Pathophysiology I

Week 5

BONE NEOPLASMSChapter 57

Bone Tumors

• Primary bone tumors are relatively uncommon (1% of all adult cancers, 15% of pediatric cancers)

• Metastatic lesions in the bone are more common

• Three main symptoms of bone tumors:

– Pain (may not occur with benign tumors)

• Not relieved by rest

– Presence of a mass

– Impairment of function

• Limp, numbness, decreased range of motion

Benign Bone Tumors

• 1. Osteoma: small

– Found of long bones, flat bones, skull

– Can be removed or left alone

• 2. Chondroma: composed of hyaline cartilage

– May be on surface or within medullary cavity

– Common in hands and feet

– Treated if it causes pain

Benign Bone Tumors

• 3. Osteochondroma: most common, originates in epiphyseal cartilage plate– Grows only during periods of skeletal growth– May affect one bone or several bones (multiple exostoses)

• 4. Osteoclastoma (giant cell tumor): aggressive, behaves like a malignant tumor– Occurs in adults in 20s-40s– Often in knee, wrist, shoulder– Begins in metaphysis then spreads to epiphysis and joint

surface– Pathologic fractures are common– Treated with excision and possibly radiation

Malignant Bone Tumors

• Lack of distinct borders

• Spread beyond the confines of the bone

• Usually suspected based on x-ray appearance

• MRI and CT scan help determine extent of spread into soft tissues and medullary cavity

• Bone scan looks for metastases

• Biopsy provides definitive diagnosis

Malignant Bone Tumors

• Osteosarcoma

– Aggressive and highly malignant

– Most common primary malignant bone tumor

• Third most common cancer overall in children & adolescents

– Often occurs near the knee

• Also occurs in proximal humerus, hands, feet, skull, jaw

– Bimodal distribution

• 75% younger than 20 years of age

• Elderly patients with Paget disease, prior radiation treatment or bone infarcts

Malignant Bone Tumors

• Osteosarcoma– Deep bone pain, often sudden onset

– Occurs at sites of and during times of maximal growth velocity (increased osteoblastic activity)

– Genetic predisposition (2 identified genes)

– Start in metaphysis, spread to periosteum then adjacent tissues

– Lung metastasis is common (usually asymptomatic)

– Treatment: surgery, chemotherapy

Malignant Bone Tumors

• Ewing’s Sarcoma

– Second most common type of primary bone tumor

– Often in early teenage years

– Sites: femur, pelvis, pubis, sacrum, humerus, vertebrae, ribs, skull

– Most caused by a reciprocal translocation of chromosomes 11 and 22

Malignant Bone Tumors

• Ewing’s Sarcoma

– Pain, decreased ROM, overlying soft tissue tenderness

– Fever, weight loss can occur

– Pathologic fractures

– Metastasizes to lungs, bone marrow, other bones

– Treated with surgery, multiagent chemotherapy, radiation

Malignant Bone Tumors

• Chondrosarcoma– Tumor of cartilage– Occurs in medullary cavity and at proximal points of

muscle attachment (knee, shoulder, hip, pelvis) – Middle or late life, slightly more in males– Can arise from a pre-existing benign bone lesion like

an osteochondroma– Often painless, slow growing, late metastasis– Early surgery is best treatment (radiation not very

effective)– Can transform into a mesenchymal chondrosarcoma-a

highly malignant tumor

Metastatic Bone Disease

• Occurs because venous blood flow in skeleton is sluggish. Pain is due to periosteal stretching or nerve entrapment

• Most often occur in spine, femur, pelvis, ribs, sternum, humerus, skull

• Breast, lung, prostate, kidney, thyroid most common• Usually several bony sites, can occur with or without other

organ involvement• Very painful, increased fracture risk, disability• Elevated calcium and alkaline phosphatase levels• Radiation can be treatment or palliative• Surgery, chemotherapy, bisphosphonates used

DISORDERS OF SKELETAL FUNCTION:RHEUMATIC DISORDERS

Chapter 59

Arthritis

• A general term that can apply to local wear and tear or systemic autoimmune disorders that result in joint inflammation

• Can affect people of all ages

• Second leading cause of disability in the US

• No cure

• Autoimmune rheumatic diseases are systemic and chronic with diffuse inflammation and degenerative changes in connective tissue

Rheumatoid Arthritis

• RA affects 0.3%-1.5% of the population

– 2-3 times more common in women

• Can happen at any age, but peaks at 40-60yrs

• Genetic predisposition (HLA DR4, HLA DRB1)

– ?infectious trigger

• Abnormal immune response that causes synovial inflammation and joint destruction

Rheumatoid Arthritis

• Immune system pathology

– Activated helper T cells

– Cytokine release

– Antibody formation

• Rheumatoid factor is present in 70-80% of patients with the disease and can aid in diagnosis. RF is an antibody that reacts with immunoglobulin G to form immune complexes

Rheumatoid Arthritis

• Immune complexes are in synovial tissue• Neutrophils, macrophages, lymphocytes are

attracted to dissolve immune complexes and inflammatory enzymes are released which cause joint destruction

• Vasodilation, synovial hyperplasia leads to warmth, redness and swelling

• Pannus: proliferation of blood vessels and inflammatory tissue in the synovium that can lead to destruction of bone and cartilage and lead to reduced joint motion

Rheumatoid Arthritis

Characterisitics:

– Joint pain, warmth, swelling

– Joint instability

– Muscle atrophy from disuse

– Ligamentous stretching

– Joint inflammation

– Irreversible joint destruction

– Progressive or with intermittent exacerbations and remissions

– Can involve few or multiple joints

Rheumatoid Arthritis

• General Symptoms:– Fatigue, anorexia, weight loss

– Generalized aches, stiffness

• Joint Symptoms:– Symmetric involvement of any diarthrodial joint

– Commonly starts in fingers, hands, wrists, knees, feet then can progress to other joints including cervical spine

– Polyarticular

– Pain and stiffness for 30 mins-several hours

Rheumatoid Arthritis

• Fingers: usually PIP and MCP joints, rarely DIP joints. Ulnar deviation of MCPs is common.

• Swelling and thickening of the synovium stretches ligaments and the joint capsule.

• Muscle imbalances result in joint deformities and increased risk of subluxation and dislocation

• Swan neck deformity: hyperextension of PIPs and partial flexion of DIPs

• Boutonnière deformity: flexion of PIP with hyperextension of DIP

Rheumatoid Arthritis

• Knee is commonly affected and results in much of the disability– Joint contractures, instability– Genu valgus– Quadriceps atrophy– Baker’s cyst: enlargement of bursa

• Ankle: limited range of motion and difficulty walking• Neck pain• Headaches • Numbness and tingling• Muscle weakness

Rheumatoid ArthritisExtraarticular manifestations

• Fatigue, weakness, anorexia, weight loss• Anemia (resistant to iron therapy)• Rheumatoid nodules: tender or nontender, usually develop over

pressure points• Small and medium artery vasculitis resulting in ischemia around nail

folds, ulcers, neuropathy• Ocular: episcleritis, scleritis• Pulmonary disease• Cardiac complications• Leukopenia• Elevation of erythrocyte sedimentation rate (ESR): a nonspecific

laboratory test that indicates inflammation. The higher the level, the more inflammation is present

Diagnosis of Rheumatoid Arthritis

• At least four of the following criteria:

– Morning stiffness (min. 1 hour for 6 weeks)

– Swelling of 3 or more joints for 6 weeks

– Swelling of wrist, MCP, PIP joints for 6 weeks

– Symmetric joint swelling for 6 weeks

– Rheumatoid nodules

– Positive rheumatoid factor (can be positive in 1-5% of healthy people who do not have the disease)

– X-ray changes consistent with rheumatoid arthritis

Treatment of RA

• Goals: reduce pain, minimize stiffness and swelling, maintain mobility, education

• Physical and emotional rest• Therapeutic exercise• Heat and cold• Posture, body mechanics, supportive shoes• Aggressive medication management to reduce risks of

irreversible destruction – NSAIDs– Disease-modifying antirheumatic drugs (DMARDs)

• Methotrexate is commonly used• Corticosteroids for pain control

Systemic Lupus Erythematosus(SLE)

• Chronic inflammatory disease that can affect any organ • 1:2000 with 10:1 female predominance• Cause is unknown (? Sex hormone imbalance, chemicals,

UV light)• A drug induced lupus-like disorder can occur and resolves

once the drug is discontinued• Genetic predisposition, more common in African Americans• Autoantibodies formed, immune complexes

– Antinuclear antibodies (ANA)– Anti-DNA antibodies – Antibodies against blood cells can lead to anemia,

thrombocytopenia

SLE

• Can affect many systems:– Arthralgia, arthritis (can be symmetric, but no joint destruction)– Ligament, tendon, joint capsule involvement can lead to joint

deformities– Tenosynovitis– Rupture of patellar and Achilles tendons– Avascular necrosis– Skin rash (malar rash, photosensitivity)– Renal involvement (50% of patients)

• Glomerulonephritis• Nephrotic syndrome

– Pulmonary: pleural effusions, pleuritis, hemorrhage– Cardiac: pericarditis, myocarditis, hypertension, ischemia– CNS: strokes, hemorrhage, seizures, depression, psychosis

SLE

• Diagnosis is based on a combination of history, physical exam, labs

• ANA: non-specific but 95% of patients with untreated SLE have high titers

• Anti-DNA: more specific

• Anemia, thrombocytopenia, abnormal white blood cell count-either leukopenia or leukocytosis can increase suspicion of disease

SLE

• Treat acute and chronic symptoms

• Prevent organ damage

• Reduce exacerbations

• Prevent complications of treatment

• NSAIDs, hydroxycholorquine, corticosteroids used mainly for renal and CNS disease, cyclophosphamide

Systemic Sclerosis (Scleoderma)

• Autoimmune disease of connective tissue where there excess collagen deposited in skin and internal organs

• Affects women 4 more times than men

• Peaks at ages 35-50

• Unknown immune system disorder

Systemic Sclerosis (Scleroderma)

• Two forms:

– Diffuse or generalized form

• Scleroderma on trunk and proximal extremities

• Severe and progressive with early organ involvement

– CREST

• Scleroderma is on hands and face

Scleroderma

• Diffuse form affects many parts of the body:– Skin: tight facial skin and lips

– Esophagus: hypomotility, trouble swallowing

– Intestine: atrophy, malabsorption

– Pulmonary: dyspnea, pulmonary artery hypertension, respiratory failure

– Kidneys: vascular problems lead to severe hypertension, renal insufficiency

– Cardiac: pericarditis, heart block, myocardial fibrosis

Scleroderma

• CREST:

– Calcinosis: subcutaneous calcium deposits

– Raynaud’s: reversible vasospasm of the arteries in the fingers, particularly in cold

– Esophageal dysmotility

– Sclerodactyly: scleroderma of the fingers

– Telangiectasias

Scleroderma

• Treatment is focused on avoiding progression of organ involvement

• Heart, lung, renal involvement tends to happen early in the disease and indicates a very poor prognosis

• Symptomatic treatment

Polymyositis & Dermatomyositis

• Chronic inflammatory myopathies

• Can have cardiac and pulmonary involvement

• Symmetric proximal muscle weakness

– Trouble styling hair, working overhead

• Muscle pain and tenderness

• Treated with corticosteroids