PATHOLOGY OF THE MUSCULOSKELETAL SYSTEM

PATHOLOGY OF THE
MUSCULOSKELETAL
SYSTEM
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Bone disorders
Metabolic bone disorders
Osteoporosis (primary or secondary)
Osteomalacia and rickets
Paget’s disease
Genetic disorders (dysplasia): osteopetrosis,
achondroplasia, osteogenesis imperfecta,
hyperostosis, fibrous dysplasia.
Infectious diseases of bones - Osteomyelitis
Bone Tumors
Bone injury

Osteoporosis (primary or secondary)
represents an increased loss of total bone
mass due to an imbalance between bone
absorption and bone formation, most often
related to the aging process and decreased
estrogen levels inpostmenopausal women.
Osteomalacia and rickets represent a
softening of bone due to inadequate
mineralization of the bone matrix caused by a
deficiency of calcium or phosphate.
Paget’s disease is a disorder involving
excessive bone destruction and repair,
resulting in structural deformities of long
bones, spine, pelvis, and cranium.

Osteoporosis
PATHOGENESIS
Osteoporosis is conventionally classified into 2 major
groups:
Primary osteoporosis results primarily from
osteopenia without an underlying disease or
medication.
Primary osteoporosis is further subdivided into 2
types:
idiopathic type found in the young and juveniles and
is less frequent
involutional type seen in postmenopausal women
and aging individuals and is more common.

Risk factors
1. Genetic factors—more marked in whites and
Asians than blacks.
2. Sex—more frequent in females than in males.
3. Reduced physical activity—as in old age.
4. Deficiency of sex hormones—oestrogen
deficiency in women as in postmenopausal
osteoporosis and androgen deficiency in men.
5. Combined deficiency of calcitonin and oestrogen.
6. Hyperparathyroidism.
7. Deficiency of vitamin D.
8. Local factors—which may stimulate osteoclastic
resorptionor slow osteoblastic bone formation.

Secondary osteoporosis is attributed to a number
of factors and conditions:
endocrine disorders (hyperthyroidism,
acromegaly, hyperparathyroidism, Cushing’s
syndrome, diabetes)
malabsorption disorders
starvation
malignancies (multiple myeloma)
alcoholism
certain medications (Glucocorticoid, aluminum-
containing antacids, corticosteroids and
anticonvulsants antiretroviral therapy, large dose of
heparin).
Immobilization

Clinical features
The first clinical manifestations of
osteoporosis are pain accompanied
by skeletal fractures: vertebrae
(compression fracture, loss of height
and kyphosis), femoral neck (hip
fracture), distal radius (Colles
fracture)
Systemic symptoms such as
weakness and weight loss.

Osteoporosis weakens the
vertebrae, resulting in
compression fractures of the
anterior aspect of the vertebral
bodies. The fractures result in
back pain and, over time,
shortening of stature, dorsal
kyphosis, and cervical lordosis.
Loss of bone in osteoporosis is
more rapid in trabecular bone
than in cortical bone; hence
vertebrae, because of their
prominent trabecular
component, are prone to
fracture. Noticeable the variation
in the width of the vertebrae, the
fractures, and that the bone is
very porous.

Osteomalacia
Produce a softening of the bones and do not involve the
loss of bone matrix
Causes of osteomalacia:
1. Insufficient calcium absorption from the intestine because of
a lack of dietary calcium or deficiency or resistance to the
action of vitamin D (among the elderly, biliary tract or
intestinal diseases, on long-term anticonvulsant, tranquilizer,
sedative, muscle relaxant, or diuretic drugs, during the
winter months, probably because of lessened exposure to
sunlight, in cultures in which the diet is deficient in vitamin D,
such as in northern China, Japan, in strict vegetarians,
persons who had a gastrectomy, long-standing primary
hyperparathyroidism.)
2. Phosphate deficiency caused by increased renal losses
(chronic renal failure, renal tubular defects) or decreased
intestinal absorption.

Clinical features
1.Bone pain, tenderness, and
fractures as the disease progresses,
muscle weakness
2.Deformities (gravity, muscle
weakness, and bone softening) -
dorsal kyphosis in the spine, rib
deformities, heart-shaped pelvis,
marked bowing of the tibiae and
femurs

This is a classic
pseudofracture and
is pathognomonic
for osteomalacia.

Paget’s disease
Is not a true metabolic disease
Localized disorder of bone remodeling,
resulting in excessive bone resorption
followed by disorganized bone replacement,
producing thickened but weak bone that is
susceptible to deformity and fracture
Begins after age 40 years and progresses
slowly over many years

Forms of involvement
1.Monostotic (15%): involving one bone
2.Polyostotic (85%): involving multiple bones
3.Common sites include the skull, pelvis,
femur, and vertebrae.
Three stages of Paget disease
1.Osteolytic: osteoclastic activity
predominates
2.Mixed osteolytic-osteoblastic
3.Osteosclerotic: osteoblastic activity
predominates “burnout stage

ETIOLOGY
1. Slow-virus infection by paramyxovirus (e.g.
respiratory syncytial virus, measles) in
osteoclasts. However, the virus has not been
cultured from the osteoclasts of Paget’s
disease.
2. Autosomal dominant inheritance and
genetic susceptibility have been proposed on
the basis of observation of 7-10 fold higher
prevalence of disease in first-degree relatives.
The susceptibility gene located on
chromosome 18q encodes for a member of
tumour necrosis factor called RANK (receptor
activator of nuclear factor).

Clinically, the monostotic form of the
disease may remain asymptomatic and the
lesion is discovered incidentally or on
radiologic examination.
Polyostotic form, however, is more
widespread and may produce pain,
fractures, skeletal deformities, and
occasionally, sarcomatous transformation.
Typically, there is marked elevation of serum
alkaline phosphatase and normal to high
serum calcium level.

 In this image, the calvarium is markedly thickened by
the growth of new bone. Secondly, in both specimens,
the density of the bone is very heterogeneous, varying
from rarefied foci to dense regions.

rat skull, especially bone brain parts, front less
often. In the latter case, a characteristic look
sick-lion's face Uploaded by: http://mbbshelp.com

Infectious diseases of bones
Osteomyelitis
Osteomyelitis represents an acute or chronic
pyogenic infection of the bone.
Inflammation of the bone marrow and other bone
items
More often affects metaphysis femoral and tibial
bone
Cause – staphylococci, hemolytic streptococci,
Escherichia coli, Mycobacterium, pathogenic
fungi.
Risk factors - endogenous microflora, acute
infectious diseases, dialysis, presence of
prosthetic orthopedic apparatus, etc.Uploaded by: http://mbbshelp.com

Course of disease:
1.Acute osteomyelitis - sometimes
lightning inflammatory diseases,
trauma, iatrogenic, postradiation.
2.Subacute
3.Chronic forms of osteomyelitis-
chronic inflammatory diseases of
chronic tuberculous osteomyelitis,
chronic syphilitic osteomyelitis.

HEMATOGENOUS OSTEOMYELITIS
Is preceded by staphylococcal or streptococcal
infections of the skin, sinuses, teeth, or middle ear→
bacteremia → Osteomyelitis
Pathogenesis - consist of bone marrow lesion
appearance of serous inflammation. Serous exudate
increases pressure in the closed space of bone
marrow and gaversov channels → joins thrombosis of
arterioles and venules bone blood flow stops
(vascular insufficiency) and focal bone necrosis
develops (ischemic necrosis of bone) → exudate
becomes suppurative inflammation and acquires the
character of phlegmon → bone marrow necrosis
develops compact bone with formation of
underperiosteum abscess and fistula formation

Clinical features: bacteremia - chills,
fever, malaise, leukocytosis; pain on
movement, loss of movement, local
tenderness followed by redness and
swelling.
Forecast - septic form of acute
hematogenous osteomyelitis causes
patients to death, acute focal
osteomyelitis can end with recovery.

Chronic Osteomyelitis
Develops as a consequence of acute when the
infection persists beyond 6 to 8 weeks and more.
Pathogenesis and morphogenesis - formation of
abscesses of bone marrow, around which the
bone resorption, necrosis and sequestration of
necrotic areas → a cavity containing bone
sequesters. Near the hearth of inflammation of
the bone thickens, deforms, fistulas are formed
through which bone small sequesters. Periosteum
is thickened and sclerosis. The skin is atrophic
changes.
Complications - pathological fractures, false
joints, bleeding from the fistula, secondary
amyloidosis, septicemia, tumors.

Tuberculous osteomyelitis
Occurs in 1% of cases of ТВ
Extrapulmonary tuberculosis.
Caused by Mycobacterium tuberculosis
Bone destruction and abscess formation,
caseating granulomas with extensive destruction
of the bones.
Local symptoms - pain, immobility, and muscle
atrophy; common symptoms - swelling, mild fever,
leukocytosis, night sweats, weight loss.
50% it affects the vertebrae, also is seen in the
hip and knee. Common site: thoracic and lumbar
vertebrae (“Pott disease”).
Complications - vertebral compression fracture,
psoas abscesses, secondary amyloidosis.

Osteomyelitis with vascular
insufficiency
Commonly associated with chronic
or ischemic foot ulcers in persons
with longstanding diabetes or other
chronic vascular disorders
Treatment: debridement and antibiotic
- good oxygen tension in the infected
site, amputation - oxygen tension is
inadequate

 Hematogenous osteomyelitis
of the fibula of 3 months’
duration. The entire shaft has
been deprived of its blood
supply and has become a
sequestrum (S) surrounded by
new immature bone,
involucrum (Iv). Pathologic
fractures are present in the
lower tibia and fibula.
 A patient with chronic
osteomyelitis of the midshaft of
the tibia. A large fragment of
necrotic cortex is visible deep
within the draining sinus
(sequestrum). The reactive
periosteum has formed a collar
of reactive bone (involucrum)
around the chronic draining
lesion.

Classification of primary bone tumors
TissueType BenignNeoplasm Malignant Neoplasm
Bone Osteoid osteoma, Benign
osteoblastoma
Osteosarcoma, Parosteal
osteogenic sarcoma
Cartilage Osteochondroma,
Chondroma,
Chrondroblastoma
Chondromyxoid fibroma
Chondrosarcoma
Lipid Lipoma Liposarcoma
Fibrous and fibroosseous
tissue
Fibrous dysplasia Fibrosarcoma,Malignant
fibrous histiocytoma
Miscellaneous Bone
marrow
Giant cell tumor Malignant giant cell,
Ewing’s sarcoma, Multiple
myeloma, Reticulum cell
sarcoma

Diseases of the joints (arthritis)
1. Infectious arthritis
2. Autoimmune
3. Metabolic
4. Degenerative arthritis or arthrosis
5. Developmental disorders of the
joints
6. Tumor
7. Joint (Musculotendinous) Injuries

Degenerative joint disease
Osteoarthritis Syndrome
Osteoarthritis (OA) - formerly called
degenerative joint disease, is the most prevalent
form of arthritis.
Men are affected more commonly at a younger
age than women, but the rate of women affected
exceeds that of men by middle age.
Obesity is a risk factor for OA

Causes of Osteoarthritis
1. Postinflammatory disorders (Rheumatoid arthritis, Septic
joint)
2. Post-traumatic disorders (Acute fracture, Ligament or
meniscal injury, Cumulative occupational or recreational
trauma)
3. Anatomic disorders (Hip dysplasia, Avascular necrosis,
Paget’s disease, Slipped capital femoral epiphysis)
4. Metabolic disorders (Calcium crystal deposition,
Hemochromatosis, Acromegaly, Wilson’s disease)
5. Neuropathic arthritis (Charcot joint)
6. Hereditary disorders of collagen
7. Idiopathic or primary variants

TYPES AND PATHOGENESIS
Primary OA occurs in the elderly, more
commonly in women than in men. The
process begins by the end of 4th decade and
then progressively and steadily increases
producing clinical symptoms.
Little is known about the etiology and
pathogenesis of primary OA. Genetic factors
favouring susceptibility to develop OA have
been observed; genetic mutations in proteins
which regulate the cartilage growth have been
identified e.g. FRZB gene.

Secondary OA may appear at any age
and is the result of any previous wear and
tear phenomena involving the joint such as
previous injury, fracture, inflammation,
loose bodies and congenital dislocation of
the hip. The molecular mechanism of
damage to cartilage in OA appears to be
the breakdown of collagen type II,
probably by IL-1, TNF and nitric oxide.

Pathogenesis
Result from the release of cytokines such as
interleukin-1 and TNF, changes synthesis
protheoglicans and collagen type II → stimulate the
production and release of proteases (enzymes) →
destructive to joint structures → Edema of the
extracellular matrix → the cartilage loses its smooth
aspect → surface cracks occur allowing synovial fluid
to enter and widen the crack → the vertical clefts form
in the subchondral bone cartilage → fragments of
cartilage to become dislodged → creating
osteocartilaginous loose bodies → sclerosis, or
formation of new bone (osteophyte) and cysts, usually
occurs in the juxta-articular bone. Small osteophytes
in the interphalangeal joints-Geberden's nodules

Clinical Manifestations
- May occur suddenly
- The pain worsens with use or activity and is usually
relieved by rest.
- Crepitus and grinding when the joint is moved.
- Joint swelling as a result of chronic inflammation in the
periarticular tissues
The most frequently affected joints - hips, knees, lumbar
and cervical vertebrae, proximal and distal joints of the
hand, the first carpometacarpal joint, and the first
metatarsophalangeal joints of the feet.
- limitations of joint motion and joint instability

In this image, the knee
joint has been opened
anteriorly under the
patella. For orientation,
the hip is to the right and
the foot to the left. There
has been extensive
destruction of the
articular cartilage of the
lower end of the femur.
The synovium is not
hyperplastic, nor is it
inflamed. There is no
evidence of pannus.

A common finding in
degenerative joint disease is
the formation of osteophytes at
the margin of affected joints. In
this image, there are three
osteophytes projecting from
the intervertebral joints.
Osteoarthritis of the hip is
common. In this typical image,
there is marked irregularity
and erosion of the articular
surface. Very little articular
cartilage remains.

Rheumatic disorders (Autoimmune)
Rheumatic disorders are characterized by
inflammation, pain, and stiffness in the
musculoskeletal system.
Systemic autoimmune rheumatic diseases
Systemic autoimmune rheumatic diseases -
group of chronic disorders characterized by
diffuse inflammatory vascular lesions and
degenerative changes in connective tissue that
share clinical features and may affect many of
the same organs, all of which share an
autoimmune systemic pathogenesis.

Rheumatoid Arthritis
Systemic inflammatory disease; 0.3% to
1.5% of the population
Women affected two to three times more
frequently than men
The ages of 40 and 60 years
Cause – uncertain, the disease is initiated
in a genetically predisposed individual by
the activation of a T cell-mediated
response to an immunologic trigger, such
as a microbial agent

Immunologic derangements
1. Detection of circulating autoantibody called rheumatoid factor
(RF) against Fc portion of autologous IgG in about 80% cases of
RA. RF antibodies are heterogeneous and consist of IgM and
IgG class.
2. The presence of antigen-antibody complexes (IgG-RF
complexes) in the circulation as well as in the synovial fluid.
3. The presence of other autoantibodies such as antinuclear
factor (ANF), antibodies to collagen type II, and antibodies to
cytoskeleton.
4. Antigenicity of proteoglycans of human articular cartilage.
5. The presence of γ-globulin, particularly IgG and IgM, in the
synovial fluid.
6. Association of RA with amyloidosis.
7. Activation of cell-mediated immunity as observed by presence
of numerous inflammatory cells in the synovium

Trigger events
Though the above hypothesis of a possible role
of autoimmunity in the etiology and pathogenesis
of RA is generally widely accepted, controversy
continues as regards the trigger events which
initiate the destruction of articular cartilage.
Various possibilities which have been suggested
are as follows:
1. The existence of an infectious agent such as
mycoplasma, Epstein-Barr virus (EBV),
cytomegalovirus (CMV) or rubellavirus, either
locally in the synovial fluid or systemic infection
some time prior to the attack of RA.
2. The possible role of HLA-DR4 and HLA-DR1 in
initiation of immunologic damage.

Immunopathogenesis
In response to antigenic exposure (e.g. infectious agent) in
a genetically predisposed individual (HLA-DR), CD4+ T cells
are activated. These cells elaborate cytokines ( tumour
necrosis factor (TNF)-α, interferon (IF)-γ , interleukin (IL)-1
and IL-6). These cytokines activate endothelial cells, B
lymphocytes and macrophages. Activation of B-cells
releases IgM antibody against IgG (i.e. anti-IgG); this
molecule is termed rheumatoid factor (RF). IgG and IgM
immune complexes trigger inflammatory damage to the
synovium, small blood vessels and collagen.
Activated endothelial cells express adhesion molecules
which stimulate collection of inflammatory cells.
Activation of macrophages releases more cytokines which
cause damage to joint tissues and vascularisation of
cartilage termed pannus formation. Eventually damage and
destruction of bone and cartilage are followed by fibrosis
and ankylosis producing joint deformities.

Clinical manifestations
The disease, which is characterized by
exacerbations and remissions, may involve only
a few joints for brief durations, or it may be
relentlessly progressive and debilitating.
- Fatigue, anorexia, weight loss, and low-grade
fever - systemic manifestations
- The erythrocyte sedimentation rate (ESR)
correlates with the amount of disease activity
- Anemia - associated with a low serum iron level
or low iron-binding capacity is common
(resistant to iron therapy)

 Joint Manifestations - symmetric and polyarticular, any
diarthrodial joint can be involved (most frequently fingers,
hands, wrists, knees, feet). Joint pain and stiffness that lasts
30 minutes and frequently for several hours. The limitation of
joint motion (pain; later it is caused by fibrosis). Subluxation of
the joints.
 Extraarticular manifestations - occur in persons with the RF.
Rheumatoid nodules (granulomatous lesions around small
blood vessels) - tender or nontender, movable or immovable,
and small or large. Vasculitis - ischemic areas - ulcerations in
the lower extremities, around the malleolar areas;
neuropathy; heart, lungs, and gastrointestinal tract, also may
be affected. Episcleritis and scleritis, hematologic
abnormalities, pulmonary disease, cardiac complications,
infection, and Felty’s syndrome (i.e., leukopenia with or
without splenomegaly).

 This is a classic presentation
of acute rheumatoid arthritis. It
is polyarthritic, affects the
proximal interphalangeal joints,
and has produced a fusiform
swelling of the soft tissue. The
lesion is usually symmetrical.
 In this case, there is marked
destruction of the epiphyseal
bone. The joint spaces are
narrowed, because of the
destruction of the articular
cartilage. In severe cases, the
joints become fused by bony
ankylosis.

Metabolic diseases of the joints
Crystal-Induced Arthropathies
Crystal deposition in joints produces arthritis.
Gout
Disease caused by purine disorders
Exchange and reflected increased levels of
uric acid in the blood (hyperuricemia) and
urine (hyperuricuria), the deposition of urates
in joints, kidneys and in soft tissues.
Almost exclusively men aged 35-50 years old

The elevation of uric acid can result
from:
1. Overproduction of purines,
2. Decreased salvage of free purine
bases,
3. Augmented breakdown of nucleic
acids as a result of increased cell
turnover
4. Decreased urinary excretion of uric
acid.

Hyperuricaemia of metabolic origin
This group comprises about 10% cases of gout
which are characterised by overproduction of
uric acid. There is either an accelerated rate of
purine biosynthesis de novo, or an increased
turnover of nucleic acids. The causes of primary
metabolic gout include a number of specific
enzyme defects in purine metabolism which
may be either of unknown cause or are inborn
errors of metabolism.
The secondary metabolic gout is due to either
increased purine biosynthesis or a deficiency of
glucose-6- phosphatase.

Hyperuricaemia of renal origin
About 90% cases of gout are the result of reduced
renal excretion of uric acid. Altered renal excretion
could be due to reduced glomerular filtration of uric
acid, enhanced tubular reabsorption or decreased
secretion.
The causes of gout of renal origin include
diuretictherapy, drug-induced (e.g. aspirin,
pyrazinamide, nicotinic acid, ethambutol and
ethanol), adrenal insufficiency, starvation, diabetic
ketosis, and disorders of parathyroid and thyroid.
Renal disease per se rarely causes secondary
hyperuricaemia such as in polycystic kidney
disease andleads to urate nephropathy.
Reinforced exchange nucleic acids and the purine
bases - myelogenous leukemia, hemoglobinорatia
and psoriasis

Pathogenesis
Hyperuricemia → monosodium urate crystals
precipitate in the joint → initiate an inflammatory
response → destructive changes to the cartilage
and subchondral bone → repeated attacks of
acute arthritis → chronic arthritis → formation of
tophi urici (contain crystalline deposits of
monosodium urate) in the synovium, olecranon
bursa, Achilles tendon, subchondral bone, and
extensor surface of the forearm → chronic
tophaceous gout (degradation of subhondral
departments of bones, ankilosis)

Clinical Manifestations
Typical acute attack is monoarticular (first
metatarsophalangeal joint). Acute gout often
begins at night and may be precipitated by
excessive exercise, certain medications,
foods, alcohol, or dieting. The attack may
last for days or weeks. After the first attack,
it may be months or years before another
attack.

Gouty node (Tophus)

PATHOLOGY OF LIGAMENT -MUSCLE
APPARATUS
Depending on the etiology of the disease of muscle are divided into the
following groups:
 neurogenic (e.g., muscle atrophy after crossing the nerve);
 hereditary-muscular dystrophy (myopathy);
 metabolic-endocrine myopathies (such as in hyperthyroidism);
 toxic-myopathy caused by salts of heavy metals, alcohol, etc.;
 Autoimmune - myasthenia gravis, polymyositis, dermatomyositis;
 infectious-viral and bacterial meningitis myositis
 traumatic-Lysis syndrome long muscle strength;
 tumor and opuholepodobnye muscle diseases.

MYASTHENIA GRAVIS
PATHOGENESIS.
The basic defect is reduction in the number of
available AChRs at the postsynaptic muscle
membrane. In addition, the postsynaptic folds are
flattened. These changes result in decreased
neuromuscular transmission leading to failure to
trigger muscle action potentials and consequent
weakened muscle contraction. The
neuromuscular abnormalities in MG are
mediated by autoimmune response.

About 85-90% patients of MG have anti-
AChR-antibodies in their sera. These
antibodies reduce the number of available
AChRs either by blocking the active sites of
the receptors or by damaging the post-
synaptic muscle membrane in collaboration
with complement. The exact mechanism
how autoimmune response is initiated is
not completely understood but the thymus
appears to play a role in this process.
Majority of patients of MG may have either
thymoma or thymic hyperplasia;
thymectomy is helpful in ameliorating the
condition. The thymus possibly sensitises B
cells to produce anti-AChR antibodies.

 The first signs-oculomotor violations (ptosis,
ophthalmoplegia, diplopia)

MYOPATHY
Myopathy or muscular dystrophy is a
group of primary diseases of striated
muscle, which combined a hereditary
nature of suffering electoral defeat of
muscle groups and progressive
increasing muscle weakness.

Type Inheritance Age at
Onset
Clinical Features Other Systems Course
1.
Duchenn
e’s type
X-linked
recessive
By age
5
Symmetric
weakness; initially
pelvifemoral; later
weakness of girdle
muscles; pseudo-
hypertrophy of calf
muscles
Cardiomegaly;
reduced
intelligence
Progressi
ve; death
by age 20
due to
respirator
y failure
2.
Becker’s
type
X-linked
recessive
By 2nd
decade
Slow progressive
weakness of girdle
muscle (minor variant
of Duchenne’s type)
Cardiomegaly Benign
3.
Myotonic
type
Autosomal
dominant
Any
decade
Slow progressive
weakness and
myotonia of eyelids,
face, neck, distal limb
muscles
Cardiac
conduction
defects; mental
impairment;
cataracts; frontal
baldness;
gonadal atrophy
Benign

4.
Facioscapul
o- humeral
type
Autosom
al
dominant
2nd-
4th
decad
e
Slowly
progressive
weakness of
facial, scapular
and humeral
muscles
Hypertension Benign
5. Limb-
girdle type
Autosom
al
recessive
Early
child-
hood
to
adult
Slowly
progressive
weakness of
shoulder and hip
girdle muscles
Cardiomyopat
hy
Variable
progressi
on
6. Oculo-
pharyngeal
type
Autosom
al
dominant
5th-6th
decad
e
Slowly
progressive
weakness of
extraocular
eyelid, face and
pharyngeal
muscles
— Rarelypro
gressive

PATHOLOGY OF THE MUSCULOSKELETAL SYSTEM

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