CONNECTIVE TISSUE Introduction
CONNECTIVE TISSUE Introduction
(CT)
By
Tilahun Alemayehu Nigatu, Assistant
Professor in Biomedical Sciences,
JU, July 2022
CONNECTIVE TISSUE (CT)
– Includes most diversified group of supportive tissues (exist
as diverse morphological and functional forms) = confer
diverse structural and functional forms.
– The most widespread tissue (widely distributed in the
body)
– named for only one of its ordinary functions i .e.
connecting or binding different tissues or organs together,
and carrying their blood & nerve supply
– Sometimes also called supportive ti ssue
– Neither of these names adequately address the
structure and function of this tissue to i ts full extent.
– derived from an embryonic tissue = Mesenchyme
FUNCTIONS of CTs
– CTs have a number of important functions:
– provide structural, metabolic, functional and nutritional
support
– form foundations or the framework of the body to/in
which other tissues are attached/supported or
protected
– Forms fibrofatty stroma of organs and glands
– provide insulating & storage depot of energy (fat)
– play a vital role in the defense mechanism of the body
& ti ssue repair after ti ssue injury.
Functions of CTs
– Binding of tissues
and organs
together
– Support
– Physical
protection
– Immune
protectio
n
– Storage
– Heat
productio
Summary of the functions of connective
1. tissues:
Bind, connect, support and form the skeleton of most
body organs or the entire human body.
2. Defense function through i ts contents of phagocytic and
other immune cells and production of antibodies.
3. Nutrition and storage of l ipids, water, electrolytes
(minerals such as calcium, phosphates, etc) and
plasma
proteins.
4. It i s a medium for the transport of different vital
materials between the blood and the connective ti ssues.
5. It i s a mirror for the different endocrinal diseases
e.g. myxedema, caused by an underactive or
atrophied thyroid gland, or dry swelling of the skin
General Characteristics of CTs
1. Consist of CT cells and abundant extracellular matrix (fibers and
ground substance)
Connective Tissue
Extracellular
CT Cells
matrix)
CT Fibers Tissue
Ground substance fluid
Source: M. Ross
CT Extracellular matrix
Ground Tissue
CT Fibers
substance fluid
Cartilage
Fibrous Connective Tissue (CT Proper)
– Most diverse and ordinary type of CT.
– Contain extremely conspicuous fibers – hence the name,
fibrous connective tissue.
– Also known as ordinary CT or CT proper because in
includes the familiar types of CTs such as tendon,
ligaments, fascia, retinacula, etc, which have
binding/connecting functions.
– Consists of cells suspended in tissue fluid, fibers, and
something called ground substance.
– Of these three, which you do suppose is typically
NOT that much abundant?
– The illustrations on the next two slides show 3 -D models of
ordinary CT with some typical CT fibers, typically made of
multiple strong filamentous proteins twisted about one
another.
Composition of ordinary connective tissue (CT
Proper)
Fibroblast Macrophage Plasma cell Mast cell
Ground
substanc
e
Elastic
fiber
Collage
n fiber
Collagen Fibers as
seen by scanning
electron microscope
1.Collagenous Fibers (KOL-a-jen; colla = glue, gen= produced)
– tough, fi rm, inelastic fibers which resist the tensile forces
upon the tissues (flexible but with extremely high tensile
strength), also called white fibers.
– the most common fibers in connective tissue and the most
abundant proteins in the body.
– Although fresh collagen fibers are colorless strands, when
present in large numbers (e.g, in tendons) they appear
white.
– The highly regular orientation of subunits in collagen fibers
makes them birefringent under the polarizing microscope.
– In the l ight microscope, collagen fibers are acidophilic;
they stain pink with eosin, blue with Mallory
trichrome stain, green with Masson tri chrome stain,
and red with Sirius red.
Blue stained collagenous tissue in Lamina
propria (Mallory Trichrome stain)
Pink stained collagenous tissue of Tunica albuginea , Testis (HE stain)
19
Collagenous Fibers
– synthesized by different types of cells in d/t tissues:
fibroblasts, chondroblasts, osteoblasts, odontoblasts,
reticular cells, adipocytes, smooth muscle fibers, etc
– ultrastructurally consists of:
– Collagen macromolecules called Tropocollagens
running parallel and overlapping each other.
– Tropocollagens form collagen fibrils, each of which
represents a structural unit (the unit fibrils of
collagen).
– Each unit fibril shows transverse bands.
– Each tropocollagen molecule is a right-handed triple
helix formed by intertwining of three procollagen -
– Each procollagen -polypeptide chain is rich in amino
acids: proline, hydroxyproline, hydroxylysine and glycine
– Every third amino acid in the chain is a glycine
molecule, except at the ends of the -chains.
– A hydroxyproline or hydroxylysine frequently precedes
each glycine in the chain, and a proline frequently
follows each glycine in the chain.
– Along with proline and hydroxyproline, the glycine is
essential for the triple-helix conformation.
– Associated with the helix are sugar groups that are
joined to hydroxylysyl residues.
Collagen Synthesis 1. Translation
polypeptide chains
of procollagen on
ribosomes of the RER.
2. Translocation into RER lumen,
removal of signal peptide at N-
and C-terminals to yield
procollagen polypeptides.
1 3. Hydroxylation (circles) of
selected prolines and lysines
4. Glycosylation (triangles) of
2 selected hydroxylysines
– Self-assembly through
interwining of three pp
3 chains into one tropocollagen
triple helix in RER cisternae.
– Vitamin C is important in
4 collagen synthesis as cofactor
for prolyl-hydroxylase.
Collagen synthesis cont’d….
(tropocollagen
)
– The procollagen chains form long left-
handed helices (~600 to 3,000 amino
acids long) consisting of repeating amino
acid triplets: Gly-X-Y (left)
– Three pp chains of the same (homo-
trimeric) or different (heterotrimmeric)
types intertwine to form a tropocollagen
triple helix (right).
– At least 42 different procollagen
chains are encoded by different genes.
– Fibrous (fiber-forming) collagens:
consists of tropocollagen molecules of
only triple helical domains.
– Non-fibrous collagens: contain tropo-
collagens of triple pp chains with
Assembly of collagen molecules into collagen fibers
– The following slide shows an aggregate of collagen
molecules into fibrils, fibers, and bundles in collagen type I.
– There is a stepwise overlapping arrangement of rod l ike
collagen molecules (tropocollagens), each measuring 300
nm in length and 1.5 nm thick (1).
– This arrangement results in the production of alternating
spaces and overlapping regions (2), which cause the cross-
striations characteristic of polymeric collagen fibrils (20-90
nm in diam, 50nm on average & several μm long) which
confer a 67 nm periodicity of dark and light bands (3).
– Collagen fibrils aggregate and are covalently cross-linked
to form fibers (4), which in collagen type I further
aggregate further to form collagen bundles (5) routinely
called collagen fibers (1 to 20 μm in diameter) seen by
This diagram shows extracellular polymerization of collagen
molecules (tropocollagens) to form fibrils, fibers, and bundles.
– Three procollagen polypeptide -chains form one tropocollagen
triple helix. Tropocollagen molecules are ~300 nm long, ~1.5 nm
wide. Tropocollagens assemble head-to-tail and side-to-side
(staggered) to form a collagen fibril (20 to 90 nm in diam & several μm long).
COLLAGEN FIBERS TYPE I BY TEM
– Around 28 types of collagens have been identified and
designated with Roman numerals (I–XXVIII) based their
chronolgy.
– Each type i s distinguishable by i ts molecular
composition,
morphologic characteristics, distribution, function, and
pathologies.
1. Type I: in ordinary connective tissues, bone, dentine, fibrocartilage,
capsule of organs.
2. Type II: in hyaline and elastic cartilages, nucleus pulposus.
3. Type III (reticular fibers): lymphoid organs, spleen, skin, lens capsule,
stroma of organs such as liver, kidneys, lung, and vessels.
4. Type IV: in basal lamina: collagen fibrils assemble as a lattice-like
network.
5. Type V: fetal membranes, placenta, & with type I.
6. Type VI: Forms part of the cartilage matrix immediately
Collagen
Form Tissue
Type
Synthesizing Cells
large banded
I bone, dentin, skin, tendons, ligaments, fibroblast, osteoblast,
cornea, fibrocartilage, internal odontoblast
fibers and bundles organs(~90% of body collagen)
Fibrils (50 nm cartilage (hyaline and elastic), and
II chondroblast
thick) nucleus pulposus of IVDs
fibroblast, reticular cell,
III Fibrils and small internal organs
(e.g., reticular fibers in lymph nodes, smooth muscle cell,
banded fibers
spleen, liver, blood vessels, skin) hepatocyte
Sheet-like, two- basal lamina (lamina densa) and epithelial cell, muscle
IV dimensional cross- external lamina cell, Schwann cell,
linked network adipocyte
same as type I (polymerizes with
V fibril, thin fibers fibroblast
type I fibril to regulate properties)
VII Networked fibrils beneath epithelia (anchoring fibrils) Epithelial cells
cartilage
IX fibril-associated chondroblast
(lateral association with type II)
forming bone
X network chondrocytes
(hypertrophic zone of growth plate)
XI fibril, thin fibril
same as type II (polymerizes with type chondroblast
Types of Collagenous fibers
Four mains structural & functional distinct groups of
collagens:
1. Fiber-forming collagens (tropocollagens): form the classic
collagen fibers (type I,II,III,V & XI) which interact with each other and
ECM component through fibril-associated collagens (type IX, XII & XIV)
2. Fibril-associated collagens (type IX, XII & XIV)
3. Network-forming collagens (type IV): are collagens which
form the lamina densa of basal lamina & external lamina.
4. Anchoring collagen (type VII)
– Collagen that forms anchoring fibrils that bind the
basal lamina to reticular fibers in the underlying CT.
– Anchors epithelial basal lamina to underlying stroma
– Has, a globular terminal domain (450 nm) at each end
Collagen type IV in basal lamina
Mutations in collagen
Collagen Diseases –
chains can lead to:
A: Failed assembly and
degradation of procollagen
molecules
B: Formation of abnormal
triple helices
(tropocollagens), fibrils, &
fibers
– Defective chains can
interfere with assembly
of normal chains; this
explains the dominant
inheritance of some
collagen diseases.
– Ehlers-Danlos syndrome - commonly shows
hyperextensible skin and joints, skin fragility, and reduced
wound healing
Lack of vitamin C
Scurvy Ulceration of gums,
(cofactor for prolyl
hemorrhages
hydroxylase)
E E
Electron micrograph of an elastic fiber. The elastin (E) of the fiber has a
relatively amorphous appearance. The fibrillin microfibrils (arrows) are
present at the periphery and within the substance of the fiber. A number
of collagen fibrils (C) are also present in this electron micrograph.
Elastic fibers in relaxed state (Elastic cartilage)
Collagen bundles
C
C
E
C
– contain an N-acetylated
sugar and a uronic acid,
which usually is glucuronic
acid or iduronic acid. Heparan sulfate
(Hydrolytic 12-17 m
enzymes and Neutrophil Cell mediated immune response
Histaminase - phagocyte
& aryl
sulftase) (Bactericidal
enzymes)
Humoral immune response
Macrophage
- phagocyte Plasma cell - antibody
Cells
Classification of CT
I. Embryonic CTs: II. Mature CT proper:
1. Mesenchyme A. Ordinary/Fibrous CTs
1. Loose CT
2. Mucoid (Mucous CT) a. Loose areolar
B. Specialized CTs/ CTs with b. Adipose
special properties: c. Reticular
1. Blood tissue 2. Dense CT
a. Dense regular
2. Bone tissue 1. Collagenous
3. Cartilage 2. Elastic
b. Dense irregular
1. Collagenous
2. Fibroelastic
Types of Fibrous Connective
• Two types based on the
Tissues
relative abundance of
fibers:
1. Loose Connective Tissue
– Lots of ground
substance
and cells. Fewer fibers.
– Leaves abundant empty
spaces in tissue sections.
2. Dense Connective Tissue
– Fibers are predominant
constituents.
– Much lower number of
cells and less ground
substance.
– Fibers appear closely
1. MESENCHYME
– i s embryonic CT mainly present in the developing embryo
– scattered between the developing organs and tissues.
– consists of a population of undifferentiated cells,
mesenchymal cells in gel-like, amorphous ground
substance containing scanty scattered reticular fibers.
Mesenchymal cells
– are typically star-like cells with many shapes, having large
euchromatic nucleus and prominent nucleoli which
indicate high levels of synthetic activity.
– multipotential stellate cells (many cytoplasmic processes)
with pale staining cytoplasm and oval nucleus.
Mesenchyme
Mesenchyme: Mesenchymal cells are surrounded by an extracellular matrix
which the y p roduced and which consists largely of a loose ground substance
rich in hyaluranon (hyaluron ic acid) . This section is stained with M asson trichro
me which stains collagen fibers blue and the lac k of collagen in mesenchyme is
apparent.
2. MUCOID (MUCOUS) CT
– present in the umbilical cord, in the teeth and eye as filling
ti ssue , and as subdermal CT of the embryo.
– loose amorphous C.T. with a jelly-like matrix containing
hyaluronic acid and little amounts of collagen types I and
III, mesenchymal cells and fibroblasts.
Characteristics:
1 Loos e ground substance (mainly Hyaluronic acid).
2 Few fibers (type I & type III collagen fibers).
3 Fibroblasts and mesenchymal cells.
Location Sites:
1. Subdermal C.T. of the embryo
2. Umbilical cord (Wharton’s jelly).
3. Dental pulp of teeth.
Wharton’s jelly
TS of Umbilical cord showing umbilical vessels housed in
Wharton’s jelly (mucoid CT) covered by a layer of amnioblast
Developing Teeth
II. CONNECTIVE TISSUE PROPER
1. LOOSE CT
A. LOOSE AREOLAR CT (AREOLAR CT )
– i s a very– common
i s a verytype
commonof CTtype
that of
supports
CT thatmanysupportsstructure
many
which are normally under some pressure and lowstructures friction.
– which are normally
has usually underdistribution
subepithelial some pressure and lowepithelia,
supporting friction.
– forming a papillary layer of the dermis, a layer around
has usually subepithelial distribution supporting epithelia,
small blood
forming and layer
a papillary lymphatic
of the vessels,
dermis, aand layerfills
around the
spaces
small between
blood and muscle and nerve
lymphatic fibers.and fills the
vessels,
spaces
– also foundbetween
in the muscle and nerve
hypodermis, in thefibers.
linings of the
– peritoneal
also found and pleural
in the cavities, in
hypodermis, glands,
in the andofinthe
linings the
mucous membranes
peritoneal (wetcavities,
and pleural membranes thatand
in glands, l ine the
in the
hollow
mucous membranes (wet membranes that l ine the
organs)
hollowsupporting the epithelial cells.
organs)
– has supporting
all the the epithelial
main components cells. CT (cells,
of ordinary
LOOSE AREOLAR CT
Loose Areolar CT
–– The
Themost
mostnumerous
numerouscells
cellsare
arefibroblasts
fibroblastsand
andmacrophages
macrophages
but
but all
all other
othertypes
typesofof ordinary
ordinaryCTCTcells
cells are
arealso
alsopresent.
present.
– less amount
– less of all
amount of CT
all fibers alsoalso
CT fibers appear in this
appear ti ssue.
in this ti ssue.
– With
– Witha moderate amount
a moderate amountof ground substance,
of ground loose
substance, loose
areolar connective tissue has a delicate consistency; i t i s
flexible, well vascularized, and not resistant to stress.
Locations
– inin papillary
papillarydermis
dermisof ofskin
skin&&subcutaneous
subcutaneoustitissue,
ssue,
– lamina
lamina propria
propria&&submucosa
submucosaof ofGIT&
GIT& respiratory
respiratorytracts,
tracts,
– around
aroundblood
bloodvessels
vessels&&organs
organsand
andserous
serousmembranes,
membranes,
around muscle
around musclefibers
fibers(endomysium)
(endomysium)and and nerve
nervefibers
fibers
(endoneurium).
– –accumulates
accumulateslarge
largeamount
amountofoftissue
tissuefluid
fluidand
andleads
leadstoto
tissue
tissu
Loose Areolar CT
– Loose arrangement
of collagenous and
elastic fibers &
some reticular
fibers. (All the 3
fiber types.)
– Scattered Cells.
– All cell types can
be present
embedded in
abundant ground
substance.
– Numerous blood
vessels. (Highly
vascular.)
Loose Areolar CT with numerous cells
Loose Areolar CT
Locations:
– Underlying nearly
all epithelia.
– Surrounding blood
vessels, nerves,
trachea, and
esophagus.
– Between muscles.
– Within
mesenteries, and
the visceral layers
of the pericardium
and the pleura.
Loose Areolar CT in Lamina propria of GIT
b. ADIPOSE TISSUE
– Loose
LooseCT
CTrich
richininadipocytes
adipocytes
– Two
Twotypes
typesofofadipose
adiposetissues:
tissues:
1. Unilocular
Unilocularadipose
adiposetissue
tissue
(yellow fat)
––
its its
fatfat
cells areare
cells of of
unilocular
unilocular
type,
type,
––
present
present in subcutaneous
in subcutaneous
tissue,
tissue,
around
around
organs
organs
andand
neurovascular
neurovascular
bundles.
2. Multilocular
2. Multilocularadipose
adiposetissue
tissue
(brown fat)fat)
(brown
––
present
present
in infants
in infants
andand
hibernating
hibernating
animals,
animals,
–
Functions of Adipose Tissue
– Energy storage
– Thermal
insulation
– Shock absorption
– Protective
cushioning for
some organs
– Accounts 15–20%
of the body
weight in men of
normal weight; in
women of normal
weight, 20–25%
of body weight.
White/Yellow Adipose Tissue
Microscopic
Appearance:
– Dominated by
adipocytes – large,
empty-looking cells
with very thin rim
of cytoplasm.
– Often paler.
– Surrounded by rich
capillaries
Unilocular (White) Adipose Tissue
– Is formed of lobules of unilocular adipose
cells.
– Highly vascular.
Function:
1 Synthesis, Storage & release of fat.
2 Thermal insulator.
3 Shock absorber.
Sites:
– Subcutaneous layers especially in buttock, hips,
palms of the hand and sole of the foot.
– Abdominal wall.
– Female breast
– Around the kidney, heart, yellow bone marrow.
N.B. White adipose T. appears only after birth.
Brown Adipose Tissue
– The color of brown adipose tissue or
brown fat is due to both the
numerous mitochondria found in
White adipose tissue
the adipocytes and the large
number of blood capillaries in this
tissue.
– Adipocytes of brown fat are
therefore called multilocular
– The many small lipid droplets,
abundant mitochondria, and rich
vasculature all help mediate this
tissue's principal function of heat Brown adipose tissue
production.
– unlike white adipose tissue, which
is present throughout the body,
brown adipose tissue has a much
more limited distribution.
FAT LOBULES of WHITE ADIPOSE TISSUE
WHITE ADIPOSE TISSUE IN THE WALL OF CECUM
126
c. RETICULAR CT
– composed
composedmainlymainlyofoftype
typeIIIIII
collagen fibers in a form of
network or mesh, fibroblasts
called reticular cells, and
lymphocytes.
– –Forms
Formssupportive
supportive
framework of liver sinusoids,
sinusoids,
red bone marrow, lymph
nodes,
red bonespleen,
marrow, smooth
lymph
muscles, i slet ofsmooth
nodes, spleen, La
ngerhans i slet of La
muscles,
ngerhans
and adiposetissues.
– and adiposetissues.
Reticular cells - synthesize
reticularcells
– Reticular fibers in lymphatic
- synthesize
ti ssues; cell
reticular
processes body
fibers and
in lymphatic
completely
ti ssues; cell body fibers
and Lymph node (silver stain)
surround reticular
RETICULAR CT
Tendon cell
= collagen fibers
cross- section of muscle & tendon
tendon
Muscle fibers
tendon
Ligamentum nuchae (Elastic ligament )
Ligamentum nuchae (cross
section)
Elastic fibers
Fibroblasts
(2) Elastic ( yellow fibrous ) tissue