Transcript Review of Musculoskeletal System

Review of Skeletal System
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Skeletal System
• Function:
– Protection
– Hematopoiesis
– Mineral homeostasis
• Calcium
• Phosphorus
• Carbonate
• Magnesium
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Structure
• Bone is a connective tissue:
– Matrix
• Collagen fibers for flexibility and
tensile strength
• Calcium for rigidity
• Hydroxyapatite Ca5(PO4)3OH
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• Cells:
– Osteoblast
• Form organic components of matrix
– Osteocyte
– Osteoblasts
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From monocytes
Secrete citric and lactic acids
Collagenases and other enzymes
Stimulated by PTH
Inhibited by Calcitonin
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Types of Bone
• Dense or Compact (85%)
– Osteon (Haversian System)
– Central (Haversian) canal
– Lamellae
– Lacunae with osteocytes
– Canaliculi
• Spongy (cancellous) bone (15%)
– trabeculae
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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
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Joints
• Degree of movement
– Synarthrosis – immovable joint
– Amphiarthrosis – slightly movable joint
– Diarthrosis – freely movable joint
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• 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
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• Synovial fluid
– Plasma filtrate
– Synovial cells and leukocytes
phagocytize debris and microbes
• Articular cartilage
– Reduce friction
– Distribute force
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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
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• 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
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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.
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• 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
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• 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.
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• 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)
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Risk factors
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Family history
White race
Increased age
Female sex
Small stature
Fair or pale skin
Thin build
Early menopause (natural or surgical)
Late menarche
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Risk factors cont.
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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.
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• 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
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Clinical manifestations
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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
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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
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Prevention
• Intake of calcium, vitamin D, magnesium
and possibly boron
• Regular, weight-bearing exercise
• Avoid tobacco and glucocorticoids
• No alcoholism
• Hormone replacement?
• Parathyroid hormone?
• Testosterone for men and possibly women
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Rickets and Osteomalacia
• Inadequate mineral deposition in
essentially normal organic matrix
• Softened bone:
– Subject to malformation and distortion –pain
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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
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www.dinf.ne.jp/.../david/dwe002/dwe00215.htm
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www.talkorigins.org/faqs/homs/rickets.html
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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.
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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.
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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
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Osteoarthritis
• When associated with known risk factors it
is secondary OA
• No risk factors – idiopathic OA
• Pathological characteristics:
– Erosion of the articular cartilage
– Sclerosis of subchondral bone
– Formation of bone spurs or osteophytes
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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
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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
• Joint mice
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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
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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
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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
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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
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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)
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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 joints of 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
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Rheumatoid Arthritis
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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
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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)
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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
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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
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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
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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
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Rheumatoid Arthritis
• Drug therapy:
– NSAIDS
– Methotrexate
– Antimalarial drugs and immunosuppression
• Surgical
– Synovectomy
– Correction of deformities
– Joint replacement
– Joint fusion
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Review of Muscular System
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Muscle
• Skeletal muscle
– > 600 muscles in body
• Cardiac muscle
• Smooth muscle
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Muscle cell structure
• Sarcolemma
motor end plate
transverse ( t- ) tubules
• Sarcoplasm
• Sarcoplasmic Reticulum – Stores Ca++
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• Proteins:
– Thick filaments – myosin
– Thin filaments – actin
• Troponin
• Tropomyosin
– Sliding Filament Model
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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.
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• 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.
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• Fibrosis → contracture distorts skeletal
development
– Lordosis
– Scoliosis
– Compromised respiration
• Respiratory insufficiency
– Respiratory infection
• Cardiac muscle
– Dysrythmias
– Congestive heart failure
• Mental sluggishness
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• Dystrophin is lacking
– Membrane damage
– Replaced by fibrous connective tissue and
fatty deposits
• Therapy
– Passive stretching, splints to prevent
deformities
– Sustain mobility
– Sustain respiratory function
– Possibly gene therapy
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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 muscle weakness and
fatigability
• Also associated with other autoimmune
disorders, such as SLE, rheumatoid
arthritis, and thyrotoxicosis
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• 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
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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 us.about 10
years
• Ocular myasthenia
– More common in males
– Weakness of eye muscles and eyelids, may
also include swallowing difficulties and slurred
speech
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• 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
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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
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• Cause is unknown.
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
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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
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• 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
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Myasthenic crisis
• Severe weakness causes quadriparesis or
quadriplegia, respiratory insufficiency and
extreme difficulty in swallowing
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Cholinergic crisis
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Anticholinesterase drug toxicity
Intestinal motility increases
Fasciculation
Bradycardia
Pupillary constriction
Increased salivation
Increased sweating
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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
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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
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Treatment
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Anticholinesterase drugs
Steroids
Immunosuppressant drugs
Cyclophosphamide
Plasmapheresis during myasthenic crisis
Thymectomy is treatment of choice for
individuals with thymoma
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