connective tissue

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CONNECTIVE TISSUE

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It is a supporting and binding tissue found widely distributed in the human body. Origin: MESODERMAL

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AREOLAR Simple squamous epithelium 1. Abundant extracellular matrix 2. Cells are far apart 3. Non-living connective tissue fibers in matrix 4. Vascular

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Types of Connective tissues: 1.Connective tissue proper 2.Cartilage 3.Bone 4.Blood

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Composition: 1.Connective tissue cells 2.Extracellular matrix * ground substance * fibers 3.Connective tissue fibers

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Functions: 1.Primarily for support and for binding tissues together. 2.Permits free diffusion of nutrients & metabolites. 3. Immunological protection.

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CONNECTIVE TISSUE PROPER

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Connective tissue cells Fixed Free cells cells

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FIXED CELLS responsible for the production and maintenance of extracellular components and storage of fuel A. Fibroblast D. Reticular cell B. Fixed Macrophage E. Pigment cell C. Fat cell/ Adipose cell F. Undifferentiated mesenchymal cells

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FREE or MOBILE or WANDERING CELLS concerned with the short term reaction to injury. A. Free Macrophage C. Mast cells B. Plasma cell D. extraneous cells

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Fibroblast or Fibrocyte or Desmocyte flattened cells with granular cytoplasm. Nucleus is oval and vesicular and has cytoplasmic processes. When inactive it contains small Golgi complex. It is bigger when dividing and active and become moderately basophilic. Golgi complex becomes prominent. This is the most common type of connective tissue cell in the areolar tissue. This is the only cell in the tendon.

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Three types of fibroblast: 1.Lamellar fibroblast 2.Spindle shaped or Fusiform 3.Stellate or star-like fibroblast

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Functions: It elaborates the precursor of extracellular fibrous and amorphous components. So this is responsible for the production of connective tissue fibers and ground substance.

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MYOFIBROBLAST a connective tissue cell with fibroblast and smooth muscle cell properties. It differs from the smooth muscle because it is not surrounded by the basal lamina while the smooth muscle is surrounded.

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MACROPHAGE or HISTIOCYTE or PHAGOCYTE A. Fixed Macrophage - stellate or fusiform cells with smaller and darker nucleus than fibroblast. Cytoplasm is granular with small vacuoles. B. Free Macrophage - with pseudopods so it shows amoeboid movements and capacity for phagocytosis. Cytoplasm contains many vacuoles, lysosomes and residual bodies. Plasma membrane may be deeply invaginated.

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M O N O C T Y E S bOnE MarroW MACROPHAGE Fixed macrophage Free macrophage

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Lipopolysaccharide (LPS) Gamma-interferon (INF)

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Functions: Serves a SCAVENGERS – for maintenance of connective tissues and for local defenses against bacterial invasion. 2.Plays a role in immunological defenses of the body by processing and presenting antigen to lymphocytes capable of producing antibodies.

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FAT CELLS or ADIPOCYTES or ADIPOSE CELLS This is the largest cells in the connective tissue. This arise from the mesenchymal cell.

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Two types of adipose cells: White fat cell (unilocular fat cell) 2.Brown fat cell (multilocular fat cell) White fat cell brown fat cell

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Functions: 1.storage of neutral fat 2.synthesizes lipids from carbohydrates and accumulated fat from the diet.

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RETICULAR CELL resembles the fibroblast and is associated with the reticular fibers. Functions: - Gives rise to other connective tissue cells (blood cells and Macrophages)

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PIGMENT CELL 1. Epidermal melanocyte - synthesizes their own pigment. - It comes from the neural crest. 2. Dermal chromatophore or melanophore - merely engulf the melanosome (yellow, brown or black) DOPA (dihydroxyphenylalanine test) - determines the presence of cells that synthesize their own pigment.

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UNDIFFERENTIATED MESENCHYMAL CELL - resembles the fibroblast but smaller. Function: - to give rise to other cell types. - it is responsible for metaplasia.

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WANDERING CELLS

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PLASMA CELL - The plasma cell shows amoeboid motility.Under the electron microscope, abundant rough-surfaced ER was seen and this is responsible for the synthesis of antibodies. When the plasma cell is degenerating, acidophilic inclusion bodies appear in the cytoplasm. This is known as Rusell bodies – these maybe accumulations of defective products of antibody synthesis. Most abundant in lymph nodes and spleen. Function: Main source of antibodies.

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Cytoplasm is finely granular and intensely basophilic. Adjacent to the nucleus is a pale staining area, occupied by the golgi apparatus, known as the perinuclear halo. spherical cell with rounded irregular nucleus, generally eccentric in location. Chromatin in the nucleus are arranged in radial pattern like the spokes of wheel.

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MAST CELL largest of all the free types of cell. It is rounded with relatively small nucleus. Its cytoplasm contains metachromatic granules. Metachromasia in the cytoplasm of mast cell is due to the presence of heparin. Origin: it comes from a hemopoietic stem cell which undergoes cell division.

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Functions: 1. Production of anti-coagulant 2. Production of anti-agglutinant 3. Contains serotonin. 4. Granules contain ß – glucoronidase, hexosaminidase and aryl-sulfatase which may degrade some of the glycosaminoglycans of extracellular matrix and may contribute to continual turn over of the ground substance.

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Substances released by Mast cells: Histamine 2. Slow reacting substance of Anaphylaxis (SRS-A) 3. Eosinophil chemotactic factor of Anaphylaxis 4. Heparin

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Location of Mast cells: 1. Chiefly in the vicinity of small blood vessels. 2. Capsule of organ 3. Meninges - in the sheet that surround the brain and spinal cord. It protects them from the disrupting effect of edema characteristic of allergic reaction. 4. Thymus and other lymphatic organs but absent in spleen.

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EXTRANEOUS CELLS LYMPHOCYTE smallest, slightly motile, non phagocytic. Small in number but increases drastically during the primary immunologic response and chronic inflammatory diseases.

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MONOCYTE in local inflammatory reactions the monocyte transform into macrophages increasing their population. While in chronic inflammatory reactions the macrophages may become closely packed and take on the appearance of epithelial cells. If foreign objects are too large and too resistant to be engulfed and destroyed by intracellular digestion, they will coalesce to form multi-nucleated foreign body giant cell.

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Types of Monocytes: 1. Activated monocyte acquires enhanced functional activity in response to environmental stimulus. 2. Resident monocyte Present at any given site in the absence of exogenous stimulus. 3. Elicited Macrophage on varying degrees of activity attracted to the same site by a given substance.

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Mononuclear Phagocytic system Members are: 1.Promonocyte of bone marrow 2.Monocytes of the blood 3.Free and fixed macrophage

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NEUTROPHILIC LEUKOCYTES or NEUTROPHILS rarely found in the connective tissue.

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Mechanism of migration of neutrophils to the tissue complements and cytokine endothelial cell adhesion molecule – I (ELAH-1) leucocyte adhesion molecule (LeuCAMS) chemoattractant C h e m o t a x i s hydrolytic enzyme

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There are two types of granules in the cytoplasm: A.) AZUROPHIL granules gives a positive reaction for the enzymes peroxidase, acid phosphatase & ß glucoronidase which corresponds to the lysosomes. B.) SPECIFIC STAINING granules gives a positive reaction for alkaline phosphatase, collagenase, lysozyme, lactoferritin phagocytins (poorly characterized basic proteins, believed to have nonenzymatic antibacterial activity). These granules lack the lysosomal hydrolases seen in the azurophil granules.

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In addition to their assault of the bacteria, neutrophils and certain other phagocytic cells generate compound that contributes in other ways to the inflammatory process. From ARACHIDONIC ACID in their plasma membrane, they synthesize a group of compound called LEUKOTRIENES (LTs). They are LTA4, LTB4, LTC4, LTD4, and LTE4. LEUKOTRIENE B4 – promotes adhesion of neutrophils to the endothelium and their migration to the tissues. - chemoattractant for eosinophils, monocytes and other neutrophils so participants in the recruitment of such cells to their sites of infection.

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CYSTEINE – containing leukotrienes LTC4, LTD4, & LTE4 increase the permeability of post capillary venules contributing to the edema & swelling at sites of inflammation. They are also potent vasoconstrictors -> responsible for respiratory distress in asthma. Drugs blocking the synthesis of leukotrienes -> prevents constrictions of bronchi and bronchioles when asthmatic are exposed to antigens to which they are sensitive.

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EOSINOPHILS contains several lysosomal hydrolases (aryl sulfatase, ß glucoronidase, acid phosphatase, histaminase and ribonuclease). is a normal constituent of connective tissues. They do not phagocytose. They attracted to the site of histamine release and their granules contain enzymes capable of degrading histamine and other mediators of inflammation. They believe that they may moderate the severity of allergic reaction. There is a recent evidence that proteins of the esinophilic granules participate in antibody-mediated, contact dependent cytotoxicity.

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Three cationic proteins of EOSINOPHIL: Major Basophilic Protein (MBP) Eosinophilic Cationic Protein (ECP) Eosinophil-Derived Neurotoxin (EDN) MBP and ECP are damaging to the Schistosomes of Schistosoma mansoni and to the larvae of Trypanosoma cruzi. Their cytotoxic effect include the creation of transmembrane pores in the target cells and the release of superoxide that damage membranes by lipid peroxidation. EDN induces paralytic syndrome when injected into the cerebro-spinal fluid of guinea pigs.

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EXTRACELLULAR MATRIX (Ground Substance)

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Importance: 1. Ensures a suitable medium for diffusion of nutrients and oxygen from the capillaries and also waste products for elimination. 2. Determines the histological characteristics of different kind of connective tissues. 3. Relative amount of amorphous component is related to aging. The older the lesser is the amount amorphous substance.

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Components: A. Proteoglycans (PG) – composed of a glycosaminoglycans covalently bound to a core protein. B. Collagen C. Elastin D. Structural proteins – fibronectin, chondronectin and laminin & thrombospondin E. Glycosaminoglycans (GAG) – composed of repeating dissacharide units one of which is a sulfated hexosamine.

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Types of glycosaminoglycans: 1. Hyaluronic acid 2. Chondroitin sulfate 3. Heparan sulfate 4. Dermatan sulfate

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Structural Glycoproteins: 1. FIBRONECTIN - a group of structurally and immunologically related glycoproteins found in connective tissues, basal lamina of epithelia and on the surface of many cells. - this protein binds to other fibrous proteins such as collagen and fibrin. Functions: A. In the blood plasma (plasma fibronectin), it binds to fibrin and may have a role in blood clotting. B. Along its length, they have cell-binding, collagen binding sites are the basis for its role in connecting the surfaces of the cells to fibrous and amorphous components of extracellular matrix.

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2. LAMININ - localized mainly in the basal lamina and seems to be involved in the attachment of epithelia to their supporting layer of Type IV collagen. It influences the function and form of the epithelial cell. 3. CHONDRONECTIN - found in the cartilage

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4. THROMBOSPONDIN - part of activated platelets secreted during blood clotting. - most abundant protein in the granules of blood platelets. - synthesized by: Fibroblast Endothelial cell Smooth muscle cell - it binds to cell surface and to components of extracellular matrix.

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CONNECTIVE TISSUE FIBER White/ collagenous Yellow/ elastic Argyrophil/ reticular

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COLLAGENOUS OR WHITE FIBERS it is a compound fiber composed of finer fibers. This is the principal and most abundant fiber in the connective tissue.

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large bundle made up of fibrils uniform in size made up of finer fibrils known as protofibrils fibrils run parallel courses which are more or less wavy They are held together by cementing substances General feature:

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COLLAGEN FIBER Collagen fibril made up of staggered collagen molecules. They are aligned end-to-end in overlapping rows with a gap between the molecules within each row. Associated with the collagen molecule are sugar groups and because of this it is designated as glycoprotein.

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Collagen molecule is made up of three polypeptide chains called alpha chains arranged as a triple helix. The alpha chains are not all – alike and their differences will result to 15 types of collagen. proline glycine hydroxyproline

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Physical Properties: A fresh collagenous fiber is dull and pearly in appearance and has a low refractive index. It does not stretch but has a remarkable resistance to pulling force. When it yields, it breaks and frays irregularly. EIM shows cross-bandings or cross-striations. These bands occur at regular interval of 640Aº (64-67 nm). These are responsible for the birefringence seen under the polarized light.

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Chemical Properties: 1. Stains with Eosin (pink), Mallory’s trichrome (blue) and Masson’s trichrome (green) 2. Composed of albuminoids called collagen or tropocollagen 3. Dissolved by boiling and yields gelatin. 4. Weak acids & Alkali – swelling of fibers 5. Strong acids & alkali – dissolution of fibers 6. Tannic acid converts collagen to tough insoluble product.

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7. Has three fractions: a. neutral soluble fractions – tropocollagen molecules had not yet polymerized b. Acid soluble fraction – further extraction with citrates. c. Insoluble fractions – remaining collagen which can be extracted by drastic procedures. These three fractions are believed to represent successive stages in the extracellular polymerization of collagen molecules to fibers.

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YELLOW or ELASTIC FIBERS Physical Properties: Always solitary, never occurring in bundles. They branch and anastomose abundantly, forming a network. They can be stretch to 1.5x the relaxed length. Beyond this the fiber breaks. Its broken end are clean cut and will retract and cut in spiral.

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Elastic fiber is much thinner than collagenous fiber. It is made up of two components: 1. Amorphous - consist of homogenous material of varying density in which the fibrillar component are embedded. 2. Fibrillar (microfibrils) When elastic fibers are fresh, they appear bright red due to its high refractivity. Fresh, massed fibers appear yellow.

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Chemical Properties: 1. Composed of albuminoid called elastin 2. Resist boiling water, acid and alkali and does not yield gelatin. 3. Elastin makes up the bulk of elastic fiber which is resistant to digestion by trypsin but is digested by an enzyme elastase.

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RETICULAR FIBERS needs a special stain. They are the first connective tissue to appear. Later they may take on collagenous properties. Some may remain permanently at the reticular stage. It is composed of collagen fibrils.

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Reticular fiber is closely related to collagenous fiber in that both are made up of collagen fiber. However, reticular fibers differ from that of the collagen fiber because they: are always narrow in diameter do not form from large bundles are arranged in a network contain higher content of sugar groups stains black with silver, while collagen gives a brown color.

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Occurrence: basal lamina around adipocytes small blood vessels nerves supporting stroma in the hemopoietic tissue lymphatic tissue liver & around smooth muscle cell

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FIBRILLIN another fibrillar component of connective tissue. It appears as a beaded chain and on cross-section, it has an electron dense cortex around a lucid core. It is often associated with elastic fibers and basal lamina of epithelium.

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Marfan syndrome a hereditary disorder where fibrillin is defective or deficient, characterized by excessively long arms and legs and dilatation of ascending aorta that may lead to fatal rupture. They believe that President Lincoln had Marfan syndrome.

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Classification of Connective Tissue Proper: I.Embryonal type a. Mesenchyme b. Mucous connective tissue II. Adult or post-natal type a. Reticular tissue b. Areolar tissue c. Adipose tissue d. Dense fibrous c.t. e. Hemopoietic tissue

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MESENCHYME a filling or packing tissue between germ layers and developing organs. P.C. : Mesenchymal cells Ground substance: coagulable fluids which becomes a mucoid jelly and contains fibers.

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MUCOUS CONNECTIVE TISSUE/ WHARTON’s JELLY scanty gelatinous semi-fluid mass in which the cells and fibers are embedded. P.C. : Fibroblast P.F. : Collagenous fibers vary in number and size with age of the specimen. During the first half of pregnancy they are fine and scanty during the second half of pregnancy they are coarse and more in number. This tissue is avascular no lymphatics nor nerves.

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RETICULAR TISSUE P.C. : primitive reticular cell & macrophage P. F. : reticular fibers/ Type III collagen Functions: 1. connecting and supporting framework. 2. component of basal lamina 3. production of lymphocytes and macrophages Occurrence: seen as framework of endocrine and lymphoid organs, bone marrow, liver, alimentary and respiratory mucous membrane.

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AREOLAR or LOOSE FIBRO-ELASTIC TISSUE P.C. : Fibroblast P.F. : all types are present but collagen fiber is the most abundant. Functions: 1. Mechanical function a. supports and permits some mobility b. provides pathway for blood vessels c. act as packing material between parts of the body. 2. Transport of metabolites 3. Defense and repair Occurrence: most widespread filling or packing tissue.

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ADIPOSE TISSUE connective tissue specialized for storage of lipids and reservoir for energy of the body. P.C. : Fat cell P. F. : Collagen and Reticular fiber This is an atypical C.T. because this is more of cells than interstitial substance and they occur in clusters as lobules bounded by a septum. Little or no areolar tissue is seen within the lobule. In muscle constitute 12-14% of its boy weight. In females its 25% or more. It represents about two months reserve of energy. This is highly to hormonal and nervous stimulation.

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There are two types of adipose tissue: White adipose tissue – widespread and makes up the bulk of the body fat. 2. Brown adipose tissue – limited to certain specific areas.

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Histogenesis of Adipose tissue: Primary Fat formation – occurs earlier in the fetus. Gland-like aggregations of epitheloid precursor cells are laid down in specific locations and give rise to the brown adipose tissue. 2. Secondary Fat formation – occurs later in fetal tissue and in the early post-natal period and gives rise to white fat in the adult human.

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Two types of obesity: 1. Hypertrophic obesity - due to accumulation of excess lipids in normal number of unilocular adipose cells. Size of the fat cells is 4x the normal size. 2. Hypercellular obesity - number of fat cells is greater that the normal. Overfeeding in the early weeks of life -> formation of greater number of adipose cell precursor. So, the level of nutrition in the early weeks of life influences the number of adipose cell precursors.

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Adipose tissue is absent in: 1. Nervous system 2. lungs 3. eyelids 4. penis Functions: 1. Storage of neutral fats 2. Act as shock absorber 3. insulator against cold 4. cosmetic purpose

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DENSE FIBROUS TISSUE This tissue have an abundance of compactly arranged fibers. The cells are proportionately fewer than in the loose connective tissue. These are therefore for a firmer support. The fibers are either regularly or irregularly arranged.

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Two types of dense fibrous tissue: A. Regularly arranged or Parallel arrangement Subclassified according to predominant fiber: 1. Tissues that are predominantly collagen: a. tendon – muscle to bone b. ligaments – bone to bone c. aponeurosos – muscle to muscle 2. Tissues that are predominantly elastic Examples: ligamentum nuchae, scarpas fascia

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B. Interwoven or irregularly arranged tissues 1. Tissues that are predominantly collagenous. These resembles the areolar tissue but is compactly arranged and the cells are crowded. Examples: a. Fascia – interwoven sheets with irregularly arranged bundles, deep fascia, dermis. b. Fibrous capsule c. Sheaths – periosteum d. Septa an trabecula 2. Tissues that are predominantly elastic-network of elastic fiber exist as tubular sheet within the blood vessel. In the large arteries, elastic tissue consolidates with elastic membranes.

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Primary tendon bundle Secondary tendon bundle Endotendineum Epitendineum peritendineum

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Hemopoietic tissue Two types: A. Lymphoid tissue/ Adenoid tissue > P.C. : lymphocyte > P. F. : reticular fiber B. Myeloid tissue

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Connective tissue disease: 1. Scurvy - due to Vit. C deficiency. mucocutaneous hemorrhages in the legs

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2. Ehlers-Danlos syndrome - inherited disease - characterized by short stature. - unusually stretchable skin. - hypermobility of the joints - poor wound healing.

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3. Osteogenesis imperfecta - unusually thin skin & multiple bone fractures & deformities.

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That’s all… thank you!