1. Review of Skeletal System 1

2. Skeletal System Function: Function: –Protection –Hematopoiesis –Mineral homeostasis Calcium Calcium Phosphorus Phosphorus Carbonate Carbonate Magnesium Magnesium 2

3. Structure Bone is a connective tissue: Bone is a connective tissue: –Matrix Collagen fibers for flexibility and tensile strength Collagen fibers for flexibility and tensile strength Calcium for rigidity Calcium for rigidity Hydroxyapatite Ca 5 (PO 4 ) 3 OH Hydroxyapatite Ca 5 (PO 4 ) 3 OH 3

4. Cells: Cells: –Osteoblast Form organic components of matrix Form organic components of matrix –Osteocyte –Osteoclasts From monocytes From monocytes Secrete citric and lactic acids Secrete citric and lactic acids Collagenases and other enzymes Collagenases and other enzymes Stimulated by PTH Stimulated by PTH Inhibited by Calcitonin Inhibited by Calcitonin 4

5. 5

6. 6

7. Types of Bone Dense or Compact (85%) Dense or Compact (85%) –Osteon (Haversian System) –Central (Haversian) canal –Lamellae –Lacunae with osteocytes –Canaliculi Spongy (cancellous) bone (15%) Spongy (cancellous) bone (15%) –trabeculae 7

8. 8

9. 9

10. 10

11. Periosteum Outer layer is dense, irregular CT with nerves and blood vessels Outer layer is dense, irregular CT with nerves and blood vessels Inner layer Inner layer –Osteoblasts –Anchored to bone by collagen fibers that penetrate into bone 11

12. Joints Degree of movement Degree of movement –Synarthrosis – immovable joint –Amphiarthrosis – slightly movable joint –Diarthrosis – freely movable joint 12

13. Synovial joints Synovial joints –Joint capsule Fibrous CT Fibrous CT Tendons and ligaments Tendons and ligaments Nerves, blood and lymph vessels Nerves, blood and lymph vessels –Synovial membrane Loose fibrous CT Loose fibrous CT Many blood vessels – good repair Many blood vessels – good repair –Joint (synovial) Cavity 13

14. 14

15. Synovial fluid Synovial fluid –Plasma filtrate –Synovial cells and leukocytes phagocytize debris and microbes Articular cartilage Articular cartilage –Reduce friction –Distribute force 15

16. Bone Pathophysiology Inherited conditions: Inherited conditions: –Osteogenesis imperfecta Inherited defect in collagen synthesis Inherited defect in collagen synthesis Osteopenia and brittle bones Osteopenia and brittle bones Often- defective tooth formation, blue sclera, faulty hearing, other defects Often- defective tooth formation, blue sclera, faulty hearing, other defects Inheritance can be dominant, recessive or by new mutation Inheritance can be dominant, recessive or by new mutation Several degrees of severity ( I,II,III,IV) Several degrees of severity ( I,II,III,IV) Biphosphate treatment can improve bone mass in all types of the disorder Biphosphate treatment can improve bone mass in all types of the disorder 16

18. 18

19. Achondroplasia 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

20. 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.

23. Acquired disorders Osteoporosis – “porous bone” 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

24. Key features: bone fracture and the associated pain. Key features: bone fracture and the associated pain. WHO defines osteoporosis by bone density: WHO defines osteoporosis by bone density: –Normal bone > 833 mg/cm 2 –Osteopenia 833 to 648 mg/cm 2 –Osteoporosis < 648 mg/cm 2 Can be generalized, involving major portions of the axial skeleton Can be generalized, involving major portions of the axial skeleton Can be regional, involving one segment of the appendicular skeleton Can be regional, involving one segment of the appendicular skeleton 24

25. 25

27. Remodeling is constant 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

28. Men also lose bone density, but start out with more bone mass so takes longer. 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 By age 90 about 17% of males have had a hip fracture, vs. 32 % of females Vertebral fractures also occur → kyphosis Vertebral fractures also occur → kyphosis Most common in whites, but affects all races. Most common in whites, but affects all races. African Americans have about half the fracture rates of whites (higher peak bone mass) African Americans have about half the fracture rates of whites (higher peak bone mass) 28

29. 29

30. 30

31. Risk factors Family history Family history White race White race Increased age Increased age Female sex Female sex Small stature Small stature Fair or pale skin Fair or pale skin Thin build Thin build Early menopause (natural or surgical) Early menopause (natural or surgical) Late menarche Late menarche 31

32. Risk factors cont. Nulliparity Nulliparity Obesity Obesity Weight below a healthy range Weight below a healthy range Acidosis Acidosis Low dietary calcium and vitamin D Low dietary calcium and vitamin D High caffeine intake High caffeine intake Sedentary life style Sedentary life style Smoker Smoker Excessive alcohol consumption Excessive alcohol consumption Liver, kidney disease, rheumatoid arthritis, etc. Liver, kidney disease, rheumatoid arthritis, etc. 32

33. Often progresses silently for decades until fracture occurs Often progresses silently for decades until fracture occurs Bones can fracture spontaneously Bones can fracture spontaneously Most severe in spine, wrist and hips Most severe in spine, wrist and hips Estrogens and androgens may be factors in both sexes 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 Rapid bone loss is osteoclast mediated Slow bone loss is osteoblast mediated Slow bone loss is osteoblast mediated 33

34. Clinical manifestations Pain and bone deformity Pain and bone deformity Kyphosis caused by vertebral collapse Kyphosis caused by vertebral collapse Fractures of long bones Fractures of long bones Fatal complications include fat or pulmonary embolism, pneumonia, hemorrhage and shock Fatal complications include fat or pulmonary embolism, pneumonia, hemorrhage and shock 20 % die as a result of surgical complications 20 % die as a result of surgical complications 34

35. Treatment No known cure No known cure Slow bone loss and promote bone deposition Slow bone loss and promote bone deposition Calcium and vitamin D supplements Calcium and vitamin D supplements Nasal or subcutaneous calcitonin Nasal or subcutaneous calcitonin Hormone replacement therapy Hormone replacement therapy Biophosphates – inhibit osteoclasts Biophosphates – inhibit osteoclasts Dual x-ray absorptiometry for diagnosis Dual x-ray absorptiometry for diagnosis PREVENTION PREVENTION 35

36. Prevention Intake of calcium, vitamin D, magnesium and possibly boron Intake of calcium, vitamin D, magnesium and possibly boron Regular, weight-bearing exercise Regular, weight-bearing exercise Avoid tobacco and glucocorticoids Avoid tobacco and glucocorticoids No alcoholism No alcoholism Hormone replacement? Hormone replacement? Testosterone for men and possibly women Testosterone for men and possibly women 36

37. Rickets and Osteomalacia Inadequate mineral deposition in essentially normal organic matrix Inadequate mineral deposition in essentially normal organic matrix Softened bone: Softened bone: –Subject to malformation and distortion –pain 37

38. Rickets Dietary vitamin D deficiency causes inadequate mineralization of the developing skeleton in infants and children Dietary vitamin D deficiency causes inadequate mineralization of the developing skeleton in infants and children Rarely seen in Western nations Rarely seen in Western nations –Poverty –Ignorance Bones are soft and easily deformed Bones are soft and easily deformed Tendency to fractures Tendency to fractures Therapy: supply vitamin D and calcium Therapy: supply vitamin D and calcium 38

39. 39

40. 40

42. Osteomalacia Rarely due to vitamin D deficiency Rarely due to vitamin D deficiency Usually GI malabsorption, renal defect or chronic kidney or liver diseases. Usually GI malabsorption, renal defect or chronic kidney or liver diseases. Elderly often affected due to inadequate diet or lack of outdoor activity Elderly often affected due to inadequate diet or lack of outdoor activity May accompany and complicate osteoporosis. May accompany and complicate osteoporosis. 42

44. Joint Disorders Osteoarthritis Osteoarthritis –Most common joint disease in North America –Minimal inflammatory component –Differentiated from inflammatory disease by: Absence of synovial membrane inflammation Absence of synovial membrane inflammation Lack of systemic signs and symptoms Lack of systemic signs and symptoms Normal synovial fluid Normal synovial fluid –Much of the pain and loss of mobility associated with aging. 44

45. Osteoarthritis Incidence increases with age: 85% of people age 65 have some joint degeneration Incidence increases with age: 85% of people age 65 have some joint degeneration Incidence similar, but women more severely affected Incidence similar, but women more severely affected Exceptional stress on joints: gymnasts, etc. Exceptional stress on joints: gymnasts, etc. Biochemical defect in cartilage Biochemical defect in cartilage Malformed joint, obesity and postural defects Malformed joint, obesity and postural defects Genetic component Genetic component Torn ACL or meniscectomy Torn ACL or meniscectomy 45

46. Osteoarthritis When associated with known risk factors it is secondary Osteoarthritis When associated with known risk factors it is secondary Osteoarthritis No risk factors – idiopathic Osteoarthritis No risk factors – idiopathic Osteoarthritis Pathological characteristics: Pathological characteristics: –Erosion of the articular cartilage –Sclerosis of subchondral bone –Formation of bone spurs or osteophytes 46

48. Osteoarthritis Begins in articular cartilage 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

49. Osteoarthritis Synovial membrane is indirectly affected 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

50. Osteoarthritis Affects one or more weight-bearing joints Affects one or more weight-bearing joints –Hand, wrist, lower cervical spine, lumbar spine and sacroiliac, hip, knees, ankles, feet Aches and stiffness Aches and stiffness –Symptoms increase with activity; diminish with rest Usually no swelling or redness of adjacent tissues Usually no swelling or redness of adjacent tissues Sometimes nocturnal pain – may be referred Sometimes nocturnal pain – may be referred 50

51. 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

52. Osteoarthritis Evaluation made through clinical assessment and radiologic studies, CT scan, arthroscopy and MRI Evaluation made through clinical assessment and radiologic studies, CT scan, arthroscopy and MRI Treatment: Treatment: Glucosamine may decrease pain and slow or stop progression – 1500 mg/day Glucosamine may decrease pain and slow or stop progression – 1500 mg/day Chondroitin sulfate – questionable absorption Chondroitin sulfate – questionable absorption 52

53. Osteoarthritis Analgesics and antiinflammatory drugs (NSAIDs) Analgesics and antiinflammatory drugs (NSAIDs) Injections of corticosteroids or sodium hyaluronate (to improve lubrication) Injections of corticosteroids or sodium hyaluronate (to improve lubrication) Range of motion exercises Range of motion exercises Reduce aggravating factors Reduce aggravating factors –Weight loss –Use of cane, crutches or walker Surgical removal of bone spurs, and other Surgical removal of bone spurs, and other Replacement of joint Replacement of joint 53

54. Rheumatoid Arthritis Systemic disease with prominent involvement of the joints Systemic disease with prominent involvement of the joints Inflammatory joint disease characterized by: Inflammatory joint disease characterized by: –Inflammatory damage in the synovial membrane or articular cartilage –Systemic signs of inflammation: fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia 54

55. Rheumatoid Arthritis Systemic autoimmune disease that causes chronic inflammation of connective tissue Systemic autoimmune disease that causes chronic inflammation of connective tissue Initially affects synovial membrane Initially affects synovial membrane Later articular cartilage, joint capsule, ligaments and tendons, and bone 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 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 Systemic effects on heart, kidney, lungs, skin and other organs 55

56. Rheumatoid Arthritis Mild to severe Mild to severe Destroys and distorts joints Destroys and distorts joints Reduces life expectancy Reduces life expectancy Remission and exacerbation Remission and exacerbation 1 – 2% of adult population 1 – 2% of adult population Women : men = 3:1 Women : men = 3:1 Onset usually in 20’s or 30’s Onset usually in 20’s or 30’s Symptoms lessen during pregnancy Symptoms lessen during pregnancy Seasonal variation Seasonal variation 56

57. Rheumatoid Arthritis Idiopathic disease Idiopathic disease Immune-mediated destruction of joints Immune-mediated destruction of joints Rheumatoid factors (IgM and IgG) target blood cells and synovial membranes forming antigen-antibody complexes Rheumatoid factors (IgM and IgG) target blood cells and synovial membranes forming antigen-antibody complexes Genetic predisposition Genetic predisposition Possibly bacterial or viral infection (Epstein-Barr) Possibly bacterial or viral infection (Epstein-Barr) 57

58. Rheumatoid Arthritis Chronic inflammation of synovial membrane Chronic inflammation of synovial membrane Cellular proliferation and damage to the microcirculation Cellular proliferation and damage to the microcirculation Synovial membrane becomes irregular Synovial membrane becomes irregular Swelling, stiffness and pain Swelling, stiffness and pain Cartilage and bone destruction Cartilage and bone destruction Ankylosis or fusing of joint Ankylosis or fusing of joint Ligaments and tendons also affected Ligaments and tendons also affected 58

59. Rheumatoid Arthritis Systemic effects: 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. 60

61. Rheumatoid Arthritis Evaluation : 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 No cure 61

62. Rheumatoid Arthritis Therapy: Therapy: Physical and emotional rest Physical and emotional rest Relieve pain and swelling and retain as much joint function as possible Relieve pain and swelling and retain as much joint function as possible Resting the joint, or binding or splinting Resting the joint, or binding or splinting Use of hot and cold packs Use of hot and cold packs Diet high in calories and vitamins Diet high in calories and vitamins Strengthening of associated muscles Strengthening of associated muscles 62

63. Rheumatoid Arthritis Drug therapy: Drug therapy: –NSAIDS –Methotrexate –Antimalarial drugs and immunosuppression Surgical Surgical –Synovectomy –Correction of deformities –Joint replacement –Joint fusion 63

64. Review of Muscular System 64

65. Muscle Skeletal muscle Skeletal muscle –> 600 muscles in body Cardiac muscle Cardiac muscle Smooth muscle Smooth muscle 65

66. Muscle cell structure Sarcolemma motor end plate transverse ( t- ) tubules Sarcolemma motor end plate transverse ( t- ) tubules Sarcoplasm Sarcoplasm Sarcoplasmic Reticulum – Stores Ca ++ Sarcoplasmic Reticulum – Stores Ca ++ 66

67. 67

68. 68

69. Proteins: Proteins: –Thick filaments – myosin –Thin filaments – actin Troponin Troponin Tropomyosin Tropomyosin –Sliding Filament Model 69

70. 70

71. 71

72. 72

73. 73

74. Muscular Dystrophy Group of rare diseases characterized by a genetic etiology and progressive degeneration of skeletal muscle. Group of rare diseases characterized by a genetic etiology and progressive degeneration of skeletal muscle. X-linked recessive defect X-linked recessive defect Most common of the muscular dystrophies Most common of the muscular dystrophies 1 in 3,500 live male births 1 in 3,500 live male births Affects males Affects males Gene located on the short arm of the X chromosome. Gene located on the short arm of the X chromosome. 74

75. 30% of cases arise as a new mutation 30% of cases arise as a new mutation Can be diagnosed immediately after birth by high serum creatine kinase 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 Muscle weakness and delayed motor skills can be detected early – obvious by age 5 Age 10 – require leg bracing Age 10 – require leg bracing Age 12 – wheelchair Age 12 – wheelchair Age 15 completely bedridden Age 15 completely bedridden Death by 20 – 30 of cardiac arrest or respiratory failure. Death by 20 – 30 of cardiac arrest or respiratory failure. 75

76. Fibrosis → contracture distorts skeletal development Fibrosis → contracture distorts skeletal development –Lordosis –Scoliosis –Compromised respiration Respiratory insufficiency Respiratory insufficiency –Respiratory infection Cardiac muscle Cardiac muscle –Dysrythmias –Congestive heart failure Mental sluggishness Mental sluggishness 76

77. Therapy Therapy –Passive stretching, splints to prevent deformities –Sustain mobility –Sustain respiratory function –Possibly gene therapy 77

78. Myesthenia gravis Autoimmune disease in which antibodies (IgG) bind with acetylcholine receptors on muscle cells. (T-lyphmocyte abnormalities) 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 Reduces the number of acetylcholine receptors at the neuromuscular junction Characterized by progressive muscle weakness and fatigability Characterized by progressive muscle weakness and fatigability Also associated with other autoimmune disorders, such as SLE, rheumatoid arthritis, and thyrotoxicosis Also associated with other autoimmune disorders, such as SLE, rheumatoid arthritis, and thyrotoxicosis 78

79. In 10-25% of people with MG thymic tumors are found 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 70 – 80 % have pathologic changes in the thymus 79

80. Classification of myasthenia Neonatal myasthenia Neonatal myasthenia –Transitory condition in which 10-15 % of infants born to mothers with MG show symptoms of the disease Congenital myasthenia Congenital myasthenia Juvenile myasthenia – onset about 10 years Juvenile myasthenia – onset about 10 years Ocular myasthenia Ocular myasthenia –More common in males –Weakness of eye muscles and eyelids, may also include swallowing difficulties and slurred speech 80

81. Generalized autoimmune myasthenia Generalized autoimmune myasthenia –Involves proximal musculature throughout the body, and has several courses: A course with periodic remissions A course with periodic remissions Slowly progressive course Slowly progressive course Rapidly progressive course Rapidly progressive course Fulminating course Fulminating course 81

82. Pathophysiology Defect in the nerve impulse transmission at the NMJ Defect in the nerve impulse transmission at the NMJ Postsynaptic acetylcholine receptors are no longer recognized as “self” and antibodies are produced against them. Postsynaptic acetylcholine receptors are no longer recognized as “self” and antibodies are produced against them. IgG blocks the binding of ACh IgG blocks the binding of ACh Eventually destroys the receptor Eventually destroys the receptor Causes diminished transmission of nerve impulse across the NMJ and lack of muscle depolarization Causes diminished transmission of nerve impulse across the NMJ and lack of muscle depolarization Cause is unknown. Cause is unknown. 82

83. Clinical manifestations Onset typically insidious Onset typically insidious May first appear during pregnancy, postpartum or with the administration of certain anesthetic agents May first appear during pregnancy, postpartum or with the administration of certain anesthetic agents Complaints are fatigue and progressive muscle weakness Complaints are fatigue and progressive muscle weakness –Fatigue after exercise –Recent history of recurrent upper respiratory infections 83

84. Clinical manifestations Muscles of the eyes, face, mouth, throat and neck are usually affected first 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 Facial droop, expressionless face; difficulties in chewing and swallowing, drooling, episodes of choking and aspiration Nasal, low volume, high-pitched monotonous speech pattern Nasal, low volume, high-pitched monotonous speech pattern 84

85. Less frequently involved are the muscles of the neck, shoulder girdle and hip flexors 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 In advanced stage all muscles are weak 85

86. Myasthenic crisis Severe weakness causes quadriparesis or quadriplegia, respiratory insufficiency and extreme difficulty in swallowing Severe weakness causes quadriparesis or quadriplegia, respiratory insufficiency and extreme difficulty in swallowing 86

87. Cholinergic crisis Anticholinesterase drug toxicity Anticholinesterase drug toxicity Intestinal motility increases Intestinal motility increases Fasciculation Fasciculation Bradycardia Bradycardia Pupillary constriction Pupillary constriction Increased salivation Increased salivation Increased sweating Increased sweating 87

88. Evaluation Improvement with edrophonium chloride (Telison) for several minutes Improvement with edrophonium chloride (Telison) for several minutes EMG – amplitude of action potentials declines EMG – amplitude of action potentials declines Antiacetylcholine receptor antibody titers Antiacetylcholine receptor antibody titers Antistriated muscle antibody titers Antistriated muscle antibody titers MRI to rule out thymoma MRI to rule out thymoma 88

89. Progression Varies Varies Appears first as a mild case that spontaneously remits with a series of relapses and symptom free intervals 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 Over time can progress leading to death Ocular myasthenia has a good prognosis Ocular myasthenia has a good prognosis 89

90. Treatment Anticholinesterase drugs Anticholinesterase drugs Steroids Steroids Immunosuppressant drugs Immunosuppressant drugs Cyclophosphamide Cyclophosphamide Plasmapheresis during myasthenic crisis Plasmapheresis during myasthenic crisis Thymectomy is treatment of choice for individuals with thymoma Thymectomy is treatment of choice for individuals with thymoma 90