Primary Tuberculosis

Primary TB (also called the primary infection stage) follows the patient’s first exposure to the TB pathogen, Mycobacterium tuberculosis. Primary TB begins when the inhaled bacilli implant in the alveoli. As the bacilli multiply over a 3- to 4-week period, the initial response of the lungs is an inflammatory reaction that is similar to any acute pneumonia (see Figure 15-1). In other words, a large influx of polymorphonuclear leukocytes and macrophages moves into the infected area to engulf—but not fully kill—the bacilli. This action also causes the pulmonary capillaries to dilate, the interstitium to fill with fluid, and the alveolar epithelium to swell from the edema fluid. Eventually the alveoli become consolidated (i.e., filled with fluid, polymorphonuclear leukocytes, and macrophages). Clinically, this phase of TB coincides with a positive tuberculin reaction—a positive purified protein derivative (PPD) skin test result (see discussion of diagnosis later in this chapter).

Unlike pneumonia, however, the lung tissue that surrounds the infected area slowly produces a protective cell wall called a tubercle, or granuloma. In essence, the tubercles work to encapsulate—that is, put in a nutshell-like structure—the TB bacilli (see Figure 17-1, A). Although the initial lung lesions may be difficult to identify on a chest radiograph, the lesions may be seen as small, sharply defined opacities. When detected on a chest radiograph, these initial lung lesions are called Ghon nodules. As the disease progresses, the combination of tubercles and the involvement of the lymph nodes in the hilar region is known as the Ghon complex.

Structurally, a tubercle consists of a central core containing TB bacilli. The central core also has enlarged macrophages with an outer wall composed of fibroblasts, lymphocytes, and neutrophils. A tubercle takes about 2 to 10 weeks to form. The function of the tubercle is to contain the TB bacilli, thus preventing the further spread of infectious TB organisms. Unfortunately, the central core of the tubercle has the potential to break down from time to time, especially in a patient with a depressed immune system. When this happens, the center of the tubercle fills with necrotic tissue that resembles dry cottage cheese. During this stage the tubercle is called a caseous lesion or caseous granuloma (see Figure 17-1, B). The patient is potentially contagious at this stage. In most cases, however, the TB bacilli are effectively contained within the tubercles.

Once the bacilli are controlled—either by the patient’s immunologic defense system or by antituberculous drugs—the healing process begins. Tissue fibrosis and calcification of the lung parenchyma slowly replace the tubercle. This tissue fibrosis and calcification cause lung tissue retraction and scarring. In some cases the calcification and fibrosis cause the bronchi to distort and dilate—that is, to develop bronchiectasis.

Finally, when the bacilli are isolated within tubercles and immunity develops, the TB bacilli may remain dormant for months, years, or life. Individuals with dormant TB (also called latent TB) do not feel sick or have any TB-related symptoms. They are still infected with TB but do not have clinically active TB. The only indication of a TB infection is a positive reaction to the tuberculin skin test, or TB blood test, and the finding of possible residual scarring on the chest radiograph. Individuals with dormant (latent) TB are not infectious and cannot spread the TB bacilli to others.

Postprimary Tuberculosis

Postprimary TB (also called reactivation TB, reinfection TB, or secondary TB) is a term used to describe the reactivation of TB months or even years after the initial infection has been controlled. Even though most patients with primary TB recover completely from a clinical standpoint, it is important to note that live tubercle bacilli can remain dormant for decades. A positive tuberculin reaction generally persists even after the primary infection stage has been controlled. At any time, TB may become reactivated, especially in patients with depressed immune systems. Most new TB cases are associated with the following risk factors:

If the TB infection is uncontrolled, cavitation of the caseous granuloma tubercle develops. The patient progressively experiences more severe symptoms, including violent cough episodes, greenish or bloody sputum, low-grade fever, anorexia, weight loss, extreme fatigue, night sweats, and chest pain. It is this gradual wasting of the body that provided the basis for the earlier name for TB—consumption. The patient is highly contagious at this stage. In severe cases a deep tubercle cavity may rupture and allow air and infected material to flow into the pleural space or the tracheobronchial tree. Pleural complications are common in TB (see Figure 17-1, C).

Disseminated Tuberculosis

Disseminated TB (also called extrapulmonary TB, miliary TB, and tuberculosis—disseminated) refers to infection from TB bacilli that escape from a tubercle and travel to sites other throughout the body by means of the bloodstream or lymphatic system. In general, the TB bacilli that gain entrance to the bloodstream usually gather and multiply in portions of the body that have a high tissue oxygen tension. The most common location is the apex of the lungs. Other oxygen-rich areas in the body include the regional lymph nodes, kidneys, long bones, genital tract, brain, and meninges.

Genital TB in males damages the prostate gland, epididymis, seminal vesicle, and testes; and in females, the fallopian tubes, ovaries, and uterus. The spine is a frequent site of TB infection, although the hip, knee, wrist, and elbow can also be involved. Tubercular meningitis is caused by an active brain lesion seeding TB bacilli into the meninges. Over time, the infection may cause mental deterioration, permanent retardation, blindness, and deafness. When a large number of bacilli are freed into the bloodstream, the result can be the presence of numerous small tubercles—about the size of a pinhead—scattered throughout the body. This condition is commonly called miliary TB.

TB is primarily a chronic restrictive pulmonary disorder. The major pathologic or structural changes of the lungs associated with TB (mainly postprimary TB) are as follows:

Mantoux Tuberculin Skin Test

The most widely used tuberculin test is the Mantoux test, which consists of an intradermal injection of a small amount of a PPD of the tuberculin bacillus (Figure 17-2). The skin is then observed for induration (a wheal) after 48 hours and 72 hours, with results interpreted as follows:

It should be stressed, however, that a positive reaction does not necessarily confirm that a patient has active TB, only that the patient has been exposed to the bacillus and has developed cell-mediated immunity to it.

Acid-Fast Staining

Because the M. tuberculosis organism has an unusual, waxy coating on the cell surface, which makes the cells impervious to staining, an acid-fast bacteria (AFB) test (also called a sputum smear) is performed instead. Several variations of the acid-fast stain are currently in use. The frequently used Ziehl-Neelsen stain reveals bright red acid-fast bacilli against a blue background (Figure 17-3, A). Another popular technique involves a fluorescent acid-fast stain that reveals luminescent yellow-green bacilli against a dark brown background. The fluorescent acid-fast stain is becoming the acid-fast test of choice because it is easier to read and provides a striking contrast (Figure 17-3, B).

Sputum Culture

Because a variety of nontuberculous strains of Mycobacterium can show up on an AFB smear, a sputum culture is often necessary to differentiate M. tuberculosis from other acid-fast organisms. For example, common nontuberculous acid-fast mycobacteria associated with chronic obstructive pulmonary disease (COPD) are Mycobacterium avium and Mycobacterium kansasii. Sputum cultures can also identify drug-resistant bacilli and their sensitivity to antibiotic therapy. M. tuberculosis grows very slowly. It takes up to 6 weeks for colonies to appear in culture. When the TB bacterium was first studied, it was given the misleading prefix Myco, which gave the impression that the TB pathogen was fungal in nature. This was because the bacterium growing in agars appeared as colonies, similar to fugal colonies (Figure 17-4). They are unrelated; TB is caused by a bacterium and not a fungus.

QuantiFERON-TB Gold Test

In 2005 the U.S. Food and Drug Administration (FDA) approved the QFT-G test. The QFT-G test is a whole-blood test used for diagnosing M. tuberculosis infection, including latent TB infection. Samples of the patient’s blood are mixed with antigens (substances that can generate an immune response) and controls. The QFT-G test contains synthetic antigens that represent two M. tuberculosis proteins (ESAT-6 and CFP-10). The mixture is then allowed to incubate for 16 to 24 hours. After this period the mixture is measured for the presence of interferon-gamma (IFN-gamma). In patients infected with M. tuberculosis, the white blood cells will release IFN-gamma when in contact with the TB antigens. An elevated IFN-gamma level is diagnostic of TB. Additional clinical evaluations, such as AFB stain of the sputum smear and chest radiograph, are recommended to further support a positive QFT-G finding.

OVERVIEW of the Cardiopulmonary Clinical Manifestations Associated with Tuberculosis

The following clinical manifestations result from the pathophysiologic mechanisms caused (or activated) by Alveolar Consolidation (see Figure 9-9) and Increased Alveolar-Capillary Membrane Thickness (see Figure 9-10)—the major anatomic alterations of the lungs associated with tuberculosis (see Figure 17-1).

CLINICAL DATA OBTAINED AT THE PATIENT’S BEDSIDE

The Physical Examination

Vital Signs

Increased Respiratory Rate (Tachypnea)

Several pathophysiologic mechanisms operating simultaneously may lead to an increased ventilatory rate:

• Stimulation of peripheral chemoreceptors

• Decreased lung compliance–increased ventilatory rate relationship

• Pain, anxiety, fever

Increased Heart Rate (Pulse) and Blood Pressure

Chest Pain, Decreased Chest Expansion

Cyanosis

Digital Clubbing

Peripheral Edema and Venous Distention

Because polycythemia and cor pulmonale are associated with severe tuberculosis (TB), the following may be seen:

• Distended neck veins

• Pitting edema

• Enlarged and tender liver

Cough, Sputum Production, and Hemoptysis

Chest Assessment Findings

• Increased tactile and vocal fremitus

• Dull percussion note

• Bronchial breath sounds

• Crackles, rhonchi, and wheezing

• Pleural friction rub (if process extends to pleural surface)

• Whispered pectoriloquy

CLINICAL DATA OBTAINED FROM LABORATORY TESTS AND SPECIAL PROCEDURES

Pulmonary Function Test Findings (Severe and Extensive Cases)* (Restrictive Lung Pathology)

FORCED EXPIRATORY FLOW RATE FINDINGS

FVC	FEVT	FEV1/FVC ratio	FEF25%-75%
↓	N or ↓	N or ↑	N or ↓
FEF50%	FEF200-1200	PEFR	MVV
N or ↓	N or ↓	N or ↓	N or ↓

LUNG VOLUME AND CAPACITY FINDINGS

VT	IRV	ERV	RV
N or ↓	↓	↓	↓
VC	IC	FRC	TLC	RV/TLC ratio
↓	↓	↓	↓	N

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^*Pulmonary function test (PFT) findings are usually normal in most cases of TB.

Arterial Blood Gases

MODERATE TUBERCULOSIS

Acute Alveolar Hyperventilation with Hypoxemia (Acute Respiratory Alkalosis)

pH	Paco2		Pao2
↑	↓	↓ (slightly)	↓

EXTENSIVE TUBERCULOSIS WITH PULMONARY FIBROSIS

Chronic Ventilatory Failure with Hypoxemia (Compensated Respiratory Acidosis)

pH	Paco2		Pao2
N	↑	↑ (significantly)	↓

ACUTE VENTILATORY CHANGES SUPERIMPOSED ON CHRONIC VENTILATORY FAILURE

Because acute ventilatory changes are frequently seen in patients with chronic ventilatory failure, the respiratory care practitioner must be familiar with and alert for the following:

• Acute alveolar hyperventilation superimposed on chronic ventilatory failure, and/or

• Acute ventilatory failure (acute hypoventilation) superimposed on chronic ventilatory failure

Oxygenation Indices*

Moderate to Severe Stages

	Do2†		C(a-)o2	O2ER
↑	↓	N	N	↑	↓

^†The Do₂ may be normal in patients who have compensated to the decreased oxygenation status with (1) an increased cardiac output, (2) an increased hemoglobin level, or (3) a combination of both. When the Do₂ is normal, the O₂ER is usually normal.

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^*C(a-)O₂, Arterial-venous oxygen difference; DO₂, total oxygen delivery; O₂ER, oxygen extraction ratio; , pulmonary shunt fraction; , mixed venous oxygen saturation; , oxygen consumption.

Hemodynamic Indices‡

Severe Tuberculosis

CVP	RAP		PCWP	CO	SV
↑	↑	↑	N	N	N
SVI	CI	RVSWI	LVSWI	PVR	SVR
N	N	↑	N	↑	N

---

^‡CO, Cardiac output; CVP, central venous pressure; LVSWI, left ventricular stroke work index; , mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RAP, right atrial pressure; RVSWI, right ventricular stroke work index; SV, stroke volume; SVI, stroke volume index; SVR, systemic vascular resistance.

ABNORMAL LABORATORY TEST AND PROCEDURE RESULTS

• Positive tuberculosis skin test (PPD)

• Positive sputum acid-fast bacillus (AFB) stain test

• Positive sputum culture

RADIOLOGIC FINDINGS

Chest Radiograph

• Increased opacity

• Ghon nodule

• Ghon complex

• Cavity formation

• Cavity lesion containing an air-fluid level (see Figure 16-2)

• Pleural effusion

• Calcification and fibrosis

• Retraction of lung segments or lobe

• Right ventricular enlargement

Chest radiography is most valuable in the diagnosis of pulmonary TB. During the initial primary infection stage, peripheral pneumonic infiltrates (Ghon nodules) can be identified. As the disease progresses, the combination of tubercles and involvement of the lymph nodes in the hilar region (the Ghon complex) can be seen. In severe cases, cavity formation and pleural effusion are seen (Figure 17-5). Healed lesions appear fibrotic or calcified. Retraction of the healed lesions or segments also is revealed on chest radiographs. In patients with postprimary TB of the lungs, lesions involving the apical and posterior segments of the upper lobes are often seen. In disseminated miliary tuberculosis, the lungs may show myriad 2- to 3-mm granulomatous foci. The radiographic result is widespread fine nodules, which are uniformly distributed and equal in size (Figure 17-6). Finally, because right-sided heart failure (cor pulmonale) may develop as a secondary problem during the advanced stages of TB, an enlarged heart may be seen on the chest radiograph.

Pharmacologic Agents Used to Treat Tuberculosis

The standard pharmacologic agents used to treat M. tuberculosis consist of two to four drugs for 6 to 9 months. Examples of these protocols are as follows:

Isoniazid (INH) and rifampin (Rifadin) are first-line agents prescribed for the entire 9 months. Isoniazid is considered to be the most effective first-line antituberculosis agent. Rifampin is bactericidal and is most commonly used with isoniazid. Although patients with TB usually are not contagious after a few weeks of treatment, a full course of treatment is necessary to kill all the bacteria. The prophylactic use of isoniazid is often prescribed as a daily dose for 1 year in individuals who have been exposed to the TB bacilli or who demonstrate a positive tuberculin reaction (even when the acid-fast sputum stain is negative).

When the TB bacterium is resistant to one or more of these agents, at least three or more antibiotics must be added to the treatment regimen and the duration should be extended. A major problem with TB therapy is noncompliance on the part of the patient to take the TB medication as prescribed. Even under the best circumstances, it is very difficult to maintain a regimen of multiple TB antibiotics on a daily basis for months. Unfortunately, most TB patients are not living under the best circumstances. In addition, failure to adhere to an antibiotic regimen often leads to antibiotic resistance in the slow-growing microorganism. In fact, many M. tuberculosis isolates are now found to be multiple drug–resistant TB (MDRTB).

In response to the problem of noncompliance, it is recommended that all patients with TB be treated by directly observed therapy (DOT)—that is, the ingestion of medication is directly observed by a responsible individual. In communities where DOT has been used, the rate of drug-resistant TB and the rate of TB relapse have been shown to decrease.

A new strain of drug-resistant M. tuberculosis was identified in Africa in 2006. It is especially lethal for HIV-infected individuals and has been named extensively drug-resistant TB (XDRTB).

Oxygen therapy is used to treat hypoxemia, decrease the work of breathing, and decrease myocardial work. Because of the hypoxemia associated with TB, supplemental oxygen may be required. The hypoxemia that develops in patients with lung abscess is usually caused by pulmonary capillary shunting. Hypoxemia caused by capillary shunting is often refractory to oxygen therapy. In addition, when the patient demonstrates chronic ventilatory failure during the advanced stages of TB, caution must be taken not to overoxygenate the patient (see Oxygen Therapy Protocol, Protocol 9-1).

Respiratory Assessment and Plan

Discussion

Two primary clinical scenarios were activated in this case. First, the Alveolar Consolidation (see Figure 9-9) identified on the chest x-ray film reflected the patient’s challenged immune response. This was further manifested by the objective data noted at the patient’s bedside—fever, dull percussion notes, and increased heart rate, blood pressure, and respiratory rate. In addition, the alveolar consolidation undoubtedly contributed to the patient’s pulmonary shunting and mild hypoxemia (see Figure 9-9).

Secondly, clinical manifestations associated with Excessive Bronchial Secretions (see Figure 9-12) also were present in this patient: daily cough, yellow sputum production, crackles, and rhonchi. His oxygen desaturation was mild (Spo₂ = 90%), and a room air ABG and subsequent oxygen titration (presumably with low-flow oxygen by nasal cannula) were appropriate.

As expected, the patient produced sputum containing acid-fast organisms. The attending physician prescribed isoniazid, rifampin, and streptomycin for 2 months, followed by an outpatient course of isoniazid and rifampin for 4 months. The patient also was instructed regarding several different Bronchopulmonary Hygiene Therapy (see Protocol 9-2) to perform at home. The patient did well through 1 year of follow-up.