Pathology of Musculoskeletal System PDF

Arab Republic of Egypt Ministry of Higher Education Egyptian Chinese University College of Physical Therapy PATHOLOGY II Dr. Ahmed Fawzi E...

Arab Republic of Egypt Ministry of Higher Education Egyptian Chinese University College of Physical Therapy PATHOLOGY II Dr. Ahmed Fawzi Elshaieb Professor of Pathology PTPAT 0307 FIFTH LEVEL  Pathology of Musculoskeletal system The musculoskeletal system provides form, support, stability, and movement to the body. It is made up of the bones of the skeleton, muscles, cartilage, tendons, ligaments, joints, and other connective tissue that supports and binds tissues and organs together  Introduction: Bone is a dynamic tissue Osteoblasts - osteoid (type 1 collagen) Calcium and phosphate (calcium hydroxyapatite) Osteoclasts are multi-nucleated cells which resorb bone (PTH). Bone Anatomy Diaphysis Metaphysis Epiphysis – Prox/Dist Epiphyseal line Periosteum Compact cortical bone Spongy bone Articular Cartilage Medullary cavity Marrow  Bone Mineralization Formation: Calcification Intramembrano us Ossification Bone Endochondral Hardness Growth: Interstitial Tensile strength Oppositional Volkmann’s canal Bone Function: Haversian canal Mineral Lacunae homeostasis. Osteon Hemopoiesis. Blood Supply to Bone:  Types of Bone tissue: Woven bone – Irregular – immature – fetus/# Lamellar bone – regular – mature. – Circumferential – Concentric – Interstitial – Trabecular Compact & Spongy - lamellar bone Enchondral / intramembranous formation. Compact Bone:  Types of Bone Cortical bone: defines shape Cancellous bone: marrow bone – Mandible, maxilla – End of long bones in the medullary canal Epiphysis – from subarticular plate to epiphyseal cartilage Metaphysis – Area between epiphyseal plate to the area where bone develops its funnel or flute shape Diaphysis – Body of bone, between metaphyses  Types of Bone Lamellar – Forms the adult skeleton – // arrangement of collagen fibers – Few osteocytes – Uniform osteocytes in lacunae // to long axis of collagen fibers Woven – Irregular – Many osteocytes of various size and shape – In adults signifies always a pathologic condition  The matrix of bone : Contains inorganic salt Calcium Hydroxyapatite in collagen framework. Osteoblasts - Calcification - Mineralization Minerals  hardness Collagen fibres  Tensile strength. Collagen is necessary for Calcification.  Cells Osteoblasts – Produce the protein – Osteoid Osteocyte – Osteoblast within bone in a lacuna Osteoclast – Multinucleated – Resorbs bone – Howship’s lacunae Osteogenic cells:  The Histologic Types: Compact bone Spongy bone Lamellar bone Woven bone Osteoid Callus  Compact Bone: Osteons or Haversian systems. Osteons contain blood vessels, lymphatic vessels, nerves, and osteocytes along with the calcified matrix. Osteons are aligned in the same direction along lines of stress - Lamellar bone. No osteons or BV in trabecular bone. Compact Bone & Spongy Bone:  Spongy (cancellous) Bone Does not contain osteons. trabeculae surrounding red marrow spaces Cancellous bone: (Polarization.M)  Endochondral Ossification: Within cartilage. Interstitial growth. Cells swell, burst, replace by osteocytes with Ca+  Endochondral Ossification: Secondary ossification - epiphysis Articular cartilage and epiphysial plate -  Membranous Ossification: Skull, mandible, clavicle. Fibrous membrane, Os. center, trabeculae Osteoblasts: Growth plate:  Osteoporosis Reduction of bone mass per unit of bone volume Metabolic bone disease Bone displays normal ratio of mineral to matrix Primary and secondary  Primary Osteoporosis Most common Uncertain etiology Postmenopausal women Elderly persons (senile) – Genetic: peak bone mass – Estrogens: decline – Aging – Calcium intake (800mg/day) – Exercise – Environmental factors: smoking leads to estrogen ↓  Primary Osteoporosis Osteopenia Decrease thickness of cortex Reduction in the number and size of trabeculae Fractures can be the first sign Compression fractures of vertebrae  Secondary Osteoporosis Corticosteroids – Inhibition of osteoblastic activity – Impair of vit. D dependant intestinal calcium absorption (secondary hyperparathyroidism) Hematologic malignancies Malabsorption: GI and liver diseases Alcoholism – Inhibition of osteoblasts, – ↓ absorption of calcium  Osteomalacia and rickets Inadequate mineralization of newly formed bone matrix (osteomalacia) Rickets: children, epiphyseal plates open; also problem with cartilage – Beaded appearance of costochondral junctions – Pectus carinatum – Dental abnormalities Vitamin D deficiency (dependent) Phosphate deficiency (resistant) Defects in mineralization process  Osteomalacia and rickets Osteopenia Exaggeration of osteoid seams Poorly localized pain Femoral neck, pubic ramus, spine, ribs  Hyperparathyroidism Parathyroid adenoma, hyperplasia, rare malignancy Parathyroid hormone – Promotes excretion of phosphate in the urine and stimulates osteoclastic activity resulting in hypercalcemia – Stimulates tubular reabsorption of calcium and excretion of phosphate – Stimulates intestinal calcium absorption  Hyperparathyroidism Stones: Kidney Bones: Brown tumors Psychiatric depression GI tract irregularities  Secondary hyperparathyroidism Renal osteodystrophy Chronic renal failure – Decreased filtration of phosphate Hyperphosphatemia – Effect on active vit. D – Decreased Ca absorption in GI Hypocalcemia – Secondary hyperparathyroidism  Osteomyelitis Inflammation of bone caused by an infectious organism Staphylococcus, streptococcus, Escherichia coli, Neisseria gonorrhea, Haemophilus influenza, Salmonella Direct penetration – Wounds, fractures, surgery Hematogenous – Bloodstream, teeth; metaphyses – Knee, ankle, hip  Complications of Osteomyelitis Septicemia Acute bacterial arthritis Pathologic fractures Squamous cell carcinoma Amyloidosis Chronic osteomyelitis Joints - Anatomy  Arthritis - Introduction Inflammation of joints - Common Common site for autoimmune injury – Heart valves & Joints - damage – Exposure of hidden antigens. Infections. Degeneration – Age/Stress/life style  Arthritis – Clinical features: Pain –  Inflammation - capsule, synovium, periosteum. Swelling: –  inflammation, effusion, proliferation. Restricted movement –  pain, fluid, synovial swelling, damage. Deformity –  mal-alignment, erosion, ankylosis  Osteoarthritis Most common joint disease Slow progressive degeneration of articular cartilage Weight bearing joints Fingers Primary: defect in cartilage, not an inflammatory disease Secondary: trauma, crystal deposits, infection Interphalangeal joints, knees, hips, cervical and lumbar spine  Osteoarthritis Narrowing of joint space (loss of disk) Increased thickness of subchondral bone – Eburnated bone Subchondral bone cysts Osteophytes (Haberden nodes) – Fingers, distal interphalangeal joints  Causes Primary Secondary as: Intra articular fracture Previous infective arthritis Rheumatoid Congenital dislocation of hip  Abnormal stresses as Paget’s disease with deformity Chronic overuse Metabolic and endocrine as : Hemochromatosis Gout Calcium phosphate deposition  Neuropathic disorders as : Peripheral neuropathy as in diabetes mellitus Intraarticular corticosteroid in excess  Osteoarthritis: Degenerative end result - (ageing) >80% in >65y. Progressive erosion & fibrillation of articular cartilage  forms Loose bodies. Large weight bearing joints. Hardened articular bone – eburnation. & Subarticular cyst formation in bone. Periarticular osteophyte formation. Mild inflammation but painful, morning stiffness. Limited range of movements Heberden nodes (F) Normal -- Femur Head -- OA Normal Osteoarthritis Femur Osteoarthritis: Joint Mice or Loose Bodies: Spine Osteophytes (OA):  Radiologic Features: no uniform joint space loss, osteophyte formation, cyst formation subchondral sclerosis Sclerosis, ankylosis & deformity. Osteoarthritis: Narrow joint space Lipping – osteophyte Dislocation Osteoporosis. Osteophyte formation: Bone cysts in OA:  Rheumatoid arthritis Systemic chronic inflammatory disease Autoimmune disease Diarthrodial joints bilaterally STARTS AS SYNOVIAL DISEASE 3:1 women Remissions and exacerbations Heredity; EBV(?)  Theory of Pathogenesis Genetically susceptible patient Infection ? Formation of Abs Abs act as new antigens Production of rheumatoid factor Deposits of immune complexes in the synovium Activation of complement cascade Inflammation Activation of macrophages Homing of T cells Secretion of cytokines  RA - Definition: Chronic Multisystem autoimmune inflammatory disorder primarily affecting joints producing a proliferative synovitis that often progresses to destruction of the articular cartilage and ankylosis.  Etiology: Genetic Susceptibility: – HLA DR4, or DR1 in 65% to 80% cases. Microbial inciting agent: – Epstein-Barr virus, Borrelia & Mycoplasma Autoimmunity: – IGM anti IgG – RA Factor. – Helper T cell (CD4) against type II collagen & cartilage glycoprotein-39  Pathology Inflammation of the joint and hyperplasia of the synovium followed by destruction of the articular structures The synovium infiltrated with lymphocytes and plasma cells Fibrin exudation on the synovial fluid forming sometimes soft loose bodies called Rice bodies Neutrophil polymorphs are present  All previous changes are reversible When granulation tissue grows over the surface of the articular cartilage Pannus interfere with the nutrition of the cartilage leads to permanent joint damage.  Histopathological features Rice bodies Hyperplastic synovium Pannus Allison-Ghormley bodies Rheumatoid nodules  Extra articular manifestation Rheumatoid nodule Vasculitis Cardiac disease Pulmonary disease Serosal inflammation Amyloidosis Anemia Eye involvement  Morphology: Proliferative synovitis with lymphocytes (CD4), plasma cell & macrophages Pannus. Organizing fibrin (rice bodies). Neutrophils on the joint surface and fluid. Juxta-articular erosions, cysts & osteoporosis Fibrous ankylosis. Skin - Rheumatoid nodules Vasculitis (commonly of digital arteries)  Early Destruction in RA: Swan Neck Deformity  RA - Clinical Features: 1. Morning stiffness. 2. Arthritis in 3 or more joint areas. 3. Arthritis of small hand joints. 4. Symmetric arthritis. 5. Rheumatoid nodules. 6. Serum rheumatoid factor. 7. Typical radiographic changes At least 4 features for diagnosis. RA - Pannus: RA - Pannus: Hyperplastic inflammed synovium  Extra-Articular RA Rheumatoid Nodules Vasculitis Pleuritis Pericarditis Tendonitis Skin RA Nodule: Skin RA Nodule:  Rheumatoid Nodule (skin): Palisading Macrophages Central Fibrinoid Necrosis Joint involvement in RA: Swan Neck Deformity in RA:  Differentiating Features: Rheumatoid Arthritis: Young, small joints Autoimmune. Synovial Inflammation synovium  Cartilage Osteoarthritis: Old, Large joints Degenerative. Cartilage degeneration. Cartilage  Synovium  Rheumatoid arthritis osteoarthritis Age Any age 25- 55 Elderly Affected joint Symetrical artheritis Hip metacarbophalangeal Knee inerphalangeal wrist Ankle shoulder Synovium Hyperplasia dense Mild secondary inflammation inflammation Articular cartilage Eroded by pannus loss of weigh bearing surface Systemic disease Yes No Pathogenesis Autoimmune disease degenerative  Juvenile rheumatoid artheritis Starts below 16 years Most common 1- 3 years High spiking fever daily or twice daily Hepatosplenomegaly Serosal inflammation ( pericarditis ) Generally involve knee, wrist, elbow, small joints of hands and feet.  Juvenile Rheumatoid Arthritis: Before age 16 Multisystem involvement - Splenomegaly, Starts with systemic involvement unlike RA. No serum RA Factor – Seronegative Antinuclear Antibody (ANA) +ve  autoimmune.  Gout Increase in serum uric acid and deposition of urate crystals in the joints and kidneys Only 15% of patients with ↑ uric acid suffer from gout Gout can result from: – Overproduction of purines – Augmented catabolism of nucleic acids – Decreased hypoxanthines ( X- linked) rare cases – Decreased uric acid excretion Primary gout Secondary gout  Primary gout Hyperuricemia in the absence of other disease - serum urate concentration greater than 7mg/dl in adult males or 6mg/dl in adult females – Asymptomatic hyperuricemia can precede gout Hyperuricemia is due to increased production and Impaired excretion by kidneys  Primary gout Affect middle aged males Those of family history Less than 10% of patients are females and usually occurs after menopause  Secondary gout Tumors – Leukemias – Lymphomas – After chemotherapy Alcoholism – Accelerated ATP catabolism  Clinical features Acute gouty arthritis – Painful, red and swollen – Involves one joint initially, then polyarticular – Start in the big toe – Podagra (painful, red metatarsophalangeal joint) Tophaceous gout – Development of tophi Chalky, cheesy, yellow-white, pasty deposits of monosodium urate crystals – May found in the pinna of ear – Achilles tendon  Gout Pathology – Formation of granulomas with needle-shaped crystals Renal failure, urate stones Big Toe in Gout: Gout Tophi: Urate Crystals (Gout):  Pseudo Gout Calcium PyroPhosphate Deposition disease CPPD Chondrocalcinosis. Calcium pyrophosphate crystal are deposited in cartilage and juxta-articular tissues The large joints particularly the menisci of the knees of the elderly are affected CPPD may be familial or secondary to hyperparathyrodism  CPPD – (Chondrocalcinosis) Type A – Pseudo gout – Knee of elderly men Type B – Pseudo rheumatoid - polyarthritis Type C – Pseudo OA + acute attacks, women Type D – Pseudo OA - acute attacks, hands Type E – Asymptomatic Type F – Pseudoneuropathic CPPD-Arthritis (pseudo gout): Pseudo Gout – Calcium pyrophoshate  Muscular dystrophy Duchenne muscular dystrophy Common genetic myopathy Is the most severe form of muscular dystrophy and the most rapid progressive Incidence 3/10,000 live born males X- linked recessive gen affect male females carriers Result in dysfunction of the sarcolemmal membrane allowing ingress of ca ions  The affected males present before the age of 5 years with delayed development of motor function especially a waddling gait and inability to run Because of weakness of pelvic-girdle muscle these children are unable to rise easily form the floor and use their arms to push the trunk into the upright position (Gower’s manoeuvre)  The majority of boys are confined to a wheelchair by 13 years of age and death due to respiratory failure or cardiac arrhythmias in the late teens Pathological findings Hyaline (prenecrotic) and necrotic fibers with adequate regeneration up to 1 year Then the regenerative capacity declines Then progressive replacement of the muscle fibers by adipose and fibrous tissue which result in pseudohypertrophy  Diagnosis Dystrophin testing is carried on muscle biopsy Carriers may be detected by - Serial serum creatine kinase estimation but negative results do not exclude this state ……why ??? - tracking the mutant gene within a family using DNA analysis  Becker’s muscular dystrophy Inherited X- linked recessive gen Incidence 0.5/ 10,000 Age onset 3- 20 years Its more benign and death is from 30-60 years of age  Myotonic dystrophy Autosomal dominant disease Due to mutation on chromosome 19 Clinically → Stiffness As delayed relaxation of muscle after contraction Distal weakness seen as foot- drop Involvement of other systems leads to cardiomyopathy, testicular atrophy and mental retardation Diagnosis by electromyography