2-Histology - Bones

Front 1

What is the relative (%) composition of bones? What type of collagen does it have?

Back 1

Organic component (30%), provides resilience, eosinophillic (pink/red), has type I collagen.
Mineral: 70%, provides rigidity and stores minerals

Front 2

For osteoblasts, explain:
-what it is derived from
- where it is found
- what it does (function/purpose)
- appearance

Back 2

- Progenitor cells
- Surface of bone matrix
- Production of osteoid

- cuboidal = active
- squamous = quiescent

Front 3

How are bone removal and bone synthesis coupled?
What is Wolff's Law?

Back 3

As osteoclasts breakdown bone matrix, growth factors and cytokines are released and stimulated osteoblasts to build new matrix.

Bone remodeling adapts to phyrical forces; greater stress = greater mass.

Front 4

What happens when serum [Ca++] falls?

Back 4

Parathyroid glands release PTH.:
1. PTH stimulates osteocytes, promoting osteocytic osteolysis
2. PTH stimulates oblasts and BM to express M-CSF and RANKL = increased oClast number & activity
= a rise in serum [Ca]

Front 5

Where are these different parts of long bone?
- Diaphysis
- Metaphysis
- Epiphysis
- Periosteum
- Endosteum

Back 5

- Diaphysis: the shaft, the cortical bone is usually thick here forming a "collar"
- Metaphysis: The wide part of the diaphysis where it approaches the epiphysis. The bone collar thins and spongy bone w/BM replaces the marrow cavity
- Epiphysis: The ends, the compact bone is thicker here and the core is filled with concellous bone and BM.
- Periosteum: dense irregular connective tissue that covers the external surface of the bone.
- Endosteum: thinner more delicate layer that lines the marrow cavity

Front 6

What are the steps involved in intramembranous ossification?
4 steps!

Back 6

1. Aggregation of undifferentiated progenitor cells (in well-vascularize CT)
2. Differentiate into oBlasts & express CBFA1 - a TF that control genes that refulate the production of bone-specific matrix proteins.
3. The oBlasts secrete and mineralize bone matrix thereby forming a spicule.
4. Spicules enlarge and merge, b.vessels get trapped (=Haversian canals)
** remaining cavities of CTissue gets replaced with BM

Front 7

List the steps in endochondral ossification? ie the process whereby a hyaline cartilage model is broken down and replaced with bone.
(4steps)
How are the marrow cavity and the articular cartilage formed?

Back 7

1. Start w/ hyalin cartilage model. Chdcytes at the centre Htrophy & some burst = acidify env = calcification = blocks diffusion so some die making cavities.
2. IHH stimulates formation of bone collar, VEGF induces penetration of b.vessels and their CT and progenitor cells = primary Osfctn centre.
3. The progenitor cells become oBlasts that lay down on the spicules of calcified cartilage. Oclasts break it down and oBlasts replace it.
4. The b.vessel branches and extends towards the ends of bone, carrying oBlasts & clasts with it.
* precess repeats at secondary centres--hyalin cartilage over the ends of the bone remains intact = articular cartilage.
** Oclasts trim the spicules towards the ends of the bone = marrow cavity
*** leaves mixed spicules that are converted to bone during normal turnover

Front 8

How do bones grow in width?

Back 8

Progenitor cells of the external periosteum, become oBlasts and they start laying down bone. Meanwhile oClasts in the endosteal layer start resorbing bone. Thus there is a net resorption around the lume and a net deposition around the periphery = bone get wider but collar doesn't get thicker!!
Sooo clever!

Front 9

How do bones grow in length?

Back 9

New cartilage is constantly being produced from the epiphysis downwards, with simultaneous ossification proceeding from the diaphysis upwards. When cartilage production < ossification, (as with age) the epiphyseal plate will become all bone and will be sealed.

Front 10

What are the 4 zones in the epiphyseal plate and what is happening in each zone?
1. (2functions)
2. (1event)
3. (1event)
4. (1)
5. (1)

*What stimulates proliferation and mitosis of the chondrocytes?

** What blocks the conversion from proliferation to hypertrophy?

Back 10

1. Reserve - quiescent chondrocytes, anchor the plate to the epiphysis bone and re-populates other zones.
2. Proliferating - "stacks of pancakes", the cells rapidly divide with mitotic spindles perpend to axis of bone.
3. Hypertrophic - chondrocytes enlarge and lay-down matrix between each other.
4. Calcification - matrix begins to calcify as chondrocytes apoptose.
5. Ossification - cells secrete VEGF to attract b.vessels from the diaphyseal side --> spicules

* Pituitary GH and Insulin-like GF1 (from liver)

** Parathyroid Hormone - related protein (PTHrP)

Front 11

What happens in each of the repair phases following a #?
1. Hematoma (days -- weeks)
2. Proliferative (weeks -- months)
- external
- internal
3. Remodeling (months -- years)

Back 11

1. Hematoma:
- Periosteum thickens
- clot is replaced by granulation connective tissue

2. Proliferative - new b.vessels sprout forming internal & ext callus
-ext: oBlasts & chndrocytes diff and make trabeculae/cartilage, that eventually merge with periosteum = external callus (replaced with bone)
-int: prog cells in edosteum & medullae prolif = cancellous bone. Prog cells in haversian canals prolife & vessels re-grow = spill into space btwn #'d ends. Prog cells --> oBlasts = new cancellous bone

3. Remodeling: Trabecular bone of ext callus --> compact bone
- oClasts breakdown dead bits of bone and lay new bone.
- Initially calluses replaced with woven bone then matures to Haversian systems (w/normal turnover)

Front 12

How does a bone heal when it has rigid fixation in place?
Hint: has to do with stuff coming out of haversian canals

Back 12

-oClasts will migrate out of Haversian canals and chew-up the dead bone.
Progenitor cells in the haversian canal will differentiate into oBlasts, which will them follow behind the oClasts, replacing the bone.
* Initially forms immature woven bone but will eventually form mature Haversian systems!

Front 13

What is osteomalacia? What 4 factors contribute to it?

Back 13

Osteomalacia = poorly mineralized matrix
1. reduced levels of dietary Ca, P, or Vit D
2. Reduced absorption of Ca, P, or Vit D
3. Reduce synthesis of calcitriol (the active form of Vit D) from not enough sunlight, liver probs, or kidney disease
4. Increased breakdown of Vit D (as can be caused by Phenytoin)

Front 14

What is osteoporosis?

Back 14

A decrease in the absolute mass of bones d/t a decrease in the # and activity of osteoblasts.
* accelerated loss in menopause b/c lowering estrogen causes increase oClast activity and decreased oBlast activity.