Sunday, December 4, 2016

Bones and Trauma

Now we're onto our final topic for PHGY350! The end is nigh!

In a bone, what are the epiphysis, metaphysis and diaphysis?

Firstly, let's start off by talking about the structure of long bones (like the ones in your arms and legs). They are made up of a shaft (diaphysis) and two ends (epiphyses, singular epiphysis). Sometimes the junction between the shaft and the end is called the metaphysis. Within the diaphysis is the medullary cavity, which contains the bone marrow. As you may recall if you have been reading my Immunology posts, haematopoiesis (development of blood cells) occurs in the bone marrow. As you get older, fewer bones take part in this process.

In a bone, what are lamellae? Lacunae? Haversian canals (a.k.a. "osteons")?
What is the difference between spongy and compact bone? What other terms are used for these structures?

Bones can be further divided down into spongy and compact bone. I've already written about these types and their components here.

Describe the role that osteoblasts and osteoclasts play in the deposition and resorption of bone.

The matrix of bones is mainly made up of collagen. Calcium compounds such as hydroxyapatite (which consists of calcium, phosphate and hydroxide) are also essential in keeping bones hard and strong. Bone composition is maintained by an equilibrium between osteoblasts, which are cells that build up bone, and osteoclasts, which are cells that break down bone. Osteoblasts have an enzyme called alkaline phosphatase which can take phosphates off other molecules to be incorporated into hydroxyapatite. Osteoblasts can also deposit calcium.

Osteoclasts, on the other hand, assist in the resorption of calcium from bone, thus breaking down the bone. They do this by releasing small amounts of acid via the action of H+ ATPases. This acid also provides the optimum pH for enzymes such as cathepsins to break down the matrix of the bone.

Describe how RANK, RANK ligand, osteoprotegrin and oestrogen regulate bone remodelling. What roles do PTH (parathyroid hormone) and Vitamin D3 play?

Osteoblasts make RANK ligand, as well as osteoprotegrin (OPG). RANK ligand can bind to RANK receptors on osteoclasts, stimulating their breakdown activity. Osteoprotegrin is the opposite- it can bind to RANK ligand, reducing the amount that can bind to RANK receptors, causing inhibition of osteoclasts. Hence, osteoprotegrin is required for making sure that bones don't break down. Oestrogen increases osteoprotegrin levels, which is why postmenopausal women (who no longer have high levels of oestrogen) are at a higher risk of osteoporosis. (As for men- they still have plenty of testosterone, which can be converted to oestrogen via aromatases in the bone.)

PTH (parathyroid hormone) is especially important for increasing serum calcium levels. (This is important because nerves go crazy if they don't have enough calcium.) PTH increases renal calcium reabsorption while simultaneously decreasing phosphate reabsorption. Since hydroxyapatite requires both calcium and phosphate, having only calcium increases serum calcium since it won't become incorporated into the bone.

Vitamin D3, also known as calcitriol, is activated by the kidneys. It increases GI absorption of calcium and phosphate, while also increasing calcium reabsorption by the kidneys. Because it increases both calcium and phosphate, vitamin D3 can help with bone mineralisation. Interestingly enough, vitamin D3 can also promote resorption of bone in some places so that it can be built up in others.

Growth hormone also plays a role in bone growth through stimulating osteoblasts.

Another important hormone is cortisol, which breaks down the matrix. Remember, cortisol stimulates gluconeogenesis (making sugar from other stuff, like proteins), and the matrix is made up of protein (collagen) that can be broken down.

Describe the process and location of bone formation in long bones.

Before a person is fully grown, their long bones have epiphyseal plates ("growth plates"). These are made up of cartilage. In the process of bone growth, chondrocytes (cartilage cells) produce cartilage, before osteoblasts invade and add calcium to build a strong, hard bone.

Describe the characteristics of the following types of fractures: oblique, comminuted, open, segmented, spiral, transverse, greenstick, Colle's, Pott's

Fractures can be characterised in several ways.

Firstly, they can be classified as complete (the bone is completely broken) or incomplete (the bone is only partially broken). Incomplete fractures are sometimes known as Greenstick fractures, and are especially common in children whose bones have a greater proportion of matrix, which helps to hold the bone together.

Secondly, they can be classified as open or closed, depending on whether or not they pierce the skin. Open fractures can be dangerous as they are at risk of infection.

Thirdly, they can be classified by the number of fracture lines. A simple fracture only has one break, a segmented fracture has several breaks close to each other, and a comminuted fracture has many breaks close to each other, so you end up with lots of really little pieces that are hard to put back together.

Fractures can also be classified by the direction. A transverse fracture goes straight across, an oblique fracture goes on a diagonal and a spiral fracture goes on, well, a spiral. The latter is often due to the bone turning as it breaks.

There are several other types of fractures that don't always fit neatly into the above categories. Impacted fractures occur when one bone is shoved into the other, and may occur between the head of the femur and the pelvis. Pathological fractures occur due to disease. Compression fractures occur when one bone compresses another, as may happen between vertebrae.

Two special types of fractures that you need to know about are Colles' fracture and Pott's fracture. Colles' fracture occurs between the wrist and distal radius. (I remember this one by thinking that carpal and Colles' are in the same area, and both begin with C.) Pott's fracture is between the ankle and distal radius.

What are the symptoms of a bone fracture?

A fracture often starts with numbness which progresses into pain. At the same time there may be swelling and loss of function. Another symptom is crepitus, which is the sound of bones grinding against each other.

What are the steps involved in healing a fracture? What factors affect the healing process?

Fracture healing occurs in five main steps:
  1. Bleeding/haematoma beneath the periosteum. (The periosteum, which is basically a connective tissue covering for bone, helps to hold the blood in place).
  2. Formation of granulation tissue.
  3. Formation of a "procallus." Essentially, chondrocytes are providing "glue" to stick the bone back together.
  4. Bony callus formation. Bone is deposited into the procallus.
  5. Remodelling. Over time, osteoblasts and osteoclasts will fine-tune things to get the bone back in shape. This process can take 3-4 months.
There are many factors that can affect healing:
  • Degree of damage- the more damage there is, the longer it takes to heal.
  • Approximation- broken ends need to be kept close together. One complication is that muscles may contract and move the bones out of position. This can be reduced via a process called reduction, which pulls the bones out a little bit.
  • Muscle spasm- bones need to be kept immobile in order to heal, but they might spasm due to the pain
  • Foreign material- the removal of this is known as debridement.
  • Diabetes
  • Glucocorticoids- break down the protein matrix, as described earlier
  • Nutrition- you need a good supply of Vitamin D, calcium, protein etc.
  • Infection
  • Ischaemia- you need a good blood supply as tissue that is healing has a higher metabolic demand.
  • Compartment syndrome- if surrounding muscles etc. swell, they can compress nerves and blood vessels, leading to ischaemia.
  • Fat emboli- fat from the bone can plug up blood vessels, again leading to ischaemia.
Complications of healing can lead to non-union (i.e. the bones not coming back together, or healing in a misaligned fashion).

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