pathology of the musculoskeletal muscles (elaborate)

PATHOLOGY OF MUSCULOSKELETA

L SYSTEM

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I. DISEASES OF THE BONES AND

JOINTS



Healing of fracture by callus formation depends upon some clinical considerations whether the fracture is: traumatic (in previously normal bone) pathological (in previously diseased bone)

1.TRAUMATIC DISEASES.FRACTURE HEALING



complete or incomplete like green-stick fracture

simple (closed) - overlying tissue is intact

comminuted (splintering of bone or displacing )

compound (communicating to skin surface).



Primary union of fractures occurs in a few special situations when the ends of fracture are approximated as is done by application of compression clamps. In these cases, bony union takes place with formation of medullary callus without periosteal callus formation. The patient can be made ambulatory early but there is more extensive bone necrosis and slow healing.



Secondary union is the more common process of fracture healing.

3 headings:1) Procallus formation2) Osseous callus formation3) Remodelling



Procallus formation1. Haematoma forms due to bleeding from torn blood vessels, filling the area surrounding the fracture. 2. Local inflammatory response occurs at the site of injury with exudation of fibrin, polymorphs and macrophages. The macrophages clear away the fibrin, red blood cells, inflammatory exudate and debris. Fragments of necrosed bone are scavenged by macrophages and osteoclasts.



3. Ingrowth of granulation tissue begins with neovascularisation and proliferation of mesenchymal cells from periosteum and endosteum. A soft tissue callus is thus formed which joins the ends of fractured bone without much strength.



4. Callus composed of woven bone and cartilage

Starts within the first few days. The cells of inner layer of the periosteum have osteogenic potential and lay down collagen as well as osteoid matrix in the granulation tissue. The osteoid undergoes calcification and is called woven bone callus. A much wider zone over the cortex on either side of fractured ends is covered by the woven bone callus and united to bridge the gap between the ends, giving spindle shaped or fusiform appearance to the union.



In poorly immobilised fractures (e.g. fracture ribs), the subperiosteal osteoblasts may form cartilage at the fracture site. At times, callus is composed of woven bone as well as cartilage, temporarily immobilising the bone ends. This stage is called provisional callus or procallus formation and is arbitrarily divided into external,

intermediate and internal procallus.



II. OSSEOUS CALLUS FORMATION

The procallus acts as scaffolding on which osseous callus composed of lamellar bone is formed. The woven bone is cleared away by incoming and the calcified cartilage disintegrates.

In their place, newly-formed blood vessels and osteoblasts invade, laying down osteoid which is calcified and lamellar bone is formed by developing Haversian system concentrically around the blood vessels.



III. REMODELLINGDuring the formation of lamellar

bone, osteoblastic laying and osteoclastic removal are taking place remodelling the united bone ends, which after sometime, is indistinguishable from normal bone.

The external callus is cleared away, compact bone (cortex) is formed in place of intermediate callus and the bone marrow cavity develops in internal callus.



COMPLICATIONS1. Fibrous union may result instead of osseous union if the immobilisation of fractured bone is not done. Occasionally, a false joint may develop at the fracture site (pseudoarthrosis). 2. Non-union may result if some soft tissue is interposed between the fractured ends.3. Delayed union may occur from causes of delayed wound healing in general such as infection, inadequate blood supply, poor nutrition, movement and old age.



Fracture healing A, Haematoma formation and local inflammatory response at the fracture site. B, Ingrowth of granulation tissue with formation of soft tissue callus. C, Formation of procallus composed of woven bone and cartilage with its characteristic fusiform appearance and having 3 arbitrary components—external, intermediate and internal callus. D, Formation of osseous callus composed of lamellar bone following clearance of woven bone and cartilage. E, Remodelled bone ends; the external callus cleared away. Intermediate callus converted into lamellar bone and internal callus developing bone marrow cavity.

Response of bone to fracture. Osteoblasts arise from pluripotent progenitor cells in the periosteum and granulation tissue. They produce woven bone, resulting in a bony callus that stabilizes the fracture site.



Contrast the morphology of the original lamellar bone to that of woven bone. Woven bone contains many more osteocytes. The necrotic lamellar bone and the reactive woven bone will be removed by osteoclasts and replaced by new, mature lamellar bone. This process is called remodeling and takes place over months to years.



Healed fracture. Femur recovered by archaeologists from a burial about 200 years ago. There has been a fracture, which has healed with a great deal of callus formation.



2.INFLAMMATORY DISEASES



RHEUMATOID ARTHRITIS

Reumatoid arthritis is a chronic systemic inflammatory disorder that may affect many tissues and organs – skin, blood vessels, heart, lungs and muscles – but principally attacks the joints, producing a nonsuppurative proliferative synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints.



ETIOPATHOGENESIS Present concept on etiology and pathogenesis proposes that RA occurs in an

immunogenetically predisposed individual to the effect of microbial agents acting as trigger antigen.

The role of superantigens which are produced by several microorganisms with capacity to bind to HLADR molecules (MHC-II region) has also emerged.



MORPHOLOGIC FEATURESARTICULAR LESIONS

RA involves first the small joints of hands and feet and then symmetrically affects the joints of wrists, elbows, ankles and knees. The proximal interphalangeal and metacarpophalangeal joints are affected most severely. Frequently cervical spine is involved but lumbar spine is spared.



HISTOLOGICALLYThe characteristic feature is diffuse proliferative synovitis with formation of pannus. Initially the synovium becomes grossly edematous, thickned and hyperplastic, transforming its smooth contour to one covered by delicate and bulbousfronds. Numerous folds of large villi of synovium.The characteristic histologic features include:

1. Infiltration of synovial stroma by a dence perivascular inflammatory infiltrate composed of lymphoid follicles, plasma cells, and macrophages filling the synovial stroma;2. Increased vascularity owing to vasodilation and angiogenesis, with superficial hemosiderin deposits 3. Aggregation of organizing fibrin covering portions of the synovium and floating in the joint space as rice bodies; Uploaded by: http://mbbshelp.com


4. Accumulation of neutrophils in the synovial fluid and along the surface of synovium but usually not deep in the synovial stroma;

5. Osteoclastic activity in underlying bone, allowing the synovium to penetrate into the boneforming juxta-articular erosions, subchondrial cysts and osteoporosis (increased of porosity of the bones resulting from a reduction in bone mass); muscle frequently accompanies the arthritis.



6. Pannus formation – the pannus is a fibrocellular mass of synovium and synovial stroma consisting of inflammatory cells, granulomatous tissue, and fibroblasts, which causes erosion of the underlying cartilage. In time, after the cartilage has been destroyed, the pannus bridges the apposing bones forming a fibrous ankylosis (loss of joint function). Inflammation in the tendons, ligaments and occasionally the adjacent skeletal muscle frequently accompanies the arthritis.



EXTRA – ARTICULAR LESIONS

Nonspecific inflammatory changes are seen in the blood vessels (acute vasculitis), lungs, pleura, pericardium, myocardium, lymph nodes, peripheral nerves and eyes. Rheumatoid nodules are particularly found in the subcutaneous tissue over pressure points such as the elbows, occiput and sacrum. The centre of these nodules consists of an area of fibrinoid necrosis and cellular debris, surrounded by several layers of palisading large epithelioid cells, and peripherally there are numerous lymphocytes, plasma cells and macrophages. Similar nodules may be found in the lung parenchyma, pleura, heart valves, myocardium and other internal organs.



FORMS OF RA1. Juvenile RA found in adolescent patients under 16 years of age is characterised by acute onset of fever and predominant involvement of knees and ankles. Pathologic changes are similar but RF is rarely present.2. Felty’s syndrome consists of polyarticular RA associated with splenomegaly and hypersplenism and consequent haematologic derangements. 3. Ankylosing spondylitis or rheumatoid

spondylitis is rheumatoid involvement of the spine, particularly sacroiliac joints, in young male patients. The condition has a strong HLA-B27 association and may have associated inflammatory diseases such as inflammatory bowel disease, anterior uveitis and Reiter’s syndrome.Uploaded by: http://mbbshelp.com


In this case, there is marked destruction of the epiphyseal bone. The joint spaces are narrowed, because of the destruction of the articular cartilage.



This specimen illustrates the inflamed synovium characteristic of acute rheumatoid arthritis. The prominent, hyperemic synovial membrane on which strands of fibrin are evident.



This image emphasizes the inflammatory nature of rheumatoid arthritis. In this section of reactive synovium, lymphocytes, plasma cells, and macrophages expand the synovium. The vascularity is increased. The synovial membrane is also hyperplastic. The inflammatory infiltrate may organize into distinct lymphoid nodules.

RANK-L, released from the surface of lymphocytes by metalloproteinases, stimulates osteoclastogenesis. The osteoclasts are important players in the destruction of the subchondral bone in rheumatoid arthritis. Inflammatory mediators released from the pannus stimulate osteoclast activity, which results in erosion and destruction of the subchondral bone. As well, the pannus isolates the articular cartilage from the synovial fluid, resulting in degeneration of articular cartilage.

Rheumatoid nodules consist of a central zone of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes and numerous lymphocytes and plasma cells. Rheumatoid nodules occur in approximately 20% to 25% of patients with definitive or classic rheumatoid arthritis. Nodules generally are associated with severe articular and systemic disease and with high titers of rheumatoid factor.

PannusUploaded by: http://mbbshelp.com


SUPPURATIVE ARTHRITIS Infectious or suppurative arthritis is invariably

an acute inflammatory involvement of the joint. Bacteria usually reach the joint space from: the blood stream but other routes of infection by direct contamination of an open wound lymphatic spread.

Immunocompromised and debilitated patients are increasingly susceptible to suppurative arthritis.

The common causative organisms are gonococci, meningococci, pneumococci, staphylococci, streptococci, H. influenzae and gram-negative bacilli.



Clinically, the patients present with manifestations of any local infection such as redness, swelling, pain and joint effusion. Constitutional symptoms such as fever, neutrophilic leukocytosis and raised ESR are generally associated.

The hematogenous infections joint involvement is more often monoarticular rather than polyarticular. The large joints of lower extremities such as the knee, hip and ankle, shoulder and sternoclavicular joints are particularly favoured sites.

The process begins with hyperemia, synovial swelling and infiltration by polymorphonuclear and mononuclear leukocytes along with development of effusion in the joint space. There may be formation of inflammatory granulation tissue and onset of fibrous adhesions between the opposing articular surfaces resulting in permanent ankylosis



3.METABOLIC DISEASES



HYPERPARATHYROIDISM

Hyperparathyroidism of primary or secondary type results in oversecretion of parathyroid hormone which causes increased osteoclastic resorption of the bone (initiate the release of mediators that stimulate osteoclasts activity). Severe and prolonged hyperparathyroidism results in osteitis fibrosa cystica. The lesion is generally induced as a manifestation of primary hyperparathyroidism (usually an adenoma of the parathyroid gland), and less frequently, as a result of secondary hyperparathyroidism such as in chronic renal failure (renalosteodystrophy). Secondary hyperparathyroidism is commonly caused by prolonged states of hypocalcemia resulting in compensatory hypersecretion of parathyroid hormone.



The clinical manifestations: susceptibility to fracture, skeletal deformities, joint pains and dysfunctions as a result of deranged weight bearing. The bony changes may disappear after cure of primary hyperparathyroidism such as removal of functioning adenoma.

The chief biochemical abnormality of excessive parathyroid hormone is hypercalcaemia, hypophosphataemia and hypercalciuria.



MORPHOLOGIC FEATURES

The bone lesions of primary hyperparathyroidism affect the long bones more severely and may range from minor degree of generalised bone rarefaction to prominent areas of bone destruction with cyst formation or brown tumours.



Grossly, there are focal areas of erosion of cortical bone and loss of lamina dura at the roots of teeth.

Histologically, the following sequential changes appear over a period of time:Earliest change is demineralisation and increased bone resorption beginning at the subperiosteal and endosteal surface of the cortex and then spreading to the trabecular bone. There is replacement of bone and bone marrow by fibrosis coupled with increased number of bizarreosteoclasts at the surfaces of moth-eaten trabeculae and cortex (osteitis fibrosa).



As a result of increased resorption, microfractures and microhaemorrhages occur in the marrow cavity leading to development of cysts (osteitis fibrosa cystica).

Haemosiderin-laden macrophages and multinucleate giant cells appear at the areas of haemorrhages producing an appearance termed as ‘brown tumour’ or ‘reparative giant cell granuloma of hyperparathyroidism’



Osteitis fibrosa cystica



OSTEOARTHROSIS Osteoarthritis (OA), also called osteoarthrosis or degenerative joint disease (DJD), is the most common form of chronic disorder of synovial joints.

It is characterised by progressive degenerative changes in the articular cartilages over the years, particularly in weight-bearing joints.



TYPES AND PATHOGENESISOA occurs in 2 clinical forms—primary and secondary. Primary OA occurs in the elderly, more commonly in women than in men. Little is known about the etiology and pathogenesis of primary OA. The condition may be regarded as a reward of longevity. Probably, wear and tear with repeated minor trauma, heredity, obesity, aging per se, all contribute to focal degenerative changes in the articular cartilage of the joints. 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.



MORPHOLOGIC FEATURESThe weight-bearing joints such as hips, knee and vertebrae are most commonly involved but interphalangeal joints of fingers may also be affected. The pathologic changes occur in the articular cartilages, adjacent bones and synovium:1. Articular cartilages. The regressive changes are most marked in the weight-bearing regions of articular cartilages. There is loss of cartilaginous matrix (proteoglycans) resulting in progressive loss of normal metachromasia. This is followed by focal loss of chondrocytes, and at other places, proliferation of chondrocytes forming clusters. Further progression of the process causes loosening, flaking and fissuring of the articular cartilage resulting in breaking off of pieces of cartilage exposing subchondral bone.



2. Bone. The denuded subchondral bone appears like polished ivory. There is death of superficial osteocytes and increased osteoclastic activity causing rarefaction, microcyst formation and occasionally microfractures of the subjacent bone. These changes result in remodelling of bone and changes in the shape of joint surface leading to flattening and mushroom-like appearance of the articular end of the bone.



The margins of the joints respond to cartilage damage by osteophyte or spur formation. These are cartilaginous outgrowths at the joint margins which later get ossified. Osteophytes give the appearance of lipping of the affected joint. Loosened and fragmented osteophytes may form free ‘joint mice’ or loose bodies.



3. Synovium. Initially, there are no pathologic changes in the synovium but in advanced cases there is low-grade chronic synovitis and villous hypertrophy. There may be some amount of synovial effusion associated with chronic synovitis.



The manifestations of OA are most conspicuous in large joints such as hips, knee and back. However, the pattern of joint involvement may be related to the type of physical activity such as ballet-dancers’ toes, karate fingers etc. Minor degree of OA may remain asymptomatic. In symptomatic cases, clinical manifestations are joint stiffness, diminished mobility, discomfort and pain. The symptoms are more prominent on waking up from bed in the morning.



Degenerative changes in the interphalangeal joints lead to hard bony and painless enlargements in the form of nodules at the base of terminal phalanx called Heberden’s nodes. These nodes are more common in females and heredity seems to play a role. In the spine, osteophytes of OA may cause compression of cervical and lumbar nerve root with pain, muscle spasms and neurologic abnormalities.



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.



GOUTGout is a disorder of purine metabolism

manifested by the following features, occurring singly or in combination:

1. Increased serum uric acid concentration (hyperuricaemia).

2. Recurrent attacks of characteristic type of acute arthritis in which crystals of monosodium urate monohydrate may be demonstrable in the leucocytes present in the synovial fluid.

3. Aggregated deposits of monosodium urate monohydrate (tophi) in and around the joints of the extremities.



The disease usually begins in 3rd decade of life and affects men more often than women. A family history of gout is present in a fairly large proportion of cases indicating role of inheritance in hyperuricaemia. Clinically, the natural history of gout comprises 4 stages:

asymptomatic hyperuricaemiaacute gouty arthritis asymptomatic intervals of intercritical periods chronic tophaceous stage. In addition, gout nephropathy and urate

nephrolithiasis may occur.Uploaded by: http://mbbshelp.com


TYPESHyperuricaemia and gout may be classified into 2 types: metabolic and

renal, each of which may be primary or secondary.

Primary refers to cases in which the underlying biochemical defect causing hyperuricaemia is not known, while secondary denotes cases with known causes of hyperuricaemia.



MORPHOLOGIC FEATURESThe pathologic manifestations of gout include: 1. Acute gouty arthritis. This stage is characterised by acute synovitis triggered by precipitation of sufficient amount of needle-shaped crystals of monosodium urate from serum or synovial fluid. There is joint effusion containing numerous polymorphs, macrophages and microcrystals of urates.



The mechanism of acute inflammation appears to include phagocytosis of crystals by leucocytes, activation of the kallikrein system, activation of the complement system and urate-mediated disruption of lysosomes within the leucocytes leading to release of lysosomal products in the joint effusion. Acute gouty arthritis is predominantly a disease of lower extremities, affecting most commonly great toe. Other joints affected, in order of decreasing frequency, are: the instep, ankles, heels, knees, wrists, fingers and elbows.



2. Chronic tophaceous arthritis. Recurrent attacks of acute gouty arthritis lead to progressive evolution into chronic arthritis. The deposits of urate encrust the articular cartilage. There is synovial proliferation, pannus formation and progressive destruction of articular cartilage and subchondral bone. Deposits of urates in the form of tophi may be found in the periarticular tissues.



3. Tophi in soft tissue. A tophus (meaning ‘a porous stone’) is a mass of urates measuring a few millimeters toa few centimeters in diameter. Tophi may be located in the periarticular tissues as well as subcutaneously such as on the hands and feet. Tophi are surrounded by inflammatory reaction consisting of macrophages, lymphocytes, fibroblasts and foreign body giant cells.Uploaded by: http://mbbshelp.com


4. Renal lesions. Chronic gouty arthritis frequently involves the kidneys. Three types of renal lesions are described in the kidneys:1) Acute urate nephropathy is attributed to the intratubular deposition of monosodium urate crystals resulting in acute obstructive uropathy.2) Chronic urate nephropathy refers to the deposition of urate crystals in the renal interstitial tissue.3) Uric acid nephrolithiasis is related to hyperuricaemia resulting in hyperuricaciduria.



This is an example of chronic gout with gouty tophi. There are numerous asymmetrical, periarticular swellings. These represent inflammatory reaction to sodium urate crystals. The lesion on the fifth digit of the left hand has ulcerated, revealing the white crystals. Tophi appear only after repeated attacks of gout in patients whose hyperuricemia has not been treated.

Histologically, tophi consist of crystals that are surrounded by macrophages, lymphocytes, and often foreign body giant cells. In routinely processed sections, the crystals are removed during processing.

Gouty tophiUploaded by: http://mbbshelp.com


Knee joint in gout. The knee joint has been

opened to show the heavy deposition of urate crystals in the

articular cartilage.



4.DISPLASTIC DISEASES



Fibrous dysplasiaIt is a benign condition, possibly of developmental origin, characterised by the presence of localised area of replacement of bone by fibrous connective tissue with a characteristic whorled pattern and containing trabeculae of woven bone. Radiologically, the typical focus of fibrous dysplasia has well demarcated ground-glass appearance. Three types of fibrous dysplasia are distinguished — monostotic, polyostotic, and Albright syndrome. The spectrum of phenotype of the disease is due to activating mutation in GNAS1 gene, which encodes for α-subunits of the stimulatory G-protein, GSα.



Monostotic fibrous dysplasia

Monostotic fibrous dysplasia affects a solitary bone and is the most common type, comprising about 70% of all cases.

The condition affects either sex and most patients are between 20 and 30 years of age.

The bones most often affected, in descending order of frequency, are: ribs, craniofacial bones (especially maxilla), femur, tibia and humerus. The condition generally remains asymptomatic and is discovered incidentally, but infrequently may produce tumour-like enlargement of the affected bone.



POLYOSTOTIC FIBROUS DYSPLASIA

Polyostotic form of fibrous dysplasia affecting several bones constitutes about 25% of all cases. Both sexes are affected equally but the lesions appear at a relatively earlier age than the monostotic form. Most frequently affected bones are: craniofacial, ribs, vertebrae and long bones of the limbs. Approximately a quarter of cases with polyostotic form have more than half of the skeleton involved by disease. The lesions may affect one side of the body or may be distributed segmentally in a limb. Spontaneous fractures and skeletal deformities occur in childhood polyostotic form of the disease. Uploaded by: http://mbbshelp.com


ALBRIGHT SYNDROMEAlso called McCune-Albright syndrome, this is a form of polyostotic fibrous dysplasia associated with endocrine dysfunctions and accounts for less than 5% of all cases. Unlike monostotic and polyostotic varieties, Albright syndrome is more common in females. The syndrome is characterised by polyostotic bone lesions, skin pigmentation (cafe-au-lait macular spots) and sexual precocity, and infrequently other endocrinopathies.



MORPHOLOGIC FEATURESAll forms of fibrous dysplasia have an identical pathologic appearance.Grossly, the lesions appear as sharply-demarcated, localised defects measuring 2-5 cm in diameter, present within the cancellous bone, having thin and smooth overlying cortex. The epiphyseal cartilages are generally spared in the monostotic form but involved in the polyostotic form of disease. Cut section of the lesion shows replacement of normal cancellous bone of the marrow cavity by gritty, grey-pink, rubbery soft tissue which may have areas of haemorrhages, myxoid change and cyst formation.

HISTOLOGICALLYThe lesions of fibrous dysplasia have characteristic benign-looking fibroblastic tissue arranged in a loose, whorled pattern in which there are irregular and curved trabeculae of woven (non-lamellar) bone in the form fish-hook appearance or Chinese letter shapes. Characteristically, there are no osteoblasts rimming then trabeculae of the bone, suggesting a maturation defect in the bone. Rarely, malignant change may occur in fibrous dysplasia, most often an osteogenic sarcoma.



Fibrous dysplasiaUploaded by: http://mbbshelp.com


Fibrous dysplasia



CHONDROMATOSIS OF JOINTS

Synovial chonromatosis is an uncommon condition of unknown cause characterized by the occurrence of multiple foci of cartilaginous metaplasia in the synovial membrane.

The cartilage appears as nodules that may undergo ossification and may become detached into the joint cavity as “loose bodies”. The knee is commonly affected, with of pain, swelling, limitation of movement, and intermittent locking. Osteoarthrosis may result.



II.DIASEASES OF THE SKELETAL

MUSCLES



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

myositistraumatic-Lysis syndrome long muscle

strength;tumor muscle diseases.

MUSCULAR DYSTROPHIES

Muscular dystrophies are a group of genetically-inherited primary muscle diseases, having in common, progressive andunremitting muscular weakness. Six major forms of muscular dystrophies are described: Duchenne’s, Becker’s,

myotonic, facio-scapulohumeral, limb-girdle and oculopharyngeal type.

Each type of muscular dystrophy is a distinct entity having differences in inheritance pattern, age at onset, clinical features, other organ system involvements and clinical course. However, in general, muscular dystrophies manifest in childhood or in early adulthood. Family history of neuromuscular disease is elicited in many cases.Uploaded by: http://mbbshelp.com


CONTRASTING FEATURES OF MUSCULAR DYSTROPHIES

Type Inheritance

Age at Onset

Clinical Features

Other Systems

Course

1. Duchenne’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

Progressive; death by age 20 due to respiratory 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 limbmuscles

Cardiac conduction defects; mental impairment; cataracts; frontal baldness;gonadal atrophy

Benign

4. Facioscapulo- humeral type

Autosomal dominant

2nd-4th decade

Slowly progressive weakness of facial, scapular and humeral muscles

Hypertension Benign

5. Limb-girdle type

Autosomal recessive

Early childhood to adult

Slowly progressive weakness of shoulder and hip girdle muscles

Cardiomyopathy

Variable progression

6. Oculo- pharyngeal type

Autosomal dominant

5th-6th decade

Slowly progressive weakness of extraocular eyelid, face and pharyngeal muscles

— Rarelyprogressive



MORPHOLOGIC FEATURESCommon to all forms of muscular dystrophies are muscle fibre necrosis, regenerative activity, replacement by interstitial fibrosis and adipose tissue.1)variation in fiber size (diameter) due to presence of both small and giant fibers, some-times with fiber splitting; 2)increased numbers internalized nuclei (beyond the normal range of 3% to 5%); 3)degeneration, necrosis and phagocytosis of muscle fibers; 4)regeneration of muscle fibers; 5)proliferation of endomysial connective tissue.



Histopathology of gastrocnemius muscle from patient who died of Duchenne myopathy. Cross section of muscle shows extensive replacement of muscle fibers by adipose cells. Uploaded by: http://mbbshelp.com

MYOSITIS (INFLAMMATION OF MUSCLE)

A large number of infectious agents affect muscle, leading to myositis.

Causes of myositis.I.Infectious diseases: 1.Bacterial: 1)local infection with pyogenic bacteria,

usually secondary to trauma; 2)bacteremic myositis (in infective

endocarditis, typhoid fever, etc.); 3)gas gangrene. 2.Viral (coxsackievirus infection, influenza, HIV

infection, etc.). 3.Parasitic (trichinosis, toxoplasmosis, cysticercosis). 4.Exotoxic – Diphtheria.


II.Immune diseases: 1.Polymyositis-dermatomyositis. 2.Systemic lupus erithematosus. 3.Progressive systemic sclerosis. 4.Sarcoidosis. 5.Myastenia gravis (associated with anti-

striated muscle antibody in serum).III.Other causes: 1.Radiation. 2.Ischemia. 3.Myositis ossificans (is characterized by bone

formation in the involved muscle). Uploaded by: http://mbbshelp.com

Classification of myositis. I.Course: 1)acute, b)chronic. II.Morphology: 1)serous, 2)purulent, 3)granulomatous.Morphology. Grossly – muscle become soft, flabby and

edematous. Microscopically – hyperemia, edema,

inflammatory infiltration with leukocytes, lymphocytes, plasma cells etc., foci of

necrosis.Uploaded by: http://mbbshelp.com

MYASTHENIA GRAVIS

Myasthenia gravis (MG) is a neuromuscular disorder of autoimmune origin in which the acetylcholine receptors (AChR) in the motor end-plates of the muscles are damaged.

The term ‘myasthenia’ means ‘muscular weakness’ and ‘gravis’ implies ‘serious’; thus both together denote the clinical characteristics of the disease.


MG may be found at any age but adult women are affected more often than adult men in the ratio of 3:2.

The condition presents clinically with muscular weakness and fatiguability, initially in the ocular musculature but later spreads to involve the trunk and limbs.

There is about 10% mortality in MG which is due to severe generalised disease and involvement of respiratory muscles.

Several other autoimmune diseases have been found associated with MG such as autoimmune thyroiditis, rheumatoid arthritis, SLE, pernicious anaemia and collagenvascular diseases. Uploaded by: http://mbbshelp.com

MORPHOLOGIC FEATURESGrossly, the muscles appear normal until late in the course of disease when they become wasted.By light microscopy, a few clumps of lymphocytes may be found around small blood vessels. Degenerating muscle fibres are present in half the cases.Electron microscopy reveals reduction in synaptic area of the motor axons due to flattening or simplification of postsynaptic folds. The number of AChRs is greatly reduced. By immunocytochemistry combined with electron microscopy, it is possible to demonstrate the complex of IgG and complement at the neuromuscularjunctions.


NEOPLASMS OF MUSCLE

1.Rhabdomyoma – benign tumor, is distinctly rare.

2.Rhabdomyosarcoma – malignant tumor; histologically subclassified into the embrional, alveolar and pleomorphic variants.

From connective tissue stroma of muscle may arise: fibroma and desmoid (benign tumors from fibrous tissue), hemangioma (benign tumor from blood vessels).


Rhabdomyoma

RhabdomyosarcomaUploaded by: http://mbbshelp.com

Rhabdomyosarcoma, AlveolarUploaded by: http://mbbshelp.com

Embryonal RhabdomyosarcomaUploaded by: http://mbbshelp.com

TUBERCULOSIS OF BONES AND

JOINTS


TUBERCULOUS OSTEOMYELITIS

The tubercle bacilli, M. tuberculosis, reach the bone marrow and synovium most commonly by hematogenous dissemination from infection elsewhere, usually the lungs, and infrequently by direct extension from the pulmonary or gastrointestinal tuberculosis.

The disease affects adolescents and young adults more often. Most frequently involved are the spine and bones of extremities.


The bone lesions in tuberculosis have the same general histologic appearance as in tuberculosis elsewhere and consist of central caseous necrosis surrounded by tuberculous granulation tissue.

The tuberculous lesions appear as a focus of bone destruction and replacement of the affected tissue by caseous material and formation of multiple discharging sinuses through the soft tissues and skin. Involvement of joint spaces and intervertebral disc are frequent.


Tuberculosis of the spine, Pott’s disease, often commences in the vertebral body and may be associated with compression fractures and destruction of intervertebral discs, producing permanent damage and paraplegia.

Extension of caseous material along with pus from the lumbar vertebrae to the sheaths of psoas muscle produces psoas abscess or lumbar cold abscess. The cold abscess may burst through the skin and form sinus. Long-standing cases may develop systemic amyloidosis.


Tuberculosis Pott'sfracture of the

vertebraeTuberculous psoas abscess.

TUBERCULOUS ARTHRITIS

Tuberculous infection of the joints results most commonly from hematogenous dissemination of the organisms from pulmonary or other focus of infection. Another route of infection is direct spread from tuberculous osteomyelitis close to the joint.

The disease may occur in adults but is found more commonly in children.

Tuberculous involvement of the joints is usually monoarticular type but tends to be more destructive than the suppurative arthritis. Most commonly involved sites are the spine, hip joint and knees, and less often other joints are affected. Tuberculosis of the spine is termed Pott’s disease or tuberculous spondylitis.


Grossly, the affected articular surface shows deposition of grey-yellow exudates and occasionally tubercles are present. The joint space may contain tiny grey-white loose bodies and excessive amount of fluid.

Histologically, the synovium is studded with solitary or confluent caseating tubercles. The underlying articular cartilage and bone may be involved by extension of tuberculous granulation tissue and case necrosis.


VASCULITIDES


Systemic damage of blood vessels

CLASSIFICATION

According to the type of inflammation: a destructive, destructive - productive, productive

In the depths of defeat: endo vasculitis, mesovasculitis, endo - meso vasculitis, panvasculitis, perivasculitis.

In topography: aortitis, arteriitis, arteriolitis, capillaritis, phlebitis, lymphangitis


CLASSIFICATION OF VASCULITIS:

1.Large vessel vasculitis (Giant cell arteritis, Takayasu arteritis).

2.Medium-sized vessel vasculitis (Polyarteritis nodosa, Kawasaki disease).

3.Small vessel vasculitis (Wegener granulomatosis, microscopic polyangiitis, Henoch - Schonlein purpura, cutaneous leukocytoclastic angiitis).


TAKAYASU ARTERITISTakayasu arteritis is a granulomatous

vasculitis of medium and larger arteries. Clinically is characterized principally by

ocular disturbances and marked weakening of the pulses in the upper extremities (pulseless disease), related to fibrous thickening of the aortic arch with narrowing or virtual obliteration of the origins or more distal portions of the great vessels arising in the arch.

Although Takayasu arteritis classically involves the aortic arch, in one third of cases, it also affects the remainder of the aorta and its branches and often the pulmonary arteries.


The gross morphologic changes comprise, in most cases, irregular thickening of the aortic or branch vessel wall with intimal wrinking. When the aortic arch is involved, the orifices of the major arteries to the upper portion of the body may be markedly narrowed or even obliterated by intimal thickening, accounting for the designation pulseless disease.

The coronary and renal arteries may be similarly affected. Sometime the lesions extend for some distance into the aortic branches and in half of cases involve the pulmonary arteries.


Histologically, the early changes consist of an adventitial mononuclear infiltrate with perivascular cuffing of the vasa vasorum. Later, there may be intence mononuclear inflammation in the media, in some cases accompanied by granulomatous changes, replete with giant cells and patchy necrosis of the media. As the disease runs its course or after treatment with steroids, the inflammatory reaction is predominantly marked by collagenous fibrosis involving all layers of the vessel wall but particularly the intima, accompanied by lymphocytic infiltration. When the root of the aorta is affected, it may undergo dilation, producing aortic valve insufficiency. Narrowing of the coronary ostia may lead to myocardial infarction.


Takayasu's arteritisThe aortic wall is thickened, and there are thick yellow plaques on the intima. The walls of the innominate and both common carotid arteries are thickened and their lumina are narrowed. The left subclavian artery is almost completely occluded.

Takayasu arteritis


Histologic appearance in active Takayasu aortitis, illustrating destruction and fibrosis of the arterial media associated with mononuclear infiltrates and inflammatory giant cellsUploaded by: http://mbbshelp.com

POLYARTERITIS NODOSA

Polyarteritis nodosa is a systemic vasculitis manifested by transmural necrotizing inflammation of small or medium-sized muscular arteries, typically involving renal and visceral vessels and sparing the pulmonary circulation.

The distributions of lesions, in descending order of frequency is kidneys, heart, liver and gastrointestinal tract, followed by pancreas, testes, skeletal muscle, nervous system and skin. Individual lesions are sharply segmental, may involve only a portion of the vessel circumference, and have a predilection of branching points and bifurcations.


Segmental erosion with weakning of the arterial wall owing to the inflammatory process may cause aneurismal dilation or localized rupture that is perceived clinically as a palpable nodule and can be demonstrated by arteriography.

Impairment of perfusion causing ulcerations, infarcts, ischemic atrophy, or hemorrhages in the area supplied by these vessels may provide the firs clue to the existence of the underlying disorder. Sometimes, however, the lesions are exclusively microscopic and produce no gross changes.


Histologically the vasculitis during the acute phase is characterized by transmural inflammation of the arterial wall with a heavy infiltrate of neutrophils, eosinophils, and mononuclear cells, frequently accompanied by fibrinoid necrosis of the inner half of the vessel wall. Typically the inflammatory reaction permeates the adventitia. The lumen may become thrombosed. In some lesions, only a portion of the circumference is affected, leaving segments of normal arterial wall juxtaposed to areas of vascular inflammation. At a later stage, the acute inflammatory infiltrate begins to disappear and is replaced by fibrous thickening of the vessel wall accompanied by a mononuclear infiltrate.


The fibroblastic proliferation may extend into adventitia, contributing to the firm nodularity that sometimes marks the lesions. At a still later stage, all that remains is marked fibrotic thickening of the affected vessel, devoid of significant inflammatory infiltration.

Particularly characteristic of polyarteritis nodosa is that all stages of activity may coexist in different vessels or even within the same vessel. Thus, whatever the inflammatory insult, it is apparently recurrent and strangely haphazard.


Polyarteritis nodosa. There is segmental fibrinoid necrosis and thrombotic occlusion of the lumen of this small artery. Part of the vessel wall at the upper right is uninvolved. Uploaded by: http://mbbshelp.com

Polyarteritis nodosaUploaded by: http://mbbshelp.com

WEGENER GRANULOMATOSIS

Wegener granulomatosis is a necrotizing vasculitis characterized by the triad of

1)acute necrotizing granulomas of the upper respiratory tract, lower respiratory tract or both;

2)focal necrotizing or granulomatous vasculitis affecting small to medium-sized vessels, most prominent in the lungs and upper airways;

3)renal disease in the form of focal or necrotizing, often crescentric glomerulitis.


Morphologically the upper respiratory tract lesions range from inflammatory sinusitis resulting from the development of mucosal granulomas to ulcerative lesions of the nose, palate, or pharynx, rimmed by necrotizing granulomas and accompanying vasculitis.

In the lung, dispersed focal necrotizing granulomas may coalesce to produce nodules that may undergo cavitation.


Microscopically the granulomas reveal angeographic pattern of necrosis rimmed by lymphocytes, plasma cells, macrophages, and variable numbers of giant cells. In association with such lesions, there is a necrotizing or granulomatous vasculitis of small and sometimes larger arteries and veins. These lesions often contain granulomas, which may be within, adjacent to, or clearly separated from the vessel wall.

These areas are generally surrounded by a zone of fibroblastic proliferation with giant cells and leukocytic infiltrate and become cavitary creating a more than superficial resemblance to a tubercule. Lesions may ultimately undergo progressive fibrosis and organization.


The renal lesions are of two types. In milder forms or early in the disease, these is acute focal proliferation and necrosis in the glomeruli, with thrombosis of isolated glomerular capillary loops (focal necrotizing glomerulonephritis). More advanced glomerular lesions are characterized by diffuse necrosis, proliferation, and crescent formation (crescentic glomerulonephritis). Patients with focal lesions may have only hematuria and proteinuria responsive to therapy, whereas those with diffuse disease can develop rapidly progressive renal failure.


Vasculitis of a small artery with adjacent granulomatous inflammation including epithelioid cells and giant cells

THROMBOANGIITIS OBLITERANS (BUERGER

DISEASE)Thromboangiitis obliterans is a distinctive

disease characterized by segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries, principally the tibial and radial arteries and sometimes secondarily extending to veins and nerves of the extremities.

The condition had occurred almost exclusively in men who were heavy cigarette smokers. The relationship to cigarette smoking is one of the most consistent aspect of this disorder. Several possibilities have been postulated for this association, including direct endothelial cell toxicity induced by or hypersensitivity to some tobacco products.


Tromboangiitis obliterans is characterized by sharly segmental acute and chronic vasculitis of medium-sized and small arteries with secondary spread to contiguous veins and nerves. Often the vascular supply to the extremities, upper as well as lower, is affected.

Microscopically acute and chronic inflammation permeates the arterial walls, accompanied by thrombosis of the lumen, which may undergo organization and recanalization. Characteristically the thrombus contains small microabscesses marked by a central focus of neutrophils surrounded by granulomatous inflammation. Chronic ulcerations of the toes, feet, or fingers may appear, perhaps followed in time by frank gangrene.


Thromboangiitis obliterans (Buerger disease). The lumen is occluded by a thrombus containing abscesses and the vessel wall is infiltrated with leukocytes.

VASCULITIS ASSOCIATED WITH OTHER DISORDERS

Vasculitis may sometimes be associated with an underlying disorder, such as an immunologic connective tissue disease.

Of the connective tissue disorders, rheumatic fever, rheumatoid arthritis and systemic lupus erythematosus commonly manifest a vasculitis.

In rheumatoid arthritis patients with severe erosive disease, rheumatoid nodules are at risk of developing vasculitic syndromes.

Rheumatoid vasculitis is a potentially catastrophic complication, particularly when it affects vital organs, usually involves small and medium-sized arteries.


Frequently, segments of small arteries are obstructed by an obliterating endarteritis resulting in peripheral neuropathy, ulcers and gangrene.

Localized arteritis is most frequently caused by the direct invasion of infectious agents – usually bacteria and fungi, particularly aspergillosis and mucormycosis.

Vascular lesions frequently accompany bacterial pneumonia or occur adjacent to caseous tuberculous reactions, in the neighborhood of abscesses, or in the superficial cerebral vessels in cases of meningitis.


Much less commonly, they arise from the hematogenous spread of bacteria, in cases of septicemia or embolization from infective endocarditis.

Vascular infections may weaken the arterial wall and result in the formation of a mycotic aneurysm.

Clinically, infectious arteritis may be important on several counts. By including thrombosis, it adds an element of infarction to tissues that are already the seat of an inflammatory reaction and worsen the initial infection. In bacterial meningitis inflammation of the superficial vessels of the brain may predispose to vascular thromboses, with subsequent infarction of the brain substance and extension of the subarachnoid infection into the brain tissue.


pathology of the musculoskeletal muscles (elaborate)

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