12_Ctb 1.11 Extracellular Matrix And Ct

Front 1

What are the two basic types of connective tissue-forming cells?

Back 1

Fibroblasts and adipocytes.

Front 2

What is another name for "fluid matrix"? What is it used for?

Back 2

Ground Substance. It's a hydrated medium for diffusion.

Front 3

Ground substance is composed of a mixture of:

Back 3

Glycosaminoglycans and Proteoglycans

Front 4

What is the difference between glycosaminoglycans and proteoglycans?

Back 4

Glycosaminoglycans are unbranched polysaccharide chains consisting of repeating disaccharide units vs proteoglycans that consist of a core protein linked to GAGs.

Front 5

So, you know that the ground substance contains two types of polysaccharides (GAGs and proteoglycans) - what two types of fibers is ECM composed of?

Back 5

Elastin and Collagen

Front 6

Describe the basic composition of collagens

Back 6

Three triple helix alpha chains

Front 7

Describe the basic composition of elastin molecules:

Back 7

Elastic fibers that are cross linked and coated with fibrillin.

Front 8

What are the two Adhesive Glycoproteins mentioned?

Back 8

Laminin and Fibronectin.

Front 9

How is the cell linked to the extracellular matrix?

Back 9

Via Laminin and Fibronect that bind to integrins.

Front 10

GAGs are composed of disaccharide units. One of the two repeating sugars is always: (give example). The partner sugar is usually:

Back 10

An amino sugar: N-acetylglucosamine or N-acetylgalactosamine. Partner sugar is usually glucoronic or iduronic acid.

Front 11

What is it about GAGs that allow them to hold water?

Back 11

The amino sugar is usually sulfated and also have carboxyl groups projecting from them - making them highly negatively charged. The charge binds Na+ which osmotically attracts water into the matrix.

Front 12

What are the four main types of GAGs?

Back 12

1. Hyaluronate 2. chondroitin sulfate and dermatan sulfate 3. heparan sulfate and heparin 4. keratan sulfate

Front 13

What is the predominant GAG? Unlike other GAGs, what is it missing? Does it form covalent links to protein molecules?

Back 13

Hyaluronate. It is nonsulfated, single disaccharide unit. It does not covalently link to protein molecutles.

Front 14

Hyaluronate is a GAG that has nothing to do with sulfate or proteins. Proteoglycans, however, are GAGs that: (re sulfate and proteins?)

Back 14

They have sulfate and covalently link with protein core.

Front 15

What is an Aggregan Proteoglycan?

Back 15

It is a large multimeric complex consisting of a hyaluronate backbone with many proteoglycans link onto the backbone.

Front 16

What is the function of proteoglycans? (physically? receptor-wise? enzyme-wise?)

Back 16

Physically: As filters of variable pore size and charge density that screen and retard macromolecules as they pass through them. Receptor-wise: They can bind sites for growth factors such as FGF and TGF. Enzyme-wise they can act as proteases and protease inhibitors.

Front 17

What is an example of a non-secreted proteoglycan? Describe it and its attachments.

Back 17

Syndecan. Instead of being released into the ECM, it remains attached to the cell membrane. It is attached to actin filaments of the cytoskeletin and to collegen and fibronectin in the ECM.

Front 18

What is the genetic disease associated with proteoglycan production problems? What's the problem specifically?

Back 18

Progeria - it's a fatal premature aging disorder of children. Galactosyltransferase thermolability in fibroblasts result in failure of dermatan sulfate chain addition to proteoglycan.

Front 19

In general, what do the following collagen groups form:
Type I, II, and II?

Back 19

1. Bone, skin, tendon,
2. Cartilage, intervertebral disc
3. Skin, blood vessels

Front 20

Describe how collagen is synthesized

Back 20

1. Preprocollagen chains called "alpha chains" are synthesized on the RER and have additional aa sequences known as propeptides at the amino and carboxy terminal ends.
2. Selected Prolines and Lysines are hydroxylated and glycosylated
3. Three preprocollagen molecules are aligned and assembled into a procollagen triple helix - it is then routed in vesicles to the cell surface via golgi.
4. Following secretion, propeptides are cleaved from preprocollagen molecules to form tropocolllagen.
5. Tropocollagen molecuels are then spontaneously assembled in a head to tail fashion
6. Covalent bonds are formed between lysine and hydroxylysine residues of neighboring tropocollagen molecules.
7. Collagen fibrils are aggregated into collagen fibers.

Front 21

Why does a lack of vitamin C cause scurvy?

Back 21

VitC is required for hydroxylation of proline residues. This renders alpha chains unable to form stable helices and the tropocollagen fibers incapable of aggregating into fibrils.

Front 22

Excess accumulation of collagen during wound healing causes:

Back 22

Keloid

Front 23

What are the three genetic diseases of collagen and what do cause problems in?

Back 23

1. Osteogenesis imperfect: Type I collagen and brittle bones
2. Chondrodysplasias: defect in Type II and cartilage join deformities.
3. Ehlers-Danlos syndrom: defect in type III collagen mutation characterized by weak skin, fragile blood vessels

Front 24

What tissue is Elastic Fibers commonly found in>?

Back 24

Skin, lung, and blood vessels

Front 25

What two fibers is elastin composed of?

Back 25

Elastin and Fibrillin

Front 26

Elastin fibers are rich in these three amino acids:

Back 26

1. Glycine
2. Lysine
3. Proline

Front 27

Elastin is synthesized by this cell and assembled here:

Back 27

Fibroblasts and ECM

Front 28

What is Marfan Syndrome caused by? Why must these patients be monitored?

Back 28

Mutations in the fibrillin gene. They must be monitored for potential rupturing aneurysms.

Front 29

What are the adhesive glycoproteins again? And what do they do?

Back 29

Fibronectin and laminin. They link the basal lamina to cell transmembrane receptors called integrins.

Front 30

Describe the structure of Fibronectin.

Back 30

A lg glycoprotein heterodimer (disulfide-linked) with Collagen, Heparin, and Cell (integrin) binding domains separated by flexible hinge peptides.

Front 31

Is there structural continuity between the cell cytoskeleton and ECM via fibronectin? If so, how.

Back 31

Yes. The fibronectin receptors within the cell membrane bind to actin filaments within the cell cytoskeleton, and to collagen and heparin sulfate in the ECM.

Front 32

What does the laminin form a link between?

Back 32

Between the cell membrane and other constituents of the basal lamina.

Front 33

Describe the basal lamina

Back 33

It is a sheet-like network of ECM proteins that act as an interface between the epithelia and underlying or surrounding connective tissue.

Front 34

What is basal lamina primarily compsed of?

Back 34

Fibrous protein type IV collagen

Front 35

Modified fibroblasts that demonstrate characteristics of both fibroblasts and smooth muscles cells are called:

Back 35

Myofibroblasts.

Front 36

What are the three functions of the basal lamina

Back 36

1. Molecular filter
2. Selective barrier to cells
3. Scaffolding for regeneration

Front 37

What enzymes allow MAs, Lymphocytes, and nerve fibers to penetrate the basal lamina?

Back 37

Matrix Metaloproteinases and Serine Proteases.

Front 38

What does Matrix Metaloproteinases and Serine Proteases degrade?

Back 38

Colagen, laminin, fibronectin

Front 39

In what four ways does proteolysis of matrix proteins contribute to cell migration?

Back 39

1. Clears a path through the matrix
2. Exposing cryptic sites on the cleaved proteins that promote cell binding, cell migration, or both
3. Promotes cell detachment so that a cell can move onward
4. Releasing extracelullar signal proteins that stimulate cell migration.

Front 40

Matrix degradation is regulated by two inhibitors:

Back 40

1. Peptide tissue inhibitors of metalloproteases (TIMPs)
2. Serine protease inhbitors (serpins)

Front 41

How do TIMPs and Serpins regulate matrix metaloproteinases and serine proteases?

Back 41

They act locally to prevent degradation of marginal matrix. The also protect cell-surface proteins required for cell adhesion and migration.

Front 42

During angiogenesis, sprouting endothelial cells penetrate the ECM by secreting these compounds:

Back 42

1. Hyaluronidase
2. Plasminogen activator (converts plasminogen to plasmin)

Front 43

Describe the cellular features of Fibroblasts:

Back 43

1. Axis runs parallel to long axis of collagen fibers reflecting stress and surrounding environment
2. Large ovoid fibroblast nucleus contain patches of marginal heterochromatin and 1 or 2 well defined nuclei
3. Prominant golgi apparatus, slender MT, abundant RER
4. Lack a basal lamina

Front 44

What is the name given to modified fibroblasts that demonstrate characteristics of both fibroblasts and smooth muscle cells? This happens via transdifferentiation - what is that?

Back 44

Myofibroblasts. Transdifferentiation is when a non-stem cell transforms into a different type of cell. In this case, from a fibroblast and smooth muscle cells.

Front 45

Adipose cells store lipids in the form of:

Back 45

Triglyceride droplets

Front 46

Adipocytes have receptors for insulin, glucocorticoids, growth hormone, and noradrenaline that modulate uptake and release of fat - reflecting its important participation in general metabolic processes. What hormone does leptin secrete to regulate appetite?

Back 46

Leptin

Front 47

How does insulin and norepinephrine affect adipose cells

Back 47

1. Insulin stimulates them to convert glucose to triglycerides
2. Norepindephrine stimulates them to convert triglycerides to fatty acids and glycerol.

Front 48

What is the difference between white adipose tissue and brown adipose?

Back 48

White has a single large lipid droplet surrounded by a thin rim of cytoplasm. Brown adipose contain multiple small lipid droplets (multilocular)

Front 49

Why is brown fat tissue reddish?

Back 49

Bc of abundant capillaries and MT.

Front 50

What are the two ways in which adults develop obesity? Briefly describe.

Back 50

1. Hypertrophic Obesity - accumulation and storage of fat in white adipose cells
2. Hypercellular Obesity - overabundance of adipocytes.

Front 51

Where are leptin receptors located? What happens when this center is activated?

Back 51

Appetite center of the hypothalamus. When activated, it stimulates the sympathetic nervous system to release norepinephrine. This shifts adipose tissue from fat storage to glycerol/fatty acid mobilization and oxidation.

Front 52

What are the wandering cell component of connective tissue? What are the subgroups of this cell?

Back 52

Leukocytes - these include MAs, lymphocytes, plasma cells, eosinophils, neutrophils and mast cells.

Front 53

What is the difference between ground substance and mucous connective tissue?

Back 53

1. Ground substance: contains reticular fibers
2. Mucous CT contains hyaluronic acid and fibrillar collagens

Front 54

Describe Loose (areolar) CT. Where is it most often found?

Back 54

1. Composed of loose arrangement of fibers and dispersed cells.
2. Found under epithelia of the body, packaging organs and surrounding capillaries.
3. It cushions organs and hold tissues together.
4. MAs found here phagocytose bacteria.

Front 55

Describe Dense Connective Tissue. What are the two types?

Back 55

1. Contain greater abundance of fibers and fewer cells than loose connective tissue. The two types are irregular and regular.

Front 56

Describe irregular vs regular dense CT.

Back 56

1. Irregular withstands tension exerted in multiple directions and provides structural strength.
2. Regular provides great tensile strength when force is applied in one direction.

Front 57

Where is Irregular Dense CT found?

Back 57

It is found in the reticular layer of the dermis of the skin, submucosa of the digestive tract, fibrous capsules of visceral organs and joints.

Front 58

What is the structure of regular dense CT? Where is Regular Dense CT found?

Back 58

It is composed of coarse collagen bundles densely packed and oriented into parallel cylinders or sheets that resist tensile forces. Located in tendons, most ligaments, and aponeurosis. They attach muslces to bones or muscles, and bones to bones. Found in cornea with overlapping Type I collagen fibers stacked a nearly right angles embedded in proteoglycans. Orderly packing makes the cornea transparent.

Front 59

Describe Reticular CT

Back 59

A network of reticular fibers composed of collagen type III in loose ground substance.

Front 60

Where is reticular CT mostly found and what is its function.

Back 60

Mostly found in liver, lymph nodes, spleen, and pancreas. It functions to support parenchyma of organs.