Connective Tissue Flashcards
Local Anesthesia and Connective Tissue
You actually do not numb the nerve directly, you inject into the connective tissue which has blood vessels in it. Blood vessels can then spread the anesthetics into the nerves
Tooth
Dentin and pulp tissues are specialized connective tissues in addition to cementum, alveolar bone, and periodontal ligaments
Embryonic Origin of Connective Tissue
o Originates from the MESODERM, middle
germ layer of the embryonic tissue.
o The mesenchyme, the multipotential cells
from mesoderm of the embryo, give rise to
the connective tissues and their cells
(different from epithelium which is derived from all embryological layers)
Composition of Connective Tissues
NOT JUST CELLS
1) Cells
> fixed and wandering
2) Fibers (extracellular)
> collagen, elastic
3) Ground Substance (extracellular)
> Glycosaminoglycans
(GAGs)
> Proteoglycans
> Adhesive proteins
Function
o CONNECTS, fills space, cushions, supports
o Protects
- bone protects underlying organs
- mast cells-inflammation
- plasma cells- antibodies
- phagocytes- engulf foreign substances
o Barrier under epithelium
o Contains nerves- sensation
o Contains blood vessels, lymphatic
- nutrient, waste, gas exchange
Classification of Connective Tissue
A) Embryonic Connective TIssue
1. Mesenchymal CT 2. Mucous CT
B) Connective tissue proper
1. Loose (areolar) CT
2. Dense CT
i. dense irregular ct
ii. dense regular ct
> colleagenous
> elastic
3. Reticular tissue
4. Adipose tissue
C) Specialized CT
1. Caritlage 2. Bone 3. Blood
Mesenchymal Connective Tissue
Found only in embryo o Mesenchymal cells o A gel-like, amorphous ground substance o Scattered reticular fibers o Frequent mitosis: pluripotential o Eventually depleted and do not exist as such in the adult except in the pulp of teeth****
Mucous Connective Tissue
A loose, amorphous connective tissue:
o fibroblasts
o a jelly-like matrix: hyaluronic acid (more solid compared to the mesenchymal ct)
o Sparse type I and type III collagen fibers
o Wharton’s jelly: found only in the umbilical cord
and subdermal connective tissue of the embryo
Loose Connective Tissue
Fills spaces beneath epithelium tissues
o Fixed connective tissue cells:
- fibroblasts
- adipose cells
- macrophages
- mast cells
- Many transient cells
- responsible for immune response
o Abundant ground substance and tissue
fluid (extracellular fluid)
-Loosely woven collagen, reticular, and elastic
fibers
- Small nerve fibers and blood vessels supply the
cells with oxygen and nutrients
Three Attributes of Loose CT
- Cells:
- Mast cells (MC): largest cells in the field and
possess a granular cytoplasm
- Fibroblasts (F): posess oval nuclei, paler and larger
- Macrophages (M): smaller, darker
- Mast cells (MC): largest cells in the field and
- Fibers:
-Collagen fibers (CF): thicker, wavy, ribbon-like,
interlacing
- Elastic fibers (EF): thin, straight, branching - Ground substance (GS): invisible
Dense Connective Tissue
More fibers and fewer cells than loose connective tissue
o Resistant to stress: collagen bundles
o Dense IRREGULAR connective tissue: collagen fiber
bundles are arranged randomly
o Dense REGULAR connective tissue: collagen fiber
bundles are arranged in parallel or organized fashion.
- collagenous
- elastic
Dense Irregular Collagenous Connective Tissue
Bundles of collagen fibers oriented in various directions (meshwork)
Limited grounds substance and cells (fibroblasts)
Scattered elastic fibers
Resist stresses from many directions
Found the dermis of the skin, fibrous coverings on the surface of nerve, cartilage and bone, tough capsules around organs and joints
Dense Regular Collagenous Connective Tissue
Primarily parallel coarse collagen bundles densely packed into sheets or cylinders; a few elastin fibers, major cell type is the fibroblast
elongated nuclei (N) of the thin, sheet-like fibroblasts lying between collagen bundles
Function: attaches muscles to bones or to muscles; attaches bones to bones; withstands great tensile stress when pulling force is applied in one direction
Achilles tendon rupture
Collagen fibers in tendons all go in one direction, so it has less capability go withstand stress from other angles; also does not have the same regenerative properties, so the tendon cannot fuse back together on its own like other parts of the body can when they tear.
Dense Regular Elastic Connective Tissue
o Very similar to the organization of fibers in the tendon, BUT the regular elastic connective tissue structure is designed to
extend and return to its original length (resilience)
o Found in the wall of large blood vessels, underlying transitional
epithelium and surrounding respiratory passages.
Can distinguish elastin fibers through specific staining with ORCEIN
Reticular Tissue 9
A network of interlacing reticular fibers and reticular cells (fibroblasts); mesh-like with many lymphoid cells interspersing between the reitcular fibers
Found in the stroma (supporting framework) of the liver, spleen, lymph nodes; portion of red bone marrow, basement membrane, and around blood vessels and muscles
Function: forms stroma of organs; binds together smooth muscle tissues; filters and removes worn out blood cells in the spleen and microbes in the lymph nodes.
Adipose Tissue
o One of the largest organs in the body
- 15–20% (normal weight men) or 20–25% (normal
weight women) of body weight
o Largest repository of energy (in the form of triglycerides)
o Very cellular (adipocytes) and has little if any matrix and few fibers; limited ground substance
o Filled with lipid in a single droplet or in small droplets
is an endocrine organ and participates in endocrine regulation; example, adipocytes can make a hormone called leptin
fat tissue is also involved inflammation and inflammation is related to PERIODONTAL DISEASE
Unilocular
white fat tissue that possess one large lipid droplet
Multilocular
brown fat tissue that possess many lipid droplets and also has mitochondria; maintain body temperature
found a lot in newborns
Types of Cells in CT
A) Fixed cells
1. Fibroblasts 2. Adipocytes 3. Pericytes 4. Mast cells
B) Some fixed and some transient
1. Macrophages
C) Transient cells
1. Plasma cells 2. Blood cells
Connective Tissue Cells Lineage
Adipocytes, fibroblasts, pericytes and other epithelial cells come from UNDIFFERENTIATED MESENCHYMAL cells
The rest are derived from HEMATOPOIETIC STEM CELLS
Macrophages come from MONOCYTES
Fibroblasts
Make collagen and secrete it, so they have big nuclei and a lot of cellular organelles like highly active mitochondria, rough ER, and golgi
Function: Synthesize extracellular matrices – Collagen – Elas4n – Glycosaminoglycans (GAG) – Proteoglycan
• Synthesize growth factors
– influence growth and differentiation
Fibroblast vs Fibrocyte
• Fibroblast- active
– abundant, irregularly branched cytoplasm
– ovoid, large pale staining nucleus
– well developed rER, golgi
• Fibrocyte- inactive (quiescent)
– spindle shaped, few cell processes
– smaller, darker, elongated nucleus
– small amount of rER
Adipocyte
- Stores lipids
- Energy supply
- Padding, protection, shock absorber
- Insulation
- Generation of heat (brown fat)
- Endocrine function
Development of Fat Cells
They come from mesenchymal stem cells which can become fibroblasts or lipoblasts and then the lipoblast can become white or brown fat cells
Lipid Transport
Adipocyte to Capillaries
1) adipocytes store fat (energy) and this energy is used when we need it to burn fat to produce energy
2) triglyceride will be cleaved, perfused into a capillary, and then picked up.
3) It can also shift back to be stored by the fat cells
Pericyte
o Surround endothelial cells (rounded cell that wraps around)
o Have characteristics of endothelial cells and smooth
muscle cells: contractile- involved in blood flow; main function is contraction
o Plays a role in the blood–brain barrier
o Angiogenesis and the survival of endothelial cells
o Multipotential: wound healing-gives rise to connective tissue and blood vessels (i.e undifferentiated stem cell-like)
Mast Cells
• Oval to round
• IgE on surface
• Filled with metachromatic secretory granules
– histamine
– heparin
– neutral proteases
– ECF-A (eosinophil chemotactic factor of
anaphylaxis)
– NCF (neutrophil chemotactic factor)
– leukotrienes
– prostaglandins
– cytokines
- have single nuclei along with course and OBVIOUS granules
- found in the loose ct in skin and under the mesentry in intestines
- Because it is actively producing proteins, it is common to see a lot of the cellular organelles needed for protein synthesis in the mast cells
Macrophage
- Phagocytic
- Antigen presenting
- long living
- fixed and wandering
“Scavenger cells that find and destroy the bad guys”
Phagocytosis
1) Recognition and Attachment: microbes bind to phagocyte receptors
2) Engulfment: Phagocyte membrane zips up around microbe
3) Kill and Degrade:
Killing of microbes by lysosomal enzymes in phagolysosome
Opsonization
- the process by which a pathogen is marked for ingestion and destruction by a phagocyte
Types of Macrophages
Monocyte - found in blood and is a precursor to macrophages
Macrophage - found connective tissue, lymphoid organs, lungs, production of cytokines, chemotactic factors, and other imflamatory dense molecules; antigen presentation
Kupffer cell - found in liver; same function as macrophages
Microglia - found in nervous tissue
Langerhans cells - found in skin
Osteoclast - found in founds; digestion of bone
Multinuclear giant cell - digestion in ct
Plasma Cell
• Arise from B-lymphocytes
• Ovoid, basophilic
• Well developed rER
• Juxtanuclear golgi
• Secretes antibodies*****
• clumps of heterochromatin create a “clock face”
pattern of nuclear chromatin in which the nucleolus is eccentrically located and surrounded by CH like clock
Connective Tissue Fibers
- Collagen
- Reticular
- Elastic
Main types of Collagen
type I = dermis, bone, capsules of organs, fibrocartilage, dentin, cementum
type II = hyaline and elastic cartilages
type III = eticular fibers
type IV = basal lamina
type V = placenta
type VII = anchoring fibrils of the basal lamina (example: anchoring the fibrils produced in epithelium; epidermis is anchored by dermis)
NOTE When you say “collagen” by default, you are referring to Type I collagen; “collagenous tissue” means having type I collagen
Collagen Organization
(largest) Collagen fiber bundle»fibers»smaller fibrils»_space; aggregates of tropocollage molecules (smallest)
Tropocollagen molecules self-assemble: gap and overlap
The gap and overlap: in register with tropocollagen molecules of neighboring rows
Hydroxyproline residues of α chains: maintain the stability of the tropocollagen molecule (3 alpha chains)
The gaps are actually stained darker compared to the areas of overlap because the gaps hold more dye
Reticular Fibers
- Type III collagen
- THINNER and MORE CARBOHYDRATES than type I fiber
- stains black with silver stain and is invisible with H&E
- produced by reticular cell
- produce a scaffolding network (MESH-LIKE and less organized than collagen so it can hold a lot of cells)
Common in lymph nodes and spleen (specifically a major constituent of splenic cords in the red pulp)
Elastic Fibers
• Can stretch 150% of length
• Fiber composed of
– Outer- microfibrils of fibrillin (glycoprotein)
– Inner- amorphous core of elastin
Stains darker than collagen fibers in H&E staining and also appear much thinner than the collagen bundles
Van Gieson staining is also a special staining that allows you to see elastic fibers (stain a dark blue/black color)
Artery Walls and Elastic Fibers
Blood vessels have an internal elastic membrane called the tunica intima under the epithelium (simple squamous) Next is the tunica media layer which is layer of smooth muscle containing elastic fibers as well and then the tunica externa is the collagen fibes
Need the elasticity for expansion and contraction of theses thick vessels
Ground Substance
• Complex of macromolecules
• Fills space between fibers and cells
– organizes Lssue topography, supports cell
migration, orients cells, induces cell behavior
– binds growth factors, cytokines-reservoir
• Three classes of compounds
– Glycosaminoglycans (GAGs)
– Proteoglycans
– Multiadhesive glycoproteins
Glycosaminoglycan (GAGs)
- Repeating disacharide: Hexozamine +uronic acid
- Hydrophilic polyanions (can bind cations such as sodium)
- Part of proteoglycan
- Osmotic pressure leads to increased water content- firmness, flexibility
- Hyaluronic acid is the most ubiquitous GAG
Structure of GAGs and Proteoglycans
Glycosaminoglycans are made up of repeated disaccharide units which then come together and attach onto one large core protein
The GAGs attached on to a core protein = a PROTEOGLYCAN (has a brush-like appearance)
Multiadhesive glycoproteins
- Protein component predominates
- Globular protein with carbohydrate, attached carbohydrates are usually branched
- Cell-cell and cell-substrate
- Fibronectin: synthetized by fibroblasts and
epithelial cells - laminin: participate in adhesion of epithelium
cells to basal lamina - Integrins: Matrix receptor
Fibronectin
Exists as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds
Three binding domains
1) cells 2) collagens 3) GAGs
Laminin
Trimeric proteins that contain three chains
participate in adhesion of epithelium cells to basal lamina
Three binding domains
1) cells 2) collagens 3) GAGs
Integrins
Have two different
chains - the α (alpha) and β (beta) subunits
Are cell-surface molecule
that bind to collagen,
fibronecytin and laminin
Are transmembrane
receptors or linker proteins
and interact also with cytoskeleton AcHn
microfilaments
Plays a role in signaling transduction and can bind to specific ligands and activate down stream cell signaling
Process of how cells react to antigens
BASICALLY, secretory granules will come to the plasma membrane, fuse, and secrete the products out and ilicit an inflammatory response
DETAILS BELOW:
1) Binding of antigen to IgE-receptor complex causes cross-linking of IgE and consequent clustering of receptors
2) Activation of adenylate cyclase
3) Activation of protein kinase
4) Phosphorylation of protein
5) Release of Ca2+
6) Fusion of granules
7_ Release of granules’ contents or secretion of leukotrienes, thromboxanes/prostaglandins
Inflammatory Response
Histamine: vasodilation and increased vascular permeability (why we have stuff noses)
Eosinophil Chemotactic Factor (ECF) recruits eosinophil to take care of
parasitic infections
Neutrophil Chemotactic Factor: released in response to bacterial infection (microorganisms)
Leukotrienes: increase vascular permeability/enhance effects of histamine
Thromboxane A2: platelet-aggregating mediator and VASOCONSTRICTION
Tissue Fluid
o Similar to blood plasma in ions
o Similar to blood plasma in diffusible substances
o Contains low molecular weight plasma proteins
o Circulation to feed cells and remove waste
Hydrostatic and Osmotic Pressure Tissue Fluid Movement
In a blood vessel, there is an arteriole end and a venule end and two pressures exist between them: hydrostatic and osmotic pressure
There is a decrease in hydrostatic pressure and an increase in osmotic pressure from the arterial to
the venous ends of blood capillaries
Fluid leaves the capillary through its arterial end and re-penetrates (enters) the blood at the venous end while some fluid is also drained by the lymphatic capillaries
Edema
when there is a decrease in colloid osmotic
pressure, water accumulates in the connective tissue
This is because water leaves blood vessel from arterial
end is not drawn back into the capillaries at venous ends
Low osmotic pressure means that the fluid will stay in the tissue and it will cause swelling (EDEMA)
Skin
Basically made of two parts: epidermis ( stratified squamous epithelium) and dermis (dense irregular collagen ct)
Skin also has appendages such as sweat and sebaceous glands, hair, hair follicles and nails
Non-Inherited CT Disorders
1) Cellulitis: infection
> Requiring intravenous antibiotics
> 80% of cases of cellulitis of the submandibular
space caused by dental procedure
2) Scarred CT in dermis
> collagen bundles are irregular in the tissue but if they are really curvy and abnormal, it is actually scar tissue
3) Keloid Formation:
>Excessively thick layer of the dermis; apparent large, eosinophilic, type I collagen
fibers
Scurvy
Non-Inherited CT disorder
Vitamin C (ascorbic acid) deficiency leads to scurvy, a disease characterized by the degeneration of connective tissue.
Ascorbic acid is a cofactor for proline hydroxylase, which is essential for the normal synthesis of collagen
More pronounced in areas in which collagen renewal takes place at a faster rate (periodontal ligament) leads to a loss of teeth.
Inherited Disorders of CT
1) Ehlers-Danlos syndrome (EDS)
2) Marfan syndrome
3) Osteogenesis Imperfecta
4) Epidermolysis bullosa
Ehlers-Danlos syndrome (EDS)
Actually a group of more than 10 disorders
Defect in collagen synthesis (col I or III):
- progressive deterioration of collagens
Characterized by over-flexible joints, stretchy skin,
and abnormal growth of scar tissue.
Depending on the specific form of EDS, other
symptoms may include:
- A curved spine
- Weak blood vessels
- Bleeding gums
- Problems with the lungs, heart valves, or digestion
Marfan Syndrome
abnormal fibrillin gene
Fibrillin gene is required to make elastic fibers
The elastin protein makes the core and then the fibrillin to cover the core protein to make the functional elastic fiber
Osteogenesis imperfecta
Autosomal domninant disease: brittle bones
Present at birth
Defect type I collagen gene or different defects
that can affect this gene
Has oral manifestions as lack of/weak dentin and cementum because type I collagen also makes these fibers so the teeth are weak and miscolored
Epidermolysis bullosa
Fragile skin: Butterfly children
Mutations in the COL7A1 gene: anchoring fibrils
Type VII collagen: connect the epidermis to the dermis. When it is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate
Causes blistering in response to minor injury, heat, or friction from rubbing, scratching or adhesive tape
Autoimmune Diseases
Body’s normally protective immune system
produces antibodies that target the body’s own
tissues for attack
Scleroderma
Excess production of collagen buildup of scar tissue (fibrosis) in the skin and other organs
Hard and thick skin, swelling or pain
Localized and systemic sclerosis
Women are four times more likely to develop
Autoimmune Diseases, exact cause is unknown
Connective Tissue related lesion in the Oral Cavity
1) Plasma Cell Gingivitis
2) Irritation Fibroma (traumatic fibroma, focal fibrous hyperplasia)
3) Peripheral Ossifying Fibroma
4) Peripheral Giant Cell Granuloma
5) Desmoplastic fibroma
Plasma Cell Gingivitis
caused by an allergic rxn which activates the plasma cells in the area
Irritation Fibroma
Also traumatic fibroma, focal fibrous hyperplasia
most common of all hyperplastic growths in the oral cavity
hyperproliferations of collagen due to injury; not true neoplasm
Peripheral Ossifying Fibroma
A form of reactive hyperplasia that frequently contains bone
the lesion arises from the PDL structures or periosteum
Peripheral Giant Cell Granuloma
Most often affects the gingival
Fibroblasts and endothelial cells: often coalesce into multinucleated
giant cell forms
May surround sinusoidal spaces.
Desmoplastic fibroma
Benign fibrous infiltrative
proliferation: very dense
mature collagen
mandible of young patients
mandibular resection
recurrence rate 25%
