Connective Tissues and Extracellular

Matrix

Prof. F.L. Chan

School of Biomedical Sciences

PFOS1(23)
Organ = parenchymal tissue + stromal tissue
e.g Mammary gland = glandular tissue (functional part) +
connective tissue, fat cells, blood vessels, lymphatics and
nerves (supporting part)
- Epithelia are avascular (no blood vessels). Epithelial cells are
functionally dependent on the underlying connective tissue for
exchange of oxygen, nutrients and supply of trophic factors (e.g.
growth factors), and removal of waste.
 General functions of connective tissues
1. Support and binding of other tissues
(e.g. epithelia, blood vessels and nerves)
2. Exchange of materials (via blood
vessels) and holding body fluids
3. Protection: defending the body against
infection (by white blood cells/leukocytes)
4. Storage of fat as reserve and insulation
(by adipose tissue)
5. Wound healing

The diversified functions of connective tissues depend on:

•Variety of cell types
•Types of extracellular fibers
•Components of ground substance
 Characteristics of connective tissues

• Found throughout the body and widespread in many

primary tissues and organs
• Connective tissues consist of cells and extracellular
matrix which includes extracellular fibers, ground
substance (gel-like non-structural material) and tissue
fluid
• Connective tissue comprises a very diverse group of
tissues with various functions
• All connective tissues are derived from embryonic
tissue mesenchyme
 Types of connective tissues
1. Embryonic connective tissue
a. Mesenchyme
b. Mucous connective tissue (e.g. Wharton’s jelly in
umbilical cord)
2. Connective tissue proper
a. Loose (areolar) connective tissue
b. Dense connective tissues: regular and irregular
3. Specialized connective tissues
a. Bone
b. Cartilage
c. Blood
d. Reticular tissues: in hemopoietic (hematopoietic)
and lymphatic tissues
e. Adipose tissue
Different types of connective tissues have a
common embryonic origin: mesenchyme
 Basic organization of connective tissues

e.g. Loose (areolar) connective tissue:

- A model connective tissue
- A common connective tissue type underlies all epithelia, surrounds
blood vessels and nerves

A. Cell types:
- Fibroblasts
- Fat cells (adipocytes)
- Mast cells
- Macrophages
- Plasma cells
- Lymphocytes

B. Extracellular matrix:
- Collagen fibers
- Elastic fibers
- Ground substance
(tissue fluid, proteoglycans &
glycoproteins)
Loose and dense connective tissues
e.g. in mammary gland

Dense irregular
connective tissue

Loose connective
tissue

Mammary gland
 Loose (areolar) connective tissues

• Fine network of
collagen/elastic/reticular fibers,
with fluid-filled spaces
• Cells: fibroblasts & blood-borne
cells
• Functions: most general
functions of connective tissues
e.g. support and binding
 Dense irregular connective tissues

• Large amount of collagen fibers, high

tensile strength/elasticity
• Fibers in random direction or layers
• Cells: mostly fibroblasts
• Functions: provides structural
strength/elasticity
Examples:
dermis of skin, submucosa of
digestive tract, fibrous capsules
of joints, fascia
 Dense regular connective tissues

• Dense parallel orientation of

collagen fibers – to withstand
tensile forces in one direction
• Cells: fibroblasts
• Functions: to attach muscles to
bones; bones to bones
• Examples: Tendons, ligaments
 Adipose tissue (white)

• Large number of adipocytes,

few fibers
Functions:
• Tissue for energy reserve and
insulation
• Endocrine function in regulation
of energy metabolism and
homeostasis
 Brown adipose tissue
- Tissue contains more blood supply; fat cells contain more mitochondria
and many lipid droplets.
- It is present in aorta, kidney, neck and more abundant in the newborn.
 Reticular connective tissues

• Locations: all lymphoid organs,

hemopoietic tissue (bone marrow), liver
• Rich in reticular fibers (type III
collagen; stained by silver staining) which
form a branched network to house various
cell types for cell-cell interactions
 Connective tissue cells

A. Fixed connective tissue cells: B. Transient connective tissue cells

1. Fibroblasts (or myofibroblasts) (blood-born, immune functions):
2. Macrophages 1. Lymphocytes
3. Adipocytes 2. Plasma cells (production of antibodies)
4. Mast cells 3. Monocytes
5. Reticular cells in reticular tissues 4. Granular leukocytes:
neutrophils, eosinophils, basophils
 Connective tissue cells

F = fibroblast; L = lymphocyte; P = plasma cell

 Fibroblasts

Functions: synthesis of
extracellular matrix
 Macrophages

- Phagocytic cells derived from monocytes in blood

- Free-moving in blood and tissues, or fixed in organs (e.g.
lymph node, spleen, liver, skin)
- Functions: phagocytose pathogens (e.g bacteria), dead
cells, RBC etc; defense and immune responses
 Adipocytes (fat cells)

- Cells contain a single large lipid droplet, with nuclei squeezed

on periphery
- Functions: synthesis and storage of fat, and endocrine
regulations
 Mast cells
• Cellular granules contain vasoactive and immunoreactive substances
e.g. histamine, heparin
• Functions: mediate inflammation and allergic reactions
 Lymphocytes

- Cells with a darkly stained nucleus and small amount of cytoplasm

- Functions: various immune responses for defense and inflammation
 Plasma cells

• Cells with well-developed Golgi apparatus and RER

• Cells are active in antibody synthesis and differentiated from B-
lymphocytes
 Monocytes
Cells of Mononuclear Phagocytic System:
- Macrophages (histiocytes) in connective tissues, peritoneal cavity
- Kupffer cells in liver
- Alveolar macophages in lungs
- Macrophages in lymphoid organs
- Osteoclasts in bone
- Microglia in CNS
- Langerhans cells in epidermis
 3 Major types of connective tissue fibers:

A. Collagen fibers (Types I, II collagens)

- Tough fibers arranged in bundles; provides great
tensile strength
B. Reticular fibers (Type III collagen + proteoglycans)
- rich in hemopoietic (bone marrow) and lymphoid
tissues, & liver
- small and branched collagen fibers that form delicate
networks to house cells for better cell-cell interactions
C. Elastic fibers (elastin) and microfibrils (fibrillins)
- long, thin fibers that allow for stretching
- rich in dermis, large blood vessels & elastic cartilage
Connective tissue fibers (I)

Collagen fibers and fibrils

Collagen fibers
 Ultrastructure of collagen fibrils and their association
with proteoglycans

• Collagen fibrils show a characteristic 67-68 nm cross-striation

pattern
 Connective tissue fibers (II)

Elastic fibers

Elastic fiber

Areolar connective tissue Aorta

Ultrastructure of elastic fibers

Elastic fiber

Microfibrils
 Extracellular matrix = connective tissue fibers + ground substance

• Ground substance is a viscous and clear substance in fresh connective

tissues and contains mainly tissue fluid, proteoglycans, glycosaminoglycans
and glycoproteins.
• It appears as empty spaces in histological sections but reacts to PAS
reaction. At EM level, it appears as amorphous substance.
• Functions: very diverse from tissue support, molecular filter, cell adhesion,
cell-matrix interactions to wound healing.
 Major components of ground substance

1. Proteoglycans = core protein + glycosaminoglycans (GAGs)

2. Hyaluronic acid (hyaluronan)
3. Glycoproteins e.g. fibronectin – adhesion proteins
A proteoglycan molecule as seen under electron microscope
 Glycosaminoglycans (GAGs)

- GAGs are unbranched long chains of polysaccharides

made up of repeating disaccharide units and components of
proteoglycans

Family of GAGs:
- Chondroitin 4-sulfate
- Chondroitin 6-sulfate
- Dermatan sulfate
- Heparan sulfate
- Heparin
- Hyaluronic acid (hyaluronan)