TB pathogenesis | Infectious diseases | NCLEX-RN | Khan Academy
12
October

By Adem Lewis / in , , , , , , , , , , , , , , , , , , , , , , , , , , , , , /


Charles Prober: Hi, I’m Charles Prober. Morgan Theis: I’m Morgan Theis. Charles Prover: Today
we’re going to talk about the pathophysiology of tuberculosis, that is how tuberculosis
makes people sick. In this cartoon, there
is an infected individual shown on the left. That person is coughing or sneezing, and all those little small white dots are particles coming out
of the person’s mouth. The person on the right is a nonsuspecting individual who is susceptible
to infection with TB. The person on the left, when they cough, if they have tuberculosis in their system, then some of those bacilli will cough out and enter the person they’re coming into close contact with, enter in the droplets. Some portion of those infected droplets, estimated to be about
10%, go all the way down the susceptible individual’s
airway and land in the lung. They have to be very, very small to get to the most distal portion of the lung called the alveoli. They have to be around 5
or 10 microns in diameter. Once those bacilli have
entered the person’s lung, the host, the person’s
immune system, kicks in at the local level. The first part of the immune
system to greet these bacilli are macrophages that
line the lung airways. These macrophages take up the bacilli and within the macrophages
the bacilli may reproduce, that is increase in numbers. The macrophage may then
release the bacilli. Other macrophages will pick them up, and eventually one has a number of cells in this distal part of the
lung that are infected. When these marcophages then come together and lung destruction occurs
in the mixture of this, they end up forming a
particular kind of lesion in the lung called a granuloma. A granuloma, which is often used in the context of TB
infections, it’s also called a tuberculoma, are a group of macrophages and other inflammatory cells that are the reaction to this TB infection. Once that granuloma becomes large enough for one to see, so if a
pathologist is looking at the lung, that is called
a Gohn focus, G-O-H-N, of course named after somebody Dr. Gohn. After the local infection
in the macrophages occurs and the granuloma has been formed, if the infection is not
controlled in that local site, there is spillover of the
infection to the regional lymph nodes, so the
lymph nodes in the lung. Then those regional lymph
nodes have an immune reaction. The regional lymph nodes
plus the infected granuloma is referred to as a Gohn complex. This may be evident on a chest x-ray that a person has done either for routine basis or for whatever reason. A radiologist seeing this will say, “Oh, this looks like a previous
infection with tuberculosis.” We’ll show later an
example both of a granuloma and a Gohn complex on radiographs. All of this infection, the
person who’s now infected, this is referred to as
a primary infection. The individual is infected
with tuberculosis. For many individuals,
that’s the end of the story. The tuberculosis remains
in what is referred to as a latent state and remains latent for the person’s entire life without causing any problem. Morgan Theis: Do they actually get rid of the bacteria entirely? Charles Prober: It’s not
clear if the bacteria ever are completely killed or not. There is some evidence that, in fact, some do clear the bacteria, but from a clinical standpoint, one has to assume that once you’ve been
infected with tuberculosis, it’s with you forever
and may cause subsequent problems, which we’ll
speak about in a moment. For 90% of people, it’s sort
of the story ends there. However, that leaves 10%. About half of that 10%,
so 5%, their primary infection is progressive, so they go on and they develop a problem shortly after they’ve been infected with tuberculosis. That problem may be represented as local progression of the infection, so that lung Gohn focus actually
becomes larger and larger, and they end up with
tuberculosis pneumonia, so pulmonary disease
caused by tuberculosis. Or, they may go on even beyond that. The infection may disseminate widely, go to many organs in the body, most especially the liver,
other parts of the lung, or even into the brain and other organs. That’s about 5% of the patients that go on to have local progression
or dissemination. One pattern that’s been
associated with this dissemination, and it’s
not the only pattern, is when the infection
seeds multiple organs of the body with tiny little spots that are called “millets”
because they’re so tiny, and this is referred to
as miliary tuberculosis. That’s most often recognized in the lungs where you see these little tiny spots all over the lungs. That’s one form of disseminated infection. That’s primary infection and that’s 5%. Now, an additional
5-10% of patients emerge from the latent state of the infection and they develop so-called
secondary disease. That represents a reactivation of a prior latent infection, or a
prior dormant infection. Again, it’s estimated that about 5% of the total population
who’ve been infected go on and have this reactivation disease. Morgan Theis: Can that happen at any point during your life? Charles Prober: It can
happen at absolutely any point during your life;
either within several months of the infection or
many, many years later. That reactivation is referred
to, as you’ve written, secondary tuberculosis in contrast to primary infection; this
is secondary infection. The likelihood that
somebody may reactivate is actually influenced by many factors including the immune state of the host. That is, if the host, the
person who’s got latent TB, has depressed immunity,
especially depressed cell mediated immunity, their likelihood of reactivating can be quite
high, relatively speaking. Some of the immune factors that are most recognized as causing an increased chance of reactivation are
co-infection with human immunodeficiency virus. That’s a big one world-wide, HIV. Another is if the individual has received a transplant or is receiving chemotherapy for some other reason,
for example, cancer. Morgan Theis: For the
transplant, we’re actually giving them immuno-suppresant medicine so they don’t reject the transplant, so that puts them at risk. Charles Prober: That
knocks down their T-cells and then they have an increased risk. Then patients who abuse
drugs intravenously also are at an increased risk, quite a substantial increased risk. These groups together, each of them are a more than 10-fold risk over the general population of reactivation. There are other host
factors that also influence reactivation to a lesser extent. They may have a 2- or
3-fold increased chance of reactivation compared
to the general population. That would include patients
who are malnourished. It would include patients
who have diabetes. Even patients whose risk factor is only, and I shouldn’t say
“only” perhaps, smoking. Those can all increase the chance of tuberculosis emerging from its latent or dormant state and becoming reactivated. Morgan Theis: What’s the increase for HIV, transplant, IV drug use? Charles Prober: Probably about 10-fold, or at least 10-fold. Some of them are actually
estimated to be up to 70-fold, but certainly
greater than 10-fold. The final thing I’d like to say about secondary tuberculosis is
that much of it results from reactivated disease,
but you can also have secondary tuberculosis
because you get reinfected. That means that it’s
not your own latent TB that’s reactivated and
caused secondary disease, but you’ve been exposed
to yet another person infected with tuberculosis
and your secondary disease results from that reinfection, that new exposure. Morgan Theis: Then once
you get that new exposure or the reactivation of your own latent TB, then you can progress
sort of down the same pathway of symptoms, is that right? Charles Prober: Exactly. You can have local progression,
as you’ve indicated, or if you’re severely
depressed immunologically, you may get more of the
disseminated infection, including the miliary
pattern and so forth. Just to end, I’d like to show
the two promised pictures. The picture that is
all pink is a zoomed in microscopic view of a granuloma. There are a couple of
features to point out. First of all, in the very
middle of this granuloma, is very pink, very homogeneous material that probably represents dead macrophages and other debris that have
eventually been reabsorbed and form this dense core. Sometimes that becomes calcified over time and that may show up on an x-ray, such as the x-ray picture we show here, as a calcified spot, a
white spot, in the lung. We’ll come back to that. The other part of the
granuloma to point out is this inflammatory reaction occurring around that dense middle. All of the cells that
are shown in the blue are lymphocytes and
monocytes and macrophages, and this is the reaction to the infection with the tubercular bacilli. Sometimes this actually becomes quite necrotic in the center. It’s not shown so much here. Then it’s referred to as caseation because it becomes sort
of cottage cheese-like. The other picture, the
picture of the x-ray, shows the calcific granuloma. That would be, again,
the original granuloma, the Gohn focus, and it
also shows some swelling of the lymph nodes at
the edge of the heart. As previously mentioned,
this lymph node reaction along with that Gohn
focus, together make up the Gohn complex. That is evidence, radiographic evidence, that this individual has been previously infected with tuberculosis,
latently infected, at risk for subsequent reactivation.


36 thoughts on “TB pathogenesis | Infectious diseases | NCLEX-RN | Khan Academy

  1. SIR,
    NAMASTHAE.
    VERY INFORMATIVE.I WOULD LIKE TO KEEP THIS VIDEO TO EDUCATE AND TO GIVE AWARENESS TO THE COMMUNITY.PLEASE SEND ME TO MY EMAIL ADDRESS.
    THANKING YOU.SIR
    TRUELY YOURS,
    CHANDRASEKAR
    11-02-2014

  2. shut up la. tell me were the bacteria come from. how they come to this earth. where do they come from
    .live before they get into humans .

  3. Thanks for the lesson, it's very informative. Why are intravenous drug users at an elevated risk of reactivation?

  4. Very  helpful , clearly  visible  video   I have ever  seen .  The best  video  for  EL [English Learner] like me.Many thanks … from  Korea  South.

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