Tuberculosis - Types, Pathogenesis, Signs and Symptoms, Diagnosis, Treatment and Prevention

tuberculosis is a serious bacterial infection caused by a group of bacteria known as Mycobacterium tuberculosis complex it is characterized by the presence of a chronic granulomatous inflammatory reaction in about 99 percent of the cases the causative organism is Mycobacterium tuberculosis mycobacterium bovis is known to cause oropharyngeal and intestinal tuberculosis but it is rarely seen now so in this video I'm going to discuss about Mycobacterium tuberculosis risk factors for tuberculosis its pathogenesis and different types of tuberculosis clinical presentation or signs and symptoms diagnosis and finally the treatment and various preventive methods for tuberculosis Mycobacterium tuberculosis is a rod-shaped obligate aerobic intracellular pathogen in contrast to other bacteria Mycobacterium tuberculosis grows very slowly the cell wall contains a high lipid content especially mycolic acid due to the high lipid content they do not stain with Gram stain here is a diagram of the cell wall of Mycobacterium tuberculosis you can see the high content of mycolic acid and they contain Manas captal appids which enabled them to bind the macrophages Mycobacterium tuberculosis has the ability to survive and multiply inside the macrophages by avoiding lysosome or killing it is the major virulence factor of the organism Mycobacterium tuberculosis is known as an acid and alcohol fast bacillus because it does not de color eyes with acid or alcohol when stained with zeal Nielsen stained human is the natural reservoir the infection is primarily transmitted via aerosol transmission and they are sensitive to heat ultraviolet light and chemical substances like alcohol formaldehyde and blue tur aldehyde the bacterium primarily infects the lungs however it can cause disease in any other organ in the body including liver intestine kidney bone brain skin eye etcetera HIV infection is a serious risk factor for tuberculosis because of the pathogenesis of tuberculosis depends upon the host immune response other risk factors include alcoholism immunosuppressive therapy such as treatment with corticosteroids diabetes mellitus and recent surgery in addition workers and health care facilities such as doctors nurses laboratory workers are also at risk of developing tuberculosis now let's discuss about the pathogenesis and different types of tuberculosis based on the pathogenesis of the disease there are two types primary tuberculosis occurs and non sensitized hosts or tuberculosis which occurs in a person who has no previous exposure to the organism secondary tuberculosis occurs in sensitized hosts or tuberculosis which occurs in a person who has previously exposed to the organism the spectrum of disease is based on the immune response of the host an active TB the bacilli are multiplying inside the host and they have the ability to cause disease if the multiplying bacilli affect only the lungs it is known as pulmonary tuberculosis if the multiplying bacilli affect the organs other than lungs it is known as extra pulmonary tuberculosis and miliary TB the bacilli spread via lymphatics and bloodstream to the other organs and cause formation of lesions which appear like millet seeds miliary TB is different from extra pulmonary TB it's infectivity is extremely high with high basilar load and it can be fatal if left untreated latent TB is caused by reactivation of dormant bacilli when the host immunity drops and during the dormant period the person is asymptomatic first let's discuss about primary pulmonary tuberculosis which occurs in a non sensitized person after inhalation of Mycobacterium tuberculosis the bacilli reached the lungs and get lodged in the upper part of the lower lobe or lower part of the upper lobe sub plurally then the bacilli are recognized and engulfed by the alveolar macrophages in contrast to other organisms Mycobacterium tuberculosis has the ability to survive inside the macrophages by avoiding lysosomal killing while surviving they multiplied within the macrophages during the first three weeks of infection then the bacilli spread to the other parts of the body via lymphatics and bloodstream at this point most of the people are asymptomatic or they have a mild flu-like illness due to the macrophage response an inflammatory reaction occurs in the lungs the lesion caused by the inflammation is known as Gon's focus the center of the guns focus undergoes caseous necrosis with time as the bacilli are taken into the lymph nodes inflammation occurs at the lymph node as well Gon's focus in this inflammatory reaction involving the lymph node are collectively known as guns complex this is a gross image of a lung with guns complex after bacilli reached the lymph node the macrophage processes mycobacterial antigens and present them to the t lymphocytes this usually occurs after about three weeks from the initial infection so as a result T cells become T helper cells and they secrete interferon gamma and interleukin 2 interfering gamma causes activation of macrophage and interleukin 2 activates other lymphocytes to become T helper cells activated macrophage has two functions one is to kill the bacilli by various mechanisms and the other one is to secrete cytokines such as tumor necrosis factor in order to kill the bacilli they secrete reactive oxygen species reactive nitrogen species and proteases these substances kill most of the bacilli but some may remain dormant for several years they can cause latent infections when the host immunity drops tumor necrosis factor induces recruitment of macrophages macrophage activation and differentiation of macrophages into epithelioid cells this will cause formation of granulomas ultimately this is an image from Robyn's textbook of pathology showing the function of an activated macrophage this diagram shows the structure of a granuloma the center of the granuloma undergoes caseous necrosis there can be many cell types in a granuloma epithelioid cells which are derived from the macrophages Lankans type giant cells which is formed by the fusion of several appetite cells in addition lymphocytes and fibroblasts can also be seen around a granuloma I have done a separate video on granulomatous inflammation if you are interested go and watch that video as well it will give a lot of information on a granuloma now let's see what would be the possible outcomes of primary pulmonary tuberculosis an immuno competent hosts the infection will be controlled by the cell mediated immunity the granuloma heels by fibrosis and ultimately it undergoes dystrophic calcification and ossification however even if the infection is contained some bacilli may remain dormant and cause latent infections and immunocompromised patients failure to control the infection causes progression of primary tuberculosis into progressive primary tuberculosis progessive primary TB most often resembles an acute bacterial pneumonia pleural effusions and lung collapse can occur in progressive primary TB cavitation is rare compared to secondary tuberculosis lower and middle lobe consolidation can be identified in a chest x-ray in addition to progressive primary TB in immunocompromised hosts the bacilli can disseminate via lymphatics and blood stream to the other organs this may lead to the development of miliary TB TB meningitis TB lymphadenitis TB spine or pots disease or TB in any other organ now let's discuss about secondary pulmonary tuberculosis which occurs in a previously sensitized person secondary TB may arise shortly after primary TB but more commonly occurs decades later the primary infection this can occur due to reinfection by the re-entry of Mycobacterium tuberculosis or reactivation of the dormant bacilli in contrast to primary TB the lesion involves the apex of the upper lobe of one or both lungs due to the existing hypersensitivity there is a marked tissue response can be seen because of this the involvement of regional lymph nodes is less prominent as secondary tuberculosis the lesion may heal by fibrosis spontaneously or if the patient is severely immunocompromised treatment is required untreated secondary TB can progress into progressive secondary TB this causes erosion of the bronchial wall and leakage of content into the Airways this is called cavitation and cavitation is prominent in secondary tuberculosis than primary tuberculosis and this may result in dissemination of bacilli through Airways so the bacilli can spread to the other lobes of the lungs as well and they can reach the trachea larynx and marriage the oral cavity when coughing if the bacilli containing sputum gets swallowed the person can develop intestinal tuberculosis local spread of bacilli to the pleura may cause pleural effusions spread of bacilli via lymphatics may cause miliary pulmonary tuberculosis dissemination of bacilli through the blood stream may result in systemic miliary tuberculosis and tuberculosis of isolated organs this image shows in a pickle lesion with cavitation and secondary TB miliary TB has gained its name due to the characteristic appearance of its lesions like millet seeds these images show the lesions in miliary pulmonary tuberculosis a person can develop miliary pulmonary tuberculosis when the bacilli draining through the lymphatics reach the venous blood and re-enter the lung tissue systemic miliary TB can occur when the bacilli disseminate via arterial blood and reached the organs like liver spleen meninges bone marrow kidney adrenals etc if left untreated miliary TB can be extremely fatal and miliary TB has a high infective 'ti due to the high basilar reload extra pulmonary tuberculosis is referred to as tuberculosis occurs in any other organ other than lungs it can involve several organs at once or it can occur in an isolated organ TB lymphadenitis is the communist form of extra pulmonary tuberculosis in addition TB meningitis pots disease or TB spine renal tuberculosis and intestinal TB are some other types of extra pulmonary TB now let's come to the clinical presentation of tuberculosis persisting chronic cough is the predominant symptom in tuberculosis it can be a drier productive cough and they have a remittent low-grade fever which appears in late afternoon and fades out by night the patient develops anorexia due to the inhibitory action of the cytokines on the hypothalamus and long-term anorexia causes loss of weight patient experiences heavy sweating during night with progressive pulmonary involvement the amount of sputum increases first it has a mucoid appearance and with time it gets a purulent appearance hemoptysis or coughing out blood indicates severe disease and some people experience a pleuritic type of chest pain this is due to the extension of the infection to the pleural surfaces here is an image which recalls the clinical presentation of tuberculosis diagnosis of TB is primarily based on the history signs and symptoms and radiographic findings ask the patient about the contact history and physical status before the commencement of COFF recommend a chest x-ray to reveal white colored consolidation on the lungs this is an x-ray of a healthy lung these are x-ray images of three tuberculosis patients see the white colored consolidations in the lungs ultimately tubercle bacilli must be identified sputum direct smear for acid-fast bacilli is one method if the bacilli present in the sputum they are stained in bright red color with zeal Nielsen stain for an accurate result three samples of sputum are required early morning sample is the best sample because it contains a large amount of bacilli this is the most commonly used method however it cannot differentiate between species and cannot do antibiotic sensitivity test mica bacterial culture is the most sensitive method of diagnosis need only one sputum sample and the species can be identified however culture takes about 4 to 12 weeks to give results as Mycobacterium tuberculosis grows very slowly PCR can give rapid results and can detect antibiotic resistant genes as well man to test is a screening method of tuberculosis it can detect the active disease or previous exposure to the Mycobacterium tuberculosis a purified protein derivative is injected intradermally this is made up of mica bacterial antigens a cell-mediated type 4 hypersensitivity reaction occurs if the person has previously been exposed to Micah bacterial antigens after 48 to 72 hours the diameter of the induration is measured cutoff value of the diameter varies in different countries finally let's come to the treatment and prevention the standard treatment for pulmonary tuberculosis is six-month treatment with four antibiotics the use of anti-tuberculosis highly supervised due to the increasing antibiotic resistance of Mycobacterium tuberculosis the four antibiotics are isoniazid rifampicin tyrosine amide and ethambutol the isolation of infected people is essential in preventing tuberculosis contact tracing and screening in healthy population can be done early detection and treatment is important a vaccine is available to prevent tuberculosis it is the BCG vaccine that is a live attenuated vaccine which consists of bacillus Calmette Garan a reduced virulence type of mycobacterium bovis it is given at birth to prevent disseminated types of tuberculosis such as miliary TB and TB meningitis but it has no impact on community spread and it does not prevent the child from developing latent and secondary tuberculosis later in life you