What are the functions of bone cells?
Osteoblasts form new bone, whereas osteoclasts remove and remodel old bone under the influence of hormones.
Define epiphysis, metaphysis, and diaphysis and explain why a knowledge of these anatomic terms is important for pathology.
epiphysis = above the growth plate
diaphysis = the central part of long bones
metaphysis = the growth plate and adjacent terminal diaphysis which represent the most metabolically active segment of the long bones
Compare endochondral and intramembranous ossification.
osseous transformation of the cartilage in the growth plate
- ceases by the end of puberty (but can still occur during healing of bone fractures)
bone formation that results from direct transformatio of fibrous matrix into osteoid, followed by mineralization
- accounts for subperiosteal bone formation of long bones
- continues through the normal life span
What are the main functions of bones?
Mechanical support for the muscles, which makes possible the movement of limbs
Protection of internal organs, such as the ribs forming the thorax or the skull protecting the brain
Support of hematopoiesis, which occurs in the bone marrow
Storage of calcium and phosphate salts
What is the basic structure and function of joints?
A joint is a junction between two or more bones, designed to provide support and structureal firmness and to allow movement.
1) moveable diarthrodial or synovial joints: knee, etc
2) limited mvmt synarthoses: head, trunk
What is achondroplasia?
Autosomal Dominant mutation in gene encoding fibroblast growth factor receptor 3.
Adversly affects endochondral ossification and growth of long bones = dwarfism.
What is osteogenesis imperfect?
Various mutations involving the encoding of collagen I.
Range of ages affected from in utero to later in life. Symptoms are not limited to the bones, and may have thin skin, thin dental enamel, defective heart valves, bluish hue to sclera.
What are the main causes of osteomyelitis?
Most common: staph aureus
Drug addicts: mixed flora hematogenous infections
Sickle cell: salmonella
Pott's disease: mycobacterium, chronic osteomyelitis of the spine
Describe the principal pathologic feature of osteomyelitis.
The bacteria reach the metaphysis through the nutrient artery. Bacterial growth results in bone destruction and formation of an abscess.
From the abscess cavity, the pus spreads between the trabeculae into the medulla, through the cartilage into the joint, or through the haversian canals of the compact bones to the outside.
These sinuses traversing the bone persist for a long time and heal slowly. The pus destroys the bone and sequesters parts of it in the abscess cavity. Reactive new bone is formed around the focus of inflammation.
What are the possible causes of aseptic bone necrosis?
Sudden onset of ischemia caused by disruption or complete interruption of blood flow.
May be related to trauma, emboli, radiation, or drugs.
A disease of growing children, but also elderly
Describe the typical clinical features of aseptic bone necrosis.
Carpal bones are especially vulnerable because of their complex blood supply.
In elderly: most important site is head of the femur
What are the causes of osteoporosis?
Primary: disease of elderly
Secondary: can occur at any age
- hormone disturbance
- dietary insufficiency or malabsorption
Discuss the pathogenesis of osteoporosis.
Bone resorption outpaces bone formation resulting in net bone loss.
What are the complications of osteoporosis?
- Type 1: trabecular bone loss predominates, mostly in the vertebrae and distal radius
Major complications = crush fractures of vertebral bodies and distal end of radius
- Type 2: proportional loss of cortical and trabecular, head of femur, wedge fractures of vertebrae
What is osteomalacia?
Inadequate mineralization of the organic bone matrix, caused by disturances of either vitamin D or phosphate metabolism.
Osteomalacia of growing bones = rickets
Explain the role of vitamin D in calcium homeostasis.
Activation of vitamin D occurs in the liver and kidneys. Several active metabolites are fromed, of which the hydroxylated 1,25 vitamin D is the most important.
This vitamin D does three things:
1) stimulation of intestinal absorption of calcium and phosphorus
2) deposition of calcium into the osteoid and movilization of calcium from calcified bone; mineralization of osteoid
3) stimulation of teh PTH dependent resorption of calcium in the kidney
Compare rickets and osteomalacia.
- growing bones
- endochonral ossification severely disturbed
- growth retardation, softening of growing bones (bowlegs), deformities
- excess of osteoid around the calcified core of the trabeculae of spongy bone and ont he endocavitary side of compact bones
- often asymptomatic
- muscle weakness
How is osteomalacia diagnosed?
- clinical symptoms
- radiographic evidence of osteopenia
- laboratory: low vit D, calcium and phosphate; elevated PTH
*but in phosphate deficiency, the serum phosphate is low while calcium and PTH are normal
What are the main pathologic features of renal osteodystrophy?
Kidneys cannot excrete phosphorus
= elevated serum phosphate
PTH stimulates bone resorption and release of Ca and phosphate.
Describe the three phases of Paget's disease.
1: destructive phase, bone resorption
2: mixed phase, bone resorption counterbalanced by new bone formation
3: osteosclerotic phase, normal compact bone is replaced by wide sclerotic dense bone
Describe various forms of fracture of long bones.
simple = single fracture line
comminuted = multiple lines and fragments
closed = overlying skin intact
complete = through entire thickenss of bone
incomplete = do not extend from one side to another
complicated = infected
Describe the healing of fractures.
Healing first requires immobilization; prevents disruption of scaffolds that can cause additional bleeding into the fracture site.
Large fractures you must remove necrotic tissue.
Compression of two sides of the fracture promotes healing.
Also depends on vitamin C, D, calcium and phosphorus.
2. Granulation tissue
3. Bony callus
What happens during joint dislocation?
Occurs as a result of force or abnormal movement; the bones forming the joint lose contact and become misaligned.
Classify bone tumors.
Bone forming cells: osteoma and osteosarcoma
Cartilate cells: chondroma and chondrosarcoma
Osteoclasts: giant cell tumor
Primitive Mesenchymal bone marrow cells: Ewing's sarcoma
Secondary tumors: outnumber primary 10:1, most common sites are breast, lung, prostate, kidney, thyroid
Describe the main pathologic and clinical features of osteosarcoma.
Most common primary malignant tumor involving bone.
- most often metaphysis of long bones
- 50% in knee joint
- also jawbone
- young people
- metastases, esp lung
Describe the main pathologic and clinical features of chrondrosarcoma.
Composed of neoplastic cartilage cells.
- originate in axial skeleton
- and adjacent long bones
- affect adults, peak 35-60
- treatment = surgery, not responseive to chemo
Describe the main pathologic and clinical features of Ewing's sarcoma.
Small cells with hyperchromatic bluish nuclei and very little cytoplasm, and abundant glycogen.
- located mostly in diaphysis
- 85% have translocation btw 11 and 22, fusion protein FLI and EWS
- cortical bone invasion
- suburst or onion skin appearance on x-ray
- occurs mostly in the young
What are the main pathologic and clinical features of giant cell bone tumor?
Originate in the epiphyses of long bones
What is osteoarthritis?
- Most common joint disease
- Possibly a metabolic disorder, or inflammation
- Usually due to stress
Compare the facts favoring the wear and tear hypothesis of osteoarthritis with those favoring a metabolic or inflammatory origin for this disease.
Wear and Tear
- develops in weight bearing joints
- prevalence increases with age
- mechanical stress accelerates the disease
- familial component of abnormal CT
- prominent inflammation
- finger joints can be affected and are not weight bearing joints
- responsive to anti-inflammatory meds
Describe the pathology of osteoarthritis.
Fragmentation and loss of cartilage denuge the subchondral bone, which undergoes sclerosis (eburnation) and cystic change. Osteophytes form on the lateral sides and protrude into the adjacent soft tissues, causing irritation, inflammation, and fibrosis.
What are the main clinical signs and symptoms of osteoarthritis?
most common symptom = pain
- reduced mobility
- crepitus (rough articular surfaces
- muscle spasm and contractures
What is rheumatoid arthritis?
A disease characterized by systemic inflammation of the joints. An autoimmune disease that primarly involves the synovial joints.
What are the roles of hormones, genes, and autoimmunity in the pathogenesis of rheumatoid arthritis?
Hormones: affects w > m
Familial predisposition: HLA loci on chromosome 6
Autoimmunity: increased incidence of autoimmune diseases
What is pannus, and how does it evolve?
Pannus is caused by exuberant synovial fronds that transform into granulation tissue. The pannus cover ths articular surfaces like a sheet. It is rich in inflammatory cells that secrete lytic enzymes and various mediators of inflammation.
Describe the pathology of rheumatoid arthritis.
Inflammation leads to pannus formation, obliteration of the articular space, and finally ankylosis (collagenous scar). The periatricular bone show disuse atrophy in the form of osteoporosis.
Whare are the clinical features of rheumatoid arthritis?
Nonspecific: low-grade fever, fatigue, loss of appetite, anemia
Rheumatoid subcutanous nodules
What are the main causes of infectious arthritis?
Most common = Lyme
pyogenic = staph or strep (rare)
What is gout?
Group of diseases characterized by hyperuricemia and the deposition of uric acid crystals in the joints, subcutaneous tissues, and kidneys.
Hyperuricemia (>7mg/dL) is a prerequisite, but only 5% of these patients develop gout.
How common is gout in men and women?
95% are male, many have family history
Compare primary and secondary gout.
Primary gout: metabolic or renal
Secondary gout: hematopoietic malignant disease, chronic hemolysis, obestiy, alcoholism, kidney disease, drugs (diuretics), lead poisoning
How does hyperuricemia lead to podagra.
Most uric acid crystals form deposit as insoluble monosodium urate . . . esp in the joints and periarticular connective tissue.
Tarsometatarsal joint of the big toe in 90%: podagra "foot seizure"
Likely because the feet are colder and reduces uric acid solubility >> crystalization inside joint. Activates complement and recruits leukocytes. Because the crystals are sharp, they pierce the lysosomes and release acid hydrolases.
Compare the clinical features of acute and chronic gout.
Acute = joint is swollen, hyperemic, warm, excruciating pain
Chronic = less inflammation, but more bone deformities
What are tophi?
Painless subcutaneous deposits of uric acid.
Most commonly on the ears, extensor sites of the arms, over the olcranon, and patella.
Encapsulated, birefringent urate crystals, surrounded by macrophages, lymphocytes, and giant cells.
What kind of urinary stones are found in persons who have gout?
Uric acid stones
Also predisposes to the formation of calcium stones.