Connective Tissue

Dr. Prapee Sretarugsa

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Connective Tissue

213Course : Microanatomy (SCAN ) : :::-: :::::: :::::::: :::

2Time : h 312001Date : October ,

:::::: ::::::::::: . : :::::: ::: :: :::::: : Faculty Of Science : :::::: ::::::::::

- 201 5424

- :::::: : ::::::::::::: . .


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Objectives

: After you have studied this lecture, you should be able to • Explain the components of connective tissue• Describe the structures and functions of all types of cells in connective tissue• Identify all fibers in connective tissue as well as their localization in the organs• Explain the composition of ground substance as well as its function• Classify the type of connective tissue


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Connective Tissue (CT)

• Derives from mesoderm • Mesenchyme pleuripotency)• Mesenchymal cells can differentiate into

- connective tissue- bone, cartilage- blood and hemopoietic cells- lymphoid cells


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Characteristic of Connective Tissue

• Consists of a large amount of extracellular matrix with a limited number of cells


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• A complex of nonliving macromolecules synthesized by the cells• Some tissue consists of small amount of ECM• Connective tissue contains a large amount of ECM with a limited number of cells• A major component of connective tissue proper• Comprises of

- Ground substance – resists forces of compression

- Fibers – provides tensile force

Extracellular Matrix (ECM)


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Ground Substance

Consists of• Glycosaminoglycans (GAGs)• Proteoglycans• Adhesive glycoproteins


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Properties of GAGs

• Long, inflexible, unbranched polysaccharides• High negative charge• Repeating disaccharide units• One of repeating unit is amino sugar which is sulfated (SO-

3)• Second sugar is uronic acid with a carboxyl gr. (COO-)• Retension of positive ions (eg. Na+) together with water, maintaining tissue architecture turgor which tend to prevent deformation by compressive force


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Structure of GAGs

- Disaccharide units form covalent linkage with protein to form proteoglycans- Proteoglycans attach to hyaluronic acid- Hyaluronic acid, nonsulfated GAG


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Types of GAGs


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Struture ofProteoglycan

• Macromolecues f ormed by sulfated

GAGs form covalen t bonds with a prot

ein core• Structures look li

ke a bottle brush• • Each proteoglycan is covalently linked to hyal

uronic acid forming huge macromolecules, Agg recan aggregates


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Proteoglycans

• Macromolecues formed by sulfated GAGs fo rm covalent bonds with a protein core

• Structures look like a bottle brush• Each proteoglycan is covalently linked to hy

aluronic acid forming huge macromolecules, Aggrecan aggregates


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Functions of Proteoglycans

• Resist compression and retard the rapid movement of microorgani and metastatic

cells• Form molecular filter (in association wit

h basal lamina) of varying pore sizes and charge distributions that selectively scree

n and retard macromolecules as they pas s through them

• Contain binding sites of certain signalin -g molecules eg. TGF ß


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Functions of Proteoglycans and H yaluronan during development

• Epithelial branching and differentiation• Eye development• Limb development


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Adhesive Glycoproteins

Large macromolecules have several domains - at least one domain usually bind to integrins - one to collagen fibers - one to proteoglycans


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The Major Types of AdhesiveGlycoproteins

• Fibronectin• Laminin• Entactin• Tenascin• Chrondronectin• Osteonectin


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The Binding Sites of AdhesiveGlycoproteins

- Fibronectin collagen, heparin, heparan sulfate, hyaluronic acid, integrin

- Laminin stricly limited to the basal lamina - heparan sulfate, type IV collagen,

entactin & cell membrane - Entactin laminin, type IV collagen - Tenascin integrin, proteoglycan & fibronectin

- distribution is limited to embryonic tissue


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The Binding Sites of AdhesiveGlycoproteins

Chrondonectin - type II collagen, chrondroitin sulfate, hyaluronic acid, & integrins of chondroblas

t and chrondocyte

Osteonectin - type I collagen, integrins of osteoblast and osteocyte


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Integrin


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Fibers

• Provide tensile strength and elasticity to ECM• Can be classified into 3 types based on their morphology and reactivity with dyes - Collagen

- Reticular - Elastic


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Collagen Fibers

• Collagen, constitue about 20% of all the bod y

proteins• Form a flexible fiber whose tensile strength is greater than that of stainless steel of comparable diameter• White fiber, colorless• No specific staining for collagen fiber• Acidophilic fiber• EM showing cross-banding at regular interval of 67 nm


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Components of collagen fibers

• Smaller subunits, tropocollagen •Formed from parallel aggregates the thinner

fibril 10 to 300 nm in d

iameter


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Tropocollagen

• 2 8 0 nm long• 1 .5 nm in diameter• -Three polypeptide chains, a chains - formed triple helical configuration - 1000each chain contains about , aa - every third aa is ::::::: - the majority of the remaining aa is proline, hydroxyproline,hydroxylysine


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Six Major types of collagen

Types Characteristics I Most common type collagen ,thick fiber II Forms slender fiber in hyalin and elastic cartilages III Reticular fiber - Highly glycosylated, thin fiber0.5-2.0 um - Rich coating of sugar likely stained with silver salt (Argyrophilic fiber) - positively stained with periodic acid - schiff (PAS) reaction


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Six Major types of collagen

Types Characteristics IV Do not display 67 nm periodicity Forms a meshwork of procollagen molecules V Forms very thin fibrils and association with Type I VI Forms small aggregates, anchoring fibrils


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Elastic Fibers

• Slender, long and branching in loose CT• Form coarse bundles in ligament ( ligamentum flavum ::: ::::::::::: :::::) ( concentric sheet in the wall of large a.)• Elastin ,a protein rich in glycine and proline - unusual aa, : ::: ::::: & ::::::: ::::: - a high degree of elasticity - forms a core of elastic fiber• Microfibrils (10 nm in diameter, glycoprotein, fibrillin), located at the periphery of elastin


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Elastic fibersA. Elastin has a random coil structure in the relax state, but reforms as a different random coil on relaxationB. Elastin molecule are covalently linked into arrays which can reversibly stretch and recoil, and may be arranged as fibers or sheets

• Elastic fibers are composed of microfilaments surrounding and organizing core region of cross- linked elastin


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Blood vessel, showing the elastic fibers

Elastic f.


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Tunica media of aorta

Show the typical wavy appearance of thick bundles of elastic fiber


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Reticular fibers

• Collagen type III• Frame work of lymphoid organs, liver ect.• Highly glycosylated, thin fiber0.5-2.0 um• Rich coating of sugar likely stained with silver salt (Argyrophilic fiber)• Positively stained with periodic acid - schiff (PAS) reaction


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Cellular components of CT

• Fixed cells - A resident population of cells have develope: and remain within CT - fibrobasts, mast cells, adipose cells, pericyte s

& macrophages• Wandering (Transeint) cells - Originate mostly in bone marrow - plasma cells, lymphoctes, neutrophils, eosinophils, basophils, monocytes, and som: macrophages


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Fibroblasts

- Produce ECM & Fibers- Active fibroblasts often reside with collagen bundles- Elongated, fusiform cells & pale-staining cytoplasm- Large ovoid nuclei with prominent nucleoli- EM, showing prominent RER, Golgi complex- Inactive, Fibrocytes ; small, elongate & deeply stained nuclei- Some movement


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Fibroblasts and Fibrocytes

Fibroblasts

Fibrocytes


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Fibroblasts, showing euchromatic nucleus, prominent RER

Collagen fibers

Collagen fibersRER


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Myofibroblasts

- Modified fibroblasts contain actin and myosin filaments- Surface profile of nucleus resembles smooth m.- Basal lamina is absent- Abundant in wound healing area (purse string effect)- Contribute to retraction and shrinkage of scar tissue


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SEM : Pericytes

- Undifferentiated mesenchymal cells- As named adventitial cells or perivascular cells- Locate around capillaries and venules- Possess characteristic of smooth muscle cells and endothelial cells


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TEM : Pericytes

P

Capillary

- Their basal lamina are directly continuous with basal lamina of endothelial cell- EM, cytoplasmic characteristics almost identical with endothelial cells- In large venules, they have characteristic of smooth m. cells

Pericyte


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Wound healing

- New connective tissue & blood vessels are formed- Undifferentiated mesenchymes lacated in tunica adventitia of venules and small veins- Fibroblast- Pericytes- Endothelial cells


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Macrophages

- They function in removing cellular debris (phagocytosis) and protceting body against foreign invaders- They also play a role in presenting antigens to lymphocytes- They are about 10-30 um in diameter- Cell surface is uneven- Basophilic cytoplasm, many small vacuoles, small dense granules-- Indented nucleus- EM showing prominent Golgi app. & RER, abundant lysosomes


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Macrophage

: :::: ::::::: :::::: : ::::: :::::::::• They congregate, enlarge and become poly

- gonal shaped epitheloid cells• If the particulate matter is excessive large, se

veral macrophages may fuse to form a -Foreign body giant cell

• Macrophage residing in CT, Fixed Macrophag: (resident Macrophage)• Free Macrophage - migrate from the blood


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Macrophage


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Macrophage Development and Distribution

• : :::::::::: :::: :::::::: :::: : ::::::::: s were derived from precursor cells in Reti

culoendothelial System, which included nonp hagocytic cells

• Presently, all members of phagocytotic cell s arise from a common stem cell in bone mar

row, possess lysosomes, can phagocytose an d display Fc receptors and receptors for com

plement, as classified to as Mononuclear Pha gocyte System


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Macrophage Development and Distribution

Macrophages localized in certain regions of the body were given specific names before their ori

gin was understood.• Kupffer cells of the liver• Dust cells of the lung• Langerhans cells of the skin• Monocytes of the blood• Macrophages of CT, spleen, lymph node, thy

mus and bone marrow• Osteoclast of the bone• Microglia of the brain


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Mast cells

• Oval shape with round or oval nucleus• 20-30 um in diameter• Abundance of the large basophilic granule• Granules show Metachromasia• Granules containing histamine, heparin, eosinophil chemotactic factor (ECF), nutrophil chemotactic factor (NCF), chondroitin sulfate protease, aryl sulfatase


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Mast cells

• Oval shape with round or oval nucleus• 20-30 um in diameter• Abundance of the large basophilic granule• Granules show Metachromasia


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Mast cells

• Granules show Metachromasia


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Mast Cell

• Granules containing histamine, heparin, eosinophil chemotactic factor (ECF), nutrophil chemotactic factor (NCF), chondroitin sulfate protease, aryl sulfatase


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Plasma cells

• Found in large numbers in area of chronic inflammation• Derived from B lymphocyte• Ovoid cells, 10-20 um, eccentric nucleus• Short life span of 2-3 weeks• Intensely basophilic cytoplasm, prominent RER• Spherical nucleus consisted of heterochromatin radiating out from the center, look like clockface appearance in LM observation• Produce circulating antibodies (r-globulin)


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Plasma cells

• Found in large numbers in area of chronic inflammation• Derived from B lymphocyte• Ovoid cells, 10-20 um in diameter, Eccentric nucleus


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Plasma Cell• Intensely basophilic cytoplasm, prominent RER

• Produce circulating antibodies (r-globulin)

• Spherical nucleus consisted of heterochromatin radiating out from the center, look like clockface appearance in LM observation


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Lymphocyte

lym

• Smallest free cells, 6-8 um in diameter• Spherical with round nucleus (heterochromatin)• Thin rim of cytoplasm


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• EM, a few organelles but a large number of free ribosome• Thin rim of cytoplasm

• Small, medium & large lymphocytes• B-Lymphocytes plasma cells• T-Lymphocytes cell-mediated immunity

Lymphocyte


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• Accumulate in Peyer's path of Ileum• Distribute in lamina propria of G.I & respiratory tract etc.

Lymphocyte

Lamina propria


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Neutrophils - Polymorphonuclear neutrophil (PMN), polymorph, 4-5 lobes- 10-12 um in diameter- There are three type of granules - Small, specific granules (alkaline phosphatse) - Large, azurophilic granules, lysosomes (peroxidase, acid phosphatase) - Tertiary granules (gelatinase, cathepsins)-


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Neutrophils

- The first cells to appear in acute bacterial infection- Phagocytose microorgansim die resulting in formation of pus


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Neutrophil


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Eosinophils

•10-12 um in diameter•Bilobes nucleus• Large elongated granules - crystalloid body- peroxidase- histamine- hydrolytic enzyme• Phagocytose Ag-Ab complex


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Eosinophils

Note : the crystalloid bodies in the granules


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Monocyte

In blood

CT

Macrophag:


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Basophil

• ::::::: :::::::• :: ::::: :::: :::: ::::::::• :::::::: ::::::::

for immunoglobuli: :: :: : ::: ::::


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Adipose Tissue

• Unilocular adipose tissue, White fat• Multiloccular adipose tissue, Brown fat


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Adipose cellsWhite fat

• Adipocytes, Adipose cells, Lipoblasts• Single lipid droplet• Variation in color from white to deep yellow, depend on carotenoid in diet• Eccentric nucleus, signet ring appearance• Lipid is usually extracted during conventional preparation


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White Fat : Sudan red• A few organelles• Mature adipocytes do not divide• Highly blood supply• Receptors for Insulin, GH, NEP, Glucocorticoid• Distribute in subcutaneous layers, mesentery• Accumulation depends on sex, age, region• Large cells, 100-120 um, thin rim cytoplasm


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• Multiple lipid droplets• Tan to reddish brown, cytochrome in mitochondria • Eccentric round nucleusExtensive vascularity• Numerous unmyelinated nerve fiber, axon ending on both blood vessels and on fat cells• Prominent in newborn• Rate of fatty acids oxidation up to 20 times the rate of white fat

Brown Fat


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• A few cell organelles• Abundant round-shaped mitochondria

Brown Fat


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Distribution of Brown Fat

New born : superficialDeep Rabbit


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Clinical correlations : Adult, obesity

• Hypertrophic obesity - accumulation and storage of fat in unilocular fat cells - increase their size• Hypercellular obesity - over abundance of adipocytes - this type of obesity is severe


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Clinical Correlations

• Lipomas, common benign tumor of adipocytes• Liposarcomas, malignant tumors of adipocytes


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Mesenchymal CT

• Numerous mesenchymal cells, oval euchromatic nucleus, prominent nucleoli• Pluripotency• Pale-staining cytoplasm, small processes• Gel-like, amorphous ground substance• Consists of reticular fibers


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• Fibroblasts• Jelly-like, amorphous ground substance composed of hyaluronic acid called Wharton's jelly• Composed of Type I and type III collagen fibers• Found in umbilical cord, subdermal C T of embryo

Mucous tissue


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Connective Tissue ProperLoose (Areolar) C.T.

• Abundant ground substance, proteoglycans• Contains all types of cells• Contains all types of fibers• Fills in the body spaces, adventisia of blood vessels, lamina propria of G.I. tract ect.


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Loose Connective Tissue displaying collagen (C) and elastic fibers


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Distribution of loose CT in lamina propria of GI tract

Lamina propria


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Dense C T

• More fibers• Fewer cells• Orientation and arrangements of the fiber make it resistance to stress


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Dense Irregular C T

• Mostly coarse collagen fibers arranged randomly that resists stress from all directions• Fibroblast, the most abundant cells• Distribution in dermis, sheath of nerves, capsule of organs ect.


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Dense irregular CT : Perichondrium (P)


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Dense irregular CT: Dermis


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Dense Regular Collagenous C T

• Collagen bundles densely packed and oriented into parallel cylinders or sheet• Resists tensile strength• Little ground substance and cells (Fibroblasts)•Tendons, ligaments, aponeuroses


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Dense Regular Collagenous C T ( Tendon )


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Dense Collagenous Connective Tissue - (Muscle tendon junction)


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Dense Regular Elastic C T

• Elastic fibers arranged parallel to each other and form thin sheets or fenestrated membrane (large bl.ves.)• Ligamentum flava of vertebral column, suspensory ligament of penis


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Reticular Tissue

• Type III collagen• Form mesh-like network• Liver sinusoid, adipose tissue, lymphoid organs

Connective Tissue

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