Muscle/Bone/Joint Overview
I.
Joints
a.
b.
Primary Osteoarthritis
c.
Secondary Osteoarthritis
d.
Infectious Arthritis
i.
Direct Infection
1.
Bacterial Infections
2.
Tuberculous Arthritis
3.
Lyme Disease
ii.
Immune-Complex Mediated Arthritis
1.
Hepatitis B
2.
Bacterial Endocarditis
iii.
Arthritis Triggered by Antecedent Infection
1.
Rheumatic Fever (post Group A beta hemolytic strep
infection)
2.
Reactive Arthritis
e.
Rheumatoid-like Arthiritides
i.
Juvenile Rheumatoid Arthritis
ii.
Sero-negative Spondyloarthorpathies (SNSA)
1.
Ankylosing Spondylitis
2.
Reiter’s syndrome
3.
Enteropathic Arthritis
f.
Crystal Induced Arthritis
i.
Gout
ii.
Pseudogout
II.
Muscle
a.
b.
Neurogenic atrophy
i.
Amyotrophic Lateral Sclerosis
ii.
Infantile Spinal Muscular Atrophy
iii.
Poliomyelitis
iv.
Peroneal Muscular
Atrophy
c.
Physiologic Atrophy
d.
Muscular Dystrophies
i.
Duchenne Muscular
Dystrophy
ii.
Myotonic Muscular
Dystrophy
e.
Inflammatory Myopathies
i.
Polymyositis and Dermatomyositis
f.
Metabolic Myopathies –
Glycogen Storage Diseases
i.
Pompe’s Disease
(Type II Glycogenosis)
ii.
McArdle’s Disease
(Type V Glycogenosis)
g.
Myasthenia Gravis
h.
Rhabdomyolisis
III.
Bone
a.
b.
Non-neoplastic Bone Disease
i.
Developmental Abnormalities
1.
Achondroplasia
2.
Osteogenesis Imperfecta
ii.
Metabolic Bone Disease
1.
Osteoporosis
2.
Osteomalcia / Rickets
3.
Hyperparathyroidism / Osteitis
Fibrosa Cystica
4.
Renal Osteodystrophy
iii.
Osteoclast Dysfunction
1.
Osteopetrosis (Marble Bone
Disease)
2.
Paget’s Disease of Bone (Osteitis
Deformans)
iv.
Fractures
1.
Osteonecrosis
v.
Osteomyelitis
c.
Neoplastic Bone disease
i.
Bone Forming (Osseous) Tumors
1.
Benign
a.
Osteoid osteoma
b.
Osteoblastoma
2.
Malignant
a.
Osteosarcoma (osteogenic sarcoma)
ii.
Cartilage Forming Tumors
1.
Benign
a.
Chondroma (enchondroma)
b.
Osteochondroma
2.
Malignant
a.
Chondrosarcoma
iii.
Fibrous Lesions
1.
Fibrous Dysplasia
iv.
Tumors of Unknown Origin
1.
Giant Cell Tumor
2.
I.
Joints
a.
composition:
chondrocytes embedded in hydrated proteoglycan
gel, Type II collagen
proteoglycan resilience: let go of water under stress
“muscle, nerve, and brain protect joints”
b.
Primary Osteoarthritis (= degenerative bone disease,
Hypertrophic osteoarthropathy)
pathogenesis:
central degeneration (loss) of cartilage
etiology
unknown: (hereditary collagen type II defect in some cases)
epidemiology:
nearly 100% incidence by 7th decade
females: knees and
hands
males: hips
theories of pathogenesis
1. fatigue failure of collagen
2. acquired abnormality of cartilage proteoglycans
3. cumulative degradative action of
enzymes from either cartilage of synovium
4. changes in underlying bone reducing cartilage viability
clinical presentations
1. generalized mild disease (without eburnation):
Heberden nodes (osteophytes
of DIP joints of hands), osteophytes, not progressing, Bouchard’s
nodes (osteophytes at PIP joints)
2. localized severe disease (with eburnation
= ivory like reaction/exposure of bone at site of cartilage erosion): pain,
deformity
c.
Secondary Osteoarthritis
severe,
localized to single joints
etiology:
post-traumatic, post-rheumatoid, post-infectious, post-metabolic disorder,
post-necrotic, congenital dysplasias
pathogenesis:
non-gradual exercise after inactivity (gradual ambulation à no osteoarthritis), lack of proprioception
basketball:
knees, pitchers: elbow, ballet dancers: ankles
obesity à OA of knee, but not hip
histopathology: initial proteoglycan loss à fibrillation of cartilage (chondrocyte
proliferation) à cartilage erosion, eburnation à pseudocysts in bone underlying fractured cartilage à osteophytes (bone spurs at non-weight
bearing periphery of joints) à detritic synovitis
(synovial inflammation around detached cartilage fragments)
d.
Infectious Arthritis
i.
Direct Infection
1.
Bacterial Infections
from
bloodstream (rarely: from adjacent bone infection)
epidemiology:
frequent bacteremia (drug addicts), immunocompromised, severe underlying joint disease (RA)
staphylococcus aureus, H. flu (children), pseudomonas (drug addicts),
salmonella (sickle cell), gonococci (STD)
virulent
organisms (
2.
Tuberculous Arthritis
involves
spine (Pott’s disease à kyphosis) or single peripheral joints (hip, knee)
usually do
not have active pulmonary TB
X-ray
3.
Lyme Disease
borelia burgdoferi (transmitted by
tics)
most:
migratory polyarthralgias which resolve
untreated à destructive joint destruction of single joints
ii.
Immune-Complex Mediated Arthritis
analogous
to serum sickness
1.
Hepatitis B
prodrome: arthritis and urticaria
(hives)
caused by
immune complexes of Hepatitis B surface antigen and antibody à complement
cleared by
serum
2.
Bacterial Endocarditis
may be
complicated by arthritis and glomerulonephritis
iii.
Arthritis Triggered by Antecedent Infection
1.
Rheumatic Fever (post Group A beta hemolytic strep
infection)
large
joints, asymmetric fashion
transitory
arthritis
etiology:
secondary to immune response
2.
Reactive Arthritis
sterile
inflammatory arthritis occurring after an infection at a remote site
prototype: Reiters syndrome following urethritis
or shigella dysentery
HLA-B27
e.
Rheumatoid-like Arthiritides
i.
Juvenile Rheumatoid Arthritis
most frequent
pediatric autoimmune disease
large
joints, excellent prognosis
symptoms: pericarditis, hepatitis, uveitis,
rheumatoid factor (20%)
Presentations
1. polyarticular: 50% (5 or more
joints, TMJ joint possible)
2. oligoarticular: 40% (4 or fewer
joints)
3. systemic: 10% (= Still’s disease); visceral involvement, fever, rash
ii.
Sero-negative Spondyloarthorpathies (SNSA)
seronegative for rheumatoid factor
HLA-B27
arthritic
disease à inflammation à ankylosis (fusion)
1.
Ankylosing Spondylitis
fibrosis
and ossification at site of insertion
of ligaments and joint capsules into bone
sacroiliac joints, spine
males usually have
more severe disease
95% HLA-B27,
< 10% RF, 25% iritis; 10% aortic insufficiency
familial
2.
Reiter’s syndrome (= reactive arthritis)
triad:
1.
arthritis
2.
non-gonococcal urethritis
3.
conjunctivitis
male, HLA-B27
3.
Enteropathic Arthritis
arthritis
in Crohn’s or Ulcerative Colitis
f.
Crystal Induced Arthritis
i.
Gout
hyperuricemia
recurrent
acute monoarticular arthritis
crystals of
sodium urate in leukocytes of synovial fluid
deposits:
in and around joints (tophi)
kidney
“stones”
underexcretion or overproduction of uric acid
interaction
of crystals with PMN’s à inflammation à release of lysosomal products in joint
ii.
Pseudogout
arthritis
from rupture of preformed clusters of calcium pyrophosphate crystals
pain,
stiffness, local heat
etiology:
abdominal surgery, stroke, MI
diagnosis:
calcification of articular cartilage on x-ray (confirmed by calcium pyprophosphate in synovial fluid)
|
|
Urate (Gout) |
Calcium
Pyrophosphate (pseudogout) |
|
Shape |
needle |
rhomboid |
|
Number |
many |
few |
|
Birefringence |
negative |
weak positive |
II.
Muscle
a.
muscle is
enclosed in: epimysium
individual
muscle fibers surrounded by: perimysium
motor unit:
lower motor neuron and muscle fibers it innervates
histochemistry
ATPase:
distinguishes fiber types
NADH-tetrazolium reductase:
sarcoplasmic reticulum and mitochondria
Myophosphorylase and PAS: glycogen storage disease
Muscle
Fiber Types (normally “checkerboard”
appearance): determined by innervation
Type
I: red, slow twitch (sustained contraction, more myoglobin, more
mitochondria)
Type
II: white, fast twitch (quick contractions, anaerobic glycolysis, darker with ATPase)
b.
Neurogenic atrophy
with
chronic disease, reinnervation occurs (seen as loss
of checkerboard appearance, type
grouping)
i.
Amyotrophic Lateral Sclerosis
degenerative
disease of corticospinal tract and anterior horn cells)
progressive
paralysis, spasticity, hyperactive tendon reflexes
death
(aspiration pneumonia secondary to dysphagia) at 2-6 years
sensation and intellect
are unaffected
chronic
neuropathy with small angular fibers, fiber type grouping, large group atrophy
ii.
Infantile Spinal Muscular Atrophy
degenerative
disease of anterior horn cells
autosomal
recessive
SMA
type I: (Wednig-Hoffman disease); congenital hypotonia, progressive
SMA
type II: (Kugelberg-Welander disease) rarer, nonprogressive
iii.
Poliomyelitis
viral
infection
destruction
of anterior horn cells
acute
illness with fever, vomiting, diarrhea, sore throat, headache à death, paralysis, mild
occasional
persisting motor units with compensatory hypertrophy
iv.
Peroneal Muscular
Atrophy
progressive
hereditary degenerative disease: peripheral nerves and nerve roots
restricted
to distal limb muscles (begins at feet), type grouping, group atrophy
sensation is also lost
c.
Physiologic Atrophy
etiology: bedrest, debilitating diseases, corticosteroid therapy
only Type II fibers are
affected
d.
Muscular Dystrophies
weakness
from progressive muscle destruction
increase in
connective tissue (collagen and fat)
fibers are
rounded, atrophic and hypertrophic (random fiber sizes), internal nuclei
i.
Duchenne Muscular
Dystrophy
most common and most
severe dystrophy
sex-linked
recessive (one-third:
spontaneous: dystrophin is largest gene known)
serum creatinine phosphokinase (CPK)
levels are initially elevated à decrease
weakness at
shoulder and pelvic girdle (3-6 yo)
fatty
infiltration of calf muscles == “pseudo-hypertrophy”
wheelchair
bound; die from inability to clear respiratory secretions
Gower’s sign
pathogenesis:
dystrophin
(stabilizes inner surface of sarcolemma), abnormal
calcium influx, sarcolemma fragility
dystrophin is largest known gene
Becker’s muscular dystrophy
milder,
later onset, slower progression
smaller
or larger dystrophin protein
ii.
Myotonic Muscular
Dystrophy
most common
adult muscular dystrophy
autosomal
dominant (chromosome 19)
anticipation
(earlier onset with successive generations: CCG trinucleotide
repeats)
myotonia (inability to relax muscle after contraction) à progressive muscle weakness, wasting
association
with other organs (to greater extent than other dystrophies)
association
with frontal balding, cataracts, gonadal atrophy, endocrine dysfunction,
conduction abnormalities
Type I fibers: selective atrophy of
e.
Inflammatory Myopathies
i.
Polymyositis and Dermatomyositis
(without and with skin lesions, respectively: ertythematous
rash)
unknown
etiology (autoimmune?)
muscle
weakness, pain, inflammation, degeneration
symmetric
proximal weakness à progressive (weeks to months)
Polymyositis : Cytotoxic T cells
Dermatomyositis: skin lesions, B-cell infiltrate
elevated ESR, CPK
myophagocytosis
inclusion body myositis
refractory to standard therapy (immunosuppression)
ii.
infectious disease
trichinosis (trichinella
spiralis): skeletal muscle parasite
symptoms : fever, fatigue, muscle tenderness,
eosinophilia (several weeks)
f.
Metabolic Myopathies –
Glycogen Storage Diseases
autosomal
recessive
inability to degrade
glycogen
skeletal
muscle is involved in 5 of the 12
i.
Pompe’s Disease
(Type II Glycogenosis)
most severe form
Acid Maltase deficiency
involves
skeletal and cardiac muscle
“floppy baby” and cardiomegaly
death in
first year
ii.
McArdle’s Disease
(Type V Glycogenosis)
myophosphorylase deficiency
symptoms:
weakness, stiffness, muscle pain associated with vigorous exercise
diagnosis: serum lactate fails to rise
with exercise
normal life
span possible
g.
Myasthenia Gravis
autoimmune
(anti-acetylcholine receptor activity)
abnormal
muscle fatigability (begins with weakness of eye muscles à head and neck)
slow and
irregular course with remissionis
death from
respiratory failure
treatment: anticholinesterase drugs
40%
of patients have an associated thymoma (75% of remaining: thymic
hyperplasia)
focal type
II atrophy may be presents
h.
Rhabdomyolisis
dissolution of skeletal
muscle with release of myoglobin into circulation
acute, subacute, or chronic
during acute:
muscles are swollen, tender, weak
etiology: influenza, metabolic disorder+mild exercise, heat stroke, alcoholism
active, noninflammatory myopathy,
scattered necrosis, degeneration and regeneration
macrophages (but not other inflammatory cells) may be seen
III.
Bone
a.
organic and
inorganic elements
type I collagen
calcium hydroxyapatite (99% of body’s calcium, 85% of body’s
phosphorus)
cell
types
osteoblasts: make matrix, have hormone receptors
osteocytes: mature bone cells, communicate with other cells
osteoclasts: multinucleated cells derived from hematopoietic cells
(bone resorption)
bone
formation
endochondral or intramembranous
woven bone à lamellar bone
b.
Non-neoplastic Bone Disease
causes
of short stature
1. achondroplasia
2. osteoporosis
3. osteogenesis
imperfecta
4. ricket’s
lead
to fracture
1. osteoporosis
2. osteogenesis
imperfecta
3. Paget’s disease
4. tumor
i.
Developmental Abnormalities
1.
Achondroplasia
autosomal
dominant
FGFR3 gene: normally inhibits cartilage formation (when mutated:
always on)
decreased chondrocytes in growth plate à decreased growth à decreased endochondral
ossification
sealed
growth plate with shortened bone length
shortened
proximal extremities (normal torso, enlarged forehead)
2.
Osteogenesis Imperfecta (brittle bone disease)
deficiency
in type I collagen (a-1 and a-2 chains)
type I
collagen is found: bone, joints, eyes, ears, skin, teeth
present
with multiple fractures
(may have: blue sclerae, dentinogenesis
imperfecta – small, blue-yellow teeth, hearing loss)
Seven
types
Type
I: most common, compatible with survival, usually acquired
Type
II: lethal; intrauterine fractures, do not survive trauma of child birth
ii.
Metabolic Bone Disease
1.
Osteoporosis
imbalance
of osteoclastic/osteoblastic action associated with
age
increased
porosity of skeleton (density: 2.5 SD below mean for young adults)
etiology:
age-related, post-menopausal, endocrine
epidemiology/risk factors: caucasian, asian,
smoking, inactivity, alcoholic
trabecular bone affected
(vertebrae) à fractures
decreased estrogen à increased IL-1, IL-6, TNFa à increased osteoclast
activity
symptoms:
back pain
diagnosis:
bone densitometry, osteoporotic trabeculae are
thinned, Haversian canals widened
treatment:
hormone replacement, physical activity, calcium supplements, calcitonin
2.
Osteomalcia / Rickets
undermineralized bone
Ricket’s: affects growth plate (bowing
of legs, short stature)
etiology:
diet (vitamin D) or
hereditary (X-Linked Hypophospatemic osteomalacia)
3.
Hyperparathyroidism / Osteitis
Fibrosa Cystica (progressive form)
can be
primary, secondary, tertiary
systemic
(all bones affected)
osteoclasts à “railroad tracks” = dissecting osteitis
microfractures à aggregation of osteoclast-like giant cells,
macrophages, fibrous tissue (Brown
Tumor = reactive lesion)
4.
Renal Osteodystrophy
à hypocalcemia
(stimulates parathyroid release à osteoclast activation) = secondary
hyperparathyroidism
metabolic
acidosis of renal failure also contributes to bone resorption
à bone loss (mimics osteitis fibrosa cystica), osteomalacia, osteosclerosis, growth retardation, osteoporosis
iii.
Osteoclast Dysfunction
1.
Osteopetrosis (Marble Bone
Disease)
rare
hereditary disorder of osteoclast dysfunction
absence of
carbonic anhydrase II (cannot resorb
or solubilize bone)
irregular, unmodeled bone (brittle)
autosomal recessive
form: early onset; affects hematopoiesis à hepatosplenomegaly, fatal infections
autosomal
dominant form: adolescent; fractures and anemia
2.
Paget’s Disease of Bone (Osteitis
Deformans)
abnormal, increased rate
of remodeling of bone
>
40 yo
common
unifocal, multifocal, or progressive
etiology
unknown (viral? paramyxovirus, canine distemper
virus, measles)
“mosaic pattern” (three phases
can occur simultaneously)
lab:
elevated alkaline phosphatase
symptoms:
may be asymptomatic,
pain, chalk stick fractures,
bowing of femur/tibia, compression of vertebrae à kyphosis, femoral head involvement à secondary osteoarthritis, facial bone involvement à deafness, Paget’s sarcoma)
diagnosis:
radiography (lytic
wedge advancing along cortex = flame sign)
treatment: bisphosphanates (suppress bone remodeling), surgery
three
phases
1. osteolytic phase (abnormal large osteoclasts
with 100+ nuclei)
2. osteoclastic-osteoblastic phase (lining of osteoblasts around trabeculae)
3. osteosclerotic phase (burnt out
phase: larger coarse
trabeculae; cortex soft, weak)
iv.
Fractures
Steps
1. hematoma/fibrin mesh à platelet release of PDGF, TGF-B, FGF, and IL’s à activation of bone progenitor cells, osteoblastic, osteoclastic
activity
2. soft tissue callus formation
(1 week later) à organizing hematoma, remodeling of fractured
ends
3. woven bone deposition (2-3 weeks later) à becomes fibrocartilage à endochondral ossificationi (bony callus)
4. remodeling
of these areas continues to accommodate stress and weight
1.
Osteonecrosis (idiopathic = avascular
necrosis)
etiology:
idiopathic, infection, fracture, tumor, thrombosis, corticosteroids, radiation
remodeling
does not fully compensate à distortion of articular cartilage
clinical presentation
1. subchondral infarcts: (pain, may collapse, predispose à osteoarthritis)
2. medullary infarcts: (may be asymptomatic)
v.
Osteomyelitis
inflammation
of bone and bone marrow due to infection
causes: bacteria, mycobacteria,
fungi, viruses, parasites
source: hematogenous, extension from contiguous site, direct implantation
from open fracture
symptoms:
localized pain, fever of unknown origin
pathology:
necrosis of entrapped bone; bacteria and acute inflammation spread through
shaft
dead bone =
sequestrum
new bone
around sequestrum = involucrum
can spread
to articular surface (especially in infants) à suppurative arthritis
treatment:
antibiotics, surgical drainage
Tb
infection = Pott’s
disease (hip and knees most common)
Bacteria
- s. aureus
(80-90%, contiguous or hematogenous spread)
- e. coli, pseudomonas, klebsiella
(urinary infections, drug abusers)
- H. influenza: (Neonatal infections)
- Salmonella: (sickle cell disease)
c.
Neoplasms of the Skeletal System
most common
neoplasm of bone is metastatic (prostate, breast, lung, kidney, thyroid)
some
undifferentiated mesenchymal tumors (sarcomas) can arise in bone and/or soft
tissue
i.
Bone Forming (Osseous) Tumors
1.
Benign
a.
Osteoid osteoma
by
definition < 2cm
epidemiology:
young males
symptoms: severe pain (ß excess prostaglandin E2), worse at night, relieved by aspirin
location: diaphysis
b.
Osteoblastoma
histologically identical to osteoma
> 2cm
symptoms: dull achy pain not responsive to
aspirin
location: spine
2.
Malignant
a.
Osteosarcoma (osteogenic sarcoma)
most common
primary malignant tumor of bone
epidemiology:
10-25 yo, males (older than 40: associated with Paget’s)
symptom:
pain
location: diaphysis - distal femur, proximal tibia
“Codman’s Triangle”
(blastic and lytic lesions erupting through cortex “sunburst lesion”, lifting
periosteum)
produce
bone and possibly other tissues (subclassified based
on predominant matrix produced: osteoblastic, chondrobastic, or fibroblastic)
prognosis:
has improved (60% survival)
ii.
Cartilage Forming Tumors
1.
Benign
a.
Chondroma (enchondroma)
small bones
of hands and feet of young
males
asymptomatic
Ollier’s disease: hereditary form, multiple enchondromas
(has increased risk of malignancy)
b.
Osteochondroma
benign cartilage-capped outgrowth
(with a bony stalk)
long,
tubular bones of young males
multiple osteochondromatosis:
hereditary form (Chr. 8,11,19) – associated with
malignancy
2.
Malignant
a.
Chondrosarcoma
intramedullary
cartilage without osteoid or bone
occur in
older patients
location:
pelvis, ribs, shoulder (appendicular: association with Ollier’s
and multiple osteochondromatosis)
prognosis: based
on grade
gross: lobulated and scalloped (looks like cartilage)
iii.
Tumors of Unknown Origin
1.
Giant Cell Tumor
composed of
primitive mesenchymal mononuclear cells (neoplastic) and osteoclast-like
giant cells
location: epiphyseal
(distal femur, proximal tibia, distal radius)
epidemiology:
females > 20 yo
benign but
locally aggressive
red-brown
surface
high
recurrence
2.
small round blue cell
tumor (c-myc, t11;22)
epidemiology:
male, 10-15 yo
symptoms: elevated sedimentation rate,
anemia, fever, leukocytosis (mimics infection)
location:
appendicular skeleton (diaphysis: femur)
very
aggressive, metastatic
“moth-eaten” lesion with a periosteal
reaction and large soft tissue mass
“steel gray” nuclei
large accumulations
of glycogen in cytoplasm
50%
prognosis
iv.
Fibrous Lesions
1.
Fibrous Dysplasia
benign,
tumor-like, dysplastic
location:
ribs, femur, tibia, jaw, skull
may be monostotic or polyostotic
polyostotic type is associated with McCune Albright syndrome (café-au-lait spots, encephalopathies, endocrinopathies)
“ground-glass”
appearance