Abnormal Fibrous and Elastic tissue Flashcards
Collagen Tissue
Connective Tissue is an abundant supportive tissue throughout the body
It provides structure and support to organs and connects tissue together
There are three components to connective tissue
An abundant supportive tissue throughout the body
Collagen
Elastin
Fibrillin
Collagen
Most abundant protein in the body
Found in bone, skin, cartilage, blood vessels, and other
Types I-IV
Associated with scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome, and Menkes disease
Since collagen is the most abundant protein in the body, we’ll start here
It’s found in bone, skin, cartilage, blood vessels, and more
There are four types, but knowing these four types is not as high yield as knowing the types a/w diseases, such as scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome and Menkes disease
Collagen Types
Collagen Synthesis
Collagen is synthesized by chondroblasts, osteoblasts, and fibroblasts
Collagen synthesis starts in the nucleus and ends in the extracellular space
In the nucleus, collagen DNA is transcribed into collagen mRNA
Collagen mRNA then enters the endoplasmic reticulum and is translated to the pro -chain
Collagen Synthesis Step 1-2
So just to recap, collagen synthesis begins with the translation of collagen mRNA to pro alpha-chain in the endoplasmic reticulum
The pro-alpha has a special sequence; it has repetitive a amino acid sequence: Gly-X-Y-Gly-X-Y, which just means that every third amino acid is glycine, the X or Y can be proline or lysine
Therefore, the amino acid with the highest concentration in collagen is glycine
In the endoplasmic reticulum, there are two more steps: hydroxylation and glycosylation
During hydroxylation, -OH molecules are added to proline and lysine residues. Vitamin C is a co-factor for these hydroxylation reactions; therefore, pt with vit c deficient may have impaired collagen synthesis, also known as scurvy.
scurvy
Scurvy decrease fruits and vegetables - decreased vitamin C deficiency to decreased collagen hydroxylation decreased collagen synthesis and connective tissue strength Swollen gums Poor wound healing Bruising Petechiae and perifollicular hemorrhages “Corkscrew” hair
Bc fruits and vegetables contain vitamin C, people who are unable to consume adequate quantities of fruits and vegetables can develop a vitamin c deficiency, which results in decrease hydroxylation, which ultimately means that less collagen is synthesized and the collagen that is synthesized is weaker, leading to decreased tensile connective tissue strength
As a result, these patients typically have
collagen synthesis step 3
After hydroxylation, the pro alpha-chain is glycosylated and now can combine with other hydroxylated and glycosylated pro a-chains, forming a triple helix
The triple helix is also known as procollagen
Defects in the formation of the triple helix can result in osteogenesis imperfecta
Osteogenesis imperfecta
- Autosomal dominant genetic disorder (COL1A1and COL 1A2 genes)
- decrease formation of procollagen and à decrease collagen
- Multiple fractures (may be confused with abuse)
- Blue sclerae (translucent connective tissue àchoroidal veins become more prominent)
- Hearing loss (abnormal ossicles)•Abnormal teeth (due to lack of dentin)
collagen syntheses 4-6
Once procollagen is formed, it’s moved to the golgi apparatus and then secreted into the extracellular space
From here, the ends of molecule are cleaved by C- and N- procollagen peptidase enzymes
When this occurs, the molecule is called tropocollagen
From here, the tropocollagen is crosslinked with other tropocollagen molecules by the enzyme, lysyl oxidase
This is the final step that results in mature collagen fibers
Defects in either of these last two steps results in Ehlers-Danlos syndrome
Also note that copper is an essential cofactor for lysyl oxidase
Impair copper absorption can lead to impaired activity of lysyl oxidase
There is an disorder that results in impaired copper absorption known as Menkes disease
Ehlers-Danlos Syndrome
- Deficiency of procollagen peptidase or lysyl oxidase
- decreased cross-linked collagen à weaker and more elastic
- Multiple types•Hypermobility type (joint instability): most common type
- Classical type (joint and skin symptoms): caused by a mutation in type V collagen
- Vascular type (vascular and organ rupture): deficient type III collagen
Menkes Disease
Elastin Synthesis
•Similar to collagen synthesis•But relies on scaffold of microfibril molecules, which fibrillin-1 is a component of•Defect in fibrillin-1 results in Marfan syndrome•Also relies on lysyl oxidase•Makes collagen strong•Makes elastin stretchy
Elastin is synthesized similarly to collagen
But elastin relies on a scaffold of microfibril molecules
Fibrillin-1 is a component of the microfibrils, and defects in fibrillin-1 can result in Marfan syndrome
And just like collagen synthesis, elastin synthesis relies on lysyl oxidase
In collagen synthesis, crosslinking results in a strong collagen fiber
In elastin synthesis, crosslinking results in stretchy elastic fibers
This stretchy property is especially important in the lungs bc it allows the lungs to expand during inspiration and recoil during expiration
A1-antitrypsin prevents degradation of elastin fibers, therefore a1-antitrypsin deficiency allows for degradation and lung disease such as emphysema
Marfan syndrome
•Defect in fibrillin-1 à microfibril scaffold for elastin is disrupted à weak connective tissue•Abundant in heart, lens, and periosteum•Features include aortic dissection, mitral valve prolapse, cataracts, tall with long extremities, and pectus excavatum
diseases in collagen and where in the effect
Disease of elastin
