8. connective tissue general structure

Connective Tissue: General Structure and Classification

Connective tissue plays a crucial role in supporting and connecting various tissues and cells within our body, ultimately forming organs. Here are some key points about connective tissue:

1. Functions of Connective Tissue:
   • Support: Connective tissue provides structural support to the body. Examples include bone and cartilage.
   • Pathways: It furnishes pathways for nerves and blood vessels.
   • Exchange: Connective tissue acts as a compartment for exchange between capillaries and active cells.
   • Immune Activities: Connective tissue is involved in immune responses.
2. Properties of Connective Tissue:
   • Constituents are mainly extracellular.
   • Collagen fibers are present.
   • Tissues and cells are not polarized.
   • Cells generally act independently.
3. Components of Connective Tissue:
   • Cells: These include fibroblasts, adipocytes, osteoblasts, and macrophages.
   • Extracellular Matrix (ECM):
     • ECM consists of protein fibers (collagen, reticular, and elastic) and amorphous ground substances.
     • Ground substances include anionic hydrophilic proteoglycans, glycosaminoglycans (GAGs), and multiadhesive glycoproteins.
     • Water in the ECM allows for nutrient exchange between cells and the blood supply.

1. Mesenchyme:
   • Mesenchyme is a type of connective tissue found mainly during embryonic development.
   • It is composed mainly of ground substance with few cells or fibers.
   • Mesenchymal cells are undifferentiated and spindle-shaped.

1. Cell Types in Connective Tissue:
   • Fibroblasts:
     • Key cells originating from mesenchymal cells.
     • Synthesize and maintain most of the ECM components (collagen, elastin, GAGs, etc.).
     • Fibrocytes are dormant fibroblasts.
     • Myofibroblasts play a role in wound healing.

1. • Adipocytes:
     • Specialized for lipid storage (white adipocytes) or heat production (brown adipocytes).

1. • Osteoblasts:
     • Bone cells that produce collagen type I and calcium for bone matrix.
   • Macrophages:
     • Phagocytic cells involved in turnover of fibers and removal of debris. Macrophages:
     • Macrophages are highly specialized cells with a remarkable phagocytic ability. They play a crucial role in the turnover of protein fibers, removal of dead cells, and other debris.
     • These cells are present in connective tissue throughout most organs and are often referred to as histiocytes.
     • Macrophages have an irregular surface with protrusions, indentations, and folds. Their well-developed Golgi complexes and numerous lysosomes enable efficient cellular processes.
     • Derived from monocytes (bone marrow precursor cells), macrophages circulate in the blood. They cross the epithelial wall of small venules to enter connective tissue, where they differentiate, mature, and acquire features necessary for phagocytic functions.
     • Macrophages are involved in debris removal, antigen processing, and presentation for lymphocyte activation.

1. • • Mast Cells (Heparinocytes):

§  Mast cells are oval or irregularly shaped cells, ranging from 7 to 20 micrometers in size.

§  Their cytoplasm is filled with basophilic secretory granules that obscure the central nucleus.

§  Due to the high content of acidic radicals in their sulfated glycosaminoglycans (GAGs), mast cells exhibit metachromasia (a color change with basic dyes).

§  The granules are not well-preserved by fixatives, making their identification challenging at times.

§  Mast cells release substances important for inflammatory responses, immunity, and tissue repair:

§  Heparin: Acts locally as an anticoagulant.

§  Histamine: Promotes increased vascular permeability and smooth muscle contraction.

§  Serine proteases: Activate various mediators of inflammation.

§  Eosinophil and neutrophil chemotactic factors: Attract eosinophils and neutrophils to specific areas.

§  Cytokines: Polypeptides that direct activities of leukocytes and other immune system cells.

§  Phospholipid precursors: Converted to prostaglandins, leukotrienes, and other lipid mediators of the inflammatory response.

§  Immediate hypersensitivity reactions (allergic reactions) occur due to the release of certain chemical mediators stored in mast cells.

1. • • Plasma Cells:

§  Plasma cells are derived from lymphocytes and are responsible for producing antibodies.

§  These large, egg-shaped cells have basophilic cytoplasm rich in rough endoplasmic reticulum (RER) and a large Golgi apparatus near the nucleus.

§  The nucleus contains heterochromatin alternating with regions of euchromatin (lightly packed).

§  Plasma cells play a vital role in the adaptive immune response by producing antibodies specific to antigens encountered by the immune system

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1. • • Fibers of Connective Tissue:

§  Connective tissue contains elongated structures formed from proteins secreted by fibroblasts. The three main types of fibers are:

§  Collagen (20-300 nm):

1. • • Collagen is a family of proteins that form fibers, sheets, and networks.
     • It is resistant to normal shearing and tearing forces.
     • Collagen is the most abundant protein in the human body and a major product of fibroblasts.
     • Staining characteristics:
     • Eosin: Pink
     • Alcian blue: Red
     • Mallory trichrome: Blue
     • Mason’s trichrome: Green
     • Sirius red: Red
     • Types of fibrillar collagens:
     • Type I: Most abundant in skin, tendons, bone, ligaments, and cornea (forms collagen fibers).
     • Type II: Found in vertebral disks (forms fibrils).
     • Type III: Forms reticular fibers.

§  Network or sheet-forming collagens (e.g., Type IV):

1. • • Subunits produced by epithelial cells; major structural proteins of external laminae and all epithelial basal laminae.
     • Type IV collagen composes the basement membrane.

1. Linking/Anchoring Collagens:
   • Linking/anchoring collagens are short collagen molecules that connect fibrillar collagens together.
   • These specialized collagens play a crucial role in maintaining the integrity and stability of the extracellular matrix (ECM).
2. Collagen Synthesis:
   • Collagen synthesis primarily occurs in fibroblasts, although various cell types contribute.
   • The process begins with procollagen alpha chains, which are polypeptides synthesized in the rough endoplasmic reticulum (RER).
   • In the RER, three alpha chains align and stabilize through disulfide bonds, forming a triple helix.
   • This procollagen helix is then exocytosed and cleaved into procollagen molecules, which serve as the building blocks for collagen fibers or sheets.
   • Key steps in collagen synthesis:
     1. Procollagen chains are produced on polyribosomes in the RER.
     2. Hydroxylase enzymes add hydroxyl groups to prolines and lysines.
     3. Glycosylation of hydroxylysine residues can occur.
     4. The amino and carboxyl terminal sequences of alpha chains lack glycine-X-Y repeats.
     5. In the RER, the C-terminus regions of the three selected chains stabilize through disulfide bonds.
     6. Procollagen peptidases remove globular peptides, converting procollagen to collagen.
     7. Certain proteoglycans and other collagens associate with new collagen fibrils, promoting larger fibril formation.
     8. Cross-links, catalyzed by lysyl oxidase, reinforce fibril structure and prevent disassembly.

1. Collagen Characteristics:
   • Collagen appears white due to its regular orientation, making it birefringent under polarizing microscopy.
   • Staining characteristics:

1. • • Eosin: Pink
     • Mallory trichrome: Blue
     • Sirius red: Red

1. • To study collagen length and diameter, spread preparations (e.g., mesentery) are used to allow light to pass through.
   • Collagenase enzymes degrade collagen, contributing to proteolytic degradation outside cells.
2. Fibrilogenesis:
   • Collagen molecules align head-to-tail, forming covalent bonds between adjacent rows.
   • Fibrils consist of more than one type of collagen (e.g., Types I, II, III, VIII).
   • Type V and XI collagen form a fibrillar core, with Type I collagen deposited on the surface.
   • Type IX collagen links to glycosaminoglycan (GAG) molecules, stabilizing the network of fibrils.
   • Fibrilogenesis occurs in tissues like hyaline and elastic cartilage.

1. Reticular Fibers:
   • Mainly composed of collagen Type III, reticular fibers form a network of thin fibers (diameter between 0.5 and 2 micrometers).
   • They support various cells and are visible in H&E preparations.
   • Staining: Black with silver salt impregnation (argyrophilic) and PAS positive due to sugar chains.
   • Found in reticular lamina of basement membranes, surrounding adipocytes, smooth muscle, nerve fibers, and small blood vessels.
   • Characterize the stroma of hemopoietic tissue, spleen, and lymph nodes.

1. Elastic Fibers:

1. • Elastic fibers, which are thinner than Type I collagen fibers, form sparse networks in organs that experience stretching or bending.
   • Within the walls of large blood vessels, elastic lamellae contain elastin in a fenestrated (containing many cavities) sheet.
   • Elastic fibers are not strongly acidophilic and stain poorly with H&E (hematoxylin and eosin). However, they stain darker with other stains such as orcein (red-brown) and aldehyde fuchsin (violet).
   • These fibers are a composite of fibrillin, forming microfibrils that are embedded in a larger mass of elastin.

1. • Microfibrils, with a diameter of approximately 10 nm, scaffold upon one another, allowing elastin to be deposited and accumulate, ultimately making up the elastic fibers.

7.      Ground Substance:

1. • Ground substance is a highly hydrated, transparent complex mixture found in connective tissue.
   • It consists of:
     1. Glycosaminoglycans (GAGs): Long polymers of repeating disaccharide units (usually hexosamine and uronic acid). The most abundant GAG is hyaluronan (hyaluronic acid), synthesized directly by hyaluronan synthase.

1. • 1. Proteoglycans: GAGs linked to protein cores. They allow for hydration, swelling pressure, and compression handling.

1. • 1. Multiadhesive Glycoproteins: These stabilize and link the ECM to cell surfaces, regulate cell movement, and play a role in cell proliferation and differentiation.
2. Major Proteoglycans:
   • Aggrecan: Found in cartilage, responsible for ECM hydration.
   • Decorin: Present in connective tissue proper, cartilage, and bone. It binds to neighboring collagen molecules and plays a role in fibrillogenesis.
   • Versican: Found in fibroblasts, skin, smooth muscle, brain, and kidney mesangial cells.
   • Syndecan: Links cells to the ECM.
3. Multiadhesive Glycoproteins:
   • These glycoproteins stabilize the ECM and link it to cell surfaces. Some examples include:
     1. Fibronectin: Abundant and has binding sites for integrin and collagen Type IV.
     2. Laminin: Present in basal lamina, anchoring cell surfaces.
     3. Tenascin: Modulates cell attachment to the ECM.
     4. Osteopontin: Binds to osteoclasts.
4. Types of Connective Tissue:
   • Connective Tissue Proper:
     1. Classified as loose or dense based on collagen content.
     2. Loose Connective Tissue (Areolar Tissue): Contains cells, fibers, and ground substance in equal proportions. Fibroblasts are the most numerous cells. It is flexible and not resistant to stress.

1. • 1. Dense Connective Tissue:
        1. Fewer cells and a predominance of bundled Type I collagen fibers.
        2. Subtypes:
           1. Dense Irregular Tissue: Collagen fibers appear randomly without orientation (e.g., deep dermis and organ capsules).

1. • 1. 1. Dense Regular Connective Tissue: Type I collagen bundles and fibroblasts align parallel to withstand repeated and prolonged stresses (e.g., tendons, aponeuroses, and ligaments).

1. Special Connective Tissue:
   • Includes mucous, reticular, elastic, adipose, and hematopoietic tissues.
   • Supporting Connective Tissue:
     1. Examples include bone, dentin (calcified tissue of the body), and cementum (surface layer of tooth roots).
   • Embryonic Connective Tissue:
     1. Mesoderm gives rise to most connective tissues, except in the head where special ectoderm-derived cells contribute.

1. • 1. Mesenchyme: Primitive connective tissue composed of small spindle-shaped cells with processes forming a 3D network. Gap junctions facilitate communication between processes. Mesenchyme:
     2. Mesenchyme is a primitive connective tissue established during early embryonic development.
     3. It consists of small, spindle-shaped cells with uniform appearances.
     4. These cells extend processes that form a 3D network.
     5. Gap junctions facilitate communication between these processes.
     6. Mucous Connective Tissue:

1. • 1. Mucous connective tissue is found in the umbilical cord and is also known as Wharton’s jelly.
     2. The ground substance in this tissue is called Wharton’s jelly.
     3. The cells within mucous connective tissue resemble fibroblasts and are separated.
     4. Overall, mucous connective tissue provides support and flexibility in the developing embryo.