Respiratory System Pathology - Tuberculosis
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| Epidemiology of Tuberculosis: | Conditions of poverty, crowding, in old people and disease states such as
a. Diabetes mellitus
b. Hodgkin lymphoma
c. Silicosis
d. Immunosuppression
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| What is the single most important risk factor for tuberculosis? | HIV, in areas where HIV is prevalent
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| Which bacterium is responsible for most cases of tuberculosis? | M. tuberculosis hominis
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| The reservoir of infection typically is found in: | persons with active pulmonary disease
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| Most infections are acquired by: | Airborne droplets
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| Which bacterium causes intestinal tuberculosis? | Mycobacterium bovis
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| How is Mycobacterium bovis contracted? | By drinking milk contaminated with the microorganism
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| In developed countries today, intestinal tuberculosis is more often a complication of | Advanced pulmonary secondary tuberculosis, resulting from swallowing of coughed up infective material
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| The microorganisms which cause tuberculosis are found where in the body? | Trapped in mucosal lymphoid aggregates of the small and large bowel
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| What happens to the bowels after infection? | Undergo inflammatory enlargement with ulceration of the overlying mucosa, particularly in the ileum
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| Pathogenesis of Tuberculosis: In the first 3 weeks; | Mycobacteria gains entry into the macrophages
Inhibit normal microbicidal responses by preventing the fusion of the lysosomes with the phagocytes
Unchecked mycobacterial proliferation
Bacillary proliferation within the macrophages - bacteremia
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| Symptoms of tuberculosis patients in the first 3 weeks: | Despite the bacteremia, most persons at this stage are
symptomatic or have a mild flu-like illness
People with polymorphisms of the NRAMP1 gene, the
disease may progress from this point without development
of an effective immune response
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| Pathogenesis of Tuberculosis 3 weeks after exposure: | Development of cell-mediated immunity
Mycobacterial antigens reach the draining lymph nodes and are presented to CD4 T cells by macrophages which secret IL-12
Activated macrophages release a variety of mediators and upregulate expression of genes
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| IL-12 generates: | TH1 subtype of CD4+ T cells that secret Gamma- IFN which activates macrophages
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| Activated macrophages release a variety of mediators. What are they? | 1) TNF, which is responsible for recruitment of monocytes,
which activate and differentiate into epithelioid histiocytes
2) Expression of the inducible nitric oxide synthase (iNOS)
gene - bactericidal
3) Generation of ROS- bactericidal
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| Infection with M. tuberculosis typically leads to the development of delayed hypersensitivity, which can be detected by: | the tuberculin (Mantoux) test
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| About 2 to 4 weeks after the infection has begun, intracutaneous injection of 0.1 mL of PPD induces | a visible and palpable induration (at least 5 mm in diameter) that peaks in 48 to 72 hours
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| What does a positive tuberculin skin test result imply? | 1) Cell-mediated hypersensitivity to tubercular antigens
2) It does not differentiate between infection and disease
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| What does a false-negative tuberculin skin test result imply? | 1) Certain viral infections,
2) Sarcoidosis
3) Immunosuppression
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| What does a false-positive tuberculin skin test result imply? | May result from infection by atypical mycobacteria
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| About 80% of the population in certain Asian and African countries is | tuberculin positive
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| Only a small fraction of those who contract an infection | Develop active disease
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| Primary tuberculosis is: | the form of disease that develops in previously unexposed and unsensitized patients
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| The inhaled bacilli implant where in the lung? | Alveoli of the of the lower part of the upper lobe or the upper part of the lower lobe,usually close to the pleura
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| 2-3 weeks after exposure , a 1-to 1.5- cm lesion develops called: | Ghon focus composed of granulomas
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| How do Tubercle bacilli spread throughout the body? | They travel in lymph drainage to the regional nodes, forming granuloma in the lymph nodes
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| The combination of Ghon focus and nodal involvement is called | Ghon focus
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| Development of cell-mediated immunity controls the infection in how many patients? | 95%
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| The Ghon complex undergoes: | Progressive fibrosis, followed by radiologically detectable
calcification
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| The radiologically detectable calcification which follows fibrosis of the Ghon complex is called: | Ranke Complex
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| What are the major consequences of primary TB? | 1) It induces hypersensitivity and increased resistance;
2) The foci of scarring may harbor viable bacilli for years, perhaps for life- reactivation
3) Uncommonly, it may lead to progressive primary TB in patients who are immunocompromised
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| Which groups of people are most susceptible to progressive primary tuberculosis? | 1) Malnourished children
2) The elderly
3) HIV+ patients with an advanced degree of immunosupression
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| What effect does immunosupression have on the cells of the body? | Immunosuppression results in an inability to mount a CD4+ T cell-mediated immunologic reaction that would contain the primary focus
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| How would a person be considered to have an advanced degree of immunosupression? | They would have a CD4+ cell count of below 200 cells/μL
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| Why is there an absence of caseating granulomas in PROGRESSIVE primary TB? | Due to the lack of a tissue hypersensitivity reaction
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| Progressive primary TB is also known as: | Nonreactive TB
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| Can patients with primary tuberculosis transmit the disease to others? | Not usually
If their immune defenses are decreased, the disease may reactivate and become communicable
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| Secondary tuberculosis arises in patients who: | are previously sensitized
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| When can secondary TB occur? | 1) May follow shortly after primary tuberculosis
2) From reactivation of dormant primary TB decades after initial infection
3) May result from exogenous reinfection
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| How many patients with primary TB develop secondary TB? | 5%
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| Secondary TB is localized to what part of the lung? | The apices of upper lobes
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| What reaction does the bacilli have to the pre-existing hypersensitivity reaction? | Excites marked tissue response to wall off the focus
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| Are the regional lymph nodes more involved in primary or secondary TB? | Primary
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| What occurs specifically in secondary TB? | Cavitation, leading to erosion into and dissemination along airways
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| This cavitation causes the patient to produce: | Sputum-containing bacilli
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| Secondary tuberculosis should always be an important consideration in what patients? | HIV-positive patients who present with pulmonary disease
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| HIV patients with CD4+ counts greater than 300 cells/mm present with what clinical manifestation? | "Usual" secondary tuberculosis
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| HIV patients with CD4+ counts below 200 cells/mm present with what clinical manifestation? | Progressive primary TB (lower and middle lobe consolidation, and, no granulomas, or cavitations)
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| General Morphology of secondary TB: | 1) Initial lesion is a small focus, less than 2 cm of the apical pleura
2) Hemoptysis
3) Healing distorts the pulmonary architecture
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| Why does hemoptysis result in secondary TB? | Erosion of blood vessels
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| If the patient's immune defenses are weakened, how can infection spread? | By direct expansion by dissemination through lymphatic channels, or within the vascular system
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| When does Miliary pulmonary TB occur? | When organisms drain through lymphatics into the lymphatic ducts, then empty into the venous return to the heart and then into the pulmonary arteries
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| Morphology of miliary pulmonary TB: | Individual lesions,small, (2 mm) foci scattered through the lung parenchyma
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| When does systemic Miliary TB occur? | When the organisms disseminate through the systemic arterial system to almost every organ in the body
Most prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis
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| Tuberculous involvement of Vertebrae is called | Pott disease
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| In Isolated-organ tuberculosis, Paraspinal"cold" abscesses may track along the tissue planes and present as | Abdominal or pelvic masses
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| What is the most frequent form of extrapulmonary TB? | Lymphadenitis
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| Lymphadenitis occurs in: | The cervical region (scrofula)
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| Nodes in lymphadenitis: | Usually focal
In HIV patients: Multiple lymph nodes
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| Clinical features of lymphadenitis: | 1) Localized secondary tuberculosis may be asymptomatic
2) Symptoms are insidious in onset
3) Malaise, anorexia, weight loss, low grade fever, and night sweats
4) Increasing amounts mucopurulent sputum
5) Some degree of hemoptysis
6) pleuritic pain
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| Extrapulmonary manifestations of tuberculosis depend on the organ system involved for example; | 1) Tuberculous salpingitis may present as infertility,
2) Tuberculous meningitis with headache and neurologic deficits
3) Pott disease with back pain and paraplegia
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| The most common methodology for diagnosis of tuberculosis is | Demonstration of acid-fast organisms in sputum by acid-fast stains or by use of fluorescent auramine rhodamine
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| Conventional cultures for mycobacteria require up to | 10 weeks
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| Liquid media-based radiometric assays that detect mycobacterial metabolism require | 2 weeks
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| Which of the following is the standard for diagnosis? PCR or tissue culture? | Tissue culture because it can detect PCR negative cases
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