Pulmonary TB has classic symptoms of night sweat, fever, dypsnea and hemoptysis. In order to correlate the pathogenesis of the disease with the presenting classical symptoms of pulmonary TB, let me overview the whole picture of the disease.
- Upon settlement in the alveolar space, after passes through the cough reflex and mucociliary clearence, mycobacterium tuberculosis (MTB) will initiate an immidiate acute inflammatory response. Detected foreign particle by macrophage through its distinctive mannose capped glycolipid, macrophage will start to engulf the MTB. Consequent to that, IL-1 will be released as soon as possible to stimulate the thermostat of the brain at the Organum Vasculasum of Lamina Terminalis (OVLT) to increase the level of body temperature with a hope to fight against the foreign particles. Through increasing the body temperature, iron serum level will drop significantly this will immobilize bacterial growth as most bacteria need iron for replication. Therefore, at the early stage of pulmonary TB, patient is presented with intermittent on and off low grade fever.
- Upon engulfment of the MTB, macrophage is now susceptible to endosomal manipulation in which will lead to ineffective digestion of MTB and finally lead to MTB multiplication inside the alveolar macrophage. Nevertheless, some alveolar macrophages resist the endosomal manipulation through a protein called Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) which is highly genetic polymorphism. This kind of mcrophage is capable of digesting the MTB and finally present the antigen in the Major Histocompatibility Complex (MHC). The 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). . In order to elicit the formation of granuloma in order to settle down and confine the infection, Helper T-cell 1 will produce Tumour Necrosis Factor (TNF). Interestingly, this TNF is produced massively at night and some extensive experiments have been done and it is believed that the sharp increase in the serum TNF level causes the classic night sweat in pulmonary TB patient. Despite of that, the hypothesis is still remained inconclusive and some scienctists are still debating the basis of TNF pathology towards night sweat.
- After the confinement of MTB inside granuloma, inflammatory response couldn’t stop to initiate further destruction over the surrounding tissues as massive inflammatory cells infiltration has lead to release of tremendous amount of free radicals to fight against the destructive MTB. Massive tissue damage has lead to destuction of pulmonary capillary endothelium which causes hemorrhage. In fact, during chronic inflammation, blood vessels surrounding the infected sites are engorged and highly susceptible to destroy. The leakage of blood vessel leads the patient to cough out not only pus containing sputum but also blood.
- On further destruction, lung function is now at the brink of compromisation as patient is now can hardly breath air as too many lung parenchyma has been obliterated. Consequently, more tissue fibrosis takes part and more lung remodelling occurs as a part of healing process. This further compromises lung function. As at the farther prognosis of the disease, patient is now starting to present with shortness of breath (dyspnea) as a part of compensatory mechanism to eleavate the oxygen partial pressure inside the systemic circulation. Since the patient is at at the state of hypoxia for quite something, total body metabolism depletes insidiously making the patient to only capable to gasp air instead of having a long and complete force ventilation (with respect to its reduced energy)