Topic 101-107: Musculoskeletal system Flashcards
What are the congenital and genetic bone abnormalities?
congenital
- dysostosis - abnormal mesenchymal cell migration causing lesions such as: aplasia (absence of a rib), formation of extra bones or abnormally fused bones
- dysplasia - interference of bone and cartilage growth
genetic
- osteogenesis imperfecta - brittle bone disease
- achondroplasia - cause of dwarfism
- osteoPETrosis - (not osteoporosis) abnormal bone resorption leads to large, bulky bones that are really fragile
osteogenesis imperfecta is what type of disease? where is the defect? what are some other symptoms?
how are the subtypes arranged?
-an autosomal dominant disease that has a gene mutation in the alpha 1 and 2 chain of type 1 collagen, thus it is not made. Type 1 collagen is used on skin, joints, and eyes too!
- brittle bones prone to fracture
- blue sclera
- hearing loss
- tooth malformation
subtypes arranged 1-9, each showing that there is an extremely large range of outcomes due to the variable penetrance in AD diseases
achondroplasia is what? what kind of disease is it and what is the mutation involved?
- causes dwarfism
- AD disease that is due to a mutation in FGFR3 which will inhibit chondrocyte proliferation, thus the epiphyseal growth is suppressed and long bone growth is stunted.
- normally they are heterozygotes because homozygotes die after birth
osteopetrosis is what sort of disease? what are the main variants? what is the generalized pathogenesis? what are some common symptoms?
-osteopetrosis (petro like rock because the bone forms rock like shapes) is a rare genetic disorder that is due to osteoclast dysfunction
- Autosomal dominant (adults, mild)
- autosomal recessive (infantile, lethal)
- pathogen: osteoclast function is disturbed, most of the time there is a carbonic anhydrase deficiency suggesting the problem lies in the hydrogen ion excretions and thus inability to demineralize bones
- bone breaks, infections (bad BM), renal tubular acidosis (due to metabolic acidosis because of carbonic anhydrase def),
- BM transplants may be able to help create functioning osteoclasts
osteoporosis is what? what is the general pathogenesis? what are the classifications and basic idea behind the problem?
osteoporosis is the increased fragility and porosity of bone that causes fractures. the basic pathogenesis is that that balance of osteoblast vs osteoclasts shifts in favor of resorption
- primary osteoporosis-
- -senile - osteoblast activity decreases
- -postmenopausal - decreased estrogen stimulates RANKL –> OPG decreases and thus osteoclasts increase in activity
- -genetic - Vit D receptor polymorphisms
- secondary osteoporosis-
- -endocrine disorders
- -GI - malabsorption of vit D/C
- -drugs/alcohol
osteoporosis diagnosis?
Difficult to diagnose
- x-ray only after 30% is gone
- DEXA scan
- NOT via serum levels because they are normal. serum is good for osteomalacia
What is the difference of osteomalacia and rickets? what are the commonalities? which bones are mostly affected?
Both are manifestations of vit D deficiency and abnormal metabolism. They are due to defective mineralization of bone osteoid (osteoporosis has total bone mass loss but the mineralization is ok)
- rickets is in children
- osteomalacia is in adults
long bones are most affected
pg 461 of asta notes highlights vit D metabolism
What are the most common ways to get osteomalacia/rickets? what are the most commonly fractured bones? what are the serum abnormalities?
-vit D deficiency
-low sunlight exposure
can also be due to: malabsorption, phosphate depletion and renal disorders impairing the vit D production
- vertebral bodies and hips are most likely to fracture
- calcium and phosphate levels will be low with inc PTH
osteomyelitis is what? what is it typically caused by? what would you see in x-ray?
inflammation of the bone and bone marrow cavity due to a systemic infection or acute/chronic disease. the bone undergoes lytic necrosis
- osteomyelitis is almost always caused by bacteria (TB especially) and it can spread to the bones via:
- blood
- adjacent tissue infection
- trauma or fracture infection
-on x-ray one would see a destructive lytic focus with sclerosis around the lesion
TB osteomyelitis occurs how frequently? what is the most prefered site of infection on or near the bone? what is the name of the disease that is common with TB bone involvement?
- 1-3% of the cases, via bloodstream
- due to the higher o2 pressure, TB like to infiltrate the synovium first and then eventually make their way to the bone
- pott’s disease. after the lymphatic system and the pleura, the vertebral bodies is the most common place of extra-pulmonary TB
pagets disease is associated with what? what kind of bone growth occurs? what may possibly be the source of the problem?
pagets disease is characterized by 3 repetitive stages that form disorganized and weak bone mass.
- osteolytic stage
- mixed osteoclastic - osteoblastic stage
- osteosclerotic stage
paramyxovirus infection may be the source of paget disease. it induces IL-1 secretion
–no virus has ever been isolated in affected tissue however!–
what does the bone morphology look like at each stage of paget’s disease? what is the treatment and some complications of the disease?
- initial lytic phase: many, large osteoclasts
- mixed: surfaces lined by osteoblasts however osteoclasts remain. BM is replaced by loose CT
- sclerotic phase: the cortex of the bone is thickened, but also softened and prone to fracture
- treat with calcitonin
- heart failure and osteosarcoma are risks
what are the primary bone tumors (3 categories)? How common are they/which are most common? what are the organs most likely to give secondary tumors
Bone:
- benign: Osteoma, osteoid osteoma, osteoblastoma
- malignant: osteosarcoma
cartilage
- benign: osteochondroma, chondroma
- malignant: chondrosarcoma
other
-malignant: ewing sarcoma, giant cell tumor
- -secondary bone tumors are more common than primary!
- -most common benign: osteochondroma
- most common malignant: myeloma, osteosarcoma, then chondrosarcoma and ewing sarcoma
— secondary tumors are formed via breast, lung and prostate most frequently
What are the 3 benign bone tumors? what are some general characteristics?
-osteoma: developmental abnormalities/reactive growths that are solitary, slow growing and hard. osteomas can be associated with gardner syndrome!
- osteoid osteoma and osteoblastoma
similar: both made of osteoblasts that form an osteoid center (radiolucent) with sclerotic rim (osteoma, visualized on x-ray)
–osteoid osteoma: long bones, small (less than 2 cm), localized pain that is relieved by aspirin
–osteoblastoma: vertebra, larger, non-localized pain and no aspirin help (think Blast!: b for big, blast! for that the pain is annoyingly hard to find and treat)
osteosarcomas are what? how common are they and in which age group? what mutations are commonly associated? where do they occur? what do you see on x-ray?
- malignant bone tumors from osteoblasts that produces osteoid
- 20% of bone tumors are osteosarcoma. most common bone tumor after myeloma
- 75% are under 20 years old! the rest are elderly people with other bone conditions like paget’s
- 60% of people with osteosarcoma also have RB gene mutations. (this mutation inc chances to 1000X)
- 60% of osteosarcomas appear in the knee region
- codman’s triangle is seen on xray
