Everything You Need to Know (at least)

Name Matric no Batch Year -

ONNAZLI0809

OSTEOGENESIS IMPERFECTA/TYPE I COLLAGEN DISEASE/BRITTLE BONE DISEASE Definition can be defined as a group of phenotypically related disorder that are caused by deficiencies in the synthesis of collagen type I. It can be classified to 4 types which the type II is the worst (resulting in death in the uterus or within days of birth) Causes mutation in genes that code 1 and 2 chains of collagen molecules inherited autosomal dominant fashion (mostly) inherited autosomal recessive fashion (rarely)

Morphology too little bone Thinning of the cortical part of bone Attenuation of the trabeculae Persistent foci of hypercellular woven bone

Clinical features Multiple fracture from minimal trauma due to extreme skeletal fragility Blue sclera sclera becomes translucent allowing partial visualization of the underlying choroid due to reduce collagen content of the sclera Hearing loss due to both sensorineural deficit and impaired conduction because of the abnormalities of the middle and inner ear bones Dental imperfections due to deficiency in dentin Heart valve disorder less collagen component Hypermobility of joints

Treatments Bisphosphonates to enhance the bone cortical thickness

ONNAZLI0809

DEVELOPMENTAL (GENETIC) AND ACQUIRED ABNORMALITIES IN BONE CELLS, MATRIX AND STRUCTURES It can be classified to; 1. Defects in nuclear proteins and transcriptional factors Failure of developmental of the bone (phalanx, rib, clavicle) Formation of extra bones Fusion of adjacent digits Craniorachischissis (failure of closure of spinal column and skull)

2. Defects in hormones and signal transduction Achondroplasia Thanatophoric dwarfism 3. Defects in extracellular structural proteins Type I collagen diseases Type 2, 10 and 11 collagen disease 4. Defects in folding and degradation of macromolecules Mucopolysaccharidoses 5. Defects in metabolic pathway (enzymes, ion channels and transporters) Osteopetrosis 6. Decrease in bone mass Osteoporosis 7. Osteoclast dysfunction Paget disease 8. Abnormal mineral homeostasis Rickets and osteomalacia Hyperparathyroidisme Renal osteodystrophy

ONNAZLI0809

OSTEOPETROSIS/MARBLE BONE DISEASE/ALBERT-SCHONBERG DISEASE Definition is a rare genetic disease characterized by reduction in osteoclast activity resulting in diffuse symmetrical skeletal sclerosis Causes Autosomal recessive malignant type Autosomal dominant benign type

Pathogenesis 1. Deficiency in Carbonic Anhydrase II (CA II) 2. Mutation of CIC-7 chloride channel gate 1. Osteoclast use CA II to acidify and resorp bones. Deficiency in CA II prevent osteoclast to acidify resorption pit and solubilising hydroxyapatite crystal

2. CIC-7 chloride channel gate located at ruffled borders of osteoclast. It is important for proton pump H+/ATPase

Morphology Gross morphology 1. Lack of medullary canal 2. Bulging end of long bone and misshapen 3. Small neural foramina, compressing the nerve 4. Bones formed are not remodelled and usually woven in architecture Histology 1. Normal number of osteoclast

ONNAZLI0809

Clinical features 1. Malignant type Fracture occurs commonly due to woven bone architecture Anaemia lack of medullary canal Hydrocephalus due to anaemia Hepatosplenomegally increase extramedullary erythropoiesis Mental retardation Infections 2. Benign type Repeated fracture Infections Increase level of acid phosphate

ONNAZLI0809

OSTEOPOROSIS Definition Increase porosity of the skeleton as a result from reduction in bone mass Types Specific region disuse osteoporosis of the limb Generalized osteoporosis Primary Secondary Postmenopausal Endocrine disorder Senile (old age) Hyperparathyroidism Idiopathic Hypo-hyperthyroidism Hypogonadism Pituitary tumors Diabetes type I Addison disease Rheumatologic disease Drugs Anticoagulants Chemotherapy Corticosteroids Anticonvulsant Alcohol

Miscellaneous Neoplasia Multiple myeloma Carcinomatosis Gastrointestinal Malnutrition Malabsorption Hepatic insufficiency Vitamin C, D deficiencies Others Osteogenesis imperfecta Immobilization Pulmonary disease Homocystinuria Anaemia

Pathogenesis (Primary osteoporosis) Genetic 1. vit D receptor allele 2. estrogen receptor 3. binding protein estrogen PEAK BONE MASS Aging 1. osteoblast replicative 2. biosynthetic potentials 3. growth factors biologic potency 4. physical activity Nutritional 1. Insufficient Ca2+ intake 2. Vitamin D insufficient Physical activity 1. Paralyze and immobilization 2. loss of bone mass Hormonal influences (menopause) 1. Estrogen low 2. IL-1, IL-6 and TNF- by blood monocytes and bone marrow 3. expression of RANK and RANKL-induce osteoclastic activity OSTEOPOROSIS

ONNAZLI0809

Morphology 1. Postmenopausal osteoporosis - Usually affects bone that have high surface area e.g. cancellous compartment of vertebrae commonly affected - Thinned osteoporotic trabeculae and lose interconnections (loss of horizontal trabeculae thickens of vertical trabeculae) - Progressive micro fractures leads to vertebral collapse 2. Senile osteoporosis - Thinning of osteoporotic cortex by subperiosteal and endosteal resorption - Widened Harvesian system Clinical features 1. Fracture 2. Vertebral crush fracture leads to severe back pain, radiating to front. Increase kyphosis, height loss and abdominal protuberance

Investigations 1. Dual energy X-ray absorptiometry reliable to measure bone density (mineral per surface area) 2. Quantitative ultrasound of calcaeneum 3. Quantitative CT scanning allows true assessment and distinct between trabecular and cortical bone

Treatment 1. 2. 3. 4. 5. 6. Exercise 700 1000 mg Calcium diet daily Cessate smoking Estrogen replacing agents Bisphophonates Recombinant PTH

ONNAZLI0809

PAGET DISEASE/OSTEITIS DEFORMANS Definition Is a chronic focal disorder of bone remodelling Causes Paramyxovirus Subacute sclerosing leukoencephalitis Measles

Pathogenesis Measles virus/paramyxovirus/subacute sclerosing leukoencephalitis infections 1. Initial osteolytic phase infected cells secrete cytokines (IL-6) and Pagetic bone produce M-CSF Both IL-6 and M-CSF are chemotactic to osteoclast leading to increase in osteoclastic activity The osteoclast are hyperactive (predispose locus on chromosome 18q) 2. Mixed phase compensatory mechanism to increase in new bone formation, increase in local blood flow as well as fibrous tissue Ends with predominantly osteoblastic activity 3. Burnt out quiescent osteosclerotic phase new bone formed but structurally abnormal Morphology Histological features 1. Mosaic pattern of lamellar bone represent jigsaw puzzle 2. Initial phase waves of osteoclastic activity and numerous resorption pit 3. Mixed phase bone surfaces are lined by prominent osteoblast. Marrow contains numerous blood vessels as well as loose connective tissue (osteoprogenitor cell) 4. Osteosclerotic phase fills with coarsely trabeculae and cortical that are soft and porous and lack of structural stability

ONNAZLI0809

Clinical features 1. Bone pain caused by microfractures and bone overgrowth that compress spinal and cranial nerve 2. Compression fracture shows sign like kyphosis or lordoisis 3. Pathological fracture 4. Deformities anterior bowing of femur and tibia, distorts femoral head leading to arthritis 5. Cardiac hypertrophy owing to increase blood supply to the bone Investigation 1. X ray 1) in lytic phase central and endosteal cortical resorption and replacement by less compact new bone 2) in sclerotic phase thickened trabeculae, loss of distinction between cortex and trabeculae 2. Bone scans 3. Serum alkaline phosphatase - increase

ONNAZLI0809

RICKETS AND OSTEOMALACIA Definition Rickets (in children) and osteomalacia (in adults) is an inadequate mineralization of bone matrix due to defects in vitamin D availability or metabolisme. Causes Vitamin D deficiency Skin synthesis Malabsorption Malnutrition Renal disease Chronic renal failure Dialysis Tubular disorder (ATN, APN) Others Vitamin D dependant rickets Tumor

Pathogenesis

Vitamin D deficiency Reduce substrate for renal 1 hydroxylase Reduce formation of 1,25-dihydroxycholecalciferol Reduce absorption of calcium and phosphate in the gut Reduce serum level of calcium and phosphate Activates parathyroid hormone Increase calcium absorption in the renal but promotes phosphate excretion via urine Serum calcium level normal but phosphate level decrease Impaired mineralization for bone formation Bone formation abnormal Rickets (children) and osteomalacia (adults)

ONNAZLI0809

Clinical features 1. 2. 3. 4. 5. 6. Pathological fractures Waddling gait Neonatal thin deformed skull Widened epiphyses at wrist Beading at costochondral junction Groove in the rib cage (Harrisons sulcus)

Investigations 1. 2. 3. 4. Increase serum alkaline phosphatise increase osteoblastic activity Serum phosphate reduce increase PTH Serum 1,25-DHCC decrease X-ray showing Loosers zones (linear area of reduce density surrounded by sclerotic body)

Treatment 1. Oral vitamin D supplement

ONNAZLI0809

OSTEOMYELITIS Definition Is an inflammation of bone and bone marrow due to infections. It can be local or systemic Causes In adults Staphylococcus aureus Escherichia coli Pseudomonas sp Klebsiella sp Mycobacterium tuberculosis In neonates Haemophilus influenza Group B streptococci sp

Pathogenesis Bacteria enters the bones via 1. Direct penetration Bacterial organism introduced directly into the bone by penetrating the wounds, fractures or surgery Staphylococcus sp and streptococcus sp are common 2. Haematogenous spread Arise from focus (skin pustules, infected teeth and gums etc) elsewhere in the body and through bloodstream, it reaches the bone. Likely to spread to the metaphyses of the long bones such as ankle, knee, hip etc Tuberculosis is the commonest bacteria causing osteomyelitis via haematogenous spread (non-neoplastic metastasis) 3. Direct seeding Pulmonary tuberculosis affecting the lung and give rise to the formation of pulmonary focus. This focus can directly transfer the bacteria to the bones such as ribs and thoracic vertebra.

Morphology Pyogenic osteomyelitis 1. Cloaca hole formed in the bone during formation of a draining sinus 2. Sequestrum fragments of necrotic bones that are embedded in the pus 3. Brodie abscess reactive bone from periosteum and endosteum whic surrounds and contains the infections 4. Involucrum lesion in which periosteal new bone formation forms a sheath around the necrotic sequestrum

ONNAZLI0809

Morphology Tuberculous osteomyelitis 1. Granuloma produce caseous necrosis of the bone marrow 2. Slow resorption of bony trabecullae 3. Formation of cystic spaces in the bone Clinical features Pyogenic osteomyelitis 1. Fever with chills and rigors 2. Malaise 3. Leukocytosis 4. Throbbing pain at the affected site Tuberculous osteomyelitis 1. Pain in motion 2. Localize tenderness 3. Low grade fever 4. Loss of appetite 5. Kyphotic and scoliotic deformities compression fracture of vertebra Treatment 1. Cloxacillin 2. Fusidic acid 3. Immobilization Complications 1. Septicaemia infection disseminated to the blood stream 2. Acute bacterial arthritis direct digestion (cytokines effect) by inflammatory cells destroy srticular cartilage, producing osteoarthritis 3. Pathological fracture 4. Squamous cell carcinoma 5. Amyloidosis 6. Chronic osteomyelitis

ONNAZLI0809

BONE TUMORS Character Diverse in their gross and morphologic features Behavior biological innocuous to rapidly fatal Target group Benign (10 30 years old) Malignant (later in adult life)

Risk factor Li Fraumeni syndrome and hereditary retinoblastoma genes (mutations in p53 and RB gene). Bone infarcts, chronic osteomyelitis, Paget disease, radiation and metal prostheses. Classification Base on normal cell tissue of origin (as stated below) 1. Bone forming tumors 2. Cartilage forming tumors 3. Fibro-osseous tumors 4. Miscellaneous tumors Bone forming tumors Osteoma Osteoid osteoma Osteoblastoma Osteosarcoma Cartilage forming tumors Osteochondroma Chondroma Chondroblastoma Chondromyxoid fibroma Chondrosarcoma Fibro-osseous tumor Miscellaneous tumors Fibrous dysplasia Giant cell tumor Ewing sarcoma Metastatic tumor

ONNAZLI0809

Pathogenesis of Bone Tumors

Normal cell Carcinogenic agents Acquired DNA damaging substance DNA damage DNA mutation Mutation in Genome Alteration in gene that regulates DNA repair* Successfully repaired

Activation of Growth Promoting Oncogenes* (oncogenic product class 1, 2 and 3)

Apoptosis Gene Alteration* (hereditary)

Cancer suppressing gene alteration* (hereditary)

Oncogenic product class 4 and 5 Expression of altered gene product Loss of regulatory gene product

Malignant Neoplasia

CANCER RELATED GENES 1. Oncogenenic Products class 1 to class 5 2. Tumour Supressing genes p53,pRb genes 3. Genes regulates apoptosis Bax, Bcl-2, bad, Bcl-xL 4. Genes regulates DNA repair Any defect in this gene, commonly inherited will increase the chances of getting cancer 4-5 folds

ONNAZLI0809

BONE-FORMING TUMORS

OSTEOMA

Definition Character

Gross morphology Histopathology

Clinical features

Radiologic findings Prognosis Treatment

A benign bone tumor, an exophytic mass from skull and paranasal sinuses - Most often arise on or inside the skull or facial bones - Often affecting middle age adults (30-50 years old) - Always associated with Gardner syndrome Bosselated, round to oval sessile tumors that project from the subperiosteal or endosteal surfaces of the cortex - Composed of lamellar and woven bone frequently deposited in a cortical pattern with Harvesian-like system - Compact lamellar cortical bone - Small amount of fibrofatty stroma - Usually asymptomatic - Symptomatic if the tumors pressed adjacent structure such as sinus obstruction, extracranial extension and nerve compression - Sharply demarcated mass protruding from the bone surface - No bone destruction and periosteal reaction - Periosteal osteoma may mimics periosteal osteosarcoma Never change or transform to malignant Simple excision

ONNAZLI0809

OSTEOID OSTEOMA AND OSTEOBLASTOMA benign bone tumors that have identical histologic features but differ in size, sites of origin and symptoms OSTEOID OSTEOMA Definition Character Tumors which the size of less than 1 cm in greatest dimension - Usually occurs in teens or twenties - Most often rise from appendicular skeleton - Mostly at tibia, femur and spine - Is a well circumscribed tumor - Mostly round to oval masses of gritty tan tissue - Well circumscribed tumor cells - Composed of randomly interconnecting trabeculae of woven bone rimmed by fibroblast - loose vascular stroma - localized pain usually worse at night - relieved by aspirin - intracortical nidus - sclerotic rim of bone reaction Never change or transform to malignant - Complete resection - Removal of nidus - Bone grafting may needed

Gross morphology Histopathology

Clinical features Radiologic findings Prognosis Treatment

OSTEOBLASTOMA Definition Character Gross morphology Histopathology A tumor of bone arises from the osteoblast - Mostly arise from the axial skeleton - Mostly affecting spine, femur and jaw Is a well circumscribed tumor Mostly round to oval masses of gritty tan tissue Well circumscribed tumor irregular cells Composed of randomly interconnecting trabeculae of woven bone rimmed by fibroblast - loose vascular stroma - presents of hyaline cartilage mimics the osteosarcoma - dull achy pain - localize - not responsive to salicylates - well-circumscribed tumor cell (irregularly demarcated) - well defined by a surrounding shell of mature bones - small extracortical mass - Radiolucent lesion (20 -100 mm diameter) - expansile lesion - variable ossification - may be aggressive with cortical destruction and soft tissue extension Less than 1 % recorded to be malignant transformation Enbloc resection ONNAZLI0809 -

Clinical features

Radiologic findings

Prognosis Treatment

OSTEOSARCOMA

Definition Character

Gross morphology

Histopathology

Malignant messenchymal tumor in which cancerous cells produce bone matrix - Arise from metaphyseal region of the long bones - Affecting the knee (60 %), hip (15%), shoulder (10%) and jaw (8%) - Affecting those who are <20 years old and adults with bone disease such as Paget disease. bone infarct and prior irradiation - Intramedullary fleshy tumor - Gritty, gray-white and often containing areas of haemorrhage and cystic degeneration - Destruction of cortex and soft tissue involvement - Usually spreading to the medullary canal - High grade sarcomatous cell - Abnormal mitosis and necrosis - Osteoid deposition by malignant cell - Stroma osteoblastic, chondroblastic, fibroblastic - Sclerosing osteoblastic variant minimal pleomorphism - Randomly distributed osteoclastic cell Pain of short duration Progressively enlarging masses Sudden fracture of the bone Soft tissue swelling Rare pathology fracture Elevated alkaline phosphatase Permeative lesions, metaphyseal centered Large, destructive, mixed lytic and blastic mass which has permeative margin Periosteal reaction Codman triangle triangular shadow between cortex and raised end of the periosteum Soft tissue extension Mineralization from purely lytic to mixed densely sclerotic

Clinical features

Radiologic findings

Prognosis Treatment

Multidrug preop chemotherapy, limb salvage or amputation

ONNAZLI0809

CARTILLAGE FORMING TUMORS OSTEOCHONDROMA Definition Character also known as exostosis is a benign cartilage-capped outgrowth that is attached to the underlying skeleton by a bony stalk - Can be solitary or multiple - Men are predominantly affected (3:1) - developed only in bones of endochondral origin - arise from metaphysis of the growth plate of long tubular bones, about the knee - mushroom-shaped (1-20 cm in size) - cortex of the stalk continuous with the medullary cavity of the osteochondroma are in continuity - cap of the tumor composed of hyaline cartilage - appearance of the disorganized growth plate - echondral ossification occurs at the growth plate Radiologic findings Prognosis Treatment slow growing mass pain of the affected area due to tumor impinge on the nerve or the stalk of the tumor fractured bowing and shortening of bone due to disturbance in epiphyseal growth outgrowth of the bone from normal cortex which is continuous Cap cannot be seen initially. As age increase, the cap undergoes calcification in a punctuate or nodular fashion well-defined peripheral margin without localize bone destruction

Gross morphology

Histopathology

Clinical features

The stalk usually stop growing at the time of growth plate closure, <1% give rise to osteosarcoma Removal of loose body, synovectomy

ONNAZLI0809

CHONDROMA Definition Benign tumor of hyaline cartilage. The terms enchondroma implicate the tumor arise from the medullary cavity while subperiosteal/juxtacortical chondroma denotes the tumor arise from the surface of the bone - most common intraosseous cartilage tumor - commonly diagnosed in patient between age 20-50 - no sex predominant - solitary and often located in the metaphyseal region of the tubular bones - multiple chondroma is called chondromatosis occurs in the Oller disease - smaller than 3 cm - enchondroma are gray blue, translucent and have a nodular configuration - nodules of the cartilage are well circumscribed and have hyaline matrix - neoplastic chondrocytes that reside in the lacunae are cytologically benign - nodules characteristic peripheral undergoes enchondral ossification, central undergoes calcification and dies Prognosis Treatment usually is asymptomatic local pain pathological fracture deformities occurs when the cartilage tumor is numerous and large presence of O ring sign, an unmineralized nodules of cartilage produce well circumscribed oval lucencies surrounded by thin rim of dense bone expansile growth of the cortex with size between 10 30 mm

Character

Gross morphology

Histopathology

Clinical features

Radiologic findings

Tumor growth usually stable, if associated with chondromatosis, it has high probability to become sarcomatous Complete excise (but may recur)

ONNAZLI0809

CHONDROBLASTOMA

Definition Character

Gross morphology Histopathology

Clinical features

Radiologic findings Prognosis Treatment

A tumor derived from chondroblast which is very rare and accounts for less than 1 % of the primary bone tumors - occurs in young patients in their late teens - male to female ratio 1:2 - mostly occurs at knee, in older patient, the tumor may occurs at pelvis and ribs - not stated - cellular tumor which composed of sheets of compact polyhedral chondroblast that have well defined cytoplasmic border - highly cellular lesion which is composed of chondroblast and giant cell - nuclei are hyperlobulated with longitudinal groove - moderate amount of pink cytoplasm - surrounded by scanty amount of hyline matrix which are deposited in a lace-like configuration - prominent haemorrhagic cystic degeneration - local pain if joint are affected - joint effusion - reduce joint (affected) range of movement - well-defined geographic lucency that has spotty calcifications - round and well-defined calcific margin Rarely distant metastases to lung, recurrence common after surgical excision Surgical excision

ONNAZLI0809

CHONDROMYXOID FIBROMA Definition Is a rare benign tumor that accounts of less than 0.5 % of biopsied primary tumor of the bones which composed of various tissue combination; fibrous, cartilaginous and myxoid - mostly occurs between 10-30 years old patient - male are predominantly affected - Usually arise in the metaphysis of long tubular bones proximal 3rd of tibia (25 %), bones of leg and distal femur (50 %) - tumor size 3-8 cm in greatest dimension - well circumscribed, solid and glistening tan gray - nodules of poorly formed hyaline cartilage and myxoid tissue delineated by fibrous septa - cellularity varies, greatest at the periphery nodules - tumor cell located in the lacunae at the cartilaginous region - tumor cells are stellate and their delicate cell processes extend through the mucinous ground substance and in contact with neighbouring cell - varying degree of cytologic atypia presence of large hyperchromatic nuclei - small foci of calcification of the cartilaginous matrix and scattered nonneoplastic osteoclast-type giant cell Prognosis Treatment localize dull and achy pain eccentric geographic lucency that is well delineated from adjacent bone by a rim of sclerosis punched out lesion involving cortex and medulla presence of soap bubble appearance

Character

Gross morphology Histopathology

Clinical features Radiologic findings

Tumor may recur but it doesnt pose a threat for malignant transformation Simple curettage

ONNAZLI0809

CONVENTIONAL CHONDROSARCOMA

Definition Character

Gross morphology

Histopathology

A malignant tumor of cartilage cell in which the cancerous cell produce cartilage matrix and occurs in the bone - occur at patient age 40 and above - affecting male twice than female - risk factor are enchondroma, osteochondroma, chondroblastoma, fibrous dysplasia and Paget diseae - composed of malignant hyaline and myxoid cartilage - myxoid is viscous and gelatinous and the matrix oozes from the cut surface - presence of spotty calcification and central necrosis creating cystic spaces - adjacent cortex is thickened and eroded - poorly differentiated sarcoma dedifferentiated chondrosarcoma - sheets of large malignant chondrocytes that have abundant clear cytoplasm, numerous osteoclast-tyoe giant cell and intralesional reactive bone formation clear cell chondrosarcoma - island of well differentiated hyaline cartilage surrounded by sheets of small round cell - cellular anaplasia, bizarre shaped nuclei, chromatin clumping and mitoses painful lesion progressively enlarge masses poorly demarcated between normal and abnormal bones presence of calcification which may be stippled, nodular or englomerate (popcorn) in a pattern of flocculent density - nodular growth pattern of cartilage produces prominent endosteal scalloping Depends on the grading, higher the grade and larger the size, poorer the prognosis (chance of survival reduce) Chemotherapy -

Clinical features Radiologic findings

Prognosis Treatment

ONNAZLI0809

OSTEOARTHRITIS Definition Is a degenerative joint disease characterized by progressive erosion of articular cartilage Classification Classify based on the causes of osteoarthritis Primary Idiopathic Secondary Metabolic Ochronosis Acromegaly Haemochromatosis Calcium crystal deposition Anatomic Slipped femoral epiphysis Epiphyseal dysplasia Congenital dislocation of the hip Leg length inequality Hypermobility syndrome Traumatic Motor vehicle trauma Fracture through joint or osteonecrosis Joint surgery Inflammatory Acute inflammatory arthropathy Septic arthritis

Pathogenesis Idiopathic caused Degeneration of chondrocytes Decrease local synthesis of collagen type II, proteoglycan produced is within normal range Water absorption normal (PG normal) but collagen network production less Unstable osmolarity between collagen network and water content leads to increase breakdown of the pre-existing collagen Osteoarthritic cartilage produce molecular messenger (IL-1, TNF- and nitric oxide) PRIMARY OSTEOARTHRITIS Erosion of the articular cartilage Production of molecular messenger predominate the compensatory mechanism Compensatory mechanism chondrocytes in the deeper layers proliferate and attempt to repair the destroyed cartilage Reduction of functional chondrocytes Apoptosis increase Trigger inflammatory reaction as well as apoptosis ONNAZLI0809

Morphology Gross morphology 1. Vertical and horizontal fibrillation and cracking of the matrix at the superficial layers of the cartilage which are degraded 2. Granular articular surface softer than normal 3. Bone eburnation friction smoothes and burnish the exposed bones 4. Mushroom shaped osteophytes (bony outgrowth) develop at the margins of articular surface which capped by fibrous and hyaline cartilage

Histology 1. Synovium is congested and fibrotic 2. Scattered chronic inflammatory cell

Clinical features 1. 2. 3. 4. 5. 6. 7. Joint pain and tenderness Joint swelling (stiffening and pain after immobility) Joint instability Crepitus on movement Limitation of range of movement Joint effusion Heberden nodes prominent osteophytes at DIP joint

Investigation 1. X-rays abnormal only when the damage is advanced 2. MRI demonstrate early cartilage and subchondral bone change 3. Arthroscopy reveals each fissuring and surface area of the cartilage

Treatment 1. 2. 3. 4. 5. NSAID Total replacement arthroplasty Realignment osteotomy of knee and hip Weight loss and exercise for strength Local heat, ice packs and massage

ONNAZLI0809

RHEUMATOID ARTHRITIS Definition Chronic systemic inflammatory disorder which principally attacks the joint, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosing of the joint

Pathogenesis Unknown antigen Bind to MHC class II (genetic susceptibility) Induce CD4+ T cells to release cytokines

B-cell activation Formation of rheumatoid factor Immune complex formation and deposition inside joint cavity Joint injury

Induce macrophage to release cytokines Proliferation of fibroblasts, chondrocytes and synovial cells Release of collagenase, stromelysin, elastase, PGE2, and other enzyms

Endothelial activation Expression of adhesion molecules Accumulation of inflammatory cells

Pannus formation; destruction of bone, cartilage leading to fibrosis and ankylosing Morphology 1. Synovial edematous, thickened and hyperplastic forming villous configuration 2. Infiltration by dense perivascular inflammatory cells such as B-cells, T-cells, plasma cell and macrophages 3. Increase vascularity

ONNAZLI0809

Clinical course 1. slowly progressive, symmetrical and peripheral polyarthritis evolving over a period of few weeks and months 2. pain and stiffness of small joints of hands PIP, DIP and feet (MTP) 3. pain and stiffness in the morning improve with physical activity

Investigations 1. 2. 3. 4. 5. 6. Blood count anaemia Increase in ESR Increase in C-reactive protein Serology test Presents of Rheumatoid factor and ANA at low titre X-rays soft tissue swelling Aspiration effusion presents and cloudy owing to white cells

Treatment 1. NSAID 2. Disease modifying anti-rheumatic drugs that inhibit cytokines and reduce inflammatory response TNF-a, corticosteroid, methotrexate etc

ONNAZLI0809