14. Connective Tissue_Hazen-Martin_NOTES.pdf

Debra Hazen-Martin, PhD Office: 792-2906 Email: [email protected] Histological Organization of Connective Tissues A. Introduction to Connective Tissue Structure and Function 1. Definition 2. Overview of Classification 3. Origin a. Mesenchymal tissue b. Mucoid (mucous) connective tissue B. Overvi...

Debra Hazen-Martin, PhD Office: 792-2906 Email: [email protected] Histological Organization of Connective Tissues A. Introduction to Connective Tissue Structure and Function 1. Definition 2. Overview of Classification 3. Origin a. Mesenchymal tissue b. Mucoid (mucous) connective tissue B. Overview of Components of Connective Tissues 1. Fixed cells 2. Fibers 3. Ground Substance 4. Transient cells C. Resident Cells of Connective Tissue 1. Fibroblast 2. Macrophage 3. Mast cell 4. Plasma cell D. Fibers of Connective Tissue Proper 1. Collagen 2. Elastin E. Ground Substance 1. GAG and Proteoglycan 2. Glycoprotein F. Connective Tissue Proper 1. Loose (areolar) connective tissue a. Impact of inflammation 2. Dense connective tissue a. Dense irregular connective tissue b. Dense regular connective tissue G. Specialized Connective Tissues 1. Reticular tissue 2. Elastic tissue 3. Adipose tissue a. White fat b. Brown fat Suggested Reading: Histology: A Text and Atlas, 7th Edition,Chapters 4 and 6 Objectives: 1. Describe the basic functions of connective tissue in organ structure. 2. Differentiate between connective tissue proper and the specialized connective tissues. 3. Describe the three basic components of all connective tissues and their role in function. 4. Describe the origin, morphology and location of embryonic mesenchymal tissue and related mucoid tissue in the fetus and newborn. 5. Describe the development of adult connective tissue proper, discussing the origin for the populations of fixed and transient cells and finally the extracellular matrix. 6. Describe the origin, morphology and function of fibroblasts, macrophages, mast cells and plasma cells in connective tissue proper. 7. Define the term, histiocyte, and provide the names of tissue-specific histiocytes. 8. Describe the synthesis of collagen and the steps in the formation and composition of collagen microfibrils and collagen fibers. 9. Describe the structure of elastic and reticular fibers and discuss their incorporation in special connective tissues. 10. Review the composition, structure and role of GAG, proteoglycans, and glycoproteins in ground substance of connective tissues. 11. Describe the types of connective tissue proper and their unique characteristics and locations. 12 Describe the histogenesis of adipose tissue, differentiating between brown and white fat. Illustrations are adapted from: Junqueira’s Basic Histology, 13th Edition: Text and Atlas and select images from Kierszenbaum, Histology and Cell Biology, 1st Edition and College of Medicine archived images. A. Introduction to Connective Tissue Structure and Function: Connective tissue comprises one of the four basic tissue types found throughout the body in various organs and systems. 1. Definition- Connective tissue is composed of cells, fibers and ground substance that provides physical support for other tissues and connects tissues and cells of the various tissue types with each other and with components of the extracellular matrix. The extracellular matrix (ECM) includes the protein fibers and macromolecules of the ground substance. 2. Classification of Connective tissues - Connective tissues are classified in several groups. Connective tissue proper includes loose connective tissue and dense connective tissue in which collagen fibers are arranged irregularly (in an interlacing network) or in a regular (parallel) pattern. Types(2) Others(2) Other types of connective tissue include embryonic connective tissues that resemble the embryonic mesenchyme from which all other connective tissue are derived. A group of specialized connective tissues include tissues with unique ratios or types of cells, fibers or ground substance. The unique components result in distinctive morphology and function. 3. Origin of Connective Tissue: All connective tissues are derived from the embryonic mesoderm. a. Mesenchymal tissue is a primitive form of connective tissue that develops from the embryonic mesoderm germ layer. Mesenchymal cells within the tissue have large nuclei with prominent nucleoli with spindle shaped Xter(4) cell bodies and function as fibroblasts synthesizing the hyaluronic acid rich ground substance. Stem cells within the tissue give rise to cells found in each of the more differentiated connective tissue type. Xter(3) Location(3) b. Mucoid (mucous) connective tissue resembles the primitive mesenchyme. Mucoid tissue is found in the umbilical cord (Wharton’s Jelly) and various fetal organs. Following birth it is found in the dental pulp cavities. B. Overview of Components of Connective Tissues Use this slide to guide your understanding of the histogenesis of connective tissues: 1. 2. 3. 4. 5. 6. 6. 7. Embryonic mesoderm forms mesenchyme including multi-potent stem cells. Mesenchymal stem cells give rise to the fixed cells of connective tissue: fibroblasts, reticular cells, adipocytes, and others in specialized connective tissues. Fibroblasts and other fixed cells secrete the proteins that form fibers and ground substance of connective tissues. Connective tissue proper supports blood vessels. Under appropriate conditions and contact with chemical mediators, blood vessels undergo altered permeability releasing fluid and cells to the extravascular space. Fluids are readily taken up in the hydrophilic ground substance and help to create a microenvironment that includes growth factors and other proteins. Blood cells and their derivatives populate connective tissue on a fairly permanent or transient basis. Many of the transient cells are involved in inflammation, the body’s response to invading foreign substances or microorganisms. C. Resident Cells of Connective Tissue Proper 1. Fibroblasts are the most abundant cell type in connective tissue and secrete the majority of the extracellular matrix (ECM) components of fibers and ground substance. The morphology of active, synthesizing fibroblasts and quiescent fibroblasts are distinct. Fibroblasts may be proliferative at the site of wound healing. Xter(2) Fxn(2) 2. Macrophages derived from circulating monocytes of the blood. Macrophages mature in the extracellular matrix of connective tissue. Activated macrophages are phagocytic and secrete growth factors and cytokines. Xter(2) Fxn(3) Macrophages that become residents of tissues are given the general name – histiocyte. Histiocytes(5) following specific histiocytes and their locations: Kupffer cells – liver Microglia – central nervous system Osteoclasts – bone Alveolar macrophages – lung Langerhans cells - skin Histiocytes that are found in specific organs acquire tissue-specific names. You should become aware of the 3. Mast cell – This cell type is similar to and likely derived from circulating basophils. Although they are transient, they are always seen in normal connective tissues where they are positioned adjacent to blood vessels and in the lamina propria of the gastrointestinal tract. Xter(4) The preformed granules of the mast cell contain many vasoactive substances that are quickly released when the cell degranulates. These substances rapidly alter vessel permeability and participate in hypersensitivity reactions. The granules contain highly sulfated GAG. This feature causes metachromasia – the granules, stained with basic dyes, appear purple/red rather than blue. 4. Plasma cells are frequently seen in the lamina propria adjacent to lining epithelia and provide immune protection. Xter Fxn Plasma cells are derived from B lymphocytes and produce protein antibodies. They have abundant arrays of RER for protein production. The cells are readily identified at the LM level due to their characteristic arrays of nuclear heterochromatin and euchromatin. The pattern imparts a “clock face” appearance. Abundant plasma cells are seen in areas of chronic inflammation. D. Fibers of Connective Tissue Proper – You should review Dr. Bradshaw’s earlier lectures and understand the composition of the extracellular matrix. Xter(4) Table 1. Collagen – This table serves to summarize the most common collagen types found in connective tissue proper, their location and function. Note that reticular fibers are mostly composed of small Type III collagen. Fibroblast and other connective tissue cells synthesize, assemble and secrete procollagen α chains in a triple helix. Fxn(2) You should be aware of these steps and the posttranslational events that precede collagen fiber formation. Fig Assembly steps(4) In the above slide, rod-like triple helix molecules (1) are assembled in a staggered fashion to create a periodicity seen in the resulting microfibrils (2,3). Numerous microfibrils are bundled to form collagen fibers (4) which are further bundled with other fibers. The scanning microscope (SEM) image seen in the inset shows multiple microfibrils within a part of on collagen fiber. H&E stained collagen fibers are seen in the light microscopic image (LM). A small area of one fiber (inset) would appear as indicated in the transmission electron micrograph (TEM) image (top left) and the area indicated in the SEM image (bottom left). The individual microfibrils are seen in the TEM image in cross-section and longitudinal sections. Note the periodicity seen in the longitudinal fibers. Collagen type? Xter(4) Fxn(2) Components(3) Components secreted by(2) Fxn(4) Reticular fibers produce delicate networks that support parenchyma in bone marrow and lymphoid organs. In addition, reticular fibers form the reticular lamina of the basement membrane. The fibers are heavily glycosylated which causes them to bind silvercontaining dyes (agyrophilic). 2. Elastic Fibers are formed from proelastin, fibrillins, and associated glycoproteins. All of these components are synthesized and secreted by the fibroblast and smooth muscle cells. Fibrillins form a model that initiates microfibril formation. The proelastin molecules assemble on the model and are stabilized by associated glycoproteins. Bundles of microfibrils form the delicate elastic fibers seen in connective tissues in various tissue sites. E. Ground Substance The ground substance is an important part of the extracellular matrix (ECM). The composition of the ground substance is hydrophilic which creates a microenvironment that can sequester growth factors and ions which are important to the cells of both the connective tissues and adjacent epithelial tissues. Fxn Ex(3) 1. GAG and Proteoglycan Free GAG, like hyaluronic acid, and GAGs that bind protein forming the proteoglycans bind water. Review the structure of GAG and proteoglycans provided in Dr. Bradshaw’s previous lecture. Fxn 2. Glycoproteins are essential for adhesion of the cells to the extracellular matrix. Transmembrane glycoproteins, like integrin, facilitate communication between the extracellular matrix and intracellular cytoskeleton. F. Connective Tissue Proper exists in both loose and dense forms. Components(3) Ex(3) 1. Loose (areolar) connective tissue makes up the lamina propria underlying epithelial linings of the skin and digestive tract. The loose network of sparse collagen provide the room for microvasculature and small nerve endings. Fluids and blood cells readily leave vessels to populate the loos connective tissue when needed to respond to invading microorganisms. The line separates the loose connective tissue of the lamina propria from the dense connective tissue of the underlying dermis of the skin. a. Impact of inflammation Fig The diagram at the left illustrates the lamina propria under the epithelial lining of the small intestine. The right panel is an area of this loose connective tissue which has become very cellular due to an inflammatory response. Note the types of transient cells and be able to identify plasma cells as well as fixed fibroblasts in this region. 2. Dense connective tissue is further classified by the arrangement of collagen fibers. Comp(3) Ex. Fxn(2) a. Dense irregular connective tissue is found in the dermis of the skin. Collagen fibers are the predominant component and are arranged in a disorganized array of crossing fiber bundles. This arrangement provides good structural support for the broad epithelium above. b. Dense regular connective tissue is found in strong tendons, ligaments, and aponeuroses of the musculoskeletal system. Collagen fibers are arranged in parallel arrays. Locations(3) Com(3) Ex Fxn G. Specialized Connective Tissues are described that contain unique cell, fiber, or ground substances that impart a special appearance and function. 1. Reticular tissue is rich in Type III Collagen and provides delicate net-like supporting structures for specific organs as described in a previous slide. 2. Elastic tissue contains parallel elastic fiber arrays organized between and around collagen fibers and fibroblasts. The addition of elastic fibers imparts the quality of recoil and is important in large arteries near the heart. 3. Adipose tissue Adipose cells are derived from mesenchymal stem cells and may be present in as isolated cells or very small aggregates of cells within connective tissues. Adipose tissue is a tissue where adipose cells are the major component with only small amounts of extracellular matrix and little ground substance. Lipoblasts may differentiate into either white or brown fat cells which have unique characteristics. As lipid droplets form in the developing white fat cells they coalesce to form a single fat droplet that fills the entire cell. In brown fat cells the multiple small lipid droplets persist. Xter(4) Fxn(2) a. Brown adipose tissue is composed of small multilocular adipocytes. The cells have abundant mitochondria and central placed nuclei. The largest amount of brown fat is seen in the newborn where it prevents heat loss. As children age, the amount of brown fat decreases. In the adult it persists in very small amounts around the kidneys and mediastinum. Brown fate supplies a readily available source of lipid for oxidation and heat generation. Xter(4) Fxn(2) b. White adipose tissue is the common form of fat after birth. It is located under the skin with focused concentrations commonly seen in the abdomen, buttocks, axilla and thigh. Variable amounts of white fat accumulate in the greater omentum and mesenteries of the abdominal cavity and other sites. White fat begins to accumulate at 30 weeks of gestation in the fetus. Unilocular white fat cells contain a single lipid droplet that crowds the cell, displacing the nucleus and other cytoplasmic elements to the periphery of the cell (signet ring appearance). White fat cells provide long-term storage of lipids. Stromal connective tissues form incomplete septa and in which blood vessels are located. Special chemicals and stains such as osmium and Oil Red O (above) allow visualization of fats in tissue sections.