GENERAL DATA

75 YEAR OLD WOMAN DIES FROM MASSIVE HEMOPTYSIS.

POSTMORTEM EXAMINATION REVEALS HILAR LYMPHAENOPATHY
WITH CASEOUS NECROSIS AND INFILTRATION AND DESTRUCTION
OF A LARGE PULMONARY ARTERY. EXTENSIVE PULMONARY
CONSOLIDATION WITH OTHER AREAS OF CASEOUS NECROSIS IS
NOTED.

SALIENT FEATURES :
- 75 Y.O. WOMAN
- DIES OF MASSIVE HEMOPATYSIS
- WITH AREAS OF NECROSIS
Differential Diagnosis
 Squamous cell Bacterial Pulmonary
carcinoma of the Pneumonia Tuberculosis
lung
hemoptysis + + +
hilar + - +
lymphadenopath
y
caseous necrosis - - +
inflammation - + +
Destruction of + - +
large pulmonary
artery
Extensive - + +
pulmonary
consolidation
 Diagnosis

 Pulmonary Tuberculosis
 ANATOMY of the LUNGS

 divided into lobes

 SEGMENTS are the gross functional
subunits of each lung
 The right lung comprises 10 segments: 3
in the right upper lobe (apical, anterior and
medial), 2 in the right middle lobe (medial
and lateral), and 5 in the right lower lobe
(superior, medial, anterior, lateral, and
posterior).
 The left lung comprises 8 segments: 4 in
the left upper lobe (apicoposterior,
anterior, superior lingula, and inferior
lingula) and 4 in the left lower lobe
(superior, anteromedial, lateral, and
posterior).
Pulmonary vasculature
 composed mainly of the pulmonary
arteries and veins.
 main pulmonary artery originates in the
right ventricle and divides into 2
branches.
 The right pulmonary artery passes
posterior to the aorta and the superior
vena cava, emerging lateral to the atria
and anterior and slightly inferior to the
right mainstem bronchus
 the left pulmonary artery is situated
anterior to the left mainstem bronchus.

The pulmonary veins originate in the alveoli and also receive drainage from the
bronchial and pleural branches. After the confluence of the small branches into
bigger ones, 2 pulmonary veins, superior and inferior, are formed on each side.
These 4 veins typically join at or near their junction with the left atrium, and usually
this common area is intrapericardial.
Pulmonary lymphatic system
 lymphatic drainage of the lungs
start with lymphatic vessels that
first drain into intraparenchymal
lymphatics and lymph nodes
 then move to peribronchial (hilar)
lymph nodes, and subsequently
move to subcarinal,
tracheobronchial, and paratracheal
lymph nodes
 The lymphatics eventually
communicate with the venous
system via the bronchomediastinal
lymphatic trunk and the thoracic
duct or via the inferior deep cervical
(scalene) lymph nodes.
TUBERCULOSIS
• Caused by M. tuberculosis (main), an acid-fast bacillus; M. africanum; M. bovis

• Certain disease states increase the risk: DM, Hodgkin lymphoma, chronic lung
disease (silicosis), chronic renal failure, malnutrition, alcoholism,
immunosuppression

Pathogenesis of Tuberculosis
• Ability to escape killing by macrophages
• Type 4 hypersensitivity reaction (Delayed hypersensitivity)
o Cord factor
 inhibits polymorphonuclear leukocyte migration
 elicits granuloma formation
 damages/attacks mitochondrial membranes
 Damages oxidative phosphorylation and respiration
o Lipoarabinomannan (LAM) – inhibits macrophage activation
o Secretion of cytokines (TNF α and IL-1) – fever, tissue damage & weight loss
• Complement activated on the surface of MTB opsonize and facilitate its uptake by
Macrophage Complement receptor
• Macrophages are the primary cells infected by M. tuberculosis
• Immunity to M. tuberculosis is primarily mediated by TH1 cells
• IFN-γ is the critical mediator that enables macrophages to contain the M. tuberculosis infection

M. tuberculosis enters macrophages by endocytosis via mannose receptors (bind

LAM, lipoarabinomannan) and complement receptors (bind opsonized mycobacteria)

Blocks phagolysosome formation

M. tuberculosis organisms replicate/proliferate in the pulmonary

alveolar macrophages and airspaces
Bacteremia and seeding of multiple sites
(<3 weeks)

Th1 response (via IL-12): activates macrophages = bactericidal

(3 weeks)

Production of IFN-γ (formation of phagolysosome and nitric oxide synthase)

**IFN-γ enables macrophages to contain the M. tuberculosis infection
Production of TNF (monocyte recruitment  epitheloid granuloma)
Activated macrophages differentiate into epitheloid histiocytes  giant cells
Clinical features of tuberculosis
Primary tuberculosis
 Initial infection
 occurs in a previously unsensitized or unexposed host
 characteristic lesion: granuloma occurring in either the upper part of the lower
lobe, or the lower part of the upper lobe, close to the pleura
 Granuloma/ Ghon focus
 1-1.5cm area of gray-white inflammation with consolidation
 known as your parenchymal focus (found in the parenchyma)
 aggregates of epitheloid cells rimmed by lymphocytes, plasma cells, and fibroblasts
 may or may not have caseation necrosis
 Ghon complex
 Ghon focus + hilar (usually) lymph node involvement
 Ranke complex
 Radiologically detectable calcification when the ghon complex undergoes progressive
fibrosis
 Lymphohematogenous dissemination may result in the development of
tuberculous meningitis and miliary tuberculosis
Primary pulmonary tuberculosis,
Ghon complex. The gray white
parenchymal focus is under the pleura
in the lower part of the upper lobe.
Hilar lymph nodes with caseations are
seen on the left.
Primary Tb

 Healed and become calcified = 90%

 Progression of TB/ spread by contiguity or by erosion into bronchi  disseminate
o develops into progressive primary tuberculosis which resembles acute
bacterial pneumonia because of middle and lower lobe consolidation,
lymphadenopathy, and pleural effusion.

• Miliary TB via hematogenous spread of TB throughout the body  numerous minute

(2mm) yellow-white foci of inflammation with consolidation (resembles bird seeds)
 Secondary tuberculosis

 Postprimary Tuberculosis
 occurs in a previously sensitized host/ previously exposed host
 occurs as a result of reactivation of the latent lesion or reinfection
 Lesion: characterized as an apical lesion which may occur in one or both lobes, and
there are cavitations
 Granuloma in the apex of the lungs due to high O2 content

 Cavitation is almost inevitable in neglected secondary tuberculosis, and erosion of the

cavities into an airway is an important source of infection -> coughs sputum that
contains bacteria
 2 features: caseation necrosis & cavities
 Resistant to TB: Heart, striated muscle, thyroid gland & pancreas
Secondary pulmonary TB. Presence of apical
lesion with cavitation.
Fates of Secondary Tuberculosis
Progressive pulmonary tuberculosis
o Apical lesion expands into adjacent lung and eventually erodes into bronchi and vessels
hemoptysis

Miliary Pulmonary Disease

o TB bacilli enters venous blood, circulates back into the lungs to form minute
(2mm) yellow-white foci in the lung
o “miliary” – resemblance to millet seeds

Endobronchial, Endotracheal and Laryngeal TB

o Spread through lymphatic channels or from expectorated infectious material

Systemic Miliary TB
o occurs when the TB bacilli is able to enter the systemic arterial system
-Meninges, Kidneys, Adrenal glands, Spleen, Liver, Bone marrow, Fallopian tubes

Lymphadenitis (Scrofula)
o most common form of extrapulmonary TB
o usually involves cervical lymph node

Intestinal TB
Diagnostic Modalities
 Tuberculin Skin Test
-Primary screening method for TB infection
-involves 5 units of PPD (0.1ml)
-induration of <5mm constitutes a negative result

 Chest X-Ray
-may show patchy or nodular infiltrates
-upper lobe most common
 Sputum Smear
- px should submit sputum for AFB smear and culture
- collected early morning on 3 cons. Days

 Culture
- Culture for AFB is the most specific test for TB and allows
direct identification and determination of susceptibility of the
causative organism.
 Drug Susceptibility Testing
DNA-Sequencing - rapid and useful method for detecting drug-resistant TB.

Automated molecular testing - uses sputum samples for the detection of M

tuberculosis and resistance to rifampin

MODS and TLA assays - are inexpensive, rapid alternatives to conventional and
molecular methods of TB drug susceptibility testing

-
Treatment for TB
Disease
 TB disease can be treated by taking several drugs for 6
to 9 months. The first-line anti-TB agents that form the
core of treatment regimens are:

 isoniazid (INH)
 rifampin (RIF)
 ethambutol (EMB)
 pyrazinamide (PZA)
Drug Susceptible TB Disease Treatment
Regimens
Continuation Phase of
Treatment
The continuation phase of treatment is given for either 4 or 7 months. The
4-month continuation phase should be used in most patients. The 7-month
continuation phase is recommended only for the following groups:
 Patients with cavitary pulmonary TB caused by drug-susceptible organisms
and whose sputum culture obtained at the time of completion of 2 months
of treatment is positive;
 Patients whose intensive phase of treatment did not include PZA;
 Patients with HIV who are not receiving antiretroviral treatment (ART)
during TB treatment; and
 Patients being treated with once weekly INH and rifapentine and whose
sputum culture obtained at the time of completion of the intensive phase
is positive.
Treatment Completion

 Treatment completion is determined by the number of

doses ingested over a given period of time.
Prognosis

 For most people who live in areas where diagnosis and

treatment is available, the prognosis of TB is good if
they complete the treatment protocols. The recurrence
rate of TB is low (0%-14%) and some may be due to
reinfection.
 Drug-resistant tuberculosis is more difficult to treat,
and the prognosis is not as good. The same poor
prognosis occurs for those patients who are
immunocompromised, elderly, and in patients with
previous infection and treatment for TB.
Serum Macrophage
Migration
Inhibitory Factor
as a Biomarker of
Active Pulmonary
Tuberculosis
Zhong-bo Shang, M.D., Jun Wang, M.D.,Shou-gang Kuai, M.D., Yin-yin Zhang, M.D., Qin-fang Ou,
M.D., Hao Pei, M.D., and Li-hua Huang, M.D.

Source: https://doi.org/10.3343/alm.2018.38.1.9
Published online October 23, 2017
Background

 Macrophage migration inhibitory factor (MIF), a pro-

inflammatory cytokine with chemokine-like functions,
has been shown to play a central role in several acute
and chronic inflammatory diseases. However, limited
information is available regarding the use of MIF as an
inflammatory pathway marker in patients with
tuberculosis. This study aimed to investigate the
association of MIF with IFN-γ and TNF-α in active
pulmonary tuberculosis (APTB) following anti-
tuberculosis treatment.
Methods

 The MIF, TNF-α, and IFN-γ serum levels were

determined in 47 patients with APTB by cytokine-
specific ELISA at four phases: prior to anti-tuberculosis
drug treatment (baseline), and following 2, 4, and 6
months of treatment. In addition, we measured the MIF,
TNF-α, and IFN-γ serum levels in 50 health controls.
Conclusions

 A reduction in the MIF serum levels in patients with

APTB following anti-tuberculosis treatment may
positively affect host immune protection
against Mycobacterium tuberculosis infection. Thus,
serum MIF levels may constitute a useful marker for
assessing therapy effectiveness in patients with APTB.