Tuberculosis b.

Blocks formation of the phagolysosome by

recruiting Coronin → Coronin activates the
Tuberculosis phosphate calcineurin → inhibition of
- Caused by Mycobacterium Tuberculosis phagosome-lysosome fusion → allows
- One of the oldest diseases affecting humans replication within the vesicle
- Top cause of infectious death globally 4. Primary tuberculosis, <3 weeks
- Emerged ~70,000 years ago in Africa a. bacteria proliferate in the pulmonary alveolar
macrophages and air spaces
Etiology b. Bacteremia and seeding of multiple sites
Mycobacteria c. Most people at this stage are asymptomatic
- Family: Mycobacretiaceae or have a mild flulike illness
- Order: Actinomycelates 5. Response of the Innate Immunity
a. Mycobacterial lipoarabinomannan binds
M. Tuberculosis TLR2
- Sensu stricto subgroup: common agent of human TB b. unmethylated CpG nucleotides bind TLR9
infection 6. Th1 Response
- Rod-shaped a. 3 weeks after the infection → Th1 response
- Non-spore-forming is mounted that activates macrophages,
- 0.5-3.0 um enabling them to become bactericidal
- Neutral on Gram-staining b. the response is initiated by mycobacterial
- Cannot be decolorized by acid alcohol antigens that enter draining lymph nodes
- Acid-fast bacilli and are displayed to T cells
- d/t high content of mycolic acids, long-chain 7. Th1-mediated macrophage activation and killing of
cross-linked fatty acids, and other cell-wall bacteria.
lipids a. Th1 cells (lymph nodes and lungs) produce
IFN-y.
Causative Agent: Mycobacterium tuberculosis (Gram-positive) b. IFN-y - critical mediator that activates
Site of Infection: Pulmonary Alveoli macrophages and enables them to contain
Immune Response: Cell-mediated Immunity the M. tuberculosis infection
8. Role of IFN-y
Pathophysiology (Robbins) a. stimulates maturation of the phagolysosome
1. Droplet nuclei containing M. tuberculosis in infected macrophages, exposing the
a. Aerosolized by coughing, sneezing, or bacteria to a lethal acidic, oxidizing
speaking environment
b. Remain suspended in the air for several b. stimulates the expression of inducible nitric
hours (<5-10 um diameter) oxide (NO) synthase, which produces NO
c. 3000 infectious nuclei per cough i. NO + other oxidants → create
d. Acquiring infection depends on endogenous reactive nitrogen intermediates,
factors which are important for the killing of
i. Immunologic defense mycobacteria
ii. Level of cell-mediated immunity c. mobilizes antimicrobial peptides (defensins)
e. Predominant cells are myeloid dendritic cells against the bacteria
2. M. tuberculosis enters macrophages by phagocytosis d. stimulates autophagy, a process that
a. Mediated by mannose-binding lectin and sequesters and then destroys damaged
type 3 complement receptor organelles and intracellular bacteria such as
3. Replication of M. tuberculosis in macrophages M. tuberculosis.
a. M. tuberculosis inhibits the maturation of the 9. Granulomatous inflammation and tissue damage
phagosome a. Th1 response orchestrates the formation of
granulomas and caseous necrosis
 b. Activated macrophages secretes TNF and
chemokines → promotes recruitment of
more monocytes

Host Susceptibility to TB
- AIDS
- Greater risk factor for progression d/t loss of
immunologic control of the organism
- Other forms of immunosuppression
- Glucocorticoids
- TNF inhibitors
- Organ or stem cell transplantation
- Renal failure
- Malnutrition

Clinical Manifestation

Primary Disease
- Occurs soon after the initial infection
- Asymptomatic or fever; occasionally pleuritic chest
pain
- Middle and lower lung zones are commonly affected
- Lesions:
- Ghon focus
- formed after initial infection
- Usually peripheral
- accompanied by transient hilar or
paratracheal lymphadenopathy
- May not be visible in CXR Phlyctenular conjunctivitis
- Associated SSX: erythema
nodosum on the legs or
phlyctenular conjunctivitis
- heals spontaneously and becomes
evident only as a small calcified
nodule
- Ghon complex
- Ghon focus, with or without
overlying pleural reaction,
thickening, and regional
lymphadenopathy

Erythema nodosum on the legs

Postprimary (Adult-type) Disease
- Aka reaction or secondary TB
- localized to the apical and posterior segments of the
upper lobes
- substantially higher mean oxygen tension
- superior segments of the lower lobes are also
frequently involved
- Extent of lung parenchymal involvement
- Small infiltrates to extensive cavitary disease
- Cavitary formation → liquefied necrotic
contents are discharged into the airways →
bronchogenic spread

Early SSx of Postprimary TB

- Non-specific and insidious
- Low grade Fever (diurnal and night sweats)
- 37.5 and 38.3 degrees C
- Absence of fever does not exclude
TB
- Weight loss
- Anorexia
- General malaise
- Weakness
- Cough (morning and initially nonproductive)
accompanied by purulent sputum with blood
streaking
- Hemoptysis
- d/t rupture dilated vessek in a cavity
(Rasmussen’s aneurysm)
- Aspergiloma formation
- Pleuritic chest pain
- Dyspnea
- Respiratory Distress Syndrome (Rare)
- Rales during inspiration, especially when
coughing
- Rhonchi and classic amphoric breath sounds
- With large cavities
- Rhonchi: continuous gurgling or
bubbling sounds typically heard
during both inhalation and
exhalation
- classic amphoric breath sounds:
low pitch bronchial breath sound
with high pitch overtones
- Finger clubbing (esp. Low karnofsky score)
- Hematologic Findings:
 - Mild anemia
- Leukpcytosis
- Thrombocytosis with slightly
elevated ESR or CRP

Extrapulmunary TB
- Common sites (descending order)
- Lymph node
- Pleura
- Genitourinary tract
- Bones and Joints
- Meninges
- Peritoneum
- Pericardium
- Seen more commonly d/t high prevalence of HIV
EPTB Clinical Manifestation Confirmatory Testing

Lymph Node TB painless swelling of the lymph nodes Fine-needle aspiration biopsy or surgical
(cervical and supreclavicular sites are excision biopsy
common) ● granulomatous lesions with or
without visible AFBs

Pleural TB Fever Thoracentesis

Pleuritic Chest Pain ● straw-colored and at times
Dyspnea hemorrhagic
● exudate with a protein concentration
PE >50% (~4–6 g/dL)
● dullness to percussion (chest) ● normal to low glucose concentration
● absence of breath sounds ● pH of ~7.3 (occasionally <7.2)
● white blood cells (usually
CXR 500–6000/μL)
● Effusion ● Neutrophils may predominate in the
● Parechymal Lesion early stage → Lymphocyte
predominance is the typical finding
later
● Rare or absent mesothelial cells

Direct Smear (Sputum)

● Rare AFBs
● False negative for M. tuberculosis

Needle biopsy of the Pleura

● granulomas and/or yields a positive
culture

Upper Airways TB Hoarseness Direct Smear (Sputum)

Dysphonia ● Positive
Dysphagia
chronic productive cough

Genitourinary TB Cryptic and Protean CXR

Nonspecific SSx ● Previous or concomitant pulmonary
● Dysuria disease
● Nocturia
● Hematuria Urinalysis
● Abdominal or flank pain ● Pyuria
● Hematuria
Female:
● Fallopian Tubes IV pyelography, abdominal CT, or MRI
● Endometrium → infertility, pelvic ● deformities and obstructions;
pain, and menstrual abnormalities calcifications and ureteral strictures

Male:
● Epididymis
● Orchitis
● Prostatitis
Skeletal TB Most common site:
● Weight-bearing joints
● Spine - 40%
● Hips - 13%
● Knees - 10%

Tuberculous Meningitis and Tuberculoma Headache Lumbar Puncture

slight mental changes after a prodrome of ● high leukocyte count (up to 1000/μL)
weeks of low-grade fever ● predominance of lymphocytes but
Malaise some- times with a predominance of
Anorexia neutrophils in the early stage
Irritability ● protein content of 1–8 g/L (100–800
severe headache mg/dL)
Confusion ● low glucose concentration
Lethargy
altered sensorium Direct Smear (CSF)
neck rigidity. ● AFBS rarely seen

CT/MRI
● Hydrocephalus
● abnormal enhancement of basal
cisterns or ependyma

GI TB Mechanisms Involve:
● swallowing of sputum with direct
seeding
● hematogenous spread
● ingestion of milk from cows affected
by bovine TB

Commonly affected sites:

● terminal ileum
● Cecum

Presentation:
● Abdominal pain (at times similar to
that associated with appendicitis)
● Swelling
● Obstruction
● Hematochezia
 ● palpable mass in the abdomen

Associated Symptoms:
● Fever
● weight loss
● Anorexia
● night sweats

Pericardial TB Dyspnea CT/MRI

Fever ● effusion and thickness across the
Dull retrosternal pain pericardial space
Pericardial friction rub
Pericardiocentesis
Complications: ● Exudative
● chronic constrictive pericarditis ● high count of lymphocytes and
with thickening of the monocytes
pericardium, fibrosis, and ● Hemorrhagic effusion
sometimes calcification (CXR)
Direct Smear (Pericardial Fluid)
● Rarely positive

Culture
● (+) M. tuberculosis

Biochemical
● High levels of deaminase, lysozyme,
and IFN-y

Miliary or Disseminated TB Lesions - yellowish granulomas 1-2 mm CXR

diameter; resembles millet seeds ● miliary reticulonodular pattern
● large infiltrates
Clinical Manifestation (Nonspecific & ● interstitial infiltrates (especially in
protean): HIV-infected patients)
● Fever ● pleural effusion
● Night sweats
● Anorexia (-) Sputum-smear microscopy
● Weakness
● Weight loss CBC
● Cough (pulmonary involvement) ● anemia with leukopenia
● Abdominal SSx ● Lymphopenia
● neutrophilic leukocytosis and
Physical Finding leukemoid reactions
● Hepatomegaly ● Polycythemia
● Splenomegaly
● Lymphadenopathy Biochemical
● Choroidal tubercles ● Elevation of alkaline phosphatase
(pathognomonic) levels
● abnormal values in liver function
tests

TST
● negative