Connective Tissue 1+2 PDF

Connective tissue 1+2 HDTD Module Histology Grade 1 Dr. Dalia Qusay Objectives Define C.T. “histologically” C.T. characteristics C.T. classification Define the ECM “histologically” C.T cells  Generally, connective tissue consists of cells and an ex...

Connective tissue 1+2 HDTD Module Histology Grade 1 Dr. Dalia Qusay Objectives Define C.T. “histologically” C.T. characteristics C.T. classification Define the ECM “histologically” C.T cells  Generally, connective tissue consists of cells and an extracellular matrix (ECM) ECM includes structural(fibers) and specialized proteins that constitute the ground substance Cells have spaces between them filled with ECM Can usually divide and have good blood supply Can be flexible or rigid in nature Types of Connective Tissue (C.T) 1. Embryonic C.T 2. Connective tissue Proper 3. Specialized Connective Tissue(cartilage, bone, & blood)  Different types of connective tissue are responsible for a variety of functions The functions of the various connective tissues are reflected in the types of cells and fibers present within the tissue and the composition of the ground substance in the ECM Connective tissue proper Connective tissues that belong to this category are divided into two general subtypes: Loose connective tissue, sometimes called areolar tissue, and Dense connective tissue, which can be further subcategorized into two basic types based on the organization of its collagen fibers: I. dense irregular connective tissue II. dense regular connective tissue Loose connective tissue Is characterized by loosely arranged fibers and abundant cells of various types. It is a cellular connective tissue with thin and relatively sparse collagen fibers It is primarily located beneath the epithelium that cover the body surfaces and line the internal surfaces of the body Most cell types in loose connective tissue are transient wandering cells that migrate from local blood vessels in response to specific stimuli Dense irregular connective tissue It is characterized by abundant fibers and few cells Contains mostly collagen fibers Cells are sparse and are typically of a single type, the fibroblast Contains relatively little ground substance Provides significant strength Typically, the fibers are arranged in bundles oriented in various directions ( the term irregular) that can with stand stresses on organs or structures  Hollow organs (e g the intestinal tract) possess a distinct layer of dense irregular connective tissue called the submucosa in which the fiber bundles course in varying planes This arrangement allows the organ to resist excessive stretching and distension Similarly, skin contains a relatively thick layer of dense irregular connective tissue called the reticular layer (or deep layer of the dermis). The reticular layer provides resistance to tearing as a consequence of stretching forces from different directions Dense regular connective tissue It is characterized by ordered and densely packed arrays of fibers and cells It is the main functional component of tendons and ligaments The fibers of dense regular connective tissue are the prominent feature, and there is little ECM However, in dense regular connective tissue, the fibers are arranged in parallel array and are densely packed to provide maximum strength The cells that produce and maintain the fibers are packed and aligned between fiber bundles Tendons Cord like structures that attach muscle to bone They consist of parallel bundles of collagen fibers Situated between these bundles are rows of fibroblasts called tendinocytes Tendinocytes are surrounded by a specialized ECM that separates them from the load bearing collagen fibrils In H&E stained cross sections of tendon, the tendinocytes appear stellate Ligaments join bone to bone which in some locations, such as in the spinal column, requires some elasticity like tendons, consist of fibers and fibroblasts arranged in parallel The fibers of ligaments however, are less regularly arranged than those of tendons Elastic ligaments: although collagen is the major extracellular fiber of most ligaments, some of the ligaments associated with the spinal column (e g ligamenta flava) contain many more elastic fibers and fewer collagen fibers Connective tissue fibers Connective tissue fibers are of three principal types. Connective tissue fibers are present in varying amounts, depending on the structural needs or function of the connective tissue. Each type of fiber is produced by fibroblasts and is composed of protein consisting of long peptide chains. The types of connective tissue fibers are: 1. Collagen fibers 2. Reticular fibers 3. Elastic fibers  Classification of connective tissue is based on the composition and organization of its cellular and extracellular components and on its functions Collagen fibers The collagens constitute a family of proteins selected during evolution for their ability to form various extracellular fibers, sheets, and networks, all of which extremely strong and resistant to normal shearing and tearing forces. Collagen is a key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells. Collagen is the most abundant protein in the human body, representing 30% of its dry weight.  They are flexible and have a high tensile strength When examined with the EM collagen fibers appear as bundles of fine, threadlike subunits; These subunits are collagen fibrils Within an individual fiber the collagen fibrils are relatively uniform in diameter Collagen fibrils often consist of more than one type of collagen Usually, different types of fibrillar collagens assemble into fibrils composed of more than one type of collagen molecule  Collagen fibers are degraded either by proteolytic or phagocytic pathways All proteins in the body are being continually degraded and resynthesized Degradation by proteinases These processes allow tissues to grow and to undergo remodeling Fibrosis is deposition and overgrowth of excess fibrous connective tissue that forms scar tissue because of injury, infection, allergy, or long term inflammation Fibrotic scarring is most common in the heart, lung, peritoneum, and kidneys Mechanisms of fibrosis include proliferation of fibroblasts activation of macrophages and lymphocytes and generation of novel cells ( that, when activated, become the main collagen producing cell Many growth factors and cytokines that increase collagen synthesis, along with chemokines and angiogenic factors, are key regulators Hence, such factors are potential targets of antifibrotic drugs for treatment of pulmonary fibrosis, hepatic cirrhosis, and Crohn’s disease Reticular fibers Reticular fibers provide a supporting framework for the cellular constituents of various tissues and organs Reticular fibers and collagen type I fibers share a prominent feature Unlike collagen fibers, however, reticular fibers are composed of type III collagen. Elastic fibers Elastic fibers allow tissues to respond to stretch and distension Elastic fibers are typically thinner than collagen fibers and are arranged in a branching pattern to form a three dimensional network The fibers are interwoven with collagen fibers to limit the distensibility of the tissue and prevent tearing from excessive stretching Elastic fibers stain with eosin but not well, so they cannot always be distinguished from collagen fibers in routine H&E preparations Extracellular Matrix (ECM) The extracellular matrix (ECM) is a complex and intricate structural network that surrounds and supports cells within the connective tissue Contains a variety of fibers such as collagen and elastic fibers that are formed from different types of structural proteins. The ECM contains a variety of proteoglycans (e.g., aggrecan, syndecan); multi-adhesive glycoproteins (such as fibronectin and laminin); and glycosaminoglycans (e.g., dermatan sulfate, keratan sulfate, hyaluronan) The last three groups of molecules constitute the ground substance Functions of Connective tissue The ECM provides mechanical and structural support as well as tensile strength for the tissue. It also functions as a biochemical barrier and plays a role in regulating metabolic functions of the cells surrounded by the matrix. The ECM anchors cells within tissues through cell-to-ECM adhesion molecules and provides pathways for cell migration (e.g., during wound repair) ECM exerts (applies) a regulatory effect on embryonic development and cell differentiation Capable of binding and retaining growth factors, which in turn modulate cell growth ECM also influences the transmission of information across the plasma membrane of the connective tissue cells with the aid of cell adhesion molecules  (Thus, the current view of ECM components (fibers and ground substance molecules) is that they form a dynamic and interactive system that informs cells about the biochemical and mechanical changes in their extracellular environment) Ground substance Ground substance is the part of the extracellular matrix that occupies the spaces between the cells and fibers It consists of glycosaminoglycans GAGs proteoglycans, and multi adhesive glycoprotein;The size and structure of the three groups of molecules vary enormously Ground substance is a viscous, clear substance with a slippery feel and high water content The ground substance, is abundant in fact, it occupies more volume than the fibers do It has a viscous to gel like consistency and plays an important role in the diffusion of oxygen and nutrients from the small vessels that course through this connective tissue as well as in the diffusion of carbon dioxide and metabolic wastes back to the vessels Connective tissue cells Connective tissue cells can be resident or wandering The cells that make up the resident cell population are relatively stable; they typically exhibit little movement and can be regarded as permanent residents of the tissue. These resident cells include fibroblasts and a closely related cell type, the myofibroblast, Other cells include macrophages, adipocytes, mast cells, and adult stem cells  The wandering cell population or transient cell population consists primarily of cells that have migrated into the tissue from the blood in response to specific stimuli. These include: olymphocytes oplasma cells oNeutrophils oeosinophils obasophils omonocytes Macrophages Lysosomes are abundant in the cytoplasm and can be revealed by staining for acid phosphatase activity The macrophage contains a large Golgi apparatus RER and SER mitochondria secretory vesicles and lysosomes When macrophages encounter large foreign bodies, they may fuse to form a large cell with as many as 100 nuclei that engulfs the foreign body These multinucleated cells are called foreign body giant cells Langhans cells Inflammation Protective response to cell injury from trauma, toxins, bacteria, viruses, and immune reactions is a connective tissue vascular reaction Leukocytes, plasma proteins, and chemical mediators defend against infection to eliminate foreign substances and facilitate tissue healing Depending on the stimulus and subsequent events, acute and chronic forms exist Acute inflammation has rapid onset and short duration (hours to days) with vasodilation, vascular leakage, edema, and emigration of leukocytes Chronic inflammation longer lasting with progressive shift to other cells (e g plasma cells, mast cells, macrophages) results in fibrosis and tissue necrosis Inflammation is linked to many autoimmune disorders (e g rheumatoid arthritis and some cancers Mast cells Mast cells are large, ovoid, connective tissue cells 20 to 30 m in diameter) with a spherical nucleus and cytoplasm filled with large, intensely basophilic granules Mast cells develop in bone marrow and differentiate in connective tissue They are not easily identified in human tissue sections unless special fixatives are used to preserve the granules The cytoplasm displays small amounts of RER, mitochondria, and a Golgi apparatus Cell surface contains numerous microvilli and folds  The mast cell is related, but not identical, to the basophil, a white blood cell that contains similar granules They both arise from a pluripotential hemopoietic stem cell ( in the bone marrow basophils differentiate and remain within the circulatory system) Mast cells initially circulate in the peripheral blood as agranular cells of monocytic appearance Most mast cell secretory products (mediators of inflammation) are stored in granules and are released at the time of mast cell activation oHistamine oHeparin oSerine proteases (tryptase and chymase) a Photomicrograph of a mast cell stained with H&E; The granules stain intensely and, because of their numbers, tend to appear as a solid mass in some areas The nucleus of the cell is represented by the pale staining area b This electron micrograph shows the cytoplasm of a mast cell that is virtually filled with granules Note a small lymphocyte present in the upper left of the figure Adult Stem Cells and Pericytes Many tissues in mature individuals contain reservoirs of stem cells called adult stem cells Compared with embryonic stem cells, adult stem cells cannot differentiate into multiple lineages Usually are capable of differentiating only into lineage specific cells Adult stem cells are found in many tissues and organs, residing in specific sites referred to as niches Adult tissue stem cells Niches of stem cells residing in tissues and organs (excluding bone marrow) are called tissue stem cells Niches of adult stem cells called mesenchymal stem cells are found in loose connective tissue of the adult These cells give rise to differentiated cells that function in the repair and formation of new tissue such as in wound healing and in the development of new blood vessels (neovascularization) Thank you