Professional Documents
Culture Documents
Scanning electron micrograph of Staphylococcus aureus bound to the surface of a human neutrophil. “Granulocytic Phagocytes,” by Frank R. DeLeo and William M. Nauseef.
Learning Objectives
To provide the basic description, pathogenesis, types, morphology (gross and
microscopic), clinical presentation(signs & symptoms) and complications of
Mycobacterium tuberculosis.
Including:
1. Describing the main pathologic characteristics of secondary (reactivation)
pulmonary tuberculosis.
2. Defining miliary tuberculosis and tuberculous bronchopneumonia.
3. Discussing the histologic and laboratory methods useful in diagnosis of
tuberculosis.
4. Understanding the epidemiology, etiology, pathophysiology, risk factors,
diagnosis and management of Mycobacterium Leprae
5. Understanding the epidemiology, pathogenesis, clinical presentation,
diagnosis and management of HIV-TB coinfected
Most frequently, patients with this initial infection are asymptomatic, and
lesions undergo fibrosis and calcification=Latent TB (tubercle bacilli residing in
macrophages)
In some instances, self-limited extension to pleura with secondary pleural effusion occurs
Less commonly, progressive spread with cavitation tuberculous bronchopneumonia, or
miliary tuberculosis may follow primary infection
Marc Imhotep Cray, M.D. 7
Primary tuberculosis (2)
Primary infection with TB occurs by inhaling bacilli into lungs phagocytized
by alveolar macrophages and carried to regional lymph nodes
During first few weeks after primary infection, bacilli replicate locally and
T-cell mediated cellular immunity develops
Lymphocytes and monocytes migrate to area of infection and form
histiocytic cells that organize into a granuloma
o granulomas most often contain infection and eventually become
calcified
o TB bacilli remain viable within macrophages in granuloma for years
and often never reactivate
Once infected patients develop lifelong immunity to re-infection as is
manifested by a positive response to PPD antigen
Patient with primary infection is not contagious as long as infection is
contained within a granuloma
Marc Imhotep Cray, M.D.
Secondary (reactivation) tuberculosis:
pathologic characteristics
Patient with secondary pulmonary tuberculosis (active disease) is contagious
Lesion is located in sites with high oxygen tension, particularly in lung apices
A diffuse, fibrotic, poorly defined lesion develops, with focal areas of caseous
necrosis
Most commonly, foci heal and calcify but some erode into a bronchus
drainage of infectious material creates a tuberculous cavity
Marc Imhotep Cray, M.D. 9
Secondary (Recrudescent* )TB (2)
Secondary (recrudescent )TB, or reactivation TB, usually occurs many
years after the primary infection
Reactivation is more prevalent in elderly, debilitated, and
immunocompromised
TB recrudescence occurs when contained bacilli begin to multiply and
proliferate as pulmonary lesions progress, they necrotize and become
caseating granulomas these can necrotize into adjacent bronchi and
become cavitary lesions
Secondary TB can also manifest as lobar infiltrates
It is during this phase that patients are contagious
PPD typically remains positive during secondary TB
Anergy, or a false-negative PPD test, often occurs in end-stage AIDS and
in miliary TB (widespread hematogenous spread of bacilli)
*Recrudescence= reappearance of a disease after a
Marc Imhotep Cray, M.D. period without signs or symptoms of its presence.
Secondary (reactivation) tuberculosis:
pathologic characteristics (3)
A yellow-grayish caseous material fills cavity, which is more or
less surrounded by fibrous tissue
Marc Imhotep Cray, M.D. Rosenthal K, Tan J: Rapid Review Microbiology and Immunology, 2nd ed. Philadelphia, Mosby, 2007 13
Pathogenesis and clinical course of
tuberculosis (TB) caused by
Mycobacterium tuberculosis
“ANOTHER LOOK”
Marc Imhotep Cray, M.D. Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2015
Caseating granuloma, microscopic
Caseating granuloma. Central necrosis
(pinkish region in upper left) with
multinucleated Langhans giant cell (arrow). Important Note: Virulent strains of tubercle bacilli
form microscopic “serpentine cords” in which
acid-fast bacilli are arranged in parallel chains
Cord formation is correlated with virulence
A “cord factor” (trehalose-6,6′-dimycolate) has
been extracted from virulent bacilli with
petroleum ether
o It inhibits migration of leukocytes, causes
chronic granulomas, and can serve as an
immunologic “adjuvant”
Cord factor is known to be most important
in triggering granulomatous reaction to
wall off and contain the infection
Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th
Step 1 2015
Ed, 2016, Pg.312
Marc Imhotep Cray, M.D. Rubin R and Strayer DS Eds. Rubin’s Pathology:
Clinicopathologic Foundations of Medicine, 7th Ed. , 2015
Secondary tuberculosis, gross
These scattered tan granulomas
are present mostly in upper lung
fields
Granulomatous lung disease
grossly appears as irregularly
sized, rounded nodules
Larger nodules may have central
caseous necrosis that includes
elements of liquefactive and
coagulative necrosis
This upper lobe pattern of
involvement is most
characteristic of secondary
(reactivation) tuberculosis,
typically seen in adults
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
PA chest radiograph on left is characteristic of primary tuberculosis with a subpleural granuloma (up arrow ) and marked hilar
lymphadenopathy (down arrow ). These two findings together constitute Ghon complex.
PA chest
Marc radiograph
Imhotep Cray, M.D.on the right reveals a miliary pattern in all lung fields. Note the stippled appearance throughout 35
Secondary tuberculosis, CT image
Axial view of upper chest
shows cavitary lesions (arrow)
typical of reactivation-
reinfection pattern of
secondary tuberculosis most
common in adults
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
PA chest radiograph on left reveals upper lobe granulomatous disease marked by irregular reticular and
nodular densities and upper lobe cavitation ( *) caused by central caseous necrosis
PA chest radiograph on right reveals extensive granulomatous disease of both lungs. Focal brighter
Marc Imhotep Cray, M.D. 37
calcifications are typical of healed tuberculosis
Pott disease from tuberculosis
infection of spine resulting in a severe
kyphoscoliosis
Note to continue skin ulceration on
right and a severe deformity caused by
this disease
FIGURE 54-5
Marc Imhotep Cray, M.D. Usatine RP etal. (Eds.) The Color Atlas of Family Medicine. 2013
Scrofula of neck caused by M. tuberculosis in a child. Scrofula of the neck caused by M. tuberculosis in an
Chronic drainage and fistulous tract formation are adult who did not complete his tuberculosis treatment. The
commonly associated with this entity, and therapy is same long duration of therapy leads to challenges for adherence, and
as for pulmonary tuberculosis drug-resistant tuberculosis commonly results.
LTBI can be treated for 9 months with isoniazid (INH) monotherapy or with
12 once-weekly doses of INH (900 mg) and rifapentine (900 mg)
Marc Imhotep Cray, M.D. Modified from: Jones CH. Mind Maps for Medical Students, 2015
Mycobacterium
(Leprosy and Tuberculosis-HIV Coinfection)
Lepromatous leprosy with leonine facies in a woman. Note loss
LEPROSY of eyebrows called madarosis and prominent ear involvement.
Patient Story
A women presents with significant
changes to her face. A slit-skin
examination is performed on the
ear lobe of the woman and many
acid-fast bacilli, characteristic of
Mycobacterium leprae, are found.
The woman is started on the WHO-
standard multidrug using rifampin,
clofazimine, and dapsone.
Figure 6-15
Usatine RP etal. (Eds.) The Color Atlas of Internal Medicine. 2015
At one time, persons with leprosy were called “lepers” and isolated to
leper colonies because disease was disfiguring and communities were
afraid that it was highly contagious
(Figure 6-16)
Usatine RP etal. (Eds.) The Color Atlas of Internal Medicine. 2015
Differential diagnosis
Superficial mycoses, vitiligo, and cutaneous filariasis all cause changes
in pigmentation similar to leprosy
Infiltrated lesions that resemble leprosy include those of leishmaniasis,
psoriasis, and sarcoidosis
Marc Imhotep Cray, M.D.
Management
Early diagnosis and multidrug therapy are essential to reducing disease
burden of leprosy worldwide
WHO has supplied multidrug therapy free of cost to leprosy patients in all
endemic countries
Marc Imhotep Cray, M.D. Usatine RP etal. (Eds.) The Color Atlas of Family Medicine.
2013
Young Ethiopian girl with HIV
since birth who has neck
swelling secondary to
tuberculosis
She also has tinea capitis
HIV is a highly stigmatizing
disease in most cultures, and
clinicians can play an
important role in mitigating
community stigma by
modeling compassionate care Figure 7-31
Usatine RP etal. (Eds.) The Color Atlas of Family Medicine. 2013
Patients with low CD4 cell counts (below 200 cells/μL) commonly have
poorly reactive skin tests for TB need a careful history of exposures,
review of symptoms, and monitoring of chest x-ray for evidence of active
disease, with repeat TB screening when CD4 cell count rises above 200
cells/μL
If CD4 count is greater than 50, ART should start within 8 to 12 weeks of TB
therapy
If IRIS does occur, both ART and TB treatment should be continued while
managing the IRIS
Textbooks:
Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010
Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York: McGraw-Hill, 2016
Marc Imhotep Cray, M.D. 74