Tuberculosis - causes, symptoms, diagnosis, treatment, pathology
Summary
TLDREl video explica la infección por tuberculosis (TB) causada por Mycobacterium tuberculosis, que afecta principalmente los pulmones. Tres semanas después de la infección primaria, el sistema inmunitario intenta contener la infección formando un granuloma, lo que lleva a la necrosis caseosa y la formación de un foco de Ghon. La TB también se extiende a los ganglios linfáticos hilares cercanos, causando necrosis caseosa. Si el sistema inmunitario se compromete, el foco de Ghon puede reactivar y la infección puede propagarse. Para diagnosticar la TB, se usan pruebas de la piel PPD o pruebas de sangre IGRA, y una radiografía de tórax puede identificar signos de enfermedad activa. El tratamiento incluye combinaciones de antibióticos administrados durante varios meses, y se utilizan regímenes especiales para la TB MDR y XDR.
Takeaways
- 📚 La tuberculosis (TB) es una infección causada por Mycobacterium tuberculosis.
- 🌐 Se estima que alrededor de 2 mil millones de personas en el mundo están infectadas por la TB.
- 🔍 Aunque la mayoría de las personas infectadas no muestran síntomas, su sistema inmunológico puede contener la infección y mantenerla en estado latente.
- 🌡️ La TB se transmite principalmente a través de la inhalación, lo que permite que las bacterias entren en los pulmones.
- 🛡️ El sistema inmunológico puede contener la infección al crear un granuloma, evitando que la bacteria se propague.
- 🏥 La infección primaria de TB puede ser asintomática o causar síntomas leves similares a los de la gripe.
- 🧬 El diagnóstico de la TB comienza con pruebas de detección de anticuerpos, como la prueba de la proteina purificada derivada (PPD) o la IGRA.
- 💊 El tratamiento de la infección latente de TB suele implicar el uso prolongado de un medicamento, como la isoniazida durante 9 meses.
- 🏥 El tratamiento de la TB activa se realiza con combinaciones de antibióticos anti-TB, como isoniazida, rifampicina, etambutol y pirazinamida.
- 🌐 Hay preocupaciones sobre las cepas resistentes a los antibióticos de la TB, como la TB multirresistente (MDR-TB) y la TB extremadamente resistente (XDR-TB).
- 🆕 La FDA de EE. UU. ha aprobado un medicamento innovador para el tratamiento de la XDR-TB llamado pretomanid.
Q & A
¿Cuál es la relación entre Osmosis y el estudio de la medicina?
-Osmosis ayuda a facilitar el estudio de la medicina al tomar las conferencias y notas de un estudiante para crear un plan de estudio personalizado con videos exclusivos, preguntas de práctica y tarjetas de memoria.
¿Cuántas personas mundialmente están infectadas con la bacteria que causa la tuberculosis?
-Es estimado que alrededor de dos mil millones de personas en todo el mundo están infectadas con Mycobacterium tuberculosis.
¿Por qué la mayoría de las personas infectadas con la tuberculosis no presentan síntomas?
-La mayoría de las personas, alrededor del 90-95%, no presentan síntomas porque su sistema inmunológico puede contener la bacteria, evitando que se multiplique y permaneciendo en estado latente en lugar de activo.
¿Cómo se pueden transmitir las micobacterias, como la que causa la tuberculosis?
-Las micobacterias se pueden transmitir a través de la inhalación, lo que permite que entren en los pulmones y se adentren en las vías respiratorias profundas y los alveolos donde las macrófagos intentan digerirlas y destruirlas.
¿Qué hace que las micobacterias sean tan resistentes?
-Las micobacterias tienen una pared celular waxy y anormalmente gruesa, principalmente debido a la producción de ácido miolíico, lo que las hace resistentes a los desinfectantes débiles y a la descomposición.
¿Qué es la reacción de la inmunidad celular mediada en la infección primaria por tuberculosis?
-La inmunidad celular mediada rodea el sitio de infección de TB creando un granuloma, un intento de aislar la bacteria y evitar su propagación, lo que resulta en una necrosis caseosa en el centro del tejido.
¿Qué es el 'Ghon focus' y cómo se forma?
-El 'Ghon focus' es una área de necrosis caseosa que se forma en el centro del granuloma durante la infección primaria por tuberculosis.
¿Qué es el 'Ghon complex' y cómo se relaciona con la tuberculosis?
-El 'Ghon complex' es una característica de la tuberculosis que se forma cuando la infección del foco de Ghon se extiende a los ganglios linfáticos hilares, causando necrosis caseosa allí también.
¿Cómo se puede detectar la tuberculosis activa mediante pruebas de laboratorio?
-La tuberculosis activa se puede detectar mediante la obtención de muestras de esputo o mediante una lavado broncoalveolar, que luego se someten a tintura, cultivo y PCR para buscar evidencia de Mycobacterium tuberculosis.
¿Cuáles son las estrategias de tratamiento para la tuberculosis latente y activa?
-El tratamiento de la tuberculosis latente suele involucrar el uso de un único medicamento por un período prolongado, como la isoniazida durante 9 meses. El tratamiento de la tuberculosis activa se realiza con combinaciones de antibióticos anti-TB como isoniazida, rifampicina, etambutol y pirazinamida.
¿Qué es la resistencia a los medicamentos en la tuberculosis y cómo se maneja?
-La resistencia a los medicamentos en la tuberculosis se refiere a las cepas de la bacteria que no mueren en presencia de los antibióticos comunes. Se maneja utilizando múltiples medicamentos juntos para evitar el desarrollo de resistencia y asegurándose de que los medicamentos se utilicen durante todo el curso de la terapia.
Outlines
📚 Aprendizaje de la Medicina y Tuberculosis
El texto comienza con una promoción de una plataforma de aprendizaje de medicina personalizada y luego se enfoca en la tuberculosis (TB), causada por Mycobacterium tuberculosis. Se menciona que aproximadamente dos mil millones de personas están infectadas, pero la mayoría no muestran síntomas ya que su sistema inmunitario puede contener la infección en un estado latente. Se describe la forma y características de Mycobacterium, cómo se transmite y cómo los macrofagos intentan combatirlo pero pueden ser engañados por la bacteria. Además, se explica cómo la infección primaria puede evolucionar a una infección activa si el sistema inmunitario se debilita.
🧬 Complicaciones y Diagnóstico de la TB
Este párrafo detalla las posibles complicaciones de la TB, como la afectación de los riñones, meninges, vértebra lumbar, glándulas adrenales, hígado y ganglios linfáticos cervicales. Se describen los métodos de diagnóstico, como la prueba de la proteina derivada purificada (PPD) y la prueba de liberación de interferón gamma (IGRA). También se menciona la importancia de realizar una radiografía de tórax y análisis de esputo para confirmar la infección activa. Se discute el tratamiento de la infección latente con isoniazida y el tratamiento activo con una combinación de antibióticos. Se enfatiza la necesidad de completar el tratamiento para evitar la resistencia a los antibióticos y se menciona la aprobación de un nuevo medicamento para el tratamiento de la TB extremadamente resistente (XDR-TB).
💊 Tratamiento de la TB y Resistencia a los Antibióticos
Este párrafo resume la información anterior sobre la TB, destacando cómo la infección puede reactivar y diseminarse si el sistema inmunitario se compromete. Se describen los métodos de diagnóstico iniciales, como la prueba de la piel PPD o la prueba de sangre IGRA, y la utilidad de la radiografía de tórax. Se menciona la recopilación de muestras de esputo para analizar la presencia de Mycobacterium tuberculosis. El tratamiento de la TB activa se detalla con una combinación de antibióticos administrados durante varios meses, y se hace especial énfasis en los regímenes especiales para tratar la TB multirresistente (MDR-TB) y la TB extremadamente resistente (XDR-TB).
Mindmap
Keywords
💡Tuberculosis
💡Latente
💡Micobacilos
💡Inhalación
💡Macrofagos
💡Granuloma
💡Ghon focus
💡Mantoux test
💡IGRA
💡MDR-TB
Highlights
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Two billion people worldwide are infected with Mycobacterium tuberculosis.
90-95% of infected individuals are asymptomatic due to their immune system containing the bacteria.
Mycobacterium tuberculosis can reactivate when the immune system is compromised.
Mycobacteria are rod-shaped and require oxygen to survive.
The waxy cell wall of Mycobacterium makes them 'acid-fast' and resistant to disinfectants.
Tuberculosis is transmitted via inhalation and can survive in the lungs.
Macrophages play a role in the body's defense against TB by phagocytizing the bacteria.
TB can inhibit the fusion of phagosomes with lysosomes to survive inside macrophages.
Primary tuberculosis often presents asymptomatically or with mild flu-like illness.
Cell-mediated immunity creates a granuloma to contain TB infection.
Caseous necrosis leads to the formation of a Ghon focus.
Ghon complex is formed by the Ghon focus and affected hilar lymph nodes.
Ranke complex refers to the calcified Ghon complex visible on X-ray.
Reactivation of TB can lead to infection spreading to the upper lobes of the lungs.
TB can disseminate to other tissues, causing various complications.
PPD intradermal skin test and IGRA blood test are used for TB screening.
Chest X-ray and sputum samples are used to diagnose active TB disease.
Treatment of latent TB involves prolonged use of a single drug like Isoniazid.
Active TB is treated with a combination of anti-TB antibiotics.
MDR-TB and XDR-TB require special treatment regimens due to drug resistance.
Pretomanid, bedaquiline, and linezolid have shown effectiveness against XDR-TB.
Transcripts
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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 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 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 done with different combinations of anti-TB
antibiotics, like isoniazid, rifampin, ethambutol, and pyrazinamide,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.
Recently, the US Food and Drug Administration has approved a breakthrough medication for
XDR-TB, called pretomanid.
According to recent studies, a combination of pretomanid, bedaquiline and linezolid has
been effective for almost 90% of XDR-TB cases.
As an added bonus, this combination therapy can be taken orally, and is also very well
tolerated compared with other XDR-TB drug regimens.
Alright, as a quick recap.
Tuberculosis, or TB, is an infection caused by Mycobacterium tuberculosis, that mainly
affects the lungs.
3 weeks after the primary infection, the immune system tries to contain the infection by creating
a granuloma, and the tissue in the middle undergoes caseous necrosis, resulting in an
area called Ghon focus.
TB also extends to nearby hilar lymph nodes, causing caseous necrosis there as well.
Ghon focus plus the affected lymph node make up the characteristic Ghon complex.
If the immune system becomes compromised, like with AIDS, or older age, Ghon focus can
reactivate, and the infection may spread to one or both upper lobes of the lungs, where
it forms cavities.
From cavities, bacteria can disseminate to other parts of the lungs, causing bronchopneumonia,
but it can also spread through the vascular system and infect almost every tissue in the
body, which is called systemic miliary TB.
Testing for TB starts with a PPD intradermal skin test, or with an IGRA blood test, and
a chest X-ray can identify signs of active TB disease.
In patients with fevers, night sweats, weight loss, and hemoptysis, a sputum sample can
be stained, cultured and PCR can be done to look for Mycobacterium tuberculosis.
Treatment of active TB includes a combination of antibiotics, given for several months,
and special regimens are used for MDR-TB and XDR-TB.
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