Walby: Bones Flashcards
unmineralized bone is called
osteoid
lie in a lacuna within the matrix; involved in exchange of nutrients (Ca++ and phosphorous) and waste with blood via canaliculi.
osteocytes
This forms 90% of the organic component of bone
type I collagen
Compare and contrast the 2 types of collagen deposition
woven bone:
fetal skeleton or in adult pathologic states (fractures), grows rapidly, pattern is weaker
lamellar bone:
seen in adults, replaces woven bone at growth plates, deposited slowly, more stable and stronger than woven bone
Most common disease of the growth plate; impaired maturation of cartilage leading to disorganized chondrocytes; results in dwarfism
achondroplasia
In achondroplasia, there is a mutation in (blank)
fibroblast growth factor receptor 3 (FGFR3)
Compare heterozygous achondroplasia to homozygous achondroplasia
heterozygous: shortened extremities, normal trunks, enlarged heads, normal life span
homozygous: comprised respiratory capacity leads to death in infancy - growth hormone not helpful
What is the problem in osteogenesis imperfecta, or brittle bone disease? What happens?
abnormality in type I collagen formation leads to too little bone; results in multiple fractures
In osteogenesis imperfecta, autosomal (blank) cases have increased survival
dominant
**type I and type 4
What are some features associated with osteogenesis imperfecta?
lax joints blue sclera in eye (thinned collagen) deafness thin skin small/discolored teeth
Osteoporosis most commonly occurs in these two populations
postmenopausal women
senile
In osteoporosis, what is the problem?
decreased bone mass/density leads to increased fragility - increased likelihood of vertebral and wrist fractures
Is there a sensitive or specific test for osteoporosis? What do we use?
no; use DEXA scans to measure bone density
In osteoporosis, what can complicate femoral neck, pelvis, and spine fractures?
pulmonary embolism and pneumonia because the pt is immobile
Compare kyphosis and lordosis
kyphosis: curvature of thoracic region
lordosis: curvature of lumbar region
Which is more effective for preventing bone loss, weight training or bicycling?
weight training
How to treat osteoporosis?
hormone replacement like bisphosphonates and calcitonin vitamin replacement (Vit D) exercise/activity stop smoking, drinking don't use corticosteroids
This is the most potent activator of osteoclasts
IL-1
What is the problem in Paget’s disease?
osteoclast dysfunction
What are the three phases of Paget’s disease?
- osteoclast/osteolytic stage –> leads to bone loss, hypervascularity
- mixed osteoclast/osteoblast stages, which end with predominance of osteoblast activity
- ends with a burnt-out osteosclerotic stage
What is the characteristic histologic feature in Paget’s disease?
mosaic pattern of bone (woven bone which is weak and prone to fracture), makes bone look like a jigsaw puzzle
**abnormal bone architecture
What is thought to cause Paget’s disease?
paramyxovirus-like particles that have been found in osteoclasts
Are most cases of Paget’s disease polyostotic or monostotic?
polyostotic
Many cases of Paget’s disease are (blank) and found incidentally on X-rays
asymptomatic
Symptoms of Paget’s disease?
usu asymptomatic
pain is the most common problem (pain in affected bone)
leonine facies (bone overgrowth in craniofacial area)
**in severe polyostotic disease, increased blood flow can cause functional arterio-venous shunt leading to high-output cardiac failure
These can be seen on plain films in the late stages of Paget’s disease
cotton wool spots
Increased incidence of these two tumors in Paget’s disease?
giant cell tumor
sarcomas
Treatment of Paget’s disease
anti-resorptive agents
bisphosphonates
calcitonin
Bones are abnormally brittle and fracture despite excess deposits and increased density
Rare, inherited, autosomal dominant and recessive states
Can cause Osteosclerosis (bone in bone appearance on radiology)
osteopetrosis
Defective mineralization (with an increase in non-mineralized osteoid
Vit-D deficiency
Deranged bone growth in children due to Vit D deficiency; overgrowth of epiphyseal cartilage
Rickets
Disease of adults due to under-mineralization of bone during remodeling process; bone is weak and prone to microfractures, most likely in vertebral bodies and femoral necks
osteomalacia
What are 3 ways that Vit D can aid in Ca+ resorption?
- stimulates intestinal absorption of Ca and P
- works with PTH in mobilizing Ca++ from bone
- stimulates PTH-dependent reabsorption of Ca in distal renal tubules
Required for normal mineralization of epiphyseal cartilage and osteoid matrix; maintains supersaturated levels of Ca and P in plasma
Vit D
Main problem with Vit D deficiency?
hypocalcemia, so you start breaking down more bone or you just get improper mineralization
Symptoms of Rickets
frontal bossing of head
pidgeon breast
lumbar lordosis and bowing of legs
What is the problem with hyperparathyroidism?
Too much PTH, which stimulates osteoblasts to release mediators which causes osteoclasts to absorb more bone
What is one notable feature of hyperparathyroidism?
microfractures of bone form a brown tumor when multinucleated macrophages infiltrate and cause reactive fibrous tissue formation
**osteitis fibrosa cystica
Why can renal insufficiency/failure lead to osteomalacia or problems with the bone?
renal failure results in phosphate retention;
when phosphate is high, Ca+ will be low which leads to secondary hyperparathyroidism (release of PTH to try and up Ca++)
**importantly, in the kidneys, Vit D is converted to its active form, so if your kidneys are not working properly, you will have less Vit D production
low vit D and Ca contributes to the osteomalacia
What is one problem when treating renal osteodystrophy?
aluminum deposition in the bone due to dialysis and aluminum containing oral meds which bind to phosphate (interfere w calcium hydroxyapatite)
If the overlying tissue is intact in a fracture, it is considered (blank);
If the fracture site communicates with the skin surface and the skin breaks, it is (blank)
simple; compound
If the bone is splintered, this is a (blank) fracture; if ends of the bone at fracture site are not aligned, it is a (blank) fracture; if the fracture develops slowly due to increased repetitive loads causing a break, it’s a (blank) fracture
comminuted; displaced; stress
T/F: Cartilage is often formed as a part of the early healing of fractures. If the fracture is not immobilized well enough, it may stay as cartilage.
True
All instances of avascular necrosis result from (blank). AVN most commonly occurs in the (blank)
ischemia; hip
Most common causes of avascular necrosis?
idiopathic
steroid administration
2 types of avascular necrosis
subchondral infarcts
medullary infarcts
This type of infarct causes chronic pain, which initially is only present during activity, but progressively becomes more persistent. Cartilage may collapse and predispose to severe osteoarthritis, which eventual joint replacement necessary
subchondral infarcts
This type of infarct is clinically silent; seen in Gaucher’s disease, dysbarism (pressure changes), hemoglobinopathies; they usually remain stable over time and do not lead to collapse
medullary infarcts
T/F: Usually in subchondral infarcts, the cartilage overlying the bone is OK because it gets nutrients from the synovial fluid, not from the underlying medullary area
True
What are most cases of osteomyelitis caused by?
bacteria which reaches the bone by hematogenous spread or spread from an adjacent infection
Most common bacteria causing osteomyelitis? Most common bacteria causing osteomyelitis in neonates? In sickle cell patients? In trauma?
Staph aureus;
E. Coli and group B strep;
Salmonella;
mixed bacterial infections
What are three complications with osteomyelitis that tend to occur commonly in children?
bone abscess periosteal lift (infected fluid elevates the periosteum) extension into the joint (infection extending into joint cavity)
Common location for osteomyelitis in children? In adults?
metaphysis;
anywhere
What happens to the residual necrotic bone, or sequestrum, in osteomyelitis?
it may be resorbed by osteoclasts, or larger areas of necrosis may be surrounded by a rim of reactive new bone, or involucrum
well-defined rim of sclerotic bone surrounds a residual abscess
Brodie’s abscess
What can be helpful in localizing osteomyelitic lesions?
radionuclide scans
What is the most common method of spread for tuberculous osteomyelitis? What bones are usually involved?
hematogenous; favors long bones and vertebrae
In cases of tuberculoid osteomyelitis, the bacillus (TB) needs oxygen, infection usually starts at (blank), then spreads into bone
synovium
In tuberculoid osteomyelitis, extension of infection to adjacent soft tissues is common in spinal lesions. Give an example.
Cold abscess of psoas muscle
Most common malignant tumor of bone
osteogenic sarcoma
4 bone forming tumors
osteomas
osteoid osteoma
osteoblastoma
osteogenic sarcoma
These bone tumors are round to oval - they project from the subperiosteal or endosteal surfaces of the cortex; they are BENIGN but may impinge upon the brain, eye, or oral cavity; they DO NOT undergo malignant transformation
osteomas
Are osteomas benign or malignant?
benign!!!!
**but they can impinge upon the brain, eye, oral cavity, etc
Multiple osteomas may be associated with (blank)
Gardner’s syndrome (familial polyposis)
What’s the difference b/w an osteoid osteoma and an osteoblastoma?
they differ in size, location, and symptoms:
osteoid osteoma: less than 2cm
osteoblastoma: greater than 2cm
osteoid osteoma: peripheral skeleton
osteoblastoma: spine
osteoid osteoma: relieved by aspirin
osteoblastoma: not relieved by aspirin
If osteoid osteomas and osteoblastomas are not completely excised, what will happen?
they will recur if not completely excised
This type of bone tumor is less than 2cm; occurs in peripheral skeleton, femur or tibia; it is painful, usually at night due to the production of PGE2; relieved by ASPIRIN
osteoid osteoma
This type of bone tumor is >2cm; involves spine more frequently; pain is usually a dull ache and is NOT relieved by aspirin
osteoblastoma
Most common malignant tumor of bone; malignant mesenchymal cells which form bone matrix
osteogenic sarcoma (osteosarcoma)
How does a primary osteosarcoma differ from a secondary osteosarcoma?
primary: arises de novo
secondary: arises in conjunction with Paget’s disease or radiation
How old are patients who get osteosarcomas?
most are <20yo
Where do most osteosarcomas occur?
most occur in metaphysis of long bones (60% in the knee)
Osteosarcomas are aggressive lesions. Where are they likely to metastasize?
to the lung
3 types of cartilaginous tumors?
- osteochondroma (osteocartilaginous exostoses)
- enchondroma
- chondrosarcoma
Most common BENIGN tumors of the bones; tumor composed of mature bone with a cartilaginous cap (cauliflower look)
osteochondroma (osteocartilaginous exostosis)
Most osteochondromas arise from (blank)
metaphysis near growth plate of long bones (leg, pelvis, shoulder blade)
pedunculated on a stalk often taking the shape of a cauliflower
osteochondroma (osteocartilaginous exostosis)
BENIGN lesions formed by mature hyaline cartilage; most occur in short tubular bones of hands and feet
enchondroma
In this disease, you get multiple enchondromas, usu on one side of the body
Ollier’s disease
In this disease, you get multiple encondromas associated w hemangiomas of soft tissue
Maffucci’s syndrome
(blank) develop in 1/3 of patients with multiple encondromas
chondrosarcomas
Where are enchondromas most likely to occur?
in small bones of hands and feet
2nd most common matrix forming tumor of bone; often associated with pre-existing enchondroma
chondrosarcoma
Where do chondrosarcomas begin?
in the medullary space, expand and spread to the surface
Where do chondrosarcomas occur?
in the central skeleton (pelvis, shoulder, ribs)
**clear cell variant in epiphyses of long bones
Neoplastic mononuclear cells; abundant reactive osteoclast-like multinucleated cells
giant cell tumor of bone
Where do giant cell tumors usually occur?
epiphyses of long bones
What do giant cell tumors look like on radiology?
soap bubbles
2nd most common childhood malignancy of bone; translocation at t(11;22); affects femur, tibia, and pelvis; pain and inflammation; sheets of small cells with uniform nuclei - small blue cell tumors
Ewing’s sarcoma
Neoplasm of plasma cells with clock-face chromatin; produces monoclonal IgG spike
multiple myeloma
Benign, tumor-like condition with possible fractures
Normal trabecular bone is replaced by proliferating fibrous tissue and disorderly islands of deformed bone
Fibrous dysplasia
What is the difference b/w the mono-ostotic and poly-ostotic forms of fibrous dysplasia?
mono-ostotic: starts during adolescence, stops when bone growth stops, seen in ribs, JAW, femur, tibia
polyostotic: can cause problems in adulthood, craniofacial involvement common
Unilateral bone lesions, with café-au-lait spots on same side
Precocious puberty
Also associated with hyperthyroidism, Cushing’s disease
Polyostotic fibrous dysplasia with endocrine abnormalities
Most common disorder of joints
osteoarthritis
Is osteoarthritis really inflammation? What is happening?
no; degeneration of articular cartilage
Primary vs secondary osteoarthritis?
primary: arises w/o predisposing factors
secondary: arises in joint that has been previously deformed
2 most important factors in osteoarthritis?
- aging
2. mechanical wear and tear
Where is osteoarthritis most likely to occur?
in weight-bearing joints
subchondral bone becomes thickened, and gives appearance of ivory
eburnation
In osteoarthritis, osteophytes form at the distal IP joints (DIP). These are called (blank)
Heberden’s nodes
2 clinical signs to be aware of in osteoarthritis
subchondral bone cysts
osteophytes
Systemic chronic inflammatory disease affecting many organ systems (joints, skin, blood vessels, muscles, lungs)
rheumatoid arthritis
Does rheumatoid arthritis affect males or females more? When does it usu occur?
F>M; onset in 4-5th decade
How does the joint involvement in RA differ from osteoarthritis?
in osteoarthritis - DIP
in RA - PIP and MP
Symptoms of RA?
morning stiffness, which gets better w application of heat and movement
joint swelling, redness, warmth
What type of RA is this:
Proliferation and hypertrophy of synovial lining cells
+/- villous projections
Infiltration of lymphocytes, macrophages, plasma cells (in synovium)(may also have some neutrophils in the synovial fluid )
+/- lymphoid follicles
Neovascularization
non-suppurative proliferative synovitis
In RA, (blank) can form along extensor surfaces of the forearm and other points of pressure
subcutaneous nodules
What are the most likely organisms to cause infectious arthritis?
staph
strep
H. influenzae
gram-negative rods
**salmonella in sickle cell patients
Predisposing factors for infectious arthritis?
immunodeficiency
joint trauma
IV drug use
This spirochete can cause damage to joints, esp large joints of the knee, shoulder, elbow. Early disease resembles RA but can have extensive erosion of large joint cartilage
Borrelia burgdorferi
Commonly called “wear and tear” joint degeneration; characterized by the breakdown of the joint’s cartilage
osteoarthritis
Characterized by inflammation of the lining of the joints; often leads to join damage, resulting in chronic pain, loss of function and disability
RA
Uric acid accumulates in tissues as monosodium urate crystals (needle-shaped and birefingent)
gout
What kind of arthritis does gout cause? Like where does it occur?
acute arthritis in the 1st metatarsal
What causes primary gout?
Secondary gout?
primary is caused by overproduction of uric acid for unknown reasons;
secondary is due to any large increase in urate production (like treatment for lymphoma or leukemia), decreased excretion of uric acid (like chronic renal insufficiency), or Lesch-Nyhan Syndrome (over production/under excretion of uric acid w lack of HGPRT)
How do urate crystals ultimately lead to arthritis?
they activate complement, generate c3a and c5a, draw in neutrophils and macrophages to the joint and synovium
Which body part is usu affected first in gout?
big toe
If you see sharp birefringent crystals in the synovial fluid, think…
gout
Deposition of Calcium pyrophosphate crystals
Derived from nucleosides in chondrocytes
Commonly found in knees after trauma/surgery
May be associated with other systemic diseases, such as hemochromatosis
pseudogout
What do the pyrophosphate crystals look like in pseudogout?
coffin-lid shaped
This occurs if muscle is deprived of normal innervation, which leads to progressive atrophy and muscle weakness; presents as floppy baby syndrome in infants
neurogenic atrophy
What kind of atrophy can be seen in cases of neurogenic atrophy?
small groups of atrophy
**peripheral nerves supply groups of muscle fibers (motor unit), so damage to the nerve leads to atrophy of the whole motor unit
This is the most common type of muscle atrophy
type II (fast-twitch) atrophy
What can cause type II (fast-twitch) muscle fiber atrophy?
disuse
long-term glucocorticoid use
hypercortisol state
Antibodies to the acetylcholine receptor (AChR) (~90%)
Antibodies either injure the receptor, or inhibit binding of the neurotransmitter acetylcholine
Titer of antibody does NOT correlate with severity of symptoms
Myasthenia Gravis
Symptoms of myasthenia gravis?
ptosis and diplopia (double vision)
weak facial and neck muscles
respiratory involvement w potential respiratory failure
What is one option for the treatment of myasthenia gravis?
anti-AChE agents
**inhibit AChE so that ACh cannot be degraded
X-linked defect; ABSENCE of dystrophin; causes muscle weakness, especially in proximal muscles
Duchenne muscular dystrophy
What would you see histologically in DMD?
increased CT in muscle
variation in muscle fiber size, some hypertrophy, some atrophy
X-linked defect; ABNORMAL dystrophin; similar to DMD in presentation and morphology, but less severe
Becker Muscular dystrophy
Most common soft tissue sarcoma in kids
rhabdomyosarcoma
Most common variant of rhabdomyosarcoma
embryonal - occurs in head, neck, GU tract, retroperitoneum
What do rhabdomycosarcomas look like morphologically?
primitive small round blue cells
In the GU tract, rhabdomyosarcomas look like gelatinous, grape-like structures and are called (blank)
sarcoma botryoides
What can cause soft tissue tumors?
radiation therapy
trauma
exposure to organic chemicals
AIDS
The most common soft tissue tumor; usu benign, slow growing, painless
lipoma
A variant of lipoma that may present w local pain on the volar surface of the forearm
angiolipoma
This type of soft tissue infection tends to appear in the 5th and 6th decade of life; usu in deep tissues of proximal extremities; lower extremities and abdomen are common sites
liposarcoma
Most common in upper extremities and trunk
History of trauma (10 - 15%)
Rapid growth
NOT a true neoplasm, is an over-reaction of fibroblasts
May be confused with sarcoma due to cellularity
nodular fasciitis
A group of fibroblastic proliferations
Grow in infiltrative fashion
Recur after excision
NOT true neoplasms
Two well-known Superficial Types:
Dupuytren’s contracture (palmar)
Peyronie’s Disease (penile)
fibromatosis
Give an example of a deep fibromatosis
Desmoid tumor
This is a superficial fibromatosis that occurs on the hand
Dupuytren’s contracture
This type of soft tissue neoplasm favors deep tissue of the thigh, knee, and trunk; mets usu to lungs; comprised of fibroblasts and arises from fibrous tissues of the bone
fibrosarcoma
Who gets fibrosarcomas?
males ages 30-40
T/F: If infants get fibrosarcomas, they usu are congenital and so they present in the first two years of life
True
What type of pattern is seen in fibrosarcoma?
storiform/herringbone pattern
This is a malignant tumor; occurs in the 5th to 7th decade of life; occurs in lower limbs and retroperitoneal areas; most common type of post-irradiation tumor**
malignant fibrous histiocytoma or pleomorphic sarcoma
Accounts for 10% of all soft tissue sarcomas; arises from mesenchymal cells around joint cavities; most develop in the vicinity of large joints of lower extremities, esp knee
synovial sarcoma
What is unique histologically about synovial sarcomas?
contain mast cells
