to easily pass through and permit their movement (think of a pulsing arterioles running through a tissue). - allow substances to also easily diffuse between fibrils. 2. Fibers - are flexible, inelastic and have high tensile strength. 3. Fiber bundles - are the strongest types of connective tissues capable of withstanding high tensile forces (e.g. tendons). iii. Types of collagen There are 28 different types of collagen. The ones you will encounter most in histology are: Collagen Type Location Organization Type I Most connective tissues Fibrils, fibers and fiber bundles Type II Cartilage specific Fibrils *Type III (reticular fibers) Distensible organs Fibrils Type IV Lamina densa Sheets Type VII Lamina reticularis Sheets *must be stained with silver stain to be visualized 4 | Page: Connective Tissue Swailes A4. Elastin fibers 1. i. Structure and synthesis of elastin proelastin is synthesized by proelastin fibroblasts 2. fibrillin microfibrils tropoelastin is formed and secreted from the cell 3. tropoelastin tropoelastin becomes surrounded by fibrillin microfibrils 4. the tropoelastin is crosslinked to form an crosslinking proteins elastin fiber (e.g. desmosine) elastin fiber Elastin fibers: - are thinner than collagen fibers - become interwoven with collagen fibers - may branch - stain poorly with eosin, therefore require a special (Verhoeff’s) stain - when present in large numbers may be refractile which makes them visible ii. Functional properties of elastin The amount of elastin fibers in a tissue increases its ability to stretch and, importantly, recoil to its original shape. 5 | Page: Connective Tissue Swailes A5. Ground substance 1. Glycosaminoglycans (GAG’s) - long unbranched polymers of i. Overview of ground substance structure repeating disaccharides - ground substance is a viscous, clear - common GAGs include keratin substance with high water content sulfate, chondroitin sulfate and - it fills the gaps between fibers heparin sulfate - in connective tissues proper it is synthesized by fibroblasts - it is composed of: 2. Proteoglycan monomer - a protein core to which GAGs are linked. These vary in size, in cartilage they are very large molecules called aggrecan Collagen fiber 3. Hyaluronan/Hyaluronic acid - in some tissues the proteoglycan monomers are also bound to a long glycosaminoglycan molecule called hyaluronan 4. Glycoproteins - macromolecules that bind all components of the ECM together and to the cells that secrete them e.g. fibronectin, laminin, chondronectin ii. Function of ground substance - GAGs are hydrophilic molecules and pull water into connective tissues. - the high water content allows the connective tissue to resist compression. - tissues that have lots of ground substance are therefore optimized for resisting compressive forces (e.g. articular cartilage, nucleus pulposus of the intervertebral discs). 6 | Page: Connective Tissue Swailes A6. Connective tissue cells Connective tissue cells can be classified as resident or wandering. i. Resident cells Stable, permanent residents of connective tissue that include: 1. Mesenchymal cells Features - irregular, elongated cells in embryonic connective tissue Function - multipotent stem cells that can differentiate into many adult cells Find - cells surrounded by ground substance with spindle-like cytoplasmic processes 2. Fibroblasts Features - the major connective tissue cell Function - synthesizes collagen, elastin and ground substance Find - spindle shaped cells associated with collagen fibers 3. Adipocytes Features - the major component of adipose tissue (fat) Function - support, cushioning, insulation and an energy store Find - large, ‘empty’ cells with peripheral nuclei ii. Wandering cells Consist of cells that have migrated into connective tissue from the blood in response to specific stimuli. They include: 1. Macrophages Features - very large, irregular shaped cells. Function: - phagocytic cells derived from monocytes (white blood cells) Find - phagocytosed debris in the cell, difficult to identify otherwise 7 | Page: Connective Tissue Swailes 2. Mast cells Features - large oval cells packed full of granules (heparin and histamine). Function - granules released in response to toxins or trauma and trigger inflammatory events a. histamine increases permeability of vessels causing edema b. heparin acts as an anticoagulant Find - don’t bother (unless granules are stained for specifically) 3. Lymphocytes Features - small, white blood cells with very large nuclei Function - B and T-cells both play a role in the immune response Find - a very common cell that is almost all nucleus and barely any cytoplasm 4. Plasma cells Features - derived from B-lymphocytes that have been stimulated by antigen Function: - produce antibodies Find: - a cell with a ‘clockface’ nucleus and large perinuclear halo 5. Eosinophils Features - white blood cells, eosinophilic granules and bi-lobed nuclei Function - phagocytic cells that migrate into connective tissue during allergic reactions and parasitic infections Find - a cell with eosinophilic granules and a bilobed nucleus 6. Neutrophils (polymorphonucleocytes; PMNs) Features - white blood cells with neutrophilic granules and multi-lobed nuclei Function - phagocytic cells that recognize and digest bacteria during the inflammatory response Find - a cell with multilobed nuclei 8 | Page: Connective Tissue Swailes Part B: How to classify connective tissues proper Connective tissues proper can be classified into one of three classes based upon the density and organization