Review of Skeletal System

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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
• Osteoclasts
• 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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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.
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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 gt 833 mg/cm2
• Osteopenia 833 to 648 mg/cm2
• Osteoporosis lt 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

• 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.

• 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

• 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?
• 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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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 Osteoarthritis
• No risk factors idiopathic Osteoarthritis
• 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

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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 (cracking sound)

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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 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

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Rheumatoid Arthritis

• Mild to severe
• Destroys and distorts joints
• Reduces life expectancy
• Remission and exacerbation
• 1 2 of adult population
• Women men 31
• Onset usually in 20s or 30s
• 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
• gt 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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• 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 progressive 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 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
• Cause is unknown.

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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

• 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

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