Normal Bone, Joint Histo, Congenital Disorders - Gupta

Question 1

At what decade does bone resorption start to exceed bone formation

Answer 1

4th decade

Question 2

Bone primarily composed of what 2 components?

Answer 2

• Type 1 collagen (osteoid)
• Hydroxyapatite

Question 3

Name the 3 cells found in bone?

Answer 3

Osteoblasts, Osteoclasts, Osteocytes

Question 4

Hydroxyapatite (bone) is main storage of what ions?

Answer 4

Calcium (99%), Phosphorus (85%), Sodium and Magnesium (65%)

% = total of body storage

Question 5

Osteoblast function?

Answer 5

synthesize bone

Question 6

Osteoclast function?

Answer 6

Resorb bone

Question 7

Osteocyte function?

Answer 7

maintain bone

Question 8

What are howship lacunae?

Answer 8

Pits created by osteoclast activity, indicating bone is undergoing resorption

Question 9

Osteoclasts are derived from the same stem cells that produce ____?

Answer 9

macrophages

Question 10

RANK ligand is found on what cells?

Answer 10

Stromal cell/osteoblast

Question 11

RANK is found on what cells

Answer 11

Osteoclasts precursors

Question 12

If RANK-ligand and RANK bind, what occurs next?

Answer 12

Osteoclast precursor cells are stimulated to produce NF-kB, causing the osteoclast precursor to differentiate into a active osteoclast

Question 13

In addition to RANK-ligand, what other stimulatory cytokine is present on osteoblasts? What is its function?

Answer 13

Macropahge colony stimulating factor (M-CSF), similar function as RANK-L/RANK binding, will stimulate NF-kB production by osteoclast

Question 14

Osteoprotegerin binds with RANK or RANK-Ligand? What happens when it binds?

Answer 14

Osteoprotegerin (OPG) binds with RANK-ligand (on osteoblasts) preventing binding of RANK, thus inhibiting NF-kb production and osteoclast differentiation.

Question 15

Epiphyseal plate made of what 3 components?

Answer 15

Periosteum, bone marrow, residual cartilage

Question 16

What are the 2 types of ossification?

Answer 16

Enchondral, Membranous

Question 17

Which type of ossification occurs at epiphyseal plates?

Answer 17

ANS: Enchondral

Membranous occurs in cranial bones and everywhere there is periosteum

Question 18

Which type of ossification occurs through a cartilage intermediate step?

Answer 18

Enchondral

Membranous does not require cartilage intermediate step. Cells from the periosteum differentiate into osteoblasts and make bone

Question 19

Which type of ossification is involved in fracture healing.

Answer 19

Trick question. Both are involved.

Question 20

What are the 2 types of bone in terms of characteristics? Vague question. I know

Answer 20

Lamellar bone, Woven bone

Question 21

Which type of bone (lamellar or woven) is produced following a fracture?

Answer 21

Woven bone

Question 22

Which type of bone (lamellar or woven) is stronger?

Answer 22

Lamellar bone

Question 23

Describe how woven bone looks?

Answer 23

Coarse with random orientation.

Question 24

In lamellar bones, what structure(s) run longitudinally, communicating with medullary cavities? Communication via what structure

Answer 24

Osteons (haversian systems) communicate with medullary cavity by volkmann’s canals

Question 25

Osteogenesis imperfecta is a group of genetic disorders caused by a defect in ?

Answer 25

defect in synthesis of Type 1 collagen

Question 26

Mode of inheritence in OI?

Answer 26

Autosomal dominant

Question 27

Mutations underlying OI involve the coding sequences for which chains of Type 1 collagen?

Answer 27

alpha 1 or alpha 2

Question 28

Besides the bones being affected in OI, what other manifestations are common? Why is this?

Answer 28

Skin, joints, teeth, and eyes are just some areas involved, bc Type I collagen (which is defective in OI) is a major component of extracellular matrix in multiple parts of the body

Question 29

Blue Sclerae is associated with which type of OI?

Answer 29

Type I

Question 30

Type I OI. Lifespan?

Answer 30

Normal lifespan

Question 31

Type 1 OI. Fracture proclivity (likelihood)

Answer 31

Modestly increased until puberty. then it decreases

Question 32

Type 1 OI. Why the blue sclera?

Answer 32

Decreased collagen content of sclera allows the underlying choroidal veins to be visible

Question 33

Hearing loss seen in Type 1 O1. Why?

Answer 33

Conduction defects in the middle and inner ear bones

Question 34

Small, misshapen teeth can be seen in Type 1 OI. Why?

Answer 34

Dentin deficiency

Question 35

Which OI type is associated with perinatal lethality?

Answer 35

Type II. Uniformly fatal in utero or immediately after birth as a consequence of multiple fractures that occur before birth

Question 36

What is the most common form of dwarfism?

Answer 36

Achondroplasia

Question 37

What mental deficits are seen in achondroplasia?

Answer 37

None. Think of tyrion lannister. "A lannister always pays his debts"

Question 38

Achondroplasia caused by what mutation? Describe what this mutation does?

Answer 38

**Activating (point) mutation** in fibroblast growth factor receptor-3 (FGFR3) FGFR3 - typically inhibits cartilage proliferation. In disease, FGFR3 turned on constantly, suppressing cartilage growth

Question 39

What form of dwarfism is associated with a lethal variant? Why do they die?

Answer 39

Thanatophoric dwarfism, small thorax leads to respiratory complications and death

Question 40

Mode of inheritance in Achondroplasia?

Answer 40

Autosomal dominant or new spontaneous mutation in 80% of cases

Question 41

Achondroplasia affects all bones that \_\_\_?

Answer 41

develop by echondral ossification. That is why the head is normal size in these patients.

Question 42

Osteopetrosis is associated with a deficiency in ?

Answer 42

defiency in osteoclast activity/function, causes overgrowth and sclerosis of cortical bone ("too much bone")

Question 43

Osteopetrosis is both autosomal dominant and autosomal recessive. Which form is more severe?

Answer 43

Autosomal recessive (more severe) lethal. Autosomal dominant is considered adult form with mild clinical manifestations.

Question 44

Osteopetrosis is associated with a deficiency of what enzyme? Consequence of this? What other organ could be affected as a result of this?

Answer 44

Carbonic anhydrase II deficiency = cant form acidic microenvironment needed for bone resorption = can't break down hydroxyapatite Renal tubular cells also require CA2. Without it, renal tubular cells cannot acidify urine. ALSO, decreased tubular resoprtion of HCO3-, leading to metabolic acidosis

Question 45

Metabolic acidosis is associated with which congenital disorder. Why?

Answer 45

Osteopetrosis, Carbonic anhydrase II mutation prevents renal tubular cells from acidifying urine and reabsorping HCO3-, causing metabolic acidosis

Question 46

Besides renal tubular acidosis, what other clinicial features are associated with osteopetrosis (3)?

Answer 46

1. Fractures 2. Anemia, thrombocytopenia, and leukopenia (due to loss of medullary cavity), with extra medullary hematopoiesis (such as spleen or liver) 3. Hydrocephalus - narrowing of foramen magnum

Question 47

Definition of rickets?

Answer 47

Accumulation of unmineralized bone matrix

Question 48

Rickets is associated with a disturbance in \_\_\_? What 3 mechanism of disturbance?

Answer 48

Vitamin D. Either defiency of Vit D, abnormal metabolism of Vit D, or calcium deficiency

Question 49

Vitamin D helps do what in both flat and long bones?

Answer 49

Vit D helps mineralize osteoid matrix and epiphyseal cartilage in both flat and long bones.

Question 50

Vitamin D also stimulates osteoblasts to synthesize what? What is its purpose?

Answer 50

Stimulates osteoblasts to synthesize osteocalcin, a Ca2+ binding protein involved during bone development

Question 51

What 4 clinical features can be seen in Rickets?

Answer 51

Pigeon Chest deformity, Rachitic rosary, Frontal bossing, bowing of the legs

Question 52

Microscopically, what can be seen in rickets?

Answer 52

non-calcified, hypertrophied growth plate, particulary on metaphyseal side. Wide osteoid seams