Connective Tissues PDF

Connective tissues  Conective tissue Structure – connective tissue consists of: 1) connective tissue CELLS are embedded in 2) abundant extracellular matrix (ECM) (consisting of ground substance and fibers)  Extracellular matrix (ECM) The extracellular matrix, composed...

Connective tissues  Conective tissue Structure – connective tissue consists of: 1) connective tissue CELLS are embedded in 2) abundant extracellular matrix (ECM) (consisting of ground substance and fibers)  Extracellular matrix (ECM) The extracellular matrix, composed of ground substance and fibers, resists compressive and stretching forces. Extracellular matrix consist of : 1. Ground substance:  proteoglycans  glycosaminoglycans (GAGs)  multiadhesive glycoproteins 2. Fibres:  collagen (including reticular fibers)  elastic fibres Figure: Co – bundles of collagen fibers, EF – elastic fibers, GS – ground substance  Ground substance: GAGs and proteoglycans Glycosaminoglycans (GAGs), proteoglycans (PGs) and multiadhesive glycoproteins are components of ground substance of ECM GAGs are unbranched, rod-like polysaccharides, nagatively charged, have capability of binding large quantities of water; resistant for compression; most of GAGs, together with protein molecules, form PGs. PGs are macromolecules with a protein core and GAGs attached to the core. Many PGs attach to hyaluronic acid (hyaluronian) particles (they are very long polymers – up to 20 m long) and form large aggregates. Ground substance: ADHESIVE GLYCOPROTEINS  Adhesive glycoproteins are multifunctional molecules whose domains bind to components of the extracellular matrix (ECM) and to receptors on the CELL surface, thereby promoting adhesion between the cell and the matrix (cell-to-ECM interaction).  Adhesive glycoproteins are of various types.  Some are generally dispersed throughout the extracellular matrix, such as fibronectin.  Some are localized preferentially to the basal lamina, such as laminin, or to cartilage and bone, such as chondronectin and osteonectin, respectively.  Fibers: COLLAGEN FIBERS Gartner, TEXTBOOK OF HISTOLOGY, 2017 Fibers of the extracellular matrix are collagen (and reticular) and elastic fibers. Collagen fibers are non-elastic and possess great tensile strength. Each fiber is composed of fine subunits, fibrils, and these of the tropocollagen molecules. At least 25 different types of collagen fibers are known. The major collagen types are: type I: in connective tissue proper, bone, dentin, and cementum, type II: in hyaline and elastic cartilages, type III: reticular fibers, types IV and VII: in basement membranes.  Components of type I The type I collagen fibril contains collagen fibril small amounts of other collagen types such as types II, III, V, and XI. The core of the fibril contains collagen types V and XI, which help initiate the assembly of the type I Pawlina, Ross: ed. 8e fibril. Histology, Fully mature collagen fibers are usually associated with collagen Junqueira Basic Histology 15th molecules of the FACIT family (Fibril Associated Collagens with Interrupted Triple helices) that reside on their surfaces – types XII and XIV for collagen type I. These collagens contribute to the three- dimensional organization of fibers within the ECM. Four categories of collagen: fibril-forming, fibril-associated, network-forming, and transmembrane collagens Collagen type Main sites Special features Type I (fibril Bones, tendons, organ Most abundant, Typical fibers forming) capsules, dentin, dermis (67 nm banding) Type II (fibril Hyaline and elastic cartilage Resistance to pressure forming) Type III (fibril Lymphatic system, lung, Very thin fibrils (35 nm). forming), reticular spleen, liver, skin, Often associated with type I fibers cardiovascular system collagen Type IV (network Basal lamina associated Amorphous (non-fibrous) forming) mainly with epithelial Type V (fibril Dermis, tendon, ligaments, Assoc. with type I collagen forming) capsules of organs, bone, placenta Type VII (network Junction of epidermis and Forms anchoring fibrils forming) dermis Type IX (fibril Cartilage Assoc. with type II collagen -associated) Type XVII (collagen- Hemidesmosomes Transmembrane protein like protein) Leslie P. Gartner: Textbook of Histology, fourth edition, 2015  Fibers: ELASTIC FIBERS Gartner, TEXTBOOK OF HISTOLOGY, 2017 An elastic fiber, showing Elastic fibers of aorta – Streching a network of microfibrils surrounding scanning electron elastin molecules the amorphous elastin microscope (SEM) image Elastic fibers are composed of fibrillin, which forms a network of microfibrils, layered over a larger mass of cross-linked elastin. These fibers are highly elastic and may be stretched to 150% of their resting length without breaking. Cells of Connective Tissue Proper The cells in CT are grouped into two categories, fixed (resident) cells and transient cells. Mesenchymal Fixed cells are a resident population of cells stem cell that have developed and remain in place within the connective tissue, where they perform their functions. The fixed cells are a stable and long-lived population that includes: fibroblasts, adipose cells, pericytes, and macrophages. Transient cells (free or wandering cells) originate mainly in the bone marrow and circulate in the bloodstream. Upon receiving the proper stimulus or signal, these cells leave the bloodstream and migrate into the connective tissue to perform their specific functions. Because most of these motile cells are usually short-lived, they must be replaced continually from a large population of stem cells. Transient cells include: plasma cells, mast cells, lymphocytes, granulocytes, monocytes, and macrophages. Note that some macrophages are fixed whereas others are Gartner, TEXTBOOK OF HISTOLOGY, 2017 transient. http://www.sciencephoto.com/media/80294/enlarge Fibroblasts Fibroblasts i cell culture; SEM the most common cell type in CT proper - the only permanent resident cell, however, able to Junqueira Basic Histology 15th ed. move long, branching, spindle-shaped cells, having features of both synthesizing and contractile cells: – abundant RER – well-developed actin cytoskeleton actively produce and secrete the ground substance and fibers AND ENZYMES which degrade them  Produce fibers and ground substance of Fibroblasts the matrix Quiescent cells - Active fibroblasts Fibrocytes Junqueira, Basic Histology text & atlas, 2005  FIBROBLAST FIBROCYTE Active Quiescent Basophilic activation Acidophilic cytoplasm RER, GA – well developed Small amount Big nucleus, prominent nucleolus Small, dark Relaxed chromatin Condensed chromatin Bigger than fibrocytes Smaller and thinner than fibroblasts Many cell projections Only few projections 2 physiological states Basic Histology, 10th ed.  Macrophages Macrophages(histiocytes) (histiocytes) Functions: 1. Phagocytosis – removing and degradation of foreign, destroyed or unnecessary cells and ECM macromolecules 2. Antigen presentation to lymphocytes (APC, antigen-presenting cell) 3. Secretion of cytokines, such as: IL-1, TNF MORPHOLOGY big cells (15-20 um), kidney-shaped nucleus, well-developed RER and AG, numerous lysosomes. Junqueira Basic Histology 15th ed. E http://pathology.wustl.edu/research/microscopy.php  Cells which make up the Mononuclear Phagocytes System Once made in the bone marrow, these cells circulate for a short time in the blood. At this stage they are called monocytes. They exit blood, mature, differentiate and specialise in respective host tissues. PLEASE, NOTICE: dendritic cells do NOT belong to MPS although they are weak phagocytes In various tissues macrophages are termed differently: Histiocytes connective tissue proper Kupffer cells liver Microglia central nervous system Septal/Alveolar macrophages in the wall of lung alveoli Dust cells inside the lumen of lung alveoli  Mast cells (mastocytes or labrocytes) The most numerous in loose CT contain basophilic granules rich in histamine, heparin, neutral proteases (tryptase, chymase) Secrete proinflammatory factors play a key role in allergy, anaphylaxis, wound healing express a high-affinity receptor (FcεRI) for IgE Basic Histology, Pawlina, Ross: 2004 Histology, 8e Human mast cell (ME), well-developed GA  Two populations of mast cells Connective tissue mast cells (CTMCs) – migrate and locate around blood vessels and nerve endings of the connective tissue Mucosa mast cells (MMCs) – associated with T cells, predominantly in the lamina propria of the mucosae of the intestine and lungs CTMCs are T cell-independent in contrast to MMCs, whose activities are T cel-dependent. The mast cell cointains cytoplasmic granules with vasoactive mediators: histamine, heparin and chemotactic mediators to attract monocytes, neutrophils, and eosinophils circulating in blood to the site of mast cell activation Plasma cells: - derived from blood B-lymphocytes - responsible for the synthesis of antibodies large ovoid cells rich in RER with dilated cisternae Junqueira, Basic Histology text & atlas, 2005 containing antibodies cytoplasm very basophilic clock-faced spherical nucleus - eccentrically placed appearance euchromatin and heterochromatin of nucleus dispersed throughout the nucleus White adipose tissue, SEM Reticular fibers found around adipocytes H. Hiller, Anatomia, Muenster The development of a fat cell. Adipocytes arise from mesenchymall stem cells and perhaps from fibroblasts. A precursor cell is converted into a mature fat cell by the accumulation and coalescence of lipid droplets. The process is at least partly reversible (arrows). The cells in the early and intermediate stages can divide, but the mature adipocytes cannot. Adipocytes are surrounded by basal lamina.  Comparison of WHITE and BROWN adipose tissue – structure WHITE ADIPOCYTES BROWN ADIPOCYTES large (50-150 um in diameter) considerable volume of cytoplasm look like a signet ring – a large fat droplet contain multiple lipid droplets of varying size a scant ring of cytoplasm around the lipid nuclei are round and almost centrally droplet contains AG and mitochondria located nuclei are flattened and eccentric polygonal in shape increased number of mitochondria  Comparison of WHITE and BROWN adipose tissue – functions White adipose tissue (WAT) Brown adipose tissue (BAT) Synthesis, storage, and release of triglycerides Heat production – due to the uncoupling of Release of hormones/cytokines oxidative phosphorylation in mitochondria Protection (cold, mechanical, physical) by thermogenin Forms body shape of a given sex Brown fat is of particular importance in neonates, small mammals in cold environments, and animals that hibernate  Adipokines are biologically active molecules (hormones, cytokines, growth factors and other) secreted by adipose tissue Adipokines which act in autocrine, paracrine and endocrine way regulate adipogenesis, adipocyte metabolism in cells and the general volume of adipose tissue within the body (obesity) immune cell migration into adipose tissue via autocrine and paracrine signalling have endocrine/systemic effects on appetite and satiety control, regulation of energy expenditure and activity, affect tissues’ sensitivity to insulin in liver, muscle and fat as well as insulin secretion in pancreatic β-cells. Regulate hematogenesis, osteogenesis, angiogenesis, clotting E Blüher M.: „Clinical Relevance of Adipokines”. Diabetes Metab J. 2012; 36(5): 317–327  Functions of adipokines - leptin (satiety hormon) – inhibits hunger - adiponektin – antinflammatory, prevents arteriosclerosis and insulin resistance - resistin – decreases the cellular sensitivity to insulin (diabetes type II) - chemerin – multifunctional adipokine with established roles in inflammation, adipogenesis and glucose homeostasis - TNF – induces the deficiency of insulin receptors, high concentration in obese individuals - IL-6 – induces the insulin resistance - Plasminogen activator inhibitor (serpin) – an inhibitor of fibrinolysis, the physiological process that degrades blood clots. E  Connective tissue Basic type of tissue that provides structural and metabolic support for other tissues and organs. Embryonic connective tissues Mesenchymal connective tissue Mucous connective tissue (Wharton jelly) Connective tissue proper Loose connective tissue Dense connective tissue Irregular OR Regular (collagenous or elastic) Specialized connective tissue Reticular tissue Cartilage Bone Adipose (white or brown) tissue Bone marrow Fluid connective tissues: blood and lymph Gartner, TEXTBOOK OF HISTOLOGY, 2017 Practical part  Embryonic connective tissue: mesenchymal tissue SLIDE No. 001  Embryonic connective tissue: mucoid (mucous) connective tissue Matrix of the fetal umbilical cord Umbilical cord, HE staining Slide 096 Fibroblasts  Loose (areolar) connective tissue 1. Fixed cells: fibroblasts, macrophages, mast cells, adipocytes and some undifferentiated cells 2. Abundant ground substance 3. Collagen, reticular and elastic fibers 002 SLIDE Collagen fibers Elastic fibers Blood vessels with erythrocytes Loose connective tissue of the MESENTERY Dense regular collagenous connective tissue: longitudinal section SLIDE No. 004 Parallel bundles of collagen Fibrocytes (tendinocytes) nuclei TENDON longitudinal section Dense regular collagenous connective tissue: cross section SLIDE No. 015 Fibrocytes (tendinocytes) nuclei TENDON cross section Loose and dense irregular connective tissue of the DERMIS (skin) Thick bundles of SKIN collagen fibers 1. Epidermis 2. Papillary layer (dermis) 3. Reticular layer (dermis) SLIDE No. 063 White (unilocular) adipose tissue (=WAT) SLIDE No. 003 Unilocular adipocytes 1. White adipose tissue. 2. Small lipid droplets in cytoplasm fuse to form one, large droplet 3. Lipid storage and mobilization 4. Adipokines secretion Arteriole and venula Capilarries Eccentrically located nuclei of adipocytes Single, large lipid droplet  Brown (multilocular) adipose tissue Multilocular adipocytes SLIDE No. 075 1. Thermogenic – energy liberated as heat (numerous mitochondria) 2. Mitochondrial enzymes uncoupled to ATP synthesis (thermogenin) 3. Superficial deposits: posterior triangle, intercapsular; deeper deposits: retrosternal, vertebral column and around kidneys Capilarries and Centrally erythrocytes located nuclei of adipocytes  HE staining CaseCenter; Kieżun J, Krazinski B, Koprowicz- Wielguszewska A. MALLORY staining