MSK Flashcards
Give 5 functions of bone.
- Houses bone marrow.
- Protection.
- Transmit body weight.
- Allows movement.
- Mineral storage.
Name 5 types of bone.
- Long bone.
- Flat bone.
- Short bone.
- Irregular bone.
- Sesamoid bone.
Give an example of a long bone.
Humerus.
Give an example of a flat bone.
The skull.
Give an example of an irregular bone.
Vertebrae.
What is the axial skeleton?
The part of the skeleton consisting of the head and trunk.
What is the appendicular skeleton?
The part of the skeleton consisting of the limbs and the supporting pectoral and pelvic girdles.
What are osteoblasts derived from?
Mesenchymal stem cells.
What is the function of osteoblasts?
They synthesise a type 1 collagen rich matrix, osteoid. (They contain large amounts of RNA for this function).
What are osteocytes?
When osteoid is mineralised with crystals of hydroxyapetite, the osteoblasts are trapped within the bone and become less synthetically active osteocytes.
What are osteoclasts?
Large and multinucleated bone resorbing cells. They contain large amounts of lysosomes.
What are osteoclasts derived from?
Hematopoietic stem cells.
Give 5 reasons for bone remodelling?
- Replace woven bone for lamellar.
- Response to exercise.
- Repair damage.
- Obtain calcium.
- Form bone shape.
Name 2 types of enzymes that are important in bone remodelling.
- Collagenases.
2. MMP’s.
What type of bone does endochondral ossification produce?
Long bone.
What type of bone does intramembranous ossification produce?
Flat bone.
What type of bone formation uses a cartilaginous pro-former?
Endochondral ossification.
Briefly describe process of endochondral ossification.
- Begins with the creation of hyaline cartilage proformers.
- A bony collar is then established around the diaphysis.
- Blood vessels penetrate the bony collar and bring in osteoprogenitor cells.
- A primary centre of ossification is established. Osteoblasts lay down primary bone.
- A secondary centre of ossification is established in the epiphyses.
- The amount of cartilage present decreases and is restricted to just to the growth plates.
Briefly describe the process of intramembranous ossification.
- Bone is directly deposited into mesenchymal tissue.
- Osteoblasts deposit isolated islands of bone until a plate of primary bone has been created.
- This primary bone is then replaced with denser, lamellar, secondary bone.
Describe primary bone.
Newly formed, poorly organised. Calcium is in an amorphous form. This bone is heavy and weak.
Describe secondary bone.
Organised collagen. Calcium is in a crystalline form (hydroxyapatite). This bone is lighter and stronger and replaces primary bone.
In the blood approximately how much calcium is bound to plasma proteins?
About 50% is bound to plasma proteins, notably albumin.
In the blood approximately how much calcium is ionised?
Just less than half.
In the blood approximately how much calcium is complexed?
A very small amount is complexed, bound to citrate/phosphate etc.
What are the 3 ways in which the calcium in the blood is distributed?
- Ionised - metabolically active and is the most important for cellular function.
- Bound to plasma proteins - non metabolically active.
- Complexed e.g. citrate, phosphate.
What is the affect of alkalosis on ionised calcium?
Alkalosis increases the pH, this increases the negative charge on albumin and so affects ionisation as more calcium binds to albumin and less is ionised.
Give 4 sources of calcium.
- Dairy products.
- Oily fish.
- Cereal.
- Broccoli.
Where in the intestine is calcium actively absorbed?
Duodenum and jejunum.
Where in the intestine is calcium passively absorbed?
Ileum and colon.
Where does the majority of Ca2+ reabsorption happen in the kidney?
At the PCT.
Where does active Ca2+ reabsorption happen in the kidney?
DCT - this is where PTH will act.
Where in the body can Calcium come from to enter the blood?
- Absorbed from the intestine.
- Resorbed from bone.
- Reabsorbed at the kidney.
What stimulates the release of PTH?
Low serum Ca2+ detected by receptors in the parathyroid.
Briefly describe the action of PTH.
- It causes bone resorption: increased Ca2+ and phosphate.
- It acts on the kidneys causing increased Ca2+ reabsorption and decreased phosphate reabsorption.
- It stimulates 1-hydroxylase which increases formation of 1,25-(OH)2-vitD and so increases the absorption of Ca2+ and phosphate from the intestine.
Where in the kidney does PTH act?
On the DCT where active reabsorption of Ca2+ takes place.
What do C-cells release?
Calcitonin.
What triggers the release of calcitonin?
High Ca2+.
What is the action of calcitonin?
It reduces bone resorption and so lowers Ca2. It is the antagonist to PTH.
What is the affect of low phosphate levels in the body?
Poor mineralisation of bone which can result in rickets, osteomalacia, pain and fractures etc.
Give 3 dietary sources of phosphate.
- Protein.
- Dairy.
- Seeds and nuts.
Give 3 regulators of phosphate.
- PTH.
- 1,25-(OH)2-vitD.
- FGF-23 = major regulator!
What is the action of PTH with regards to phosphate homeostasis?
It increases phosphate absorption at the intestine and decreases phosphate reabsorption at the kidney.
What triggers the release of FGF-23?
- High phosphate levels.
- PTH.
- 1,25-(OH)2-vitD.
What is the action of FGF-23?
It acts to decrease phosphate levels!
- It increases phosphate excretion at the kidneys.
- It decreases 1-hydroxylase meaning less 1,25-(OH)2-vitD is produced and so less phosphate will be absorbed from the intestine.
What is the function of PHEX?
It breaks down FGF-23 when phosphate levels have decreased.
What could happen if there was a dysfunction of PHEX?
FGF-23 wouldn’t be broken down and so serum phosphate would be very low and urinary phosphate would be high. You would be unable to mineralise bone - osteomalacia.
What is klotho and what is its function?
Klotho is a transmembrane protein that modifies FGF receptors making them specific for FGF-23.
What would be the affect on FGF-23 if you were vitamin D deficient?
You would have low phosphate levels as less will be absorbed from the intestine and so FGF-23 would be low as its trigger is high phosphate levels.
Define coupling.
Bone formation occurs at sites of previous resorption.
Define balance in osteoblast/osteoclast communication.
The amount of bone removed by osteoclasts should be replaced by osteoblastic activity.
What cell releases RANK ligand?
Osteoblasts.
What is the function of RANK ligand?
It is essential for osteoclast formation, activation and survival.
What is OPG?
OPG inhibits osteoclast formation, function and survival.
How does OPG work?
It has a similar binding site as the RANK receptor and so binds RANK ligands which prevents them from stimulating osteoclasts.
Name 2 things that regulate the balance between OPG and RANK?
Cytokines and hormones.
What would be the affect on bone if you had unopposed RANK ligands?
There would be increased bone loss as more osteoclasts would be stimulated due to the lack of OPG.