Connective Tissues

Cells of the Connective Tissue : 

Cells of the Connective Tissue By Dr. Seharish Zulfiqar Asstt. Prof. Anatomy Dept. University Medical & Dental College Faisalabad, Pakistan.

Slide 2: 

Some cells of the connective tissue are produced locally and remain in the connective tissue, these type of cells are called RESIDENT CELL POPULATION Other with defensive functions come from other areas called MIGRANT CELLS

Slide 3: 

RESIDENT CELL Fibroblasts Adipose Cells Mesenchymal Stem Cell MIGRANT CELLS Macrophages Lymphocytes Mast Cells Plasma Cells Leukocytes

Fibroblasts : 

Fibroblasts Synthesize Collagen Elastin Glycosaminoglycans Proteoglycans Multiadhesive Glycoproteins Most numerous resident cells in connective tissue Responsible for synthesis of most of Extracellular Matrix components Two stages of activity are observed in these cells Active Quiescent Cells with intense synthetic activity are morphologically distinct from the quiescent fibroblast that are scattered within the matrix they have already synthesized

Slide 5: 

Some histologists reserve the term Fibroblast to denote the active cell and Fibrocyte to denote the quiescent cell

Slide 6: 

The Active Fibroblast an abundant and irregularly branched cytoplasm Its nucleus is Ovoid Relatively large Pale staining (Euchromatic) Euchromatin: Chromosomal material that is genetically active and stains lightly with basic dyes With fine chromatin A prominent nucleolus In young highly active cells, the cytoplasm is abundant and basophilic (Reflecting the high concentration rough endoplasmic reticulum) Mitochondria are abundant The golgi complex is well developed (Several sets present)

Section of rat Skin. A connective tissue layer (dermis) shows several fibroblasts (F), wich are elongated cells. H & E stain. : 

Section of rat Skin. A connective tissue layer (dermis) shows several fibroblasts (F), wich are elongated cells. H & E stain.

Quiescent fibroblasts are elongated cells with thin cytoplasmic extensions and condesed chromatin : 

Quiescent fibroblasts are elongated cells with thin cytoplasmic extensions and condesed chromatin

Slide 10: 

The Quiescent Fibroblast or fibrocyte is smaller than the active fibroblast and tends to be spindle-shaped The cytoplasmic volume is reduced It has Fewer processes A smaller, elongated, flattened nucleus Nucleus is heterochromatic Heterochromatic: Tightly coiled chromosomal material that stains deeply during interphase and is believed to be genetically inactive An acidophilic cytoplasm Small amount of rough endoplasmic reticulum

Slide 12: 

Synthesize proteins such as Collagen Elastin This collagen & elastin form the collagen, reticular and elastic fibers It also form the glycosaminoglycans, proteoglycans, and glycoproteins of the extracellular matrix In some highly cellular structures, e.g. liver, kidney, spleen & in most lymphoid tissue Fibroblasts and delicate collagenous fibers (Type III collagen; reticular fibers) form fibrocellular networks which are often called RETICULAR TISSUE The fibroblasts may then be termed as RETICULAR CELLS

Slide 13: 

Involved in the production of growth factors that influence the cell growth and differentiation Fibroblasts are particularly active during wound repair, when they proliferate and lay down a fibrous matrix that becomes invaded by numerous blood vessels (granulation tissue) Contraction of wounds is at least in part caused by the shortening of specialized contractile fibroblast (myofibroblast) that arise in such areas

Slide 14: 

Fibroblasts activity is influenced by various factors such as steroid hormone concentrations, dietary content and prevalent mechanical stresses In Vitamin C deficiency there is impairment of collagen formation

Macrophages and Mononuclear Phagocyte System : 

Macrophages and Mononuclear Phagocyte System Macrophages have a wide spectrum of morphologic features that correspond to their state of functional activity and to the tissue they inhabit When a vital dye such as trypan blue or india ink is injected into an animal, macrophages engulf and accumulate the dye in their cytoplasm in the form of granules or vacuoles visible in the light microscope Macrophages are typically numerous in connective tissues, where they are either attached to matrix fibers or are motile and migratory Were discovered and initially characterized by their phagocytic ability

Slide 17: 

Their cytoplasm, under the light microscope is Slightly basophilic Contains many lysosomes Typically has a foamy appearance They are relatively large cells 15-20 μm in diameter Usually have an oval or kidney shaped nucleus located eccentrically Relatively heterochromatic nucleus A prominent nucleolus

Section of pancreas from a rat injected with the vital dye trypan blue. Note that 3 macrophages (arrows) have engulfed and accumulated the dye in the form of granules. H & E stain : 

Section of pancreas from a rat injected with the vital dye trypan blue. Note that 3 macrophages (arrows) have engulfed and accumulated the dye in the form of granules. H & E stain

Slide 19: 

In the electron microscope They are characterized by an irregular surface with pleats, protrusions, and indentations, a morphologic expression of their active pinocytotic and phagocytotic activities They generally have A well developed Golgi Complex Many lysosomes A prominent rough endoplasmic reticulum

Electron micrograph of a macrophage. Note the secondary lysosomes (L), the nucleus (N), and the nucleolus (Nu). The arrow indicate the phagpcytic vacuoles : 

Electron micrograph of a macrophage. Note the secondary lysosomes (L), the nucleus (N), and the nucleolus (Nu). The arrow indicate the phagpcytic vacuoles

Slide 21: 

They are also the source of a number of secreted cytokines that have profound effects on many other cell types Macrophages derive from bone marrow precursor cells that divide, producing monocytes that circulate in the blood In a second step, these cells cross the walls of venules and capillaries to penetrate the connective tissue, where they mature and acquire morphologic features of macrophages Therefore, monocytes and the macrophages are the same cell in different stages of maturation Tissue macrophages can proliferate locally, producing more such cells

Slide 22: 

They are important phagocytes, They can engulf and digest particulate organic materials, such as bacteria, and are also able to clear dead or damaged cells from a tissue Form part of the mononuclear phagocyte system They are long living cells and may survive for months in the tissues Macrophages, which are distributed throughout the body, are present in most organs In certain regions, macrophages have special names, eg Kupffer cells in the liver Microglial cells in the central nervous system Langerhans cells of the skin Osteoclasts in the bone tissue

Mast Cells : 

Mast Cells Oval to round connective tissue cells 20-30 μm in diameter Cytoplasm is filled with basophilic secretory granules The rather small, spherical nucleus is centrally situated; it is frequently obscured by the cytoplasmic granules The principal function of mast cells is the storage of chemical mediators of the inflammatory response

Slide 31: 

The secretory granules are 0.3-2.0 μm in diameter Their interior is heterogeneous in appearance, with a prominent scroll like substructure that contains pre-formed mediators such as histamine and proteoglycans Mast cell granules are metachromatic because of high content of acidic radicals in the glycoaminocans Metachromasia is a property of certain molecules that changes the color if some basic aniline dyes The structure containing the metachromatic molecules takes on a different color (Purple-Red) from that of the applied dye (Blue)

Slide 34: 

Other constituents of mast cell granules are Histamine Which promotes an increase in the vascular permeability, that is important in inflammation Neutral proteases Eosinophil chemotactic factor of anaphylaxis (ECF-A) Mast cell also release leukotrienes (C4, D4, E4), but these substances are not stored in the cell Rather, they are synthesized from the membrane phospholipids and immediately released to the extracellular microenvironment upon appropriate stimulation, such as interaction with fibroblasts

Slide 35: 

Although they have similar morphology, there are at least two populations of mast cells in the connective tissues One type is called the connective tissue mast cells, found in the skin and peritoneal cavity The second type, the mucosal mast cell, is present in the intestinal mucosa and in the lungs These two cell populations also differ in their granular content

Slide 36: 

The surface of mast cells contains specific receptors for IgE, a type of immunoglobulin produced by plasma cells Most IgE molecules are bound to the surface of mast cells and blood basophils; very few remain in the plasma

Slide 37: 

Mast cells originate from progenitor cells in the bone marrow These progenitor cells circulate in the blood, cross the walls of venules and capillaries, and penetrate the tissues, where they proliferate and differentiate Although they are, in many respects, similar to basophilic leukocytes, they have a separate stem cell

Slide 38: 

Sensitization develop after the initial encounter with an antigen During this first encounter, the immune system recognizes the antigen as “non-self” Immune System cells (B-Cells) that express antibody molecules on their surface specific for the antigen (cognate antibodies) proliferate and differentiate into specialized antibody-secreting cells, Plasma Cells

Slide 41: 

These cells then produce antibodies against the antigen Several major classes of antibodies, called “Immunoglobulin”, are produced Immunoglobulins of the IgE class are released by the plasma cells and bind to the Fc receptors located on the plasma cell of the mast cells On subsequent exposure to the same antigen, an antigen-antibody reaction occur at the mast cell surface that cause the discharge of mast cell granules

Plasma Cells : 

Plasma Cells Plasma cells are large, ovoid cells that have a basophilic cytoplasm due to their richness in rough endoplasmic reticulum The juxtanuclear Golgi complex and the centrioles occupy a region that appears pale in regular histologic preparations

Slide 44: 

The nucleus of plasma cell is spherical and eccentrically placed, containing compact, coarse heterochromatin alternating with lighter areas of approximately equal size This configuration resembles the face of clock, with the heterochromatin clumps corresponding o the numerals Thus, the nucleus of a plasma cell is commonly described as having a clock-face appearance There are few plasma cells in most connecive tissues Their average life is short, 10-20 days

Portion of a chronically inflamed intestinal villus. The plasma cells are characterized by their size and abundant basophilic cytoplasm (Rough endoplasmic reticulum) and are involved in the synthesis of antibodies. A large Golgi complex (arrows) is where the terminal glycosylation of the antibodies (glycoproteins) occurs. Plasma cells produce antibodies of importance in immune reactions. : 

Portion of a chronically inflamed intestinal villus. The plasma cells are characterized by their size and abundant basophilic cytoplasm (Rough endoplasmic reticulum) and are involved in the synthesis of antibodies. A large Golgi complex (arrows) is where the terminal glycosylation of the antibodies (glycoproteins) occurs. Plasma cells produce antibodies of importance in immune reactions.

Lymphocytes : 

Lymphocytes Connective tissue lymphocytes are the smallest of the cells in the connective tissue They have thin rim of cytoplasm surrounding a deeply staining, heterochromatic nucleus Often, the cytoplasm of connective tissue lymphocytes may not be visible Normally, small numbers of lymphocytes are found in the connective tissue throughout the body

Slide 50: 

The number increases dramatically, however, at sites of tissue inflammation caused by pathogenic agents Lymphocytes are most numerous in the lamina propria of the respiratory and gastrointestinal tracts Where they are in immunosurveillance against pathogens and foreign substances that enter the body by crossing the epithelial lining of these systems

Section of an inflamed intestinal lamina propria. Inflammation was caused by nematode parasitism. Aggregated eosinophils and plasma cells function mainly in the connective tissue by moduating the inflammatory process. Giemsa Stain. Low magnification : 

Section of an inflamed intestinal lamina propria. Inflammation was caused by nematode parasitism. Aggregated eosinophils and plasma cells function mainly in the connective tissue by moduating the inflammatory process. Giemsa Stain. Low magnification

Electron Micrograph of a plasma cell showing an abundance of rough endoplasmic reticulum ® Note that many cisternae are dilated. Four profiles of the Golgi complex (G) are observed near the nucleus (N). (M) mitochondria (Courtes; of P. Abrahamsohn) : 

Electron Micrograph of a plasma cell showing an abundance of rough endoplasmic reticulum ® Note that many cisternae are dilated. Four profiles of the Golgi complex (G) are observed near the nucleus (N). (M) mitochondria (Courtes; of P. Abrahamsohn)

Classification of connective tissues : 

Classification of connective tissues

Slide 54: 

Connective tissue develop from the mesenchyme, an embryonic type of tissue With exception of blood and lymph, connective tissue consist of Cells Extra-cellular material called matrix Matrix consist of Connective tissue fibers Ground substance Tissue fluid The names given to the various types denote either the component that predominates in the tissue or a structural characteristic of the tissue

CONNECTIVE TISSUE PROPER : 

CONNECTIVE TISSUE PROPER There are 2 classes of connective tissue proper: Loose Dense

Loose connective tissue : 

Loose connective tissue It is very common type of connective tissue & is extensively distributed Its chief function is to bind structures together, while still allowing a considerable amount of movement to take place Supports many structures that are normally under pressure and low friction It fills spaces between groups of muscle cells Supports epithelial tissue Forms a layer that sheathes the lymphatic and blood vessels

Loose connective tissue : 

Loose connective tissue Comprises all the main components of connective tissue proper There is no predominant element in this tissue proper The most numerous cells are Fibroblasts Macrophages Mast cells But all the other types of connective tissue cells are also present It also contains Adipocytes Usually in small groups, and particularly around blood vessels A moderate amount of Collagen fibers Elastic fiber Reticular fiber appear in this tissue Loose connective tissue Delicate in consistency It is flexible Well vascularized Not very resistant to stress A variant of loose connective tissue occurs in the choroid and the sclera of the eye where large numbers of pigments cells (melanocytes) are also present

Slide 61: 

Also found in The papillary layer of the dermis In the hypodermis In the serosal linings of peritoneal and pleural cavities In glands and the mucous membranes (wet membranes that line the hollow organs) supporting the epithelial cells

Dense connective tissue : 

Dense connective tissue Is adapted to offer resistance and protection It consists of the same components found in loose connective tissue, but there are Fewer cells A clear predominance of collagen Fiber Is less flexible Far more resistant to stress than in loose connective tissue

Dense Irregular connective tissue : 

Dense Irregular connective tissue It is known Dense Irregular connective tissue coz when the collagen fibers are arranged in bundles without a definite orientation The collagen fibers from a 3-dimensionlal network in dense irregular tissue and provide resistance in such areas as the dermis Dense irregular connective tissue occurs in The reticular layer of the dermis The connective tissue sheaths of muscle and nerves and the adventitia of large blood vessels The capsules of various glands and organs (e.g. testis, sclera of the eye, periostea and perichondria)

Dense Regular connective tissue : 

Dense Regular connective tissue The collagen bundles are arranged according to a definite pattern Regular connective tissues include highly fibrous tissues in which fibers are regularly orientated, either to form sheets such as Fasciae Aponeuroses Or present as thicker bundles such as ligaments Tendons

Slide 66: 

The direction of the fibers within these structures is related to the stresses which they undergo The fibroblasts that secrete the fibers may eventually become trapped within the fibrous structure where they become compressed, relatively inactive cells with stellate profiles and small heterochromatic nuclei Fibroblasts on the external surface may be active in continued fiber formation and they constitute a pool of cells available for repair of injured tissue. Although regular connective tissue is predominantly collagenous, some ligaments contain significant amounts of elastin, e.g. The ligamenta flava of the vertebral laminae The vocal folds

Slide 71: 

Tendons are the most common example of dense regular connective tissue Tendons Are elongated cylindrical structures attach striated muscle to bone; by virtue of their richness in collagen fibers They are white and inextensible They have parallel, closely packed bundles of collagen separated by a small quantity of intercellular ground substance Their Fibrocyte contain elongated nuclei parallel to the fibers and sparse cytoplasmic folds that envelop portions of the collagen bundles The cytoplasm of these Fibrocytes is rarely revealed in H&E stains, not only because it is sparse but also because it stains the same color as the fibers

Slide 74: 

The collagen bundles of the tendons (Primary bundles) aggregate into larger bundles (Secondary bundles) that are enveloped by loose connective tissue containing blood vessels and nerves Externally, the tendon is surrounded by a sheath of dense connective tissue In some tendons, this sheath is made up of 2 layer is attached to the tendon, and the neighboring structures A cavity containing a viscous fluid (similar to the fluid of synovial joints) is formed between the two layers This fluid, is a lubricant that permits and easy sliding movement of the tendon within its sheath. It contains Water Proteins Glycosaminoglycans Glycoproteins Ions

FUNCTIONAL CORRELATIONSGround Substance and Connective Tissue : 

FUNCTIONAL CORRELATIONSGround Substance and Connective Tissue The ground substance in connective tissue consists primarily of amorphous, transparent, and colorless extracellular matrix, which has the properties of Semifluid gel High water content It supports and surrounds the connective tissue and all its cells and fiber types Hyaluronic acid constitutes the principal glycosaminoglycan of connective tissue Except for hyaluronic acid, the various glycosaminoglycans are bound to a core protein to form much larger molecules called proteoglycan aggregates These proteoglycans attract water, which forms the hydrated gel of the ground substance

Slide 76: 

The semifluid consistency of ground substance in the connective tissue facilitates diffusion of oxygen, electrolytes, nutrients, fluids, metabolites, and other water-soluble molecules between the cells and the blood vessels Similarly, waste products from the cells diffuse through the ground substance back into the blood vessels Because of its viscosity, the ground substance also serves as an efficient barrier, preventing the movement of large molecules and the spread of pathogens from the connective tissue into the bloodstream However certain bacteria can produce hyaluronidase, an enzyme that hydrolyzes the hyaluronic acid and reduces the viscosity of the gel-like ground substance, thereby allowing pathogens to invade the surrounding tissues

Slide 77: 

The density of ground substance depends on the amount of extracellular tissue fluid or water that it contains Mineralization, caused by increased calcium deposition, changes the density, rigidity, and permeability of ground substance, as seen in normally developing cartilage models and bones In addition to proteoglycans, connective tissue also contains several cell adhesive glycoproteins, which bind cells to the fibers One glycoprotein, fibronectin, binds cells, collagen fibers, and proteoglycans, thereby interconnecting all three components of the connective tissue Integral proteins of the plasma membrane, called integrins, bind to extracellular collagen fibers Laminin is a large glycoprotein and a major component of the cell basement membrane; this protein binds epithelial cells to the basal lamina

MUCOID TISSUE : 

MUCOID TISSUE Mucoid tissue is a fetal or embryonic type of connective tissue Found chiefly as a stage in the development of connective tissue from mesenchyme It exists in Wharton's jelly Which forms the bulk of the umbilical cord Consists substantially of extracellular matrix Largely made up hydrated mucoid material and a fine meshwork of collagen fibers, in which Nucleated, fibroblast-like cells with branching process are found Fibers are usually rare in typical mucoid tissue, although the full-term umbilical cord contains perivascular collagen fibres Postnatally; mucoid tissue is seen in The pulp of a developing tooth The vitreous body of the eye ( a persistent form of mucoid tissue that contains few fibers or cells) The nucleus pulposus of the intervertebral disc

MUCOSA (MUCOUS MEMBRANE) : 

MUCOSA (MUCOUS MEMBRANE) A mucosa or mucous membrane lines many internal hollow organs of which the inner surfaces are moistened by mucus, such as The intestines Conducting portions of the airways The genital and urinary tracts The mucosa proper consists of An epithelial lining, which may have mucosal glands opening on to its surface The underlying loose connective tissues, the lamina propria A thin layer of smooth muscle, the muscularis mucosa This last layer is either absent from some mucosae, or is replaced by a layer of elastic fibers.

Slide 80: 

The term mucous membrane reflects the fact that these tissues can all be peeled away as a sheet or membrane from underlying structures The plane of separation occurs along the muscularis mucosa

Submucosa : 

Submucosa Is a layer of supporting connective tissue Usually lies below the muscularis mucosae It may contain mucous or seromucous submucosal glands, which convey their secretions through ducts to the mucusal surface

Slide 82: 

Most mucusae are also supported by one or more layers of smooth muscles, the muscularis externa Contraction of this muscle may constrict the mucosal lumen), cause peristaltic movements of the viscus and the contents of its lumen e.g. in the airway Where there are two or more muscle layers orientated in opposing directions (e.g. in the intestines) The outer surface of the muscle may be covered by a serosa or, where the structure is retroperitoneal or passes through the pelvic floor, by a connective tissue adventitia

SEROSA (SEROUS MEMBRANE) : 

SEROSA (SEROUS MEMBRANE) Serosa consists of A single layer of squamous mesothelial cells Supported by an underlying layer of loose connective tissue that contains numerous blood and lymphatic vessels Serosal cells are derived from embryonic mesenchyme and so share a common lineage with connective tissue cells However, structurally they resemble squamous epithelia and they express keratin intermediate filaments Serosa lines the pleural, pericardial and peritoneal cavities, covers the external surfaces of organs lying within those cavities and in the abdomen, the mesenteries that envelop A potential space, filled with a small amount of protien containing serous fluid (largely an exudate of interstitial fluid) exists between the outer parietal and the inner visceral layer of the serosa

MUCUS : 

MUCUS Mucus is a viscous suspension of complex glycoproteins (mucins) of various kinds Is secreted by scattered individual epithelial (goblet) cells, a secretary surface epithelium (e.g. the stomach) Or secreted by mucous and sero-mucous glands The precise composition of the mucus varies with the tissue and secretary cells that produce it

Slide 85: 

The long polymeric carbohydrate chains bind water and protect surface against drying They also provide good lubricating properties In concentrated form mucins form viscous layers that protect the under lying tissues against damage

FASCIA : 

FASCIA Fascia is a term applied to masses of connective tissue large enough to be visible to the unaided eye Its structure is highly variable but, in general, collagen fibers in fascia tend to be interwoven and show the compact, parallel orientation seen in tendons and aponeuroses

Slide 87: 

Fascia that is organized into condensations on the surfaces of muscles and other tissues is termed investing fascia, but this may not be its sole function Between muscles that move extensively , it takes the form of loose areolar connective tissue and provides a degree of mechanical isolation It constitutes the loose packing of connective tissue around peripheral nerves, blood and lymph vessels as they pass between other structures and often links them together as neurovascular bundles It forms a dense connective tissue layer investing some large vessels, e.g. the common carotid and femoral arteries, and its presence here may be functionally significant, aiding venous return by approximating large veins to pulsating arteries

SUPERFICAL FASCIA : 

SUPERFICAL FASCIA Superficial fascia is a layer of loose connective tissue of variable thickness that merges with the deep aspect of the dermis It is often adipose, particulary between muscle and skin It allows increased mobility of skin, and the adipose component contributes to thermal insulation and consitutes a store of energy for metabolic use Subcutaneous nerves, vessels and lymphatic travel in the superficial fascia; their main trunks lie in its deepest layer, where adipose tissue is spars In the head and neck, superficial fascia also contains a group of striated, muscles (collectively termed the muscles of facial expression). which are remnant of more extensive sheets of skin-associated musculature found in other mammals

Slide 89: 

The quantity and distribution of subcutaneous fat differs in the genders It is generally more abundant and widely distributed in females In males, it diminishes from the trunk to the extermities; this distribution becomes more obvious in middle age, when the total amount increases in both genders There is an association with climate (rather than race), and superficial fat is more abundant in colder geographical regions Superficial fascia is most distinct on the lower anterior abdominal wall, where it contains much elastic tissues and appears many-layered as it passes through the inguinal regions into the thigh

Slide 90: 

It is well differentiated in the limbs and the perineum But is thin where it passes over the dorsal aspects of the hands and feet, the sides of the neck and face, around the arms and over the penis and scrotum, and is almost absent from the external ears Superficial fascia is particularly dense in the scalp, palms and soles where it is permeated by numerous strong connective tissue, bands that bind the superficial fascia and skin to underlying structures

DEEP FASIA : 

DEEP FASIA Deep fascia is also composed mainly of collagenous fibers, but these are compacted and in many cases arranged so regularly that the deep fascia may be indistinguishable from aponeurotic tissue In limbs, where deep fascia is well developed, the collagen fibers are longitudinal or transverse and condense into though, inside sheaths around the musculature.