pathology of masculoskeletal disorders..

Musculoskeletal Presentation:

A musculoskeletal presentation refers to the clinical manifestation of disorders affecting the muscles, bones, joints, and associated tissues. These presentations can result from various factors, including:

- Trauma or injury
- Inflammatory conditions (arthritis, tendinitis)
- Degenerative diseases (osteoarthritis, disc degeneration)
- Infections (osteomyelitis, septic arthritis)
- Tumors (bone, soft tissue)
- Congenital or developmental disorders (scoliosis, clubfoot)

Common musculoskeletal presentations include:

- Pain or tenderness in muscles or joints
- Limited range of motion or stiffness
- Swelling, redness, or warmth around affected areas
- Weakness or fatigue in muscles
- Deformities or abnormalities in posture or gait
- Instability or locking of joints

Accurate identification and evaluation of musculoskeletal presentations are essential for timely diagnosis and effective management of musculoskeletal disorders, enabling healthcare providers to develop appropriate treatment plans and improve patient outcomes.

1. Group 9 musculoskeletal system 1

2. GROUP MEMBERS AH/PAS/22/0086 AH/PAS/22/0087 AH/PAS/22/0088 AH/PAS/22/0089 AH/PAS/22/0090 AH/PAS/22/0091 AH/PAS/22/0092 AH/PAS/22/0093 AH/PAS/22/0094 AH/PAS/22/0146 AH/PAS/22/0113 2

3. INTRODUCTION 3

4. BASIC STRUCTURE AND FUNCTION OF BONES BONE MATRIX: is composed of an organic component known as osteoid (35%) and a mineral component (65%) s. Osteoid is made up predominantly of type I collagen with smaller amounts of glycosaminoglycans and other proteins. CELLS; osteoblast :synthesize the bone matrix. OSTEOCLAST: multinucleated macrophages which are responsible for bone resorption OSTEOCYTES: helps to control calcium and phosphate levels and responsible for mechanotransduction . During embryogenesis, long bones develop from a cartilage mold by the process of endochondral Intramembranous ossification, by contrast, is responsible for the development of flat bones. 4

5. Congenital bone and cartilage disoders Achondrolasia Definition: is the most common skeletal dysplasia and a major cause of dwarfism, is an autosomal dominant disorder resulting from retarded cartilage growth PATHOTHGENESIS: the diseas e is caused by gain of function mutations in the fibroblast growth factor receptor 3. normally the FGF inhibits endochondral growth. FGFR3 mutation results in a constitutively active receptor, thereby exaggerating this effect and suppressing growth. MANIFESTATION Short proximal extremities,enlarged head and a conspicuous depression of the root of nose NB: it has no effect on their cognitive abilities TREATMENT Surgical treatment Voxzogo injection 5

6. TYPE I collagen disease Osteogenesis imperfecta (OI), the most common inherited disorder of connective tissue, is a phenotypically diverse disorder caused by deficiencies in the synthesis of type I collagen.leading to brittle and fragile bones Pathogenesis: It usually results from autosomal dominant mutations in the genes that encode the α1 and α2 chains of type I collagen. These defects cause misfolding of the mutated collagen polypeptides, and they interfere with the proper assembly of wild-type collagen chains . the fundamental abnormality in OI is too little bone causing extreme skeletal fragility. Clinical manifestations blue sclerae caused by decreased collagen Decreased hearing Triangular shaped face Treatment Surgery Biphosphate to inhibit osteoclast activity and facilitate osteoblast activity 6

7. OSTEOPETROSIS Osteopetrosi s, refers to a group of rare genetic diseases that are characterized by reduced bone resorption and diffuse symmetric skeletal sclerosis resulting from impaired formation or function of osteoclasts. Pathogenesis: These include autosomal recessive mutations in the enzyme carbonic anhydrase 2 (CA2), or mutations in the TCIRG1 gene, which encodes a component of a vacuolar ATPase that helps to maintain acidic pH in osteoclasts, which is essential for breaking down bone. Clinical manifestation stunted growth and deformity Subceptible to fractures Cranial nerve paralysis Anemia,hepatosplenomegaly Hearing impairment TREATMENT AND MANAGEMENT Bone marrow transplant Gene therapy Symptomatic and sportive treatment 7

8. METABOLIC DISORDERS OF BONE OSTEIPENIA AND OSTEOPOROSIS OSTEOPENIA : it refers to the decrease in bone mass OSTEOPOROSIS : it is a type of osteopenia that is severe, which significantly increase the risk of fracture there are two main types of osteoporosis; senile and postmenopausal Senile type: it is when the osteoblast activity has reduced proliferative and biosynthetic potential and reduced growth factor response. Postmenopausal: decreased level of estrogen in the body,mostly females increases both the activity of osteoclast and osteoblast but the osteoblast activity can not keep with the osteoclast activity. Clinical manifestation vertebral fractures that involves the thoracic and lumber can cause loss of height and deformities such as lordosis and kyphoscoliosis. Complications Pulmonary embolism and pneumonia DIAGNOSIS Dual energy x-ray absorptiometry, quantitative computed tomography PREVENTION AND TREATMENT Exercise, appropriate calcium and vitamin D intake, biophosphates (alendronate) 8

9. FRACTURE HEALING 9

10. Rickets and osteomalacia Rickets: disorder in children which interferes with the deposition of bone in the growth plate. Osteomalacia : a disorder in which bone formed during remodelling is under mineralized resulting in predisposition to fractures. Pathophysiology: The fundamental defect is an impairment of mineralization and a resultant accumulation of unmineralized matrix and vitamin D deficiency Clinical presentation Bow legs(genu varum),knocked knees Treatment and prevention Vitamin D supplement, calcium supplement,biophosphates 10

11. Paget disease of bone(osteitis deformans) PAGET DISEASE : is a chronic bone disorder characterized by excessive and abnormal remodeling of bone tissues leading weakened and deformed bones. Stages Initial osteolytic stage Mixed osteoclastic-osteoblastic Osteosclerotic stage Pathogenesis: mutations of the SQSTM1( Seqestosome-1) gene which activates the NF-kB in turn increases the osteoclast activity and also mutation in RANK. CLINICAL MANIFESTATION Bone pain and tenderness, enlarged craniofacial skeleton,osteoarthritis,heavy cranium,lion face TREATMENT AND PREVENTION Bisphosphonates, calcitonin, surgery 11

12. OSTEONECROSIS DEFINITION : It refers to the infarction of bone and bone marrow cells. CAUSES Thrombotic occlusions Extravascular compression Mechanical disruption of vessels Drugs such as corticosteroids Clinical manifestation Early stage is asymptomatic. Eventually the affected bone when weight is put on it or when lying down. TREATMENT Surgery, physiotherapy and medication 12

13. OSTEOMYELITIS Osteomyelitis denotes the inflammation of the bone and the bone marrow virtually always secondary to infection Pyogenic : it is a caused by pyogenic bacterials such as S. aureus, S.pyogens,E . coli, which produce pus and cause severe infection. Mode of spread, hematogenous,direct inoculation, contaguous spread. In neonatal period, haemophilus influenzae and S.agalactiae are frequent pathogens. MYCOBACTERIAL: it is caused by mycobacteria,including non tuberculous mycobacteria and mycobacterium tuberculosis. mosty occurs in immunocompromised individuals. Clinical manifestation Fever,chills,leukocytosis , pain Diagnosis Biopsy and bone cultures,radiography TREATMENT Antibiotics,antimycobaterial therapy,surgical debridement 13

14. Bone tumors and tumor like lesions Osteoid Osteoma and Osteoblastoma: They are benign bone producing tumors that have similar histologic features but differ clinically and radiographically. Osteoid osteoma has a small diameter(<2cm) and mostly common in children and occurs at the tibia or femur, therein arise from the cortex. Osteoblastoma is larger than 2 cm and involves the posterior components of the vertebrae (laminae and pedicles) TREATMENT: osteoid osteoma is treated by radiofrequency ablation whereas osteoblastoma is treated by surgical excison . OSTEOCHONDROMA : known clinically as exostosis, is a benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk. PATHOGENESIS: mutations in the EXT2 and EXT1 genes SITE: Metaphysis of long bones TREATMENT Symptomatic tumors are cured by simple excision. Rarely in sporadic cases, but more commonly in those with multiple hereditary exostosis 14

15. OSTEOSARCOMA: Osteosarcoma is a malignant tumor that produces osteoid matrix or mineralized bone. PATHOGENESIS: mutations in RB,TP53,CDKN2A,CDK4 genes Sites: metaphyseal regions of the distal femur and proximal tibia Risk factors: Li-Fraumeni syndrome,hereditary retinbastoma Treatment 1) neoadjuvant chemotherapy, (2) surgery CHONDROSARCOMA: They are malignant tumors that produce cartilage . subclassified into conventional (hyaline cartilage–producing), dedifferentiated, clear cell, and mesenchymal types PATHOGENESIS: Mutations the EXT1 and EXT2 , IDH1 and IDH2 mutations. Mutation of the collagen COL2A1 gene and silencing of the CDKN2A tumor NB: Tumor grade predicts outcome, which ranges from 80% 5-year survival for Grade 1 tumors to 43% for Grade 3 tumors. Grade 1 chondrosarcomas rarely metastasize, whereas 70% of grade 3 tumors spread hematogenously , TREATMENT: surgical excision 15

16. JOINTS:ARTHRITIS OSTEOARTHRITIS : it is considered an intrinsic disorder of cartilage in which chondrocytes respond to biochemical and mechanical stresses resulting in the breakdown of the matrix and failure of its repair. characterized by degeneration of cartilage that results in structural and functional failure of synovial joints . PATHOGENESIS: The lesions of OA stem from degeneration of the articular cartilage and its disordered repair.Cytokines imbalances Clinical manifestation: joint pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement. Treatment and management Surgery, , NSAIDs to reduce inflammation, intra-articular corticosteroids, activity modification, and, for severe cases, arthroplasty. 16

17. Rheumatoid arthritis is a chronic inflammatory disorder of autoimmune origin that principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis PATHOGENESIS : The pathologic changes are mediated by antibodies against self-antigens and inflammation caused by cytokines, predominantly secreted by CD4+ T cells , presentation of modified proteins to T cells , production of anti-citrullinated protein antibodies,causing synovial inflammation and joint damage NB: RA can be distinguished from other forms of polyarticular inflammatory arthritis by the presence of ACPA and by characteristic radiographic findings . TREATMENT The treatment for RA consists of corticosteroids, other immunosuppressants such as methotrexate, and, most notably, TNF antagonists. 17

18. GOUT is marked by transient attacks of acute arthritis initiated by urate crystals deposited within and around joints. OTHER CAUSES: Gout is associated with male sex, obesity, metabolic syndrome, excess alchohol intake, renal failure, and age greater than 30 years,genetic predisposition(X-linked abnormalities of HGPRT TREATMENT Treatment of gout aims at lifestyle modification and medication to reduce symptoms (e.g., NSAIDs) and lower urate levels (e.g., xanthine oxidase inhibitor). 18

19. JOINT TOMORS AND TUMOR LIKE LESIONS GANGLION AND SYNOVIAL CYST(BENIGN TUMORS) Ganglion cyst is a fluid filled lumps that are usually formed on the joints or tendons f the hands or feet. Painful when it presses a nearby nerves. Synovial cyst;are fluid filled sacs that develop in the synovial membrane, which lines joints and tendons. May be associated osteoarthritis Pathogenesis: Ganglion cyst by repetitive strain or injury to the joints which causes inflammation and fluid accumulation in the joint or tendon. Synovial cyst on the other hand is by inflammation and irritation of the synovial membrane, often due to conditions such as OA and RA. CLINICAL DIAGNOSIS: physical examination ,imaging tes CLINICAL MANIFESTATION: visible lump ,pain ,weakness in the hand s or affected area ,limited mobility,redness . TREATMENT Self limited,sugery,NSAIDs,physical therapy 19

20. TENOSYNOVIAL GIANT CELL TUMOR is the term for a benign neoplasm that develops in the synovial lining of joints, tendon sheaths, and bursae. Clincally classified into,diffuse type(involves large joints) and the localized type(discrete nodule attached to a tendon sheath, commonly in the hand . ) PATHOGENESIS: Diffuse and localized types of this tumor both harbor a reciprocal somatic chromosomal translocation, t(1;2) (p13;q37), resulting in fusion of the type VI collagen α-3 promoter to the M-CSF gene. This causes mutations in the CSF1,CD34,H3F3A leading to the formation of the tumor. CLINICAL PRESENTATION Diffuse tenosynovial giant cell tumor presents in the knee in 80% of cases. Affected individuals typically complain of pain, locking, and recurrent swelling .usually palpable mass is present. The localized variant manifests as a solitary, slow-growing, painless mass that frequently involves the hand TREAMENT Surgical excision, M-SCF antagonist pathway 20

21. DUCHENNE MUSCULAR DYSTROPHY (DMD) Is a genetic disorder caused by a mutation in the dystrophin gene leading to muscle weakness and degeneration PATHOGENESIS ;mutation in the dystrophin gene disrupt the production of dystrophin protein which is necessary for maintaining muscle cell membrane intergrity . TREATMENT : corticosteroids ,assistive devices 21

22. SOFT TISSUE TUMORS LIPOMA : a fatty lump most often situated in the skin and underlying muscle layer LIPOSARCOMA ; Liposarcomas are malignant tumors of adipose tissue. Liposarcoma is one of the most common sarcomas of adulthood. It occurs mainly in people in their 50s to 60s in the deep soft tissues and retroperitoneum 22

23. FIBRMATOSIS SUPERFICIAL FIBROMATOSIS Superficial fibromatosis is an infiltrative proliferation that can cause local deformity but has an innocuous clinical course. SUBTYPES; Palmar ( Dupuytren contracture), Plantar, Penile ( Peyronie disease). Palpable induration or mass on the dorsolateral aspect of the penis. DEEP FIBROMATOSIS Deep fibromatoses, also called desmoid tumors, are large, infiltrative masses that frequently recur but do not metastasize. 23

24. SKELETAL MUSCLE TUMORS RHABDOMYOSARCOMA Rhabdomyosarcoma is a malignant mesenchymal tumor with skeletal muscle differentiation. Three main subtypes are recognized: alveolar (20%), embryonal (60%),(both commonly seen in children) and pleomorphic (20%) moslty seen in adults PATHOGENESIS; alterations in the genes PAX3,PAX7,FOX01 and TP53 contribute to the tumor development. 24

25. LEIOMYOMA LEIOMYOMA, a benign tumor of smooth muscle, is most common in the uterus but can arise in any soft tissue site PATHOGENESIS : germline loss-of-function mutation in the fumarate hydratase (FH) gene located on chromosome 1q42.3 leads to multiple cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma . COMMON SITES : erector pili muscles ,uterus ,gastrointestinal tract,vulva COMPLICATIONS ;infertility and menorrhagia ,renal cell carcinoma 25

26. LEIOMYOSARCOMA is a malignant tumor of the smooth muscles cells ,often in the uterus ,stomach or small intestine. Same pathogenesis as to leiomyoma. TREAMENT Chemotherapy,surgery,radiation therapy 26

27. REFERENCES Vinay k,Abdul,k.A .& J on,C.A .(2018). R obbins B asic Pathology.(10 th ed.).Elsevier Vinay,K.,Abdul,K.A.& Jon,C.A .(2013). R obbins B asic P athology.(9 th .ed ). elsevier 27