CONNECTIVE TISSUE

I. Introduction

 Consists of:
 Abundant extracellular matrix
 Various types of connective tissue
cells
 Functions:

 Provides structural support for organs and

cells
 Serves as a medium for exchange of
nutrients and wastes between the blood
and tissues
 Aids in protection against microorganisms
 Helps in repair of damaged tissues
 Provides a site for storage of fat
 II. Extracellular Matrix

 Ground substance
 Fibers
 Tissue fluid
 Ground Substance

 Gel-like material that fills the space

between the cells and fibers of
connective tissues.
 Is a complex mixture of
glycosaminoglycans, proteoglycans and
adhesive glycoproteins
 Along with water and other small
molecules (ex. nutrients ions) constitutes
the extracellular environment
 Acts as a lubricant and helps prevent the
penetration of tissues by foreign particles
 GLYCOSAMINOGLYCANS
(GAGs)

The sulfated GAGs include:

 Keratan sulfate
 Heparan sulfate
 Heparin
 Chondroitin-4-sulfate
 Chondroitin-6-sulfate
 Dermatan sulfate
 The only non-sulfated glycosaminoglycan
is hyaluronic acid
 PROTEOGLYCANS

 When sulfated GAGs form covalent bonds

with a protein core, they form a family of
macromolecules known as proteoglycans
 Aggrecan-a macromolecular proteoglycan
found in cartilage and connective tissue
proper attached to hyaluronic acid
 This is responsible for the gel state of the
extracellular matrix and acts as a barrier
to fast diffusion of aqueous deposits
ADHESIVE GLYCOPROTEINS
 Fibronectin
 Fibronectin receptor
 Laminin
 Entactin
 Tenascin
 Chondronectin
 Osteonectin
 The ability of cells to adhere to
components of the intercellular matrix is
mediated by adhesive glycoprotein
 Fibronectin

 Types and location

 Matrix fibronectin
 An adhesive glycoprotein that forms fibrils in
the extracellular matrix
 Cell-surface fibronectin
 A protein that transiently attaches to the
surface of cells
 Plasma fibronectin
 Is a circulating plasma protein that function in
blood clotting, wound healing and phagocytosis.
 Functions

 Is a multifunctional molecule
possessing domains for binding
collagen, heparin, various cell-
surface receptors, and cell-adhesion
molecules
 Mediates cell adhesion to the
extracellular matrix by binding to
fibronectin receptors on the cell
surface
 Fibronectin receptor

 Is a transmembrane protein, consisting of 2

polypeptide chains
 Belongs to the integrin family of receptors, and is
known as a cell-adhesion molecule (CAM), since it
enables cells to adhere to the extracellular matrix
 Function:
 To link fibronectin outside the cell with
cytoskeletal components (ex. actin) inside the cell
 Laminin
 Is located in the basal (external) lamina
and is synthesized by adjacent cells
 Possess binding sites for cell-surface
receptors (integrins), heparan sulfate,
type IV collagen and entactin
 Functions to mediate interaction
between epithelial cells and the
extracellular matrix by anchoring the cell
surface to the basal lamina.
 Entactin

 Is a component of all basal

(external) laminae
 Is a sulfated adhesive glycoprotein
that binds laminin
 Functions to link laminin with Type
IV collagen
 Tenascin

 Is an adhesive glycoprotein, most

abundant in embryonic tissues
 Is secreted by glial cells in the
developing nervous system
 Function:
 Promotes cell-matrix adhesion in
cell migration
 Chondronectin

 Is a glycoprotein in cartilage that

attaches chondrocytes to type II
collagen
 Is a multifunctional molecule with
binding sites for collagen,
proteoglycans and cell-surface
receptors
 Functions in the development and
maintenance of cartilage by
influencing the composition of its
 Osteonectin

 Is an extracellular matrix in bone

 Functions to link minerals to Type I
collagen and to influence
calcification by inhibiting crystals
growth
 Fibers

 Collagen fibers
 Reticular fibers
 Elastic fibers
 Collagen Fibers
 Is very abundant constituting about 20%
of all the proteins in the body
 Forms of a flexible fiber whose tensile
strength is greater than that of stainless
steel of comparable diameter
 Referred to as white fibers
 Stained with H & E, they appear as long,
wavy pink fiber bundles
 Have the characteristics cross-banding at
regular intervals of 67nm
 There are 15 different types of collagen
known depending on the amino acid
sequence of their chains
 Important types of collagen

 Type I
 Type II
 Type III
 Type IV
 Type V
 Type VI
 Elastic Fibers
 Are usually slender, long and branching
in loose connective tissue
 May form coarser bundles in ligaments
and fenestrated sheets (found in
ligamentum flava of the vertebral
column, and concentric sheets in the
walls of larger blood vessels)
 Are manufactured by fibroblasts of
connective tissue as well as by smooth
muscle cells of blood vessels
 Composed of elastin, a protein rich in
glycine and proline and also contain the
unusual amino acids desmosine and
isodesmosine
 Elastic Fibers

 Form considerable cross-linking of the elastin

molecules, imparting a high degree of elasticity
to elastic fibers
 May be stretched to about 150% of their resting
lengths prior to breakage
 Return to resting length after being stretched
 Core of elastic fibers is composed of elastin and is
surrounded by a sheath of microfibrils, composed
of the glycoprotein fibrillin.
 During the formation of elastic fibers, the
microfibrils are elaborated first, and the elastin is
deposited into the space surrounded by the
microfibrils
 Tissue Fluid

 Plasma from capillaries and venules

enters the connective tissue spaces
as tissue fluid which percolates
through the ground substance.
Tissue fluid re-enters the venule as
well as lymphatic capillaries.
 Connective Tissue Cells
 Fixed cells
 Transient cells
 Fixed cells

 Are resident population of cells that have

developed and remain in place within the
connective tissue, where they perform their
functions
 Are a stable and long-lived population
 Include:
 Fibroblasts
 Adipose cells
 Mast cells
 Pericytes
 Macrophages like Kupffer cells of the liver can be
considered fixed connective tissue cells
 Transient cells

 Free or wandering cells

 Originate mostly in the bone marrow and
circulate in the bloodstream
 Upon receiving the proper stimulus or signal
these cells leave the bloodstream and migrate
into the connective tissue to perform their
specific functions.
 Because most of these motile cells are usually
short-lived, they must be replaced continuously
from a large population of stem cells
 Transient cells include:

 Plasma cells
 Lymphocytes
 Neutrophils
 Eosinophils
 Basophils
 Monocytes
 Some macrophages
 FIBROBLASTS
Most widely distributed and abundant
 Arise from undifferentiated

mesenchymal cells
 Normally have an oval nucleus and

often have 2 nucleoli

 Active fibroblasts
 Are spindle-shaped with long tapering
ends (fusiform)
 Contain well-developed rough
endoplasime reticulum (RER) and Golgi
complex
 Are synthetically active, producing
procollagen and other precursors of the
extracellular matrix components
 Often reside in close association with
collagen bundles, where they lie parallel to
the long axis of the fiber
 With H & E pale-staining cytoplasm with
darker stained, large granular ovoid
nucleus containing a well-defined
 Inactive fibroblast
 Smaller and more ovoid, with acidophilic
cytoplasm
 Nucleus is smaller, elongated and more
deeply stained
 EM reveals sparse amounts of RER but an
abundance of free ribosomes
 Seldom undergo cell division, but may do
so during wound healing
 May differentiate into:
 Adipose cells
 Chondrocytes (during formation of
fibrocartilage)
 Osteoblasts (under pathological
conditions)
 Myofibroblasts
 Are modified fibroblasts
 Have characteristics similar both
fibroblasts and smooth muscle cells
 EM shows bundles of actin filaments and
dense bodies similar to those of smooth
muscle cells
 External lamina (basal lamina) is absent
 Abundant in areas undergoing wound
healing
 Found in the periodontal ligament where
they probably assist in tooth eruption
 PERICYTES
 Derived from undifferentiated
mesenchymal cells
 Partly surround the endothelial cells of
capillaries and small venules
 Possess characteristics of smooth muscle
cells and endothelial cells, suggesting that
under certain conditions, they may
differentiate into other cells
 Technically pericytes are outside the
connective tissue compartment because
they are surrounded by their own basal
lamina which maybe fused with that of the
endothelial cell.
 ADIPOSE CELLS
 Derived from undifferentiated
mesenchymal cells
 Fibroblasts may also give rise to
adipose cells
 Are fully differentiated and do not
undergo cell division
 Function:
 Synthesis and storage of triglycerides
 2 types of fat cells
 Unilocular fat cells
 form white adipose tissue
 cells with a simple large lipid droplet

 Multilocular fat cells

 Form brown adipose tissue
 Cells with multiple, small lipid droplets
 Unilocular Adipocytes
 Are large cells, polyhedral in adipose
tissue
 Continually store fat in the form of a
single droplet, which enlarges so
much displacing the cytoplasm and
nucleus peripherally against the
plasma membrane, giving these cells
the “Signet ring” profile on light
microscopy
 EM reveals only few mitochondria,
sparse RER, abundant free ribosomes
 Multilocular Adipocytes
 Are smaller and more polygonal than
unilocular fat cells
 Nucleus is spherical & not squeezed
against the cell membrane because
fat is stored in small droplets
 EM reveal many mitochondria, fewer
free ribosomes, lacks RER, smooth
ER is present
 MAST CELLS

 Arise from myeloid stem cells during

hematopoiesis
 Nucleus: small, ovoid, pale-staining
 Cytoplasm:
 filled with coarse, deeply stained
metachromatic granular
 Metachromasia is due to its content
of heparin,a sulfated GAG
 Granules contain:
 Heparin
 Histamine
 Neutral proteases
 Aryl sulfatase
 Most cells also synthesize LEUKOTRIENES
from membrane arachidonic acid
precursors
 Mast cells is connective tissue contain
mostly heparin in their granules, whereas
those located in the alimentary tract
mucosa contain chondroitin sulfate
(mucosal mast cells)
 MACROPHAGES

 Some behave as fixed cells and some

are transient cells
 Function in removing cellular debris
and in protecting the body against
foreign invaders
 MONONUCLEAR PHAGOCYTE
SYSTEM
 All members of the system:
 Arise from a common stem cell in the bone marrow
 Possess lysosomes
 Capable of phagocytosis
 Display Fc receptors and receptors for complement
 Macrophage development
 Monocyte develop in the bone marrow and circulate in the
blood
 At the proper signal, they leave the bloodstream by
migrating through the endothelium of capillaries or venules
 In connective tissue compartment they mature into
macrophages, which normally have a lifespan of about 2
months
 Distribution in the body

 Kupffer cells – liver

 Dust cells – lung
 Langerhans cells – skin
 Monocytes – blood
 Macrophages – connective tissue
 Osteoclasts – bone
 Microglia – brain
 Under chronic inflammatory conditions,
macrophages congregate, greatly enlarge and
become polygonal-shaped epithelioid cells.
 When the particulate matter to be disposed is
excessively large, several to many macrophages
may fuse to form foreign-body giant cell. ( a giant
multinucleated macrophage)
 Resident macrophages
 Residing in the connective tissues
 Elicited macrophages
 Those that developed as a result of an exogenous
stimulus and migrated to a particular site.
 Macrophages
 Size: 10-30 nm in diameter
 Irregularly shaped
 Cell surface presents short, blunt projections or
finger-like filopodia
 Cytoplasm:
 Basophilic with many small vacuoles and small
dense granules
 Nucleus:
 Ovoid indented on one side, eccentric in location,
small more darkly stained, usually does not
display nucleoli
 EM demonstrate
 Well developed Golgi apparatus
 Prominent RER
 Abundance of lysosomes, appearing as small,
dense granules in LM
 Functions of Macrophages
 Phagocytose senescent, damaged and
dead cells and cellular debris and digest
the ingested material by action of
hydrolytic enzymes in their lysosomes
 Assist in defense of the body by
phagocytosing and destroying
microorganisms
 During the immune response, factors
released by lymhocytes activate
macrophages, increasing their phagocytic
activity

 PLASMA CELLS
 Found in greatest numbers in areas of chronic
inflammation and where foreign substances or
microorganisms have entered the sinuses
 Are derived from B lymphocytes
 Secrete antibodies upon encountering an antigen
 Plasma cells are large, ovoid cells, 20 nm in
diamter
 Nucleus eccentric in location, with
heterochromatin clumps at the periphery giving it
the characteristic “clock-faced” appearance
 Cytoplasm:
 Intensely basophilic as a result of a well-
developed RER with closely spaced cisternae
 EM show a large juxtanuclear Golgi complex and
a pair of centrioles
 LM show a juxtanuclear negative Golgi image
 LEUKOCYTES

 Are white blood cells that circulate in the

bloodstream
 Frequently migrate through the capillary
walls to enter the connective tissues
especially during inflammation, when they
carry out various functions
 Neutrophils
 Eosinophils
 Lymphocytes
 CLASSIFICATION OF
CONNECTIVE TISSUE

 Embryonic Connective Tissue

 Connective Tissue Proper
 Specialized Connective Tissue
 Embryonic Connective
Tissue
 Mesenchymal Tissue
 Mucuous Tissue
 Mesenchymal Tissue

 Connective tissue present in embryos

 Consists of mesenchymal cells in a gel-like
amorphous ground substance containing
scattered reticular fibers
 Mesenchymal cells:
 Are pleuripotential cells
 Give rise to most of the cells of loose connective
tissue
 Nucleus: oval, exhibiting fine chromatin network
and prominent nucleoli
 Cytoplasm: sparse, pale-staining, extending small
processes in several directions
 Mucuos Tissue

 Loose, amorphous connective tissue

exhibiting a jelly-like matrix
primarily composed of hyaluronic
acid and sparsely populated with
Type I and Type III collagen fibers
and fibrobalsts
 Also known as Wharton’s jelly
 Found in the umbilical cord
 Connective Tissue Proper
 Loose Connective Tissue
 Dense Connective Tissue
 Dense Regular Collagenous
Connective Tissue
 Dense Regular Elastic Connective
Tissue
 Dense Irregular Connective Tissue
 Loose Connective Tissue
 Also called areolar tisse
 Posseses relatively fewer fibers but more cells
than dense connective tissue
 Is well vascularized, flexible, and not resistant
to sress
 Abundant ground substance and tissue fluid
 Cells are: fibroblasts, adipose cells,
macrophages and mast cells & some
undifferentiated cells
 Scattered are loosely woven collagen, reticular,
and elastic fibers
 The loose connective tissue of mucous
membrane is called the lamina propria
 Contains many transient cells responsible for
 Dense Connective Tissue

 Contains more fibers but fewer cells

than loose connective tissue
 Classified according to orientation
of fiber bundles
 Dense Regular Collagenous
Connective Tissue

 Composed of coarse collagen bundles

densley packed and oriented into parallel
cylinders or sheets that resist tensile
forces
 Thin sheet-like fibroblasts are located
between bundles of collagen with their
long axis parallel to the bundles
 Examples are tendons, ligaments and
aponeuroses
 Dense Regular Elastic
Connective Tissue

 Possesses coarse branching elastic

fiber with only a few collagen fibers
forming networks
 Elastic fibers are arranged parallel
to each other and form either, thin
sheets (ex. ligamentum flava,
suspensory ligament of penis) or
fenestrated membranes. (Ex. tunica
media of aorta)
 Dense Irregular Connective
Tissue

 Contains mostly coarse collagen fibers

interwoven into a meshwork that resists stress
from all directions
 Fine networks of elastic fibers are often
scattered about the collagen bundles
 Fibroblasts are the most abundant cells in this
tissue
 Found in the dermis of the skin, sheaths of
nerves, capsules of spleen, testes, ovary,
kidney and lymph node
Specialized Connective Tissue

 Reticular Tissue
 Adipose Tissue
 Pigment Connective Tissue
 Reticular Tissue

 Type III collagen is the major fiber

component of reticular tissue
 Fibers form mesh-like networks with
fibroblasts and macrophages
 Forms the framework of liver sinusoids
adipose tissue, bone marrow, lymph
nodes
 Reticular fibers readily stain with silver-
argyrophilic fibers
 Adipose Tissue

 White adipose tissue

 Composed of unilocular adipose cells
 Brown adipose tissue
 Composed of multilocular adipose
cells, containing numerous large
mitochondria
 Pigment Connective Tissue

 Contains pigmented connective

tissue cells - Melanophages
 Ex. dermo-epidermal junction