Muscle, Tendon & Ligament Composition and Function What you need to get out of this lecture Collagen structure And Three Diseases! Block 2: 2012 Edward Via Virginia College of Osteopathic Medicine Dr. Carol Brenner

Muscles, Tendons and Ligaments A tendon is a fibrous connective tissue which attaches muscle to bone. May also attach muscles to structures such as the eyeball. A tendon serves to move the bone or structure. A ligament is a fibrous connective tissue which attaches bone to bone Serves to hold structures together and keep them stable.

Ligaments Ligaments help w/ movement and prevent excessive or undesirable motion more ligaments = stronger joint Ligaments can stretch due to undue tension or trauma can stretch only 6% of its length before it snaps This is one reason why dislocated joints must be set as quickly as possible: if the ligaments lengthen too much, then the joint will be weakened, becoming prone to future dislocations (instability of the joint) Instability of a joint can over time lead to wear of the cartilage and eventually to osteoarthritis Athletes perform stretching exercises to lengthen their ligaments, making their joints more supple

http://www.tendinosis.org/injury.html

http://www.tendinosis.org/injury.html

Collagen Most abundant protein body Strong and Stiff 25% Total protein in body Most Abundant Collagens: I, II, III, IV, V, VI High hydroxyproline! Hbds and crosslinking = stability Collagen provides the extracellular framework for all multicellular organisms. triple helix of three polypeptide α chains, gly-x-y repeat Currently 27 different types of collagens are known Type IV is nonfibrillar (forms sheets instead of fibrils) and is the main component of the basement membrane, together with laminin. Other collagens may form meshworks and may function as anchors in epidermal-dermal junctions, cartilage, and blood vessel wall Primary component of ECM is collagen, contains hydroxyproline, an AA not found in other proteins Most abundant protein it has a triple helical structure that is stiff and provides the backbone of the ECM Collagen occurs in many places throughout the body. Over 90% of the collagen in the body, however, is of type One. So far, 29 types of collagen have been identified and described. The five most common types are: Collagen One: skin, tendon, vascular ligature, organs, bone (main component of bone) Collagen Two: cartilage (main component of cartilage) Collagen Three: reticulate (main component of reticular fibers), commonly found alongside type I. Collagen Four: forms bases of cell basement membrane Collagen Five: cells surfaces, hair and placenta

Fibrillar collagen is synthesized from procollagen, a precursor molecule derived from preprocollagen After hydroxylation of proline and lysine residues and lysine glycosylation, three procollagen chains align in phase to form the triple helix Procollagen is secreted from the cell and cleaved by proteases to form the basic unit of the fibrils Collagen fibril formation is associated with the oxidation of specific lysine and hydroxylysine residues by the extracellular enzyme lysyl oxidase. This results in cross-linking between the chains of adjacent molecules, thus stabilizing the array that is characteristic of collagen. Cross-linking is a major contributor to the tensile strength of collagen Vitamin C is required for the hydroxylation of procollagen, a requirement that explains the inadequate wound healing in scurvy

Scurvy Vitamin C is required for the hydroxylation of procollagen, a requirement that explains the inadequate wound healing in scurvy – very important!! A deficiency of vitamin C leads to the development of scurvy, characterized principally by bone disease in growing children and hemorrhages and healing defects in both children and adults. Scurvy in a growing child is far more dramatic than in an adult. Hemorrhages constitute one of the most striking features. Because the defect in collagen synthesis results in inadequate support of the walls of capillaries and venules, purpura and ecchymoses often appear in the skin and in the gingival mucosa. The loose attachment of the periosteum to bone, together with the vascular wall defects, leads to extensive subperiosteal hematomas and bleeding into joint spaces after minimal trauma. Retrobulbar, subarachnoid, and intracerebral hemorrhages may prove fatal.

Pathophysiology of Scurvy Ascorbic acid accelerats hydroxylation rxs. In the synthesis of collagen, it is required as a cofactor for prolyl hydroxylase and lysyl hydroxylase. Which are responsible for the hydroxylation of the proline and lysine Hydroxyproline and hydroxylysine are important for stabilizing collagen by cross-linking the propeptides in collagen. Defective collagen fibrillogenesis impairs wound healing. Collagen is also an important part of bone, so bone formation is also affected. Defective connective tissue also leads to fragile capillaries, resulting in abnormal bleeding.

Ehlers-Danlos Syndrome (Collagen 5) fibrillar Collagens 1, 3, and 5 (most) Sleep Apnea Mitral Valve Prolapse 1/5000 & Autosomal Dominant Vertebral column defects Miscarriages abnormal collagen fibers = lack adequate tensile strength,skin is hyperextensible, and the joints are hypermobile. Uterus Easy bruising & bleeding Cornea Premature births The skin is also extremely fragile, and vulnerable to trauma. Hip dislocations Asthma Trachea collapse w/anaesthesia Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders, caused by a defect in the synthesis of collagen The major signs and symptoms include: Loose, unstable joints that are prone to: sprain, dislocation, subluxation (partial dislocation) and hyperextension (double jointedness)  Early onset of osteoarthritis Easy bruising Dysautonomia typically accompanied by Valvular heart disease (such as mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, as well as possibly progressing to a life-threatening degree of severity of the prognosis of mitral valve prolapse)  Chronic fatigue Flat feet High and narrow palate, resulting in dental crowding Vulnerability to chest and sinus infections Fragile blood vessels resulting from cystic medial necrosis with tendency towards aneurysm (even abdominal aortic aneurysm) Velvety-smooth skin which may be stretchy, is often translucent, and can contribute to underestimations of chronological age Abnormal wound healing and scar formation Low muscle tone and muscle weakness Migraines and headaches, including postural headaches from spontaneous intracranial hypotension Myalgia and arthralgia

Osteogenesis Imperfecta lethal type II has numerous fractures of virtually all bones, resulting in accordion-like shortening of the limbs. Autosomal Dominant group of disorders caused by deficiencies in type 1 collagen. Although osteogenesis imperfecta, or brittle bone disease, has prominent skeletal manifestations, other anatomic structures rich in type I collagen, such as joints, eyes, ears, skin, and teeth, are affected as well. Mutations resulting in the production of normal collagen synthesized in decreased amounts = mild skeletal abnormalities. More severe or lethal phenotypes result from genetic defects producing abnormal polypeptide chains that cannot assemble into a triple helix configuration, which is required for functional collagen molecules