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Review of Skeletal System 1 Skeletal System Function: – Protection – Hematopoiesis – Mineral homeostasis Calcium Phosphorus Carbonate Magnesium 2 Structure Bone is a connective tissue: – Matrix Collagen fibers for flexibility and tensile strength Calcium for rigidity Hydroxyapatite Ca5(PO4)3OH 3 Cells: – Osteoblast Form organic components of matrix – Osteocyte – Osteoclasts From monocytes Secrete citric and lactic acids Collagenases and other enzymes Stimulated by PTH Inhibited by Calcitonin 4 5 6 Types of Bone Dense or Compact (85%) – Osteon (Haversian System) – Central (Haversian) canal – Lamellae – Lacunae with osteocytes – Canaliculi Spongy (cancellous) bone (15%) – trabeculae 7 8 9 10 Periosteum Outer layer is dense, irregular CT with nerves and blood vessels Inner layer – Osteoblasts – Anchored to bone by collagen fibers that penetrate into bone 11 Joints Degree of movement – Synarthrosis – immovable joint – Amphiarthrosis – slightly movable joint – Diarthrosis – freely movable joint 12 Synovial joints – Joint capsule Fibrous CT Tendons and ligaments Nerves, blood and lymph vessels – Synovial membrane Loose fibrous CT Many blood vessels – good repair – Joint (synovial) Cavity 13 14 Synovial fluid – Plasma filtrate – Synovial cells and leukocytes phagocytize debris and microbes Articular cartilage – Reduce friction – Distribute force 15 Bone Pathophysiology Inherited conditions: – Osteogenesis imperfecta Inherited defect in collagen synthesis Osteopenia and brittle bones Often- defective tooth formation, blue sclera, faulty hearing, other defects Inheritance can be dominant, recessive or by new mutation Several degrees of severity ( I,II,III,IV) Biphosphate treatment can improve bone mass in all types of the disorder 16 18 Achondroplasia – Involves a defect in normal cartilage development – Epiphyseal plates close early in long bones; individual has short arms and legs, but normal spine and skull – Dominant inheritance, but frequent new mutations – Other organs develop normally – Individuals live a normal lifespan 19 Jyoti Amge, 15, just about 59.69 cm in height and 5.25 kg in weight, is the world's smallest girl recognized by the Indian Book of Records. Acquired disorders Osteoporosis – “porous bone” – Most common metabolic bone disease in North America – Can be attributed to genetics, diet or hormones – Most osteoporosis is idiopathic osteoporosis – Bone loss due to an identifiable cause is secondary osteoporosis – Bone tissue is mineralized normally, but over time the structural integrity of bone is lost and it becomes thinner and weaker, and more prone to fractures. 23 Key features: bone fracture and the associated pain. WHO defines osteoporosis by bone density: – Normal bone > 833 mg/cm2 – Osteopenia 833 to 648 mg/cm2 – Osteoporosis < 648 mg/cm2 Can be generalized, involving major portions of the axial skeleton Can be regional, involving one segment of the appendicular skeleton 24 25 Remodeling is constant – Teen years more bone is laid down than reabsorbed – Peak bone mass or maximum density reached at around 30 years of age – After age 30, bone is reabsorbed faster than it is laid down (loss of about 0.7% /year) – In women, bone loss is most rapid in the first years after menopause, but continues throughout postmenopausal years – Est. 55% of people over 50 have osteoporosis or low bone mass. 27 Men also lose bone density, but start out with more bone mass so takes longer. By age 90 about 17% of males have had a hip fracture, vs. 32 % of females Vertebral fractures also occur → kyphosis Most common in whites, but affects all races. African Americans have about half the fracture rates of whites (higher peak bone mass) 28 29 30 Risk factors Family history White race Increased age Female sex Small stature Fair or pale skin Thin build Early menopause (natural or surgical) Late menarche 31 Risk factors cont. Nulliparity Obesity Weight below a healthy range Acidosis Low dietary calcium and vitamin D High caffeine intake Sedentary life style Smoker Excessive alcohol consumption Liver, kidney disease, rheumatoid arthritis, etc. 32 Often progresses silently for decades until fracture occurs Bones can fracture spontaneously Most severe in spine, wrist and hips Estrogens and androgens may be factors in both sexes – Testosterone is converted into estrogen in peripheral tissues and decreases bone loss Rapid bone loss is osteoclast mediated Slow bone loss is osteoblast mediated 33 Clinical manifestations Pain and bone deformity Kyphosis caused by vertebral collapse Fractures of long bones Fatal complications include fat or pulmonary embolism, pneumonia, hemorrhage and shock 20 % die as a result of surgical complications 34 Treatment No known cure Slow bone loss and promote bone deposition Calcium and vitamin D supplements Nasal or subcutaneous calcitonin Hormone replacement therapy Biophosphates – inhibit osteoclasts Dual x-ray absorptiometry for diagnosis PREVENTION 35 Prevention Intake of calcium, vitamin D, magnesium and possibly boron Regular, weight-bearing exercise Avoid tobacco and glucocorticoids No alcoholism Hormone replacement? Testosterone for men and possibly women 36 Rickets and Osteomalacia Inadequate mineral deposition in essentially normal organic matrix Softened bone: – Subject to malformation and distortion –pain 37 Rickets Dietary vitamin D deficiency causes inadequate mineralization of the developing skeleton in infants and children Rarely seen in Western nations – Poverty – Ignorance Bones are soft and easily deformed Tendency to fractures Therapy: supply vitamin D and calcium 38 39 40 Osteomalacia Rarely due to vitamin D deficiency Usually GI malabsorption, renal defect or chronic kidney or liver diseases. Elderly often affected due to inadequate diet or lack of outdoor activity May accompany and complicate osteoporosis. 42 Joint Disorders Osteoarthritis – Most common joint disease in North America – Minimal inflammatory component – Differentiated from inflammatory disease by: Absence of synovial membrane inflammation Lack of systemic signs and symptoms Normal synovial fluid – Much of the pain and loss of mobility associated with aging. 44 Osteoarthritis Incidence increases with age: 85% of people age 65 have some joint degeneration Incidence similar, but women more severely affected Exceptional stress on joints: gymnasts, etc. Biochemical defect in cartilage Malformed joint, obesity and postural defects Genetic component Torn ACL or meniscectomy 45 Osteoarthritis When associated with known risk factors it is secondary Osteoarthritis No risk factors – idiopathic Osteoarthritis Pathological characteristics: – Erosion of the articular cartilage – Sclerosis of subchondral bone – Formation of bone spurs or osteophytes 46 Osteoarthritis Begins in articular cartilage – Yellow-grey or brownish gray – Thin, irregular, frayed – Cracks or fissures develop (fibrillation) – Fluid filled cysts may form – Microfractures of subchondral bone – Formation of fibrocartilage repair plugs – Bone surface exposed – Bone responds by becoming dense and hard 48 Osteoarthritis Synovial membrane is indirectly affected – Fragments of fibrocartilage cause inflammation –pain – Fibrous repair of joint capsule restricts motion – Osteophytes form – pain and loss of motion 49 Osteoarthritis Affects one or more weight-bearing joints – Hand, wrist, lower cervical spine, lumbar spine and sacroiliac, hip, knees, ankles, feet Aches and stiffness – Symptoms increase with activity; diminish with rest Usually no swelling or redness of adjacent tissues Sometimes nocturnal pain – may be referred 50 Osteoarthritis Primary signs and symptoms of joint disease are: pain, stiffness, enlargement or swelling, tenderness, limited range of motion, muscle wasting, partial dislocation, and deformity, crepitus (cracking sound) 51 Osteoarthritis Evaluation made through clinical assessment and radiologic studies, CT scan, arthroscopy and MRI Treatment: Glucosamine may decrease pain and slow or stop progression – 1500 mg/day Chondroitin sulfate – questionable absorption 52 Osteoarthritis Analgesics and antiinflammatory drugs (NSAIDs) Injections of corticosteroids or sodium hyaluronate (to improve lubrication) Range of motion exercises Reduce aggravating factors – Weight loss – Use of cane, crutches or walker Surgical removal of bone spurs, and other Replacement of joint 53 Rheumatoid Arthritis Systemic disease with prominent involvement of the joints Inflammatory joint disease characterized by: – Inflammatory damage in the synovial membrane or articular cartilage – Systemic signs of inflammation: fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia 54 Rheumatoid Arthritis Systemic autoimmune disease that causes chronic inflammation of connective tissue Initially affects synovial membrane Later articular cartilage, joint capsule, ligaments and tendons, and bone Affects small joints more like hands, wrists, ankles, and feet, but shoulders, hips and cervical spine may also be involved Systemic effects on heart, kidney, lungs, skin and other organs 55 Rheumatoid Arthritis Mild to severe Destroys and distorts joints Reduces life expectancy Remission and exacerbation 1 – 2% of adult population Women : men = 3:1 Onset usually in 20’s or 30’s Symptoms lessen during pregnancy Seasonal variation 56 Rheumatoid Arthritis Idiopathic disease Immune-mediated destruction of joints Rheumatoid factors (IgM and IgG) target blood cells and synovial membranes forming antigen-antibody complexes Genetic predisposition Possibly bacterial or viral infection (Epstein-Barr) 57 Rheumatoid Arthritis Chronic inflammation of synovial membrane Cellular proliferation and damage to the microcirculation Synovial membrane becomes irregular Swelling, stiffness and pain Cartilage and bone destruction Ankylosis or fusing of joint Ligaments and tendons also affected 58 Rheumatoid Arthritis Systemic effects: – Generalized weakness and malaise – Up to 35% develop granulomas called rheumatoid nodules – Systemic inflammation of blood vessels – rheumatoid vasculitis – Serous membranes may be affected 59 60 Rheumatoid Arthritis Evaluation : – history – Physical examination – X-ray – Serologic tests for rheumatoid factor and circulating antigen-antibody complexes, esp. antibodies against cyclic citrullinated peptide (CCP) No cure 61 Rheumatoid Arthritis Therapy: Physical and emotional rest Relieve pain and swelling and retain as much joint function as possible Resting the joint, or binding or splinting Use of hot and cold packs Diet high in calories and vitamins Strengthening of associated muscles 62 Rheumatoid Arthritis Drug therapy: – NSAIDS – Methotrexate – Antimalarial drugs and immunosuppression Surgical – Synovectomy – Correction of deformities – Joint replacement – Joint fusion 63 Review of Muscular System 64 Muscle Skeletal muscle – > 600 muscles in body Cardiac muscle Smooth muscle 65 Muscle cell structure Sarcolemma motor end plate transverse ( t- ) tubules Sarcoplasm Sarcoplasmic Reticulum – Stores Ca++ 66 67 68 Proteins: – Thick filaments – myosin – Thin filaments – actin Troponin Tropomyosin – Sliding Filament Model 69 70 71 72 73 Muscular Dystrophy Group of rare diseases characterized by a genetic etiology and progressive degeneration of skeletal muscle. X-linked recessive defect Most common of the muscular dystrophies 1 in 3,500 live male births Affects males Gene located on the short arm of the X chromosome. 74 30% of cases arise as a new mutation Can be diagnosed immediately after birth by high serum creatine kinase Muscle weakness and delayed motor skills can be detected early – obvious by age 5 Age 10 – require leg bracing Age 12 – wheelchair Age 15 completely bedridden Death by 20 – 30 of cardiac arrest or respiratory failure. 75 Fibrosis → contracture distorts skeletal development – Lordosis – Scoliosis – Compromised respiration Respiratory insufficiency – Respiratory infection Cardiac muscle – Dysrythmias – Congestive heart failure Mental sluggishness 76 Therapy – Passive stretching, splints to prevent deformities – Sustain mobility – Sustain respiratory function – Possibly gene therapy 77 Myesthenia gravis Autoimmune disease in which antibodies (IgG) bind with acetylcholine receptors on muscle cells. (T-lyphmocyte abnormalities) Reduces the number of acetylcholine receptors at the neuromuscular junction Characterized by progressive muscle weakness and fatigability Also associated with other autoimmune disorders, such as SLE, rheumatoid arthritis, and thyrotoxicosis 78 In 10-25% of people with MG thymic tumors are found – More common in males than females 70 – 80 % have pathologic changes in the thymus 79 Classification of myasthenia Neonatal myasthenia – Transitory condition in which 10-15 % of infants born to mothers with MG show symptoms of the disease Congenital myasthenia Juvenile myasthenia – onset about 10 years Ocular myasthenia – More common in males – Weakness of eye muscles and eyelids, may also include swallowing difficulties and slurred speech 80 Generalized autoimmune myasthenia – Involves proximal musculature throughout the body, and has several courses: A course with periodic remissions Slowly progressive course Rapidly progressive course Fulminating course 81 Pathophysiology Defect in the nerve impulse transmission at the NMJ Postsynaptic acetylcholine receptors are no longer recognized as “self” and antibodies are produced against them. IgG blocks the binding of ACh Eventually destroys the receptor Causes diminished transmission of nerve impulse across the NMJ and lack of muscle depolarization Cause is unknown. 82 Clinical manifestations Onset typically insidious May first appear during pregnancy, postpartum or with the administration of certain anesthetic agents Complaints are fatigue and progressive muscle weakness – Fatigue after exercise – Recent history of recurrent upper respiratory infections 83 Clinical manifestations Muscles of the eyes, face, mouth, throat and neck are usually affected first – Levator and extraocular muscles affected most -Diplopia, ptosis, and ocular palsies – Muscles of facial expression, mastication, swallowing and speech are the next most involved Facial droop, expressionless face; difficulties in chewing and swallowing, drooling, episodes of choking and aspiration Nasal, low volume, high-pitched monotonous speech pattern 84 Less frequently involved are the muscles of the neck, shoulder girdle and hip flexors – Fatigue requires periods of rest – Weakness of arms and legs – Difficulty maintaining head position – Respiratory muscles of chest wall and diaphragm become weak In advanced stage all muscles are weak 85 Myasthenic crisis Severe weakness causes quadriparesis or quadriplegia, respiratory insufficiency and extreme difficulty in swallowing 86 Cholinergic crisis Anticholinesterase drug toxicity Intestinal motility increases Fasciculation Bradycardia Pupillary constriction Increased salivation Increased sweating 87 Evaluation Improvement with edrophonium chloride (Telison) for several minutes EMG – amplitude of action potentials declines Antiacetylcholine receptor antibody titers Antistriated muscle antibody titers MRI to rule out thymoma 88 Progression Varies Appears first as a mild case that spontaneously remits with a series of relapses and symptom free intervals Over time can progress leading to death Ocular myasthenia has a good prognosis 89 Treatment Anticholinesterase drugs Steroids Immunosuppressant drugs Cyclophosphamide Plasmapheresis during myasthenic crisis Thymectomy is treatment of choice for individuals with thymoma 90