review of skeletal system
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Review of Skeletal System. Skeletal System. Function: Protection Hematopoiesis Mineral homeostasis Calcium Phosphorus Carbonate Magnesium. Structure. Bone is a connective tissue: Matrix Collagen fibers for flexibility and tensile strength Calcium for rigidity - PowerPoint PPT PresentationTRANSCRIPT
Review of Skeletal Review of Skeletal SystemSystem
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Skeletal SystemSkeletal System Function:Function:
– ProtectionProtection– HematopoiesisHematopoiesis– Mineral homeostasisMineral homeostasis
CalciumCalcium PhosphorusPhosphorus CarbonateCarbonate MagnesiumMagnesium
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StructureStructure
Bone is a connective tissue:Bone is a connective tissue:– Matrix Matrix
Collagen fibers for flexibility Collagen fibers for flexibility and tensile strengthand tensile strength
Calcium for rigidityCalcium for rigidityHydroxyapatite CaHydroxyapatite Ca55(PO(PO44))33OHOH
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Cells:Cells:– OsteoblastOsteoblast
Form organic components of matrixForm organic components of matrix– OsteocyteOsteocyte– OsteoclastsOsteoclasts
From monocytesFrom monocytes Secrete citric and lactic acidsSecrete citric and lactic acids Collagenases and other enzymesCollagenases and other enzymes Stimulated by PTHStimulated by PTH Inhibited by CalcitoninInhibited by Calcitonin
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Types of BoneTypes of Bone Dense or Compact (85%) Dense or Compact (85%)
– Osteon (Haversian System)Osteon (Haversian System)– Central (Haversian) canalCentral (Haversian) canal– LamellaeLamellae– Lacunae with osteocytesLacunae with osteocytes– CanaliculiCanaliculi
Spongy (cancellous) bone (15%)Spongy (cancellous) bone (15%)– trabeculaetrabeculae
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PeriosteumPeriosteum Outer layer is dense, irregular CT Outer layer is dense, irregular CT
with nerves and blood vesselswith nerves and blood vessels Inner layerInner layer
– OsteoblastsOsteoblasts– Anchored to bone by collagen fibers Anchored to bone by collagen fibers
that penetrate into bonethat penetrate into bone
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JointsJoints Degree of movementDegree of movement
– Synarthrosis – immovable jointSynarthrosis – immovable joint– Amphiarthrosis – slightly Amphiarthrosis – slightly
movable jointmovable joint– Diarthrosis – freely movable Diarthrosis – freely movable
jointjoint
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Synovial jointsSynovial joints– Joint capsuleJoint capsule
Fibrous CTFibrous CTTendons and ligamentsTendons and ligamentsNerves, blood and lymph vesselsNerves, blood and lymph vessels
– Synovial membrane Synovial membrane Loose fibrous CTLoose fibrous CTMany blood vessels – good repairMany blood vessels – good repair
– Joint (synovial) CavityJoint (synovial) Cavity1313
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Synovial fluidSynovial fluid– Plasma filtratePlasma filtrate– Synovial cells and leukocytes Synovial cells and leukocytes
phagocytize debris and microbesphagocytize debris and microbes Articular cartilageArticular cartilage
– Reduce frictionReduce friction– Distribute forceDistribute force
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Bone PathophysiologyBone Pathophysiology Inherited conditions:Inherited conditions:
– Osteogenesis imperfectaOsteogenesis imperfecta Inherited defect in collagen synthesisInherited defect in collagen synthesis Osteopenia and brittle bonesOsteopenia and brittle bones Often- defective tooth formation, blue Often- defective tooth formation, blue
sclera, faulty hearing, other defectssclera, faulty hearing, other defects Inheritance can be dominant, Inheritance can be dominant,
recessive or by new mutationrecessive or by new mutation Several degrees of severity ( I,II,III,IV)Several degrees of severity ( I,II,III,IV) Biphosphate treatment can improve Biphosphate treatment can improve
bone mass in all types of the disorderbone mass in all types of the disorder1616
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AchondroplasiaAchondroplasia– Involves a defect in normal cartilage Involves a defect in normal cartilage
developmentdevelopment– Epiphyseal plates close early in long Epiphyseal plates close early in long
bones; individual has short arms and bones; individual has short arms and legs, but normal spine and skulllegs, but normal spine and skull
– Dominant inheritance, but frequent new Dominant inheritance, but frequent new mutationsmutations
– Other organs develop normallyOther organs develop normally– Individuals live a normal lifespanIndividuals live a normal lifespan
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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 disordersAcquired disorders Osteoporosis – “porous bone”Osteoporosis – “porous bone”
– Most common metabolic bone disease in North Most common metabolic bone disease in North AmericaAmerica
– Can be attributed to genetics, diet or Can be attributed to genetics, diet or hormoneshormones
– Most osteoporosis is Most osteoporosis is idiopathic osteoporosisidiopathic osteoporosis– Bone loss due to an identifiable cause is Bone loss due to an identifiable cause is
secondary osteoporosissecondary osteoporosis– Bone tissue is mineralized normally, but over Bone tissue is mineralized normally, but over
time the structural integrity of bone is lost and time the structural integrity of bone is lost and it becomes thinner and weaker, and more it becomes thinner and weaker, and more prone to fractures.prone to fractures.
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Key features: bone fracture and the Key features: bone fracture and the associated pain.associated pain.
WHO defines osteoporosis by bone WHO defines osteoporosis by bone density:density:– Normal bone > 833 mg/cmNormal bone > 833 mg/cm22
– Osteopenia 833 to 648 mg/cmOsteopenia 833 to 648 mg/cm22
– Osteoporosis < 648 mg/cmOsteoporosis < 648 mg/cm22
Can be generalized, involving major Can be generalized, involving major portions of the axial skeletonportions of the axial skeleton
Can be regional, involving one Can be regional, involving one segment of the appendicular skeletonsegment of the appendicular skeleton
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Remodeling is constantRemodeling is constant– Teen years more bone is laid down than Teen years more bone is laid down than
reabsorbedreabsorbed– Peak bone mass or maximum density Peak bone mass or maximum density
reached at around 30 years of agereached at around 30 years of age– After age 30, bone is reabsorbed faster than After age 30, bone is reabsorbed faster than
it is laid down (loss of about 0.7% /year)it is laid down (loss of about 0.7% /year)– In women, bone loss is most rapid in the In women, bone loss is most rapid in the
first years after menopause, but continues first years after menopause, but continues throughout postmenopausal yearsthroughout postmenopausal years
– Est. 55% of people over 50 have Est. 55% of people over 50 have osteoporosis or low bone mass.osteoporosis or low bone mass.
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Men also lose bone density, but start out Men also lose bone density, but start out with more bone mass so takes longer.with more bone mass so takes longer.
By age 90 about 17% of males have had By age 90 about 17% of males have had a hip fracture, vs. 32 % of femalesa hip fracture, vs. 32 % of females
Vertebral fractures also occur Vertebral fractures also occur →→ kyphosiskyphosis
Most common in whites, but affects all Most common in whites, but affects all races.races.
African Americans have about half the African Americans have about half the fracture rates of whites (higher peak fracture rates of whites (higher peak bone mass)bone mass)
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Risk factorsRisk factors Family historyFamily history White raceWhite race Increased ageIncreased age Female sexFemale sex Small statureSmall stature Fair or pale skinFair or pale skin Thin buildThin build Early menopause (natural or surgical)Early menopause (natural or surgical) Late menarcheLate menarche
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Risk factors cont.Risk factors cont. NulliparityNulliparity ObesityObesity Weight below a healthy rangeWeight below a healthy range Acidosis Acidosis Low dietary calcium and vitamin DLow dietary calcium and vitamin D High caffeine intakeHigh caffeine intake Sedentary life styleSedentary life style SmokerSmoker Excessive alcohol consumptionExcessive alcohol consumption Liver, kidney disease, rheumatoid arthritis, Liver, kidney disease, rheumatoid arthritis,
etc.etc.3232
Often progresses silently for decades Often progresses silently for decades until fracture occursuntil fracture occurs
Bones can fracture spontaneouslyBones can fracture spontaneously Most severe in spine, wrist and hipsMost severe in spine, wrist and hips Estrogens and androgens may be Estrogens and androgens may be
factors in both sexesfactors in both sexes– Testosterone is converted into estrogen in Testosterone is converted into estrogen in
peripheral tissues and decreases bone lossperipheral tissues and decreases bone loss Rapid bone loss is osteoclast mediated Rapid bone loss is osteoclast mediated Slow bone loss is osteoblast mediatedSlow bone loss is osteoblast mediated
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Clinical manifestationsClinical manifestations Pain and bone deformityPain and bone deformity Kyphosis caused by vertebral Kyphosis caused by vertebral
collapsecollapse Fractures of long bonesFractures of long bones Fatal complications include fat or Fatal complications include fat or
pulmonary embolism, pneumonia, pulmonary embolism, pneumonia, hemorrhage and shockhemorrhage and shock
20 % die as a result of surgical 20 % die as a result of surgical complicationscomplications
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TreatmentTreatment No known cureNo known cure Slow bone loss and promote bone Slow bone loss and promote bone
depositiondeposition Calcium and vitamin D supplementsCalcium and vitamin D supplements Nasal or subcutaneous calcitoninNasal or subcutaneous calcitonin Hormone replacement therapyHormone replacement therapy Biophosphates – inhibit osteoclastsBiophosphates – inhibit osteoclasts Dual x-ray absorptiometry for diagnosisDual x-ray absorptiometry for diagnosis PREVENTIONPREVENTION
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PreventionPrevention Intake of calcium, vitamin D, Intake of calcium, vitamin D,
magnesium and possibly boronmagnesium and possibly boron Regular, weight-bearing exerciseRegular, weight-bearing exercise Avoid tobacco and glucocorticoidsAvoid tobacco and glucocorticoids No alcoholismNo alcoholism Hormone replacement?Hormone replacement? Testosterone for men and possibly Testosterone for men and possibly
womenwomen
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Rickets and Rickets and OsteomalaciaOsteomalacia Inadequate mineral deposition in Inadequate mineral deposition in
essentially normal organic matrixessentially normal organic matrix Softened bone:Softened bone:
– Subject to malformation and distortion –Subject to malformation and distortion –painpain
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Rickets Rickets Dietary vitamin D deficiency causes Dietary vitamin D deficiency causes
inadequate mineralization of the inadequate mineralization of the developing skeleton in infants and developing skeleton in infants and childrenchildren
Rarely seen in Western nationsRarely seen in Western nations– PovertyPoverty– IgnoranceIgnorance
Bones are soft and easily deformedBones are soft and easily deformed Tendency to fracturesTendency to fractures Therapy: supply vitamin D and calciumTherapy: supply vitamin D and calcium
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OsteomalaciaOsteomalacia Rarely due to vitamin D deficiencyRarely due to vitamin D deficiency Usually GI malabsorption, renal Usually GI malabsorption, renal
defect or chronic kidney or liver defect or chronic kidney or liver diseases.diseases.
Elderly often affected due to Elderly often affected due to inadequate diet or lack of outdoor inadequate diet or lack of outdoor activityactivity
May accompany and complicate May accompany and complicate osteoporosis.osteoporosis.
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Joint DisordersJoint Disorders OsteoarthritisOsteoarthritis
– Most common joint disease in North Most common joint disease in North AmericaAmerica
– Minimal inflammatory componentMinimal inflammatory component– Differentiated from inflammatory disease Differentiated from inflammatory disease
by:by: Absence of synovial membrane inflammationAbsence of synovial membrane inflammation Lack of systemic signs and symptomsLack of systemic signs and symptoms Normal synovial fluidNormal synovial fluid
– Much of the pain and loss of mobility Much of the pain and loss of mobility associated with aging.associated with aging.
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OsteoarthritisOsteoarthritis Incidence increases with age: 85% of people Incidence increases with age: 85% of people
age 65 have some joint degenerationage 65 have some joint degeneration Incidence similar, but women more severely Incidence similar, but women more severely
affectedaffected Exceptional stress on joints: gymnasts, etc.Exceptional stress on joints: gymnasts, etc. Biochemical defect in cartilageBiochemical defect in cartilage Malformed joint, obesity and postural Malformed joint, obesity and postural
defectsdefects Genetic componentGenetic component Torn ACL or meniscectomyTorn ACL or meniscectomy
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OsteoarthritisOsteoarthritis When associated with known risk When associated with known risk
factors it is secondary Osteoarthritisfactors it is secondary Osteoarthritis No risk factors – idiopathic No risk factors – idiopathic
OsteoarthritisOsteoarthritis Pathological characteristics:Pathological characteristics:
– Erosion of the articular cartilageErosion of the articular cartilage– Sclerosis of subchondral boneSclerosis of subchondral bone– Formation of bone spurs or osteophytesFormation of bone spurs or osteophytes
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OsteoarthritisOsteoarthritis Begins in articular cartilageBegins in articular cartilage
– Yellow-grey or brownish grayYellow-grey or brownish gray– Thin, irregular, frayedThin, irregular, frayed– Cracks or fissures develop (fibrillation)Cracks or fissures develop (fibrillation)– Fluid filled cysts may formFluid filled cysts may form– Microfractures of subchondral boneMicrofractures of subchondral bone– Formation of fibrocartilage repair plugsFormation of fibrocartilage repair plugs– Bone surface exposedBone surface exposed– Bone responds by becoming dense and Bone responds by becoming dense and
hardhard4848
OsteoarthritisOsteoarthritis Synovial membrane is indirectly Synovial membrane is indirectly
affectedaffected– Fragments of fibrocartilage cause Fragments of fibrocartilage cause
inflammation –paininflammation –pain– Fibrous repair of joint capsule restricts Fibrous repair of joint capsule restricts
motionmotion– Osteophytes form – pain and loss of Osteophytes form – pain and loss of
motionmotion
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OsteoarthritisOsteoarthritis Affects one or more weight-bearing jointsAffects one or more weight-bearing joints
– Hand, wrist, lower cervical spine, lumbar Hand, wrist, lower cervical spine, lumbar spine and sacroiliac, hip, knees, ankles, spine and sacroiliac, hip, knees, ankles, feetfeet
Aches and stiffnessAches and stiffness– Symptoms increase with activity; diminish Symptoms increase with activity; diminish
with restwith rest Usually no swelling or redness of adjacent Usually no swelling or redness of adjacent
tissuestissues Sometimes nocturnal pain – may be referredSometimes nocturnal pain – may be referred
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OsteoarthritisOsteoarthritisPrimary signs and symptoms of joint Primary signs and symptoms of joint
disease are:disease are:pain, stiffness, enlargement or pain, stiffness, enlargement or swelling, tenderness, limited range of swelling, tenderness, limited range of motion, muscle wasting, partial motion, muscle wasting, partial dislocation, and deformity, crepitus dislocation, and deformity, crepitus (cracking sound)(cracking sound)
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OsteoarthritisOsteoarthritis Evaluation made through clinical Evaluation made through clinical
assessment and radiologic studies, assessment and radiologic studies, CT scan, arthroscopy and MRICT scan, arthroscopy and MRI
Treatment:Treatment: Glucosamine may decrease pain and Glucosamine may decrease pain and
slow or stop progression – 1500 slow or stop progression – 1500 mg/daymg/day
Chondroitin sulfate – questionable Chondroitin sulfate – questionable absorptionabsorption
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OsteoarthritisOsteoarthritis Analgesics and antiinflammatory drugs Analgesics and antiinflammatory drugs
(NSAIDs)(NSAIDs) Injections of corticosteroids or sodium Injections of corticosteroids or sodium
hyaluronate (to improve lubrication)hyaluronate (to improve lubrication) Range of motion exercisesRange of motion exercises Reduce aggravating factorsReduce aggravating factors
– Weight lossWeight loss– Use of cane, crutches or walkerUse of cane, crutches or walker
Surgical removal of bone spurs, and otherSurgical removal of bone spurs, and other Replacement of jointReplacement of joint
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Rheumatoid ArthritisRheumatoid Arthritis Systemic disease with prominent Systemic disease with prominent
involvement of the jointsinvolvement of the joints Inflammatory joint disease Inflammatory joint disease
characterized by:characterized by:– Inflammatory damage in the synovial Inflammatory damage in the synovial
membrane or articular cartilagemembrane or articular cartilage– Systemic signs of inflammation: fever, Systemic signs of inflammation: fever,
leukocytosis, malaise, anorexia, leukocytosis, malaise, anorexia, hyperfibrinogenemiahyperfibrinogenemia
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Rheumatoid ArthritisRheumatoid Arthritis Systemic autoimmune disease that causes Systemic autoimmune disease that causes
chronic inflammation of connective tissuechronic inflammation of connective tissue Initially affects synovial membraneInitially affects synovial membrane Later articular cartilage, joint capsule, Later articular cartilage, joint capsule,
ligaments and tendons, and boneligaments and tendons, and bone Affects small joints more like hands, wrists, Affects small joints more like hands, wrists,
ankles, and feet, but shoulders, hips and ankles, and feet, but shoulders, hips and cervical spine may also be involvedcervical spine may also be involved
Systemic effects on heart, kidney, lungs, Systemic effects on heart, kidney, lungs, skin and other organsskin and other organs
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Rheumatoid ArthritisRheumatoid Arthritis Mild to severeMild to severe Destroys and distorts jointsDestroys and distorts joints Reduces life expectancyReduces life expectancy Remission and exacerbationRemission and exacerbation 1 – 2% of adult population1 – 2% of adult population Women : men = 3:1Women : men = 3:1 Onset usually in 20’s or 30’sOnset usually in 20’s or 30’s Symptoms lessen during pregnancySymptoms lessen during pregnancy Seasonal variationSeasonal variation
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Rheumatoid ArthritisRheumatoid Arthritis Idiopathic diseaseIdiopathic disease Immune-mediated destruction of jointsImmune-mediated destruction of joints Rheumatoid factors (IgM and IgG) Rheumatoid factors (IgM and IgG)
target blood cells and synovial target blood cells and synovial membranes forming antigen-antibody membranes forming antigen-antibody complexescomplexes
Genetic predispositionGenetic predisposition Possibly bacterial or viral infection Possibly bacterial or viral infection
(Epstein-Barr)(Epstein-Barr)5757
Rheumatoid ArthritisRheumatoid Arthritis Chronic inflammation of synovial Chronic inflammation of synovial
membranemembrane Cellular proliferation and damage to the Cellular proliferation and damage to the
microcirculationmicrocirculation Synovial membrane becomes irregularSynovial membrane becomes irregular Swelling, stiffness and painSwelling, stiffness and pain Cartilage and bone destructionCartilage and bone destruction Ankylosis or fusing of jointAnkylosis or fusing of joint Ligaments and tendons also affectedLigaments and tendons also affected
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Rheumatoid ArthritisRheumatoid Arthritis Systemic effects:Systemic effects:
– Generalized weakness and malaiseGeneralized weakness and malaise– Up to 35% develop granulomas called Up to 35% develop granulomas called
rheumatoid nodulesrheumatoid nodules– Systemic inflammation of blood vessels Systemic inflammation of blood vessels
– rheumatoid vasculitis– rheumatoid vasculitis– Serous membranes may be affectedSerous membranes may be affected
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Rheumatoid ArthritisRheumatoid Arthritis Evaluation :Evaluation :
– historyhistory– Physical examinationPhysical examination– X-rayX-ray– Serologic tests for rheumatoid factor Serologic tests for rheumatoid factor
and circulating antigen-antibody and circulating antigen-antibody complexes, esp. antibodies against complexes, esp. antibodies against cyclic citrullinated peptide (CCP)cyclic citrullinated peptide (CCP)
No cureNo cure
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Rheumatoid ArthritisRheumatoid Arthritis Therapy:Therapy: Physical and emotional restPhysical and emotional rest Relieve pain and swelling and retain Relieve pain and swelling and retain
as much joint function as possibleas much joint function as possible Resting the joint, or binding or Resting the joint, or binding or
splintingsplinting Use of hot and cold packsUse of hot and cold packs Diet high in calories and vitaminsDiet high in calories and vitamins Strengthening of associated muscles Strengthening of associated muscles
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Rheumatoid ArthritisRheumatoid Arthritis Drug therapy:Drug therapy:
– NSAIDSNSAIDS– MethotrexateMethotrexate– Antimalarial drugs and immunosuppressionAntimalarial drugs and immunosuppression
SurgicalSurgical– SynovectomySynovectomy– Correction of deformitiesCorrection of deformities– Joint replacementJoint replacement– Joint fusionJoint fusion
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Review of Muscular Review of Muscular SystemSystem
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MuscleMuscle Skeletal muscle Skeletal muscle
– > 600 muscles in body> 600 muscles in body Cardiac muscleCardiac muscle Smooth muscleSmooth muscle
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Muscle cell structureMuscle cell structure SarcolemmaSarcolemma
motor end platemotor end platetransverse ( t- ) tubulestransverse ( t- ) tubules
SarcoplasmSarcoplasm Sarcoplasmic Reticulum – Stores Sarcoplasmic Reticulum – Stores
CaCa++++
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Proteins:Proteins:– Thick filaments – myosinThick filaments – myosin– Thin filaments – actinThin filaments – actin
Troponin Troponin TropomyosinTropomyosin
– Sliding Filament ModelSliding Filament Model
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Muscular DystrophyMuscular Dystrophy Group of rare diseases characterized by a Group of rare diseases characterized by a
genetic etiology and progressive genetic etiology and progressive degeneration of skeletal muscle.degeneration of skeletal muscle.
X-linked recessive defectX-linked recessive defect Most common of the muscular Most common of the muscular
dystrophiesdystrophies 1 in 3,500 live male births1 in 3,500 live male births Affects malesAffects males Gene located on the short arm of the X Gene located on the short arm of the X
chromosome.chromosome.7474
30% of cases arise as a new mutation30% of cases arise as a new mutation Can be diagnosed immediately after Can be diagnosed immediately after
birth by high serum creatine kinasebirth by high serum creatine kinase Muscle weakness and delayed motor Muscle weakness and delayed motor
skills can be detected early – obvious by skills can be detected early – obvious by age 5age 5
Age 10 – require leg bracingAge 10 – require leg bracing Age 12 – wheelchairAge 12 – wheelchair Age 15 completely bedriddenAge 15 completely bedridden Death by 20 – 30 of cardiac arrest or Death by 20 – 30 of cardiac arrest or
respiratory failure.respiratory failure.7575
Fibrosis Fibrosis → → contracture distorts contracture distorts skeletal developmentskeletal development– LordosisLordosis– ScoliosisScoliosis– Compromised respirationCompromised respiration
Respiratory insufficiencyRespiratory insufficiency– Respiratory infectionRespiratory infection
Cardiac muscleCardiac muscle– DysrythmiasDysrythmias– Congestive heart failureCongestive heart failure
Mental sluggishnessMental sluggishness7676
TherapyTherapy– Passive stretching, splints to prevent Passive stretching, splints to prevent
deformitiesdeformities– Sustain mobilitySustain mobility– Sustain respiratory functionSustain respiratory function– Possibly gene therapyPossibly gene therapy
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Myesthenia gravisMyesthenia gravis Autoimmune disease in which Autoimmune disease in which
antibodies (IgG) bind with acetylcholine antibodies (IgG) bind with acetylcholine receptors on muscle cells. (T-receptors on muscle cells. (T-lyphmocyte abnormalities)lyphmocyte abnormalities)
Reduces the number of acetylcholine Reduces the number of acetylcholine receptors at the neuromuscular junctionreceptors at the neuromuscular junction
Characterized by progressive muscle Characterized by progressive muscle weakness and fatigabilityweakness and fatigability
Also associated with other autoimmune Also associated with other autoimmune disorders, such as SLE, rheumatoid disorders, such as SLE, rheumatoid arthritis, and thyrotoxicosisarthritis, and thyrotoxicosis
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In 10-25% of people with MG thymic In 10-25% of people with MG thymic tumors are found tumors are found – More common in males than More common in males than
femalesfemales 70 – 80 % have pathologic changes 70 – 80 % have pathologic changes
in the thymusin the thymus
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Classification of Classification of myastheniamyasthenia Neonatal myastheniaNeonatal myasthenia
– Transitory condition in which 10-15 % of Transitory condition in which 10-15 % of infants born to mothers with MG show infants born to mothers with MG show symptoms of the diseasesymptoms of the disease
Congenital myastheniaCongenital myasthenia Juvenile myasthenia – onset about 10 Juvenile myasthenia – onset about 10
yearsyears Ocular myasthenia Ocular myasthenia
– More common in malesMore common in males– Weakness of eye muscles and eyelids, Weakness of eye muscles and eyelids,
may also include swallowing difficulties may also include swallowing difficulties and slurred speechand slurred speech 8080
Generalized autoimmune myastheniaGeneralized autoimmune myasthenia– Involves proximal musculature Involves proximal musculature
throughout the body, and has several throughout the body, and has several courses:courses: A course with periodic remissionsA course with periodic remissions Slowly progressive courseSlowly progressive course Rapidly progressive courseRapidly progressive course Fulminating courseFulminating course
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PathophysiologyPathophysiology Defect in the nerve impulse transmission at Defect in the nerve impulse transmission at
the NMJthe NMJ Postsynaptic acetylcholine receptors are no Postsynaptic acetylcholine receptors are no
longer recognized as “self” and antibodies longer recognized as “self” and antibodies are produced against them.are produced against them.
IgG blocks the binding of AChIgG blocks the binding of ACh Eventually destroys the receptorEventually destroys the receptor Causes diminished transmission of nerve Causes diminished transmission of nerve
impulse across the NMJ and lack of muscle impulse across the NMJ and lack of muscle depolarizationdepolarization
Cause is unknown.Cause is unknown.8282
Clinical manifestationsClinical manifestations Onset typically insidiousOnset typically insidious May first appear during pregnancy, May first appear during pregnancy,
postpartum or with the administration postpartum or with the administration of certain anesthetic agentsof certain anesthetic agents
Complaints are fatigue and Complaints are fatigue and progressive muscle weaknessprogressive muscle weakness– Fatigue after exerciseFatigue after exercise– Recent history of recurrent upper Recent history of recurrent upper
respiratory infectionsrespiratory infections
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Clinical manifestationsClinical manifestations Muscles of the eyes, face, mouth, Muscles of the eyes, face, mouth,
throat and neck are usually affected throat and neck are usually affected firstfirst– Levator and extraocular muscles affected Levator and extraocular muscles affected
most -Diplopia, ptosis, and ocular palsiesmost -Diplopia, ptosis, and ocular palsies– Muscles of facial expression, mastication, Muscles of facial expression, mastication,
swallowing and speech are the next most swallowing and speech are the next most involvedinvolved
Facial droop, expressionless face; difficulties in Facial droop, expressionless face; difficulties in chewing and swallowing, drooling, episodes of chewing and swallowing, drooling, episodes of choking and aspirationchoking and aspiration
Nasal, low volume, high-pitched monotonous Nasal, low volume, high-pitched monotonous speech patternspeech pattern
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Less frequently involved are the Less frequently involved are the muscles of the neck, shoulder girdle muscles of the neck, shoulder girdle and hip flexorsand hip flexors– Fatigue requires periods of restFatigue requires periods of rest– Weakness of arms and legsWeakness of arms and legs– Difficulty maintaining head positionDifficulty maintaining head position– Respiratory muscles of chest wall and Respiratory muscles of chest wall and
diaphragm become weakdiaphragm become weak In advanced stage all muscles are In advanced stage all muscles are
weakweak
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Myasthenic crisisMyasthenic crisis
Severe weakness causes Severe weakness causes quadriparesis or quadriplegia, quadriparesis or quadriplegia, respiratory insufficiency and extreme respiratory insufficiency and extreme difficulty in swallowingdifficulty in swallowing
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Cholinergic crisisCholinergic crisis Anticholinesterase drug toxicityAnticholinesterase drug toxicity Intestinal motility increasesIntestinal motility increases FasciculationFasciculation BradycardiaBradycardia Pupillary constrictionPupillary constriction Increased salivationIncreased salivation Increased sweatingIncreased sweating
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EvaluationEvaluation Improvement with edrophonium Improvement with edrophonium
chloride (Telison) for several chloride (Telison) for several minutesminutes
EMG – amplitude of action potentials EMG – amplitude of action potentials declinesdeclines
Antiacetylcholine receptor antibody Antiacetylcholine receptor antibody titerstiters
Antistriated muscle antibody titersAntistriated muscle antibody titers MRI to rule out thymomaMRI to rule out thymoma
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ProgressionProgression VariesVaries Appears first as a mild case that Appears first as a mild case that
spontaneously remits with a series of spontaneously remits with a series of relapses and symptom free intervals relapses and symptom free intervals
Over time can progress leading to Over time can progress leading to deathdeath
Ocular myasthenia has a good Ocular myasthenia has a good prognosisprognosis
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TreatmentTreatment Anticholinesterase drugsAnticholinesterase drugs SteroidsSteroids Immunosuppressant drugsImmunosuppressant drugs Cyclophosphamide Cyclophosphamide Plasmapheresis during myasthenic Plasmapheresis during myasthenic
crisiscrisis Thymectomy is treatment of choice Thymectomy is treatment of choice
for individuals with thymomafor individuals with thymoma9090