lec

• Connective tissue


  Second type of tissue, composed of fibroblasts and other cells and an extracellular matrix (ECM) of various protein fibers, all of which are surrounded by watery ground substance
• Functions of connective tissue

  • Acts as the binding tissue of the other three types of tissue
  • Maintains the form of organs throughout the body
  • Provides a matrix that supports and physically connects other tissues and cells together to form the organs of the body
  • Interstitial fluid of connective tissue gives metabolic support to cells as the medium for diffusion of nutrients and waste products
• Extracellular matrix (ECM)


  Major constituent of connective tissue, consists of different combinations of protein fibers (such as collagens and elastic fibers) and ground substance
• Ground substance


  A complex of anionic, hydrophilic proteoglycans and glycosaminoglycans (GAGs), and multi-adhesive glycoproteins (laminin, fibronectin, and others), a complex material, somewhat like a glue, that holds everything together
• Mesenchyme


  All connective tissue originates from the embryonic mesenchyme, a tissue developing mainly from the middle layer of the embryo, the mesoderm, consisting largely of viscous ground substance with few collagen fibers, and includes stem cells for other tissues such as blood, the vascular endothelium, and muscle
• Mesenchymal cells


  • Undifferentiated and have large nuclei, with prominent nucleoli and fine chromatin, often said to be "spindle-shaped," with their scant cytoplasm extended as two or more thin cytoplasmic processes, mesodermal cells migrate from their site of origin in the embryo surrounding and penetrating developing organs
• Connective tissue cells


  • Resident cell population
  • Wandering cell population (Transient cell population)
• Fibroblast


  Most common cells in connective tissue, produce and maintain most of the tissue's extracellular components, synthesize and secrete collagen, elastin, GAGs, proteoglycans, and multi-adhesive glycoproteins that comprise the ground substance
• Active fibroblast


  Denoted as fibroblast, more abundant and irregularly branched cytoplasm, large, ovoid, euchromatic nucleus with prominent nucleolus, much rough endoplasmic reticulum (RER) and well-developed Golgi apparatus
• Quiescent fibroblast


  Denoted as fibrocyte, smaller than active fibroblast, usually spindle-shaped with fewer processes and much less RER, contains a darker, more heterochromatic nucleus
• Myofibroblasts


  An elongated, spindly connective tissue cell not readily identifiable in routine H&E preparations, fibroblasts involved in wound healing

  
• Adipocytes (fat cells)


  Large, mesenchymally derived cells specialized for cytoplasmic storage of lipids as neutral fats, less commonly for the production of heat, when they accumulate in large numbers they are called adipose tissue which serves to cushion and insulate the skin and other organs
• Macrophages


  Key component of an organism's innate immune defense, removing cell debris, neoplastic cells, bacteria, and other invaders, have highly developed phagocytic ability and specialized in turnover of protein fibers and removal of dead cells, tissue debris, or other particulate material, being especially abundant at sites of inflammation, a typical macrophage measures between 10 and 30 μm in diameter and has an eccentrically located, oval or kidney-shaped nucleus, size and shape vary considerably, corresponding to their state of functional activity, have different names depending on their location
• Cells of the mononuclear phagocytotic system

  • Macrophage (Histiocyte)
  • Perisinusoidal macrophage (Kupffer cell)
  • Alveolar macrophage
  • Fetal placental antigen-presenting cell (Hoffbauer cell)
  • Macrophage
  • Pleural and peritoneal macrophage
  • Osteoclast
  • Microglia
  • Langerhans cell
  • Fibroblast-derived macrophage
  • Dendritic cell
• Mast cells


  Oval or irregularly shaped connective tissue cells between 7 and 20 μm in diameter, with cytoplasm filled with basophilic secretory granules, the nucleus is centrally situated and often obscured by abundant secretory granules, display metachromasia, functions in the localized release of many bioactive substances with roles in the local inflammatory response, innate immunity, and tissue repair, important molecules released include heparin, histamine, serine proteases, eosinophil and neutrophil chromatic factors, cytokines, and phospholipid precursors
• Types of mast cells

  • Perivascular mast cells
  • Mucosal mast cells
• Plasma cells


  1. lymphocyte derived, antibody-producing cells, large, ovoid cells that have basophilic cytoplasm due to their richness in RER, the nucleus is generally spherical but eccentrically placed, many contain compact, peripheral regions of heterochromatin alternating with lighter areas of euchromatin, giving the nucleus a "clock-face" appearance, average lifespan is only 10-20 days
• Leukocytes


  Make up a population of wandering cells in connective tissue, leave blood by migrating between the endothelial cells lining venules to enter connective tissue by a process called diapedesis, chemotaxis draws larger numbers of leukocytes into inflamed tissues
• Fibers of connective tissue

  • Collagen fibers
  • Reticular fibers
  • Elastic fibers
• Collagen


  A key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells, extremely strong and resistant to normal shearing and tearing forces, most abundant protein in the human body, 30% of its dry weight, a pathological presence of an excess amount of collagen is usually referred to as keloid and it usually happens during wound healing
• Fibers


  Elongated structures formed from proteins that polymerize after secretion from fibroblasts
• Three main types of fibers

  • Collagen
  • Reticular
  • Elastic
• Collagen & reticular fibers


  Formed by proteins of the collagen family
• Elastic fibers


  Composed mainly of the protein elastin
• These fibers are distributed unequally among the different types of connective tissue, with the predominant fiber type usually responsible for conferring specific tissue properties
• Collagen


  • A key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells
  • Extremely strong and resistant to normal shearing and tearing forces
  • Most abundant protein in the human body, 30% of its dry weight
• Keloid


  A pathological presence of an excess amount of collagen, usually returned to during scar formation
• Bundles of collagen appear white and are birefringent under the polarizing microscope
• Collagen renewal


  Collagen must first be degraded, initiated by specific enzymes called collagenases, which are members of an enzyme class called matrix metalloproteinases (MMPs)
• 6 classes of collagens identified on the basis of their polymerization pattern

  • Fibrillar collagens
  • Fibril-associated collagens with interrupted triple helixes (FACITS)
  • Hexagonal network-forming collagens
  • Transmembrane collagens
  • Multiplexins
  • Basement membrane-forming collagens
• Fibrillar collagens


  • Often densely fill the connective tissue, forming structures such as tendons, organ capsules, and dermis
  • Characterized by uninterrupted glycine–proline–hydroxyproline repeats and aggregate to form 68-nm-banded fibrils
• Fibrillar collagen types


  • I
  • II
  • III
  • V
  • XI
• Fibril-associated collagens with interrupted triple helixes (FACITS)


  • Have interruptions in their triple helixes that provide flexibility to the molecule
  • Located on the surface of different fibrils
• Fibril-associated collagen types


  • IX
  • XII
  • XIV
  • XVI
  • XIX
  • XX
  • XXI
  • XXII
• Hexagonal network-forming collagen types

  • VIII
  • X
• Transmembrane collagen types


  • XIII
  • XVII
  • XXIII
  • XXV
• Multiplexins


  Collagens with multiple triple-helix domains and interruptions
• Multiplexin collagen types


  • XV
  • XVIII
• Basement membrane-forming collagen types

  • IV
  • VI
  • VII
• Collagen type locations


  • Type I: Connective tissue of skin, bone, tendon, ligaments, dentin, sclera, fascia, and tension, and stretch organ capsules
  • Type II: Cartilage (hyaline an elastic), notochord, and intervertebral disk
  • Type III: Prominent in loose connective tissue and organs (uterus, liver, spleen, kidney, lung, etc.); smooth muscle; endoneurium; blood vessels; and fetal skin
  • Type IV: Basal laminae of epithelia, kidney glomeruli, and lens capsule
  • Type V: Distributed uniformly throughout the connective tissue stroma; may be related to reticular network
  • Type XI: Cartilage