Connective tissue
Part 1
• Connective tissue consists of cells and an extracellular
matrix (ECM). • ECM includes structural (fibers) and the ground substance. • The functions are reflected: the types of cells fibers present within the tissue the composition of the ground substance in the ECM.
Classification of connective tissue is based on the composition and organization of its cellular and extracellular components and on its functions.
Connective tissue Connective tissue proper
Cartilage
Loose
Dense
Hyaline
Areolar
Dense regular
Elastic
Adipose
Reticular
Dense irregular
Elastic
Fibrocartilage
Bone
Blood
Connective tissue Connective tissue proper
Cartilage
Loose
Dense
Hyaline
Areolar
Dense regular
Elastic
Adipose
Reticular
Dense irregular
Elastic
Fibrocartilage
Bone
Blood
Loose connective tissue is characterized by loosely arranged fibers and abundant cells of various types.
The ground substance is abundant and occupies more volume than the fibers do.
Dense irregular connective tissue is characterized by abundant fibers and few cells.
Dense irregular connective tissue contains mostly collagen fibers. Cells are sparse and are typically of a single type, the fibroblast. This tissue also contains relatively little ground substance. Because of its high proportion of collagen fibers, dense irregular connective tissue provides significant strength.
Dense Regular CT = tendon
Parallel bundles of collagen (pink) with aligned fibroblasts
Connective tissue fibers are of three principal types. • Collagen fibers • Reticular fibers • Elastic fibers
Collagen synthesis and organization A single collagen molecule consists of three polypeptides known as chains.
The chains intertwine, forming a right-handed triple helix
Collagen fiber formation involves events that occur both within and outside the fibroblast. The production of fibrillar involves a series of events within the fibroblast that leads to production of procollagen, the precursor of the collagen molecule.
Formation of collagen fibrils (fibrillogenesis) involves extracellular events.
Elastic fibers are typically thinner than collagen fibers and are arranged in a branching pattern to form a three dimensional network Elastin is synthesized by fibroblasts and vascular smooth muscle cells.
Elastin (72 kilodaltons) is a protein that, like collagen, is rich in proline and glycine.
Elastic material is a major extracellular substance in vertebral ligaments, larynx, and elastic arteries.
Reticular fibers provide a supporting framework for the cellular constituents of various tissues and organs.
Reticular fibers are composed of type III collagen.
Reticular fibers also function as a supporting stroma in hemopoietic and lymphatic tissues
In addition to fibers, the ECM contains a variety of proteoglycans (e.g., aggrecan, syndecan); multiadhesive glycoproteins (such as fibronectin and laminin); glycosaminoglycans (e.g., dermatan sulfate, keratan sulfate, hyaluronan). The last three groups of molecules constitute the ground substance.
Ground substance is the part of the extracellular matrix that occupies the spaces between the cells and fibers; it consists of glycosaminoglycans
Glycosaminoglycan Structure
Proteoglycan A schematic representation of a proteoglycan. It consists of a protein core molecule bound with many different types of Glycosaminoglycans (GAGs). For example, a proteoglycan from cartilage matrix can have 30 keratan sulfate and 100 chondroitin sulfate GAG chains.
Aggregan – the largest extracellular proteoglycan complex Aggregan – the largest extracellular proteoglycan complex
Core hyaluronic acid (GAG in blue) complexed with numerous proteoglycans .
Core hyaluronic acid (GAG in blue) complexed with numerous proteoglycans .
Connective tissue cells can be resident or wandering.
The cells that make up the resident cell population are relatively stable; they typically exhibit little movement and can be regarded as permanent residents of the tissue. These resident cells include fibroblasts and a closely related cell type, the myofibroblast, macrophages, adipocytes, mast cells, adult stem cells Pericytes.
Fibroblasts are responsible for the synthesis of collagen, elastic and reticular fibers, and the complex carbohydrates of the ground substance
Adipocytes (fat cells) The adipocyte is a connective tissue cell specialized to store neutral fat and produce a variety of hormones. When they accumulate in large numbers, they are called adipose tissue.
Macrophages are phagocytotic cells derived from monocytes.
Niches of adult stem cells called mesenchymal stem cells are found in loose connective tissue of the adult. These cells give rise to differentiated cells that function in the repair and formation of new tissue such as in wound healing and in the development of new blood vessels (neovascularization).
Pericytes, also called adventitial cells or perivascular cells, are found around capillaries and venules Pericytes are surrounded by basal lamina material that is continuous with the basal lamina of the capillary endothelium; thus, they are not truly located in the connective tissue compartment
Mast cells develop in bone marrow and differentiate in connective tissue. Most mast cell secretory products (mediators of inflammation) are stored in granules and are released at the time of mast cell activation.
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Histamine is a biogenic amine that increases the permeability of small blood vessels, causing edema in the surrounding tissue and a skin reaction demonstrated by an itching sensation. In addition, it increases mucus production in the bronchial tree and prompts contraction of smooth muscle in the pulmonary airways.
Heparin is a sulfated GAG that is an anticoagulant. Its expression is limited essentially to the granules of mast cells and basophils.
Leukotrienes are released by mast cells during anaphylaxis Similar to histamine, leukotrienes trigger prolonged constriction of smooth muscle in the pulmonary airways, causing bronchospasm.
Eosinophil chemotactic factor (ECF) and neutrophil chemotactic factor (NCF), which attract eosinophils and neutrophils, respectively, to the site of inflammation. The secretions of eosinophils counteract the effects of the histamine and leukotriens.
The wandering cell population or transient cell population consists primarily of cells that have migrated into the tissue from the blood in response to specific stimuli. These include lymphocytes, plasma cells, neutrophils, eosinophils, basophils, monocytes.
Lymphocytes are principally involved in immune responses. Lymphocytes are a heterogeneous population of at least three major functional cell types: 1. T cells, 2. B cells, and 3. natural killer (NK) cells.
Plasma cells are antibodyproducing cells derived from B lymphocytes.
Eosinophils, monocytes, and neutrophils are also observed in connective tissue.
Part 2
Connective tissue
Connective tissue proper
Cartilage
Loose
Dense
Hyaline
Areolar
Dense regular
Elastic
Adipose
Reticular
Dense irregular
Elastic
Fibrocartilage
Bone
Blood
Three types of cartilage that differ in appearance and mechanical properties are distinguished on the basis of characteristics of their matrix
Cartilage is a form of connective tissue composed of cells called chondrocytes and a highly specialized extracellular matrix. More than 95% of cartilage volume consists of extracellular matrix Hyaline cartilage provides a model for the developing skeleton of the fetus.
Hyaline cartilage matrix is produced by chondrocytes and contains three major classes of molecules. Collagen molecules. Collagen is the major matrix protein. Type II collagen Proteoglycans. The ground substance of hyaline cartilage contains three kinds of glycosaminoglycans: hyaluronan, chondroitin sulfate keratan sulfate.
Cartilage is an avascular tissue. The large ratio of glycosaminoglycans (GAGs) to type II collagen fibers in the cartilage matrix permits diffusion of substances between blood vessels in the surrounding connective tissue and the chondrocytes
A firmly attached connective tissue, the perichondrium, surrounds hyaline cartilage. The perichondrium is a dense connective tissue composed of cells that are indistinguishable from fibroblasts Hyaline cartilage of articular joint surfaces do not possess a perichondrium
Perichondrium
Chondroblasts
Chondrocytes in cell nests
Elastic cartilage is characterized by elastic fibers and elastic lamellae in addition to the matrix material of hyaline cartilage. Elastic cartilage is found in the external ear, the walls of the external acoustic meatus, the auditory (Eustachian) tube, and the epiglottis of the larynx. The cartilage in all of these locations is surrounded by a perichondrium similar to that found around most hyaline cartilage.
Elastic cartilage – darker staining matrix
Elastic cartilage – elastin fibers in the matrix Perichondrium
Chondroblasts
Chondrocytes
High mag of elastic cartilage
Extracellular matrix of fibrocartilage is characterized by the presence of both type I and type II collagen fibrils.
Fibrocartilage consists of chondrocytes and their matrix material in combination with dense connective tissue. Fibrocartilage is a combination of dense regular connective tissue and hyaline cartilage. The chondrocytes are dispersed among the collagen fibers singularly, in rows, and in isogenous groups
Low mag of fibrocartilage between two pieces of bone
High mag of fibrocartilage – aligned cells with bundles of collagen
Diagram of intervertebral joints
Intervertebral joint
N = nucleus pulposa
Cartilage is capable of two kinds of growth, appositional and interstitial. Interstitial growth, the process that forms new cartilage within an existing cartilage mass Appositional growth, the process that forms new cartilage at the surface of an existing cartilage
Part 2
Connective tissue
Connective tissue proper
Cartilage
Loose
Dense
Hyaline
Areolar
Dense regular
Elastic
Adipose
Reticular
Dense irregular
Elastic
Fibrocartilage
Bone
Blood
Bone is a connective tissue characterized by a mineralized extracellular matrix.
Chemical Composition of Bone A. Organic 1. Cells 2. Osteoid: organic part of matrix; made by osteoblasts B. Inorganic 1. Hydroxyapatites (mineral salts)
Bone matrix contains lacunae connected by a network of canaliculi. Within the bone matrix are spaces called lacunae, each of which contains a bone cell, or osteocyte. In addition to osteocytes, 3 other cell types are associated with bone. • Osteoprogenitor cells are cells derived from mesenchymal stem cells; they give rise to osteoblasts. • Osteoblasts are cells that secrete the extracellular matrix of bone; once the cell is surrounded with its secreted matrix, it is referred to as an osteocyte.
Osteoclasts are bone-resorbing cells present on bone surfaces where bone is being removed or remodeled (reorganized) or where bone has been damaged.
Multinucleated osteoclast
The major structural component of bone matrix is type I collagen The four main groups of noncollagenous proteins found in the bone matrix are the following: 1. Proteoglycan macromolecules 2. Glycoproteins - osteonectin (which serves as a glue between the collagen and hydroxyapatite crystals) 3. Bone-specific, vitamin K–dependent proteins, which include osteocalcin (which captures calcium from the circulation) 4. Growth factors and cytokines (bone morphogenic proteins (BMPs))
The mineral is calcium phosphate in the form of hydroxyapatite crystals [Ca10(PO4)6(OH)2].
Bones are the organs of the skeletal system; bone tissue is the structural component of bones. Bone tissue is classified as either compact (dense) or spongy (cancellous).
Diagram of a long bone with compact and cancellous bone
Microscopic Structure of Compact Bone Structural unit: Haversian System - Osteon 1. Elongated cylinders parallel to bone long axis a. Concentric rings: lamella i. Unidirectional collagen fibers along long axis ii. Adjacent lamella have collagen in opposite directions 2. Central (Haversian) canal: core of osteon a. Blood vessels and NT 3. Perpendicular canals (perforating or Volkmanns) a. Connect periosteum to central and medullary cavities 4. Lacunae: cavities containing osteocytes 5. Canaliculi: connect lacunae to each other and central canal
Compact Bone
Haversian system (osteon) with central canal and osteocytes in lacunae connected by canaliculi
Microscopic Structure Spongy Bone A. Trabeculae: needle-like (flat) pieces B. Trabeculae appear less organized than structures of compact bone No osteon Organization is based on lines of stress Lamella and osteocytes are irregularly organized
Periosteum Double layer Fibrous outer layer; dense irregular CT Osteogenic—bone forming cells (osteoblasts); Vascular, includes lymph Sharpey’s fibers: connect periosteum to bone; Endosteum: covers trabeculae of spongy bone in marrow cavites Contain osteoblasts and osteoclasts
Formation of Bone Two modes of bone formation 1. Endochondral - cartilage template formed that is replaced by bone (e.g. vertebral column, long bones of limbs – most bones in body) 2. Intramembranous - direct formation of bone structure with no cartilagenous template (e.g. flat bones of skull)
Intramembranous ossification (Skull, clavicles, flat bones) a. Ossification center forms in fibrous connective tissue membrane i. Mesenchymal cells differentiate into osteoblasts b. Bone matrix is secreted into membrane i. Osteoblast secrete osteoid c. Woven bone and periosteum is formed i. Network of trabeculae encloses local blood vessels ii. Exterior mesenchyme differentiates into periosteum d. Trabeculae thicken and form bone collar i. Replaced by lamellar bone ii. Spongy bone persists to form red marrow
Endochondral ossification
Endochondral ossification 1. Cartilage bone are used as a pattern for bone construction a. Primary ossification center at the center of the hyaline cartilage 2. Hyaline cartilage is broken down during ossification 3. Process prior to ossification a. Perichondrium becomes infiltrated by blood vessels i. Becomes periosteum ii. Underlying mesenchymal cells differentiate into osteoblasts
Ossification a. Bone collar forms around hyaline model i. Osteoblasts in periosteum secrete osteoid against hyaline cartilage b. Cartilage in center of the diaphysis calcifies c. Periosteal bud invades internal cavities i. Bud brings blood vessels, NT, lymph tissue, osteoblasts and osteoclasts d. Medullary cavity forms i. Proximal and distal growth of ossification center ii. Osteoclasts break down spongy bone and open medullary cavity e. Epiphyses ossify i. At birth, diaphysis surround spongy done, medullary cavity is widening, and epiphyses are cartilaginous ii. Secondary ossification centers form in epiphyses prior to birth and follow same course as that described above for primary ossification center
Postnatal Bone Growth
Length of long bones (Parallel events of endochondral ossification) Epiphyseal side; cartilage is added to top; bone lengthens Chondrocytes close to shaft; cartilage matrix ossifies Epiphyseal/diaphysis junction; cartilage spicules covered with bone matrix to form spongy bone Spongy bone is digested by osteoclasts allowing medullary cavity to grow
Bone remodeling: maintain proper proportion by selective resorption and appositional growth Bone thickness: appositional growth
Bone Homeostasis Remodeling - Balance of bone formation and resorption at periosteal and endosteal surfaces (Remodeling units - Packets of osteoblasts and osteoclasts)
Control of remodeling Hormonal mechanism: not related to strength; associated with mineral balance Parathyroid hormone (parathyroid gland) - PTH released in response to low ionic calcium in blood Calcitonin (thyroid gland) - is released in response to high calcium in blood Osteoclasts are activated to digest bone matrix and release calcium into blood Calcium salts are deposited into bone
Repair of fractures Phases of simple fracture repair a. Hematoma: clot of damaged vascular tissue b. Fibrocartilaginous callus formation: soft callus i. New vascular tissue ii. Osteoblasts migrate and begin reconstruction iii. Fibroblasts bring gap with collagen iv. Osteoblast begin to form spongy bone c. Bony callus formation: formation of woven bone d. Remodeling
Thank you for attention
