+

Connective Tissue
Dr. Samia Farrara MBS University of
Denver USA
+
Function, origin

◼Structure

◼Protection

◼Filling

◼Carrier

◼Defensive

◼Repair
+
Structure

◼ Cells

◼ Fibers

◼ Ground substance

◼ The classification of connective tissues is based on

cellular and extracellular components and special
function.
+
+
Classification
◼ Connective tissue proper(loose and dense)

◼ Embryonic connective tissue(mesenchymal and mucoid)

◼ Specialized connective tissue:

1. adipose tissue

2. Blood

3. Bone.

4. Cartilage

5. Reticular connective tissue

+
Cells
◼ Fibroblast:present in connective tissue proper. Produce
the Extracellular component ( collagen and elastin) and
matrix).

◼ Macrophage

◼ Plasma cells.

◼ Mast cells

◼ Leukocytes.(diapedesis) inflamation. Few hours to days.

◼ Adipocyte
+ Fibroblasts typically have large active nuclei and eosinophilic cytoplasm that
tapers off in both directions along the axis of the nucleus, a morphology often
referred to as “spindle-shaped.” Nuclei (arrows) are clearly seen, but the
eosinophilic cytoplasmic processes resemble the collagen bundles
+
Both active and quiescent fibroblasts may sometimes be distinguished, as
in this section of dermis. Active fibroblasts have large, euchromatic nuclei
and basophilic cytoplasm, while inactive fibroblasts (or fibrocytes) are
smaller with more heterochromatic nuclei (arrows).
+

◼ 1 Fibroblast
 Characteristic features of macrophages seen in this TEM of one such
+ cell are the prominent nucleus (N) and the nucleolus (Nu) and the
numerous secondary lysosomes (L). The arrows indicate phagocytic
vacuoles near the protrusions and indentations of the cell surface.
+
Mast cells are components of loose connective tissues, often located near small blood vessels (BV). (a)
They are typically oval shaped, with cytoplasm filled with strongly basophilic granules.(b)
Ultrastructurally mast cells show little else around the nucleus (N) besides these cytoplasmic granules
(G), except for occasional mitochondria (M). The granule staining in the TEM is heterogeneous and
variable in mast cells from different tissues; at higher magnifications some granules may show a
characteristic scroll-like substructure (inset) that contains preformed mediators such as histamine and
proteoglycans. The ECM near this mast cell includes elastic fibers (E) and bundles of collagen fibers (C).
+
Mast cell.
+
Plasma cells are large, ovoid cells, with basophilic cytoplasm. The round nuclei frequently
show peripheral clumps of heterochromatin, giving the structure a “clock-face”
appearance.
Plasma are often more abundant in infected tissues, as in the inflamed lamina propria shown
here. A large pale Golgi apparatus (arrows) at a juxtanuclear site in each cell is actively
involved in the terminal glycosylation of the antibodies (glycoproteins). Plasma cells leave
their sites of origin in lymphoid tissues, move to connective -tissue, and produce antibodies
that mediate immunity.
+
Embryonic CT

◼ Mesenchymal : contain progenitor cells for all adult

connective tissue cells. Undifferentiated cells. Active
mitosis. Matrix. Few collage. Mesenchymal layer of
early embryo.

◼ Mucoid :fibroblast and collage in viscous matrix.

Support large blood vessels. Matrix of fetal umbilical
cord.
 +
Mesenchyme consists of a population of undifferentiated cells, generally elongated but with
many shapes, having large euchromatic nuclei and prominent nucleoli that indicate high levels
of synthetic activity. These cells are called mesenchymal cells. Mesenchymal cells are
surrounded by an ECM that they produced and that consists largely of a simple ground
substance rich in hyaluronan (hyaluronic acid), but with very little collagen.
+
Connective tissue proper

Loose areolar CT: much ground substance and many cells.

Little collage randomly distributed. support microvasculature.
Nerve and immune defense cells. Lamina propria below the
epithelial. Most common. All types of cells and fibers.

Dense regular CT: filled with parallel bundle of collage. Few

fibroblast. Strong connection within the musculoskeletal.
Strong resistance to force. Ligament. Tendon.

Dense irregular CT :few cells and little ground substance

randomly arranged. Protect and support the organ. Dermis.
Organ capsules. Submucosa digestive system.
+
LOOSE AND DICT
+
DRCT
+ networks of delicate, black reticular fibers are prominent. These fibers serve as
a supportive stroma in most lymphoid and hematopoietic organs and many
endocrine glands. The fibers consist of type III collagen that is heavily
+ The diagram shows only the fibers and attached reticular cells (free, transient
cells are not represented). Reticular fibers of type III collagen are produced and
enveloped by the reticular cells, forming an elaborate network through which
interstitial fluid or lymph and wandering cells from blood pass continuously
+
Fibers
◼ Collagen types
◼ Type I : abundant. fibroblast. Osteoblast. tendon.ligament bone(
Fibrillar aggregate to form fibrils. Collagen bundles )

◼ TYPE II: cartilage, resistance to pressure ( fibrillar)

◼ TYPE III: reticular tissue ( silver stain black) fibroblast.

◼ TYPE VI: ( non fibrillar) basement membrane . Endothelial.

Epitheilal and shcawn cells( sheet forming collagens)

◼ TYPE V: fetal membrane. Placenta and blood vessels. With type I in

bone

◼ TYPE VII linking or anchoring collagens anchor basal lamina to

underlying reticular lamina in B.M
+

◼ Fibrillar collagen: type I , II , III.

◼ Sheet forming collagen Type IV

◼ Linking or anchoring Type VII

+
Reticular tissue

◼ Collagen type III

◼ Heavily glycosylated ( silver stain)argyrophilic.

◼ Produced by fibroblast,smooh muscle,

+
Elastic fibers

◼ Thinner than collagen type I.

◼ Elastin molecules rich in glycine and proline

◼ Bending. Stretching

◼ Wall of blood vessels esp arteries. Elastic lamellae.

◼ Composite of fibrillin microfibrils embeded in large masss of

cross linked elastin.( fibroblast).

◼ Fibrillin plus several glycoprotein form microfibril.

+
Subunits of type I collagen, the most abundant collagen, assemble to form extremely strong fibrils, which are
then bundled together further by other collagens into much larger structures called collagen fibers.
(a) TEM shows fibrils cut longitudinally and transversely. In longitudinal sections fibrils display alternating dark
and light bands; in cross section the cut ends of individual collagen molecules appear as dots. Ground substance
completely surrounds the fibrils. (b) The large bundles of type I collagen fibrils (C) appear as acidophilic collagen
fibers in connective tissues, where they may fill the extracellular space. Subunits for these fibers were secreted
by the fibroblasts (arrows) associated with them.
FIGURE 5-8 Copyright © McGraw-Hill Companies
+
FIGURE 5-10 Copyright © McGraw-Hill Companies
+
FIGURE 5-13 Copyright © McGraw-Hill Companies
FIGURE 5-12 Copyright © McGraw-Hill Companies
+
Ground Substances

◼ Is highly hydrated colorless, transparent and homogenous substances

fill the spaces between the cells and fibers( extracellular or
intercellular).

◼ Secreted by fibroblast act as a lubricant and barrier against the

penetration of bacteria and other microorganism.

◼ Composed mainly of:

1. Glycosaminoglycan

2. Proteoglycan

3. Glycoprotein
+

◼ Itis viscous and negatively charged attract cations

and restrict the move of water and ions and
bacteria.

◼ Bind the CT fibers to one another. Strength.

◼ Reservoir for GF.

◼ Reform matrix. Gel like or firmer.

+ GAG

◼ Located on cell surface or in ECM.

◼ Consists of repeated pairs of disaccharide of uronic acid (
glucuronic or iduronic).and hexosamine ( glucosamine or
galactoseamine).
◼ GAC include two groups:
◼ Non-sulfated : hyaluronic acid. bind large amount of water allow
diffusion of nutrition. Lubrication.( UC. SV. VH). Synthesis in ECM by
hyalornate synthase in cell membrane of many cells.(glucosamine-
glucuronate).M.W 100-1000 kDa.
◼ Sulfated : GAC bind to long protein core to give proteoglycan
Strong hydrophilic, hydroxyl sulfate carboxyl group. MW 10-40 KDa
+ GAG

◼ Highly viscous.

◼ Types of sulfated GAG:

◼ Dermatan sulfate: skin. tendon

◼ Keratan sulfate : corne. Cartilage

◼ Chondotin sulfate: bone. Skin. UC

◼ Heparan sulfate: lung. Liver. basal lamina.

+
Proteoglycans

◼ Formed of fibrillar protein core covalently bind to four

SGAC.

In cartilage the molecules of proteoglycan bind the chain of

hyaluronic acid producing larger proteoglycan aggregates.

Fibrillar protein core. Non branched sugar chains.

Synthesis in RER, Golgi

Aggrecan: ECM cartilage

Syndecan: cell surface

+
+
Structural glycoprotein

◼ Made of globular protein bound to branched chains of

monosaccharide.

◼ Types

◼ Fibronectin secreted by fibroblast and some epithelial

cells. Helps in depositions and orientation of collagen and
mediate nromal cells adhesion and migration
◼ Laminin. Non-filamentous cross-shaped, secreted by
epithelial and glial cells. It helps in adhesion of epithelial
cells to laminin-rich basal lamina. Collagen IV .all external
and internal almina rich in laminin.
+
◼ Entacin : epithelial and glial cell. Bind laminin to collagen
IV.

◼ Tenascin: embryo. Binding sites for fibronectin and

integrin.

◼ Integrins: Transmembrane proteins on cell membrane of

connective tissue cells act as matrix receptors to bind to
collagen, fibronectin and laminin mediated by the
inintracellukar proteins.
+
+
Adipose Tissue
◼ CT adipocytes predominate. 15-20% of B.W.

◼ Storage depot for neutral fat ( triglyceride)

◼ Regulation of body energy metabolism. Insulation.

◼ Male
and female fat distribution depends on the sex
hormones..

◼ Adipocytes concentrating triglyceride as lipid droplets.

◼ Adipocytes
metabolically active respond to both nervous
and hormonal stimuli.

◼ Shape the surface of the body.( subcutaneous fat).

+
◼ Helps cushion and keep some organ in place.

◼ Synthesis
lipoprotein lipase which hydrolyze chylomicron
and VLDL at luminal surface of capillary. Leptin control
the amount of adipose tissue in the body by acting on
hypothalamus to decrease food intake.

◼ Rich in nerve and blood supply.

+
White( unilocular) adipose tissue
◼ The most common type.

◼ Composed of cells contain one very large droplets of

whitish-yellow fat in their cytoplasm.

◼ Long term energy storage..

◼ Adipocytes are spherical when isolated but are polyhedral

in adipose tissue.

◼ Unilocular
adipose tissue usually empty in standard light
microscope prep by Xylen and other solvents.

◼ Fat
droplets are not enclosed by a membrane but show many
vimentin filaments at their periphery.
FIGURE 6-1 Copyright © McGraw-Hill Companies
+

◼ The cells has signet-ring appearance, with lipid droplet

displace and flat the nucleus against the cell mem.with thin rim
of cytoplasm.
◼ Cytoplasm surround the nucleus and contain mitochondria and
small G.A and SER and few RER.
◼ Adipocytes surround by a thin external lamina contain collagen
IV.
◼ White adipose tissue subdivided into incomplete lobules by
partitions of connective tissues containing vascular bed and
nerve network.
◼ Almost all the tissue in adult are unilocular. The color of fresh
dissection vary from white to yellow depended on diet. amount
of carotenoid dissolved in the lipid.
FIGURE 6-2 Copyright © McGraw-Hill Companies
FIGURE 6-3 Copyright © McGraw-Hill Companies
+
Brown fat or multilocular Fat

◼ Constitutes 2 -5 % of the new born B.W

◼ Located mainly in the back, neck and shoulders.

◼ Reduced during the childhood. In adult it is found only in

scattered area. Esp around the kidney, adrenal glands, aorta,
and mediastinum.

◼ The color is brown due to both very abundant mitochondria

(containing the cytochrome pigments) and the large number

of blood capillaries in this tissue. This help in heat production.
+
◼ The cells are polygonal and smaller than cells of white fat.

◼ Cytoplasm contains a great number of fat droplets of various

size and nuclei often centrally located.

◼ Adipocytes of brown fat are often closely packed around

large capillaries. Tissues is subdivided by a partitions of CT
into lobules. cells receive direct sympathetic innervation.

◼ Themain function is production of heat by nonshivering

thermogenesis .

◼ Norepinephrine activate lipase promoting hydrolysis of TG

to F.A and glycerol. F.A not released but metabolized lead to
heat production.
FIGURE 6-4 Copyright © McGraw-Hill Companies
+

◼ Increase temperature within the tissue and warm the

locally circulating blood which distribute the heat through
the body.
◼ Innermitochondrial membrane of brown fat cells has a
transmembrane integral protein called thermogenin which
allow the back flow of proton so energy dissipated as heat.
◼ Thenumber of brown adipocytes increase during cold
adaptation often appear as a clusters of multilocular cells
in white adipose tissue.
◼ Autonomic nerves promote brown adipocytes
differentiation and prevent apoptosis in mature brown
cells.
FIGURE 6-5 Copyright © McGraw-Hill Companies