Connective & Adipose Tissue PDF

Categories of connective tissues q Embryonic connective tissues Ø Mesenchymal Ø Mucous q Adult connective tissues q Specialized connective tissues ØConnective tissue proper ØSupporting tissues § Loose (alveolar) § Cartilage...

Categories of connective tissues q Embryonic connective tissues Ø Mesenchymal Ø Mucous q Adult connective tissues q Specialized connective tissues ØConnective tissue proper ØSupporting tissues § Loose (alveolar) § Cartilage § Reticular § Bone § Dense irregular § Blood § Dense regular ü Collagenous ü Elastic § Adipose  CONNECTIVE TISSUES Ø They have the same origin – mesenchyme and the same structure (cells and extracellular matrix) Ø Unlike epithelial cells, connective tissue cells are widely seperated by components of extracellular matrix Cells of connective tissue + extracellular matrix (ECM)  Connective tissue is composed of two elements: Ø Cells Ø Extracelullar matrix (ECM) ü Fibers - collagen fibers, elastic fibers, reticular fibers ü Ground substance Extracellular matrix = Fibers + ground substance Cells of connective tissues (CTs) v Connective tissue proper - fibroblasts, fibrocytes v Adipose tissue – adipoblasts, adipocytes v Cartilage – chondroblasts, chondrocytes v Bone – osteoblasts, osteocytes v Blood – formed elements (erytrocytes, leukocytes)  The function of connective tissues Ø Providing structural support Ø Serving as a medium for exchange Ø Aiding in the defense and protection of the body Ø Forming a site for storage of fat The function of connective tissue proper Ø Forms the capsules of organs and membranes that enveloped the central nervous system (meninges) Ø Forms trabeculae and walls inside several organs – components of the stroma within organs Ø Medium for exchange of metabolic waste, nutrients and oxygen between the blood and many of cells in the body  Cells of Connective Tissue (CT) proper ØThe cells spend all their live in the tissue § Fibroblasts – originate from undifferentiated mesenchymal cells, produce ECM components, can proliferate § Fibrocytes – quiescent fibroblasts Two stages of activity The active cells The quiescent cells ¯ ¯ Fibroblasts Fibrocytes ü Fibroblasts Fibroblasts _ Fibrocytes § the most common cells in connective tissue ü Fibrocytes §branched cytoplasm § smaller than § ovoid, large and pale fibroblasts staining nucleus with § fewer processes nucleolus § smaller, darker, § rich in RER and well elongated nucleus developed Golgi § small amount of § complex RER §cells responsible for the synthesis of ECM components § produce the growth factors ® influence growth and cells differentiation § proliferate when the additional fibroblasts are required  Pericytes and Myofibroblasts Pericytes are a major source of myofibroblasts during fibrosis in multiple organs Ø The cells with features of fibroblasts – produce ECM and smooth muscle cells (SMC) – contain actin and myosin filaments Ø They are observed during wound healing ØThe activity of myofibroblasts is responsible for wound closure after tissue injury – wound contraction The cells which reside in the tissue § Macrophages § Mast cells § Plasma cells § Leukocytes § Adipocytes  f 10 – 30 mm Macrophages ® the Mononuclear Phagocyte System ØMorphological features reflect functional activity of macrophages: § they have pseudopodia, only in macrophages § irregular surface with protrusions – pinocytotic and phagocytic activity § oval or kidney-shaped nucleus located centrally § well-developed Golgi complex, many lysosomes, prominent rough endoplasmic reticulum (RER) ü Macrophages derive from monocytes of blood ü Monocytes cross the wall of venules and capillaries to penetrate the connective tissue ü They mature and acquire morphological features of macrophages Ø Macrophages are long-living cells, can proliferate locally and may survive for months in tissues. Ø The cells are distributed throughout the body, and in certain regions have special name: § histocytes – the connective tissue proper § Kupffer cells – the liver § microglia cells – the central nervous system § osteoclasts – the bone § dust cells in the lung Macrophages function Ø phagocytosis of foreign substances and bacteria Ø antigen processing and presentation to other cells (Antigen Presenting Cells – APC) Ø secretion of cytokines and other molecules § enzymes, e.g. collagenase Ø removing cell debris and damaged extracellular components Ø Macrophages when stimulated § may increase in size and are arrangement in clusters forming epithelioid cells; § may fuse to form multinuclear giant cells Ø Epithelioid cells and giant cells are found in pathological conditions. Multinuclear giant cells  Mast cells derive from stem cells of the bone marrow f 10 – 13 mm Ø Oval to round connective tissue cells Ø The cytoplasm is filled with basophilic secretory granules Ø Small, spherical nucleus, situated centrally v Secretory membrane-bound granules of mast cells § they contain biological active substances: ü histamine - promotes an increase in vascular permeability ü heparin - (sulfated glycosaminoglycan is blood anticoagulant) ü neutral proteases ü chemotactic factor for eosinophils and neutrophils § substances not stored in the granules: ü leukotriens (C4, D4, E4), tromboxanes, platelet-activating factor, interleukins…..  Mast cells q The connective tissue mast cells § skin and peritoneal cavity q The mucosal mast cells § the connective tissue of the intestinal mucosa and lungs vThe surface of mast cells contains specific receptors for immunoglobulin E (IgE), a type of immunoglobulin produced by plasma cells  Mast cells secretion (degranulation) 1. Initial contact with alergen with B lymphocytes 2. IgE molecules production by plasma cells 3. IgE molecules are bound to the surface receptors 4 After a second exposure to an antigen (eg. bee venom) IgE molecules bound to surface receptors are cross-linked by the antigen 5. Intracellular fusion of specific granules and exocytosis of their content The degranulation process does not damage the cell, which synthesize new granules. Release of the chemical mediators stored in mast cells promotes the allergic reactions. The release of histamine and leukotriens from mast cells increase capillary permeability, Resulting in an exceses accumulation of extracellular fluid and, thus, gross swelling (edema)  Leukocytes or white blood cells Ø the wandering cells of the connective tissue Ø they migrate through the walls of capillaries and postcapillary venules from the blood into connective tissue (diapedesis) Diapedesis v Granulocytes v B and T Lymphocytes  Plasma cells B lymphocyte + antigen ®B lymphoblast (mitotic division) ®B lymphocyte + plasma cell Ø large, ovoid cells with basophilic cytoplasm, very well developed RER Ø the Golgi complex occupy pale region in histological slides Ø spherical nucleus, placed excentrically containing compact, coarse heterochromatin and lighter areas Ø Average of plasma cells live is short, 10 – 20 days. Ø B lymphocyte ® plasma cell ® synthesis of immunoglobulins (antibodies)  Adipose cells Ø Adipose cells, adipocytes, fat cells § the connective tissue cells for storage of neutral fats or for the production of heat.  Fibroblasts − The extracellular matrix Ø Fibers Ø Ground substance § Collagen fibers § Glycosaminoglycans (GAGs) § Elastic fibers § Proteoglicans § Reticular fibers § Multiadhesive glycoproteins Fibers The connective tissue fibers are formed by proteins that polymerize into elongated structures. v Collagen fibers ü are formed by protein collagen ü the collagen is the most abundance protein in the human body (30% of dry weight) ü the collagens belong to a family of more than 25 members Ø The cell type responsible for collagen synthesis § fibroblasts, chondrocytes, osteoblasts § odontoblasts § endothelial cells § vascular smooth muscle cells  Collagen fibers ØThe collagen profile the principal amino acids – glycine (33.5%), proline (12%), hydroxyproline (10%) amino acids that are characteristic of the collagen – hydroxyproline and hydroxylysine Collagen types v Type I - the abundant: skin, tendon, bone, dentin, cementum v Type II - cartilage, vitreous body v Type III - reticular fibers: skin, muscle, blood vessels v Type IV - all basement membranes (lamina densa of the basal lamina) v Type V - fetal tissue, skin, bone, placenta v Type VII – epithelia – anchors skin epidermal basal lamina to underlying stroma (anchoring fibrils) Collagen is a protein polymer composed of monomeric units of the protein Tropocollagen Tropocollagen Three a chains § elongated protein 280 nm in length and 1.5 nm in width Structural arrangement of collagen: 1) Collagen is arranged into microfibrils. 2) Microfibrils are arranged into fibrils. 3) Fibrils are grouped into a fiber. 4) Fibers are grouped into a collagen bundle H-E Alanin blue  Collagen synthesis Fibroblast v Procollagen (3a chains) synthesis § Registration peptides on both amino-terminal and carboxy-terminal ends § precursor of tropocollagen v Hydroxylation of proline and lysine § peptidyl proline hydroxylase § peptidyl lysine hydroxylase Co-factors: O2, Fe, vit. C v Glycosylation of hydroxylysine § transferases Mn v Removing of registration peptides § procollagen peptidases § tropocollagen v Formation of covalent cross- links between tropocollagen molecules § lysyl oxidase Cu and O2 ions Vitamin C (ascorbic acid) deficiency leads to the scurvy, disease characterized by the degeneration of connective tissue. Scurvy characterized by bledding gums and loose teeth among other symptoms Vitamin C deficiency ® abnormal hydroxylation of procollagen ® synthesis of defective collagen  Reticular fibers Ø consist mainly of type III collagen Ø extremely thin Ø they form extensive network in certain organs Ø stain black by impregnation with silver salts – agyrophylic fibers Ø Localization § are particularly abundant in smooth muscle tissue § endoneurium § spleen, lymph nodes, bone marrow § constitute a network around the cells of parenchymal organ, eg. liver, endocrine glands § the wall of arteries Silver salts Reticular fibers  Elastic fibers Ø Elastin – the main component + microfibrills Ø Precursor of elastin - proelastin v Elastoblasts Ø Elastin is hydrolyzed by pancreatic elastase § Fibroblasts Ø Elastin is rich in glycin and proline § Chondrocytes Ø Contains two unusual amino acids – desmosine § Vascular SMC and isodesmosine formed between four lysines § Endothelial cells Ø has rubberlike qualities They are composed of an amorphous elastin surrounded by a microfibrillar component consisting of fibrillin Orcein Resorcin--fuchsin  The elastic fibers system Ø Oxytalan fibers Ø Elaunin fibers Ø Elastic fibers § zonule fibers of the eye § around sweet glands § the wall of large arteries § dermis § dermis § connective tissues q do not contain elastin q irregular deposits of q elastin located q consist of a bundle of 10nm elastin between centrally and thin microfibrils composed of the microfibrils sheath of microfibrils glycoproteins: q the most numerous fibromodulin I and II, component of and fibrillin. the system Microfibrils Elastin  Ground substance Ø highly hydrated, colorless and transparent complex mixture of macromolecules Ø it fills the space between cells and fibers Ø it is viscous and acts as lubricant and barrier to the penetration of invaders v Glycosaminoglycans (GAGs) v Proteoglycans v Multiadhesive glycoproteins  Glycosaminoglycans (GAGs) Ø called mucopolysaccharides - dermatan sulfate - chondroitin sulfate - keratan sulfate - heparan sulfate - hyaluronic acid Ø with the exception of hyaluronic acid GAGs are bound covalently to a protein core, forming proteoglycans Ø with the exception of hyaluronic acid all other GAGs are sulfated Ø GAGs are intensely hydrophilic and act as polyanions  Proteoglycan aggregate Proteoglycan monomer Core protein Proteoglycans Link Ø are composed of a protein core associated protein GAGs with the four main GAGs (without hyaluronic acid) – monomer Hyaluronan Ø proteoglycan (monomer) is Type I collagen three-dimensional structure (can be fibril pictured as test tube brush) Ø Monomers bind to hyaluronan forming Hyaluronan giant macromolecules – proteoglycan aggregates q Proteoglycans of extracellular matrix (ECM) Mucopolysaccharidoses are a group of metabolic § aggrecan – the most important, the disorders caused by the absence or malfunctioning dominant in cartilage of lysosome enzymes needed to break down § syndecan, fibroglycan proteoglycans v Proteoglycans are degradated by several cell types (lysosomal enzymes). The lack of lysosomal enzymes causes several disorders in humans Some functions of glycosaminoglycans and proteoglycans  Multiadhesive glycoproteins Ø contain protein moiety with carbohydrates Ø play an important role in the interaction between neighboring adult and embryonic cells Ø play role in the adhesion of cells to their substrate v Fibronectin § the product of fibroblasts and epithelial cells Protein § has sites to bind cells, collagen and GAGs, the interactions help to mediate normal cell adhesion and migration v Laminin § the adhesion of epithelial cells to basal lamina v Matrix receptors are cell-surface molecules. Cells bind to collagen, fibronectin, laminin § Integrins – transmembrane linker proteins, interact with the cytoskeleton v Intracellular proteins – the interaction between integrins, ECM, cytoskeleton elements § Paxilin § Vinculin § Talin  Embryonic connective tissues Mesenchyme Ø The precursor embryonic tissue for all types of connective tissue Ø Stellate undifferentiated cells and ground substance Ø The lack of fibers Ø Under specific stimuli the cells differentiate into the cells of connective tissue - fibroblasts, adipoblasts, chondroblasts, osteoblasts, blood cells  Embryonic connective tissues Mucous Ø Mucous connective tissue § has a abundance of ground substance rich in hyaluronic acid § is jellylike tissue containing very few collagen fibers type I and type III § the cells – mainly fibroblasts § is found in umbilical cord and is referred to as Wharton’s jelly § is found in the pulp of young teeth Umbilical cord  ADULT CONNECTIVE TISSUES THE CONNECTIVE TISSUE PROPER Ø Loose connective tissue § the very common type of connective tissue § fills spaces between groups of muscle cells, supports epithelial tissue, forms layer around lymphatic and blood vessels. § is found in dermis, hypodermis, mucous membranes § has delicate consistency, it is flexible, well vascularized, not very resistant to stress Ø Reticular connective tissue § consists of reticular fibers (type III collagen) and specialized fibroblasts named reticular cells § reticular tissue creates the special microenvironment for hematopoietic organs and lymphoid organs (bone marrow, lymph nodes, spleen), and envelops certain cells (eg. hepatocytes) Reticular cell Reticular fibers  Dense connective tissue (CT) Ø is adapted to offer resistance and protection Ø there are fewer cells than loose connective tissue and high amount of collagen fibers Ø Dense irregular CT § the collagen fibers are arranged in bundles without a definite orientation § provide resistance to stress from all directions § is found in dermis Collagen fibers Fibrocytes Ø Dense regular CT (collageneous tissue) § the collagen bundles are arranged in the definite pattern § it is found in tendons Tendon § the collagen fibers have parallel, closely packed bundles of collagen separated by a small quantity of intracellular ground substance § fibrocytes (tendinocytes) have elongated nuclei parallel to the fibers § the cytoplasm of fibroblasts stains the same color as the fibers Nuclei of fibrocytes Collagen fibers Ø Dense regular CT (elastic) § is composed of bundles of thick parallel elastic fibers § the spaces between the fibers are occupied by thin collagen fibers and flattened fibroblasts § is found in yellow ligaments of the vertebral column, suspensory ligament of the penis Aorta fibrocytes Elastic laminae beetwen them vascular smooth muscle cells Adipose tissue  Ø Special type of the connective tissue with predomination of adipose cells (adipocytes, fat cells) ü Adipocytes § as isolated cells, in small aggregates (adipose tissue) Functions: Adipose tissue is found in a variety of places: 1] the hypodermis 1] stores energy 2] surrounding and protecting certain organs 2] contributes to the thermal 3] the medullary cavity of long bones insulation of the body Adipose tissue 3] protects delicate organs from mechanical trauma v Unilocular adipose tissue v Multilocular adipose tissue (common or yelow) (brown)  Unilocular (common or yelow) adipose tissue Ø The color varies from white to dark yelow (depends on diet – carotenoids) Ø It is found throughout the human body except § eyelids, the penis, the scrotum, the entire auricle of the external ear (without the lobule) ü The distribution is determined by age and sex § in the newborn has uniform thickness in the body § its distribution is partly regulated by sex hormones and adrenocortical hormones (different distribution in male and female body) Spherical, isolated cell Signet ring cells Polyhedral cells in adipose tissue Lipid droplet Sudan III Lipids are removed in routine Nucleus histological techniques Cytoplasm  Unilocular (common or yelow) adipose tissue Ø Cytoplasm f 50 – 150 mm § Golgi complex § mitochondria § poorly developed RER § SER § free polyribosomes § pinocytotic vesicles Basal lamina Vimentin intermediate filament v Adipose tissue ü is richly vascularized  Unilocular (common or yelow) adipose tissue Ø Large depot of energy for organism Ø Lipids in adipose cells – triglycerides, glycerol Ø Adipose cells can synthesize fatty acids from glucose ® insulin Ø Metabolism of adipose tissue is regulated by hormones § The autonomic nervous system plays important role in mobilization of fats Adipose tissue as a secretory organ Ø enzymes – lipoprotein lipase Ø leptin – peptide hormone (ob gene, acts on receptors in the hypothalamus of the brain where it inhibits appetite) Ø adiponectin – protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism Ø adipsin - serine protease that is secreted by adipocytes into the bloodstream. Ø TNFa (Tumor Necrosis Factor a) Ø source of estrogens (estrone) in postmenopausal women (cytochrome P450 aromatase)  Obesity in adults The disorders of energy, when energy intake exceeds energy expenditure Obesity in adults Ø Adipose tissue (the largest organ in the body) § in men of normal weight represents 15 – 20% of the body § in woman of normal weight = 20 - 25% of the body q Hypertrophic obesity q Hyperplastic obesity q Genetic influences There is no question that profound genetic influences affect weight regulation. Leptin (its discovery in 1994), an appetite-suppressing hormone secreted by adipocytes. Leptin receptors - in neurons of the hypothalamus (target organ). Complex leptin/receptor: the appetite-stimulating neuropeptide Y (NPY) is suppressed by leptin. Role of obesity in disease pathogenesis Multilocular adipose tissue (brown fat) Ø Multilocular tissue cells are polygonal and smaller than unilocular adipose cells ØThe cytoplasm contains § great number of lipid droplets of various sizes § spherical and central nucleus § numerous mitochondria with abundant long cristae (containing colored cytochromes) ØThe cells receive direct sympathetic innervation ØThe tissue is rich in capillaries  Distribution of multilocular adipose tissue Ø In humans the tissue is important mainly in the first postnatal life (produces heat and protects the newborn against cold) Ø It is greatly reduced in adulthood Ø The tissue is more abundant in hibernating animals – hibernating gland In human newborn the multilocular adipose tissue constitutes 2 - 5% of the body weight v Mainly around the shoulder blades and kidneys  Function of the multilocular adipose tissue ØThe main function is to produce heat ØThe production is stimulated when human newborn or animals are exposed to the cold environment Ø Nerve impulses release epinephrine ® the stimulation of lipase in adipocytes ® the release of fatty acid, that are metabolized ® heat production (temperature of tissue is elevated) Ø Mitochondria of multilocular adipocytes contain transmembrane protein – thermogenin (known as uncoupling protein 1, or UCP1) ØThe energy is not used to synthesize ATP but is dissipated as heat Ø Warmed blood circulates throughout the body Slides v Mesenchyme Embryo head ØMucous tissue The umbilical cord - Warthon’s jelly Vein Arteries  ü Nuclei of fibrocytes and others cells ØLoose connective tissue ü Collagen fibers ü Elastic fibers Collagen fibers Elastic fibers ØDense connective tissue v Dense regular CT v Dense irregular CT Tendon Skin ØAdipose tissue Sudan III Signet ring cells