Topic 7 Connective Tissue

1. Topic 7Connective Tissue

2. Literature • http://www.lab.anhb.uwa.edu.au/mb140/ (notes) • http://www.anatomyatlases.org/MicroscopicAnatomy/MicroscopicAnatomy.shtml

3. Connective Tissue Connective tissue fills the spaces between organs and tissues, and provides structural and metabolic support for other tissues and organs. Connective tissue is made up of cells and extracellular matrix. The extracellular matrix is made up of fibres in a protein and polysaccharide matrix, secreted and organised by cells in the extracellular matrix. Variations in the composition of the extracellular matrix, determines the properties of the connective tissue. For example, if the matrix is calcified, it can form bone or teeth. Specialised forms of extracellular matrix also makes up tendons, cartilage, and the cornea of the eye. General connective tissue is either loose, or dense, depending on the arrangment of the fibres. The cells sit in a matrix made up of glycoproteins, fibrous proteins and glycosoaminoglycans, which have been secreted by the fibroblasts, and the major component of the matrix is water.

4. Development • Mesoderm Neuroectoderm

5. Mucous connective tissue • Mucous connective tissue (or mucous tissue) is a type of connective tissue found during fetal development. It is composed mainly of ground substance with few cells or fibers. It can also be referred to a group of mucoproteins found in certain types of cysts (etc.), resembling mucus. It is most easily found as a component of Wharton's jelly. • Mucous connective tissue forms the umbilical cord. • The vitreous of the eyeball is a similar tissue.

6. Mesenchyme, also called mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some is derived from other germ layers; e.g. neural crest cells and thus originates from the ectoderm. Most embryologists use the term "mesenchyme" only for those cells that develop from the mesoderm. The term mesenchyme essentially refers to the morphology of embryonic cells, however, they do persist as stem cells into adulthood. Mesenchymal cells are able to develop into the tissues of the lymphatic and circulatory systems, as well as connective tissues throughout the body, such as bone and cartilage. Mesenchyme is characterized morphologically by a prominent ground substancematrix containing a loose aggregate of reticular fibrils and unspecialized cells. Mesenchymal cells can migrate easily.

7. Classification • 1. Connective tissue proper • a. Loose Connective Tissue • i. Areolar • ii. Adipose • iii. Reticular • b. Dense Connective Tissue • i. Dense regular • ii. Dense irregular 2. Embryonic 3. Cartilage 4. Bone (osseous tissue) 5. Blood http://www.highlands.edu/academics/divisions/scipe/biology/labs/rome/histology.pdf

8. Connective tissues contain a large amount of non-living material referred to as the matrix. • fibers • ground substance Typically, this material is manufactured and secreted by the cells of the specific connective tissues.

9. Fibers Fiber Components Location Collagenous Fibers Elastic fibers Reticular fibers Alphapolypeptide chains elastic microfibril & elastin Type-III collagen tendon, ligament, skin, cornea, cartilage, bone, blood vessels, gut, and intervertebral disc. extracellular matrix (blood vessels) liver, bone marrow, lymphatic organs

10. Ground substance • Ground substance is found in all cavities and clefts between the fibres and cells of connective tissues. Water, salts and other low molecular substances are contained within the ground substance, but its main structural constituent are proteoglycans.Ground substance is soluble in most of the solvents used to prepare histological sections and therefore not visible in ordinary sections. • Proteoglycans are responsible for the highly viscous character of the ground substance. Proteoglycans consist of proteins (~5%) and polysaccharide chains (~95%), which are covalently linked to each other. The polysaccharide chains belong to one of the five types of glycosaminoglycans. • Hyaluronan (or hyaluronic acid) is the dominant glycosaminoglycan in connective tissues. MW 1,000,000. Length of about 2.5 µm. • Hyaluronan serves as a "backbone" for the assembly of other glycosaminoglycans in connective and skeletal tissue.

11. The large polyanionic carbohydrates of the glycosaminoglycans bind large amounts of water and cations. • The bound water in the domains forms a medium for the diffusion of substances of low molecular weight such as gases, ions and small molecules, which can take the shortest route, for example, from capillaries to connective tissue cells. • Large molecules are excluded from the domains and have to find their way through the spaces between domains. • The restricted motility of larger molecules in the extracellular space inhibits the spread of microorganisms through the extracellular space. A typical bacterium ( 0.5 x 1 µm) is essentially immobilised in the meshwork formed by the domains. • The pathogenicity of a bacterium is indeed to some extent determined by its ability to find its way through the mesh, and some of the more invasive types produce the enzyme hyaluronidase, which depolymerises hyaluronic acid.

12. Connective Tissue Cells Resident cells Immigrant cells Specialised cells Fibroblasts Adipocytes Pigment cells Monocytes/ histocytes/ macrophages Plasmocytes Mast cells Reticular cells (reticular tissue) Pericytes (blood vessels) Shwan cells (nerve fibers) Glial cells (CNS) Hondriocytes (cartillage) Osteocytes (bone) Blood cells

14. Fibroblasts • Fibrocytes are the most common cell type in connective tissues. They are the "true" connective tissue cells. • Flattened nuclei are visible in LM sections. The cytoplasm of inactive fibrocyte does not contain many organelles. • Developed intermediate filaments – vimentin. • This situation changes if the fibrocytes are stimulated. Fibrocyte can be transformed into a fibroblast with large amounts of the organelles which are necessary for the synthesis and excretion of proteins. • Fibrocytes are able to perform amoeboid movement. • The terms fibrocyte and fibroblast refer here to the inactive and active cells respectively - at times you will see the two terms used as synonyms without regard for the state of activity of the cell.

15. Fibroblasts

17. Adipocytes • Fat cells or adipocytes are fixed cells in loose connective tissue. Their main function is the storage of lipids. The cytoplasm only forms a very narrow rim around a large central lipid droplet. The flattened nucleus may be found in a slightly thickened part of this cytoplasmic rim - if it is present in the section, which may not be the case since the diameter of an adipocyte (up to 100 µm). • A "starving" adipocyte may contain multiple small lipid droplets and gradually comes to resemble a fibrocyte. • Lipid storage/mobilisation is under nervous (sympathetic) and hormonal (insulin) control. Adipocytes also have an endocrine function - they secrete the protein leptin which provides brain centers which regulate appetite with feedback about the bodies fat reserves. • Adipocytes are very long-lived cells. Their number is determined by the number of preadipocytes (or lipoblast) generated during foetal and early postnatal development.

18. Adipocytes http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/ Each adipocyte is covered with basal membrane.

20. Pigment cells Melanocytes are melanin-producing cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),[1] the inner ear,meninges, bones, and heart.Melanin is the pigment primarily responsible for skin color. http://en.wikipedia.org/wiki/Melanocyte http://www.meddean.luc.edu/lumen

21. The color of the melanin is dark and it absorbs all the UV-B light and it blocks it from passing the skin layer.[6] • Since the action spectrum of sunburn and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism.[7] The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of cyclobutane pyrimidine dimers (CPDs) - direct DNA damage.

22. Once synthesised, melanin is contained in a special organelle called a melanosome and moved along arm-like structures called dendrites, so as to reach the keratinocytes. Melanosomes are vesicles which package the chemical inside a plasma membrane. The melanosomes are organized as a cap protecting the nucleus of the keratinocyte. • http://www.vetmed.ufl.edu/sacs/histo/con01.htm

23. Monocytes/histocytes/macrophages • A histiocyte is a tissuemacrophage or a dendritic cell (histio, diminutive of histo, meaning tissue, and cyte, meaning cell). • Histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and enter various organs, where they undergo differentiation into histiocytes, which are part of the mononuclear phagocytic system (MPS).

24. Histiocytes have common histological and immunophenotypical characteristics (demonstrated by immunostains). Their cytoplasm is eosinophilic and contains variable amounts of lysosomes. They bear membrane receptors for opsonins, such as IgG and the fragment C3b of complement. They express LCAs (leucocyte common antigens) CD45, CD14, CD33, and CD4 (also expressed by T Helper Cells).

25. Macrophages and dendritic cells are derived from common bone marrow precursor cells that have undergone different differentiation (as histiocytes) under the influence of various environmental (tissue location) and growth factors such as GM-CSF, TNF and IL-4. The various categories of histocytes are distinguishable by their morphology, phenotype, and size. Macrophages are highly variable in size and morphology, their cytoplasm contains numerous acid phosphatase laden lysosomes - in relation to their specialised phagocytic function. They express CD68. Dendritic cells have an indented (bean-shaped) nucleus and cytoplasm with thin processes (dendritic). Their main activity is antigen presentation; they express Factor XIIIa, CD1c, and Class II Human leukocyte antigens.

26. A subset of cells differentiates into Langerhans cells; this maturation occurs in the squamous epithelium, lymph nodes, spleen, and bronchiolar epithelium. Langerhans cells are antigen-presenting cells but have undergone further differentiation. Skin Langerhans cells express CD1a, as do cortical thymocytes (cells of the cortex of the thymus gland). They also express S-100, and their nucleus contains tennis-racket like ultra-structural inclusions called Birbeck granules.

27. Mast cells A mast cell (also known as mastocyte and labrocyte[1]) is a resident cell of several types of tissues and contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens.[2] The mast cell is very similar in both appearance and function to the basophil, a type of white blood cell. However, they are not the same, as they arise from different cell lines.[3]

28. Mast cells are very similar to basophil granulocytes (a class of white blood cells) in blood. Both are granulated cells that contain histamine and heparin, an anticoagulant. • Both cells also release histamine upon binding to immunoglobulin E.[3] These similarities have led many to speculate that mast cells are basophils that have "homed in" on tissues. Furthermore they share a common precursor in bone marrow expressing the CD34 molecule. • Basophils leave the bone marrow already mature, whereas the mast cell circulates in an immature form, only maturing once in a tissue site. The site an immature mast cell settles in probably determines its precise characteristics.[2]

29. Mast cells play a key role in the inflammatory process. When activated, a mast cell rapidly releases its characteristic granules and various hormonal mediators into the interstitium. Mast cells can be stimulated to degranulate by direct injury (e.g. physical or chemical [such as opioids, alcohols, and certain antibiotics such as polymyxins]), cross-linking of Immunoglobulin E (IgE) receptors, or by activated complement proteins.[2] Mast cells express a high-affinity receptor (FcεRI) for the Fc region of IgE, the least-abundant member of the antibodies. This receptor is of such high affinity that binding of IgE molecules is essentially irreversible. As a result, mast cells are coated with IgE, which is produced by plasma cells (the antibody-producing cells of the immune system). IgE molecules, like all antibodies, are specific to one particular antigen.

30. http://en.wikipedia.org/wiki/Mast_cell

31. Plasmocytes • Plasma B cells (also known as plasma cells, plasmocytes, and effector B cells) are large B cells that have been exposed to antigen and produce and secrete large amounts of antibodies, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytes and activation of the complement system. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasm. These are short lived cells and undergo apoptosis when the inciting agent that induced immune response is eliminated. This occurs because of cessation of continuous exposure to various colony-stimulating factors which is required for survival.

33. http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/

34. Loose connective tissue and dense connective tissues These two tissues are distinguished according to the relative amounts of fibres they contain. Dense connective tissues are completely dominated by fibres. They are subdivided according to the spatial arrangement of the fibres in the tissue. In dense irregular connective tissue the fibres do not show a clear orientation within the tissue but instead form a densely woven three-dimensional network (dermis). Dense connective tissue are if the fibres run parallel to each other ( tendons, ligaments and the fasciae and aponeuroses of muscles). Loose connective tissue is relatively cell rich, soft and compliant. It is also rich in vessels and nerves. Loose connective tissue may occur in some special variants: mucous connective tissue, reticular connective tissue and adipose tissue.

35. Loose connective tissue • Loose connective tissue is a category of connective tissue which includes areolar tissue, reticular tissue, and adipose tissue. Loose connective tissue is the most common type of connective tissue in vertebrates. It holds organs in place and attaches epithelial tissue to other underlying tissues. It also surrounds the blood vessels and nerves. Cells called fibroblasts are widely dispersed in this tissue; they are irregular branching cells that secrete strong fibrous proteins and proteoglycans as an extracellular matrix. The cells of this type of tissue are generally separated by quite some distance by a gel-like gelatinous substance primarily made up of collagenous and elastic fibers. • Loose connective tissue is named based on the "hair weave" and type of its constituent fibers.. http://en.wikipedia.org/wiki/Loose_connective_tissue

36. Areolar tissue • Areolar tissue (areol(-a) being Latin for a little open space) is a common type of connective tissue, also referred to as "loose connective tissue". It is strong enough to bind different tissue types together, yet soft enough to provide flexibility and cushioning. • It exhibits interlacing,[1] loosely organized fibers,[2] abundant blood vessels, and significant empty space. Its fibers run in random directions and are mostly collagenous, but elastic and reticular fibers are also present. Areolar tissue is highly variable in appearance. • In many serous membranes, it appears as a loose arrangement of collagenous and elastic fibers, scattered cells of various types; abundant ground substance; numerous blood vessels. In the skin and mucous membranes, it is more compact and sometimes difficult to distinguish from dense irregular connective tissue. It is the most widely distributed connective tissue type in vertebrates.

37. The cells (dark spots within the tissue) are called fibroblasts (fibro= fiber, blast= to make or create). These are the cells responsible for secreting the fibers present. The larger fibers (typically pink) are called collagen fibers. The small black fibers are elastic fibers. Collectively, the fibers and the rest of the substance surrounding the cells would be referred to as the matrix.

38. Reticular connective tissue • Reticular connective tissue is a type of connective tissue.[1] It has a network of reticular fibers, made of type III collagen.[2] Reticular fibers are not unique to reticular connective tissue, but only in this type are they dominant.[3] • Reticular fibers are synthesized by special fibroblasts called reticular cells. The fibers are thin branching structures. • Reticular connective tissue is named for the reticular fibers which are the main structural part of the tissue. • The cells that make the reticular fibers are fibroblasts called reticular cells. Reticular connective tissue forms a scaffolding for other cells in several organs, such as lymph nodes and bone marrow. • You will never see reticular connective tissue alone--there will always be other cells scattered among the reticular cells and reticular fibers.

40. Dense irregular connective tissue • Dense irregular connective tissue (DICT) consists of a somewhat dense arrangement of thick collagen type I fibers embedded, along with a smattering of fibroblasts, in an amorphous ground substance. • Characteristically, dense irregular connective tissue differs from loose connective tissue in three basic ways: The most abundant part of dense irregular connective tissue are the collagen type I fibers, not the amorphous ground substance. • The extracellular fibers of DCT are nearly entirely collagen type I fibers. • The cells of DCT are less abundant and are virtually all fibroblasts; few other cells, if any, are present. • Dense irregular connective tissue has an irregular, somewhat disorderly, dense weave of thick collagen type I fibers, with bundles of fibers oriented in all directions. With its high tensile strength, dense irregular connective tissue effectively binds various tissues together to form organs and passively translates mechanical forces in all directions without tearing. Unlike loose connective tissue, it is NOT a designed to be a theatre of inflammation. • Dense irregular connective tissue is found in several locations: the dermis of the skin, the walls of large tubular organs, such as the alimentary canal, in glandular tissue, and in organ capsules.

42. Dense regular connective tissue • Tendons • Ligaments • Fascia Elastic tissue • Aorta

44. Tendons

45. http://www.umdnj.edu/~khochtah/ligament.html

46. http://education.vetmed.vt.edu/Curriculum/ VM8054/Labs/Lab12b/EXAMPLES/Exlasart.htm