ANA 201P - CONNECTIVE TISSUES.pdf

ANA 201P BASIC TISSUES TOPIC: CONNECTIVE TISSUES  LEARNINGS GOAL: CONNECTIVE TISSUE Learning Objectives - At the end of the class, students should be able to: Describe the functions as well as identify the cells commonly found in connective tissue. Identify interst...

ANA 201P BASIC TISSUES TOPIC: CONNECTIVE TISSUES  LEARNINGS GOAL: CONNECTIVE TISSUE Learning Objectives - At the end of the class, students should be able to: Describe the functions as well as identify the cells commonly found in connective tissue. Identify interstitial collagens and elastic fibers Distinguish between elastic, type I collagen, type III (reticular) collagen, and elastic fibers Use knowledge about the physical characteristics of collagen and elastin in explaining the functions of tissue where these molecules occur Identify the types of connective tissue (e.g., dense irregular, dense regular, loose, adipose) and provide examples where different types of connective tissue are found in the body. Identify a basement membrane (or basal lamina) in sections or micrographs where the structure is conspicuously present and understand its functions.  CONNECTIVE TISSUES Supporting/connective tissue is a basic type of tissue of mesodermal origin which provides structural & metabolic support for other tissues and organs throughout the body. It is one of the basic types of tissues in the body (epithelial, connective, muscle & nervous tissues). In addition to structural & mechanical roles, they mediate the exchange of nutrients, metabolites & waste products between tissues and the circulatory system. The connective tissues generally contain blood & lymphatic vessels.  Connective Tissue Epithelium Epithelium Connective Tissue ridge (peg) papilla Connective Tisue Muscle Found throughout the body; most abundant and widely distributed in primary tissues. CT include: Embryonic CT Connective tissue proper Cartilage Bone Blood CONNECTIVE TISSUES  Characteristics: Cells (fibroblasts and others) Mesenchyme as their common tissue of origin Varying degrees of vascularity Fibres and extracellular matrix, consisting of ground substance and fibers  Functions: Binding & support Wound repair / inflammatory response Protection Insulation Transportation Connective Tissue  Extracellular Matrix - Fibers – collagen, elastic, reticular - Ground substance  Cells Resident cells: Fibroblasts Adipocytes Tissue macrophages Migrating cells: Immune cells (lymphocytes) Inflammatory cells (neutrophils & activated macrophages)  Components of Connective Tissue Ground substance – unstructured material that fills the space between cells Fibers – collagen, elastic, reticular Cells – fibroblasts, chondroblasts, osteoblasts, and hematopoietic stem cells  Ground Substance Interstitial (tissue) fluid Glycosaminoglycans (GAGs) Proteoglycans Multidhesive glycoproteins – fibronectin and laminin Functions as a molecular sieve through which nutrients diffuse between blood capillaries and cells  Ground Substance 1.Glycosaminoglycans (GAG) linear (unbranched) polysaccharides, e.g. heparan sulfate, condroitin sulfate, keratan sulfate, hyaluronic acid very hydrophilic due to abundant negative charges (e.g. SO4- groups). except for hyaluronic acid, are usually bound covalently to protein core as part of a proteoglycan 2.Proteoglycans core protein + GAG side chains (like a bottle brush) bind cells, other proteins, and/or ECM components 3. Multiadhesive glycoproteins small glycosylated proteins containing NUMEROUS binding sites to cells, signaling molecules, and other ECM components e.g. fibronectin and laminin: important for adhesion of epithelial cells to the basal lamina via transmembrane integrin receptors. Ground Substance: Proteoglycan Structure Figure 4.6b  Fibers in Connective Tissue Collagen Fibers – most abundant protein in human body (up to 30% dry weight) – multiple types: fibril-forming or fibril-associated (in skin, tendon, cartilage, bone, dentin, blood vessels); cross-linked networks (in all basement membranes) – tough; provides high tensile strength Reticular Fibers – long thin specialized type of collagen (Type III; reticulin) form a delicate supporting framework for many highly cellular organs such as endocrine glands, lymph nodes & liver as well as around smooth cells. Elastic Fibers –thin branched fibers or fenestrated (network) sheets composed of various glycoproteins, including the protein elastin, providing elastic properties to tissues that experience repeated deformation (in skin, blood vessels, lung, bladder)  Major Collagen Fiber Types (out of at least 20) Collagen Type Tissues Function Fibril-forming collagens (these are visible) I Skin, tendon, bone, dentin Resistance to tension (most abundant) II Cartilage, vitreous of eye Resistance to pressure III Skin, muscle, blood vessels, Structural framework and (reticulin) liver, etc. stability Network-forming collagens IV All basement membranes Support and filtration Fibril-associated collagens with interrupted triple helices (FACIT) Associated with type I and II VI, IX Fibril-fibril / fibril-ECM binding fibrils Anchoring filament collagens VII Epithelia Epidermis to basal lamina Collagen fibers viewed by light microscopy H&E Trichrome Reticular (Reticulin) Fibers Form a delicate supporting framework for highly cellular tissues (endocrine glands, lymph nodes, liver, bone marrow, spleen, smooth muscle). Composed mainly of Type III collagen, with a carbohydrate moiety (that reduces Ag+ to metallic sliver = argyrophilic). Thinner than type I collagen (Type III fibrils are 30-40 nm diameter; type I fibrils are ~200 nm diameter)  Reticular Fibers (type III collagen) Made by reticular cells (specialized fibroblasts) and vascular smooth muscle cells  Clinical disorders resulting from defects in collagen synthesis Type Disease Symptoms I Osteogenesis Spontaneous fractures, progressive imperfecta hearing loss, cardiac insufficiency III Ehlers-Danlos Hypermobility of digits, early (type IV) morbidity/mortality from rupture of aorta or intestine multiple Scurvy (lack of vit. C, Ulceration of gums, hemorrhages a cofactor for prolyl and lysyl hydroxylase) Ehlers-Danlos Syndromes A series of genetic diseases with faulty assembly of collagens (lysyl hydroxylase deficiency). Hyperextensible skin and hypermobile joints In some forms (e.g., type IV), weakness in blood vessels or intestines are life threatening.  Elastic Fibers Elastin: occurs as short branching (cross-linked) fibres which form an irregular network throughout the tissue. Rich in glycine and proline, but it contains little or no hydroxyproline and hydroxylysine. Contains desmosine and isodesmosine, which are thought to cross-link the molecules into a network of randomly coiled chains. This cross-linking is responsible for its rubber-like properties. Confers elasticity: present in large amounts in ligaments, lung, skin, bladder, and walls of blood vessels. Marfan Syndrome: defect in elastic fiber synthesis; reduced elasticity in skin and lungs, skeletal defects (bones are longer and thinner than usual), cardiovascular complications (aneurism, valve prolapse)  Elastic and Collagen Fibers elastin stain (“Weigert’s”, “aldehyde fuchsin”, “Verhoeff”): H&E stain: collagen stains orange/pink; elastic fibers stain elastic fibers are purple/black glassy red (generally only visible if in great abundance) collagen fibers stain orange/pink or blue/green depending on other stains used (von Gieson’s or trichrome, respectively)  Ground Substance  Basement Membrane – (Collagen Types IV, VII, and III) Basement membranes are sheets of extracellular matrix proteins located at the interface of parenchyma (epithelia, endothelia, muscle, nerves, adipocytes) and connective tissue / ECM. Main constituents are glycosaminoglycans (heparan sulfate), fibrous proteins (collagen types IV, VII, III), structural glycoproteins fibronectin, laminin and entactin. This is NOT a plasma membrane. Basement membranes vary in thickness Thick Thin -- requires special stain to visualize BM BM BM Intestinal glands, PAS trachea, H&E PAS reacts with carbohydrate-rich molecules such as perlecan, laminin and type III collagen associated with the basement membrane.  Basement Membrane (LM): Three layers in the EM hemidesmosomes basal lamina 1. lamina lucida (LL) or rara 10-50 nm 2. lamina densa (LD) 20-300 nm (type IV collagen) fibroreticular lamina 3. Fibroreticular FL LL LD lamina (FL) merges with underlying CT (type III* and type VII collagen fibrils) Connective tissue (the “basement membrane” is the basal lamina + the fibroreticular lamina) Cell to basal lamina Hemidesmosome Type IV collagen Integrin/laminin Basal lamina to underlying connective tissue: Type IV collagen Type VIII collagen Fibrillin Type III collagen  CELLS IN CONNECTIVE TISSUE 1. Fibroblasts 2. Chondroblasts Fixed 3. Osteoblasts (permanent/ 4. Adipose (fat) cells resident cells) 5. Tissue Macrophages** 6. Mast cells** Free (transient/migrant 7. Lymphocytes & Plasma cells) Cells (differentiated B-cells) ** 8. Leukocytes** (specifically, granulocytes: neutrophils, eosinophils, & basophils) ** derived from hematopoietic stem cells and involved in immune function and inflammation - are the defence cells of the connective tissue. Connective Cell Lineages  Fibroblasts: the most common cells in connective tissue Synthesize and secrete components of the ECM: fibers and ground substance. Active and quiescent stages (when quiescent sometimes called fibrocytes or mature fibroblasts). – Synthesize growth factors Rarely undergo cell division unless tissue is injured, which activates the quiescent cells. Play a major role in the process of wound healing and respond to injury by proliferating and enhanced fiber formation. Adipocytes: predominate in adipose tissue Very active cells with many functions: Triglyceride storage and glucose metabolism (insulin and glucagon receptors) Secretion of many bioactive molecules:  leptin (regulates satiety)  angiotensinogen (blood pressure)  steroids (glucocorticoids & sex hormones),  growth factors (e.g. insulin-like growth factor, tumor necrosis factor )  cytokines (e.g. interleukin-6)  Adipocytes Lipid (fat) droplet Nucleus Capillaries  Brown (Multilocular) Adipose Tissue Present in newborns (and hibernating mammals) and involved in thermoregulation Mitochondria of brown fat cells express uncoupling protein which “short white circuits” the electron transport chain producing HEAT rather than ATP. White adipose: the most common type, provides insulation, serves as an energy store and cushion against mechanical shock for organs. brown Macrophages Monocytes escape from blood vessels into connective tissue where they differentiate into macrophages Function: phagocytosis and antigen presentation Plasma Cells: mature B lymphocytes that constitutively secrete antibodies Black arrows indicate several plasma cells White arrows = Golgi regions Mast Cells Principal function is storage in secretory granules and REGULATED release (degranulation) of histamine and other vasoactive mediators of inflammation. Responsible for the immediate hypersensitivity response characteristic of allergies, asthma and anaphylactic shock. Connective tissue mast cells are found in skin (dermis) and peritoneal cavity; mucosal mast cells are in the mucosa of the digestive and respiratory tracts. Mast Cell Secretion  Neutrophils Enter connective tissue from blood vessels as the “first wave” in acute inflammatory responses Small cells with multi-lobed, heterochromatic nuclei (also known as “polymorphonuclear neutrophils”, “PMNs”, “polys”) Function: anti-bacterial (are phagocytic like marcrophages, but SHORT-lived and NOT antigen presenting)  EMBRYONIC CONNECTIVE TISSUE Mesenchyme – embryonic connective tissue Gel-like ground substance with fibers and star-shaped mesenchymal cells Gives rise to all other connective tissues Found in the embryo  CONNECTIVE TISSUE PROPER Apart from bone, cartilage and blood all mature connective tissues belong to the Connective Tissue Proper. These are further divided into loose connective & dense connective tissues.  Loose Connective Areolar connective tissue A subtype of loose connective tissue. Gel-like matrix with all three connective tissue fibers (collagen fibers, reticular fibers and a few elastic) Fibroblasts, macrophages, mast cells, and some white blood cells Wraps and cushions organs Widely distributed throughout the body  Loose connective tissue: Delicate, vascularized, flexible; facilitates transport of cells and materials (secretion, absorption, immunity) small intestine lamina propria mammary gland intralobular connective tissue Adipose connective tissue Matrix similar to areolar connective tissue with closely packed adipocytes Stores food, provides insulation, support & protection Found under skin, around kidneys, within abdomen, & in breasts Local fat deposits serve nutrient needs of highly active organs Reticular connective tissue Loose ground substance with reticular fibers Reticular cells lie in a fiber network Forms a soft internal skeleton, or stroma, that supports other cell types Found in lymph nodes, bone marrow, & the spleen Reticular connective tissue reticular fibers bile duct portal vein  Dense Connective Tissue Dense Regular Parallel collagen fibers with a few elastic fibers Major cell type is fibroblasts Attaches muscles to bone or to other muscles, & bone to bone Found in tendons, ligaments, & aponeuroses Dense Regular CT (collagenous) Tendon, H & E Dermis of Skin has both Loose and Dense Irregular CT Loose CT sweat gland H&E Dense Irregular Irregularly arranged collagen fibers with some elastic fibers Major cell type is fibroblasts Withstands tension in many directions providing structural strength Found in the dermis, submucosa of the digestive tract, and fibrous organ capsules  Dense Irregular CT Densely packed collagen fibers, often in perpendicular bundles; resists tension in many directions and provides mechanical support. Collagen Fibroblast nucleus Skin dermis, H &E  CARTILAGE A specialized form of connective tissue, Provides – a smooth articular surface at bone ends, – structural support in special areas & – also important in one form of new bone formation. Hyaline cartilage – Amorphous, firm matrix with imperceptible network of collagen fibers – Chondrocytes lie in lacunae – Supports, reinforces, cushions, and resists compression – Forms the costal cartilage – Found in embryonic skeleton, the end of long bones, nose, trachea, and larynx Elastic Cartilage Similar to hyaline cartilage but with more elastic fibers Maintains shape and structure while allowing flexibility Supports external ear (pinna) and the epiglottis  Similar to hyaline cartilage but with more elastic fibers Maintains shape and structure while allowing flexibility Supports external ear (pinna) and the epiglottis Fibrocartilage Cartilage Matrix similar to hyaline cartilage but less firm with thick collagen fibers Provides tensile strength and absorbs compression shock Found in intervertebral discs, the pubic symphysis, and in discs of the knee joint  Matrix similar to hyaline cartilage but less firm with thick collagen fibers Provides tensile strength and absorbs compression shock Found in intervertebral discs, the pubic symphysis, and in discs of the knee joint  BONE (OSSEOUS TISSUE) Hard, calcified matrix with many collagen fibers Osteocytes are found in lacunae and are well vascularized Supports, protects, and provides levers for muscular action Stores calcium, minerals, and fat Marrow inside bones is the site of hematopoiesis  BLOOD Red and white cells in a fluid matrix (plasma) Contained within blood vessels Functions in the transport of respiratory gases, nutrients, and wastes Connective Tissue: Blood