?

what are the differential diagnosis of this case -1

●Nontuberculous mycobacterial infection (NTM) – Symptoms of NTM include

fatigue, dyspnea, and occasional hemoptysis; fever and weight loss occur less
frequently than in patients with tuberculosis. NTM is distinguished from TB by
culture results and/or molecular diagnostic testing.

●Fungal infection – Fungal pneumonia can present with a range of manifestations

including pneumonia, pulmonary nodule, and cavitary lung disease.
Hematogenous dissemination frequently occurs, especially in an
immunocompromised host. It is distinguished from TB by epidemiologic exposure
and culture results.

●Sarcoidosis – Sarcoidosis most commonly presents with diffuse interstitial lung

disease. It rarely forms cavities and is distinguished from TB by histopathologic
detection of noncaseating granulomas.

●Lung abscess – Lung abscess generally presents with fever, cough, and sputum
production but without shaking chills or true rigors. Chest radiographs usually show
infiltrates with a cavity. The diagnosis is established based on culture results.

●Lung cancer (Non-small cell lung cancer) – Lung cancer most commonly presents
with cough, hemoptysis, chest pain, Weight loss , loss of appetite
and dyspnea. It is distinguished from TB by histopathology.

●Lymphoma – Lymphoma typically presents with a rapidly growing mass together

with fever, night sweats, and weight loss. It is distinguished from TB by
histopathology.

Actinomycosis– is a subacute-to-chronic bacterial infection caused by ●

filamentous, gram-positive, non–acid-fast, anaerobic-to-microaerophilic bacteria.
It is characterized by contiguous spread, suppurative and granulomatous
inflammation, and formation of multiple abscesses and sinus tracts that may
.discharge sulfur granules

? what is TB and its classification-2

Tuberculosis (TB) is an acute or chronic mycobacterium infection characterized by
pulmonary infiltrates and the formation of granulomas with caseation, fibrosis, and
cavitation. The main site of infection is the lung, but approximately 15% of infections are
.extrapulmonary

Tuberculosis is a communicable chronic granulomatous disease caused by Mycobacterium

tuberculosis. It usually involves the lungs but may affect any organ or tissue in the body.
Typically, the centers of tubercular granulomas undergo caseous necrosis

:Classification
:Primary Tuberculosis -1

is the form of disease that develops in a previously unexposed and therefore unsensitized
.patient

Elderly persons and profoundly immunosuppressed patients may lose their sensitivity to the
tubercle bacillus, so they may develop primary tuberculosis more than once. About 5%

.of those newly infected acquire significant disease

The major consequences of primary tuberculosis are that

;it induces hypersensitivity and increased resistance )1(

.the foci of scarring may harbor viable bacilli for years ,perhaps for life )2(

:Secondary Tuberculosis (Reactivation Tuberculosis) -2

develops in previously exposed (sensitized) to infection individuals -1

:it may arise from -2

a- reactivation of latent primary lesion (more common)

b- exogenous reinfection
?what are the risk factor of TB and etiology-3
The following factors increase an individual’s risk of acquiring active tuberculosis:
1-HIV infection
2- Intravenous (IV) drug abuse
3- Alcoholism
4- Diabetes mellitus (3-fold risk increase)
5- Silicosis
6- Immunosuppressive therapy
7- Tumor necrosis factor–alpha (TNF-α) antagonists
8- Cancer of the head and neck
9- Hematologic malignancies
10- Smoking - Smokers who develop TB should be encouraged to stop smoking
to decrease the risk of relapse 
11- Age below 5 years
12-Poverty.
13-Old age.
14-crowding.
: Etiology

?what is the pathogenesis of TB-4

mycobacteria reach the pulmonary alveoli, where they invade and
replicate within endosomes of alveolar macrophages. Macrophages
identify the bacterium as "foreign" and attempt to eliminate it by
phagocytosis. During this process, the entire bacterium is enveloped by
the macrophage and stored temporarily in a membrane-bound vesicle
called a phagosome .. The phagosome then combines with a lysosome
to create a phagolysosome. In the phagolysosome, the cell attempts to
use reactive oxygen species and acid to kill the bacterium. However, M.
tuberculosis has a thick, waxy mycolic acid capsule that protects it from
these toxic substances. M. tuberculosis actually reproduces inside the
macrophage and will eventually kill the immune cell.
they able to inhibit normal microbicidal response by:
1- arrest endosomal maturation
2- manipulation of endosomal pH
3- ineffective phagolysosome formation
this results in:
1- bacterial proliferation within macrophages and airspaces
2- bacteremia with seeding of multiple sites

Second stage :

- bacterial antigens reach draining lymph nodes and are presented to

CD4+ T cells
- under influence of IL-12 T cells generated capable of secreting
interferon gamma
- interferon gamma activates macrophages which in turn release
mediators:
1- TNF: stimulates recruitment of monocytes which differentiated
into epithelioid
 2- NO: capable of oxidative destruction of mycobacteria
3- free radicals: can have antibacterial activity

- defect in any of the steps of T cells response (IL-12, INF, TNF, NO, free
radicals) results in:
1- poorly formed granulomas
2- absence of resistance and disease progression

Tuberculosis is classified as one of the granulomatous inflammatory

diseases. Macrophages, T lymphocytes, B lymphocytes,
and fibroblasts aggregate to form granulomas, with
lymphocytes surrounding the infected macrophages

Tissues within areas of caseation necrosis have high levels of fatty acids,
low pH, and low oxygen tension, all of which inhibit growth of the
tubercle bacillus.
? what are the sign and symptom of TB-5
 what is the pathophysiology of TB and collate the sign and symptom with -6
? underlying disease

Fate of primary tuberculosis: either

a- is controlled with no viable bacteria
(healed lesion)
b- the foci of fibrosis may harbor viable
bacteria for years which reactivated
when host defenses compromised with
development of secondary tuberculosis
(Latent lesion)
c- uncommonly the disease may develop
into progressive primary tuberculosis
(immunocompromised, malnourished,
elderly) with lymphohematogenous
dissemination and development of miliary TB

-Fate of secondary pulmonary tuberculosis:

a- may heal by fibrosis (spontaneously or after therapy)
b- or the disease may progress into:
Progressive secondary tuberculosis:
- The localized lesion enlarges with erosion into
bronchi (cavity) and blood vessels ( hemoptysis)
- If treatment is adequate, the process may be arrested
(healing by fibrosis)
- If the treatment is inadequate, or if host defenses are impaired, the
infection may spread:
1- by direct expansion
2- via airways
3- lymphatic channels
 4- vascular system
- leading to:

1- Miliary pulmonary disease:

- organisms through lymphatics reach the
right side of the heart and then into the
pulmonary arteries and into lungs
- multiple small, visible, scattered foci
- complications: pleural effusion, empyema, pluritis

2- Endobronchial, endotracheal, laryngeal tuberculosis:

- organisms spread either: - through lymphatics or
- from expectorated infectious material

3- Systemic miliary tuberculosis

- occurs when organisms through pulmonary veins
reach the left heart and then to systemic
testicular
- every organ in the body may be seeded
- common in the liver, bone marrow, spleen,
adrenals, meninges, kidneys, fallopian
tubes, and epididymis
4- Isolated-organ tuberculosis:
occurs in any organ or tissue hematogenously -
what are related investigation and the montoux skin test and X-ray -7
?finding
:Images
:X-ray-1
,An abnormal chest X-ray is often found with no symptoms
shows patchy or nodular in the upper zones, loss of volume and fibrosis
.with or without cavitation. Calcification may be present

:CT scanning-2
.may reveal lung parenchymal abnormalities at an earlier stage

. Staining : ((microscope for sputum))

:Ziehl neelsen stain-1
The waxy mycolic acid of cell wall of Mycobacterium tuberculosis allows
it to retain the carbol fuschin even after exposure to strong acid
.solutions, thus called acid-fast
AFB ---pink
Background ---blue

:Auramine rhodamine staining-2

Flourocrome dyes Auramine-Rhodamine have affinity with mycolic acid
in the cell walls of Mycobacteria, which appear bright yellow against a
.dark background

: Sputum culture
Culture on solid media
:Egg based-1
Lowenstein Jensen(LJ) medium
Selective for mycobacterium
MTB is slow growing and colonies take 4-6 weeks to grow
Colony appearance is dry, rough, raised with wrinkled surface and
creamy white in color

:Agar based-2
Middlebrook 7H10 agar
Growth in two weeks

Semiautomated/Automated culture methods-3

MGIT 960
The MGIT tube contains a fluorochrome that is suppressed by oxygen in
tube. During bacterial growth within the tube, the free oxygen is
utilized by bacteria. With depletion of free oxygen, the fluorochrome is
. no longer inhibited, resulting in fluorescence within the MGIT tube
This flourescence is measured by the machine . The intensity of
.fluorescence is directly proportional to the bacterial growth
Fully automated
Growth in less than 9 days
Antibiotic susceptibility testing

: Montoux skin test

is the standard method of determining whether a person is
.exposed to Mycobacterium tuberculosis or not
The TST is performed by injecting 0.1 ml of tuberculin purified -
protein derivative (PPD) into the inner surface of the forearm. The
.TST is an intradermal injection
The skin test reaction should be read between 48 and 72 hours after -
.administration
screening test to detect those who may have been exposed to TB. It is -
not for diagnosis of active TB, but rather of latent (primary)
TB (if positive, a chest x-ray is used to diagnose active TB). PPD is not a -
screening test for everyone, only patients with one or more of the risk
factors mentioned above should have this test. If patient is -
symptomatic or has abnormal chest x-ray, order a sputum acid-fast test,
.not a PPD
Tuberculin skin test (PPD test)
:Positive result is interpreted as follows
The result is positive if induration ≥15 mm in patients with no risk •
.factors
In certain high-risk populations (e.g., those who live in high-prevalence •
areas, immigrants in the last 5 years, the homeless, prisoners, health
care workers, nursing home residents, close contact of someone with
.TB, alcoholics, diabetics), 10 mm of induration is considered positive
For patients with HIV, steroid users, organ transplant recipients, close •
contacts of those with ACTIVE TB, or those with radiographic evidence
.of primary TB, induration of 5 mm is positive

If PPD test is positive, a chest x-ray is needed to rule out active disease.
Once active disease is excluded, 9 months of isoniazid treatment is
initiated. A patient with a positive PPD test has a 10% lifetime risk of TB,
.and this risk is reduced to 1% after 9 months of isoniazid treatment

?recall the zones of the lungs and what is the suitable site with TB -8
:Primary tuberculosis
:Morphology
the inhaled bacilli implant in the lower part -
of the upper lobe or the upper part of the
.lower lobe, usually close to the pleura

:Secondary tuberculosis
:Morphology -3
a- secondary tuberculosis is classically located
to apex of one or both upper lobes
:)Localized secondary lesion(
.Grossly: firm, gray-white with caseation

?why the physicion did not wait the culture-9

?what are the relevance of soci-economic with TB-10

?what is the rout of transmission of TB -11

M. tuberculosis is carried in airborne particles, called droplet nuclei, of
1– 5 microns in diameter. Infectious droplet nuclei are generated when
persons who have pulmonary or laryngeal TB disease cough, sneeze,.
Depending on the environment, these tiny particles can remain
suspended in the air for several hours. M. tuberculosis is transmitted
through the air, not by surface contact. Transmission occurs when a
person inhales droplet nuclei containing M. tuberculosis, and the
droplet nuclei traverse the mouth or nasal passages, upper respiratory
tract, and bronchi to reach the alveoli of the lungs
?what is the management of TB-12
?how can we prevent TB-13
:BCG vaccine (Bacillus Calmette-Guérin vaccine)-1

-2

?what is the complication of TB-14

: Hemoptysis
Sources of massive hemoptysis due to TB include the pulmonary artery,
bronchial arteries, intercostal arteries, and other vessels supplying the
lung. "Rasmussen's aneurysm" refers to the formation of an aneurysm in
the setting of cavitary infection ,resulting in inflammation and thinning of
the vessel wall . This aneurysm subsequently ruptures into the cavity,
.producing massive hemoptysis

:Pneumothorax
Pneumothorax appears to result from the rupture of a peripheral cavity
or a subpleural caseous focus with liquefaction into the pleural space .
Inflammation can lead to development of a bronchopleural fistula, which
can persist or seal off spontaneously. The lung may reexpand if the
bronchopleural fistula seals spontaneously, but more commonly tube
.drainage is required

:Bronchiectasis
Following primary TB infection, extrinsic compression of a bronchus by
enlarged nodes may cause bronchial dilation distal to the obstruction.
.There may be no evidence of parenchymal TB
:malignancy
The causal relationship is not clear but mycobacterial cell wall components
may induce production of nitric oxide and reactive oxygen species, which
have been implicated in DNA damage leading to carcinogenesis

: Septic shock
TB can cause septic shock; the manifestations are similar to bacterial septic  
shock

?what is the epidemiology of TB in KSA-15