Collagens and Disease (Clinical Correlation 1)

I. Collagen
a. Signaling roles, structural roles (reinforcing agent)
b. Normal vs. mutation
c. Macro-architecture: Cartilage
d. Tissue distributions
i. Type 1- bone, skin, tendon
ii. Type 2- Cartilage, vitreous (eye)
iii. Type 3- Large vessels, uterus, gut
iv. Type 4- large vessels, cornea, helps organize type 1
v. Type 11- cartilage, helps organize type 2
II. Too much collagen (crowds out normal tissue)
a. Make too much, make appropriate amount but can’t get rid of it or both (make
too much and can’t get rid of it)
i. Liver- cirrhosis, increased resistance of vessels/ducts  portal
hypertension and biliary obstruction
ii. Lung- interstitial fibrosis, impaired diffusion, stiff lungs
iii. Bone marrow- myelofibrosis
b. Progressive systemic sclerosis (scleroderma)
i. Excess collagen in multiple organs (skin, lung, heart, muscle) 
characteristic hands
c. Diabetic hand
i. Excess collagen in tissues binds thick skin in palm to underlying tendon
sheath (Dupuytren’s)
ii. Collagen molecules with many crosslinks
iii. Advanced glycation end products  fibroblasts make more collagen
d. Post-inflammatory/myelofibrosis
III. Too little collagen
a. Make too little, make enough but doesn’t arrive at destination, make enough but
rapidly disappears
b. Scurvy
i. Vitamin C is important for intracellular synthesis and secretion of
collagen type 1 and 2
ii. Dermal appendages not anchored, bleeding (blood vessels not strong),
advanced bleeding from gums, loose teeth
c. Milwaukee Shoulder Syndrome
i. Unstable shoulders, dissolution of rotator cuff and cartilage, excess
collagenase/protease, calcium phosphate crystals  provoke protease
secretion, cell proliferation of lining cells
IV. Wrong kind of collagen
a. Abnormal physical-chemical properties, molecular suicide/susceptibility to
degradation  too little collagen
i. Collagen thermal denaturation (no hydroxyproline  melts at body
temperature)
b. Osteogenesis imperfecta (Brittle/malformed bones)- fragile bones, blue sclera,
dental problems and hearing loss, autosomal dominant
i. Osteogenesis imperfecta I (60% of OI patients)
1. osseous fragility, limited skeletal deformity, blue sclera, A-
dental problems, B- no dental problems
ii. Osteogenesis imperfecta II
1. Usually lethal
iii. Osteogenesis imperfecta III (rare)
1. Variable osseous fragility, severe deformities of long bones
2. Scoliosis- chest wall deformities  poor lung function
3. growth retardation/short stature
iv. Treatment
 1. Biphosphonates- bind to appetite and stabilize it
2. Ca/VitD supplementation
3. Caught early
4. Surgical intervention, heating swimming pool exercises
c. Ehlers-Danlos (Skin/joint laxity)- hypermobile, extensible skin, bruising
i. Classic- type 1 and 2
1. Beighton score
2. Abnormal type 5 collagen  organization of type 1
3. Pulmonary complications, aortic root dilation, skeletal-
peripheral and central joints
ii. Hypermobility- type 3
iii. Vascular- type 4
1. Skin, blood vessels, uterus (Type 3 collagen)
2. Repeated arterial rupture, rupture of viscera, uterine/perineal
tissue tears
iv. Kyphoscoliosis- type 6
1. Autosomal recessive, deficiency of lysyl hydroxylase
2. Ocular tissue involvement, hyper-extensibility of joints
v. Arthrocalsia- type 7A and 7B
d. Stickler’s Disease (Type II Collagen)
i. Gliding surface between joints
ii. Not enough  lateral compartment of knee joint (cartilage GONE)
iii. Premature osteoarthritis
iv. Eye problems
e. Alport’s (Type 4 collagen)
i. Basement membrane- crucial to function of kidneys
ii. Kidneys leak protein into the urine  renal failure
f. Fibrillin  Martan Syndrome
i. Autosomal dominant (Fibrillin 1 gene)
ii. Ocular, cardiovascular, musculoskeletal, pulmonary, skin and CNS
involvement
iii. Steinberg test, Walker-Murdoch sign, lens in eye can dislocate
iv. Large aortic aneurysms- close to heart in ascending aorta
v. Treatment
1. Lifelong beta blockers, moderate restriction of physical activity
 reduce pressure to prevent aneurysm/rupture
2. Pregnancy