Tuberculosis – causes, symptoms, diagnosis, treatment & pathology

It’s estimated that about two billion people
worldwide are infected with mycobacterium tuberculosis, often just shortened to tuberculosis
or simply ‘TB’. Two billion is a ton of people, but even though
they’re infected, that doesn’t mean all those people have symptoms, the vast majority,
about 90-95%, aren’t even aware they’re infected. And this is because usually the immune system
can contain it such that it isn’t able to multiply, and often remains latent, or dormant,
as opposed to active, which usually causes symptoms and can be spread to others. If the host’s immune system becomes debilitated
at some point down the road, like with AIDS or some other illness, or as a person grows
older, it can be allowed to reactivate, or basically wake up and become very serious,
especially if it spreads through the body. Mycobacteria are an interesting bunch, they’re
slender, rod-shaped, and need oxygen to survive, in other words, they’re “strict aerobes”. They’ve got an unusually waxy cell wall,
which is mainly a result of the production of mycolic acid. Because of this waxy cell wall, they’re
“acid-fast”, meaning that it can hold on to a dye in spite of being exposed to alcohol,
leaving it bright red colored when a Ziehl–Neelsen stain is used. The wall also makes them incredibly hardy,
and allows them to resist weak disinfectants and survive in on dry surfaces for months
at a time. Now Mycobacterium tuberculosis is usually
transmitted via inhalation, which is how they gain entry into the lungs. Now, we breathe in all sorts of virus and
bacteria all the time, but we’ve got 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. If and when a person’s immune system becomes
compromised, like with AIDS or with aging, the Ghon focus can become reactivated, and
the infection can spread to either one or both upper lobes of the lungs, it’s thought
that this is because oxygenation is greatest in these areas, and TB being an aerobe, prefers
areas of greater oxygenation. Since they were previously exposed, the immune
system’s memory T cells quickly release cytokines to try and control the new outbreak,
which forms more areas of caseous necrosis, this time, though, it tends to cavitate, or
form cavities, which can allow the bacteria to disseminate, or spread through airways
and lymphatic channels to other parts of the lungs, which can cause bronchopneumonia; but
it can also spread via the vascular system and infect almost every other tissues in the
body, called systemic miliary TB. When TB spreads to other tissues, it causes
complications related to the organ affected. Kidneys are commonly affected, resulting in
sterile pyuria, or high levels of white blood cells in the urine. It might also spread to the meninges of the
brain, causing meningitis, the lumbar vertebrae, causing Pott disease, the adrenal glands causing
addison’s disease, the liver causing hepatitis, and the cervical lymph nodes causing lymphadenitis
in the neck, also known as scrofula. Testing for TB often starts with a purified
protein derivative or PPD intradermal skin test, sometimes known as a tuberculin skin
test, Mantoux test, or simply TB test. With this test, tuberculin is injected between
layers of the dermis, tuberculin is a component of the bacteria, and if a person has previously
been exposed to TB, the immune system reacts to the tuberculin and produces a small, localized
reaction within 48 to 72 hours; if the reaction creates a large enough area of induration
(rather than just redness), it’s considered to be a positive test. Positive tuberculin tests simply mean the
patient’s been exposed at some point to TB—it doesn’t differentiate between active
and latent disease. As an alternative to tuberculin skin tests,
there are also interferon gamma release assays (or IGRAs) which look for evidence in the
blood of previous exposure to TB proteins. Since this one’s a blood test, you don’t
need to show up again to have the test read like you do with the PPD. Also, the IGRA is more specific to TB rather
than other types of mycobacterial infections and is unlikely to be positive as a result
of having BCG vaccine in the past, a vaccine that protects against TB. And this is a pretty useful feature of IGRAs,
since BCG vaccine is given to many children around the world to prevent disseminated TB. After doing a screening test with PPD or IGRA,
anyone with a positive result typically gets a chest Xray to look for signs of active TB
disease. In patients with symptoms like as fevers,
night sweats, weight loss, and coughing up blood, or hemoptysis. it’s important to collect samples from either
the sputum, or via a bronchoalveolar lavage, which is where a bronchoscope is inserted
through the mouth or nose into the lungs, fluid is squirted, and then the fluid is collected. These samples can get sent to the lab for
staining, culture, and PCR to look evidence of mycobacterium tuberculosis. Treatment of latent TB infection typically
involves using a single drug for a prolonged period of time—the most common approach
is Isoniazid for 9 months. Treatment of active TB disease is typically
a combination of antibiotics, which results in patients being non-infectious to others
usually within a few weeks. Until that point, though, patients can spread
TB to others and it’s typically adults with reactivated TB that are the most infectious. As a result, patients are typically kept in
negative pressure rooms and visitors are asked to wear protective N-95 masks that can’t
filter out oil aerosols (N for “not resistant to oil”) but can filter out at least 95%
of other aerosols (in this case TB). Even after patients are no longer contagious,
they’re typically kept on multiple medications for many months to be sure the bacteria are
destroyed usually with directly observed therapy or DOT where somebody watches and confirms
that you’re taking the medication. Additionally, there’s an enormous worry
about new drug-resistant strains of TB that are causing infections in various parts of
the world. You may hear of MDR-TB or Multi-drug resistant
TB or even XDR-TB which is Extremely drug resistant TB which is incredibly hard to treat
because they don’t die in the presence of our usual antibiotics. The bottom line is that to get an effective
treatment, it’s super important to make sure that the drugs being used will work against
the specific strain of TB, that multiple medications are used together to prevent drug resistance
from developing, and that medications are used for the entire course of therapy so that
all of the mycobacterium tuberculosis is killed off.


  1. Doctor: Come in come in
    Patient: Thank you doctor
    Doctor: Have a seat.
    Patient: Ok doctor cough cough
    Doctor: So what seems to be the matter?
    Patient: Well, since yesterday, I've been coughing a lot.
    Doctor: Hmmm… Okay, open your mouth and say ahhhhhhhh
    Patient: ahhhhhhhh
    Doctor: Hmm….. okay. I think I know what it is
    Patient: What is it doc?
    Doctor: You've got tuberculosis son. A hell of a disease.
    Patient: Damn, I don't know what to say doc
    Doctor: Yeah. Wait a sec lemme get a remedy.
    Patient: What is it doc?

  2. My great grandfather died from tuberculosis, just a few years after surviving world war 1 a tiny bug would kill him and

  3. The internet is officially deemed an unsafe place. You can't even watch a video about a disease without accidentally reading spoilers for a highly anticipated game.

  4. Thank you, there is this cowboy friend of mine that in the last days lamented these symptoms, I'll make sure to send him this video.
    Can you please do one about Lumbago? Uncle told me it's very serious.

  5. Ive become so attached to Arthur that im looking up the disease to see if its treatable or not.
    Goddamit Rockstar Games.

  6. Great short summary. I've studied TB for a year and you added a thing or two to my knowledge. But I've been in health care as a respiratory therapist (the sputum specialists) for 30 years in western US and never heard "spit-um" pronounced as you did. It's a long 'u' sound in the first syllable "sput" like "spew" to rhyme with Butte, Montana or coot-ies. Hearing you say spitum is a 'hoot.' Other than that your video is a "beaut."

  7. 8:50 I believe XDR-TB stands for eXtensive Drug Resistant TB as resistance has extended to second line TB drugs.

  8. Types of Mycobacterium
    Micobacterium tuberculosis
    Micobacterium fortuitum
    Mycobacterium kansasii
    Mycobacterium malmoensa

  9. People are actually making fun of this sickness it’s not a joke! Just because you played rdr2 doesn’t mean you go to YouTube and write ohh Arthur morgen ,man you don’t have a heart.

  10. So many questions.. so 2 billion people are affected by it, but when someone gets it we treat them like a zombie quarantine. So it’s treated like it’s super dangerous but it sounds like it’s super common so does it only affect certain people? I mean what determines wether or not the bacteria spread or get stopped when you initially get infected? I guess just their immune system ?

  11. Isoniazid,or INH, is one of the most useful agents used in treating TB. Why we give vitamin B6 during treatment?
    Please answer my question quickly because I have an exam 😭😭😭😭💔

  12. Worked in Microbiology for 30 years. Was put on sick leave in 2005. Am now 71 years old and I have a positive smear. Lovely, huh?

  13. What I learned. It is not as much as TB bacteria that makes the symptoms worse but, what our own immune system does that creates more opportunities for the bacteria to proliferate and into other organs that causes the most damage. i.e. memory T-cells that produced cytokines created cavities on the organ that lead to systemic miliary TB.

  14. Hi Sim. I am wondering whether you are Vietnamese or not. Why do you decide to make videos in English? Because I am pharmacist and I want to make videos about interaction drugs. Should I make it in English or Vietnamese ? Do you think about it?
    Thank you very much
    Em cám ơn nhiều ạ

  15. Teacher: Anyone heard of tuberculosis?

    Student: I know, sir, I am an expert on it cuz my boy died from it

  16. This is really helpful; I love watching history documentaries and tb was a pretty common cause of death..of course they had no idea what was causing it… I had no idea really either…so here I am…

  17. I came here to find some advice or some related comments on the matter, instead I see RDR2 comments….

  18. As someone with TB, it's wierd that the person who has brought TB to light to the public, was a video game character.

  19. your info is extremely nice but you have to be slow during your explanation , that will help our mined to collect the knowledges from you.

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