Question

A 24-year-old female was hospitalized with a 10 day history of increasing fever, one or two severe shaking chills daily, and progressive weakness. A chronic, nonproductive cough, which the patient attributed to moderately heavy smoking, probably had become more prominent during the two or three weeks preceding hospitalization. A diagnosis of primary thrombocytopenia had been established approximately one year previously, based on the presence of splenomegaly. Initial physical findings included a temperature of 102 F orally, a pulse of 110 per minute, respiration’s 24 per minute, and a blood pressure of 110/70 mm Hg. The patient appeared acutely ill, dyspneic, and extremely apprehensive. Conversation was difficult because of intermittent paroxysms of coughing, which produced no sputum. Several nontender lymph nodes, up to 1 cm in diameter, were readily palpable in each axilla. The spleen was enlarged, with a firm, nontender edge descending at least 6 cm below the left costal margin on deep inspiration. Initial lab data include a total leukocyte count of 20,800 per cubic mm, a differential of 42% neutrophils, 25% band forms, and 19% lymphocytes, and a hematocrit of 42; the platelet count was 2,120,000 per cubic mm. Chest X-ray revealed a moderately dense pulmonary infiltrate extending out from the right hilum into the right lower lobe. One of the two blood cultures obtained at the time of admission to the hospital and before any antimicrobial agents were administered yielded a slow growing gram-negative bacillary rod. It was identified as Pseudomonas aeruginosa. The attending physician elected to initiate antimicrobial therapy with penicillin G administered intravenously, 2.5 million units every six hours. Because of the febrile course, with spiking fever ranging as high as 105.6 F, evidence of an increase in the right lower lobe infiltrate on a subsequent X-ray, and the report of a gram-negative bacilli in one of the two blood cultures, penicillin therapy was discontinued and cephalothin therapy was initiated. A lung biopsy of the right lower lobe was performed and the specimen revealed many focal granulomas consisting largely of histiocytes and epithelioid cells, with some areas of necrosis and caseation. Innumerable acid-fast bacilli were present.

What is the microbe?

Answer 1

The organism is Mycobacterium tuberculosis.

• They appear aa small ,slightly curved, pink coloured bacilli on ziehl neelsen staining. They are called as acid fast bacilli as they resist decolorization. The mycolic acid layer present in the cell wall of the organism responsible for the acid fastness.
• Tuberculosis- risk factors in this case scenario , sex, moderate heavy smoking are some of the risk factors.
• Tuberculosis - pathology :

Host immune response

Macrophages present in the mycobacterial antigens to T helper cells and activate them T-helper 1, 2 subsets. Activation of T-helper cells leads to development of two host response: macrophage activating response and tissue damaging response.the balance between the two determines the outcome of the disease.

Macrophage activating response:

Interferon alpha activates the resting alveolar macrophages into activated macrophages which are able to kill and digest the tubercle bacilli.These activated macrophages aggregate around the centre of the lesion and forms granuloma called tubercle.

Tubercles are essential pathological findings in tuberculosis.There are two types of tubercles-soft and hard. Hard tubercles-tuberculous initially hard composed of central zone of epithelioid and giant cells and peripheral zone of lymphocytes and fibroblast. Soft tubercle - the central part of tubercles undergo caseous necrosis later.

Tissue damaging response :

In minority of cases, macrophage activating response is weak. The bacilli become more virulent, there is development of delayed hypersensitivity reaction which leads to lung tissue destruction.

Humoral immune response

T helper 2 cells derived cytokines such as interleukin 4, 5 activates B cells to produce antibodies. Mycobacteria, being obligate intracellular organism , humoral immunity plays a minor role.

Secondary tuberculosis :

• Secondary tuberculosis develops in previously sensitized individuals. The regional lymph node involvement is not significant and prominent as in primary tuberculosis.
• In secondary tuberculosis patients, the fate of infection is either healing or progression. Progressive pulmonary tuberculosis mainly occurs in elderly individuals and immunocompromised individuals. Complications of secondary TB are hemoptysis, bronchopleural fistula, aspergilloma.

Findings suggestive of tuberculosisin this case are x-ray shows infiltration of the right lower lobe of lungs, biopsy shows multiple granulomas with necrosis and caseation.