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) Cavity

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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 After age 30, bone is reabsorbed faster

than it is laid down (loss of about 0.7% than it is laid down (loss of about 0.7% /year)/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 Men also lose bone density, but start out with more bone mass so takes out with more bone mass so takes longer.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 Dual x-ray absorptiometry for

diagnosisdiagnosis 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 calcium3838

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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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OsteoarthritisOsteoarthritis

Primary 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, Affects small joints more like hands,

wrists, ankles, and feet, but shoulders, wrists, ankles, and feet, but shoulders, hips and cervical spine may also be hips and cervical spine may also be involvedinvolved

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)

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Rheumatoid ArthritisRheumatoid Arthritis Chronic inflammation of synovial Chronic inflammation of synovial

membranemembrane Cellular proliferation and damage to Cellular proliferation and damage to

the microcirculationthe microcirculation 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 Antimalarial drugs and

immunosuppressionimmunosuppression 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

SarcolemmaSarcolemmamotor 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 Group of rare diseases characterized by

a genetic etiology and progressive a 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 skills can be detected early – obvious by age 5by age 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 antibodies (IgG) bind with acetylcholine receptors on muscle acetylcholine receptors on muscle cells. (T-lyphmocyte abnormalities)cells. (T-lyphmocyte abnormalities)

Reduces the number of acetylcholine Reduces the number of acetylcholine receptors at the neuromuscular receptors at the neuromuscular junctionjunction

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 7878

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 Facial droop, expressionless face; difficulties

in chewing and swallowing, drooling, episodes in chewing and swallowing, drooling, episodes of choking and aspirationof choking and aspiration

Nasal, low volume, high-pitched monotonous Nasal, low volume, high-pitched monotonous speech patternspeech pattern 8484

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 thymoma

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