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.