General Pathology 601 for Dental Students
Musculoskeletal System
Part II: Diseases of Joints and Skeletal Muscles
(Robbins Basic Pathology, 7th edition, p. 771)
N. R. Ghatak, MD, Sanger Hall, 5th Floor; (804) 828-9735; nrghatak@hsc.vcu.edu
The following is a brief outline (For details read text book).
Joint Diseases
Any inflammatory condition of joints is called arthritis.
Types:
1.
Rheumatoid arthritis
2.
Osteoarthritis (Degenerative joint disease)
3.
Gout (crystal arthropathy)
4.
Bacterial and viral Infections
I.
Rheumatoid arthritis (RA): Affects joints and many other organs of the body
such as skin, muscle, blood vessels, lungs. It is a relatively common condition
with particular predilection for women, about 3-5 times more common than in
men. The disease is initiated in a genetically predisposed individual by
activation of helper T-cells which produce cytokines and activate
macrophages and other cells in the joint space resulting in inflammation and
tissue damage. They also activate B-cells with production of antibodies
causing further damage of the joints. What activates the CD+ T-cells is not
known. RA affects both small and large joints including TMJ and vertebra.
Pathology: The initial changes are seen in the synovium and consist of
lymphocytic and monocytic infiltrate followed by proliferations of synovial cells
and blood vessels forming villous-like structures containing lymphoid
collections. Vascular granulation tissue (pannus) invades and destroys the
articular cartilage causing fibrosis (ankylosis) and deformity of the joints.
Clinical features: It starts slowly usually in the small joints of hands with pain
subsequently affects the joints and causes progressive deformity to a variable
extent in different patients. In some patients various extra-articular
manifestations are seen. The course of the disease is variable with active
and inactive phases for many years eventually resulting in crippling deformity
in some patients. There are effective treatments for RA.
II.
Osteoarthritis: It is the most common type of joint disease and is usually
seen in older individuals. It may be seen in younger people as a result of prior
trauma. In most cases the weight-bearing joints (knee and the hip) are
involved. The vertebral and metacarpal joints are also involved.
Clinical features: Pain and limitation of movement are the major symptoms.
This is the commonest indication for joint replacement surgery.
Pathology: The articular cartilage is the primary site of lesion. The cartilage
becomes friable with splitting and fissures with eventual fragmentation and
loss. Fragments of cartilage and bone in the joint space are called “joint
mice”. Loss of cartilage makes the bone surfaces to come in direct contact
causing various degenerative bone changes including subchondral sclerosis
and cyst formation.
III.
Gout (crystal arthropathy): Gout is caused by overproduction and
precipitation of monosodium urates in the joint space causing mechanical
irritation and inflammatory changes. Majority of the patients are male with
high blood uric acid level (>7 mg/dl) due to an inborn abnormality of purine
metabolism. Some patients may develop gout due to massive destruction of
cancer cells such as treated leukemia with deposition of uric acid crystals
(secondary gout). Crystals other than urates are also known to cause similar
manifestations.
Clinical features: The major symptom is severe pain usually in the joints of
the big toe and sometimes in other sites. The synovial fluid contain urate
crystals which can be helpful in the diagnosis. Gout can be effectively treated
with drugs that lower the blood uric acid levels.
Pathology: Deposition of crystals evokes a granulomatous inflammatory
reaction in the joints and other tissues forming tophus. Kidneys may also be
involved leading to impaired renal function (gouty nephropathy).
Infectious arthritis: Suppurative - streptococcus, staphylococci, and other
pus-forming bacteria.
Non-suppurative: TB, lyme disease, virus.
Muscle Diseases
The functional and structural integrity of skeletal muscle depend on its nerve supply.
Each motor neuron in the spinal cord or brain stem supplies many muscle fibers,
usually several hundreds in large muscles. The motor neuron, its axon together with
the muscle fibers supplied by it are known as a motor unit. With certain enzyme
histochemical staining techniques, two types of fibers are recognized in human
skeletal muscle.
Type 1: These fibers are rich in oxidative enzymes and stain darkly by NADHtetrazolium reductase technique (NADH-TR).
Type 2: These fibers are low in oxidative enzymes.
The diseases of muscle are classified into two broad categories:
Neurogenic or denervation atrophy which means that the primary lesion is in the
nervous system either in the cell body of the lower motor neuron or its axons
comprising the peripheral nerves.
Myopathy refers to the remaining disorders and includes various forms of
dystrophic, congenital, inflammatory, toxic and other types of disorders.
NEUROGENIC
There is a large number of conditions that affect lower motor neurons or their axons
such as:
Amyotrophic Lateral Sclerosis in adults.
Spinal muscular atrophy usually in children.
Poliomyelitis - now rare.
Peripheral neuropathy of various types.
Histologic Changes:
The denervated myofibers become smaller and more angular but otherwise remain
intact. In progressive disease large group atrophy results.
MYOPATHY:
In many disorders in this category, the pathologic changes in the muscle are
nonspecific. However, these changes when analyzed in light of the clinical
manifestations are usually helpful in the diagnosis of these disorders. Some of the
common myopathic changes includes necrosis, phagocytosis, regeneration, random
variation of fiber size, hypertrophy, fiber splitting, vacuolation, etc.
Muscular Dystrophies: In this group of familial disorders, muscle involvement is the
predominant feature. They are usually classified on the basis of mode of inheritance,
age of onset, pattern of involvement, etc. There are many types of muscular
dystrophy.
Duchenne Muscular Dystrophy:
This is the most severe type of muscular dystrophy and is transmitted as an X-linked
recessive trait. Sporadic cases are also seen. The disease begins in early childhood
and progresses relentlessly. The patients usually die during the second or third
decades. The myocardium is also involved in most cases. Duchenne dystrophy is
due to a mutation at X p 21, a specific locus on the short arm of X chromosome. This
gene is considered to be the largest in the entire human genome and its product is
named "dystrophin." This protein is located in the membrane of muscle cells and can
be visualized by immunostaining. Duchenne dystrophy patients lacks dystrophin. In
some other X-linked muscle dystrophies such as Becker's Dystrophy, there is severe
reduction of dystrophin.
The histologic findings vary with the duration of the disease. In the early stages,
there is focal necrosis, phagocytosis and regeneration of myofibers. Subsequently,
there is marked variation of the fiber size with increased endomysial fibrosis. Central
displacement of sarcolemmal nuclei are common. Eventually, the skeletal muscles
are almost totally replaced by fibroadipose tissue.
Inflammatory Myopathy:
This group of disorders occurs at all ages and includes two major types:
Polymyositis and Dermatomyositis. Several subtypes are recognized on the basis of
age, clinical manifestations and other associated conditions. The pathologic changes
in all types are basically similar. In early and active stages of the disease, necrosis
of myofibers and inflammatory mononuclear cellular infiltrate in the endo and
perimysium are characteristic features. Other nonspecific myopathic changes may
be present at different stages of the disease.
Metabolic and Endocrine Myopathies:
Muscle weakness may be seen in association with certain endocrine disorders.
Pathologic changes in these conditions when present, are mild and non-specific.
Several metabolic disorders are recognized in which skeletal muscles are affected.
Glycogen storage diseases are important in this category. Several types of glycogen
storage disorders are known to involve skeletal muscle.
Congenital Myopathy:
Several types of disorders are included in this class. They are distinguished from
one another by characteristic morphologic appearance. Some of these are inherited.
They usually share the common manifestation of infantile hypotonia (Floppy Baby)
and slowly progressive or nonprogressive muscular weakness. Some of these
conditions cause severe generalized weakness with fatal outcome during
pregnancy.
Myasthenia Gravis:
This is an autoimmune disorder of the postsynaptic side of the neuromuscular
junction due to blockage of the acetylcholine receptor sites by antibodies.
Morphologic changes consist of reduction of acetylcholine receptor sites and
simplification (loss of foldings) of the myoneural junction. Hyperplasia and/or tumors
of the thymus are often seen in patients with this disorder.
Tumors:
Tumors arising from skeletal muscle are called rhabdomyosarcoma. They are
usually in children in different parts of the body.