Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
1. Define “connective tissue” as a general tissue type
a. Tissue that connects all the other cells of different TISSUE types both mechanically
and metabolically
2. List the developmental origin of all connective tissue
a. All CT is derived from the embryonic mesenchyme
3. List and be able to classify the different types of connective tissue (CT) either as CT proper
or special CT
a. Embryonic CT
i. Mesenchymal Connective Tissue: Embryo and fetus
ii. Mucous Connective Tissue: Umbilical cord
b. Connective Tissue Proper
i. Loose (Areolar) Connective Tissue
1. Few EC fibers, mostly ground substance
2. Found surrounding, supporting most organs/tissues
ii. Dense Connective Tissue
1. Dense Irregular
a. Strength in all directions
b. Dermis, organ capsules, periosteum, perichondrium
2. Dense Regular
a. Fibers run in parallel
b. Collagenous: Tendons, ligaments, aponeurosis
c. Elastic: Ligamentum nuchae, flava
iii. Reticular Tissue
1. Gentle support, many reticular fibers
2. Lymphatic tissue, Bone marrow
iv. Adipose Tissue
1. In subcutaneous fascia and omentum
c. Specialized CT
i. Cartilage: Costal cartilage, trachea, Pina, Epiglottis
ii. Bone: Skeleton
iii. Blood: Cardiovascular, Hematopoietic Tissues
4. List and describe the three major components common to all types of CT (cells, extracellular
fibers, and ground substance, the last two comprising the extracellular matrix)
a. RULE OF 3’S
b. Cells
i. Fixed: synthesis & maintenance of ECM
ii. Wandering: migrate into and out of ECM of the CT
iii. Associated: cells that are always present, but associated with blood vessels
c. Fibers
i. Collagen: for strength
ii. Reticular: for delicate support
iii. Elastic: for stretch & flexibility
d. Ground Substance
i. Interstitial Fluid: water
ii. Preteoglycans: slippery, complex macromolecules with protein-core and
attached glycoaminoglycans (GCGs)
iii. Glycoproteins: for adhesion, sugar attached to protein-core
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
5. List all common locations in the body of each type of CT
a. This is found in the answer to Objective 3
6. List and describe the three types of fibers in CT. Classify them according to size,
morphology, chemical composition, and function
a. Collagen: for Strength
i. Most abundant protein in the body
ii. Inelastic, yet flexible
iii. Fasicles: Bundles of fibers found in CT Proper
iv. Collagen Fiber
1. Straight, unbranched fibrous protein
2. 64 nm periodicity
3. Made of collagen fibrils
v. Collagen Fibril
1. Singular unit of FIBER
2. Same Periodicity
3. Made of up Tropocollagen Molecules
vi. Tropocollagen Molecules
1. Consist of 3 Consist of 3 polypeptide chains
a. Each ~1000 a.a.
b. Rich in Glycine, Proline, Hydroxyproline, and Hydroxylysine
c. 3 chains held together by h-bonding b/t hydroxyproline
d. These molecules line up end-to-end and side-by-side to form
fibril
e. Quarter Stagger Theory: describes alignment of
tropocollagen and accounts for periodicity
f. Covalent bonding b/t hydroxylysine in adjacent tropocollagen
molecules holds together collagen fibril
vii. Types of Collagen
1. Type I: Strength; Skin, Tendons, Organ capsules, Bone, Dentin
2. Type II: Resist Pressure; Hyaline & Elastic cartilage
3. Type III: Delicate Support; Lymph system, spleen, liver, Lungs, CV
4. Type IV: Attachment Filtration; Basal Lamina
b. Reticular Fibers
i. Small, branched, and squiggly; intersect at Right Angles
ii. Composed of Collagen Type III fibrils covered with a Sugar Coat
iii. Reticular cells wrap each fiber
iv. Found in regions with many wandering cells
v. Function to provide “delicate support”
c. Elastic Fibers
i. Y-branched, fuse at acute angles, not squiggly *diagnostic character*
ii. Consist of 2 Components
1. Amorphous Component: made of elastin, rich in Glycine, but also
contains desmosine & isodesmosine
2. Microfibril Component: different glycoprotein
iii. Function to add elasticity to tissue (up to 150% stretch memory)
iv. Found in areas with a much stretching: vessels, aorta, skin, lungs, uterus
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
7. Describe how the precursors of different fibers are secreted by the cell and aggregate to form
fibers outside of the cell. Be able to characterize disease related to improper fiber formation
a. Secretion and Aggregation
i. Collagen
1. Multiple steps
2. Transcription in nucleus
3. Translation in rER
4. Hydroxylation of proline & lysine in rER
5. Formation of procollagen
6. Secretion via Golgi
7. Cleavage of procollagen into tropocollagen by Procollagen peptidase
on the cell’s exterior
8. Self-assembly of tropocollagen into fibril in ECM
9. Covalent linking of hyrodxylysine by Lysyl Oxidase to form
insoluable fibril
10. Constant turnover due to breakdown of collagen by collagenase
ii. Reticular Fibers: same as collagen
iii. Elastic fibers
1. Proelastin  tropoelastin outside of cell
2. Covalent bond formation by Lysyl oxidase to form elastin in a mesh of
microfibrils
3. Elastic fiber system composed of 3 types of elastic fibers
a. Oxytalan fibers: microfibrillar component
b. Eulanin fibers: microfibrils and amorphous elastin
c. Elastic fibers: as previously described
4. Continuous turnover due to breakdown of elastic fiber by elastase
b. Related Disease States
i. Collagen-related
1. Scurvy:
a. Lack of Vitamin C (necessary co-factor in hydroxylation of
proline
b. Results in weak collagen, no wound-healing, etc
2. Ehlers-Danlos, Type VII
a. Change in procollagen peptidase
b. Hyperflexibilty, soft skin, dislocations
c. Indicated by increased [Gly] in urine
ii. Reticular fiber-related
1. Ehler-Danlos, Type IV
a. Deficiency of Type III collagen
b. Aneurysms, Intestinal rupture
iii. Elastic fiber-related
1. Marfan’s
a. Poor microfibrillar (fibrillin) component formation
b. Tendency of aorta and blood vessels to rupture
2. Emphysema
a. Lung dysfunction caused by breakdown of elastic fibers
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
8. List and describe the components of the amorphous ground substance (water, proteoglycans,
and glycoproteins). Relate their structure to their function.
a. Proteoglycans
i. Protein core with sulfated glycsoaminoglycans attached to form a porous,
hydrated gel.
ii. Can be non-sulfated or sulfated
1. Non-Sulfated: Hyaluronic Acid
a. Large macromolecule, highly coiled
b. Carries a net negative charge which attracts Na and Ca, and
subsequently water
c. Slippery, lubricating
d. Resists Compression
e. Acts as physical barrier to prevent migration of bacteria, except
pathogenic species use hyaluronidase to cleave it and migrate
f. Acts to inhibit cellular adhesion and facilite cell migration, esp
during development and wound healing
2. Sulfated GAGs
a. Keratin sulfate: cartilage
b. Heparin Sulfate: basement membrane
c. Chondroitin-6- and Chondroitin-4-: skin, bone, cartilage
d. Dermatin sulfate: dermis
iii. Can be free or transmembrane
1. Free Proteoglycan: present within ground substance of loose CT
a. Aggrecan: free in areolar CT matrix
b. Aggrecan Aggregate: hyaluronic acid with 100s of aggrecan
i. very gel-like
c. Perlacan: found in basal lamina, contains much heparin
2. Transmembrane: Proteoglycans which span cell membrane
a. Syndecan: rich in heparin and chondroitin; one end in
cytoplasm, one in ECM
b. Fibroglycan: Binds 3 types of collagen and fibronectin
b. Glycoproteins
i. Smaller molecules, protein core with branched sugars attached
ii. Typically act as adhesion molecules to hold cells to EMC
iii. Fibronectin: found in basal lamina, binds heparin and Type IV Collagen
iv. Laminin: Lacated in BM; binds heparin and Type IV
v. Entactin: Located in BM; binds laminin and Type IV
vi. Tenascin: Located in BM; binds syndecan and fibronectin
c. Interstitial Fluid
i. Water found in interstitial space
ii. Important for material transport
iii. Bound by proteoglycans (hyaluronic acid)
9. Describe how the components of the extracellular matrix enable it to act as a medium for
transfer of nutrients and wastes between the blood stream and any other cells or tissues.
a. Much of the water in the interstitial fluid flows out of capillaries, along parenchyma
and back into either the lymphatic system or other capillaries. This movement brings
along nutrients.
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
10. Describe the process of edema and relate this to its various causes
a. Edema: abnormal buildup of interstitial fluid in extracellular matrix
b. Pitting vs Myxedema: Myxedema does not pit, caused by hypthyroidism (increased
[GAG])
c. Causes:
i. Blocked Lymphatics: sugery, elephantiasis
ii. Blocked Venous Return: compromised veins
iii. Liver disease: insufficient albumin
iv. Increased vascular permeability: histamine (mast cells), anaphylaxis
v. Hypertension: increased hydrostatic pressure at arterial end of capillary
vi. Starvation: decreased albumin = decreased veinule osmotic pressure
11. Describe and understand the components of the basement membrane and relate its structure
to its function.
a. Basement membrane:
i. Visible with light microscopy, located in extracellular space
ii. Functions to connect NERVE, MUSCLE, EPITHELIAL, & ADIPOSE tissue
to connective tissue (i.e. no BM around CT, except for adipose tissue)
iii. Three layers (from closest to plasma membrane, out)
1. Lamina lucida: contains integrins, laminins, entactin
2. Lamina densa: contains Type IV collagen, perlancan (heparin
sulfate), fibronectin, carries (-) charge
3. Lamina reticularis: reticular fibers (Type III) and type IV/VII and
anchoring fibers
iv. Basal lamina: Lamina lucida and Lamina densa
v. Function: anchor cells to connective tissue, act as macromolecular sieve
12. List and describe the morphology and function of each cell type normally found in the
connective tissue. Classify them as “fixed,” “wandering,” or “associated.”
a. Fixed Cells: cells that produce and maintain ECM of a particular CT type
i. Fibrocyte
1. Most common fixed cell
2. Can’t see cytoplasm, vesicular nucleus with nucleolus
3. Secretory cell
4. –blast: Immature, divisible, production of fibers
5. –cyte: not able to divide, upholds matrix
ii. Mesenchymal Cell
1. Embryonic, pluripotential
2. Looks like fibrocyte (only difference is location)
iii. Reticular Cell
1. Found in reticular tissue
2. Processes wrap around reticular fibers
3. Form cell-lined fiber network
iv. Adipose cells
1. White Adipocytes
a. Large, spherical
b. Unilocular: single, large lipid droplet
c. Empty due to lipid extraction during processing,
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
d. “Signet Ring” appearance
e. Location: Loose CT, subcut. Fascia
f. Function: Lipid storage
i. Lipid leaves blood and broken down by Lipoprotein
Lipase into free fatty acid and glycerol
ii. Fatty acid taken up by adipocyte and complexed with
glycerol into neutral lipid (triglyerides)
iii. Lipid released from adipocyte by Hormone Sensitive
Lipase, which breaks up triglyceride back to free fatty
acid which complexes with albumin in blood
g. Produce Leptin: which acts to decrease appetite and increase
energy consumption.
h. Acted on by insulin to form triglycerides from glucose,
increase glucose uptake, and produce Lipoprotein Lipase
i. Norepi/Epi act in opposition to insulin: fight or flight, increase
Hormone sensitive lipase
2. Brown Adipocytes
a. Found in hibernating animals and newborn humans near aorta,
axilla, mediastinum, scapulae
b. Multilocular: many lipid droplets
c. Function: heat generation
i. Fatty acid accumulation acts to uncouple oxidation
process
ii. Thermogenin: Mitochondrial membrane protein
permitting flow of H+ to make heat instead of generate
ATP
3. Others
a. Chondrocyte: Cartilage
b. Osteocyte: Bone
c. Blood cells: “Fixed” cell of blood
b. Wandering Cells: transient cells which migrate into and out of connective tissue
i. Macrophage: Big eaters
1. Phagocytic
2. Part of Mononuclear Macrophage System
a. Monocyte  Macrophage once in CT
3. Only identifiable by using vital dye
4. Oval, indented nucleus with vesicular chromatin pattern
5. Lots of lysosomes
6. Functions: Phagocytic, Antigen-presenting
ii. Mast Cells
1. Granular, oval cells associated with small blood vessels
2. Clear nucleus, obscured by granules
3. Granules include: Heparin, Histamine (Vasodilator, Increase Vascular
permeability, Bronchiole constriction), Eosinophilic Chemotaxic
factor, Neutrophilic Chemotaxic factor, Leukotrienes
4. Function: Store mediators of inflammation,
Connective Tissue
August 27, 2010
Robert Crissman, Ph.D
5. Bind IgE and interact with antigens. Upon first antigenic exposure,
form IgE’s. Upon second antigenic exposure, antigen binds to IgE
and causes cascade which releases granular contents
6. Potential to cause anaphylactic shock
7. Located along capillaries of mucosa, respiratory, digestive and urinary
tracts
8. Paracine secretion
iii. Plasma
1. Eccentrically located nucleus, cartwheel chromatin, lots of rER**
diagnostic
2. Normally found only in CT (i.e. not in blood)
3. Derived by B-lymphocytes
4. Function: produce antibodies
c. Associated Cells: Cells found in blood vessels which are always surrounded by CT
i. Endothelial Cells: Lining of blood vessel
ii. Smooth Muscle Cells: surround endothelium and control size
iii. Pericytes: MPSCs for vessel repair/growth
13. Describe and discuss how the mount and type of the individual components determine the
structural and functional characteristics of the individual types of connective tissues
a. Different types of connective tissue have cells/fibers/ground substance in varying
proportions to serve specific function. Structure determines function.
14. List the general functions of connective tissues.
a. Mechanical support: “mother natures packing material”
b. Mechanical protection
c. Energy storage/temp control
d. Material transport
e. Protection from infection
f. Repair after injury
15. Understand that adipose tissue is a special type of connective tissue. Identify the major cell
type found in the two different types of adipose tissue and its function with its specific
morphology. Be able to locate the 2 different types of adipose tissue in the body.
a. See above objective
16. Describe and identify the characteristic morphology and function of the specific types of CT
(areolar CT, mucous CT, mesenchyme, dense irreguluar, dense regular, elastic, reticular,
and adipose).
a. See above objective
17. Know the meaning of the following terms and how they are related to connective tissues
a. Review list on page 252 of packet