Connective tissue premed II

1. Connective tissue premed II -support for the basement membrane undersurface.

3. Function of CT • Responsible for providing and maintaining form in the body.(mechanical role) • Provide a matrix that connects and binds cells and organs and ultimately supports body. • The capsules that sorround the organs of the body and the internal architecture that supports their cells are composed of connective tissue. • This tissue also makes up tendons,ligmts, and the areola tissue that fills the spaces btw organs.

4. Components of CT • Cells • Extracellular matrix • Fibers • Collagenous, reticular, elastic • Ground substance • Hydrophilic macromolecules (glycoproteins, glycosaminoglycans, proteogycans) bind to receptors on cells and add strength and rigidity to matrix • ***the major constituent of c.t is its extracellular matrix.*****

6. Origins of CT • Mesenchyme • Embryonic tissue, undifferentiated • Develops from mesoderm • Cells migrate from origins, penetrate and surround organs • Develop into other types of structures: blood cells, muscles, bones • ****Mesodermal cells migrate from their site of origin,sorrounding and penetrating organs.These are MESENCHYMAL CELLS*****

8. Connective tissue cells Two types 1. cells that are formed locally and remain in the connective tissue -fibroblasts and adipocytes 2. cells that are transient inhabitant of the tissue (cells of defense system) – macrophages, mast cells, plasma cells, leukocytes

9. Connective tissue cells

11. Fibroblasts: • most common cell type • actively synthesizng cells- synthesize fibres and components of ECM • have large nucleus, abundant rER, Golgi apparatus. • have branched cytoplasmic processes • Fibrocytes: mature fibroblasts; not active (quiescent) • small and spindle shaped with elongated nucleus • small amount of rER • upon stimulation can revert to fibroblasts • Myofibroblasts: have high content of microfilaments (actin and myosin); • contractile in function; involved in wound closure.

12. Fibroblasts: • most common cell type • actively synthesizng cells- synthesize fibres and components of ECM • have large nucleus, abundant rER, Golgi apparatus. • have branched cytoplasmic processes • Fibrocytes: mature fibroblasts; not active (quiescent) • small and spindle shaped with elongated nucleus • small amount of rER • upon stimulation can revert to fibroblasts • Myofibroblasts: have high content of microfilaments (actin and myosin); • contractile in function; involved in wound closure.

13. Fibroblast strucute

15. Macrophages ( large + eating): - histiocytes, tissue fixed macrophages • derived from bone marrow as monocytes • circulating monocytes enter the connective tissue, mature to form macrophages (tissue scavengers) • can proliferate locally • along with other phagocytes (Kupffer cells in liver, osteoclasts in bone, microglia in CNS, Langerhan cells in skin) they constitute mononuclear phagocytic system

16. Macrophages when activated show cytoplasmic protrusions (pseudipodia) and indentations, enhanced metabolic and lysosomal activity

17. Characterised by surface pleats,protrusions and indentations, a morphologic expression of their active pinocytotic and phagocytotic activities. When adequately stimulated, these cells may increase in size forming EPITHELOID RESEMBLANCE.)cells or several epitheloid cells may fuse to form MULTINUCLEATED GIANT CELLS.

18. Macrophages are the first cells that encounter antigens - present the antigen to lymphocytes are thymocytes for destruction ( antigen presenting cells) Phagocytic activity of the macrophages-involution in the uterus.(post-paturition). In pathological conditions macrophages fuse to form multicellular giant cells Which in certain clinical conditions are diagnostic for certain diseases.

19. PHAGOCYTOSIS OF FOREIGN PARTICLE: • COATING OF FOREIGN PARTICLE BY SUBSTANCES SUCH AS Ig (opsonins) FOR WHICH THE PHAGOCYTE HAS RECEPTORS. • UPTAKE OF THE OPSONIZED PARTICLE INVOLVING SEQUENTIAL INTERACTION OF PHAGOCYTE MEMBRANE RECEPTORS WITH THE PARTICLE.(ZIPPERING) • THERE IS FORMATION OF PHAGOSOME(PHAGOCYTIC VACUOLE) AND WITH LYSOSOMES (PHAGOLYSOSOME) AND KILLING AND DIGESTION OF THE FOREIGN PARTICLE.

20. Mast Cells small round cells involved in inflammatory response wide spread in dermis of skin(connective tissue mast cell) and in the digestive and respiratory system (mucousal mast cell) similar to basophils in function ,derived from bone marrow Has few organelles in its cytoplasm.

21. Mast Cells Cytoplasm contains metachromatic( dye toludine blue) granules that contain heparin, histamine, leukotrienes and eosinophilc-chemotactic-factor of anaphylaxis (ECF –A)

22. Mast cells release chemical mediators stored in the cell,this promotes allergic reactions known as immediate hypersensitivity reaction occurs in a few mins after penetration of an antigen of an individual previously sensitized. To the same or very similar antigen . There are many examples of immediate hypersensitivity reaction,a dramatic one is ANAPHYLACTIC SHOCK. The process of anaphylaxis consists of the following sequential events,the first exposure to an antigen (allergen),such as bee venom,results in production of IgE class of antibodies by plasma cells. The surface of mast cells contains specific receptors for IgE, a type of Ig produced by plasma cells. Most IgE molecules are bound to the surface of mast cells and blood basophils;very few remain in plasma. IgE avidly binds to the surface of mast cells. A second exposure to the antigen results in binding of the antigen to IgE on the mast cells . This then triggers the release of mass cell granules ,liberating histamine, leukotrienes, Ecf-A, and heparin. Histamine -causes contraction in smooth mm (mainly brochioles)and dilates and increases the pemeability of blood capillaries ,increase bronchial mucus secretion. Leukotrienes produce slow contraction in smooth mm and ECF-A attracts bld eosinophils. Heparin.

23. Mast cells liberate their content in response to allergen – in rhinitis and asthma • - histamine induces hypersensitivity response (immediate hypersensitivity) within minutes of penetration by allergen • Anaphylactic shock: ( potentially fatal condition): • in response to toxic substance (bee venom) contents of mast cell are released to cause • - bronchiolar constriction, capillary dilatation and increase permeability (histamine) • prevention of blood coagulation (heparin) • slowing of smooth muscle contraction of blood vessel (leukotrienes) and eosinophil attraction (ECF-A)

24. Plasma cells • relatively large ovoid cells with basophilic cytoplasm (rich in rER) • Nucleus with characteristic cart – wheel (clock face) appearance as heterochromatin alternating with lighter areas • derived from lymphocytes; seldom divide, life span is 10 –20 days secrete antibodies

25. Leukocytes • neutrophils, eosinophils, basophils and lymphocytes migrate from blood into the connective tissue • - only lymphocytes return to blood • -perform functions related to defense system

26. Extracellular Matrix - ECM • - a dynamic system of complex structures that fills intercelluar space • major constituent of the support tissue • determines the physical property of the tissue – the softness of loose connective tissue, resilience of cartilage, hardness of bone and fluidity of blood • Constituents: • -1. ground substance • - 2. tissue fluid • - 3. protein fibres

27. 1. Ground substance - amorphous, viscous, clear (transparent) substance having a slippery feel -LM does not present this for examination – appear as empty background belying its functional importance Composition: - 1. proteoglycans and 2. glycoproteins with tissue fluid loosely attached to it - Function: has the ability to permit diffusion of oxygen and nutrients between the tissues and microvasculature - binds cells to the fibres of the extracellular matrix of connective tissue.

28. 1. Proteoglycans: • large molecules in the ground substance • -composed of gylycosaminoglycans (GAGs) and proteins • GAGs (acid mucopolysaccharides): formed by linear polysaccharides composed of uronic acid (glucuronic acid or iduronic acid) and hexosamine (glycosamine and galactosamine) • - negatively charged because of high content of -OH, -COOH and sulfate ions (acidic ions) that stain with basic dyes and attract cations (Na+ ) and water to form highly hydrated gel giving turgor to the tissue. • - allow rapid diffusion of water and water soluble solutes but NOT to large molecules and bacteria

29. Types: 5 major types based on specific sugar residues, their linkage and degree of sulfation

30. - With the exception of hyaluronic acid all GAGs are covalently linked to protein core forming proteoglycans giving the appearance of bottle brush • *hyaluronic acids are large molecules with thousands of carbohydrate chains compared to 100 s or less in other GAGs • bound by electrostatic bounds to the protein core to form proteoglycans and does not have sulfated side group however other proteoglycans are indirectly linked to it.

31. A glycosaminoglycans is an unbranched(linear) polysaccharide made up of repeating disaccharide. One component is an amino sugar,and the other is a uronic acid. Proteoglycans contain a greater amount of carbohydrates than do glycoproteins. Glycoproteins: Are globular protein molecules to which branched chains of monosaccharides are covalently attached. They are compounds that contain a protein moiety to which carbohydrates are attached. In contrast to proteoglycans,the protein moiety usually predominates,and these molecules do not contain the linear polysaccharides formed by the repeating disaccharides containing hexosamines. Instead, the carbohydrates moiety of glycoproteins is frequently a branched structure.

32. Degradation of proteoglycans is carried out by several cell types and depends on the presence of several lysosomal enzymes. The turnover of proteoglycans is rapid i.e ,2-4days for hyaluronic acid and 7-10 days for sulfated proteoglycans. Several disorders have been described in which a deficiency in lysosomal enzymes causes GAG degradation to be blocked ,with consequent accumulation in tissues. The lack of specific acid hydrolases in lysosomes has been found to be the cause of several disorders in humans.

33. proteoglycans are synthesised in rER and modified in Golgi apparatus. • degraded in lysosomes. Deficeincy of enzymes cause diseases like hurler , hunter, sanfilipo , morquio etc syndromes. • gives high viscosity and acidity to ground substance and hence a barrier to bacteria; • however bacteria that produce “hyaluronidase” can hydrolyses hyaluronic acid and proteoglycans to reduce the viscosity and acidity and invade the tissue

34. synthesis of collagen involves a casdcade of unique events within rER and Golgi apparatus. • -there are many points at which the synthesis process can be altered or interrupted by faulty enzyme or absence of enzyme leading to many pathological conditions. • Vitamin C is important in the binding of polypeptide chains in the synthesis of tropocollagen; deficiency of this produce abnormal collagen; patients exhibits scurvy – leading to blood vessel rupture, teeth fall out, wounds fail to heal etc. • Abnormal accumulation of collagen leads to sclerosis, fibrosis of organs (GI tract, kidney, muscles) causing hardening of the organs and loss of function. • - keloid is thickening and swelling of scar tissue due to over accumulation of collagen- may lead to disfiguring but excision is almost followed by recurrence.

35. Vitamin c (ascorbic acid) deficiency leads to scurvy, a disease characterised by degeneration of connective tissue without this vitamin, fibroblasts synthesize defective collagen and the defective fibres are not replaced.This process leads to a general degeneration of connective tissue that becomes pronounced in area where collagen renewal takes place at faster rate. The periodontal ligament that holds the teeth in the socket exhibits relatively high collagen turnover rate;consequently ,this ligament is markedly affected by scurvy ,which leads to loss of teeth. Ascorbic acid is a co-factor for proline hydroxylase ,which is essential for the normal synthesis of collagen.

36. Fibrous Protein: collagen and elastin • form three types of fibres • collagen , reticular and elastic fibres • Collagen – 12 types • Type I – present in bundles in general connective tissue, ligaments, tendon bone • Type II – not in bundles; present in hyaline and elastic cartilage • Type III - reticular fibres • Type IV - in basal lamina • Type VII – form anchoring fibres connecting basal lamina to the underlying connective tissue

37. Classification of connective tissue

38. Connective tissue proper depending on the density of the fibres and the way cells are arranged, they are classified into various types.