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CONNECTIVE TISSUE

Connective Tissue
- originates from mesoderm
a. Connective Tissue Proper
b. Specialized Connective Tissue

Composed of
Cells
Extracellular Matrix
a. CT fibers
b. Ground substance
c. Tissue fluid

Functions of the Connective tissue:

- provides structural support
- serves as medium of exchange
- aids in defense and protection of the body

Classification
A. Dense Connective Tissue B. Loose Connective Tissue

1. Dense irregular - fixed cells

2. Dense regular - free cells

I. Extracellular Matrix
A. Ground Substance Hyaluronic acid In vitreous humor and
translucent matrix synovial fluid
surrounds the cells and fibers of CT Very high viscosity in
viscous solution aqueous solution
composed of glycosaminoglycans
Chondroitin Sulfate In cartilage, bone, large
blood vessel

B. Fibers Dermatan Sulfate In skin, lungs, tendon,and

Collagen Fibers - 0.5-2.0 μm in diameter elsewhere
inelastic
are tough fibrous proteins that are thick Keratan Sulfate Cornea, cartilage
and do not branch
most abundant Heparan Sulfate In liver, aorta, and lungs
each fiber is composed of fine subunit
called tropocollagen molecule

Type I Collagen - Flexible, greater resistance to tension

- Dermis, bone, tendon, fascia, and capsules of organs
Type II Collagen - Hyaline and elastic cartilage
- Nucleus pulposus of intervertebral discs
- Vitreous body
Type III Collagen - Loose CT
- Blood vessels
- Stroma of various glands
- Spleen
- Kidney
- Uterus
- Forms the argyrophilic fibers = Reticular fibers
Type IV Collagen - In lamina densa
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Type V Collagen - Very small amounts

- Associated with type I collagen and in the placenta
Type VI Collagen - At sites where types I and II are found
- 0.5% in kidney, liver, uterus
- 25% in cornea
Type VII Collagen - Dermo-epidermal junction of skin
- Its molecules are the largest
Type VIII - Discovered as secretory product of endothelial cells sometimes
called endothelial collagen
- Major component of Descemet’s membrane

Type IX - In cartilage

Type X - Cartilage, and in matrix surrounding hypertrophic chondrocytes

involved in endochondral bone formation
- Play some role in initiating calcification of the matrix

Fibrillin - 8-10 nm diameter

non-sulfated 350 KD glycoprotein
appear as beaded chain
closely associated with elastic fibers or with the basal lamina
defective or deficient in Marfan Syndrome
by molecular genetic analysis = defect is localized to a single gene on chromosome 15

Elastic Fibers – uniform small diameter

tendency to branch and rejoin to form a loose network
have less tensile strength
in walls of aorta and pulmonary trunk, bladder
consist of amorphous core of elastin surrounded by microfibrillar glycoprotein FIBRILLIN
contains little hydroxyproline and no hydroxylysine
higher alanine content than that of any known protein
2 amino acids = desmosine and isodesmosine
rubber like
resistant to boiling and to hydrolysis by dilute acid or alkali
selectively digested by pancreatic enzyme elastase

C. Adhesion Glycoproteins
– involved in interaction of cells with EC matrix
maintains adhesion of cells to their substrate

Fibronectin – constituent of extracellular matrix of connective tissue, basal lamina, and external lamina that
envelops smooth and striated muscle fibers
- synthesized by fibroblasts in blood plasma

Laminin – most abundant constituent of basal lamina and layer investing muscle fibers

Thrombospondin – product of activated platelets

- most abundant proteins in the granules of blood platelets
- binds to fibrinogen, plasmalogen, and plasmalogen activator
- synthesized by fibroblasts of connective tissue, endothelial cells and smooth muscle cell
- exact function is poorly understood
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II. Cellular Components

1. Fixed Cells
Fibroblasts – secrete and maintain EC components
Adipose cells – store and release lipids
Mesenchymal cells Small fusiform or stellate
Cells not easily distinguished from fibroblasts
Fibroblasts Produce the extracellular components of developing connective tissue
Fibrocytes – when inactive in fiber formation
Usually deployed along bundles of collagen fibers
Fusiform cells with long tapering ends
Elongated nucleus
o
Adipose Cells Derived from undifferentiated mesenchymal cells and from fibroblasts
Fixed cell of CT for synthesis and storage of lipid
Accumulate lipid
Macrophages (Histiocytes) Role in maintenance of normal tissues by ingesting dead cells and debris and
particulate matter

Free macrophages Motile cells

Fixed macrophages Sessile cells stretched out along collagen fiber
arise from monocytes
Resident Macrophages Present at a given site, in the absence of an
exogenous stimulus
Elicited Macrophages Mobilized at the site in response to a stimulus
Activated Macrophages Have acquired enhanced phagocytic and antigen
processing activity in response to a local
stimulus
Unstimulated resident Fusiform or stellate cells widely distributed
macrophages among the bundles of collagen fibers
- tend to be more abundant in the
vicinity of small blood vessels
In Pathologic conditions:
- Chronic inflammation – epitheloid cells
o macrophages gather around foreign bodies
o too large to be engulfed → foreign body giant cells

2. Free cells– or wandering cells

- eosinophils , monocyte, lymphocytes, macrophages, plasma cells that differentiate from lymphocytes, and mast
cells
Mononuclear Phagocyte System Monocytes
M<acrophages of CT, lymphoid organs and bone marrow
Alveolar phagocytes of lungs
Kuppfer cells (liver)
Osteoclasts of bone
Neutrophils Rarely found in normal connective tissue
Gather in great numbers at sites of inflammation
Chemotaxis and chemokinesis
Eosinophils Normal constituents of connective tissue
Numerous in CT of nasal cavity, lungs, skin, and lamina propria of the
intestine
Have surface Fc and C3 receptors and their specific granules contain
hydrolytic enzymes
Increase in allergies
Responsive to parasitic infestations
Eosinophil cationic protein (ECP)
major basic protein of eosinophil granules
Enzyme peroxidase
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Lymphocytes Small number in connective tissue

Abundant in stroma of lymphoid organs, and lamina propria of intestinal
tract
T- lymphocytes
B- lymphocytes
Plasma cells Arise from B-lymphocytes
Large ovoid cells 20 um in diameter
Eccentrically placed nucleus
Short lifespan of 2-3 weeks
Occasionally contain spherical inclusions 2-3 μm in diameter
Russell bodies – accumulations of defective products of Ab synthesis
Mast cells Largest
Numerous basophilic granules in cytoplasm which may obscure the nucleus
Granules stain metachromatically with toluidine blue
Change color of dye from blue to magenta, due to content of sulfated
glycosaminoglycan heparin
Contain histamine, neutral proteases tryptase and chymase, and an
eosinophil chemotactic factor
Found only in tissues and lifespan of weeks or months
More numerous along the course of blood vessels, beneath the epithelium of
respiratory and intestinal tracts = Ag likely to gain access
Function:
Initiate an inflammatory response
Causes release of primary and secondary mediators of inflammation as:
Histamine
Eosinophil Chemotactic factor
Neutrophil chemotactic factor
Leukotrienes C4 & D4
Prostaglandin
Neutral Proteases

SEROUS MEMBRANES
Membrane – thin sheet or layer of tissue that covers a structure or lines a cavity
- lines major cavities of the body
- consists of thin layer of typical loose connective tissue covered by mesothelium - squamous
- Serous membrane according to location:
Pleura
Peritoneum – mesenteries

2 categories – mucous membranes, serous membranes

Omentum
1. Lesser Omentum
2. Greater Omentum

- has milky spots - small white patches scattered throughout its unfenestrated areas = aggregations of
macrophages, lymphocytes, and eosinophils
- adheres to sites of inflammation

VARIANT TYPES OF LOOSE CONNECTIVE TISSUE

occur in sites where little resistance to stress is required
supports the epithelial parenchyma of the major organs and in the tissue through which their blood vessels are
distributed
occupies spaces around and between muscles
underlies mesothelium lining the pleural and peritoneal cavities
Abundant ground substance housing fixed and transient connective tissue cells
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Reticular Connective Tissue – form of loose CT

- major fiber component is Type III collagen
- cells = stellate with slender radiating processes deployed along the intersecting strands of the reticulum
- forms the stroma of the bone marrow, spleen, lymph node, and thymus

Mucous Connective Tissue – very large amount of amorphous ground substance

- hyaluronic acid
- common in the embryo
- principal component of the umbilical cord = Wharton’s jelly
- also found in the pulp of developing teeth

Dense Connective Tissue – preponderance of fibers, few cells

1. Dense Irregular Connective Tissue – collagen fibers are arranged randomly
- elastic fibers in interspersed among the collagen fibers
- fibroblasts are lodged between bundles of collagen
- few free cells
- found in : dermis, capsules of spleen, liver and LN, tunica albuginea of testis, dura mater, sheaths of large
nerves
2. Dense Regular Connective Tissue – made up of parallel type 1 collagen fibers
- fibers are oriented in the direction best suited to resist the mechanical stresses to which they are subjected
Ex.
Tendons – made of type 1 collagen, closely packed with very little intervening space for ground substance
Ligaments – are strong bands of parallel collagen bundles
- few elastic fibers among collagen

Histophysiology of Connective Tissue

Functions:
- Mechanical support
- Exchange of metabolites between blood and tissues
- Storage of energy reserves
- Protection against infection
- Repair after injury
- activated phagocytes →release interleukin 1 →diffuse into circulation
- in the brain → acts on thermoregulatory center → prostaglandin → fever
-
- On reaching the Bone Marrow
- stimulates the release of Neutrophils
-

Inflammation
- invasion of tissues by microorganisms triggers local response of connective tissue → acute inflammation

- at site of infection → bacterial products activate resident macrophages

- previous exposure to same kind of microorganism: →develop antibodies → bind to mast cells → release histamine
and other mediators →cause local dilatation and increase permeability of BV → cardinal signs of inflammation

Chronic Inflammation
- macrophages and neutrophils decline in number
- increase number of lymphocytes and plasma cells
- fibroblasts proliferate and increase production of collagen fibers to form dense wall of fibrous tissue around the
site

Repair – after an Injury

- fibroblast proliferation and enhanced fibrogenesis → healing process

Connective Tissue Diseases

Severe Vit. C deficiency – scurvy
Osteogenesis Imperfecta – deficient Type I collagen
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Adipose Tissue
1. White (Unilocular) Adipose Tissue – bulk of body fat
- single large lipid droplet
- nucleus → displaced to one side of the cell and flattened by the accumulated lipid
- cytoplasm → reduced to thin rim around lipid droplet
- each adipose cell has a glycoprotein envelope
- found in subcutaneous tissue
- infants/young children → continuous subcutaneous layer of fat over the whole body = panniculus adiposus
- adults → subcutaneous layer thins out in some areas but persists and grows thicker in certain regions

2 Processes of Adipose Tissue Formation:

a. Primary fat formation - gland-like aggregations of epitheloid precursor
- cells are laid down in specific locations.
- these accumulate multiple lipid droplets and become brown adipose tissue
b. Secondary fat formation - results in the widely disseminated deposits of unilocular fat found in adult

Obesity:
a. Hypertrophic Obesity – accumulation of excess lipid in a normal number of unilocular adipose cells
- fat cells increase size by 4x
b. Hypercellular Obesity – in early weeks of life or infants
- overabundance of adipocytes or increase number of adipose cells