CONNECTIVE

• Connective Tissue


  Provides a matrix → supports and physically connects other tissues and cells to form organs of the body
• Interstitial fluid of Connective Tissue

  • Gives metabolic support to cells
  • Serves a medium for diffusion of nutrients and waste products
• Extracellular matrix (ECM)


  • Major constituent
  • Consists of protein fibers (collagen, elastic fiber) and ground substance
  • Ground substance: Anionic, hydrophilic, Proteoglycans, Glycosaminoglycans, Multiadhesive glycoproteins - laminin, fibronectin
  • Help stabilize ECM by binding to other components
  • Water - allows exchange of nutrients and metabolic wastes
• Anlage: Embryonic mesenchyme


  • Developed from mesoderm
  • Mesenchymal cells - undifferentiated, large nucleated, spindle shaped, prominent nucleoli, fine chromatin, scant cytoplasm
  • Includes CT proper, specialized CT, stem cells of blood, vascular endothelium, and muscle
• Types of Connective Tissue

  • Connective Tissue Proper
  • Loose
  • Adipose
  • Reticular
  • Mesenchyma
  • Mucoid
  • Dense
  • Regular
  • Irregular
  • Supportive Connective Tissue
  • Bone
  • Compact
  • Spongy
  • Cartilage
  • Hyaline
  • Elastic
  • Fibrocartilage
  • Fluid Connective Tissue
  • Blood
  • Lymph
• Cells of Connective Tissue

  • Fibroblasts
  • Adipocytes
  • Macrophages and Mononuclear Phagocyte System
  • Mast cells
  • Plasma cells
  • Leukocytes
• Fibroblasts


  • Key cells in CT proper
  • Originate from mesenchymal cells
  • Produce and maintain most of the tissue's extracellular components
  • Synthesize and secrete collagen and elastin
  • Collagen is the most abundant protein of the body
  • All components of the ECM is derived from fibroblast, especially collagen
• Fibroblast


  Active cell: has more abundant & irregularly branched cytoplasm, more RER, well-developed GA, with a large, ovoid, euchromatic nucleus, and prominent nucleolus
• Fibrocyte


  Quiescent cell: smaller, spindle-shaped with fewer processes, less RER, and a darker, more heterochromatic nucleus
• Adipocytes


  • Fat cells, found in CT of many organs
  • Large, specialized cells for cytoplasmic storage of lipids as neutral fats, or less commonly to produce heat
  • Adipose CTs - serves to cushion & insulate the skin and other organs
• Macrophages


  • Derived from monocytes (anlage)
  • Monocytes enter the epithelial cells of venules entering CTs, where they differentiate
  • Transformation involves: increase in cell size, increased protein synthesis, & increase in number of golgi complexes & lysosomes
  • 10-30 um, eccentrically located, oval or kidney shaped nucleus
  • Referred to as "Histiocytes"
• Macrophages


  • Have a highly developed phagocytic ability
  • Specialize in turnover of protein fibers
  • Removal of apoptotic cells, tissue debris, or other particulate material
  • Abundant at sites of inflammation
  • Play an important role during inflammation and tissue repair
• Macrophages


  • Key part of innate immune system
  • Antigen presenting cell, required for activation and specification of lymphocytes
  • Activated macrophages have increased capacity for phagocytosis and intracellular digestion, exhibit enhanced metabolic and lysosomal enzyme activity
• Macrophages


  • Are also secretory cells: enzymes, growth factors, cytokines - help regulate immune cells and exhibit reparative functions
  • May increase in size and fuse to form "multinuclear giant cells" found in pathologic conditions
• Mononuclear Phagocyte System Cells

  • Monocyte
  • Macrophage
  • Kupffer Cell
  • Microglial Cell
  • Langerhans Cell
  • Dendritic Cell
  • Osteoclast
  • Multinuclear Giant Cell
• Mast Cells


  • Oval, irregularly shaped cells, 7-20 um
  • Positive for basophilic granules
  • Positive for metachromasia - they can change the color of some basic dyes
  • Granules are poorly preserved by fixatives - making it hard to identify in prepared slides
• Mast Cells


  Originate from progenitor cells in BM, enter circulation, cross walls of venules, enter CT where they would differentiate
• Molecules released from mast cell secretory granules

  • Heparin: anticoagulant
  • Histamine: promotes increased vascular permeability & smooth muscle contraction
  • Serine proteases: activate various mediators of inflammation
  • Eosinophil & Neutrophil Chemotactic factors: attract leukocytes
  • Cytokines: directing activities of leukocytes and other immune cells
  • Phospholipid precursor: converted to prostaglandins, leukotrienes, which are important mediators of inflammatory response
  • ECF-A: Eosinophil chemotactic factor of anaphylaxis
• Mast Cells


  • Important in local inflammatory response, innate immunity, and tissue repair
  • Occur in many CT organs: near small BVs - "Perivascular mast cells", tissues that line digestive and respiratory tracts - "Mucosal mast cells"
• Mast Cells


  • Release certain chemical mediators which promote allergic reactions - "Immediate Hypersensitivity Reactions"
  • Anaphylactic Shock - dramatic immediate hypersensitivity reaction, potentially fatal condition, treatment: Epinephrine
• Plasma Cells


  • Lymphocyte-derived, antibody-producing cells
  • Derived from B lymphocytes
  • Function: synthesis of immunoglobulins
  • Each Ab is specific for one Ag
  • Bound Ag-Ab complexes are quickly removed from tissues by phagocytosis
• Plasma Cells


  • Large, ovoid cells with basophilic cytoplasm rich in RER and a large Golgi apparatus
  • Eccentric nucleus
  • Lifespan: 10-20 days
• Leukocytes


  • Also known as "white blood cells"
  • Comprise of population of wandering cells in CTs
  • Derived from circulating blood cells - enter the CTs by migrating between endothelial cells of venules, this process increases during inflammation
• Inflammation


  • Vascular & cellular defensive response to injury or foreign substances
  • Starts with local release of chemical mediators from various cells
• Events characteristic of Inflammation

  • Increased blood flow
  • Increased vascular permeability
  • Entry and migration of leukocytes
  • Activation of macrophages for phagocytosis
• Cardinal Signs Of Inflammation

  • Calor - heat
  • Rubor - redness
  • Tumor - swelling
  • Dolor - pain
  • Functio Laesa - loss of function
• Fibers


  • Fibrous components of CT are elongated structures formed from proteins that polymerize after secretion from fibroblasts
  • 3 main types: Collagen fibers, Reticular fibers, Elastic fibers - elastin protein
• Collagen


  • Key element of all connective tissue
  • Most abundant protein in the body
  • Categorized according to structures formed by their interacting α-chain subunits: Fibrillar collagens, Network or sheet-forming collagens, Linking/anchoring collagens
• Fibril-forming Collagen Types


  • Type I - Skin, tendon, bone, dentin, Resistance to tension
  • Type II - Cartilage, vitreous body, Resistance to pressure
  • Type III - Skin, muscle, vessels, frequently with type I, Structural maintenance in expansible organs
  • Type V - Fetal tissue, placenta, skin, bone, interstitial tissues, Participates in Type II collagen function
  • Type XI - Cartilage, Participates in Type II collagen function
• Network or Sheet-forming Collagen Types

  • Type IV - Basal lamina, external lamina, Filtration & support of epithelial cells
  • Type X - Hypertrophic cartilage in endochondral ossification, Increases matrix density
• Linking or Anchoring Collagen Types

  • Type VII - Epithelial basement membrane, Anchors basal lamina to reticular lamina
  • Type IX - Cartilage, vitreous body, Binds proteoglycans; associated with type II
  • Type XII - Placenta, skin, tendons, Interact with type I collagen fibrils with type V & type XIV
  • Type XIV - Placenta, bone, Binds type I collagen fibrils with type V & type XII
• Reticular Fibers


  • Found in delicate CT of many organs (notably in the immune system)
  • Consist mainly of collagen type III
• Elastic Fibers


  • Form sparse networks interspersed with collagen bundles in many organs
  • In the wall of large blood vessels (especially arteries), elastin also occurs as fenestrated sheets called elastic lamellae
  • Have "rubber-like" properties that allow tissue containing these fibers (e.g., stroma of the lungs) to be stretched or distended and return to their original shape
• Ground Substance


  • Highly hydrated (with much bound water), transparent, complex mixture of three major kinds of macromolecules: Glycosaminoglycans (GAGs), Proteoglycans, Multiadhesive glycoproteins
  • Filling the space between cells and fibers in connective tissue, ground substance allows diffusion of small molecules and, because it is viscous, acts as both a lubricant and a barrier to the penetration of invaders
• Loose Connective Tissue


  • Common, forms layer beneath the epithelial lining of many organs, fills the spaces between fibers of muscles and nerves
  • Also called "Areolar Tissue"
  • Collagen fibers predominate but elastic and reticular fibers are also present
  • Moderate amount of ground substance
  • Has a delicate consistency; it is flexible and not very resistant to stress
• Loose Connective Tissue


  • Lamina propia of digestive tract
  • Papillary layer of dermis
• Dense Connective Tissue


  • Has similar components as loose connective tissue but with fewer cells, mostly fibroblasts
  • Clear predominance of bundled type I collagen over ground substance
• Loose Connective Tissue


  • Common
  • Forms layer beneath the epithelial lining of many organs
  • Fills the spaces between fibers of muscles and nerves
  • Collagen fibers predominate but elastic and reticular fibers are also present
  • Moderate amount of ground substance
  • Has a delicate consistency; it is flexible and not very resistant to stress
• Loose Connective Tissue


  • Lamina propia of digestive tract
  • Papillary layer of dermis
• Dense Connective Tissue


  • Has similar components as loose connective tissue but with fewer cells
  • Mostly fibroblasts
  • Clear predominance of bundled type I collagen over ground substance
  • The abundance of collagen protects organs and strengthens them structurally