14-1: Bone Pathology

Front 1

What is the diaphysis?

Back 1

Central shaft of long bone

Front 2

What is the epiphysis?

Back 2

End of long bone

Front 3

What is the metaphysis?

Back 3

Bone between epiphysis (end of bone) and diaphysis (central shaft)

Front 4

Most bones are formed from _____ via _______.

Back 4

Most bones formed from cartilage via endochonral ossificaiton

Front 5

Cranial bones are formed from _____ via ______.

Back 5

Cranial bones formed from embryonic mesenchyme (without intermediate cartilage) via intramembranous ossificaiton.

Front 6

Role of osteoblasts

Back 6

Synthesize type I collagen, proteoglycans, glycoprots for bone matrix

New bone laid down is called osteoid and is then calcified

Front 7

Role of osteocytes

Where are they found?

Back 7

Osteocytes maintain bone matrix

Found in lacunae; one osteocyte per lacuna!

Front 8

Role of osteoclasts

Back 8

Secrete substances to digest collagen and dissolve Ca2+ crystals

Front 9

What cells must osteoclasts be differentiated from?

Back 9

Megakaryocyte (also multinuc'd)

Front 10

Where are osteoclasts derived from?

Back 10

Derived from monocyte precursors in BM

Front 11

What is periosteum?

Role?

Back 11

Outer layer of collagen and fibroblasts; has potential to form bone during growth/fracture healing.

Front 12

What is endosteum?

Back 12

Vascular membrane of bone lining marrow; contains osteoblasts/clasts, fibroblasts

Front 13

What is an osteon?

Back 13

Basic unit of bone: central ore (Haversian Canal) with BV's and nerves surrounded by lamellae

Front 14

What is woven bone?

When is it seen?

Back 14

Primary bone; temporary

Either replaced by lamellar bone or resorbed to form marrow cavity

Found in growing skeletons and in adults during fracture repair

Front 15

Spongy bone aka?

Back 15

Cancellour bone

Front 16

Cortical bone aka?

Back 16

Compact bone

Front 17

What is micromelia?

Back 17

Shortening of one or more limbs

Front 18

What is rhizomelia?

Back 18

Shortening of proximal segment of limbs

Front 19

What is acromelia?

Back 19

Shortening of distal segment of limbs

Front 20

Osteogenesis imperfecta:
Pathophys
Presentation

Back 20

Mutation-->defective alpha1/2 chains in type I collagen

Subject to fractures (live normal lifespan)
Blue sclerae
Hearing loss, misshapen teeth

Front 21

Osteogenesis Imperfecta Type II:
Pathophys

Back 21

Mutation in COL1A1/2 gene-->faulty collagen I formation; fetus suffers fractuers in utero

Results in pulmonary hypoplasia as a result of chest compression

NEONATAL FATAL

Front 22

Achondrolplasia:
Homozygote vs Heterozygote effects

Back 22

Common form of dwarfism (may arise de novo)

Homozygote-->fetal/neonatal death

Heterozygote-->ambulatory

Front 23

FGFR3

Back 23

FGFR3 mutation inhibits chondrocyte proliferation-->disorganized growth plates-->ACHONDROLPLASIA

Also seen in THANATOPHORIC dysplasia

Front 24

Thanatophoric Dysplasia:
What is it?

Back 24

Chest underdeveloped due to homozygous achondroplasia-->fetus dies of pulmonary hypoplasia

Front 25

Telephone receiver femur

Back 25

Thanatophoric dysplasia

Front 26

Osteopetrosis:
Pathophys

Back 26

AKA marble bone dz

Malfunction of osteoclasts result in improper bone remodeling (osteoclasts may be normal numerically)

Bones are solid but fracture readily

Can tx w/BM transplant

Front 27

Paget Disease:
What is it?

Back 27

Osteoclast dysfn in elderly

Involved bone subject to many tumors (benign and malignant)

Front 28

Effect of hyperparathyroidism on bone.

Back 28

Inc'd osteoclastic activity

Bone resorption-->cortical bone more than cancellous bone

Leads to microfractures-->brown tumors (result of hemorrhage and hemosiderin)

Front 29

Fracture pathology:
Steps in repair

Back 29

1) form hematoma
2) firbin mesh
3) inflammatory cells (granulation tissue)
4) Soft-tissue callus formed
5) new cartilage formed along fracture lines
6) bony callus formed after 2-3 weeks via endochondral ossificaiton

Front 30

What is a pseudoarthrosis and how does it arise?

Back 30

Nonunion of fracture repair; synovial cells may line nonunited surfaces nad prode pseudoarthrosis (false joint)

Front 31

Avascular necrosis:
Medullary vs Subchondral

Back 31

Medullary: clinically silent, but may be large and clinically evident in sickle cell anemia/Gaucher dz

Subchondral (at the joint)--can cause severe osteoarhtritis when collapse occurs

Front 32

Osteomyelitis:
Pathophys
Most common cause

Back 32

Related to infection (viruses, protozoa, fungi, bacteria)

Most common cause = staph aureus

Front 33

How does the location of osteomyelitis differ based on age?

Back 33

Neonate-->metaphysis and/or epiphysis

Children-->metaphysis

Adults-->epiphysis and subchondral bone

Due to differences in vasculature (hematogenous spread)

Front 34

Involucrum vs Sequestrum:
Definition

Back 34

Sequestrum = infected area surrounded by fibrous tissue and new bone

Involucrum = sleeve of tissue forming

Front 35

Osteosarcoma:
Benign/malignant
Age distribution
Sites affected
Metastatic sites

Back 35

Malignant bone forming tumor

Bimodal age distribution; biggest peak in patients under 20

50% affect knee joint

Mets to lung (20%) and other bone/brain

Note: survival rate is 80-90%!

Front 36

Osteosarcoma vs Chondroblastic Osteosarcoma

Back 36

Osteosarcoma = malignant tumor cells producing bone (osteoid)

If malignant cartilage is also produced = chonrdoblastic osteosarcoma

Front 37

Fibrous Dysplasia:
Neoplasm vs Hamartoma (definitions)
Monostotic vs Polyostotic vs Polyostotic with syndrome

Back 37

Neoplasm = malignant growth
Hamartoma = all bone elements present but bone does not develop

Monostotic (one location affected) - most common
Polyostotic = 1/4 of cases

Polyostotic w/syndrome = 3%; McCube-Albright, hyperthy, pituitary adenomas secreting GHs

Front 38

This growth can develop in prior lesions such as bone infarcts, previously radieted tissue or Paget disease.

Back 38

Fibrosarcoma

Can also arise in previously benign tumors; also can arise denovo.

Front 39

This growth appears aggressively lytic on x-ray but behaves benignly.

Back 39

Aneurysmal bone cyst

Front 40

This growth comprises the majority of bone tumors.

Back 40

Cartilage-forming tumors

Front 41

This growth consists of cartilage capping attached to bone by a stalk.

Back 41

Osteochondroma

Only in bones of enchondral origin and arise near growth plate, i.e., will not arise on skull.

Front 42

This growth is an intramedullary tumor that extends through the cortex to form a soft tissue mass.

Back 42

Conventional chondrosarcoma

Front 43

How does a conventional chondrosarcoma differ from a chondroblastic osteosarcoma?

Back 43

Conventional chondrosarcoma isn't forming any bone!

Front 44

90% of SLE patients exhibit this deficiency.

Back 44

C1q/C1r/C1s (complement) deficiency

Front 45

SLE:
Environmental Factors (risks)
Sex

Back 45

EBV (90% of pts have it)
UV exposure (exacerbation of dz)

FEMALES

Front 46

Immunologic basis of SLE

Back 46

Pathogenic autoAbs against nucleus

Most are IgG and consume complements

Front 47

Describe apoptosis in SLE.

Back 47

Apoptosis is inefficient due to phag deficiency, complement def

Excessive apoptosis in UV exposure (causes dz syx)

Front 48

Role of neutrophils in SLE.

Back 48

Nphil cell death impaired in pts w/SLE

Release human nphil peptide (HNP) wich act as pro-inflammatory agents

Front 49

This cytokine is overexpressed in SLE.

Cell that releases it?

Back 49

IFN-alpha

Released by plasmacytoid DCs; then activates TNF-alpha and IL-6

Front 50

Which autoantibodies directly correlated with clinical disease? With which symptoms?

Back 50

Anti-SSA: photosensitive rash, congenital heart block
Andi-dsDNA: renal dz

Front 51

Role of immune complexes in SLE.

Back 51

attack organs, deplete complement

Front 52

What is serositis?

Back 52

pleuritis, plerual effusion
pericarditis, pericardial effusion
ascites

All syx of lupus

Front 53

Blood abnormalities in SLE.

Back 53

Leukocytopenia
Lymphopenia
Hemolytic Anemia
Thrombocytopenia

Front 54

Anti-cardiolipin antibody results in _______.

Back 54

Thrombosis

Front 55

At what age do SLE patients present?

Back 55

65% between 16 and 55

Front 56

Constitutional symptoms of SLE.

Cause?

Back 56

Fever, malaise, fatigue; flu-syx
Due to cytokines:
TNF-alpha
IL-6
IFN-alpha

Front 57

Pathophysiology of malar rash.

Back 57

Immune complex deposition at dermal-epidermal jn

Front 58

Pathophysiology of photosensitivity in lupus.

Back 58

UV-->apoptosis/necrosis (triggers worsening systemic disease and skin rash eruption)

Front 59

Renal effects of SLE.

Back 59

Proteinuria; >500mg/24h
Cellular casts

Front 60

Renal pathophys of SLE.

Back 60

Immune complex formation in Bowman's capsule/glomerulus

Can result in nephrotic or nephritic syndrome

Front 61

Anti-SSA is associated with _____.

Back 61

1) Photosensitive rash
2) Neonatal heart block

Both in SLE obvs.

Front 62

What is Libman-Sacks endocarditis?

Back 62

Non-bacterial thrombotic valvular lesion; most commonly in left heart valves (mitral; aortic)

Front 63

What is the most common cause of death in patients with SLE?

Back 63

Premature coronary atherosclerosis, age 35-40 years (CAD)

Front 64

This antibody is associated with the pulmonary manifestations of SLE.

Back 64

Antiphospholipid antibody