Pathogenesis of Pulmonary Tuberculosis |Pathology|

Tuberculosis is a communicable chronic granulomatous infection caused by atypical bacteria called Mycobacterium tuberculosis. Classically, tuberculosis happens at the lungs as by which it is called as Pulmonary Tuberculosis but it may also occur at almost any organs and it is called Extra-pulmonary Tuberculosis. This necrotizing infection may result in production of mucopurulent cough with blood and classical on and off intermittent fever with night sweats.

In order to discuss the pathogenesis of the disease, let me categorize it into two basic categories which are Primary Tuberculosis and Secondary Tuberculosis.

Primary Tuberculosis

  1. Once the virulent mycobacteria gain an entry into the alveolar spaces, it will initiate an immediate acute inflammatory response by attracting alveolar macrophages and other acute inflammatory cells especially neutrophils. Macrophage will then recognize glycolipid capped mannose on the mycobacteria as an antigen and start to engulf the organism. Nevertheless, due to its distinctive capability to conduct Endosomal Manipulation which includes maturation arrest, neutralization of lysosomal acidic pH and ineffective fusion of lysosome with phagosome, mycobacteria is capable to arrest macrophagial digestion.
  2. However, it must be cleared that there is a genetic polymorphism in controlling the susceptibility of macrophage towards mycobacterial endosomal manipulation, and that genetic polymorphism involves Natural Resistance-Associated Macrophage Protein 1 (NRAMP-1). Some macrophage do have this protein which makes it capable to over-stand endosomal manipulation. Therefore, this kind of macrophage is able to complete its mycobacterial digestion.
  3. Upon digesting and processing the mycobacterial antigen, this processed antigen will be presented in the Major Histocompatibility Complex (MHC) on its surface. Macrophage is now an Antigen Presenting Cell (APC).
  4. MHC will then recognize by the T-cell and APC will in turn release  IL-12 to initiate the production of T-cell subtype which is Helper T-cell type 1 (TH1). Once TH1 is produced in the course of 3 weeks of time, it will instantaneously initiate delayed hypersensitivity response (Type 4) by which B cells are now starting to produce antibody against mycobacteria. ONLY AFTER THIS, ANY EXPOSURE TOWARDS MYCOBACTERIAL ANTIGEN WILL PRODUCE POSITIVE RESULT FOR MANTOUX TEST.
  5. Consequently, in a hope to fight and eradicate the remaining mycobacteria, TH1 will produce Interferon Gamma to activate alveolar macrophage into epitheloid cells. In a hope to confine the infection into certain location, epitheloid cells will now produce extensive amount of Tumour Necrosis Factors (TNF) in order to recruit more monocytes from the circulation. The recruited macrophages will coalesce together to form a further larger phagocytic cell called the Langerhan type Giant cell. The accumulation of inflammatory cells and a ring of fibroblasts will confine the infection in a prison called the Granuloma. Due to the absent of previous infection, primary tuberculosis usually disseminated across the lung parenchyma until the level of pleura due to slow inflammatory response. This granulomatous lesion is called as Ghon focus, and if this focus involved the regional lymph nodes including tracheobronchial lymph nodes and hilar lymph nodes, it is now known as a Ghon complex. Upon fibrosis, calcification and healing process, Ghon focus/complex is called as Ranke’s complex.
Consequences to all these events are the fate of primary pulmonary tuberculosis infection. To simplify it, I categorized them into 2, depends on the immune status of the patient.
Immunocompetent Patients
There are two fates for immunocompetent patients having primary TB which are
  1. The immune system is so intact, whole mycobacteria are completely eradicated from the body. This kind of patient is still susceptible to have a secondary infection if they go to a highly dense contagions area. This patient will only leave a scar due to fibrosis
  2. Even though with an intact immunity, some mycobacteria are capable to lay dormant inside alveolar macrophage without duplication and becoming infectious. This state is called as the latent stage. Latent stage is capable to be reactivated into secondary infection only if the host immunity is compromised.
Immunodeficient Patients
When mycobacteria strikes for the first time, immunodeficient patients are incapable of fighting against it, and therefore the infection can easily progress into a severe form of infection called the progressive primary tuberculosis (PPT). PPT is characterized by formation of massive lesions without granuloma in the whole lobe of a lung and the organism can eventually disseminated across lymphatic drainage to cause pulmonary milliary tuberculosis and even worse, the organism is capable to enter the systemic circulation once the engorged blood vessels ruptured and spread hematogenously into extrapulmonary organs especially liver and spleen causing the so-called systemic milliary tuberculosis. Milliary tuberculosis is characterized by formation of numerous gray white granulomas represent that of millet seeds. Prognosis of the disease is often poor.
Secondary Pulmonary Tuberculosis
It is a pattern of disease secondary to the primary tuberculosis, which happens due to either reactivation or reinfection of previously sensitized individuals. Secondary tuberculosis is very distinctive with its classical localized lesion at the apex of the lung and with cavitation upon chest X-ray.
  1. Upon reactivation or reinfection, both will initiate a tremendous inflammatory response with respect to the presensitized immune system, leading to massive infiltration of inflammatory cells. Production of numerous granulomas with a classical caseation at the center, secondary tuberculosis is nothing more than uncontrolled inflammatory response which leads to massive tissue destruction. Caseating necrosis is characterized by center amorphous substances indicating formation of necrotic debris with classical infiltration of inflammatory cells like Langerhan giant cells and lymphocytes, confined by connective tissue stroma lied down by a ring of fibroblasts.
  2. Due to massive tissue destruction, stroma couldn’t hold the necrotic debris, and the granulomas start to tear apart leaving cavities all over the lung parenchyma and pus will start to appear in the sputum. Destruction often includes blood vessels, and once the blood vessels burst, patients will start to cough out blood, and even worse, mycobacteria are now spreading across the systemic circulation causing systemic milliary tuberculosis.
  3. Consequently, multiple organs failure will take part and body system will start to deteriorate. Even upon extensive therapy, patient’s lung function will forever remain compromised due to massive tissue fibrosis and lung remodelling.

That are pretty much about pathogenesis of pulmonary tuberculosis through my understandings. Thanks for

Lung with pulmonary TB. Classical apical cavitations with numerous caseating necrosis and massive tissue consolidation of lung parenchyme

Lung with pulmonary TB. Classical apical cavitations with numerous caseating necrosis and massive tissue consolidation of lung parenchyme

passing by my blog, and enjoy your studies =)


3 responses to “Pathogenesis of Pulmonary Tuberculosis |Pathology|

  1. I as well as my guys have been reading through the nice tricks found on
    your website while then came up with an awful suspicion I
    never expressed respect to the website owner for those techniques.
    The men were absolutely happy to study them and have in effect definitely been tapping into
    those things. Appreciate your really being simply thoughtful and for going for certain
    beneficial ideas millions of individuals are really wanting to understand about.
    Our sincere apologies for not expressing appreciation to you sooner.

  2. It is an excellent article on TB pathogenesis ..
    I read it top to bottom… even that I will reserve it in myself as a preparation of MBBS exam..

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s