ECM and connective tissue Flashcards
Components of CT
Fixed cells- relatively stable population numbers of long lived cells (weeks-months) cells that develop from the mesenchyme. Include fibroblasts which form the ECM, adipocytes which form fat
Free wandering cells: changing populations of specific defense cells (WBC) that are short lived and enter the CT from the blood vessels: macrophages, eosinophils, neutrophils, lymphocytes, plasma cells, mast cells
Extracellular matrix: fibers plus the ground substance The dominant component of CT and determines the physical properties of each type of supporting tissue
Functions of CT
Mechanical support- bundles cells of the same tissues together and anchors the tissues to each other to form organs and binds different organs together
Exchange of metabolites between blood and tissues: ground substance in ECM proveds hydrated medium for diffusion
Storage of energy reserves: storage of lipids in fat cells and proteins (albumnin, immunoglobulin) in the ECM and blood
Protection against infection: phagocytosis by macrophages, neutrophils, and mast cell degranulation during inflammation
Repair following injury: fibroblast proliferation and secretion in wound healing
All tissues are composed of cells and an ECM
the ECM is complex of nonliving macromolecules manufactured and transported in extracellular space by the cells that make up the tissue.
ECM is a hydrated gel-like ground substance (mix of GAGs and proteoglycans, which resists forces of compression) with fibers embedded (collagen and elastin, withstand tensile force) in it
Macromolecules provide structural stability and determine the properties of the tissue
the matrix:cell ratio is high in connective tissue to low in nervous tissue
adhesive glycoproteins: laminin and fibronectin link the cell to the extracellular matrix by binding to integrins located in the cell membrane
The interface between the epithelium and CT is the basment membrane (made by matrix) which controls cell behavior
GAGs
glycosaminoglycans are long inflexible polysaccharide chains composed of repeating disaccharide units. One of the 2 is always an amino sugarwith the parter being uronic acid (gluco or idu)
GAGs are negatively charged, the amino sugar is sulfated and gags have carbosyl groups projecting from them. The negative charge allows for Na to bind and water to follow, making a cushion to absorb and disperse compression
4 gags (hyaluronate, condroitin/dermatin sulfate, heparan sulfate and heparin, keratan sulfate) Hyaluronate is the predominant GAG in loose tissues. Hylauronate is the only GAG that isnt sulfated, its a disaccharide which is very long. Doesnt link to protein molecules. It lubricates joints and is important for resiting compression, produced in large quantities during wound healing)
Proteoglycans and Aggregans
Sulfated GAGS (other than hyaluronate) covelenty link to proteins and form proteoglycans give the bottle brush apperance. The GAGs attach to a core protein in the golgi, with the core protein and number of attached gags differing
Link proteins attach proteoglycans to hylauronate backbone to make an aggregan proteoglycan. found ing cartilage and CT
Collagens
a family of fibrous proteins constituing the largest pecentage 25% of the protein mass
triple helix composed of 3 alpha chains Gly-X Y (with hydroxyproline and proline), synthesized and secreted by CT fibroblasts
synthesis, post translation mod, and tribble helix assembly occur intracellularly and secreted as procollagen. Then extracellulary the procollagen cleave the terminal peptides by proteases. Tropocollagen self assembles into collagen fibrils 1 2 3 7
Cross linking collagen fibrils form mature collagen fibers (9 and 10)
Collagen1- (90%) bone skin tendon cornea organs
3- skin, blodd vessels. visceral organs (reticular fibers)
4- sheets in the basal lamina
7- anchoring fibrils (skin)
Scurvy (vitamin C deficiency- no hydroxylation of prolines)
Keloid: too much collagen during wound healing, elevated scarring
Genetic disease of Collagen
osteogenisis imperfecta: defect in type 1 collagen yielding easily fractured bones (brittle bone)
chondrodysplasia: defect in type 2, joint deformaties and dwarfism
Ehlers danlos: type 3, weak skin fragile blood vessels and hypermobile joints, sprains and dislocation
Elastic fibers
Elastin is synthesized by fibroblasts and assembled in the ECM into elastic fibers consisting of elastin core surrounded by sheath of microfibrils composed of fibrilin (an elastic glycoprotein)
The chains of elastin are covalently linked by lysine residue. Theres a network of elastic fibers in the ECM of skin, lungs and blood vessels- stretch and recoil
Marfan syndrome: mutation in fibrilin gene- danger of aortic anuerism
Adhesive glycoproteins
fibronectin and laminin: extracellular proteins that help cells attach to ECM, linked to intermediate filaments (hemidesosomes) or actin in (adhesion plaques) in the cytoskeleton via integrins
Fibronectin- large glycoprotein heterodimer (disulfide linked) contains collagen, heparin, and cell-intgrin binding domains separted by flexible hinge peptides
Laminin: very large glcoprotein, chicken foot. A major component of the basement membrane that attached cell membrane and basement membrane
Basement membrane
aka basal lamina
flexible, thin mats of specialized ECM that undelie all epitheliul cell sheets, separating the cells and the epithelia from the underlying or surrounding it. synthesized largely by the cells that rest on it. Composed of type 4 collagen. Layers of collagen fibrils tethers the basement membrane to the underlying CT (made of type 7 collagen)
Functions of basement membrane:
- molecular filter
- Selective barrier to cells: fibroblasts and enothelial cells normally dont penetrate the basement membrane
- Scaffolding for regeneration: skeletal muscle fiber regeneration
ECM degredation
Matrix components are degraded by extracellular proteases secreted locally by cells: matrix metaloproteinases and serine proteases degrade matrix components
metaloproteinases: regulated by Peptide tissue inhibitors of metalloproteases (TIMPS) and serpins (for serine)
They also help clear the path to get stuff into the tissue, but if unregulated could lead to metastis
Fibroblasts
most abundant and widely distributed cells of connective tissue. Responsible for the synthesis of almost all ECM in CT. Associated with collagen bundles. Nucleus has a patch of parcinal heterochromatin and 1/2 well defined nuclei
the cytoplasm contains mostly golgi apparatus and RER
Adipocytes
fully differentiated cells that funtion in the synthesis, storage and release of fat
Store lipids in the form of TG droplets from 3 main sources (chylomicrons, liver fat, adipose fat). They have receptors for insulin GCs, GH, and adrenalines secrete leptin that regulates apetite (without it, constantly hungry)
White adipose cells: single droplet (unilocular surrounded by a thin cytoplasm). Heavily supplied with blood vessels, and partition the fat into lobules. 20% in males 25% in females
Brwon fat: newborns, multilocular and lots of mitochondria, nonshivering thermogenisis
Hypertrophic obesity: cells increase in volume
Hypercellular : cells increase in number
Embryonic Connective tissue
mesenchymal CT only present in embryo, give rise to most of the cells in loose CT. in a gell like ground substance with lots of reticular fibers
Loose areolar CT
Composed of a looses arrangement of fibers and disperesed cells (fibroblasts and some WC). imbedded in gell like ground substance
Found in epithelia of body, packaging organs and capillaires
Wraps and cusions organs
