Pathology- Bones and Soft Tissue Flashcards
What is deficient in the mother to cause cretinism?
iodine
What are the bone growth problems in cretinism?
linear growth impared, fontanel closure of skull fails, failure of ossification of chondrocytes
What type of mucopolysaccharidosis is Morquio syndrome?
type IV
What is deposited in the developing bones in Morquio syndrome?
glucosaminoglycans (GAGs)
What is the tell-tale sign of Morquio syndrome?
dental defects
What are some other Sx of Morquio syndrome?
dental defects, mental retardation, corneal opacities, dearing defects, cardiac valve disturbances
What causes achondroplasia?
Arrest of growth plate by a defect in FGFR3 signalling
What is the inheritance of achondroplasia?
Autosomal dominant
Are achondroplasia patients mentally retarded?
No. Just short.
What is deficient in osteogenesis imperfecta?
Type I collagen
Where is type I collagen prevalent?
Bones, joints, eyes, ears, skin and teeth
What is the inheritance of osteogenesis imperfecta?
autosomal dominant
Scenario: You’re on the set of the new movie “Die Hard 8- I’m a Geriatric about to Die.” After passing the elderly Bruce Willis, you bump into the new girl working on the set. After a casual conversation about tentacle porn, you notice something strange as you creepily stare at her. Having taken MSK and reflecting back on inherited diseases, you remember a tell-tale sign of osteogenesis imperfecta. What did you notice on the girl’s face that clued you into this diagnosis?
Blue sclera of the eyes
What causes the blue sclera of the eyes?
Type I collagen is missing and you can see the veins in the eyeball
What is defective in Osteopetrosis?
Osteoclasts (usually in # or fxn)
What are the morphologies of the bones in osteopetrosis?
stone-like, but they are abnormally brittle and fracture easily, like chalk
What type of inheritance is the malignant form of osteopetrosis?
autosomal recessive
What type of inheritance is the benign form of osteopetrosis?
autosomal dominant
What are the most common forms of osteoporosis?
senile and post menopausal
When is peak bone mass achieved during your life?
young adulthood
What % of bone loss occurs per year?
0.7%/year (this is normal)
What are the main physiological causes of bone loss?
osteoblats don’t replicate or regulate as well
Why does decreased physical activity increase the rat eof bone loss?
weight loading increases bone formation
What important vitamin is seen in increased or decreased bone mass?
Vitamin D
When adolescent girls don’t drink their milk and are deficient in Ca intake, what can happen?
Bone mass is shunted and this increases susceptibility to osteoporosis
Women may lose what % of cortical bone mass?
35%
Women may lose what % of trabecular bone mass?
50%
What % of women suffer osteoporotic fractures?
1 out of 2 women
Decreased estrogen causes which cytokines to increase?
IL-6 and IL-1
What are the roles of IL-6 and IL-1?
Stimulates osteoclasts, which eat bone.
Tx with which type of drug increases osteoporosis by increasing bone resorption and decreasing bone formation?
Glucocorticoids
What drug can reverse the osteoporotic symptoms of glucocorticoid treatment?
biphosphonates
It’s hard to Dx osteoporosis because you really only see it when 30-40% of bone is lost. However, which type of Dx can you use for it?
Specialized radiographs which measure bone density
What are the Tx’s for osteoporosis?
exercise, appropriate Ca and Vit D diet, estrogen replacement, PTH and biphosphonates.
What causes Paget disease?
haphazard bone resorption and synthesis cuz of osteoclast dysfxn
What are the 3 stages of Paget?
- Osteolytic stage
- mixed osteoclastic-osteoblastic stage
- osteoblastic stage ending into quiescent osteosclerotic stage
Though Paget increases bone mass, why is it problematic?
the framework is disordered and architecturally unsound
What age does Paget occur?
Mid adulthood
What is the viral cause of Paget?
paramyxovirus infection –> IL-6 produced –> osteoclasts go crazy
What is the physiological cause of Paget?
osteoclasts are hypersensitive to vit D and RANKL
What are the clinical features of Paget?
most are mild and found incidentally on X ray, enlarged bone, increased serum alk phos, pain possible, bowing of legs, “chalkstick fracturs
~80% of cases of Paget occur in what bones?
axial skeleton or proximal femur
What types of tumors occur in 0.7-0.9% of pagets disease?
osteosarcomas
What vitamin is deficient in rickets and osteomalacia?
D
What happens when vitamin D is deficient?
there is ineffective mineralization of the bone, and an increase in nonmineralized osteoid
Who does rickets affect?
kids
Who does osteomalacia affect?
adults
What makes osteomalacia different than rickets?
it represents defective mineralization of bone that has completed its normal development
What is the role of PTH on bone?
stimulates osteoclasts to increase bone resorption and Ca++ metabolism
What factor mediates PTH’s affect on osteoclasts?
RANKL
What is the role of PTH on the kidney?
Increase Ca++ reabsorption in the renal tubule and synthesize vitamin D
What is the role of vitamin D?
increase Ca++ reabsorption by the gut and to increase Ca++ metabolization from the bone.
Overall, what molecule does PTH increase in the blood?
Ca++
What are the 4 skeletal changes in renal osteodystrophy?
increase osteoclast activity, osteomalacia, osteosclerosis, growth retardation
What is osteomyelitis?
inflammation of bone and marrow
What causes osteomyelitis?
bacteria, typically pyogenic and mycobacteria
What are the 3 routes that pyogenic osteomyelitis can reach the bone?
blood, neighboring tissue and trauma
Which pyogenic bacteria is most common in osteomyelitis?
staph aureus
Which pyogenic bacteria is most common in osteomyelitis in patients with sickle cell anemia?
Salmonella
Case scenario: a patient has been given treatment for TB for the past few days but complains of pain in the upper extremities and vertebrae. You take a sample and find granulomatous inflammation with caseous necrosis of the bone. What type of bacteria is likely to be at fault?
mycobacteria (tuberculosis osteomyelitis)
What is it called when there is a TB infection in the vertebrae?
Pott disease
What are the 5 primary site for metastatic bone tumors?
prostate, breast, lung, kidney and GI
What is an osteoma?
benign lesion in the bone that are not invasive
Where are osteomas common?
head and neck
Where do osteoid osteomas frequently occur?
femur and tibia (<2cm in dimension)
Do osteoid osteomas affect men or women more?
men
Where do osteoblastomas occur?
spine
What is the most common Sx and Tx for osteoid osteomas?
local pain, Tx with ASA
How do you Tx a osteoblastoma?
CUT IT OUT YEAAAAAAAAAAAAAA
What is the size of osteoblasomas vs osteoid osteomas?
osteoblastomas can grow larger than 2 cm
What are osteosarcomas?
malignant tumor of the bone
What are conventional osteosarcomas?
~75% of cases, occur most often during 2nd decade of life, occur around knee, males more affected, etiology is unknown
What are osteochondromas?
benign bone tumors that are fairly common
What type of tissue accumulates in osteochondromas?
hyaline cartilage
What is Ollier disease?
multipel chondromas, especially in the hands and feet
What is Maffuci syndrome?
multiple chondromas associated with benign vascular tumors of soft tissue
What are chondrosarcomas?
malignant tumors that typically occur in older patients
Where are common sites of chondrosarcomas?
shoulder, pelvis, proximal femur and ribs
What are giant cell tumors?
rare, agreessive bone tumors that occur between ages 20-40 almost entirely in the epiphysis
What are the 2 members of the Ewing sarcomas family of tumors?
- EWS of bone (Ewing sarcoma of bone)
2. Primitive neuroectodermal tumor (PNET)
What % of bone tumors are of the Ewing sarcoma family?
6-10%, second most common form of bone tumor in children (following osteosarcoma)
What gene is translocated in Ewing sarcomas?
t11;22 or q24;q12
Where do Ewing sarcomas occur?
metadiaphysis (femur) or flat bones of pelvis
What is the most common disease of the joints?
osteoarthritis
What happens in osteoarthritis?
degeneration of the articular cartilage
What is primary osteoarthrits?
arises without any caustive agent
What is secondary osteoarthritis?
changes developing in previously injured joint
Is osteoarthritis an inflammatory diesease?
NO. inflammation may occur secondarily and aid in progression of the disease
Aging, mechanical and genetic factors can cause what cells to lose the capacity to maintain articular cartilage?
chondrocytes
The risk of osteoarthritis is linked directly to what factor?
bone density
What are characteristic changes in osteoarthritis?
weakening and breakdown of type II collagen. TNF, IL-1 and NO are possible mediators
Where does osteoarthritis common affect?
hips, knees, lower lumbar and cervical vertebrae
Is rheumatoid arthritis an inflammatory disorder?
YES. a chronic systemic one, at that.
Which HLA antigen is increased in rheumatoid arthritis?
HLA-DRB1
What tissues are affected with rheumatoid arthritis?
skin, blood vessel, heart, lungs, muscles. mainly the joints.
What happens at the joints in rheumatoid arthritis?
articular cartilage is destroyed and there is ankylosis of the joints (bent, crooked, stiff)
When does juvenile rheumatoid arthritis occur?
<16 y/o
How is juvenile rheumatoid arthritis different than adult?
more large joints affected, systemic disease more common, rheumatoid factor absent, ANA sero + is common, oligoarthritis more common
What causes gout?
an icnreease in tissue uric acid
What are the Sx of gout?
recurrent episodes of gout because of crystalline aggregates of urate crystals.
What can cause gout?
Overproduction of uric acid with decreased renal excretion or vice versa
How can the urate crystals in gout activate immune responses?
activate C3a and C5a which accumulates neutrophils and macrophages in joints, macrophages release cytokines, proinflammatory mediators released (IL-1, TNF, IL-6 and IL-8)
What is pseudo-gout?
when there is deposition of calcium pyrophosphate crystals in the tissues (CPPD)
What is hereditary CPPD?
associated with osteoarthritis, mutation in ANKH affecting the pyrophosphate channels
What is secondary CPPD assocaited with?
previous joint damage, hemochomatosis, mypomagnesemia, hypothyroidism and diabeeeeetus
What is the etiology of CPPD/ pseudo-gout?
UNKNOWN
Where are soft tissue tumors/lesions derived from?
mesenchymal cells
Are most soft tissue tumors benign or malignant?
benign (1:100)
What are some causes of soft tissue tumors?
Burns, chemicals, kaposi sarcomas with herpes virus 8.
What genetic mutations can cause soft tissue tumors?
NF1 mutations, P53 mutations (Li Fraumerie), Osler-Weber-Rendu syndrome (hereditary telangectasia)
What are the clinical features of herediary telangectasia?
autosomal dominant, dilated capillaires/veins, present from birth, widely distributed
What are lipomas?
benign subcutaneous tissues of fat. most common soft tissue tumor of adulthood
What are the clinical features of lipomas?
soft, mobile, painless and cured by excision
What are liposarcomas?
fat tumors of the deep soft tissue of the peroximal extremities and retroperitoneum, one of the most comm on sarcomas of adulthood.
What are the 3 types of liposarcomas?
well differentated (indolent), myxoid type (intermediate malignant behavior), and pleomorphic (aggressive and readily metastasize)
What are rhabdomyosarcomas?
skeletal muscle tumors, most common soft tissue sarcomas in children to adolescence.
Where do rhabdomyosarcomas commonly occur?
head, neck or GI tract
What are some clinical features of rhabdomyosarcomas?
genetic mutations can cause dysregulation of muscle differentiation, aggressive. Tx with surgery + chemo and radiation
What is the most common subtype of rhabdomyosarcomas?
embryonal
What are the clinical presentation of embryonal rhabdomyosarcomas?
typical in nasal cavity, orbit, middle ear, prostate, vagina, bile ducts or paratesticular. this type has the worst prognosis.
What are leiomyomas?
Benign tumors of smooth muscle that typically arise in the uterus
What are leiomyosarcomas?
smooth muscle tumors that affect adult women, occur in skin and soft tissues of extremties and retroperitoneum
