Connective tissue fibres and types of the connective

Connective tissue fibres and types of the connective tissue Viktória Vereczki MD. , Ph. D. Semmelweis Egyetem Anatómiai, Szövet- és Fejlődéstani Intézet 5/10/2018 8: 55 am

n Basic concept of the connective Connective tissue cells n Extracellular matrix n fibres n n collagen reticular elastic amorphous background substance n n n glycosaminoglycans: unbranched polysaccharides made up of repeating disaccharides proteoglycans: a core protein is equipped with numerous GAG molecules glycoproteins: globular proteins with branching chains of monosaccharids

Connective tissues: properties are basicly determined by the extracellular matrix (ECM).

Basic concept of the connective tissue n n Connective tissue cells Extracellular matrix n fibres n n collagen reticular elastic amorphous background substance n n glycosaminoglycans proteoglycans glycoproteins electrolyte (water, salts)

Connective tissue fibres from Dr. Puskár collagen fibres reticular fibres elastic fibres Collagen and reticular fibres are the polimers of the collagen molecule, while elastic fibres are formed by elastin and microfibrils.

Synthesis and structure of collagen and elastin

Collagen synthesis procollagen alphachain procollagen triple helix cleavage by procollagen peptidase: insoluble tropocollagen Tropocollagene glycine, proline, hydroxy-proline, hydroxylysine

Medical application: Keloid is a local swelling caused by abnormally large amount of collagen that form is scars of the skin. Keloids occur most often in individuals of African descent. Not only they can be disfiguring but excision is almost always followed by recurrence.

n Collagen types Fibrillar collagens linking/anchoring collagens sheet-formingcollagens Type I, III, V, XI Type. IX, XII or VII binds to type IV Type IV

Constitution of fibrillar collagen Tropocollagen covalent cross-links by lysyl oxidase enzyme: collagen fibrils (crossstriation) collagen fibers collagen bundles

Instead of getting lost in the details and the charts of the histology textbooks. . . What you really have to know: • Collagen I: everywhere, 90% of total collagen in the body: skin, tendon, bone, dentin • Collagen II: main component of cartilage • Collagen III: main component of reticular fibers • Collagen IV: in the basement membrane (within the basal lamina) • Collagen V: hair and placenta Note that type I, III and V are fibril-forming, while type IV forms delicate networks!

Elastin synthesis Resambles collagen synthesis: water soluble proelastin is synthesized in the r. ER, secreted into the extracellular space where it is cleaved by proelastin peptidase to form insoluble tropoelastin. Tropoelastin combines with microfibrills and is cross-linked into mature fibres by lysyl oxidase. glycine, proline, lysine, alanine, valine (hydrophobic side-chains and are responsible for elasticity.

Elastin polipeptides , the major components of elastic fibers have multiple random-coil domains that strenghten or strech under force, and then relax. Most of the cross-links between elastin subunits consist of the covalent, cyclic structure desmosine, each of which involves four converted lysisns into elastine molecules.

Medical application Mutation of fibrillin genes results in Marfan syndrome : lack of resistance in tissues rich in elastin fibers. The degree to which people are affected varies. People with Marfan tend to be tall, and thin, with long arms, legs, fingers, and toes. They also typically have flexible joints and scoliosis, The most serious complications involve the heart and aorta with an increased risk of mitral valve prolapse and aortic aneurysm.

Basic histological properties of connective tissue fibers or how to recognize them in the histology lab. . .

Collagen fibers Collagen is the most common type of fibers in the ECM and the only clearly visible fiber when HE staining is used!

Reticular fibers Form delicate branching network and contribute to the inner skeleton of all parenchymal organs. They are of small diameter and resistant to most of the dyes. Silver impregnation is commonly used to make them visible

Elastic fibers Thin wavy fibres frequenty aggragating into thick elastic membranes. Bind resorcin-fuchsin.

Note: each connective tissue fiber type requires different staining method! collagen fibres (HE) reticular fibres (silverimpregnation) elastic fibres (resorcinfuchsin)

Basic concept of the connective tissue n n Connective tissue cells Extracellular matrix n fibres n n collagen reticular elastic amorphous background substance n n n glycosaminoglycans: unbranched polysaccharides made up of repeating disaccharides proteoglycans: a core protein is equipped with numerous GAG molecules glycoproteins: globular proteins with branching chains of monosaccharids

Glucosaminoglycans (GAGs) or mucopolisaccharides hexuronic acid or hexose hexosamine glucuronic acid, iduronic acid, galactose COOH/CH 2 OH O glucosamine, galactosamine CH 2 OH O -OH HO- COOH/CH 2 OH O NH 2 -O - monome r S S NH 2 S S S S

n Hyaluronic acid: the largest (100 to 1000 k. Da) and the only nonsulphated GAG. n Chondroitin 4 -sulphate Chondroitin 6 -sulphate Dermatan sulphate Heparan sulphate Keratan sulphate n n smaller (10 to 40 k. Da) GAGs covalently bound to proteins to form proteoglycans All the GAGs are intensly hydrophilic and bind a lot of water being responsible for the high viscosity of the ground substance. GAGs are also polyanions binding a great number of cations, mainly sodium ions.

Proteoglycans in the ECM AGGRECAN monomer Acidic groups of proteoglycans bind to the basic groups of collagen.

Glycoproteins Glycoprotein Fibronectin and laminin: multiadhesive glycoproteins connecting cells through their surface integrin moleculeswith the extracellular matrix structures. Support adhesion and migration.

Summary of the ECM n n n In contrast to the epithelial tissues, the extracellular space of the connective tissues is abundant and basicly determins the properties of the connective tissues. Glycosaminoglycans and proteoglycans due to their highly hydrophilic character and sugar content bind a lot of water providing high viscosity, a jelly-like consistance to the ground substance. This gelatinous substance is structured and fixed by the connective tissue fibres. Mainly glycoproteins are responsible for linking connective tissue cells to the ECM. These cells might be involved in synthesis of ECM (e. g. fibroblast, osteoblasts) or protect ECM from the invasion of infective agents (immune cells) or contribute to the renewal/remodelling/transformation of the connective tissue (macrophages, chondroclast, osteoclasts).

Classification of connective tissues 1. Embryonic connective tissue (umbilical cord) 2. Loose connective tissue (submucosa, adventitia) 3. Dense connective tissue irregular (dermis, tunica albuginea, capsules of organs) regular (ligaments, tendons, cornea) 4. Cell rich connective tissue reticular (hemopoetic and lymphatic tissues) spinocellular (ovarium, uterus) 5. Specialized connective tissues blood adipose tissue supporting bone tissues cartilage

1. Embryonic connective tissue from Dr. Puskár Mesenchymal cells (undifferentiated connective tissue cells) and hyaluronic acid predominantly in the early stage. Later mesenchymal cells differentiate into fibroblast which produce more and more fibres, but the amorphous ground substance remains abundant resulting in a jelly-like consistence (Wharton jelly). Basophilic staining of the mesenchymal cells and fibroblast can be explained by intense protein synthesis and well-developed r. ER. T is also called as mucoid tissue. It is aslo found in the pulp cavities of young teeth as a postnatal

2. Loose connective tissue The most common type of connective tissues: connects and separates, fills the gaps everywhere, i. e. tunica adventitia of the vessels and tubular organs; tela submucosa.

3 a. Dense, irregular connective tissue Rich in collagen (type I and elastic fibers), no preferred orientation. (e. g. dermis of the skin, tunica albuginea of the testicles)

3 b. Dense, regular connective tissue Paralelly arranged bundles of collagen and tendocytes (a special type of fibrocytes).

4 a. Cell rich connective tissue reticular splee n reticulum cells and reticular fibres (type III collagen) tonsil

Ag-impregnation: reticular fibres in the lymph node.

Star-shaped, fibroblast-like reticulum cell in a lymphatic organ.

4 b. Cell rich connective tissue spinocellular ovary uteru s

Classification of connective tissues 1. Embryonic connective tissue 2. Loose connective tissue (submucosa, adventitia) 3. Dense connective tissue irregular (dermis, tunica albuginea, capsules of organs) regular (ligaments, tendons, cornea) 4. Cell rich connective tissue reticular (hemopoetic and lymphatic tissues) spinocellular (ovarium, uterus) 5. Specialized connective tissues blood adipose tissue supporting tissues – bone cartilage

Adipose tissue "Empty" signet ring cells - adipocytes Energy storage, thermal insulation, thermogenezis in brown adipose tissue, shock absorbtion, , endocrine functions (e. g. leptin)

unilocular, white adipocytes multilocular, brown adipocytes unilocular and multilocular cells frozen section, Sudan III staining

Thank you for your attention!

References Ross et al: Histology a text and Atlas, 3 rd ed. 1995 Junqueira’a Basic Histology text and Atlas 13 th ed. 2013 Dr. Márk Kozsurek’s lecture about Connective tissue fibres Prof. Mihály Kálmán’s lecture about Connective tissue fibres Szentagothai J, Réthelyi M: Funkcionális anatómia, Medicina, 2014