Y2B3 Path- Bone Pathology

Front 1

what two cells are derived from osteoprogenitor cells? what celll is derived from hematopoeitic progenitor cells?

Back 1

osteoprogenitor cells: osteoblasts and osteocytes
Hematopoeitic progenitor cells:osteoclasts

Front 2

what regulates the osteoclast formation and function?

Back 2

directly or indirectly via paracrine molecule mechanism

Front 3

T/F
the osteoclast cannot be a functioning osteoclast without an osteoblast.

Back 3

true

Front 4

what is the histological unit of the bone? what is the functional unit of the bone?

Back 4

histo: osteon
functional unit: Basic Multicellular Unit (BMU)

Front 5

what constitutes the strength of bone? what must hydroxyapatite be attached to to make sure the bone is strong?

Back 5

Bone matrix constitutes the strength of bone. Hydroxyapatite must be attached to calcium to make the bone strong, otherwise it will be very soft and brittle

Front 6

what are the two types of protein of bone matrix?

Back 6

collagenous and non-collagenous proteins

Front 7

what two proteins are specific serum markers for osteoblast activity?

Back 7

osteocalcin and alkaline phosphatase

Front 8

what are the growth factors that help cell formation and differentiation of bone?

Back 8

collagenous Growth factors
cytokines
IL-1, IL-6, PGs

Front 9

T/F

Osteoid tissue is a pathology in adults, but not in kids and infants.

Back 9

True

Front 10

what type of collagen is deposited by osteoblasts?

Back 10

type 1

Front 11

what type of bone do adults have? fetuses?

Back 11

adult: lamellar bone
fetus: woven bone, no haversian system. weaker than lamellar bone

Front 12

T/F

Woven bone found in adults is considered normal.

Back 12

FALSE

Woven bone found in adults is indicative of a pathologic state.

Front 13

where does remodeling of bone usually occur?

Back 13

as sites experiencing fatigue or microdamage as well as after fracture healing.

Front 14

where does endochondral ossification not occur? what type of ossification does occur there?

Back 14

skull and clavicle; intramembranous ossification.

Front 15

what does a defect in nuclear proteins and transcription factors cause?

Back 15

dysostoses (abnormality of bone formation)--> absence of a bone, incomplete bone growth, extra bone, bone fusion

Front 16

what does a defect in hormones and signal transduction mechanisms cause?

Back 16

dysplasias- abnormality in the bone development itself.

Front 17

what gene mutation is involved in achondroplasia? what does it result in?

Back 17

FDFR3 receptor

resulting in short stature, rhizomelic shortening of limbs, frontal bossing, midface deficiency.

Front 18

what gene mutation is involved in thantophoric dwarfism? what does it result in?

Back 18

FGFR3

severe limb shortening and bowing, frontal bossing, depressed nasal bridge.

Front 19

what is the pathophysiology behind achondroplasia?

Back 19

chromsome 4 leads to constant activation of FGFR3 inhibiting cartilage proliferation of the growth plate leading to growth suppression. Cartilage will grow into a fibroblast instead of bone.

Front 20

what is most lethal form of dwarfism? what will they be plagued with after birth?

Back 20

Thanatophoric Dwarfism- they will be plagued by repeated infection and chest pain d/t narrowed chest cavity. They will have pulmonary hypoplasia w/ respiratory insufficiency causing frequently death at birth or soon after.

Front 21

how do you differentiate achondroplasia and thantophoric dwarfism?

Back 21

Thanatophoric dwarfism: diminshed chondrocyte proliferation, but normal size.

achondroplasia: hypertrophic growth plate clusters of large chondrocytes.

Front 22

what gene is mutated in osteogenesis imperfecta type 1-4? what does it result in?

Back 22

COL1A1 type 1 collagen

results: bone fragility, hearing loss, blue sclerae.

Front 23

what gene is mutation in achondrogenesis II? what does it result in?

Back 23

COL2A1 type 2 collagen

results: short trunk, severly shortened extremities, relatively enlarged cranium, flattened face.

Front 24

what is the main problem in osteogenesis imperfecta?

Back 24

in the quantity of collagen that is formed not the quality because once it forms its great.

Front 25

T/F

All 4 types of osteogenesis Imperfecta are autosomal dominant

Back 25

true

Front 26

what gross manifestations are visible in a pt of osteogenesis imperfecta?

Back 26

skin and bone laxity and subluxed lenses, distorted teeth, fractures and eye problems (crossed-eyes). and they will have blue sclera.

Front 27

what fractures and nonskeletal manifestations help distinguish osteogenesis imperfecta from child abuse?

Back 27

fractures: sternal, scapular, ribs and true skull fractures along w/ metaphyseal corner fractures are common in child abuse.

nonskeletal: retinal hemorrhage, visceral intramural hematomas, intracranial bleeding are also indications of child abuse.

Front 28

what is mucopolysaccharoidoses?

Back 28

Lysosomal storage diseases due to enzyme deficiency of any of the lysosomal acid hydrolases

Front 29

what causes osteopetrosis? what does it result in?

Back 29

Deficiency of carbonic anhydrase II OR mutation in the CIC-7 (creates this acidic medium) chloride channel gene results in osteoclast dysfunction & reduced osteoclast bone resorption resulting in disturbed bone homeo-stasis with more bone deposition & thickness. Bulky and very heavy.

Front 30

pts presents w/ anemic and a series of repeated infections. you do a bone biopsy and notice that the bone contains no medulla cavity. Dx

Back 30

Osteopetrosis

Front 31

what are the pathologic changes of osteopetrosis?

Back 31

end of long bones become bulbous, obliteration of medullar cavities w/ repeated infections, hepatosplenomegaly, nerve compression, and fractures.

Front 32

Pt presents with multiple fractures, anemia, repeated infections, cranial nerve deficits, and hepatosplenomegaly. dx

Back 32

osteopetrosis

Front 33

what is osteoporosis? what population do you see this in?

Back 33

reduction of bone mass which causes increased bone porosity, fragility and liability to fracture.

pop: old people or post menopausal

Front 34

what are the 3 determinants of bone mass magnitude?

Back 34

genetic factors, physical activity/ muscle strength and diet.

Front 35

what are the two causes of primary osteoporosis?

Back 35

postmenopausal and senile

Front 36

why does menopause cause osteoporosis?

Back 36

high bone turnover--> estrogen has a very big job in calcium and phosphorous deposition so as it decreases so does the deposition of calcium and phosphorous.

Front 37

what does an increased RANK/RANKL cause?

Back 37

greater resorption than deposition--> high turnover rate = osteoporosis.

Front 38

how does senility lead to osteoporosis?

Back 38

low bone turnover, formation of osteoclasts will be reduced and bone forms very slowly.

Front 39

what will you see on histology and pathology of a pt w/ osteoporosis?

Back 39

1) thinning of spongy bone trabeculae (honeycomb appearance) w/ microfractures.
2) thinning of cortical bone and widening of Haversian canals (mimicking cancellous bone)

Front 40

what is the clinical course of osteoporosis?

Back 40

it is insiduous and early on asymptomatic.It usually manifests clinically w/ deformity and or fractures/ Multilevel spine fracture causes short stature. In the case of fractures it is painful.

Front 41

what type of scans do you use to diagnose osteoporosis?

Back 41

DEXA scan or quantitative CT scans.

Front 42

how do you prevent and tx osteoporosis?

Back 42

exercise, high calcium and vit D, estrogen replacement, bisphosphonates, recombinant PTH.

Front 43

why should you use bisphosphonates instead of estrogen replacement?

Back 43

because estrogen replacement causes increased heart issues and other health issues. Bisphosphonates do not.

Front 44

what does recombinant PTH do for a pt suffering from osteoporosis?

Back 44

stimulates bone formation more than bone resorption leading to increased skeletal mass.

Front 45

what is paget's disease?

Back 45

repetitive and overlapping sequence of bone turnover w/ predominance of bone deposition (collage of matrix madness), idiopathic etiology.

Front 46

34 yo white female presents w/ legs bowed anteriorly and laterally. Upon palpation you notice that the legs are warmer than they should be and you find an enlarged spleen and liver. You do a CT and notice the bone is starting to get rarified. Dx

Back 46

Paget's dz

Front 47

what are the three stages of Paget's dz?

Back 47

1)initial: osteolytic stage in which the bone starts to get rarified
2) Mixed: Osteoclastic-osteoblastic stage w/ more bone deposition (osteoclast and osteoblast work in tandem)
3) osterosclerotic stage: gain in bone mass making heavy bones.

Front 48

what will you see on histopathology of paget's dz?

Back 48

mosaic pattern: haphazardly oriented lamellar or woven bones

Front 49

You are a radiologist and you come across a CT of the calvarium that has multiple patches of sclerotic bone in the calvarium, almost like a cotton wool appearance. dx

Back 49

Paget's dz

Front 50

what is leontiasis ossea? polyostotic? what disease has these two manifestations?

Back 50

leontiasis ossea: bony overgrowth of craniofacial skeleton

polyostotic: that leontiasis ossea affecting multiple bones (85%)

-paget's dz

Front 51

what is the 2 biggest complication that you worry about in a pt w/ Paget's Dz?

Back 51

tumor transformation--> malignant osteosarcoma.

high-output cardiac failure.

Front 52

how do you tx paget's dz?

Back 52

calcitonin and bisphosphonates for sxs

Front 53

what is PTH's role in maintaining homeostasis?

Back 53

it goes to the major source of calcium (usu bone) and resorbes the calcium from the bone to give to the blood when calcium is low. Phosphorous follows calcium causing a restoration of calcium levels and increasing the phosphorus through your kidneys.

Front 54

There is an intimate relationship between _____, ______ and ______

Back 54

Bone, kidney and GI tract

Front 55

in what organ system is Vitamin D turned into its active form?

Back 55

Kidneys :)

Front 56

what is rickets? what does it result in?

Back 56

Vitamin D deficiency in children which leads to decreased bone calcification and increased osteoid tissue.

Front 57

4 year old pt presents w/ bowing of the legs and a waddling gait with a protruding abdomen. You notice that his fontanelles are still present, particularly the anterior one. dx and what else might you find on examination to confirm.

Back 57

dx: Rickets

others: Rachcitic rosary- thickening of the costochondral junctions which causes strong of beads like appearance.
harrison's groove: depression along the line of insertion of the diaphragm into the rib cage.
Pigeon Chest: protrusion of the sternum.
craniotabes- thinning and softening of occipital and parietal bones.

Front 58

what is osteomalacia? what does it result in? what can you see on XRay?

Back 58

vitamin D deficiency in adults w/ defective calcification of osteoid matrix that causes osteopenia, deformities and potential insufficiency fractures.
XRay: diffuse radioluscency

Front 59

what is the main difference between osteomalacia and osteoporosis?

Back 59

the production of osteoid matrix is abundant in osteomalacia, but reduced in osteoporosis.

Front 60

what would osteomalacia be called if it was secondary to renal dx?

Back 60

renal osteodystrophy

Front 61

what does primary hyperparathroidism result from? what does secondary hyperparathyroidism?

Back 61

autonomous hyperplasia or a tumor--> parathyroid adenoma

secondary: commonly caused by prolonged states of hypocalcemia resulting in compensatory hypersecretion of PTH ie renal osteodystrophy

Front 62

how are increased PTH level detected?

Back 62

by receptors on osteoblasts that release molecules to stimulate osteoclast actiity and bone resorption.

Front 63

how does kidney damage cause renal osteodystrophy? what part of the bone is affected by this dz?

Back 63

damaged kidneys cause a decrease in renal alpha hydroxylase enzymes which decreases the amount of active Vitamin D--> leading to hypocalcemia and bone resorption. Also, Damaged kidneys cause increased phosphates leading to secondary hyperparathyroidism w/ bone resorption and metabolic acidosis (w/ bone resorption).

this affects the cortexes of the bone, not the medulla or renal cavity.

Front 64

what are the two types of bone disorders of renal osteodystrophy in end-stage renal failure?

Back 64

high-turnover osteodystrophy (bone resorption> bone formation)- osteomalacia is common

low turnover (aplastic) osteodystrophy--> bone w/ lil osteoclastic and osteoblastic activity- osteomalacia is less common.

Front 65

what are the complications of renal osteodystrophy?

Back 65

worsening osteomalacia (d/t iron and aluminum deposits)
Dialysis encephalopathy and microcytic anemia (d/t aluminum deposits)
Amyloid deposits in bone (d/t increase in serum B2 microglobulin).

Front 66

what lab values are indicative of osteitis fibrosa cystica? what can you see on Xray?

Back 66

lab: Increased PTH, increased serum calcium, decreased serum phosphorus.

Xray: expansile areas of lucency causing pain and predisposes to deformity and fracture--> along radial aspect of middle phalanges of index and middle fingers

Front 67

what will you see histologically of a pt w/ osteitis fibrosa cystica? what will you see if hemorrhage occurs?

Back 67

the cystic focal lesions undergo reactive fibrous tissue proliferation mixed w/ multinucleated giant cells and BVs. Full of macrophages and inflammatory cells.

hemorrhage: hemosiderin deposits and macrophage infiltrate giving "brown tumor"

Front 68

in what dz will you see cortical cutting cones composed of osteoclast sheets on a histological sample?

Back 68

osteitis fibrosa cystica

Front 69

what will osteitis fibrosa cystica cause in cancellous bone on a histological sample?

Back 69

osteoclast dissection centrally along length of trabeculae (tunnel into) creating railroad tracks appearance producing dissecting osteitis

Front 70

what are the three stages of bone healing after a fracture? explain what happens in each step.

Back 70

1) inflammatory phase- hematoma formation (immediately after fracture)
2) reparative phase- a) procallus formation (by end of 1st wk)--> fibrous tissue. B) bony callus formation- end of 3rd week (early phase) --> activated osteoprogenitor cells deposit subperiosteal trabeculae of women bone inside the medullary cavity. Late phase- ossification of the soft callus- new cartilage forms and undergoes enchondral ossification.
3) remodeling phase- longest in the healing cycle where woven bone is plreaced by lamellar bone. Medullary canal is reconstituted and excess bone is resorbed by osteoclasts.

Front 71

what are the 4 bolded causes of osteonecrosis?

Back 71

trauma
corticosteroid therapy
infections
sickle cell anemia

Front 72

what bone is mainly affected in osteonecrosis? what does it cause?

Back 72

cancellous bone and marrow = becomes pale and ischemic

Front 73

what is the clinical course of osteonecrosis?

Back 73

subchondral infarct triggers chronic pain associated w/ physical activity that becomes progressively constant and undergoes secondary changes like collapse w/ secondary OA.

Front 74

8 year old white male presents to your office with a limp and hip pain. He denies any previous trauma. dx

Back 74

legg-calve-perthes dz:

idiopathic interrupted blood supply of capital femoral epithysis of children 2-12

Front 75

14 year old male presents with pain at the upper tibia and knee joint. He says it gets worse after soccer practice. dx

Back 75

Osgood-schlatter dz

sports and growth spurt related disorder involving epiphysis of tibial tuberosity. Self-limited and stops by the end of puberty.

Front 76

what are the typical site of infections for osteomyelitis in neonates, children and adults?

Back 76

neonates: metaphyses, epiphysis or both
children: metaphyses
adults: epiphyses and subcondral regions

Front 77

Name that bug (that causes osteomyelitis):
1) in IVDA (3)
2) neonates (2)
3) sickle cell (1)

Back 77

1) E. coli, pseudomonas and klebsiella
2) H influ and group B strept
3) salmonella

Front 78

what is the acute stage of osteomyelitis?

Back 78

bacteria spread to shaft through Haversian canals to subperiosteum causing subperiosteal abscess causing localized suppurative and ischemic injury w/ segmental bone necrosis (sequestrum). That abscess then bursts and spreads to surrounding soft tissue w/ formation of draining sinus tract to skin surface.

Front 79

what is the chronic stage of osteomyelitis?

Back 79

leukocytes release cytokines that activate osteoclasts and bone resorption. Fibrous tissue and reactive bone deposit in the periphery leading to bone sclerosis.

Front 80

what is an involucrum?

Back 80

fibrous tissue and reactive bone deposit in the periphery that then surrounds a sequestratedpiece of bone. It is viable fibrous tissue.

- chronic stage of osteomyelitis.

Front 81

what can the spread of epiphyseal infection to adjacent joints cause?

Back 81

septic or suppurative arthritis

Front 82

25 year old female presents to your office with a fever and throbbing pain of the distal part of her humerus. On X-ray you find a lytic focus surrounded by sclerotic zone. Blood culture comes back positive for organisms. dx

Back 82

acute hematogenous osteomyelitis

Front 83

12 year old male presents to your office with chills, night sweats and weight loss. He admits that he recently immigrated with his family from Mexico. You do a osteopathic evaluation and notice pain illicited upon palpation of the spine at T5-6. You order and MRI, what do you expect to see on MRI?

Back 83

on MRI you expect to see an abscess destroying the intevertebral disc in betwen T5-6.

-Tuberculous osteomyelitis

Front 84

what does TB osteomyelitis cause in long bones?

Back 84

extensive necrosis through the medullar cavity.

Front 85

how do you differentiate btwn cancer and pott's dz?

Back 85

cancer will destroy the vertebra itself, while pott's dz destroys the Intervertebral discs.

Front 86

when does congenital syphilis start? where are the organisms generally located? what can you see histologically?

Back 86

congenital syphilis starts at 5 months of gestation
the organisms are located at areas of active endochondral ossification (long bones) causing osteochondritis and periosteum--> periostitis
histologically: granulation tissue, plasma cells and necrotic bone

Front 87

when is bone affected in acquired syphilis? what bones are involved? what will you see histopathologically?

Back 87

- tertiary stage (2-5 years after inital infection)
- bones involved: nose, palate, skull and long bones
- histopathologically: same as congenital syphilis + GUMMATA (oft, non-cancerous growth resulting from the tertiary stage of syphilis)

Front 88

what are the 2 most frequently occuring benign bone tumors? 3 most frequently occuring malignant bone tumors?

Back 88

bengin: osteochondroma and giant cell tumor
malignant: osteosarcoma, chondrosarcoma, and Ewing's sarcoma

Front 89

Metastatic tumors to which organ will cause a completely osteoblastic reaction of bone? what about a completely osteolytic reaction of bone?

Back 89

osteoblastic: prostate- bone dz
osteolytic: kidney, liver, thryoid gland (rarification)

Front 90

Metastatic tumors of which organs will cause a MOSTLY osteolytic response of bone? what about MOSTLY osteoblastic? what about 50/50?

Back 90

MOSTLY osteolytic: lung
MOSTLY osteoblastic: colon, melanoma, bladder cancer, soft tissue sarcoma
50/50: breast

Front 91

define hamartoma and give an example.

Back 91

hamaryoma:a focal growth that resembles a neoplasm but results from faulty development in an organ.
eg: osteochondroma

Front 92

what population is generally afflicted with osteochondroma? where is it primarily located? what is the worry associated here?

Back 92

pop: men <25 yo
location: metaphysis of long bones particularly lower end of femur and upper end of tibia
worry: it may form malignant chondrosarcoma in multiple familial osteochondromatosis.

Front 93

You are a radiologist and you come across an X-Ray of a 30 yea old woman who's X-ray shows a "bubble soap" appearance in the epiphyses of the femur. You ask for a histological sample of the bone and find osteoclast-like multinucleated cells swimming in mononuclear stromal cells. first dx and then how do you tx it.

Back 93

giant cell tumor

(common in women 2-40 yoa, MC epiphyses of long bones, 50% around knee joint).

tx: removal of the bubble soap and replacement w/ a tissue graft.

Front 94

22 year old man presents to your office with pain that wakes him up in the middle of the night. He says that aspirin makes the pain go away immediately and he falls back asleep quickly. He tells you that the pain is deep in his femur and on bone biopsy you find haphazardly interconnecting trabeculae of irregular reactive woven bone that is rimmed by prominent osteoblasts. Dx and how do you tx?

Back 94

dx: osteoid osteoma

(males 10-25, benign tumor. dev in bone cortex of femur and tibia. causes nocturnal pain d/t PGs, responds dramatically to aspsirin)

tx: cured by local resection.

DO NOT DO RADIOTHERAPY--> may induce malignant transformation.

Front 95

This benign bone tumor is similar to osteoid osteoma, but its is bigger and more aggressive. What is it and what else makes it different?

Back 95

Osteoblastoma (Giant Osteoid osteoma).

It has a central nidus (A place in which bacteria have multiplied or may multiply; a focus of infection) and usually affects irregular bone (like spine). Cortical bones are rarely affected.

Front 96

what is an enchondroma?

Back 96

benign neoplasma, cartilagenous involving mainly bones of hand and feet, intra-medullar, multilobal lytic lesion w/ flecks of calcification and cortical thinning.

Front 97

what is the MC primary malignant bone tumor?

Back 97

osteosarcoma

Front 98

15 year old male presents with pain, swelling and a fracture just superior to his knee joint (distal end of the femur). You do a blood test and Xray and find an increase of alkaline phosphatase and a codman triangle and sunburst pattern of growth on X-ray. dx and what is the worry associated with this?

Back 98

Osteosarcoma

(males 10-20 yoa around knee joint; codman triangle: triangular area of new subperiosteal bone that is created when a lesion)

worry: tumor may spread hematogenously to lungs, liver and brain.

Front 99

Bone biopsy reveals: lacelike pattern of neoplastic bone produced by anaplastic malignant tumor cells with funny shaped mitotic figures. dx

Back 99

osteosarcoma

Front 100

what tumor can come secondary to familial osteochondromatosis or multiple enchondromatosis?

Back 100

malignant cartilagenous tumor

Front 101

45 year old man presents with a painful, progressively enlarged mass on his pelvis. He has a family history of multiple enchondromatosis. dx

Back 101

Malignant cartilagenous tumor

clear cell variarnt would affect the epiphyses of long bones proximally.

Front 102

This malignant bone tumor resembles lymphoma. what is it and what is the genetic change that causes it?

Back 102

Ewing's sarcoma

11:22 chromosomal translocation

(Patrick Ewings number was 33--> 11+22= 33)

Front 103

You come across an XRAY of a 6 year old boys femur. The Xray shows an onion-skin appearance and a bone biopsy shows sheets of small round cells w/ small amounts of clear cytosplasm. Dx and tx

Back 103

dx: ewings sarcoma
tx: chemotherapy