Flashcards in CH18 - Musculoskeletal Pathology Deck (244)
What is achondroplasia?
Impaired cartilage proliferation in the growth plate
What is achondroplasia a common cause of?
What is achondroplasia due to?
an activating mutation in fibroblast growth factor receptor 3 (FGFR3) Autosomal dominant
What does the overexpression of FGFA3 do?
It inhibits growth
What are most mutations for achondroplasia?
they are sporadic and related to increased paternal age.
What are the clinical features for achondroplasia?
Short extremities with normal-sized head and chest?
In achondroplasia, why is there short extremities with normal-sized head and chest?
its due to poor endochondral bone formation; intramembranous bone formation is not affected.
How is endochondral bone formation characterized?
by formation of a cartilage matrix, which is then replaced by bone; it is the mechanism by which long bones grow.
How is intramembranous bone formation characterized?
by formation of bone without a preexisting cartilage matrix; it is the mechanism by which fiat bones (e.g., skull and rib cage) develop.
In achondroplasia, what aspects are not affected?
Mental function, life span, and fertility are not affected
What is osteogenesis imperfecta?
It?s a congenital defect of bone resorption resulting in structurally weak bone
What is osteogenesis imperfecta most commonly due to?
an autosomal dominant defect in collagen type 1 synthesis
What is blue sclera?
thinning of scleral collagen reveals underlying choroidal veins.
What are the clinical features for osteogenesis imperfecta?
1) Multiple fractures of bone (can mimic child abuse, but bruising is absent) 2) blue sclera?3) Hearing loss
Why is there hearing loss in osteogenesis imperfecta?
Bones of the middle ear easily fracture
What is osteoporosis?
inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
What is osteoporosis due to?
Its due to poor osteoclast function
What is an example for the multiple genetic variants that exist for osteoporosis?
carbonic anhydrase II mutation leads to loss of the acidic microenvironment required for bone resorption
In osteoporosis, why is there anemia in osteoporosis?
It is due to bony replacement of the marrow (myelophthisic process)
What are the clinical features for osteoporosis?
1) Bone fractures 2) Anemia, thrombocytopenia, and leukopenia with extramedullar hematopoiesis 3) Vision and hearing impairment 4) hydrocephalus 5) renal tubular acidosis
In osteoporosis, why is there vision and hearing impairment?
due to impingement on cranial nerves
In osteoporosis, why is there renal tubular acidosis?
Its seen with carbonic anhydrase II mutation, a lack of carbonic anhydrase results in decreased tubular reabsorption of HCO3 leading to metabolic acidosis.
What is the treatment for osteoporosis?
It is bone marrow transplant; osteoclasts are derived from monocytes.
What do Ricketts and osteomalacia result in?
Defective mineralization of osteoid
What do osteoblasts normally produce?
Osteoid which is then mineralized with calcium and phosphate to form bone
What are Rickets and osteomalacia due to?
low levels of vitamin D, which results in low serum calcium and phosphate
What is vitamin D normally derived from?
the skin upon exposure to sunlight (85%) and from the diet (15%).
What does activation of Vitamin D require?
25-hydroxylation by the liver followed by 1-alphahydroxylatton by the proximal tubule cells of the kidney
What does active vitamin D do?
it raises serum calcium and phosphate