Mycobacterium tuberculosis (Tuberculosis)

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Mycobacterium tuberculosis (Tuberculosis)

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Mycobacterium tuberculosis (Tuberculosis)

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Mycobacterium tuberculosis is a mycobacterial species that thrives in high oxygen environments, flourishes in the apex of the lung, and presents with

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A 65-year-old man comes to the emergency department because of fever, chills, and a blood tinged productive cough for 2 weeks. He says he is homeless, drinks a pint of vodka per day, and has smoked a pack of cigarettes per day for the past 19 years. His temperature is 38.3°C (101°F), pulse is 100/min, and blood pressure is 141/80 mm Hg. Chest X-ray reveals small lung nodules in the right upper and left upper lobes. A lung biopsy is obtained (depicted below). Which of the following is the most likely diagnosis?

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Content Reviewers:

Rishi Desai, MD, MPH

Contributors:

Tanner Marshall, MS

As of 2017, about two billion people worldwide are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis disease, commonly known as ‘TB’.

However, for the vast majority, (90-95%) of infected individuals, the infection is contained by the immune system and cannot multiply.

In other words, the TB disease remains latent, or dormant, as opposed to active, which usually causes symptoms and can easily be transmitted to others.

When the host’s immune system becomes compromised, e.g. due to HIV or malnutrition and aging, TB can reactivate, and become very serious, especially if the infection spreads through the body.

Moreover, people with active TB can easily infect 10-15 other people via close contact within a year.

Mycobacteria are slender, rod-shaped, and need high levels of oxygen to survive, i.e.,“strict aerobes”.

They possess a waxy cell wall that is capable of retaining dyes even when exposed to alcohol.

Thus they are referred to as “acid-fast”, appearing as bright- red colored rods when a Ziehl–Neelsen stain is used.

The wall also makes them incredibly hardy, and allows them to resist weak disinfectants and survive on dry surfaces for months.

M. tuberculosis is usually transmitted via inhalation, which is how they gain entry into the lungs.

Although, we breathe in all sorts of viruses and bacteria all the time, we have defenses that take care of most of them.

For one, air that we breathe in is turbulent in the upper airways, and drives most bacteria against mucus which is then cleared pretty quickly.

Ultimately, though, TB can avoid the mucus traps and make its way to the deep airways and alveoli where we have macrophages which eat up foreign cells, digest, and destroy them.

With TB, they recognize foreign proteins on their cell surface, and phagocytize them, or essentially package them into a space called a phagosome.

With most cases, the macrophage then fuses the phagosome with a lysosome, which has hydrolytic enzymes that can pretty much break down any biochemical molecule.

TB’s tricky, though, and once inside the macrophage, they produce a protein that inhibits this fusion, which allows the mycobacterium to survive.

It doesn’t just survive, though, it proliferates, and creates a localized infection.

At this point somebody has developed primary tuberculosis, which means that they have signs of infection soon after being exposed to TB.

Even though it sounds bad, most people at this stage are actually asymptomatic or maybe have a mild flu-like illness.

About 3 weeks after initial infection, cell-mediated immunity kicks in, and immune cells surround the site of TB infection, creating a granuloma, essentially an attempt to wall off the bacteria and prevent it from spreading.

The tissue inside the middle dies as a result, a process referred to as caseous necrosis, which means “cheese-like” necrosis, since the dead tissue is soft, white, and looks a bit like cheese. This area is known as a “Ghon focus”.

TB also gets to nearby hilar lymph nodes, either carried over by immune cells through the lymph or by direct extension of the Ghon focus infection and causes caseation there as well, and together, this caseating tissue and associated lymph node make up the characteristic “Ghon complex”. Ghon complexes are usually subpleural and occur in the lower lobes of the lungs. The tissue that’s encapsulated by the granuloma undergoes fibrosis, and often calcification, producing scar tissue that can be seen on x-ray, this calcified ghon complex is called a “Ranke complex”. In some cases, although a scar is leftover, the mycobacteria is killed off by the immune system, and that’s the end of that.

In other cases, even though they were walled off, they remain viable, and are therefore still alive, but they’re just dormant.