9 - Bones and Joints Flashcards
adult skeleton has how many bones
206
bones account for what percent of body weight
12%
bone consists of what
extracellular matrix and various cells
bone function includes what
- mech support
- force transmission
- internal organ projection
- mineral homeostasis
- major site of hematopoiesis during post natal life
what are the anatomic classification of bones
- Long bones (bones of arms and legs)
- Short bones (carpal and tarsal bones of hands and feet)
- Flat bones (skull, ilium, sternum, and rib cage)
- Sesamoid bones (small bones embedded in tendon to decrease stress on tendon)
- Irregular bones (maxilla, mandible, temporal, sphenoid, ethmoid)
structural (macroscopic) classification of bone
- cortical (80% skeleton)
- cancellous (spongy 20%)
what has high turnover to remodel during stress
cancellous bone
what are the microscopic bone classification
- woven (immature bone; not stress prone)
- lamellar (remodeled woven bone; stronger and less flexible)
what is bone matrix composed of
- osteoid (35%) and minerals (65%)
what is in bone matrix osteoid
- type 1 collagen
- small amount GAGs and other proteins
what is in bone matrix osteoid
primarily HAP
what does HAP do for bone
give it hardness and acts as repository for 99% of calcium and 85% of phosphorus in body
what is on the surface of osteoid matrix, synthesize, tranport and assemble matric and regulate mineralization
osteoblasts
can osteoblasts remain on surface of become embedded within matrix as osteocytes
YES
what are interconnected by dentritic cytoplasmic processes; help control calcium and phosphate levels and detect mechanical forces and translate them into biologic activity
osteocytes
what are specizlied multinucleated macrophages that are derived from circulating monocytes and resorb bone
osteoclasts
what are disorders of bone and cartilage
- inherited mutations apparent during early stages of bone formation
- acquired diseases that appear in adulthood
acquired disease anomalies of bone and cartilage disorders could result from what
- localized disruption of migration and condenstion of mesenchyme
- global disorganization of bone and cartilage (dysplasia)
what are developmental disorders of bone and cartilage
- defects in nuclear proteins and transcription (CLEIDOCRANIAL DYSPLASIA)
- defects in hormones and signal transduction (ACHONDROPLASIA)
- defects in extracellular structural protein (OSTEOGENESIS IMPERFECTA)
- defects in metabolic pathways (OSTEOPETROSIS aka ALBERS-SCHONBERG DISEASE)
- diseases associated w/ defects in degradation of macromolecules (MUCOPOLYSACCHARIDOSES)
is cleidocranial dysplasis AD or AR? it is a mutation in what gene
AD - loss of function in RUNX2 gene
what is this:
Characterized by patent fontanelles, delayed closure of cranial sutures Wormian bones (extra bones that
occur within the cranial sutures), delayed eruption of secondary teeth and supernumerary teeth, primitive
clavicles, and short stature
cleidocranial dysplasia
what is the most common skeletal dysplasia and a major cause of dwarfism
achondroplasia
is achondroplasia AR or AR? what gene mutation
AD - gain of function in FGFR3 gene
what is this:
Characterized by retarded cartilage growth resulting
in shortened proximal extremities, an enlarged head
and budging forehead and depression of the root of
the nose, and a trunk of relatively normal length
achondroplasia
what is the most common inherited disorder of CT
osteogenesis imperfecta
is osteogenesis imperfecta AD or AR? what gene mutation?
AD - mutation in genes encoding type 1 collagen
what is a phenotypically heretrogenic disorder caused by deficiends of type 1 collagen synthesis
osteogenesis imperfecta
what does osteogenesis primarily affect? what else can it affect?
primary: bone
other: tissues rich in type 1 collagen (joints, skin, teeth, eyes, and ear)
what is thi:
Characterized by extreme skeletal fragility, blue sclera,
hearing loss, and small misshaped, and blue-yellow teeth
(secondary to dentin deficiency)
osteogenesis imperfecta
what is this
Comprises a group of rare genetic diseases characterized by
reduced bone resorption, which leads to diffuse, symmetrical
skeletal sclerosis; bones are brittle and fracture easily
osteopetrosis
what is this:
Most of the mutations interfere with acidification of the
osteoclast resorption pit, which is required for the dissolution of
calcium hydroxyapatite within the matrix
osteopetrosis
is osteopetrosis AD or AR
AR - (severe infantile osteopetrosis) becomes evident in utero or soon after birth0
AD - (milder) may not be detected until later, incidentally or due to repeat fractures
erlenmeyer flask deformation is related to what
OSTROPETROSIS
what is this:
Lysosomal storage disease; caused by deficiencies in enzymes,
primarily acid hydrolases that degrade extracellular matrix
mucopolysaccharidoses
what is this:
Mesenchymal cells, particularly chondrocytes, degrade
extracellular matrix mucopolysaccharides; in these diseases
mucopolysaccharides accumulate within chondrocytes and
induce apoptosis
mucopolysaccharidoses
extracellular mucopolysaccharide accumulation leads to structural defect in what
articular cartilage
how do affected individuals with mucopolysaccharidoeses look
short stature with malformed boens
what are metabolic diseases of bone
- ostopenia
- osteoporosis
what is decreased bone mass (1 to 2.5 standard deviation below peak bone mass)
osteopenia
what is defined as osteopenia that is severe enough to significantly increase risk of fracture (bone mas at least 2.5 standard deviation beflow bone mass); may be localized or generalized
osteoporosis
in osteoporosis, when is peak bone mass achieved
during young adulthood
once max skeletal mass attained, bone resorption slightly exceeds formation, resulting in age related bone loss that average ___% per year
0.7%
magnitude of osteoporosis is determined by wat
hereditary factors
what are the second most reasons that contribute to osteoporosis
physical activity, muscle strength, diet, and hormonal state
what is the most common form of osteoporosis
senile (M+W) and postmenopausal
what are the categories of generalized osteoporosis
- primary
- secondary
what are primary forms of generalized osteoporosis
- idopathic
- postmenopausal
- senile (old age)
what are secondary forms of generalized osteoporosis
- endocrine disorders
- GI
- drugs
- misc (anemia, immobilization, osteogenesis imperfecta, pulmonary disease)
what endocrine disorders cause sceondary generalized osteoporosis
addison disease, DM type I, hyperparathyroidism, hyperthyroidism, hypothyroidism , pituitary tumors, neoplasia, multiple myeloma
what GI disorders caused secondary generalized osteoporosis
hepatic insufficiency, malabsorption, malnutrition, vitamin C, and D deficiences
what drugs cause secondary generalized osteoporosis
alcohol, anticoag, anticonvulsants, chemotherapy, corticosteroids
fractures of what lead to immobilization
femoral neck, pelvic, or spine
can osteoporosis be reliably deteced in plain radiographs?
Osteoporosis cannot be reliably detected in plain
radiographs until 30%-40% of bone mass is lost
how to prevent and do therapeutic management for osteoporosis
Prevention and therapeutic management include
exercise, appropriate calcium and vitamin D intake,
and pharmacologic agents, most commonly
bisphosphonates, which reduce osteoclastic activity and
induce their apoptosis
who gets osteoporosis
everyone
what is a manifestation of impaired mineralization of bone matrix
osteomalacia and rickets
undermineralized matrix results from abnormal what
abnormal vitamin D metabolism or Vitamin D deficiency
___ refers to the disorder in children, in which it interferes with the deposition of bone in the growth plates
Rickets
___ is the adult counterpart of rickets, in which the bone formed during remodeling is underminaralized and predisposed to fractures
Osteomalacia
what thyroidism causes increased bone resorption
hyper para thyroidism
how does PTH indirectly have a central role in calcium homeostasis
- activateion of osteoclasts
- increasing calcium resorption
- incerasing urinary phosphate excretion
- increasing synthesis of active vitamin D by kidneys
net result of PTH action is elevated serum calcium which inhibits what?
inhibits PTH release from parathyroid gland
what can hyperparathyroidism results from
- autonomous parathyroid secretion (primary hyper PTH)
- chronic renal disease (secondary hyperPTH)
what produces a change throughout the skeleton as a consequence of unrestricted osteoclast activity
hyperparathyroidism
symptomatic untreated primary hyperPTHism manigests what skeletal abnormalities
- osteoporosis
- brown tumors
- osteitis fibrosa cystica
Bone loss in hyperparathyroidism predisposing to microfractures, secondary hemorrhage, macrophage recruitment, and ingrowth of reparative fibrous tissue to create a mass lesion called ___
brown tumor
what does the brown color in hyperPTHism reflect
vascularity, hemorrhange and hemosiderin deposits (cystic degeneration of brown tumor is common)
The combination of increased bone cell activity, peritubular fibrosis, and cystic brown tumors is the hallmark of severe hyperPTHism and is known as ___
generalized osteitis fibrosa cystica (von
Recklinghausen disease of bone)
___ describes the collective
skeletal changes that occur in chronic renal disease, including those associated with dialysis
Renal osteodystrophy
manifestations of renal osteodystrophy
- Osteopenia/osteoporosis
- Osteomalacia
- Secondary hyperparathyroidism
- Growth retardation
what is a disorder marked by increased but disordered and structurally unsound bone mass
Paget disease of bone
what are the 3 sequential phases of Paget disease
- An initial osteoclastic phase
- A mixed osteoclastic-osteoblastic stage
- A burnt-out quiescent osteosclerotic stage in which osteoblastic activity predominates
when does paget disease of bone present? when does it become more common?
late adulthood and gets more common with increasing age
what race gets paget disease
caucasians
cause of pagets
uncertain but has both genetic and environmental contributions
what gene mutation associated with pagets
SQSTM gene mutation
clinical findings of pagets
- polyostotic in majority of cases
- most are asymptomatic
what bones are most invovled in pagets
Pelvis, vertebrae, femur, tibia, and skull are involved
most commonly
what happens to afected bones in pagets
Affected bones become thickened, enlarged, and
weakened, with an increased risk of fractures
Enlargement of the craniofacial skeleton in Pagets may produce ___
leontiasis ossea (lion faces)
what causes progressive increase in head circumference
skull enlargement
nerve compression from paget disease may lead to what
deafness and visual impairment
paget disease is also called what
osteitis deformans
what happens to alveolar ridges in pagets
Alveolar ridges tend to remain symmetrical but become grossly enlarged; results in spacing between teeth and edentulous patients complain that the dentures feel too tight
what do radiographic images in late disease of pagets show
patchy sclerotic areas (cotton wool apperance)
paget disease affected individuals have what levels of serum alkaline phosphatase, serum calcium, and phosphate leves?
ELEVATED serum alkaline phosphatase
NORMAL serumc alcium
NORMAL phosphate levels
what is the most dreaded complicatino of paget disease
sarcoma (usually osteosarcoma or fibrosarcoma)
paget disease with sarcoma looks like what radiographically
Diagnosis can be made radiographically; bone is
typically enlarged with thick, coarsened cortices and
medulla
most individuals with pagets have mild symptoms that can be suppressed by what
calcitonin and bisphosphonates
what is the loss of bone integrity, one of hte most common pathology affecting bone
fracture
what fracture:
overlying skin is intact
simpl
what fracture:
bone communicates with skin surface
compound
what fracture:
the bone is fragmented
comminuted
what fracture:
the ends of bone at fracture site are not aligned
displaced
what fracture:
a slowly developing fracture that follows period of increased physical activity (e.g., runner) in which bone is subjected to repetitive loads
stress
what fracture:
extending only partially thru bone; common in infants when bones are soft
greenstick
what is osteonecrosis also called
avascular necrosis
___ is relatively common; can be limited to the medullary cavity or involve both the medulla and cortex
Osteonecrosis or Infarction of bone and marrow
2 common causes of osteonecrosis
fractures and corticosteroids
other causes of osteonecrosis
Alcohol abuse
Bisphosphonate therapy/ Denosumab
Connective tissue diseases
Chronic pancreatitis
Gaucher disease
Pregnancy
Radiation therapy
___ denotes inflammation of the bone and marrow, virtually always secondary to infection
Osteomyelitis
can all types of organisms produce OM? what are the most common culprits?
All types of organisms (viruses, parasites, fungi, and
bacteria) can produce OM; certain pyogenic bacteria
and mycobacteria are the most common culprits
why is diagnosis and tx in US become challenging
- unsual infections in immigrants from low countries
- opportunistic infections in immunosuppressed individuals
what almost always causes pyogenic OM
bacterial infection
how do organisms reach bone in pyogenic OM
Organisms may reach the bone via hematogenous
spread, extension form a contiguous site, or direct
implantation (traumatic injury)
what bacteria is responsible for most culture positive pyogenic OM
staph aures
what bacteria is responsible for pyogenic OM in individuals with genitourinary tract infections or IV drug users?
e. coli, pseudomonas, and Klebiseilla
what happens during acute phase of pyogenic OM
bacteria proliferate and recruit neutrophils
when does necrosis of bone cells and marrow occur in pyogenic OM
within 48 hours
in pyogenic OM, bacteria and associated inflammatory response spread ___ and acess the ___ to reach the ___
Bacterial and associated inflammatory response then
spread longitudinally and access the Haversian system
to reach the periosteum
what can form after preiosteal rupture in pyogenic OM? these can channel to the skin as what?
soft tissue abscesses; drainage sinuses
in pyogenic OM, what can crumble and release fragments into the sinus tract?
dead bone or SEQUESTRUM
in pyogenic OM, as the inflammatory process evolves, ___ recruited during the first week release cytokines that stimulate bone resorption, fibrous tissue ingrowth, and peripheral deposition of reactive bone
chronic inflammatory cells
new bone formation in pyogenic OM forms hat around the devitalized, infected bone
forms a living shell called INVOLUCRUM
___ may present acutely as a systemic illness with malaise, fever, chills, leukocytosis, and intense throbbing pain over the infected bone; the presentation may also be subtle with localized pain
Hematogenous OM
Characteristic radiographic findings of a ___ surrounded by sclerosis strongly suggests OM
lytic foci of bone destruction
what is required to identify pathogen in OM
biopsy and bone culture
combination of what is usually curative of OM
antibiotics and surgical drainage
Acute OM fails to resolve and persists as chronic OM in ___% cases
5%-25%
what is more destructive and resistant to control than pyogenic OM
myobacterial OM
how does bone involvement occur in myobacterial OM
Bone involvement may occur by direct extension
or following spread via blood vessels and
lymphatics
histologic findings of what are typical of tuberculosis
granulmatous inflammation and caseous necrosis
40% of mycobacterial OM involving the spine is what disease
Pott disease
what is the most common malignant bone cancer
metastasis of other cancer going to bone (e.g., colon, breast, etc.)
what is the most common primary bone cancer
osteosarcoma
location of osteochondroma? age?
metaphysis of long bone
10-30 years
what tumor has bone excrescene with cartilage cup
osteochondroma
location and age of chondroma
location: small boens of hands and feet
age: 30-50 years
what tumor has circumscribed hyaline cartilage nodule in medulla
chondroma
location and age of chondroblastoma
location: epiphysis of long bones
age: 10-20 years
what tumor cicum scribes primary bone and has pericellular calcification
chondroblastoma
what are benign cartilage forming primary boen tumros
- osteochondroma
- chondroma
- chondroblastoma
what is a malignant cartilage forming primary bone tumor
chondrosarcoma
common location of chondrosarcoma and age
location: pelvis, shoulder
age: 40-60 years
what tumor extends from medulla thru cortex into soft tissue, chondrocytes w/ increased cellularity and atypica
chondrosarcoma
what are beign bone forming primary bone tumors
- osteoid osteoma
- osteoblastoma
location and age of osteoid osteoma
location: metaphysis of long bone
age: 10-20 years
what tumoe is LESS THAN 2 cm in diameter, present with severe nocturnal pain caused by prostaglandin E2 which is relieved by aspiring and other NSAIDS; cortical interlacing microtrabecular of woven bone
osteoid osteoma
common location and age of osteoblastoma
location: vertebral column (back)
age: 10-20 years
what tumor is GREATER THAN 2 cm, causing paint that is NOT relieved by aspiring, posterior elevemts of vertebrae, histology similar to osteoid osteoma
osteoblastoma
what are malignant bone forming primary bone tumors
osteosarcoma
common locaiton and age of osteosarcoma
location: metaphysis of distal femur, proximal tibia
age: 10-2o years
what tumor extends from medulla to lift periosteum, malignant cells produce woven bone
osteosarcoma
what age do adult jaws get osteosarcoma
33
what are benign bone forming tumors of unknown origin
- giant cell tumor
- aneurysmal bone cyst
location and age of giant cell tumor
location: epiphysis of long bones
age: 20-40 years
what tumor destroys medulla and cortex, sheets of osteoclasts
giant cell tumor
age and location of aneurysmal bone cyst
location: proximal tibia, distal femur, vertebra
age: 10-20 years
what tumor occurs in vertebral body, hemorrhagic spaces, separated by cellular fibrous septae
aneurysmal bone cyst
what are malignant bone forming tumors of unknown origin
ewing sarcoma
location and age of ewing sarcoma
location: diaphysis of long bones
age: 10-20 years
what tumor has an affected site that is frequently tender, warm, and swollen and there may be systemic findings that mimic infection, including fever, elevated ESR, anemia and leukocytosis; sheets of primitive round cells; radiographic images show ONION-SKIN reaction of periosteum
ewing sarcoma
what allow movement while providing mechanical stability
joints
how are joints classified
- solid (nonsynovial)
- cavitated (synovial)
___ provide structural integrity, lack a
joint space, and allow only
a minimum movement
Solid joints (synarthrosis)
solid joints are also called what
synarthrosis
what is the cranial bones and bond between roots of teeth and jaw bones
fibrous synarthrosis
what are solid joints
- fibrous synarthrosis
- cartilaginous joints
___ have a joint space
that allows for a wide range of motion
Synovial joints
where are synovial joints situated? how are they formed? how are they strengthened?
Situated between the ends of bones formed via
endochondral ossification, they are strengthened by a
dense fibrous capsule reinforced by ligaments and
muscles
The boundary of the synovial joint space consists of the ___, which is firmly anchored to the underlying capsule and does not cover the articular surface
synovial membrane
___ is a hyaluronic acid-rich plasma filtrate that acts as a viscous lubricant and provides nutrients for the articular hyaline cartilage
Synovial fluid
what is inflammation of the joints
arthritis
what are the clinically important forms of arthritis
osteoarthritis (old age, mechanical wear)
rheumatoid arthritis (autoimmune)
what cause different types of arthritis
immune rxn, infection, crystal deposition
primary pathogenic abnormality of osteoarthritis
mechanical injury to articular cartilage
role of inflammation of osteoarthritis
secondary; inflammatory mediators exacerbate cartilage damage
joints involved in osteoarthritis
primarily weight beaing (hips and knees)
pathology of osteoarthritis
cartilage degeneration and fragmentation, bone spurs, subchondral cysts; minimum inflamamtion
serum antibodies of osteoarthritis
NONE bc not autoimmune duh
does osteoarthritis involve all other organs
no
primary pathogenic abnormality of rheumatoid arthritis
autotimmunity
role of inflammation of rheumatoid arthritis
primary; cartilage destruction caused by T cells and antibodies reactiev w/ joint antigens
joints involved in rheumatoid arthritis
being with small joints of fingers; progression leads to multiple joint involvement
pathology of rheumatoid arthritis
inflammatory pannus invading and destroying cartilage; severe chronic inflammation; joint fusion (ankylosis)
serum antibodies in rheumatoid arthritis
various, inlcuding anticitrullinated peptide antibody (ACPA)
does rheumatoid arthritis invovle other organs
YES (lungs, heart, other organs)
what is characterized by cartilage degeneration that results in structural and functions failure of synovial joint (bone rubbing on bone)
osteoarthritis
what are a common form of osteoarthritis
bone spurs
what results in pannus formation, cartilage destruction, and synovitis. begins with malaise, fatigue and generalized musculoskeletal pain; joint involvement develops after weeks or months
RA
what is pannus
inflammation of synovial membrane and cartilage destruction
what are the infectious arthritis
- suppurative
- myobacterial
- viral
- lyma
___: H influenzae arthritis than 2 years predominates in children younger of age; S. aureus is the main causative agent in older children and adults
Suppurative arthritis
___: caused by M. tuberculosis
Mycobacterial arthritis
___: can occur in a variety of infections; most common are alphavirus, parvovirus B19, rubella, Epstein-Barr virus, and hepatitis B and C viruses
Viral arthritis
___: caused by spirochete Borrelia burgdorferi, which is transmitted by deer ticks; Lyme disease involves multiple organs; arthritis occurs in <10% of cases
Lyme arthritis
what are types of crystal induced arthritis
- endogenous crystals
- exogenous crystals
what are endogenous crystals
- monosodium urate (gout)
- calcium pyrophosphate dehydrate (pseudogrout)
- basic calcium phosphate
what are exogenous crystals
biomaterials used in prosthetic joints, that can induce arthritis as they accumulate with wear
what refer to non-epithelial tissue excluding the skeleton, joints, central nervous system, and hemopoietic and lymphoid tissues
soft tissue tumors
With the exception of skeletal muscle neoplasms, ___ tumors are 100-fold more frequent than their malignant counterparts, the sarcomas
benign soft tissue
where do most soft tissue tumors arise?
extremities (particularly the thigh)
tumor type, age, and features of:
benign adipose
tumor type: lipoma
age: 40-60
features: well-circumscribed mass of mature adipose tissue
tumor type, age, and features of:
malignant adipose
tumor type: liposarcoma (well-differentiated, myxoid, and pleomorphic)
age: 50-60
features: recur locally and repeatedly unless adequately excised; pleomorphic LS are aggressive
tumor type, common location, age, and features of:
malignant skeletal muscle
tumor type: alveolar rhabdomyosarcoma
common location: extremities, sinuses
age: 5-15 year
tumor type: embryonal rhabdomyosarcoma
common location: genitourinary
age: 1-5 year
features: aggressive, painless, infiltrative mass that may grow rapidly; treated by surgical recession and chemo with or without radiation therapy