Bone Physiology and Pathology Quiz

Musculoskeletal System

• The musculoskeletal system provides form, support, stability, and movement to the body.
• Composed of: bones, muscles, cartilage, tendons, ligaments, joints, and connective tissue.

Bone

• Dynamic tissue with osteoblasts (forming bone) and osteoclasts (resorbing bone).
• Osteoblasts produce osteoid, a protein matrix composed of type 1 collagen.
• Calcium and phosphate are incorporated into the matrix, forming calcium hydroxyapatite, which gives bone its hardness.
• Bone anatomy consists of:
  • Diaphysis: shaft of the bone
  • Metaphysis: wider portion at the end of the diaphysis
  • Epiphysis: end of the bone, further divided into proximal and distal epiphyses
  • Epiphyseal line: growth plate between the epiphysis and metaphysis
  • Periosteum: outer covering of bone
  • Compact (cortical) bone: dense outer layer
  • Spongy bone: inner layer with trabeculae
  • Articular cartilage: smooth surface covering the joint ends
  • Medullary cavity: central space within the bone
  • Marrow: tissue within the medullary cavity (red marrow produces blood cells)

Types of Bone Tissue

• Woven bone: irregular, immature bone found in the fetus and during fracture repair
• Lamellar bone: regular, mature bone found in adults, further divided into:
  • Circumferential lamellae: outer layers
  • Concentric lamellae: layers arranged around a central haversian canal
  • Interstitial lamellae: remnants of old osteons
  • Trabecular lamellae: found in spongy bone
• Compact and spongy bone are both lamellar bone.
• Bone formation can be endochondral (cartilage template) or intramembranous (directly from mesenchymal tissue).

Bone Growth Plate

• Located at the epiphyseal line.
• Responsible for longitudinal bone growth.
• Composed of zones of proliferating chondrocytes (cartilage cells).

Osteoporosis

• Reduction in bone mass per unit of bone volume.
• Metabolic bone disease with normal mineral to matrix ratio.
• Primary osteoporosis: most common, uncertain etiology, common in postmenopausal women and elderly.
  • Affects peak bone mass, involves estrogen decline, and aging.
  • Calcium intake (800mg/day), exercise, and environmental factors like smoking (decreases estrogen) are important.
• Secondary osteoporosis: caused by other conditions, including:
  • Corticosteroids: inhibit osteoblastic activity and impair vitamin D's role in calcium absorption.
  • Hematologic malignancies: can impact bone mass
  • Malabsorption: GI and liver diseases
  • Alcoholism: inhibits osteoblasts and reduces calcium absorption

Osteoporosis Manifestations

• Osteopenia: decrease in bone thickness, especially cortical bone.
• Reduction in the number and size of trabeculae, the thin, bony struts within spongy bone.
• Fractures can be the first sign, particularly compression fractures of vertebrae.

Osteomalacia and Rickets

• Inadequate mineralization of the newly formed bone matrix.
• Osteomalacia: in adults
• Rickets: in children, affecting the open epiphyseal plates and cartilage.
• Characterized by:
  • Beaded appearance of costochondral junctions (where ribs meet cartilage)
  • Pectus carinatum (pigeon chest)
  • Dental abnormalities
• Caused by:
  • Vitamin D deficiency
  • Phosphate deficiency
  • Defects in mineralization process

Osteomalacia and Rickets Manifestations

• Osteopenia
• Exaggeration of osteoid seams (unmineralized bone matrix)
• Poorly localized pain, often in the femoral neck, pubic ramus, spine, and ribs

Hyperparathyroidism

• Excess parathyroid hormone (PTH) due to:
  • Parathyroid adenoma (tumor)
  • Parathyroid hyperplasia (overgrowth of glands)
  • Parathyroid malignancy (rare)
• PTH causes:
  • Increased phosphate excretion in urine and stimulation of osteoclastic activity, leading to hypercalcemia (high blood calcium).
  • Increased tubular reabsorption of calcium and excretion of phosphate.
  • Increased intestinal calcium absorption.

Hyperparathyroidism Manifestations

• Stones: kidney stones
• Bones: brown tumors (bone lesions)
• Psychiatric depression
• GI tract irregularities

Secondary Hyperparathyroidism

• Occurs due to chronic renal failure.
• Leads to:
  • Decreased filtration of phosphate, causing hyperphosphatemia (high blood phosphate).
  • Impaired active vitamin D production.
  • Decreased calcium absorption in GI tract, leading to hypocalcemia (low blood calcium).
  • Secondary hyperparathyroidism develops as a response to these abnormalities.

Osteomyelitis

• Inflammation of bone caused by an infectious organism, often bacteria like:
  • Staphylococcus
  • Streptococcus
  • Escherichia coli
  • Neisseria gonorrhea
  • Haemophilus influenza
  • Salmonella
• Infection can occur via:
  • Direct penetration: wounds, fractures, surgery
  • Hematogenous spread: through the bloodstream (common in metaphyses of long bones, especially the knee, ankle, and hip)

Osteomyelitis Complications

• Septicemia: blood poisoning
• Acute bacterial arthritis
• Pathologic fractures: fractures caused by weakened bone
• Squamous cell carcinoma: a type of skin cancer
• Amyloidosis: abnormal protein deposits
• Chronic osteomyelitis: persistent infection

Joints - Anatomy

• Joints are the points where two or more bones meet
• Different types of joints with varying degrees of movement
• Articular cartilage covers the ends of the bones, providing a smooth surface
• Synovial fluid lubricates the joint

Arthritis

• Inflammation of joints, a common condition.
• Often a site for autoimmune injury due to exposure of heart valves and joints to hidden antigens.
• Can be caused by infections and degeneration.
• Clinical features:
  • Pain caused by inflammation of the capsule, synovium, and periosteum.
  • Swelling due to inflammation, effusion (fluid accumulation), and synovial proliferation (growth).
  • Restricted movement caused by pain, fluid, synovial swelling, and joint damage.
  • Deformity caused by mal-alignment, erosion, and ankylosis (joint fusion).

Osteoarthritis

• Most common joint disease, a slow progressive degeneration of articular cartilage.
• Affects weight-bearing joints (hips, knees) and fingers.
• Primary osteoarthritis: defect in cartilage, not inflammatory.
• Secondary osteoarthritis: caused by various factors like trauma, crystal deposits, and infection.
• Narrowing of the joint space is a key sign, indicating loss of cartilage.
• Increased thickness of subchondral bone: the bone beneath the cartilage becomes thickened (eburnation).
• Subchondral cysts: fluid-filled cavities within the bone beneath the cartilage.
• Osteophytes: bony growths (bone spurs), also known as Heberden nodes on the fingers.

Osteoarthritis Causes

• Primary: intrinsic cartilage defect
• Secondary:
  • Intra-articular fracture
  • Previous infective arthritis
  • Rheumatoid arthritis
  • Congenital dislocation of hip
  • Abnormal stresses (Paget's disease)
  • Chronic overuse
  • Metabolic and endocrine disorders (hemochromatosis, gout, calcium phosphate deposition)
  • Neuropathic disorders (peripheral neuropathy in diabetes mellitus)
  • Excess intra-articular corticosteroids

Osteoarthritis Histopathology

• Fibrillation: fraying and roughening of the articular cartilage
• Loose bodies: pieces of cartilage floating in the joint space
• Eburnation: hardened articular bone
• Subarticular cyst formation
• Rice bodies: small, white, rice-shaped bodies in the joint fluid, comprised of fibrin.
• Hyperplastic synovium: thickened synovium
• Pannus: a thick, abnormal layer of tissue that can form in the synovium and over the cartilage.
• Allison-Ghormley bodies: small, round bodies found in the joint fluid.
• Rheumatoid nodules: firm, rubbery lumps that can appear in the skin or other organs.

Rheumatoid Arthritis (RA)

• Autoimmune, chronic inflammatory disease.
• Inflammation of the synovium (lining of the joint), which eventually destroys cartilage.
• Affects small joints, especially in the hands and feet, bilaterally (symmetrically).

RA - Clinical Features

• Morning stiffness that lasts at least an hour.
• Arthritis in at least 3 joint areas.
• Arthritis in the small hand joints.
• Symmetrical arthritis.
• Rheumatoid nodules.
• Positive serum rheumatoid factor (antibody).
• Typical radiographic changes
• At least 4 of these features are required for diagnosis.

RA Pannus

• Hyperplastic and inflamed synovium.
• Infiltrates the joint space, destroying cartilage and bone.

Extra-Articular RA

• Can affect other parts of the body:
  • Rheumatoid nodules: firm, rubbery lumps in the skin, caused by inflammation.
  • Vasculitis: inflammation of blood vessels, affecting small arteries, especially those in the fingers.
  • Pleuritis: inflammation of the pleura (lining of the lungs).
  • Pericarditis: inflammation of the pericardium (lining of the heart).
  • Tendonitis: inflammation of tendons.

RA Nodule Microscopic Features

• Central fibrinoid necrosis: a central area of dead tissue, often with a granular appearance.
• Palisading macrophages: macrophages (immune cells) arranged around the necrotic area.

Joint Involvement in RA

• Swan neck deformity: a bending of the finger joint at the middle joint (PIP) and straightening of the end joint (DIP), resulting in a swan-neck shape.

Differentiating RA from Osteoarthritis

Pseudogout (Calcium Pyrophosphate Deposition Disease - CPPD)

• Deposition of calcium pyrophosphate crystals in cartilage and juxta-articular tissues.

Types of CPPD

• Type A (Pseudo Gout): primarily affects the knee of elderly men.
• Type B (Pseudo Rheumatoid): affects multiple joints, causing polyarthritis, similar to RA.
• Type C: Combines features of OA and acute attacks, more common in women.
• Type D: Pseudo OA, acute attacks, primarily affect the hands.
• Type E: Asymptomatic, without symptoms.
• Type F: Pseudoneuropathic, associated with nerve damage, resembling Charcot joint.

CPPD Clinical Features

• Often found in patients with hyperparathyroidism.
• Frequent in elderly.
• Affects joints like the knee.
• Characterized by joint swelling and inflammation, commonly triggered by trauma.

CPPD Histopathology

• Calcium pyrophosphate crystals present in the cartilage, synovium, and joint fluid.

Muscular Dystrophy

• Group of genetic diseases affecting muscle, causing weakness and degeneration.
• Duchenne muscular dystrophy (DMD) is the most common type, X-linked recessive.

Duchenne Muscular Dystrophy (DMD)

• Affects males primarily because the gene is on the X chromosome.
• Onset before age 5: Delayed motor development, waddling gait, difficulty running.
• Gower's manoeuvre: using arms to push the body up from a squatting position due to weakness in pelvic girdle muscles.
• Wheelchairs needed by 13 years old.
• Death from respiratory failure or cardiac arrhythmias in late teens.

DMD Pathological Findings

• Hyaline (prenecrotic) and necrotic muscle fibers with initial good regeneration.
• Regeneration decreases over time.
• Progressive replacement of muscle fibers with adipose and fibrous tissue, causing pseudohypertrophy (muscle feels larger due to fat and connective tissue).

DMD Diagnosis

• Dystrophin testing on muscle biopsy (dystrophin is a protein important for muscle function).
• Serum creatine kinase estimation: Elevated in carriers, but negative results don't rule out the possibility of being a carrier.