PATHOPHYSIOLOGY
We can understand the pathogenesis of TBCP through two main aspects-inflammation caused by tubercle bacilli and constriction of the pericardium.
Tubercle bacilli access the pericardium through 3 primary mechanisms, which include retrograde lymphatic spread from mediastinal, paratracheal and peri-bronchial lymph nodes, hematogenous spread (mainly in immunocompromised hosts), and rarely direct contiguous spread from adjacent structures such as the lungs, pleura, and spine[7,21]. The stage or progression of the disease is the result of a game between bacteria and the human immune system. Due to a competent immune system, the tuberculous pericardial disease is usually limited to the pericardial space. The immune response to the acid-fast bacilli penetrating the pericardium is associated with the incidence of TBP. Once into the pericardium, viable mycobacterial protein antigens presented by macrophages to CD4+ T lymphocytes trigger activation of lymphocytes, macrophages, and complement-fixing antibodies, which leads to inflammation, production of fibrinous exudate and granuloma formation. This is called delayed hypersensitivity responses induced by tubercle proteins. TBCP is the final manifestation of TBP, and there are four pathologic stages from TBP to TBCP[22]: (1) fibrinous exudation with initial polymorphonuclear leukocytosis, relatively abundant mycobacteria, and early granuloma formation with the loose organization of macrophages and T cells; (2) serosanguineous effusion with a predominantly lymphocytic exudate with monocytes and foam cells; (3) effusion absorption with the organization of granulomatous caseation and pericardial thickening caused by fibrin, collagenosis, and ultimately, fibrosis; and (4) constrictive scarring, which involves fibrosis of the visceral and parietal pericardium. The scarred (and sometimes calcified) pericardium encases the heart in a fibrocalcific skin that impedes diastolic filling and causes the classic constrictive pericarditis syndrome. (Figure.2)
When TB is linked to AIDS, some things become different. In HIV-infected hosts, tubercle bacilli spread to the pericardium mainly via a hematogenous route[23]. Dysfunctional immunity in HIV/AIDS patients, EPTB such as TBP, becomes more frequent as part of a disseminated process associated with TB bacteremia accompanied by active mycobacterial replication and high bacterial load. HIV alters the natural history and outcomes of TB pericarditis. Fewer granulomas were observed than in non-HIV patients because of severely depleted CD4+ T lymphocytes[24]. Immunocompromised participants appear less likely to develop constrictive pericarditis but have significantly higher mortality compared with their immunocompetent counterparts[13]. However, when CP present in HIV-positive patients is usually due to tubercle bacilli[25].
It seems to be a fundamental difference in the susceptibility between HIV patients and T2DM patients to TB[26]. Macrophage function is altered during T2DM in tubercle bacilli-naïve individuals, which include reducing binding or phagocytosis of tubercle bacilli[27]. Chronic inflammation and dysregulation of the inflammasome, a common immunological characteristic to obesity and T2DM, may be associated with the increased susceptibility to TB[28]. What’s more, tubercle bacilli can reside and persist in adipose tissues, and evade recognition by the host immune system so that forming a reservoir for possible re-activation[29]. However, the relationship between T2DM and TB still mostly unknown.
Except for some pathological factors above, pregnancy can also make the management of TB more difficult. For pregnant women, the increased blood volume during pregnancy is undoubtedly worse for the scarred heart. In women co-infected with tuberculosis and HIV, neonates born to these women also have increased morbidity and mortality[30].
The restriction is another property of TBCP. As is known to all, the pericardial space contains up to 50ml of plasma ultrafiltrate, which can reduce friction on the epicardium and equalizes gravitational, hydrostatic, and inertial forces over the surface of the heart, so that transmural cardiac pressures neither change during acceleration nor differ regionally within cardiac chambers. Besides, pericardial reserve such as oblique sinus, transverse sinus, and pericardial recesses, together with the histological components of pericardium like collagen and short elastin fibers neutralize the effects of respiration and change of body position[31]. When inhaling, the intrathoracic pressure decreases, and this pressure difference is transmitted into the heart chambers so that the pressure changes in the heart and intrathoracic are synchronous. When the restriction occurs, a thickened, inelastic, and even calcified pericardium limits diastolic filling[32] and prevents the regular inspiratory decrease in intrathoracic pressure from being transmitted to the heart chambers, causing dissociation of intracardiac and intrathoracic forces. Since the pericardium does not surround the pulmonary veins, so the pulmonary venous pressure but not left atrium (LA) pressure usually drops during inspiration, which causes a reduction of flow from pulmonary venous into LA, and then a reduction in left ventricle (LV) volume[33]. With this slight reduction in LV filling, the interventricular septum bows to the left and right ventricle (RV) filling increases slightly. (Figure.3) The opposite effects occur during expiration due to ventricular interdependence. Subsequently, intracardiac pressures rise, and there is eventual equalization of diastolic pressures. Although the systolic ventricular function is reasonable, the impaired ventricular filling will lead to a reduction of stroke volumes and cardiac output[34]. The restricted pericardium can also cause the right-side heart failure (HF) of patients with symptoms of edema, hepatomegaly, and effusion in serous cavities develop[35]. To make matters worse, TBCP is often accompanied by calcification. As the disease progresses, calcification may penetrate the myocardium, leading to remodeling of the heart structure. As a result, the mortality rate increases.