IUHS Student-2-Student USMLE Step 1 Recall
Musculoskeletal
Abnormal Development and Bone Pathology
Achondroplasia
most common disease of the growth plate and is a major cause of dwarfism....
mutation in fibroblast growth factor receptor 3 (FGFR3)...altered cell signaling...
defect in cell signaling, and it manifest as a reduction in the proliferation of the chondrocytes in the growth plate...
point mutation (usually Arg for Gly)....inhibits cartilage proliferation, and in achondroplasia the mutation causes the receptor to be in the state of the constant activation...
automsomal dominant disorder...although, most are through spontaneous new mutations...
Morphology: histologic abnormalities are found in the growth plates...zones of proliferation and hypertrophy are narrowed and disorganized and contain clusters of large chondrocytes instead of well-formed columns...at the base of the growth plate, there is premature deposition of horizontal struts of bone that seals the plate and prevents further growth
zones of proliferating cartilage is either absent or greatly thined...
Osteogenesis Imperfecta (Type 1 Collagen Disease)
incorporation
of defective alpha2 chains that cause instability and degradation of the triple
helix...
deficiency in synthesis of type 1 collagen....genetic defects in osteogenesis imperfecta reside in mutation in the genes that code for the alpha1 and alpha2 chains of the collagen molecule...
mutations can be found on chromosome 7 or 17 which makes osteogenesis imperfecta a great example of locus heterogeneity, which is when the same disease can be caused by mutations in different loci...
extreme skeletal fragility...acquired
Type II
fatal in utero or during the perinatal period...fetus is still within the womb...
blue sclerae caused by a decrease in collagen content, exposing the coridal veins...hearing loss related to both a sensorineural deficit and impeded conduction owing to abnormalities in the bones of the middle and inner ear...dental imperfections due to a deficiency of dentin...
Types 2, 10, and 11
result in abnormal metabolism...early destruction of joints...type 2 collagen molecules are not secreted by the chondrocytes, and insufficient bone formation occurs..
Mucopolysaccharidoses
lysosomal storage diseases that are caused by deficiencies in the enzymes that degrade dermatan sulfate, heparan sulfate, and keratan sulfate...
abnormalities in hyaline cartilage, including the cartilage and large growth plates, costal cartilages, and articular surfaces...
patients are frequently of short stature and have chest wall abnormalities and malformed bones...
Hunter's syndrome is associated with increased tissue stores and excretion of dermatan sulfate and heparan sulfate...
Osteoporosis
characterized by a decrease in bone mass...
Senile Osteoporosis
continuous loss of bone at both the trabecular and cortical layers, which become thinner by internal resorption
Steroid-induced Osteoporosis
catabolic effect of corticosteroids may affect trabecular bone, producing a decrease in bone formation...steroids also decrease intestinal absorption and renal resorption of calcium, so that less calcium reaches the bone...
Post-menopausal osteoporosis
most common after the fifth decade of life...decreased remodeling and decreased amount of bone deposited by osteoblasts...b/c lack of estrogen...
Immobilization osteoporosis
confinement of bed results in a loss of 30% of initial bone volume...lack of exercise seems to be the cause...
anorexia nervosa leads to osteoporosis in women b/c of loss of menstrual period...
reduction in bone mass with normal bone mineralization...
Osteopetrosis (Marble bone disease, Albers-Schonberg disease)
osteoclast dysfunction...stonelike quality of the bones; however, the bones are abnormally brittle and fracture like a piece of chalk...
on xray, characteristic "Erlenmeyer flask" is apparent...
carbonic anhydrase II deficiency...it is required for osteoclasts and renal tubular cells to excrete hydrogen ions and acidify their environment...absence of this enzyme prevents osteoclasts from solubilizing and resorbing matrix and blocks the acidification of urine by the renal tubular cells...
Morphology
deficient osteoclast activity...bones lack a medullary canal, and the ends of long bones are bulbous and misshapen...bone that form is not remodeled and tends to be woven in architecture...bone is brittle...osteoclasts lack the usual ruffled borders and show decreased functioning...
Clinical features
fractures, anemia, hydrocephaly are often seen...
Paget Disease (Osteitis Deformans)
can
often lead to bell's palsy if impinging on the CN VII...
affects 3% to 4% of the population over age 40, most commonly men...
haphazard arrangement of cement lines...
has a predilection for the skull, pelvis, tibia, and femur...possible involvement from Paramyxovirus...
Clinical Features
bone pain, fractures, and deformities...deafness when skull is affected...height distortion due to vertebral compression...serum alkaline phosphatase level is markedly elevated...radiologic findings of bone lysis and reformation are characteristic...pathognomic for CHF...increased levels of urinary hydroxyproline...
Pathology -
marked medullary
fibrosis is present...numerous osteoclasts appear abnormal b/c of an
increased number of nuclei...local increase
in bone mass and disorganization of the normal trabecular pattern...
numerous osteoclasts and osteoblasts, an increased calcification rate, and accumulation of woven bone...this turnover leads to a typical "mosaic" pattern...so termed b/c of cement like material forms narrow boundaries
often associated with Osteosarcoma...
Treatment - administration of calcitonin, which decreases the resorption
Osteonecrosis (AvascularNecrosis)
1) mechanical vascular interruption (fracture)
2) corticosteroids
3) thrombosis and embolism (nitrogen bubbles in dysbarism)
4) vessel injury (vasculitis, radiation therapy)
5) increased intraosseous pressure with vascular compression
6) venous hypertension
Morphology - necrosis is spotty and involves the cancellous bone and marrow
Clinical Course - chronic pain that is initially associated only with activity but then becomes progressively more constant until finally it is present at rest
bilateral segmental osteonecrosis or avascular necrosis (AVN) of the femoral head is most often associated with systemic steroid therapy...
Osteomyelitis
inflammation of the medullary and cortical portions of bone, including the periosteum...in children, the long bones are most often affected; in adults, the vertebrae
the metaphyseal region is part of the long bone initially involved in hematogenous osteomyelitis...
Pathogenesis: - bone infections results from
1) Most commonly, the hematogenous spread of bacteria from a distant focus of sepsis
2) Invasion of bone from adjacent septic arthritis or soft tissue abscesses
3) Penetrating trauma
4) Complication of fractures
5) Complications of surgery
increased risk are persons with sickle cell disease, hemodialysis patients, patients with bone or joint prostheses, and intravenous drug abusers...
Pyogenic Osteomyelitis
Reaches bone by:
1) hematogenous spread
2) extension from a contiguous site
3) direct implantation
Staphylococcus aureus is responsible for 80% to 90% of the cases of pyogenic osteomyelitis
most commonly affects children and young adults and involves the femur, tibia, humerus, and radius
Clinical Course - acute systemic illness with malaise, fever, chills, leukocytosis, and marked to intense throbbing pain over the affected region