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Connective Tissue Unit I


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What is connective tissue and where is derived from?
Connect all other cells of different tissue types both mechanically and metabolicaly. They are all derived from the common origin of embryonic mesenchyme.
Three Groups of connective tissue
Embryonic - Mesenchymal and mucous
Connective tissue proper - Loose (areolar), Dense, Reticular, Adipose

Specialized Connective Tissue- Cartilage, Bone, Blood
Seven functions of connective tissue
1) Mechanical Support- structural support to organs, packing material, rigid structural support (cartilage and bones)
2) Mechanical Protection-
Bony protection, cushion
3) Energy storage and temperature regulation- Fat cells store energy and act as insulation
4) Metabolic support- mediates the exchange of all metabolites between the blood and the cells in the tissue
5) Transportation of materials- done by blood and lymphatics
6) Protection against infection- contains immune system cells, mechanical barrier to infection, macrophage system cells also located
7) Repair after injury- Scar formation
3 Elements of all types of CT
Cells, Extracellular fibers, Ground substance
CT cells (3 types)
Fixed cells, Wandering cells, Associated cells
Fixed Cells
Responsible for the synthesis and maintenance of the extracellular matrix
Wandering Cells
Transient cells that migrate into and out of the extracellular matrix (immune cells)
Associated cells
Cells associated with blood vessels that are always found surrounded and supported by connective tissue
Three types of Extracellular fibers and their function
Collagen fibers for strength
Elastic fibers for stretch and flexibility
Reticular fibers for delicate support
Ground Substance: What is it and what 3 things does it contain?
Is an amorphous clear area that contains:
Interstitial Fluid (Water)
Proteoglycans (Complex macromolecules consisting of core protein with glycoaminoglycans (GAGs) attached to it)
Glycoproteins (Core protein with sugars attached, form adhesion molecules)
Extracellular Matrix
Space between the cells which consits of extracellular fibers and ground substance. Is secreted by fixed cells.
Fixed Cell

-Most common fixed cell of connective tissue proper
-Appearance: Vesicular nucleus with nucleoulus, can't see cytoplasm
-Secretory cell
-Fibro blasts make new matrix and can differentiate and divide
- Fibro cytes can't differentiate and maintain the matrix around them
Mesenchymal cell
Fixed Cell

-Looks like a fibroblast
-Found in the embryonic tissue and has the same function as a fibroblast
-Pluripotential cell
Reticular cell
Fixed Cell

-Found in Reticular tissue
-Cell processes wrap around reticular fibers
-Form cell lined fiber network
-Secretes reticular fiber (glycoprotein) which sperates cells and prevents clotting
Two types of Adipose cells
White and Brown
White Adipocyte: Morphology, Location, Function
Morphology: Large spherical cell with a Unilocar (single large lipid droplet)
May be empty due to extraction of lipid during processing
"signet ring" appearance
Fat tissue is lacy and very light staning
Location: Normal component of areaolar (loose) CT, subcutaneous fascia
Function: Lipid storage, leaves blood vessel and broken down by Lipoprotein Lipase
Free fatty acids are taken up and complexed with glycerol to form triglycerides
Produces Leptin
Insulin acts on adipocytes
Mobilized by epinephrine or norepinephrine
Lipoprotein Lipase
Protein on endolthelial cells that breaks down white adipocytes into free fatty acids and glycerol
Hormone sensitive Lipase
Breaks down triglycerides into free fatty acids that complex with albumin to be transported around the body
a protein produced by adipocyte that targets the hypothalamus. Decreases food intak and increase energy consumption.
Insulin w/adipocytes
Acts on adipocytes to form trigycerides from glucose, increases uptake of glucase and the production of lipoprotein lipase
Epinepherine and norepinephrine action on adipocytes
"Flight or flight" response
Stimulate hormone sensitive lipase system to break down lipids and release glycerol and free fatty acids
Hypercellular Obesity
(hyper plastic obesity)
Increased number of fat cells
Usually due to overfeeding as infant and is serious
Hypertrophic obesity
Increased size (more lipid) of same number of fat cells, most common
Brown adipocytes: Morphology, Location, Function
Fixed Cell

Morphology: Smaller size, numerous mitochondria, are multilocar (numerous small droplets of lipid in cytoplasm)
Location: along aorta, mediastintum, axilla and between scapulae
Function: Generate heat w/ uncoupled oxidation process and use of Therminigen (unique to brown fat and used in hibernation and newborns)
A mitochondrial protein permits the back flow of protons instead of using them for ATP production
Fixed cell of the cartilage
Fixed cell of bone tissue
Blood Cells
Fixed cell of blood
Wandering Cells (3 types)
Macrophages, mast and plasma cells that migrate into and out of the connective tissue.
Also all leukocytes
Macrophages: Function, Origin, Appearance
Wandering Cell

Phagocytic- ingests particulate material

Are antigen presenting Cells

part of mononuclear macrophage system

Arise from monocytes (Granulocytic Mononuclear Stem Cell) in the circulating blood that once the moncyte leaves the blood vessel it becomes a macrophage

Has different dnames based on the organ where it is located

Appearance: Oval indented nucleus with vesicular chromatin pattern (more condensed than fibroblast nuclei), lots of lysosomes
Wandering macrophage found in immune system
VonKupffer cells
Wandering macrophage found in the liver
Wandering macrophage found in the brain
Alveolar macrophage
Wandering macrophage found in the lungs
Foreign body giant cells
Wandering macrophages found near wounds
Mast Cells: Morphology, Function, Location
Wandering Cell

Morphology: granular appearing, oval cells asssociated with small blood vessels, Nucleus is clear and mostly obscured by granules

Granule contents: Heparin, Histamine, Eosinophilic Chemotaxic Factor
Neutrophilic CHemotaxic Factor, leukotrines, cytokines. (Paracrine secretion - localized action)

Location: Along capillaries in mucosal membranes in respiratory, digestive and urinary tracts where Ag's (antigens) can easily enter.
-Increased vascular permeability
-Constriction of Smooth Muscle Cells of bronchioles
Immune system signalling molecule eg; tumor necrosis factor alpha
Action of Mast Cells
1) Store mediators of inflammatory response
2) bind IgE to its surface and then interacts with antigens
3) First exposure to Ag (antigen) causes formation of IgE's
4) IgE's bind to receptors on mast cell surface
5) Second exposure Ag binds to IgE on surface and activates adenyl cyclase
6) this causes phosphorylation of proteins that release Ca++ and causes fusion of granules and release of contents on surface.
Anticoagulant binds and inactivates histamine
Plasma cells: Morphology, Location, Function
Morphology: Diagnostic characteristics are the eccentric nucleus and cartweel chromatin pattern, lots of RER at EM level

Location: normally found only in connective tissue, not in peripheral blood

Derived from B-lymphocytes

Function: Produce Antibodies
Associated Cells (3 Types)
Endothelial Cells - line blood vessels
Smooth Muscle Cells- surround endothelium and control vessel size
Pericytes - Multipotential stem cells for vessel repari and growth
Extracellular Fibers (3 Types)
Collagen, Reticular Fibers, Elastic Fibers
what is Collagen's function? What percentage of dry weight and total protein does it make up?
Most abundant protein in the body
Makes up 30% of dry weight and 20% of all protein
Has high tensile strength, elastic yet flexible

Added to connective tissue where strength is needed.
Bundles of fibers usually found in the connective tissue proper
Collagen fiber
Straight unbranched fibrous protein
Has periodicity
Made up of collagen fibrils
Collagen Fibril
Smaller than a Fiber
Has periodicity
Made up of Tropocollagen molecules
Tropocollagen Molecules
What are they? What holds them together? What are they made of?
Consists of 3 alpha polypeptide chanis
Rich in glycine, proline, hydroxyproline and hodroxylysine.
Hydrogen bonding between hydroxyproline molecules of adjacent polypeptide chains hold the chains together.

Covalent bonding between the hydroxylysine molecules in adjacent tropocollagen molecules hold the fiber together
Type I Collagen (function, location)
Function: Strength
Location: Dermis, tendon, bone, dentin
Type II Collagen (function, location)
Function: Resists Pressure
Location: Hyaline and eleastic cartilage
Type III Collagen (function, location)
Function: Forms a delicate support meshwork
Location: Cardiovascular system, Lungs, Liver
Type IV Collagen (function, location)
Function: Attachment, Filtration
Location: Basal Lamin
Describe the synthesis of collagen
1) Transcription within nucleus
2) Translation within rER
3) Hydroxylation of proline and lysine occures in rough ER
4) Formation of procollagen in rER
5) Merocrine secretion via Golgin apparatus
6) Procollagen peptidase cleavage of procollagen to form tropocollagen molecules outside the cell membrane
7) Self assemply of tropocollagen molecules to form collagen fibril in extracellular matrix.
8) Lysyl oxidase covallently links hydroxyllysine molecules of adjacent tropocollagen molecules to form insoluble fibrils
Disease casued by lack of Vitamin C
Vitamin C is a cofactor required for hydroxylation of proline
Ehlers-Dalos Type VII
Due to one AA change in procollagen peptidase
Cause hyperflexible joints, dislocations, soft skin
What are collagen fibers broken down by?
Excessive action of this enzyme will present elevavated glycine in urine
Reticular Fibers (Morphology and Composition)
Morphology and composition: Small branched fibers forming branched network (squiggly), Branching fibers intersect at right angles
At EM level fibers composed of thin collagen type III fibrils covered with a sugar coat
Reticular fibers wrap each fiber
Secreted the same way as collagen fibers
Location: Found in regiond with lots of wantering cells, i.e. areolar connective tissue, reticular tissue, lymphatic tissue, liver
Function: Where delicate support is needed (holds space open for wandering cells)
Ehler-Danlos type IV
Reticular Fiber disease
Due to dificiency in type III collagen, causes Aneurysms and intestinal rupture common
Elastic fibers (Morphology, Function, Location, Formation)
Morphology: Y-branched fibers which form a continuous network within the tissue by fusing with adjacent fibers
Also be found as sheets or lamella in large blood vessels, intersect at acute angles not right angles
Consists of 2 components at EM level (Amorphous and Microfibril)

Function: Stretches to 150% of original length without breaking.
Springs back to original shape without using muscle energy

Location: Found in organs normally subjected to large amounts of stretching and repositioning i.e. blood vessels, aorta, lung, skin, ligamentum nuchae and uterus

Formation: Like collagen, proelastin to tropoelastin at cell membrane to elastic fibers outside cell. Lysyl oxidase forms covalent cross links between tropo elastin molecules to form elastin in a mesh of microfibrils.
Amorphous component
Part of elastic fibers, contains elastin, also rich in glycine like collagen but contains unique amino acids desmosine and isodesmosine
Microfibril Component
Part of Elastic Fibers
A glycoprotein
Elastic fiber system has 3 types of elastic fibers
Oxytalan fibers consisting primarily of microfibrillar component
Eulanin fibers consisting of microfibrils and some amorphous elastin
Elastic fibers
Disease of elastic fibers, causes lung dysfunction
Breaks down elastic fiber for contiuous turnover
Marfan's Syndrome
Casued by poor microfibril formation in elastic fiber, Tendency to rupture aorta and other blood vessels
Ground Substance (what does it look like, what is it?)
Has no visible structure, and is what remains after the cells and extracellular fibers have been removed
3 Components that make up ground substance
Proteoglycans, interstitial fluid, and glycoproteins
Part of Ground substance
Holds water
Is a protein core with glycosaminoglycans (GAGs) attached
"Bottle Brush Appearance)
Forms a porous hydrated gel which is slippery and resists compression
6 Different GAGs
Hyaluronic Acid (Non-sulfated), Keratan sulfate, Heparan sulfate, Chondroitin-6-sulfate, Chondroitin-4-sulfate, dermatan sulfate
Hyaluronic Acid (Appearance, Morpholgy, Function)
Nonsulfated GAG
Large highly coiled molecule
Negatively charged molecule that pulls in Na+ and Ca++ and holds water
Is slippery,resilient, lubricating
Gel like consistency that resists compression
Contains channels through which diffusion of materials is allowed
Forms a physical barrier that prevents migration of bacteria through ECM
Inhibits cell adhesion and facilitates cell migration.
Higher levels of HA during embryogenesis and repair
5 Sulfated GAGs and Locations
Keratan sulfate: Cartilage
Heparan sulfate: Located in basement membrane
Chondroitin-6-sulfate: located in cartilage, skin and bone
Chondroitin-4-sulfate: located in cartilage, skin and bone
Dermatan sulfate: located in dermis
Free Proteoglycans
Present within ground substance
Free Proteoglycan
Free in areolar CT matrix
Core protein with chondroitin sulfate and keratin sulfate attached
"bottle brush appearance"
Aggrecan Aggregate
Hyaluronic Acid with Hundreds of Aggrecan molecules
Found in cartilage matrix and much more gel-like and compression resistant
A free Proteoglycan that contains primarily heparin sulfate
Found in the basal lamina
Transmembrane Proteoglycan
PGs that extend throug hte cell membrane
A transmembrane PG, one end in the cytoplasm and the other end in the EMC
Rich in heparin sulfate and chondroitin sulfate
Heparin sulfate binds to other PG's with heparin sulfate and chondroitin sulfate.
A transmembrane Proteoglycan that is rich in heparin sulfate, Binds to 3 types of collagen and fibronectin
Protein core with branched sugars attached
Typically they are all adhesion molecules to help hold cells to the EMC
7 Examples of Glycoproteins
Fibronectin, Laminin, Entactin, Tenascin, Chondronectin, Oseonectin
Interstitial fluid
Water found in extracellular space, AKA tissue fluid
Important in the transport of nutrients and wastes between blood vessels and the parenchyma
Bound by the proteoglycans and hyaluronic acid
Formation of Interstitial Fluid
Hydrostatic pressure on arterial end forces fluid out of capillary into ECM
Circulated through channels in HA and Proteoglycans towards venous end of capillary
Most fluid reenters capilllary due to higher oncotic pressure (due to loss of fluid) and large albumin molecules still in blood
Always excess fluid left in ECM this is drained away in lymphatic capillaries
Production and resorption of fluid creates continuous circulation through ECM
Supplies nutrients and removes wastes from parenchymal cells
Abnormal build up of interstitial fluid in ECM
Causes Pitting Edema (leaves a dent when pushed on)
Causes of Edema
Blocked lympahtics-surgery, elephantiasis
Blocked venous return- compromised veins in pregnancy
Liver disease - insufficent albumin (produced by liver) to pull H2O back in vessel
Increase vascular permeability- asthma, hypersensitivity, anaphylactic shock, histamine from mast cells
Hypertension- due to increased hydrostatic pressure at arterial end of capillary bed.
Starvation - causes lack of plasma proteins that results in H2O remaining and ECM
due to over production of GAGs during hyperthyroidism
"mucous edema"
Basement Membrane
Light microscope term
Located in extracellular space
Functions to connect cells (epithelial, muscle and nerve cells) to connective tissue
Surrounds all cells except connective tissue cells (fixed and wanderin)
3 Layers of Basement Membrane
Lamina lucida (light)
Lamina densa
Lamina reticularis
Lamina lucida (structure/function)
light layer next to cell membrane
Contains integrins, laminin, entactin
Lamina densa
Dense fuzzy band, contains collagen IV, perlecan (heparan sulfate) and fibronextin
negatively charged
acts as a flexible macromolecular filter
Lamina reticularis
containes reticular fibers (collagen III) and also IV and VII of anchoring fibrils
Basal lamina
Basal lamina consits of both the lamina lucida and lamina densa (not lamina reticularis) used when looking at the epithelium
Alternative view of what the basal lamina is
Just the lamina densa
Appears this way in muscle cells but really only has a reduced amount of lamina lucida
Function of Basal lamina (2)
Holds cells to surrounding connective tissue
Acts as macromolecular filter

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