Bone Path; Bone Tumors

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Embryological origin of osteocyte and osteoblast

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mesechymal

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Embryological origin of osteoclast

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derive from the same hematopoietic precursor as the monocytes and macrophages

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inactive osteoblast is aka

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Osteocyte

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Osteoid: defn

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organic matrix of bone.

Consists of: type I collagen + osteonectin + osteocalcin + alkaline phosphatase + other proteins

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What is the mineral component of bone?

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calcium hydroxyapatite Ca5(PO4)3(OH)

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lamellar osteoid: defn

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mature bone. Collagen fibers in parallel rows.

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woven osteoid: defn

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active new matrix and collagen fibers are interwoven

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Levels of ____ in blood and urine can be used to assess bone remodeling.

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hydroxyproline

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Osteoid is 95% ____________

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Type I collagen

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________ levels are a measure of osteoblastic activity.

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alkaline phosphatase

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Primary organ of action of Vitamin D

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INTESTINES - absorption of calcium and phosphorus

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Lack of vitamin D is usually the result of what processes?

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End stage liver and kidney disease, NOT usually lack of dietary intake.

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Where does activated vitamin D come from?

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sun exposure --> dihydrocholesterol in skin transformed to Vitamin D3

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What happens to Vitamin D3 after it's made in the skin?

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Converted to activated form in liver and kidney

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osteomalacia: defn

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lack of vitamin D in adults. Poorly structured osteoid.

Hyperosteoid Production
Inadequate Mineralization

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osteomalacia: sx

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Generalized bone pain
Bone tenderness
Osteosclerosis with cysts
Bone is weak and vulnerable
to microfractures (spine,
femoral neck).

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Primary Hyperparathyroidism: defn

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Action of PTH produces elevated blood calcium and fall in phosphorous

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What is most Primary Hyperparathyroidism due to?

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Parathyroid adenoma

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How does PTH act to increase blood calcium?

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Stimulates osteoclasts to resorb bone

Increases renal tubular reabsorption of calcium

decrease renal absorption of phosphorous

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Osteolitis fibrosa cystica: defn and pathophys

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Subperiosteal reabsorption of bone leading to csysts within bone. Due to hyperparathyroidism

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hyperparathyroidism, if untreated, can lead to what bone changes?

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Subperiosteal bone resorption
Dissecting Osteitis
Osteitis fibrosa cystica

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osteoporosis: defn

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Decreased amount of normally mineralized bone

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Blood chemistry changes in osteoporosis

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NONE. they're normal.

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Specific test for osteoporosis

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bone density measurement

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most vulnerable bones for osteoporotic fractures

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femoral head (hip)

wrist (Colle's fracture)

Vertebral column

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Cause/associations of primary osteoporosis

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Postmenopause (reduced estrogen) and older age

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Hypercortisolism: how does it lead to osteoporosis?

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Steroids directly inhibit osteoblasts.

Steroids have anti Vit D effect and anti-PTH effect --> lower calcium levels

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Gout: pathophys

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deposition of uric acid in cartilage or articular joint surfaces

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Paget Disease of the Bone is aka

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osteitis deformans

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Paget Disease of the Bone: cause

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myxovirus infection

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Paget Disease of the Bone: pathophys

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Marked overgrowth of poorly mineralized osteoid ("matrix madness"). Leads to thickened and irregular bone.

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Paget Disease of the Bone: risks of other diseases

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1) Fractures
2) Osteosarcoma

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Paget Disease of the Bone: what lab changes are found

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extremely elevated alk phos in blood

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pathologic bone fractures: defn

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those not associated with sufficient external cause (trauma)

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pathologic bone fractures: causes

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Most common are osteoporosis and cancer lytic mets to bone

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How is osteomyelitis acquired in children vs adults?

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Adults: most often from direct inoculation from trauma

Children: more from hematogenous spread

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Organism causing most osteomyelitis

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S. aureus

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avascular necrosis: defn

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due to loss of end arteries of long bones

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avascular necrosis: most common site

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femoral head

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avascular necrosis: male: women ratio

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3:1 (more common in men)

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most common primary malignant bone tumor

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osteosarcoma (still very rare)

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Osteosarcoma (Osteogenic Sarcoma): age

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young (10-25 years)

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Codman’s triangle: defn

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Radiographic sign of Periosteal elevation

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Osteosarcoma : symptoms

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1) Pain
2) Mass
3) Pathological fracture

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Osteosarcoma : radiographic findings

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Destructive and lytic lesion of bone.

Elevation of the periosteum (Codman’s triangle)

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Osteosarcoma : tx

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Establish the diagnosis
Preoperative chemotherapy
Excision, limb sparing or amputation
Pathologic evaluation of extent of necrosis

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A tumor of malignant chondroblasts

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chondrosarcoma

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chondrosarcoma: age

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middle aged - older

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chondrosarcoma: location

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proximal skeleton: especially pelvic bones and proximal femur, ribs.

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5 cancers that are prone to metastasizing to bone

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BLT with a Kosher Pickle

Breast
Lung
Thyroid
Kidney
Prostate

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Giant cell tumor:defn

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A Tumor of Bone Mesenchymal Cell Origin
Probably all are low grade malignancies
Behavior of any given tumor is unpredictable

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Ewing’s Sarcoma : defn

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Non-hematologic small round cell tumor with characteristic
translocation chromosomes 11 & 22

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2nd most common primary bone tumor in children

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Ewing's sarcoma

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Ewing's sarcoma: gross appearance

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"onion-skin" effect

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Ewing’s Sarcoma : pathophys

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Translocation of chromosomes 11 and 22 leads to a new protein that gives you cancer.

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most lytic bone tumor

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multiple myeloma

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multiple myeloma: histology

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See eosinophilic cytoplasm with clock-face like appearance of nuclei

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multiple myeloma: associated abnormalities

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hypercalcemia (due to breakdown of bone releasing Ca into blood).

Over production of globulins provokes proteinuria.

Anemia - destruction of bone marrow

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multiple myeloma: symptoms

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intense bone pain and fractures of involved bone, especially compression fractures

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Metastatic cancer to bone: most common locations

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axial skeleton, vertebra, pelvis, ribs, skull. (Rare distal to the knee or elbow)

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osteoblastoma: presentation

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bone pain that does NOT respond to aspirin

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osteoid osteoma: presentaiton

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bone pain that responds to aspirin

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most common benign bone tumor

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osteochondroma.

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osteochondroma: pathophys

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Lateral projection and growth of growth plate:
As growth plate expands, bone elongates linear. Lateral projection of growth plate --> projection of bone with surface of cartilage. results in osteochondroma

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osteosarcoma: risk factors for teens

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Familial retinoblastoma

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osteosarcoma: risk factors for elderly

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Paget's disease of bone

Radiation exposure.

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osteosarcoma: place of origin

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metaphysis of long bones (distal femur or prox tibia classically)

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periosteum: defn

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surface of bone

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Osteosarcoma: histology

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large pleimorphic cells producing osteoid (pink)

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Giant Cell tumor: location

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epiphysis of long bones (ONLY tumor on epiphysis)

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Giant Cell tumor: xray appearance

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soap bubble appearance - due to reactive bone formation on surface of tumor.

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Ewing sarcoma cells derive from ______

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neuroectoderm

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Ewing sarcoma: location

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diaphysis of long bones

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Chondroma: defn

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benign tumor of cartilage

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Where do cartilage tumors arise?

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medulla

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Chondroma: where?

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small bones of hands and feet, distally

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Chondrosarcoma: where?

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Malignant cartilage forming tumor arising in medulla of PELVIS or central skeleton

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Mets to bone: what type of lesion, typically?

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osteolytic - punched out

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Which cancer produces mets to bone that are osteoblastic?

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prostate

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Type I Collagen: where found?

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Most common type. It is present in scar tissue, the end product when tissue heals by repair. It is found in tendons, skin, artery walls, cornea, the endomysium of myofibrils, fibrocartilage, and the organic part of bones and teeth.

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Type II Collagen: where found?

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Hyaline cartilage; vitreous humor

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Type III Collagen: where found?

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This is the collagen of granulation tissue, and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized. Reticular fiber. Also found in artery walls, skin, intestines and the uterus.

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reticular fiber: defn

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Networks of Type III collagen that form mesh networks in connective tissue. This network acts as a supporting mesh in soft tissues.

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the collagen of granulation tissue

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Type III

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Type IV Collagen: where found?

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Basement membranes (aka basal lamina).

Also lens of eye.