Histology: Connective Tissue

Dr. Douglas Hamilton

Objectives DSB 0071 -dhamil2@uwo.ca
The student will be able to:
1) name the different types of connective tissue and be able to give an example of where
they occur in the body
2) describe the components of connective tissue
a) name cell types and their properties
b) identify the fibers associated with different connective tissue
c) describe the differences between collagen and elastic fibers
d) provide characteristics of non-fibrillar components of the extracellular matrix
3) give examples of the location of individual types of connective tissue in the body
4) name the characteristics of white and brown adipose tissue

Text: Histology: A Text and Atlas :With Correlated Cell and Molecular Biology (Ross and Pawlina)

WHAT IS CONNECTIVE TISSUE?

Three tissue layers emerge from the neural crest during development: ectoderm= outside,
mesoderm = middle, and endoderm = inside. The middle layer or mesoderm is composed of
cells (termed mesenchymal cells - pluripotential fibroblasts) that eventually give rise to the various
types of connective tissue throughout the body.
Function: Connective tissue joins, supports, and provides structure for tissues and organs. It mediates
exchange of nutrients, metabolites, and waste products between tissues and the circulation.
Types: Various forms of connective tissue occur throughout the body: embryonic, loose, dense,
reticular, and elastic. Specialized connective tissue include adipose(fat), cartilage, and bone.

Components of Connective Tissue

Cells

Extracellular matrix
Fibers
Non-fiber components (once know as ground substance)
 Cells:
Connective tissue p. 2

Mesenchymal (primitive), fibroblastic, and

reticular (more specialized) cells comprise the
cellular component of connective tissue.
More differentiated cells with designated
functions produce and maintain the
specialized connective tissues.

Other cells derived from blood or bone

marrow origin can immigrate to connective
tissue = macrophages, mast cells, plasma
cells.
Loose connective tissue
From Gartner and Hiatt- Color Testbook of Histology 2nd Ed

Fibroblasts = synthesize and maintain extracellular matrix of connective tissue

Endothelial cells = line blood and lymphatic vessels
Pericyte = found in association with blood vessels and capillaries, potential source of
fibroblasts and smooth muscle cells
Tissue macrophages, mast cells, plasma cells= often transient, deal with inflammation,
allergic reactions, and immune responses
Adipocytes = fill space, store lipid, and provide energy storage

Extracellular matrix
Fibers microfibril

Microfibrils = grouping of molecules (1-20 nm)

Fibrils = grouping of microfibrils (20-90 nm)

FIBERS = grouping of many fibrils (m m)

 Connective tissue p. 3
Types of Fibers
Collagen Fibers

From Kierszenbaum, Histology and Cell Biology fig 4-3

Collagens are a major component of the

majority of connective tissues, are synthesized by
fibroblasts, are proline rich, and are organized into
fibers (0.5-15µm). Numerous types of collagen exist
(fibrillar versus non-fibrillar) and help define various
connective tissues. Fibrils made up of type I
collagen have a striated appearance due to a very
regular organization of individual collagen
molecules with an offset of 64 nm resulting in
regions of overlap. Reticular fibers (0.1-1.5µm) are
synthesized by reticular cells (a specialized
fibroblast) and consist of type III collagen and
glycoproteins organized in a loose network to allow
migration of cells.
 Connective tissue p. 4

Fibers

Cells

T= transverse & L= longitudinal

Section of the fiber

Collagen is eosinophilic and shows up pink on hematoxylin & eosin

staining (nuclei stain dark purple).

Wheater’s Fig 5.6

 Connective tissue p. 5
Elastic Fibers

From Kierszenbaum, Histology and Cell Biology fig 4-6

of fibrillin
Wheater’s Fig 4.10
From Gartner and Hiatt- Color Testbook of Histology 2nd Ed

Elastic fibers (0.1 -10µm) contain elastin and convey the property of” stretch and
return to original shape” to various tissues such as arterial walls, components of
lung, vocal ligaments and cartilages, and the vertebral column. For proper
assembly and organization, the core of elastin must be coated with the
glycoprotein fibrillin. Fibrillin is a thread-like molecule (350 kDa) that has a
requirement for calcium to organize into microfibrils that convey stability to elastin-
containing fibers. Elastic fibers can be stretched up to 150% of their resting length!
 Connective tissue p. 6

Non-fiber components= non-collagenous proteins and sugars

The semi-fluid gel component of the extracellular matrix is composed of proteoglycans
(proteins + glycosaminoglycans) and glycoproteins. Glycosaminoglycans (GAG) are acidic
and consist of chains of various lengths of repeating disaccharide units (typically a uronic acid
with an amino sugar such as N-acetyl glucosamine or N-acetyl galactosamine). Hyaluronic
acid (or hyaluronan) is the predominant GAG in loose connective tissue. The GAGs associated
with proteoglycans include: chondroitin-4-sulfate, chondroitin-6-sulphate, dermatan sulphate,
heparan sulphate, heparin sulphate, and keratan sulphate). The GAGs help retain fluid in the
tissue.

1) Proteoglycans

From Kierszenbaum, Histology and Cell Biology fig 4-11

2) Glycoproteins
Glycoproteins serve as bridge molecules from the cell to the
extracellular network as they have binding sites for several components
of the extracellular matrix as well as for receptors on cell plasma
membranes called integrin molecules. Glycoproteins include
fibronectin, fibrillin, laminin, entactin, and tenascin.
 Connective tissue p. 7

Embryonic -Mesenchymal/Mucous
**For another visual example see Wheater’s Fig 4.3
relatively undifferentiated (not specialized)
Function: space occupying, gives rise to precursor cells of
future connective tissue, source of pluripotential
“stem cells” and pericytes
Cell types: mesenchymal - highly proliferative to populate
the tissue to be formed
Elongated cells with short cellular processes randomly distributed.
Characteristics: Cellular with few fibers (mostly type I and
III collagen) and gel-like ground substance
BV = blood vessel; MeC = mesenchymal cell, N = nucleus, C=
cytoplasmic extensions of the cell
Gartner &Hiatt 3rd Ed Atlas plate3-1 fig 2

Loose Connective Tissue

**For another visual example see Wheater’s Fig 4.7e
Function: space occupying, site where body first attacks
antigens, bacteria, and other foreign invaders
Cell types: Fibroblasts, mesenchymal cells, mast cells,
macrophages, adipocytes, plasma cells, leukocytes
Characteristics: Abundant non-fiber compents with variety
of cells although fibroblasts being the source of extracellular
matrix. Type I and III collagen as well as elastic fibers
assembled in a loose woven organization. Nerves, blood
vessels also present.
Distribution:around blood vessels and nerves, under
epithelia (covering and lining)
Gartner &Hiatt 2nd ed Textbook Fig 6-2 Pathological: site of edema accumulation
C= collagen fibers, E= elastic fibers

Dense Regular Connective Tissue

**For another visual example see Wheater’s Fig 10.31
Function: Very strong tissue - resistant to stress/
stretch
Cell type: fibroblasts (majority)
Characteristics:Parallel arrangement of collagen
bundles of fibers, densely packed, very little space
for non-fiber components or cells. Fibroblasts are
flattened between fiber bundles with the nuclei having
and elongated look in longitudinal sections and
scarcely apparent in cross-section.
Distribution: tendons, ligaments, joint capsule

N= nucleus
Gartner &Hiatt 2nd ed Textbook Fig 6-18 - tendon

C=capsule, A= Adrenal gland
Wheater’s Fig 4.8
Gartner & Hiatt Plate3-3 fig 3 (Aorta)
Connective tissue p. 8
Dense Irregular Connective Tissue
**For another visual example see Wheater’s Fig 4.7a
Function: strong resilient tissue serving a protective role
Cell type: fibroblasts (majority)
Characteristics: Collagen fibers are interwoven to
create a mesh-like tissue to resist stress in all directions.
As with regular connective tissue, there is little room for
cells and non-fiber components however, the cells find
space near intersections of fibers allowing the cells
to maintain a 3-D shape with rounded nuclei.
Distribution: Reticular layer of the dermis, most
organ capsules(spleen, testes, ovary, kidney, lymph nodes)
Reticular Tissue
Function: provides a lattice for hemopoietic cells
Cell type: reticular (specialized fibroblasts)
Characteristics: Fibers are mostly composed of
type III collagen synthesized by the reticular cells,
Very little non-fiber components.
Distribution: bone marrow, lymph nodes, spleen,
BV= blood vessel
Elastic Tissue
**For another visual example see Wheater’s Fig 4.9c
Function: To allow but control directional stretch
Cell type: fibroblasts
Characteristics: Elastic fibers are arranged in
parallel to form sheets or fenestrated membranes
through out typically an irregular connective tissue.
Little ground substance with cells dispersed
randomly.
Distribution: large blood vessels, vocal ligaments
EM = Elastic membranes, CF = collagen fibers

ADIPOSE TISSUE = FAT
specialized connective tissue = specialized cells
Fat is derived from 3 main sources:
1) dietary fat circulating in the bloodstream (chylomicrons)
2) triglycerides synthesized in the liver and transported in blood
3) triglycerides synthesized from glucose within adipocytes
Rate of fat deposition is determined by
- energy intake versus energy expenditure
- hormones: insulin, growth hormone, norepinephrine/noradrenalin, glucorticoids
- activity of the adrenergic nerve fibers of the sympathetic nervous system
General properties of adipocytes
- mature adipocytes do not typically divide
- adipocytes are long lived
White adipose tissue
Up to 20% of total body weight in men
Prevalence Up to 25 % of total body weight in women
Localized to deep layers of skin
Both men and women:omenal apron,
Distribution mesenteries, buttocks and hips
Men: neck, shoulders, and with age:
abdominal wall
Women: breasts, lateral aspects of thighs
Adipocyte with signet ring appearance
Cell type Fat droplets coalesce to form a large
central droplet, nucleus is squeezed to
edge
Rich blood supply
Characteristics White appearance due to lipid soluble
carotene
Important energy store for the body =
Function thermal insulator under the skin
Cushions against mechanical shock for
areas such as kidneys
Connective tissue p. 9
Brown adipose tissue
Predominantly found in newborn
mammals, typically the first few
months after birth (less prevalent in
human adult)
Newborns: 2-5 % of body weight
Lateral neck region and abdomen,
shoulder girdle, rib cage region, and
internal abdominal organs
Adipocyte
Smaller cells what in white fat, lipid is
stored in multiple droplets, nucleus
remains central
Rich capillary blood supply
Brown colour results from presence of
numerous larger mitochondria with a
richness in cytochromes involved in
oxidative energy production
Important role in temperature
regulation
Provides heat during newborn stage
and for those undergoing hibernation
 Connective tissue p.10

White adipose tissue Brown adipose tissue

Wheater’s Fig 4.11a Wheater’s Fig 4.13c

N = nucleus, C = capillaries

Clinical relevance of understanding the fundamentals of Connective Tissue

Excess deposition of fibers:
Scleroderma - excess collagen deposition in skin, heart, lung, intestine, kidneys, esophagus
Predominant features: tight, inflexible skin, reduced elasticity of organs
Prevalence: 4:1 Female to Male

Abnormal deposition of fibers:

Ehlers-Danlos Syndrome - various etiologies: mutation in cleavage sites for the N-terminal
propeptide, defect in the procollagen
peptidase, defect in the lysyl hydroxylase
- reduced cross-linking and tensile strength of connective tissue
- tendons are particularly affected
- predominant features:
1) hypermobility of joints
2) hyperelasticity of the skin
- prevalence: 1/5000 - 1/10,000 (male & female)

Marfan’s Syndrome - lack of organization of elastic connective tissue in

arteries, lungs and ligaments = too elastic
- genetic mutation of fibrillin gene (deleted exon)
- predominant features:
1) Ocular defects: myopia & detached lens
2) Skeletal defects: long and thin arms, legs & fingers; hollow chest;
scoliosis
3) Cardiovascular defects: ** life-threatening**
prolapse of mitral valve and dilation of the
ascending aorta = aneurysm
Prevalence: Female = Male
 Connective tissue p. 11

Review (Questions that you should be able to answer after studying this section)

1. Name the different types of connective tissue -how are they similar and how are
they different
2. What three components serve to define connective tissue
3. What cells synthesize matrix molecules in connective tissue?
4. Name 2 types of fibers -how are they similar and how are they different?
5. What would happen to a connective tissue if the ratio of cells to fibers to ground
substance were to change? Think about different scenarios, for example, more
cells, more elastin,or less proteoglycan
6. Compare and contrast white and brown adipose tissue.
What has happened to the connective tissue in these pictures?

A. B. Normal Aorta