Advanced Pathophysiology

Osteomyelitis

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Speaker 2: The word osteomyelitis can be broken down. Osteo refers to bones, myel stands for myelo and relates to the bone marrow, and lastly, itis refers to inflammation. So osteomyelitis is an inflammation of the bone or bone marrow, and it typically results from an infection.

Normally, if we look at a cross section of a bone, we can see that it has a hard external layer known as the cortical bone and a softer internal layer of spongy bone that looks like honeycombs. There's also another layer called the periosteum that covers the cortical bone, like the lamination of a basketball card. And that's where the muscles, tendons and ligaments are attached.

If we zoom into a cross section of cortical bone, we can see that it has many pipe-like structures called osteons running through the length of the bone. Each pipe has an empty center called a haversian canal, which contains the nerves and blood vessels that supply the osteon. At the outer border of the osteon is a ring of cells called osteoblasts, which synthesize bone. Along with these cells are osteoclasts that break down bone. In bones like the long femur, the tips are called the epiphysis, while the shaft is called the diaphysis. Between them, we have the metaphysis, which contains the growth plate, the part of the bone that grows during childhood.

In osteomyelitis, microorganisms, such as bacteria, reach the bone to cause an infection in a few different ways. Bacteria particularly affect certain high risk individuals, like those with a weak immune system and those with poor blood circulation due to uncontrolled diabetes. In fact, a major way that bacteria reach the bone is through the bloodstream, and that's called hematogenous spread. For example, this might happen in a person who uses contaminated needles to inject drugs, or in individuals undergoing hemodialysis that may be contaminated by a bacteria, or even through the dental extraction of an infected tooth.

Through the bloodstream, the microorganisms may reach specific places in the body, and this mostly depends on the age of the person. In older adults, for example, the microorganisms may reach the vertebrae and cause vertebral osteomyelitis. This usually affects two adjacent vertebrae and the intervertebral disc between them. In children, the metaphysis of long bones, like the femur, is commonly affected.

The second way that bacteria causes osteomyelitis is through trauma. For example, in an open fracture after an accident, the bone may get exposed to the outside environment and come into direct contact with bacteria. A third way is during surgery, when there's bacteria that's introduced into the bone. A fourth way is when an infection spreads from one area, like cellulitis, which is an infection of the dermis layer of the skin, to an adjacent area, like the bone. And this is known as contiguous spread.

There can also be combinations of these. For example, when a prosthetic joint becomes contaminated with bacteria during surgery, and then, that bacteria contiguously spread to nearby bone. Another example is when people with diabetes mellitus develop a severe vascular compromise. A small trauma to the foot can lead to the formation of a foot ulcer, which then becomes infected and spreads to the nearby bone.

Now, once the bacteria reach the bone by any of these roots, they start to proliferate. This alerts nearby immune cells, specifically dendritic cells and macrophages, that try to fight off the infection. This represents the acute phase of the disease and occurs over a course of weeks. The immune cells release chemicals and enzymes that break down bone and cause local destruction. Usually acute osteomyelitis comes to a resolution, meaning that the immune system eventually destroys all of the invading bacteria. If the lesion is not that extensive and there's viable bone, the osteoblasts and the osteoclasts begin to repair the damage over a period of weeks.

However, in some cases, the process turns into chronic osteomyelitis, lasting months to years. In that situation, the affected bone sometimes becomes necrotic and separates from the healthy part of the bone, and that's called a sequestrum. At the same time, the osteoblasts that originate from the periosteum may form new bone that wraps the sequestrum in place. This is called an involucrum.

Occasionally in both acute and chronic osteomyelitis, the inflammation may involve the periosteum. The periosteum is loosely attached to the compact bone, especially in children, so the two layers can separate and allow an abscess to form between them. That sort of an abscess tracks along the periosteum, lifting it up away from the compact bone. The infection can also spread further to involve a nearby joint, particularly the knee or hip joint in young children, as well as overlaying muscle, skin, and even get into the blood vessels, causing thrombophlebitis.

Many microorganisms cause osteomyelitis, but the most common is staphylococcus aureus, a grape-looking bacteria that lives on the skin. It can invade the skin and spread contiguously to the bone, or it can reach the bone through the bloodstream. Another one is salmonella, a rod-shaped bacteria that particularly affects individuals with sickle cell disease. Unfortunately, individuals with sickle cell disease are therefore at risk of getting both staphylococcus aureus, as well as salmonella infections. Another pathogen is pasteurella multocida, a pill shaped bacteria. It usually spreads from the skin to the bone from a bite or scratch from a cat or dog.

Now, acute osteomyelitis typically causes pain at the site of infection, as well as fevers. Depending on the location, it may affect use of the bone. In chronic osteomyelitis, there can be prolonged fevers and weight loss due to the chronic inflammatory state. Osteomyelitis is usually diagnosed by using a complete blood count, or CBC, which shows an increase in white blood cells, as well as an elevated erythrocyte sedimentation rate, or ESR, and C-reactive protein, or CRP. These are both nonspecific markers of inflammation.

Now, in addition, sometimes an X-ray is done and it might show thickening of the cortical bone and periosteum, as well as an elevation of the periosteum. Other findings may include loss of the normal architecture of the bone, especially of the trabecular architecture. There's also osteopenia, or loss of bone mass, that becomes evident when more than half of the bone matrix is destroyed. Typically, a bone scan or MRI is done to help confirm the presence of osteomyelitis and to identify a possible abscess. When possible, a bone biopsy is also taken to help culture and identify the pathogen responsible, as well as confirm the diagnosis.

Now, treatment typically involves weeks of antibiotics directed at the organism causing the infection. If there's an abscess, particularly a vertebral abscess, causing neural compression or spinal instability, then surgery may also be required. In addition to draining abscesses, surgery is often needed to remove any necrotic bone, particularly in chronic osteomyelitis, where the sequestrum has to be removed.

All right. As a quick recap, osteomyelitis is a bone infection, in which the symptoms are inflammation, fever and weakness. Staphylococcus aureus is the most common pathogen responsible for osteomyelitis, and the most common form of infection is through the bloodstream.

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