Connective Tissue - Proper & Blood

• Connective tissue (CT)

  • Originates from embryonic mesenchyme (a tissue which develops from the mesoderm)
  • Provides a matrix that supports and physically connects other tissues and cells together in organs
  • Consists of cells and an extracellular matrix (ECM) which consists of fibres & ground substance
• Connective tissue cells

  • Fibroblasts
  • Adipocytes
  • Macrophages
  • Plasma cells
  • Mast cells
  • Leukocytes
• Connective tissue cells - Fibroblasts

  • Principal cells of CT
  • Active cells (fibroblasts) are morphologically distinct from quiescent/inactive cells (fibrocytes)
  • Synthesize and secrete collagen, elastic and reticular fibers
  • Secrete components of ground substance
  • Myofibroblast is a type of fibroblast
• Connctive tissue cells - Adipocytes

  • Fat storing cells
  • Found in CT of many organs
  • Cytoplasmic storage of lipids as neutral fats
  • Production of heat
  • Cushions and insulates skin and other organs (mainly adipose CT)
• Connective tissue cells - Macrophages (histiocytes)

  • Derived from monocytes
  • Removes dead cells, tissue debris and other particulate matter through phagocytosis
  • Immune function (antigen presentation)
  • Secretion of enzymes that breakdown ECM and growth factors
• Connective tissue cells - Plasma cells

  • Derived from B-lymphocytes
  • Large, ovoid cells with abundant rER in cytoplasm (stains basophilic), spherical and eccentrically placed nucleus
  • Antibody production
• Connective cells - Mast cells

  • Promote "immediate hypersensitivity reactions" when an antigen binds to the surface of Fc receptors
  • Release many bioactive substances (through exocytosis) during inflammation (e.g. histamines, heparin and cytokines)
  • Play a role in innate immunity and tissue repair
• Connective tissue cells - Leukocytes

  • White blood cells
  • Make-up a population of wondering cells in CT
  • Immune response
  • Inflammation
• Types of leukocytes

  • Lymphocyte
  • Neutrophil
  • Eosinophil
  • Basophil
  • Monocyte
• Connective tissue fibers

  • Collagen (H & E stain)
  • Reticular (silver impregnation method)
  • Elastic (elastin stain)
• Collagen fibers

  • Key component of CT and basement membranes
  • Resistant to shearing and tearing forces
  • Collagen fibers are the most abundant structural components of CT
  • Flexible and has high tensile strength
  • Mainly secreted by fibroblasts, but may also be secreted by other cell types
• Reticular fibers

  • Forms an extensive network of extremely thin fibers composed of collagen fibrils
  • Provides a supportive framework of parenchymal secretory cells in various tissues and organs
  • Found in reticular lamina of basement membrane, surrounds adipocytes, smooth muscle, nerve fibers and small blood vessels
• Elastic fibers

  • Thinner than collagen fibers
  • Arranged in a branching pattern and form sparse networks interspersed with collagen bundles
  • Facilitates stretching or distention in organs
  • In large vessels forms fenestrated sheets called elastic lamellae
• Classification of connective tissue proper

  • Loose irregular (areolar)
  • Dense irregular
  • Dense regular
  • Elastic
• Loose irregular (areolar) CT

  • Lies beneath epithelium in a layer called lamina propria and fills spaces between muscle and nerve fibers
  • Contains abundant cells, loosely arranged fibers and abundant ground substance
  • Contains lots of blood vessels and nerves
  • Function: flexible and not resistant to stress
• Dense irregular CT

  • Found in the dermis of skin, organ capsules and submucosa layer of digestive tract
  • Contains fewer cells, more collagen fibers (randomly interwoven) and little ground substance
  • Function: provides resistance to stretching and distension from all directions
• Dense regular CT

  • Found in tendons, ligaments and aponeuroses
  • Fibers and cells densely packed and arranged in an orderly manner (parallel) to provide maximum strength
  • Contains very little ground substance
  • Function: provides resistance to prolonged stresses exerted in the same direction
  • Poorly vascularised
• Ground substance

  • Viscous, clear substance consisting of a hydrated mixture of proteoglycans, glycosaminoglycans (GAGs) and multiadhesive glycoproteins
  • Occupies the spaces between cells and fibers
  • Function: medium for exchange of nutrients and metabolic wastes between cells and the blood
• Blood consists of cells suspended in fluid extracellular matrix called Plasma
• Total volume of blood in normal adults is ~6L
• Functions of blood

  • Transport (nutrients,O2,wastes,CO2)
  • Delivery of hormones
  • Maintenance of homeostasis by coagulation and thermoregulation
  • Transport of humoral agents and cells of the immune system
• Hematocrit

  The volume of packed erythrocytes in a blood sample
• Normal Hematocrit is 39% - 50% for Males and 35% - 45% for Females
• Plasma

  Liquid, protein rich extracellular matrix that imparts fluid properties to blood
• Plasma is composed of 90% water, 7-8% proteins, and 1-2% other solutes
• Difference between plasma and serum

  Plasma contains fibrinogen while serum does not
• Blood smear preparation

  Modified Romanovsky-type stain (methylene blue, related azures, metachromatic, eosin)
• Hemopoiesis


  Blood cell formation
• Erythrocytes

  • Anucleate, biconcave discs
  • 7.8µm in diameter
  • Lack organelles
  • Function within the bloodstream
  • Contain protein haemoglobin
• Leukocytes

  • White blood cells
  • Involved in immune responses
  • Not permanent members of blood - migrate
• Leukocyte shape

  • Spherical, but flatten when motile
  • Leave capillaries and enter connective tissue (transient cells in CT)
• Leukocyte classification

  • Granulocytes: Specific granules, Azurophilic granules & Nucleus = 2/more lobes. Includes: Neutrophils, eosinophils and basophils
  • Agranulocytes: Lack specific granules, Azurophilic granules & Nucleus = round/indented. Includes Lymphocytes & monocytes
• Neutrophils (WBCs granulocyte)

  • Most common (50-70%)
  • 10-12µm in diameter
  • Nuclei have 2-5 lobes
  • Barr body in females (inactive X chromosome)
  • Granules (specific, azurophilic and tertiary)
  • Active phagocytes at the site of inflammation
• Eosinophils (WBCs granulocyte)

  • Constitute ~ 1-3% of circulating leukocytes
  • 10-12µm in diameter
  • Bilobed nucleus
  • Cytoplasm abundant with large, round, eosinophilic specific granules
  • Azurophilic granules
  • Normally found in connective tissue
  • Associated with allergic reactions, parasitic infections and chronic inflammation
• Basophils (WBCs granulocyte)

  • Least numerous (<1%)
  • 10-12µm in diameter
  • Nucleus has two irregular lobes (often obscured by granules)
  • Cytoplasm is filled with large basophilic specific granules
  • Azurophilic granules
  • Release vasoactive agents involved in inflammation and hypersensitivity reactions
• Lymphocytes(WBCs agranulocyte)

  • Constitute about 30% of circulating leukocytes
  • Small, medium, large (6-30µm in diameter)
  • Slightly indented spherical nucleus with scant cytoplasm
  • Effector and regulatory cells of the immune system
  • Functionally divided into T lymphocytes, B lymphocytes, and NK cells
  • Involved in immune response (innate/adaptive)
• Monocytes (WBCs agranulocyte)

  • Largest (diameter=18µm)
  • Have a distinct indented (or kidney shaped) nucleus
  • Azurophilic granules
  • Precursors of cells of the mononuclear phagocyte system
  • Differentiate into macrophages (phagocytes and antigen presenting cells)
• Platelets

  • Anucleate cytoplasmic fragments
  • Very small (2-3µm in diameter)
  • Originate from megakaryocytes in bone marrow
  • Appear in small clumps
  • Function in clot formation
• Types of collagen fibres - Fibrillar collagens (Type I, II, III): subunits that aggregate to form large fibrils 


   Type I: consists of fibers and constitutes 90% of all collagens in the body (most abundant) [e.g. organ capsule, dermis, tendons]

   Type II: occurs as fibrils but does not form fibers or bundles [e.g. cartilage].

   Type III: occurs as a thin network [e.g. forms reticular fibers in organs] 
• Types of collagen fibres - Basement membrane –forming collagens


   Sheet-forming collagens (Type IV)are major structural proteins of external laminae and epithelial basal laminae.

   Linking/anchoring collagens (Type VII): short collagens that link fibrillar collagens to one another and to other components of the ECM