Connective Tissue

Connective tissue
By Asfaw B.(MSc.)
02/17/2024 12:07 PM By Asfaw B. medicine class 1

Objectives of cession
• At the end of the session, students will be effectively able:
• To identify cells of connective tissue
• To describe ECM of connective tissue
• Demonstrate types of connective tissue
• To sketch microscopic feature of CT

Introduction
• Connective tissue is one of the most abundant and widely distributed
tissues in the body
• Connective tissue maintains the form of organs throughout the body.
• The major constituent of connective tissue is the ECM.
• ECM consist of protein fibers and ground substance
• The hydrated nature of ECM provides the medium for the exchange of
nutrients and metabolic wastes between cells and the blood supply.

Con’t…
• Differences in composition and amount of the cells and ECM are

responsible for the structural, functional, and pathologic diversity
of connective tissue
• Connective tissues originate from embryonic mesenchyme, a

tissue developing mainly from the mesoderm.
• Mesenchyme consists of a population of undifferentiated cells

Functions of connective tissues
It binds together, supports, and strengthens other body tissues.
It protects and insulates internal organs.
It compartmentalizes structures such as skeletal muscles.
It serves as the major transport system.
It is the primary location of stored energy reserves.
It is the main source of immune responses.
By Asfaw B. medicine class 02/17/2024 12:07 PM 5

Cells of connective tissue
1. Fibroblasts
• They most common cells in connective tissue proper.
• Synthesize and secrete most of the ECM.
• Histologically, 2 levels of fibroblast activity observed
 Quiescent fibroblasts
 Active fibroblasts
• Fibroblasts are targets of growth factors that

influence cell growth and differentiation.
• In adults, connective tissue fibroblasts rarely undergo

division.
• Fibroblasts originate locally from mesenchymal cells
Con’t…
2. Adipocytes
• They are found in connective tissue of many organs.
• They are specialized for cytoplasmic storage of lipid as neutral

fats, or less commonly for the production of heat.
• The large deposits of fat in the cells also serve to cushion and
insulate the skin and other organs.

Con’t…
3. Macrophages
• They are characterized by their well-developed phagocytic ability
• They are specialized in turnover of protein fibers and removal of dead cells
and tissue debris.
• They have an eccentrically located, oval or kidney-shaped nucleus.
• They have a characteristic irregular surface with pleats, protrusions, and
indentations.
• These morphologic features helps in pinocytotic and phagocytic activities.
• They generally have a well-developed Golgi apparatus and many
lysosomes.
• They are specialized from the monocytes.
• They patrol for potential pathogens by amoeboid movement
Macrophages

Con’t…
• Different name of microphages in different tissue

 Osteoclasts- in bone
 Kupffer cells- in liver
 Microglial- in CNS
 Langerhans- in skin
 Monocytes- in blood
 Dendritic cell- Lymph nodes, spleen
 Hofbauer cells- in placenta
 mesangial cells- in kidneys
 Multinuclear giant cell- pathologic tissue

Con’t…
4. Mast Cells
• Mast cells filled with basophilic secretory granules.
• The nucleus is obscured by abundant secretory granules.
• They function in localized release of bioactive substances with roles in the
local inflammatory response, innate immunity, and tissue repair.
• Secretory granules includes the following:
 Heparin-a sulfated GAG that acts locally as an anticoagulant
 Histamine-promotes increased vascular permeability and smooth muscle
contraction
 Serine proteases-activate various mediators of inflammation
 Eosinophil and neutrophil chemotactic factors- attract those leukocytes
 Cytokines- directs activities of leukocytes and other cells of the immune
system
 Phospholipid precursors for conversion to prostaglandins, leukotrienes, and
other lipid mediators of the inflammatory response.
Medical application
• Increased vascular permeability is caused by the action of

vasoactive substances such as histamine released from mast cells
during inflammation.
• Increased blood flow and vascular permeability produce local
swelling (edema) redness, and heat.
• Pain is due mainly to the action of the chemical mediators on nerve
endings.
• All these activities help protect and repair the inflamed tissue.
• Chemotaxis is the phenomenon by which specific cell types are
attracted by specific molecules, draws much larger numbers of
leukocytes into inflamed tissues.

Con’t…
5.Plasma Cells
• They are B-lymphocyte–
derived, antibody-
producing cells.
• They have basophilic
cytoplasm due to their
richness in RER.
• The nucleus of the
plasma cell is generally
spherical but
eccentrically placed.

Con’t…
6. Leukocytes
• Leukocytes, or white blood cells, make up a population of
wandering cells in connective tissue.
• They leave blood by migrating between the endothelial cells lining

venules to enter connective tissue by a process called diapedesis.
• This process increases greatly during inflammation, which is a

vascular and cellular defensive response to injury or foreign
substances

Con’t…
• The major signs of inflamed tissues include “redness and swelling

with heat and pain”.
• Inflammation begins with the local release of chemical mediators

from various cells, the ECM, and blood plasma proteins.
• These substances act on the local microvasculature, mast cells,

macrophages, and other cells to induce events characteristic of
inflammation
o increased blood flow and vascular permeability,
o diapedesis and migration of leukocytes, and
o activation of macrophages
02/17/2024 12:07 PM By Asfaw B.
for phagocytosis.
medicine class 16
Cells of CT

Summary of connective tissue cells
Cell Type Major Product or Activity
Fibroblasts (fibrocytes) Extracellular fibers and ground substance
Plasma cells Antibodies
Lymphocytes Various immune/defense functions
Eosinophilic leukocytes Modulate allergic/vasoactive reactions and defense
against parasites
Neutrophilic leukocytes Phagocytosis of bacteria
Macrophages Phagocytosis of ECM components and debris;
antigen processing and presentation to immune cells;
secretion of growth factors, cytokines, and other agents
Mast cells and Pharmacologically active

basophilic molecules (eg, histamine)
leukocytes
Adipocytes
02/17/2024 12:07 PM Storage of B.neutralmedicine
By Asfaw fats class 18
Fibers
• Formed from polymerize proteins after secretion from fibroblasts.
• The three main types of fibers:
1. Collagen fibers
• Made of collagens protein
• Extremely strong and resistant to normal shearing and tearing forces.
• Collagen is a key element of all connective tissues, as well as epithelial

basement membranes and the external laminae of muscle and nerve cells.
• Collagen is the most abundant protein in the human body, representing

30% of its dry weight.
Con’t…
• Grouped into three
a. Fibrillar collagens- collagen types I, II, and III, have subunits that
aggregate to form large fibrils, forms structures such as tendons, organ
capsules, and dermis.
b. Sheet-forming collagens such as type IV collagen have subunits

produced by epithelial cells. A major structural proteins of external
laminae and the basal lamina in all epithelia.
c. Linking/anchoring collagens (VII, IX) are short collagens that link

fibrillar collagens to one another and to other components of the ECM.
Medical application
• A keloid is a local swelling caused by abnormally large amounts

of collagen that form in scars of the skin.
• Keloids occur hyperactivity of fibroblasts in collagen synthesis.
• Not only can they be disfiguring, but excision is almost always

followed by recurrence.

Con’t…
2. Reticular Fibers
• Found in delicate connective tissue of
many organs
• Consists mainly of collagen type III
secreted by reticular cells.
• Reticular fibers crosslink to form a
fine meshwork
• Characteristically stained black by
impregnation with silver salts.
• Are termed argyrophilic
• It acts as a supporting mesh in soft
tissues such as liver, bone marrow,
and organs of the lymphatic system.
Con’t…
3. Elastic fibers
• consists of molecules of the protein
elastin surrounded by a glycoprotein
named fibrillin, which adds strength
and stability.
• They have physical properties similar
to those of rubber, allowing tissues to
be stretched or distended and return to
their original shape.
• In the wall of large blood vessels,
especially arteries, elastin also occurs
as fenestrated sheets.
Ground substance
• The ground substance a highly hydrated, transparent, complex mixture of
macromolecules.
• It fills the space between cells and fibers in connective tissue
• Principally of three classes:
1. Glycosaminoglycans (GAGs)- consisting of repeating disaccharide units
with
 uronic acid(glucuronic or iduronic acid) and
 hexosamine(glucosamine or galactosamine)
• The four major GAGs found in proteoglycans are dermatan sulfate,
chondroitin sulfates, keratan sulfate, and heparan sulfate
2. proteoglycans- composed of a core protein to which are covalently
attached sulfated GAGs
3. multiadhesive glycoproteins- have multiple binding sites for cell surface
receptors (integrins) and for other matrix macromolecules.

Sulphated GAGs and proteoglycans

Types of Connective Tissue
• Different combinations and densities of the cells, fibers, and

extracellular macromolecules just described produce graded
variations in histological structure within connective tissue.
• Descriptive names or classifications used for the various

types of connective tissue denote either a major component
or a structural characteristic of the tissue

Classification of Connective Tissues
I. Embryonic connective tissue

A. Mesenchyme C. Cartilage
B. Mucous connective tissue 1. Hyaline cartilage
2. Fibrocartilage
II. Mature connective tissue
3. Elastic cartilage
A. Loose connective tissue
D. Bone tissue
1. Areolar CT
2. Adipose tissue E. Liquid connective tissue
3. Reticular CT 1. Blood tissue
2. Lymph
B. Dense connective tissue
1. Dense regular CT
2. Dense irregular CT
3. Elastic CT

Embryonic Connective Tissues
A. Mesenchyme
• General Organization: Sparse, undifferentiated cells, uniformly
distributed in matrix with sparse collagen fibers
• Major Functions: Contains stem/progenitor cells for all adult connective
tissue cells
• Examples: Mesodermal layer of early embryo
B. Mucoid (mucous) connective tissue
• General Organization: With abundant ground substance composed
chiefly of hyaluronic acid, sparse collagen fibers and scattered
fibroblasts in viscous matrix
• Major Functions: Supports and cushions large blood vessels
• Examples: Matrix of the fetal umbilical cord (Wharton’s jelly) and fetal
organs

Embryonic Connective Tissues

Adult connective tissue
a. Connective Tissue Proper

• Loose connective tissue
• Dense connective tissue
• Dense irregular connective tissue
• Dense regular connective tissue
b. Specialized connective tissue
• Reticular connective tissue
• Adipose Tissue
• Cartilage
• Bone
• Blood

Loose aerolar connective tissue
• It is very common and generally supports
epithelial tissue.
• General Organization: Much ground

substance; many cells and little randomly
distributed collagen.
• Major Functions: Supports microvasculature,

nerves, and immune defense cells
• Examples: Lamina propria beneath epithelial

lining of digestive tract

Loose connective tissue

Dense connective tissue
It is adapted to offer stress resistance and protection.
a) Dense irregular connective tissue- bundles of collagen fibers appear randomly
interwoven, with no definite orientation.
• General Organization- Little ground substance; few fibroblasts; much randomly
arranged collagen fibers
• Major Functions: Protects and supports organs; resists tearing
• Examples: Dermis of skin, fascia, organ capsules, submucosa layer of digestive tract

Dense connective tissue…
b) Dense regular connective tissue

• General Organization: Almost completely filled with parallel
bundles of collagen; few fibroblasts
• Major Functions: transmit force from the muscles to skeleton;
strong resistance to force
• Examples: Ligaments, tendons, aponeuroses, corneal stroma

Dense regular CT

Reticular connective tissue
• General Organization: Delicate network of reticulin/collagen III

with attached fibroblasts (reticular cells)
• Major Functions: Supports blood-forming cells, many secretory

cells, and lymphocytes in most lymphoid organs
• Examples: Bone marrow, liver, pancreas, adrenal glands, all

lymphoid organs except the thymus

Adipose Tissue
• Adipocytes are dominant cells in adipose tissue.
• Adipose tissue represents 15%-20% of the body weight in men
• Adipocytes specialize in concentrating triglycerides as lipid droplet(s)
• Adipocytes are very active cells metabolically, responding to both

nervous and hormonal stimuli.
• Adipose tissue conducts heat poorly and helps thermally insulate the
body.
• Adipose tissue also fills up spaces between other tissues and helps
cushion and keep some organs
02/17/2024 12:07 PM
in place.
By Asfaw B. medicine class 39
Adipose Tissue….

Types of adipose tissue
• There are two types of adipose tissue: structures, colors, and pathologic
characteristics.
• White adipose tissue, the more common type, is composed of cells that
contain one very large droplet of whitish-yellow fat in their cytoplasm. .
• White adipocytes are called unilocular because the triglycerides are

stored in this single large droplet.
• Brown adipose tissue contains cells with multiple lipid droplets

interspersed among abundant mitochondria, which give these cells a
darker appearance.
white and white adipocytes

Brown and white adipocytes

Histogenesis of adipocytes

Summary of CT

References
• Junqueira’s Basic Histology, 13th edition
• diFIORE’S ATLAS OF HISTOLOGY WITH FUNCTIONAL

CORRELATIONS, ELEVENTH EDI T ION
• Gerard J. Tortora, Principles of HUMAN ANATOMY 12th

Edition

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Connective tissue

02/17/2024 12:07 PM By Asfaw B. medicine class 1

• At the end of the session, students will be effectively able:

• To identify cells of connective tissue

• To describe ECM of connective tissue

• Demonstrate types of connective tissue

• To sketch microscopic feature of CT

02/17/2024 12:07 PM By Asfaw B. medicine class 2

• Connective tissue maintains the form of organs throughout the body.

• The major constituent of connective tissue is the ECM.

• ECM consist of protein fibers and ground substance

02/17/2024 12:07 PM By Asfaw B. medicine class 3

• Differences in composition and amount of the cells and ECM are

• Connective tissues originate from embryonic mesenchyme, a

• Mesenchyme consists of a population of undifferentiated cells

02/17/2024 12:07 PM By Asfaw B. medicine class 4

It binds together, supports, and strengthens other body tissues.

It protects and insulates internal organs.

It compartmentalizes structures such as skeletal muscles.

It serves as the major transport system.

It is the primary location of stored energy reserves.

It is the main source of immune responses.

By Asfaw B. medicine class 02/17/2024 12:07 PM 5

• They most common cells in connective tissue proper.

• Synthesize and secrete most of the ECM.

• Histologically, 2 levels of fibroblast activity observed

• Fibroblasts are targets of growth factors that

• In adults, connective tissue fibroblasts rarely undergo

• They are specialized for cytoplasmic storage of lipid as neutral

02/17/2024 12:07 PM By Asfaw B. medicine class 8

02/17/2024 12:07 PM By Asfaw B. medicine class 10

• Different name of microphages in different tissue

 Kupffer cells- in liver

 Dendritic cell- Lymph nodes, spleen

 Hofbauer cells- in placenta

 mesangial cells- in kidneys

 Multinuclear giant cell- pathologic tissue

• Increased vascular permeability is caused by the action of

02/17/2024 12:07 PM By Asfaw B. medicine class 13

02/17/2024 12:07 PM By Asfaw B. medicine class 14

• They leave blood by migrating between the endothelial cells lining

• This process increases greatly during inflammation, which is a

02/17/2024 12:07 PM By Asfaw B. medicine class 15

• The major signs of inflamed tissues include “redness and swelling

• Inflammation begins with the local release of chemical mediators

• These substances act on the local microvasculature, mast cells,

o diapedesis and migration of leukocytes, and

02/17/2024 12:07 PM By Asfaw B. medicine class 17

Mast cells and Pharmacologically active

• The three main types of fibers:

• Made of collagens protein

• Extremely strong and resistant to normal shearing and tearing forces.

• Collagen is a key element of all connective tissues, as well as epithelial

• Collagen is the most abundant protein in the human body, representing

b. Sheet-forming collagens such as type IV collagen have subunits

c. Linking/anchoring collagens (VII, IX) are short collagens that link

• A keloid is a local swelling caused by abnormally large amounts