Module 5, slides 12-14 display a granulomatous disease: Tuberculosis

 

 

 

 

 

Slide Description:

This granuloma exhibits caseous necrosis, referred to as a “soft” tubercle, as a consequence of tuberculosis, in a slide prepared by H&E staining. The cells stain eosinophilically.

 

IMDEPSAASIAC:

Identify:

Lung caseous necrosis granuloma

 

Morphology:

In this close-up microscopic view, the lung tissue is stained with H&E, note the necrotized area (for a zoomed-out view, see ROBBINS, pg 57, Figure 2-23). On the periphery of the necrotized area, activated epithelioid macrophages, multiple giant cells: 40-50microns in diameter, and peripheral accumulation of lymphocytes are normally seen.

 

Disease:

Granulomatous tuberculosis with caseating necrosis.

(Definition: Granuloma is a tumor like compact nodule composed of epithelioid cells with/without giant cells, which comes about from cell mediated or delayed-type (Type IV) hypersensitivity).

 

Etiology (main):

Infection of the Mycobacterium tuberculosis bacteria.

 

Pathogenic mechanism:

Mechanism is not really clear, however, it is postulated that upon ingestion of the Mycobacterium tuberculosis bacteria, the mycolic acid produced by the bacilli may be responsible for inducing the necrosis, which the body responds to by production of a granuloma to "contain" the pathogen. This is a cell mediated process (Type IV).

 

Mycobacterium tuberculosis is an obligate aerobe. For this reason, in the classic case of tuberculosis, the bacilli complexes are always found in the well-aerated upper lobes of the lungs. The bacterium is a facultative intracellular parasite, usually of macrophages, and has a slow generation time, 15-20 hours, a physiological characteristic that may contribute to its virulence. (This is why growing culture in lab can take weeks to months!)

 

Also: "Mycobactium tuberculosis is not classified as either Gram-positive or Gram-negative because it does not have the chemical characteristics of either, although the bacteria DO contain peptidoglycan (murein) in their cell wall. If a Gram stain is performed on M.TB., it stains very weakly Gram-positive or not at all (referred to as "ghosts"). Mycobacterium species are classified as acid-fast bacteria due to their impermeability by certain dyes and stains. Despite this, once stained, acid-fast bacteria will retain dyes when heated and treated with acidified organic compounds. One acid-fast staining method for Mycobacterium tuberculosis is the Ziehl-Neelsen stain. When this method is used, the M.TB. smear is fixed, stained with carbol-fuchsin (a pink dye), and decolorized with acid-alcohol. The smear is counterstained with methylene-blue or certain other dyes. Acid-fast bacilli appear pink in a contrasting background. In order to detect Mycobacterium tuberculosis in a sputum sample, in excess of 10,000 organisms per ml of sputum are needed to visualize the bacilli with a 100X microscope objective. One acid-fast bacillus/slide is regarded as "suspicious" of an M.TB. infection."

INFO FROM: http://textbookofbacteriology.net/tuberculosis.html

 

 

 

Structural changes (specific, gross, and micro):

Macroscopicially, caseous necrosis have a "cheesy-milky" appearance. Microscopically, with H&E staining, the necrotized area takes an eosinophillic staining with the periphery contianing activated epithelioid macrophages, multiple giant cells, and peripheral accumulation of lymphocytes are normally seen. (Recall that TB does NOT Gram stain-since it is an Acid-fast bacteria)

 

Color retouched EM images of M. tuberculosis bacteria:

 

 

Are there any other sites of involvement in the body?

With dessimenation from the lung due to a non-caseating infection, the bacilli can travel systemically and affect the heart (constrictive pericarditis), CNS (chronic meningitis, tuberculoma of brain tissue), liver and spleen (hepatosplenomegaly); endometrium (female infertility); and the adrenal gland (Addison's Disease/primary medullary insufficiency). Additionaly, the gastrointestinal tract (ileocecal ulcers, obstruction, peritonitis), bones & joints, and kidneys (hematuria, pyuria) can also be affected.

 

Are there any other diseases where similar changes can be seen?

Caseating necrosis is a characteristic description reserved for tuberculosis. Recall that caseous necrosis is a combination of coagulative and liquefactive necroses.

 

Signs / Symptoms:

Fever; cough with bloody sputum (hemoptesis); chest pain with spread of infection to pleura; night sweats.

 

NOTE: classical histological response take about 3 weeks to develop, hence is a Type IV hypersensitivity reaction.

 

Investigations (confirmation / gauge extent):

CXR, sputum analysis should reveal presence of bacilli, fine needle biopsy.

 

Advanced tuberculosis CXR

Note: location is mainly in the upper inferior upper lobes

 

 

Are there any other diseases you have studied where such tests can be positive?

Need to rule out other non-bacterial factors for radiological changes, ie-bronchogenic lung cancer (refer to Module VI). Usually, sputum analysis will reveal TB, if this is the causitive agent.

 

Course of disease progress (complications, monitoring, outcome):

Primary tuberculosis results from primary exposure to TB and can progress into Secondary tuberculosis via reactivation (if all bacilli not destroyed/irradicated from a previous infection become "reactivated" when immune suppression occurs) or reinfection (another exogenous TB exposure). Reinfection will elicit a more rapid development of caseation (few days) since memory T-cells have been generated from the primary infection. Cavity formation ensues when necrotized area is coughed up in sputum leaving an empty cavity. Additionally, Secondary TB can progress into pneumonia, Bronchiectasis, and Miliary TB.

 

Primary lesion in the lung, refered to as Ghon's lesion takes about 3 weeks to develop. A primary complex (Ghon's lesion + lymphatics + lymph nodes) in most cases heal via fibrosis and calcification, however, this is where bacteria can also remain dormant for later reactivation. Progression of a primary complex results in Miliary TB.

 

Lab Questions:

1. Why should we try to distinguish a caseating from a noncaseating granuloma?

A caseating granuloma could indicate a TB infection; noncaseating granulomas could be due to sarcoidosis, a multisystemic disease of unknown etiology, characterized by noncaseating granulomas in many tissues and organs.

 

Granuloma formation: epithelioid cells, giant cells, macrophages, lymphocytes, and enclosed by fibroblasts.

 

Also see: http://www-medlib.med.utah.edu/WebPath/INFLHTML/INFL052.html

 

2. How differently does a patient with AIDS respond to tuberculosis infection?

 

In countries with high a incidence of AIDS, it is the most important risk factor for TB. In AIDS, there is no T-cell mediated response due to the attack on CD4 helper T-cells that are the integral part of granulomas. The TB becomes widespread but with no granulomas and extensive noncaseating necrosis.

 

3. What is the basis of difference between primary and secondary tuberculosis?

 

Primary tuberculosis is a newly infected case with no hypersensitivity reaction, therefore, patient has been previously unexposed, and has been unsensitized.

 

Secondary tuberculosis (also called postprimary) is a reinfected case with a hypersensitivity reaction. This occurs in a previously sensitized host, usually in the form of reactivation of dormant primary lesions when a host’s resistance is weakened. Secondary tuberculosis of the lung is usually classically localized to the apex of one or both upper lobes.

 

4. What is the relationship between the terms secondary, reinfection, and reactivation tuberculosis? Which term would be best applicable in a given patient?

 

Secondary TB can either be due to reinfection or reactivation. In reinfection, another external infection is introduced for a second time. In reactivation, a dormant bacteria from a previous infection becomes active for a second time. This is shown in the Hypersensitivity Type IV response DTH Tuberculin skin test. When positive showing an induration (hard swelling), it shows that the patient has had a previous TB exposure.

 

5. How does pulmonary tuberculosis spread in the body and what sites can it reach?

 

Pulmonary TB establishes itself as Ghon’s lesion (page 487 in Robbins) which can then take two paths: (1) entering lymphatics to hilar lymph nodes which drain to the heart; now in the bloodstream, the pulmonary TB can disseminate to other organs. (2) Ghon’s lesion can invade the rest of the lung causing a caseating granuloma which then ruptures into the blood stream, again, allowing it to disseminate to other organs.

 

 

 

Vignette

A 55-year old asian male presents with a productive cough x1 week. He is a recent (14 mos ago) immigrant from the Philippines. He states that he has been coughing more and more and came to you since he now has blood in his sputum, which he recalls having had the same symptoms as a child and states that his mother brought him to the doctor and was not allowed to be around other children or members of his own family for 3 mos. He remembers being given medication that did not taste good but doesn't know what disease he had. He has been under heavy stress since he hasn't been able to find a job and his wife and son are both quite ill. He also has a fever and has lost several pounds within this past week. He complains of frequent night sweats and states that it just hurts to breathe. What can you do for this patient?

 

 

 

 

 

 

Slide Description:

This is a slide of a gross morphology of the lung, with Millet sized yellow-white lesions.

 

IMDEPSAASIAC:

Identify:

Gross, unstained section of the lung with Millet seed appearance (yellow-white lesions).

 

Morphology:

Presence of the yellow-white Millet sized lesions with the openings of bronchioles along side (black holes).

 

Disease:

Granulomatous Tuberculosis of the lung

 

Etiology (main):

See slide 12 alphabet soup

 

Pathogenic mechanism:

See slide 12 alphabet soup

 

Structural changes (specific, gross, and micro):

See slide 12 alphabet soup

 

Are there any other sites of involvement in the body?

See slide 12 alphabet soup

 

Are there any other diseases where similar changes can be seen?

See slide 12 alphabet soup

 

Signs / Symptoms:

See slide 12 alphabet soup

 

Investigations (confirmation / gauge extent):

In this case...autopsy!!!

See slide 12 alphabet soup

 

Are there any other diseases you have studied where such tests can be positive?

See slide 12 alphabet soup

 

Course of disease progress (complications, monitoring, outcome):

See slide 12 alphabet soup

 

Lab Questions:

(No lab questions associated with this slide)

 

Vignette

See slide 12 alphabet soup

 

 

 

 

 

 

Slide Description:

This is a slide of the gross morphology of the kidney with Millet sized yellow-white lesions.

 

IMDEPSAASIAC:

Identify:

Gross bisected kidney showing the cortex and medulla (no clear division) with Millet sized yellow-white lesions throughout the entire kidney. Pyramids and calyces draining into the renal pelvis also seen.

 

Contrast this with a normal bisected kidney:

 

Morphology:

Presence of Millet sized yellow-white lesions in the renal cortex and medulla: indicative of disseminated tuberculosis

 

Disease:

Miliary tuberculosis affecting the kidney

 

Etiology (main):

See slide 12 alphabet soup

 

Pathogenic mechanism:

See slide 12 alphabet soup

 

Structural changes (specific, gross, and micro):

See slide 12 alphabet soup

 

Are there any other sites of involvement in the body?

See slide 12 alphabet soup

 

Are there any other diseases where similar changes can be seen?

See slide 12 alphabet soup

 

Signs / Symptoms:

See slide 12 alphabet soup

 

Investigations (confirmation / gauge extent):

With disseminated TB, CXR usually primary indication to look elsewhere and can perform a kidney biopsy, in addition: See slide 12 alphabet soup

 

Are there any other diseases you have studied where such tests can be positive?

See slide 12 alphabet soup

 

Course of disease progress (complications, monitoring, outcome):

See slide 12 alphabet soup

 

Lab Questions:

 

1)Differentiate disseminated T.B. and miliary T.B.

 

Disseminated TB is a diffuse spread of tuberculosis. Miliary TB is a description of the miliary-type nodules. Miliary TB can be either localized or disseminated.

 

 

2)Why is it called miliary tuberculosis?

 

Miliary TB contains nodules that are reminiscent of millet seeds.

 

3)What other infection can produce similar histologic and radiologic appearances?

 

Histoplasma will look similar to TB on an X-ray—i.e. opaque nodules peppering the lungs.

 

 

Vignette

A 36 year old caucasian known HIV+ female presents to you with a productive cough with hemoptesis and weight loss. She is on a cocktail of antiviral agents and has a CD4 count of 300 (this is low!). She is also a known prostitute and IV-drug user. She also complains of hematuria and dysuria. She wants you to make her "all better" since she is concerned about being able to pay back some debts she has incurred to pay for "her medications". Where do you begin??? What tests should you order? What do you suspect makes up her entire medical history? (Just wanted to throw this out to y'all to get your hamsters running...he he)