Pathoma: Skeletal System

Question 1

What causes achondroplasia?

Answer 1

An activating mutation in FGFR3

The activating mutation turns off cartilage growth in growth plates.

Question 2

Why does achondroplasia only affect the long bones?

Answer 2

Bone grows by two mechanisms: intramembranous growth (hand bones, ribs) and endochondral bone growth (long bones). Achondroplasia disrupts the cartilage growth that is necessary for endochondral bone growth.

Question 3

Describe osteogenesis imperfecta.

Answer 3

An autosomal dominant defect in type I collagen synthesis

Remember that bONE is type ONE collagen.

Question 4

Why does the sclera appear blue in OI?

Answer 4

The choroidal veins are exposed.

Question 5

_______________ results from a defect in bone resorption.

Answer 5

Osteopetrosis

Question 6

The most common defect that leads to osteopetrosis is _______________.

Answer 6

lack of carbonic anhydrase II; without this enzymes, osteoclasts are unable to create the acidic environment that dissolves calcium from bone

Side note: the reason alkaline phosphatase is involved in bone growth is that it makes an ALKALINE environment that allows for calcium to deposit in bone.

Question 7

What signs and symptoms are typical of osteopetrosis?

Answer 7

• Anemia
• Fractures
• Thrombocytopenia
• X-rays showing complete whiteout of bone
• Hydrocephalus (from occlusion of the foramen magnum)

The hematologic abnormalities arise from the sclerotic bone growing into the medulla.

Question 8

Describe why defective carbonic anhydrase (as seen in osteopetrosis) causes renal tubular acidosis.

Answer 8

The tubular cells convert H2O and CO2 to HCO3 and H+ using carbonic anhydrase. The proton is excreted when it binds NH3 in the nephron and be excreted, while the HCO3 is resorbed.

Without carbonic anhydrase, that net absorption of HCO3 does not occur and metabolic acidosis develops.

Question 9

What can treat osteopetrosis?

Answer 9

Bone marrow transplant

BMT will give new monocytes to the patient which will properly dissolve bone.

Question 10

Osteomalacia results in defective _________________.

Answer 10

mineralization of osteoid

Question 11

What is rachitic rosary?

Answer 11

Rickets often presents with bumps along the sternum that resemble a rosary.

Question 12

What labs are suggestive of osteomalacia?

Answer 12

• Low vitamin D
• Low calcium
• High PTH (because of the low calcium)
• High alkaline phosphatase (because bone is trying to be formed but is not being adequately mineralized)

Question 13

True or false: osteoporosis presents with the same pattern of labs as osteomalacia.

Answer 13

False!

Osteoporosis results from the loss of bone density that is characteristic of aging –not from serum abnormalities.

Question 14

Osteoporosis typically presents with pain in _______________.

Answer 14

weight-bearing bones (like the long bones of the leg and the vertebrae)

Question 15

What causes the aberrant activation of osteoclasts seen in Paget’s disease of the bone?

Answer 15

The etiology is debated, but it’s thought that it might arise from viruses from dogs.

Question 16

It’s important to know that Paget’s disease usually affects just _________________.

Answer 16

some of the bones –not the entire skeleton

Question 17

What histologic pattern is typical of Paget’s disease of the bone?

Answer 17

The bone will have lines between the osteocytes that represent failed fusion. That is, normally osteoid would fuse together, but in Paget’s disease of the bone they have not and look like puzzle pieces.

Question 18

The only serum sign of Paget’s disease of the bone is __________________.

Answer 18

elevated alkaline phosphatase

Question 19

What treatments are given to treat Paget’s disease of the bone?

Answer 19

Bisphosphonates and calcitonin

Both of these are “like the anti-PTH” that prevents the aberrant activation of osteoclasts.

Question 20

What two outcomes can occur from Paget’s disease of the bone?

Answer 20

• High-output cardiac failure: the new bone creates AV shunts that force the heart to work harder
• Osteosarcoma: with increased osteoblast activity, the osteoblasts are more likely to mutate

Question 21

Where does osteomyelitis usually seed?

Answer 21

• Children: metaphysis

* Adults: epiphysis

Question 22

Pseudomonas osteomyelitis is most common in _______________.

Answer 22

IV drug abusers and diabetics

Question 23

Osteomyelitis leads to ______________ necrosis.

Answer 23

liquefactive