1

Review of Skeletal System

2
Skeletal System
Function:
Protection
Hematopoiesis
Mineral homeostasis
Calcium
Phosphorus
Carbonate
Magnesium
3
Structure
Bone is a connective tissue:
Matrix
Collagen fibers for flexibility and
tensile strength
Calcium for rigidity
Hydroxyapatite Ca
5
(PO
4
)
3
OH
4
Cells:
Osteoblast
Form organic components of matrix
Osteocyte
Osteoblasts
From monocytes
Secrete citric and lactic acids
Collagenases and other enzymes
Stimulated by PTH
Inhibited by Calcitonin
5
6
7
Types of Bone
Dense or Compact (85%)
Osteon (Haversian System)
Central (Haversian) canal
Lamellae
Lacunae with osteocytes
Canaliculi
Spongy (cancellous) bone (15%)
trabeculae
8
9
10
11
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
12
Joints
Degree of movement
Synarthrosis immovable joint
Amphiarthrosis slightly movable
joint
Diarthrosis freely movable joint
13
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
14
15
Synovial fluid
Plasma filtrate
Synovial cells and leukocytes
phagocytize debris and microbes
Articular cartilage
Reduce friction
Distribute force
16
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
17
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
18
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.
19
Key features: bone fracture and the
associated pain.
WHO defines osteoporosis by bone
density:
Normal bone > 833 mg/cm
2
Osteopenia 833 to 648 mg/cm
2
Osteoporosis < 648 mg/cm
2
Can be generalized, involving major
portions of the axial skeleton
Can be regional, involving one segment of
the appendicular skeleton
20
21
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.
22
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)
23
24
25
26
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
27
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.
28
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
29
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
30
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
31
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
32
Rickets and Osteomalacia
Inadequate mineral deposition in
essentially normal organic matrix
Softened bone:
Subject to malformation and distortion pain

33
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
34
www.dinf.ne.jp/.../david/dwe002/dwe002
15.htm
35
www.talkorigins.org/faqs/homs/rickets.
html
36
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.
37
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.

38
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
39
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
40
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
41
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

42
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
43
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
44
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
45
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
46
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)
47
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
48
Rheumatoid Arthritis
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 20s or 30s
Symptoms lessen during pregnancy
Seasonal variation
49
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)
50
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
51
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
52
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
53
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

54
Rheumatoid Arthritis
Drug therapy:
NSAIDS
Methotrexate
Antimalarial drugs and immunosuppression
Surgical
Synovectomy
Correction of deformities
Joint replacement
Joint fusion
55
Review of Muscular System
56
Muscle
Skeletal muscle
> 600 muscles in body
Cardiac muscle
Smooth muscle
57
Muscle cell structure
Sarcolemma
motor end plate
transverse ( t- ) tubules
Sarcoplasm
Sarcoplasmic Reticulum Stores Ca
++
58
59
60
Proteins:
Thick filaments myosin
Thin filaments actin
Troponin
Tropomyosin
Sliding Filament Model
61
62
63
64
65
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.
66
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.
67
Fibrosis contracture distorts skeletal
development
Lordosis
Scoliosis
Compromised respiration
Respiratory insufficiency
Respiratory infection
Cardiac muscle
Dysrythmias
Congestive heart failure
Mental sluggishness
68
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
69
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
70
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

71
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
72
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

73
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.
74
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

75
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
76
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
77
Myasthenic crisis
Severe weakness causes quadriparesis or
quadriplegia, respiratory insufficiency and
extreme difficulty in swallowing
78
Cholinergic crisis
Anticholinesterase drug toxicity
Intestinal motility increases
Fasciculation
Bradycardia
Pupillary constriction
Increased salivation
Increased sweating
79
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

80
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
81
Treatment
Anticholinesterase drugs
Steroids
Immunosuppressant drugs
Cyclophosphamide
Plasmapheresis during myasthenic crisis
Thymectomy is treatment of choice for
individuals with thymoma