block III: CT video 2

Question 1

Which collagens are present in the basement membrane?

Answer 1

Type IV
Type VII
Type III collagen fibrils!!!

Question 2

Mention the function of type IV collagen in BM?

Answer 2

The major component of the lamina densa of the basal lamina. This is a non-fibril forming collagen

Question 3

Mention the function of type VII collagen in BM?

Answer 3

Forms thin anchoring fibrils that link lamina densa of basement membrane to underlying lamina reticularis

Question 4

Mention the function of type III collagen fibrils in BM?

Answer 4

Associated with the reticular layer of
the basement membrane. Made by
CT cells.

Question 5

identify

Answer 5

EM showing the attachment of the basal lamina to the underlying lamina reticularis collagen fibers by type VII collagen anchoring fibrils and fibrillin microfibrils

Question 6

identify

Answer 6

Question 7

What pathologies involve mutations in collagen or its synthesis?

Answer 7

Scurvy, osteogenesis imperfecta and Ehlers-Danlos

Question 8

What happens in Scurvy syndrome?

Answer 8

Defective synthesis of collagen due to lack of vitamin C and iron as cofactors for hydroxylation of proline and lysine in collagen synthesis.

This results in unstable collagen molecules or in poor crosslinking of the collagen molecules in the collagen fibril

Question 9

Why does scurvy happen and what are some of the symptoms?

Answer 9

Typically due to a lack of fruits and meat in diet. Characterized by weakness & fatigue, bleeding gums, easy bleeding, poor wound healing, and fragile skin. Still present in under-developed countries where the diet is poor

Question 10

what happens in osteogenesis imperfecta?

Answer 10

defects in type I collagen characterized by easily fractured brittle bones, abnormal teeth, weak tendons, blue sclera, and progressive hearing loss (defective bones in middle ear).

Question 11

WHat are some symptoms of osteogenesis imperfecta?

Answer 11

Note that in cases of suspected child
abuse, this disease may need to be considered as it also may present as multiple bone fractures similar to those seen in child abuse (but not related to abuse in this case)

Question 12

What is the general overview of Elhers danlos syndrome?

Answer 12

are a family of disorders resulting from defects in collagen molecule synthesis. Currently there are at least 13-subtypes. These subtypes vary in severity and whether the defect is in specific collagen protein chains or in the enzymes
involved in the processing of the procollagen chains.

Although these syndromes were initially
named using roman numerals, this has been changed and the various syndromes are classified according to effects

Question 13

What is classical Ehlers-Danlos syndrome?

Answer 13

is relatively mild and typically results from
defects in collagen type V, although it can also involve defects or mutations in type I
collagen not involving glycine residues in the Type I collagen.

Question 14

By what is classical Ehlers-Danlos characterized?

Answer 14

Characterized by hyperextensibility of skin & joints, easy bruising of skin, fragile skin, and poor wound healing.

It illustrates that the involvement of type V collagen in formation of type I
collagen fibrils may be important.

Question 15

What is Vascular Ehlers-Danlos?

Answer 15

one of the most severe and results primarily from defects in collagen type III (reticular fibers).

Question 16

By what is vascular Ehlers-Danlos characterized?

Answer 16

Characterized by ruptures of walls of major tubes in vascular and gastrointestinal tract.

The vascular effects involving dissection and rupture of the aorta or other large arteries or ruptures in the GI tract often results in early death (~ 50 yrs or younger)

Question 17

what is the diameter of elastic fibers and its stain?

Answer 17

1. typically 1-2 microns in diameter. Frequently branch
2. Require special elastic stains to be easily seen. Are not easily visualized just with H&E staining

Question 18

what is the ability of elastic fibers?

Answer 18

ability to reversibly stretch up to 150% of their length without breaking

Question 19

What function of elastic fibers is important?

Answer 19

while providing some mechanical
strength are important in adding elasticity in the connective tissue and to that region of the organ

Question 20

identify

Answer 20

Elastic fibers stained in dermis of skin

Question 21

identify

Answer 21

Elastic fibers stained in wall of aorta (elastic lamellae)

Question 22

how does elastic fibers appear in EM?

Answer 22

the elastic fiber appears as an amorphous central area composed of the crossliked elastin molecules with beaded-like
microfibrils composed of the protein
Fibrillin-1 both embedded in it, and
surrounding the surface of the fiber

Question 23

identify

Answer 23

EM of elastic fiber showing region of elastin and fibrillin 1 containing microfibrils (arrows)

Question 24

explain the crosslinking of elastic fibers

Answer 24

Within the elastic fiber, individual elastin molecules are crosslinked by unusual ring-shaped amino acids called desmosine and
isodesmosine which crosslink pairs of lysine (or modified lysine) residues present on one elastin monomer to a similar pair of lysine residues on an adjacent elastin molecule

Question 25

How does lysine in elastin should be?

Answer 25

must be only 2 or 3 amino acids apart in the polypeptide chain. Lysl oxidase required for cross-linking.

Question 26

why is cross-linking in elastic fibers necessary?

Answer 26

necessary for the elastic properties of the elastic fiber

Question 27

identify

Answer 27

Question 28

how is elastin in unstretched way?

Answer 28

Elastin in the unstretched state takes up a more globular shape or conformation as its lowest free energy state

Question 29

WHat happens to elastin when it is streched?

Answer 29

When external stretching forces are applied, the molecule can unfold into a more linear conformation. Upon removal of these external forces it will return to its original conformation

Question 30

What does crosslink between elastin molecules allow?

Answer 30

allow change in state (stretch or unstretched) to occur across all the molecules in the fiber giving it its elasticity

Question 31

What is the role of fibrillin microfibrils?

Answer 31

form first by a head-to-tail bonding of fibrillin-1 molecules giving a beaded appearing structure;main role formation of elastic fibers

Question 32

what is MAGP-1 and what does it do?

Answer 32

Microfibril-associated glycoprotein-; binds to fibrillin-1 at the beaded regions, and facilitates the secondary binding of tropoelastin molecules along the microfibrils

Question 33

WHat does lysyl oxidase crosslinks and what does it do?

Answer 33

Lysyl oxidase crosslinks the tropoelastin molecules by way of the pairs of lysine residues on adjacent tropoelastin molecules which subsequently appear to form the amorphous structure of the elastin

Question 34

What is Marfan's syndrome?

Answer 34

(pathologies involving elastic fibers) mutation in the fibrillin-1 gene on chromosome 15. Typically seen in very tall thin individuals who have abnormally long fingers, and lax joints

Question 35

What are some symtpms and issues of marfan's syndrome?

Answer 35

* Pulmonary problems due to reduced elastic fibers in lungs * Dislocations of the lens since the lens suspensory fibers are composed of fibrillin * Valve defects due to less elastic tissue in valves or its defective elasticity * Fragile vascular walls which can lead to early death

Question 36

What characteristic may suggest possibility of marfan's syndrome?

Answer 36

both the long fingers and frequent dislocations of the lens together

Question 37

Why do patients with marfan's syndrome are prone to death by mid 40s?

Answer 37

because of dissection and catastrophic ruptures in the wall of the aorta

Question 38

identify

Answer 38

Aorta from individual with Marfan’s syndrome. Note fragmented or absent elastic lamellae in wall

Question 39

What happens with the aortas of some marfan's syndrome individuals?

Answer 39

display cystic medial degeneration, a condition in which the fenestrated elastic membranes (lamellae) as well as the smooth muscles of the tunica media of the aorta are reduced in quantity or are partially absent, and replaced with ground substance

Question 40

Why does wrinkles and photoaging of skin occur and what is disrupted in this?

Answer 40

Both with age and exposure to sunlight the number of elastic fibers decreases but in addition with photo-aging there is an abnormal increase in diameter and stiffness of the remaining defective fibers. This may involve effects of sunlight on fibrillin-1 in the elastic fibers of skin. This can result in the extreme wrinkled appearance of the skin seen both with age and with exposure to sun light.

Question 41

What is also related with photoaging and age?

Answer 41

associated decreases in production of type I and type III collagens and faulty collagen fibers due to defects in crosslinking of the collagen

Question 42

What is the general composition of ground substance?

Answer 42

composed predominantly of glycosaminoglycans (GAGS), proteoglycans, proteoglycan aggregates, and multiadhesive glycoproteins

Question 43

What are the major GAGS?

Answer 43

* hyaluronic acid (non-sulfated) * chondroitin 4-sulfate * chondroitin 6-sulfate * keratan sulfate * dermatan sulfate * heparan sulfate * heparin

Question 44

Which GAGS are sulfated?

Answer 44

all except hyaluronic acid

Question 45

What are GAGS?

Answer 45

linear chains of repeating disaccharide (sugar) units composed of a sugar amine (N-acetylgalactosamine or Nacetylglucoseamine) and a uronic acid sugar such as glucuronate

Question 46

Where do GAGS bind to?

Answer 46

GAGS (except hyaluronic acid) bind to core proteins to form proteoglycan monomers

Question 47

Which monomers bind to hyaluronic acid?

Answer 47

Proteoglycan monomers may in turn then bind to hyaluronic acid by way of link proteins to form proteoglycan aggregates up to 20 microns long

Question 48

What are polyanions and what do they bind to and their role?

Answer 48

negatively charge molecules; GAGS, proteoglycans, & proteoglycan aggregates are polyanions that bind large amounts of water to form hydrated gels that play a role in filtration of ions and molecules in extracellular space & resist compression for example in cartilage

Question 49

What are multi adhesive extracellular glycoproteins and their function?

Answer 49

are multidomain molecules with multiple binding sites for other glycoproteins, collagen, and cell surface molecules. They act to stabilize the extracellular matrix and play a role in binding of cells to it. Some are in basal lamina and attach epithelial cells to CT

Question 50

WHat are some of the multi-adhesive extracellular glycoproteins?

Answer 50

* Fibronectin * Laminin * Tenascin * Osteopontin * Chondronectin * Osteonecti