NIDUS LUNG TUBERCULOSIS. LUNG INFILTRATIVE TUBERCULOSIS. CASEOUS PNEUMONIA. 

 

NIDUS LUNG TUBERCULOSIS

 

The small form of tuberculosis that is characterized by the presence of a nidus (a specific injury up to 1 cm in diameter) or a group of nidi withiot more than two segments of one or both lungs. Among first diagnosed lung tuberculosis patients the nidus form makes up 18,9 %.

 

Pathogenesis and pathanatomy.. The nidus lung tuberculosis may develop as a result of exogenous superinfection or endogenous MBT spreading from concealed tubercu-lous nidi in intrathoracic lymphatic nodes, bones, kidneys, more often – from old encapsulated or calcified nidi in lungs at aggravation. The third way of forming nidus tuberculosis is the involution of other forms – infiltrative, disseminated tuberculosis (fig.1).

 

fig. 1  Focal lung tuberculosis

 

 

Pathogenesis and pathanatomy. FLT belongs to secondary tuberculosis, meaning that it develops in long-time infected organisms the with presence of some infectious immunity and has features of limited organ injury.

        

     Theories of secondary tuberculosis development:

        – exogenic super infection;

        – endogenic reactivation of remining foci of infection.

 

According to exogenic theory, secondary tuberculosis is a result of repeatedly getting virulent tubercular infection into the lungs – super infection. Proof of this is more frequency of diseases on secondary tuberculosis of people being in contact with patient, who excrets MBT (for about 5-10 times). Development of such fresh exogenic foci starts with endobronchitis of subsegmentary bronchus that transforms into panbronchitis, sometimes caseous. Around it there is formed focus of specific pneumonia firstly exudative, then productive character. Formed caseous masses are aspirated into neighbouring bronchi and become basis for new foci formation. During progressing of process there is possible increase of infiltration zone, formation of small destruction cavities.

By endogenic theory, for development of secondary tuberculosis new infection is not obligatory. It may occur as a result of reactivation of tuberculosis infection in residual tubercular changes after primary tuberculosis that might take place without considerable clinical symptoms. In such old changes mycobacteria may stay living for a long time. Under the influence of different endogenic and exogenic factors which influence negatively on immunity; they are able to revert into virulent and reproductive. Such favourable factors may be hyperinsulation or overcooling, psychical and physical traumas, other diseases, viral infections (AIDS), pregnancy and delivery, hard working conditions, insufficiency of nutrition. Superreinfection may be the reason of hypersensivity of organism and endogenic reactivation of MBT in old residual changes.

Sources of reactivation rarely may be residues of lung affect of primary complex – Gon’s focus. More frequently tuberculosis spreads from residual changes in intrathoracic lymph nodes, from there infection may get into lung tissue by lymphogenic, hemogenic and bronchogenic ways.

    Initial stage of reactivation of old focus is penetration into its capsule of lymphocytes and neutrophils, which excrete ptoteolitic enzymes leading to solvation of caseous masses. In fluid caseous reproduction of MBT is activated and they spread  with formation of new areas of specific inflammation.

Third way of formation of focal tuberculosis is involution of other forms – infiltrative, disseminated and even cavernous. Thus, pulmonary infiltrate may eliminate, and in its place will stay single or multiple foci with limited fibrosis. If in treating process of disseminated tuberculosis many foci are in 2 segments, not more. It is also FLT. Some focal changes with limited fibrosis may rest after closing of lesion.

Thus, focal tuberculosis includes very different processes: fresh foci formed as a result of exogenic superinfection or endogenic reactivation by lymphogenic, hematogenic or bronchogenic ways and old foci formed in process of back development of other tuberculosis forms. So, it may be at the start of lung tuberculosis or its finish. But focal tuberculosis includes only processes with active, not finished specific inflammation. FLT is divided into soft focal (acute) with fresh foci of exudative or productive character and fibrouse focal (chronic) at which foci are surrounded with a connective tissue capsule, sometimes with elements of calcination; but places of active inflammative process could be found. Lung tissue is sclerotized; there is possible bronchial deformation, and pleural layers. Fibrous-focal tuberculosis may be the next stage of development of soft-focal tuberculosis or involution of other forms.

   Focal tuberculosis is localized on apical parts or under clavicles. It is connected with limited mobility of apices, their insufficient aeration, weak vascularisation, slow lymph circulation, hypersenssensivity. There is also possible of MBT coming from tonsils of cervical lymph nodes

Clinic. Phenomena of intoxication at nidus tuberculosis are weakly expressed or absent. However, it should be noted, that only processes with an active, uncompleted specific process are attributed to nidus tuberculosis.

Mild-nidus(inphiltration phase) and fibrous-nidus (scarring phase) lung tuberculosis are discriminated.

Mild-nidus lung tuberculosis is always a fresh and active specific process. Fibrous-nidus lun g(chronic) tuberculosis is manifested by the presence of compact nidi with inclusion of lime, sometimes also caseose, fibrous changes in the form of traces and sections of hyperpneumatosis. At revealing fibrous-nidus changes by the method of roentgenofluorography it is necessary to perform a thorough examination of a patient with a view to ascertain the process activity.

Nidus lung tuberculosis is predominantly revealed during prophylactic fluorographic examinations, as clinical symptoms are weakly expressed or absent.

It is only in 1/3 of patients that intoxication symptoms or complaints, connected with the injury of broncho-pulmonary system, are observed. Intoxication symptoms are more often observed at mild-nidus tuberculosis, while the symptoms of injury of respiratory organs – at that of fibrous nidus one.

Percussion and auscultation at nidus tuberculosis are of no great importance. The haemogram in the predominant majority of patients is without changes. Mycobacterial secretion is scanty and does not exceed 15 % of thoroughly examined patients.

Reaction on Mantu’s test with 2 TU (tubercular units) in sick people with FLT is positive, but it isn’t much different from reaction in healthy infected people.

 

Roentgenologic examination is the principal and the most informative method of revealing nidus lung tuberculosis. With this aim in view fluorographic examination at inhalation and expiration, target roentgenogram, tomograms on optimum microscopic sections are applied.

Roentgenologic signs of nidus tuberculosis are: nidi withiot more than two segments; at mild-nidus form – nidi of small and middle intensity with vague contours on the background of strengthened vessel picture of an injured section of the lung; at fibrous-nidus form – nidi of big intensity with distinct contours on the background of deformed lung picture and fibrous traces.

Sometimes at fibrous-nidus tuberculosis there arises the necessity of determining the process activity (i.e. when the specific process is not yet completed and dynamics towards progression or regression is possible) (fig. 2).

fig.2 Roentgenogram. Focal lung tuberculosis of right lung

 

 So, X-ray examination plays first role for diagnosis of FLT. As the most frequent localization at the clavicles, focal shadows are often covered with bone formations, that’s why, besides common fluorographic investigation, it is necessary to provide fluorogram in posterior angled position, roentgenogram, tomograms on optimum section.

      The main X-ray criteria of FLT diagnosis:

              – Presence of foci in the lungs (shadows up to 1 cm);

              – Spreading in 2 segments.

 

The activity of tuberculous process is defined on the basis of the following criteria:

1. Clinical (bronchopulmonary or intoxication symptoms are present);

2. Roentgenologic (nidi of small intensity, with vague contours, a considerable number of nidi and of big sizes);

3. Bacteriological (revealing of MBT);

4. Changes in haemogram (leucocytosis, shift of leucocytic formula to the left, lymphopenia, accelerated ESR);

5. Tuberculin tests (hyperergic Mantoux test with 2 TU, positive local, nidus and general reactions after subcutaneous transfusion of tuberculin (Koch test);

6. If preliminary tests do not allow to settle the problem as to the activity of lung pathologic changes, experimental treatment is applied, which consists in administering 2-3 antituberculous preparations (isoniazidum, ethambutolum and (or) streptomycini (no more than 2 months)) during 3-4 months.

Afterwards roentgenologic examination is repeated; positive roentgenologic dynamics testifies about active tuberculous process and the patient’s treatment proceeds. At stable roentgenologic picture – the process in inactive and antimycobacterial therapy discontinues. However, it should be noted, that the most informative tests of the activity of tuberculous process are roentgenologic, bacteriological and experimental treatment.

Differential diagnostics. Unspecific pneumonia, neoplasms or metastatic lung injuries may have clinico-roentgenologic symptomatics similar to that of lung nidus tuberculosis.

Similar clinical and X-ray picture may be present at focal pneumonia that has low-revealed symptoms from previous years. Anamnesis data about overcooling, acute beginning, symptoms of laryngitis, rhinitis, high body temperature, severe cough, chest pain, dyspnea are more characteristic for pneumonia. During physical examination are heard rhonchi with rough breathing. Leukocytosis, moving of leukoformular to the left and increased ESR are in pneumonia. Foci are often of small intensity, monomorphic without clear borders; they are localized more often in lower parts of lungs, but their upper localization is also possible. Mantu test in people with pneumonia infected with tuberculosis may be also positive, but MBT are not found in sputum. When diagnostic of tuberculosis is firm, patient is prescribed with antibiotics of wide action spectrum, avoiding remedies of anti- tuberculosis action (streptomycin, kanamycin, rifampicin etc.). Clinical reconvalescense, elimination of focal shadows during 2-3 weeks proves diagnosis of pneumonia.

Treatment of lung active nidus tuberculosis patients should be started with three antimycobacterial preparations: isoniazidum, rifampicinum and pyrazinamidum during 2 months. Afterwards the treatment is continued with isoniazidum in combination with rifampicinum during to 6 months. Illness progressing is possible in 2-5 % of lung nidus tuberculosis patients. In these cases indications to a partial lung resection may arise.

 

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LUNG INFILTRATIVE TUBERCULOSIS. CASEOUS PNEUMONIA. 

 

LUNG INFILTRATIVE TUBERCULOSIS.

Lung infiltrative tuberculosis is a specific exudative-pneumonic process, of the size over 1 cm, inclined to quick progressing and decay.

At present time it is the most widely spread form of lung tuberculosis and it comprises 54,9 % among firstly diagnosed patients.

 

Pathogenesis and pathanatomy. Infiltrative lung tuberculosis develops as a result of perifocal inflammation around old tuberculous nidi, or as a result of mild-nidus tuberculosis progressing. The development of infiltration is the result of hyperergic reaction of lung tissue to a great number of virulent MBT, that multiply rapidly. Here of essential importance are the superinfection solidity, presence of various illnesses, psychological traumas and other factors, which lower body resistance.

ILT belongs to secondary forms and is met mostly in adults. Infiltrate develops as a result of perifocal inflammation around fresh foci that appeared due to exogenic superreinfection or endogenic reactivation. Thus it may be continuation of soft-focal tuberculosis. Often the stage of development in the lungs of fresh foci stays not revealed, and sickness is revealed with formed infiltrate.

         Tuberculosis infiltrate may be a result of perifocal, inflammation around severed old foci formed at involution of lung tuberculosis. Fast development of infiltrate is a result of hyperergic reaction of lung tissue to a high quantity of virulent MBT that quickly reproduces. Different endogenic and exogenic factors also have some value, they decrease the organism’s resistance.

At ILT there are injured several pulmonary lobules, segments, subsegment or whole lobe in zone of perifocal pneumonia around fresh or old severed foci at exudative type of alveolar inflammation are filled with exudative matter with addition of alveolar phagocytes, polynuclears. Sometimes an advantage of productive reaction the quantity of inflammatory exudates is not much, alveoli are filled with macrophages, plasmatic and epitheloid cells. Interalveolar septa are thickened, infiltrated with lymphocytes, histocytes. Lymphatic vessels are dilated. Inflammatory process spreads on bronchus in each case. Specialty of hyperergic tissue reaction at ILT  is its predict ability to fast caseous necrosis. Areas of caseous are usually formed in the center of infiltrate. Under the action of proteolysis enzymes caseous is dissolved, excreted through draining bronchus and cavity of destruction is formed (fig. 3).

 

 

 

fig. 3. Infiltrative tuberculosis (lobitis)

 

Caseous masses may be partly aspirated into other (usually inferior) parts of lungs; they become basis for formation of fresh foci of broinchogenic dissemination. New tuberculosis foci around infiltrate appear also by lymphogenic way.

      In process of ILT treatment there is possible its complete elimination, but more often in its place there stays group of dense foci with less or more reflected fibrosis changes. Sometimes focal infiltration eliminates and caseous center encapsulates. Depending on its size there is formed Pool’s focus or tuberculoma. If infiltrate is not completely eliminated and there develops connective tissue, in its place is formed an indurative field. The result of dense lobar infiltrates may be cirrhosis of pulmonary lobulus. At non-effective treatment destruction cavity doesn’t eliminate, there are formed its fibrosis walls, process may transform into cavernous and fibrosis-cavernous tuberculosis.

 

Clinic. Infiltration and caseous pnuemonia are discriminated (the latter is classified into a separate clinical form). Clinico-roentgenologically the following variants of lung infiltrative tuberculosis are discriminated:

1. Cloudsimilar infiltration is characterized by the presence of tender, weak intensity of inhomogeneous shade with vague washed off contours and inclined to rapid desrtuction (fig.4).

fig. 4. Cloudlike infiltrate

 

 

2. Rounded infiltration – almost homogeneous shade of average intensity of rounded form with distinct contours (Assman-type) (fig.5).

Fig. 5.  Round shaped infiltrate

 

 

 

3. Lobular infiltration looks like an inhomogeneous shade, which is a nidi conglomerate, which coalesced.

4. Lobar infiltration (lobit) is a spread infiltrative process, which embraces a whole part of a lung, often of inhomogeneous character and with the presence of individual or some decay cavities (fig.6).

Fig. 6. Lobitis.

 

 

5. Periscysurite is an infiltration, disposed along interpartial fissure, as a result this contour is distinct, and the opposite one is washed off.

Clinical course of infiltrative tuberculosis depends on the morphological structure, sizes of infiltration and caseose. More often infiltrative tuberculosis begins acutely or subacutely and as to the clinical course it resembles influenza, an acute respiratory virus infection or pneumonia. One of the symptoms of infiltrative tuberculosis may be haemoptysis under the patient’s general satisfactory condition. Sometimes the progress of infiltrative tuberculosis is asymptomatic (inaperceptive), though here too insignificant signs of intoxication may be revealed at thorough examination. Physical data depend on the process sizes and phase. If the infiltration exceeds 4 cm in diametre, the percussioote dullness is noted, rough respiration, damp rale at infiltration destruction.

Roentgenologically infiltrative tuberculosis is characterized by:

1.     A shade of over 1 cm in diameter

2.     A shade of inhomogeneous character

3.     Average or weak intensity, connected by a “path” with a root,

4.     Predominantly localized in I, II or VI segments

5.     The decay cavity in the infiltration centre, and

6.     Around or in other lung sections – nidi of bronchogenic dissemination (fig.7,8).

fig.7 Roentgenogram. Infiltrative lung tuberculosis

С6 left lung with decay

 

fig.8 Roentgenogram. Cloudlike infiltrate

of left lung.

 

 

In haemogram – leucocytosis, not exceeding 15,0 х 10⁹/l in the predominant majority of patients, shift of the leucocytic formula to the left, lymphopenia, accelerated ESR. Reaction to Mantoux test with 2 TU is positive (normergic).

In 40-50 % of cases infiltrative tuberculosis of lungs is accompanied by bacterial excretion, while at infiltration destruction – in 95 % of patients.

 

The treatment of patients comes to conducting uninterrupted antimycobacterial therapy during 6-9 months. The first 2-3- months antituberculous preparations in optimum doses (isoniazidum, rifampycinum, streptomycini, ethambutolum or pyrazinamidum) are administered against the background of desensitized, vitamine – and symptomatic therapy. Often the course of glucocorticoid therapy is expedient at the first phase of the treatment. In 2 months streptomycini is cancelled, the treatment is proceeded during 4 months with isoniazidum, rifampycinum, ethambutolum (or pyrazinamidum) to the decay cavity closure. In cases of ineffective treatment during 3-6 months, surgical intervention – a partial lung resection, is indicated.

 

 

Differential diagnostics of lung infiltrative tuberculosis

 

 

 

 

Differential diagnostics of lung infiltrative tuberculosis is done first and fore-most with unspecific pneumonia, eosinophil infiltration, lung cancer, lung infarction (fig.9,10,11,12 )(table 1).

fig.9 Roentgenogram.Pneumonia of inferior part of left lung.

 

 

fig.10 Roentgenogram. Eosinophilic pneumonia.

 

fig.11 Roentgenogram. Central cancer of left lung.

 

 

fig.12   Tomogram of right lung. Infarct of lung .

 

 

Differential diagnosis at infiltrative tuberculosis                                                                                                                                                   (table1)

Main signs	Infiltrative tuberculosis	Pneumonia	Infarct of lung	Eosinophilic infiltrate	Cancer of lung
ANAMNESIS	Sometimes contact with tb patients, previous tb	Caught a cold, catharrh of upper respiratory ways, angina	Operation, trauma, trombophlebitis, heart diseases	Allergic diseases, helminths	Patients are men after 40, smoking
COURSE	Beginning often is gradual, acute. At tuberculostatic therapy regress is slow	The beginning is acute, fast regress after antibiotics	The beginning is acute	The beginning is not visible, rare acute	Gradual beginning, progressive worse condition
SYMPTOMS	Moderate toxication, fever, sweating, cough. Few ausculatative changes	High temperature, dyspnea, cough. Full ausculataive picture (wet and dry rhonchi)	Pain in chest, dyspnea. Above the infiltrate zone, there is dullness, bronchial breathing	None complains, sometimes cough, impermanent dry or wet rhonchi	Pain in chest, dyspnea, cough, a big tumor or complicated with atelectasis – dullness, sometimes dry rhonchi above infiltrate
ROENTGENO–LOGIC  PICTURE	Not homogenic infiltrate in1, 2 or 6 segment. Road to root, injured places on the background and around infiltrate	Shadow in most cases is homogenic	Triangle homogeny shadow, apex towards the root. Rare shadow is round or oval. High state of diaphragm	Shadow with unclear margins like cotton tampon, often homogeny. Rapid appearance and disappearance of infiltrate.	At peripheral cancer the shadow is homogenic and tuberose. At central one the shadow goes out of root
OTHER METHODS OF INVESTIGATION	Positive Mantu test. At bronchoscopy there is a specific endobronchitis	At bronchiscopy there is unspecific endobronchitis	On ECG there are signs of overloading of right heart	Positive skin tests with specific allergen	Direct and indirect signs of tumor at bronchoscopy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CASEOUS PNEUMONIA

 

Caseous pneumonia is an acute specific pneumonia, which is characterized by considerable caseous-necrotic changes in the lungs, sharply expressed indications of intoxication, grave progressing course and frequent lethal result.

During the recent 5-8 years its frequency has increased 3-5-fold and it comprises 20-25 % in the general structure of lung infiltrative tuberculosis.

 

Pathomorphism. Caseous pneumonia breaks out in patients with sharply decreased body resistance, called forth by various factors, at high MBT virulence as well as their resistance to antimycobacterial preparations.

Caseous pneumonia, as primary independent form of tuberculosis, occurs extremely rarely. In recent years secondary caseous pneumonia is more often observed, which develops on the ground of lobite, a cloudsimilar infiltration, after lung haemorrhages, against the background of aspirational pneumonia or grave progressing form of tuberculosis – fibrous-cavernous, subacute disseminated lung tuberculosis.

Depending on the form of pathomorphologic changes, lobar and lobular caseous pneumonia are discriminated.

At lobar caseous pneumonia the process captures all the lung particle, and infiltrative-pneumonic form of the process is rapidly changed in caseous-destructive one. The reason of such a violent formation of caseous necrosis and spreading the process to the whole particle is probably sharp decrease of body resistance, high degree of macroorganism sensibilization, high virulence and massiveness of the infection. At this form of tuberculosis, in addition to big sections of caseous necrosis, multiple decay cavities or a big cavern are always formed, as a result of putrefaction (fig.13).

fig. 13  Lobar caseous pneumonia.

 

 

Lobular caseous pneumonia more often develops as a result of aspirational pneumonia after haemorrhages, as a complication of disseminated lung tuberculosis, of terminal stage of fibrosis-cavernosis tb of lung.

   

    Thus they’re the following variants of caseous pnemonia:

1. Lobar is a total caseous necrosis of cloudlike infiltrate or lobitis.

2. Lobuluar:

    –  As a result of aspirative pnemonia after bleeding;

    – Malignant course of subacute disseminative tuberculosis of

       lung;

    – Complications of terminal stages of chronic form of

       tuberculosis;

    – Spreading of caseous masses in bronchi and lungs through the

       fistula with lymphatic nodes.

 

 

Clinic. An acute sudden beginning with high body temperature, rapidly increasing intoxication symptoms, profuse perspiration, shortbreathing, pain in chest, cough with excretion of a big amount of sputum with blood admixtures. The skin is pale, mucous are of cyanotic tint. Tachycardia and hypotonia are expressed. Percussively – the blunting of a percussioote over the injured sections, auscultatorily – a great number of sonour damp rales of various calibers.

In roentgenogram at lobar pneumonia – massive dark of a lung part without distinct limits with the presence of decay cavities, subsequently a large cavern is formed; at lobular caseous pneumonia – big dark focuses of flood character, multiple decay cavities appear at progressing, as well as fresh nidi of bronchogenic dissemination (fig.14).

fig.14 Caseous pneumonia of left lung. Bronchogenic dissemination of right lung.

 

All this is accompanied by sharply expressed changes of haemogram, in particular by hypochromic anemia, expressed leucocytosis, eosinopenia, increase of the number of bacillarnuclear neutrophiles, lymphopenia, sharply accelerated ESR (up to 70 mm/hr.). MBT are found in the sputum. Tuberculin test may be negative (negative anergia).

Differential diagnostics of caseous pneumonia is performed to distinguish croupous and staphylococcal pneumonia.

Differentiated diagnosis of lobar caseous pneumonia should be made with simple (croup) pneumonia, which is also develops acute, but sometimes begins with rhinitis, herpes; those are not specific signs for caseous pneumonia. Body temperature during croup pneumonia is persistent, while during caseous pneumonia it is irregular with remissions. For caseous pneumonia profuse night sweat is usual, while during croup pneumonia it appears during crisis. More expressed leukocytosis (20-40*1012/l) can be during croup pneumonia.

X-ray signs of croup pneumonia are the following (fig. 15):

           Homogeny shadow limited in a lobe.

  X-ray signs of caseous pneumonia:

         1. Uneven shadow, that can be spread;

         2. Appearing of lightening because of emptiness destruction;

         3. Injured places of bronchogenic dissemination in other

             places in the same lung or another lung

 
fig. 15. Croup pneumonia of left lung

 

 

        For full determination of tubercular origin of disease multiple searching of mycobacterium tuberculosis in sputum is necessary. Diagnosis of lobular pneumonia, which develops as a complication of other forms lung tb is difficult.

 

Treatment of caseous pneumonia consists in applying maximum tolerated doses of isoniazidum, rifampycinum, streptomycini, ethambutolum, pyrazinamidum with simultaneous administering of desintoxicating, symptomatic therapy and vitamin means, as well as fluorinechinolones (ofloksacini, cyprofloksacini) with a view to suppress the secondary infection. However, full recovery occurs extremely rarely; more often fibrous-cavernous or cirrhotic lung tuberculosis is formed. Taking all this into account, the plan of treatment of caseous pneumonia patients should envisage a surgical intervention, like a lung resection or its part, after the operation antimycobacterial therapy is proceeded during 6 months.

DISSEMINATED LUNG TUBERCULOSIS. MILIARY TUBERCULOSIS.

TUBERCULOSIS OF CENTRAL NERVOUS SYSTEM AND CEREBRAL MEMBRANES. CONIOTUBERCULOSIS.

DIFFERENTIAL DIAGNOSTICS AT DISSEMINATED LUNG TUBERCULOSIS

 

 

 

DISSEMINATED LUNG TUBERCULOSIS. MILIARY TUBERCULOSIS.

 

 

Disseminated lung tuberculosis is a clinical form of tuberculosis that arises as a result of lympho-haematogenous spreading of infection and is characterized by bilateral, symmetric nidal injury with predominant localization in upper, subcortical lung sections.

At present time, among firstly diagnozed lung tuberculosis patients, disseminated form is found in 23 % of cases.

Pathogenesis. The following conditions are necessary for the disseminated lung tuberculosis to break out: availability in an organism of a nidus of tuberculous injury, bacteriemia, hypersensibility of an organism and first of all the increase of permeability of the lung vessels wall, as well as the decrease of the body’s resistance to various provocative factors. The nidus of specific injury is predominantly tuberculous injury of intrathoracic lymphatic nodes, from which through thoracic duct, subclavian vein MBT get into the right half of the heart, and further into the lung artery and the lungs.

Besides lympho-haematogenous spreading of infection, disseminated tuberculosis can arise as a result of MBT dispersion by bronchogenic or mixed ways, by what symmetry or asymmetry of lung injury is explained. Depending on the massiveness, virulence of the infection, the state of the macroorganism as well as various negative provocative factors, acute, subacute or chronic disseminated lung tuberculosis may develop. These forms of disseminated tuberculosis, depending on the way of MBT spreading, may be of haematogenous or lymphobronchogenous genesis (fig.1).

 

fig1. Ways of MBT spreading.

1 – haematogenous

2 – lymphogenous

3 – bronchogenous

 

 

Acute disseminated tuberculosis of haematogenous genesis is most often manifested as miliary one. It stands out for a separate clinical form in connection with the increase of its frequency under present conditions, the worsening of tuberculosis epidemiological situation.

Subacute disseminated tuberculosis develops at lowering of the body resistance, it has a severe progressing course, sometimes of caseous pneumonia type, with lethal outcome in 6 and more months.

Pathomorphism. The main components of subacute disseminated tuberculosis is a specific granuloma (tubercle), vasculite and alveolite, that is the basis for the formation of large nidi of exudative character in upper and middle sections or throughout all the lung fields. On the background of the nidi thin-walled caverns with perifocal inflammation may form. More often caverns are found on symmetric sections of the lungs. There may be extralung injuries.

Clinic. The main syndromes are: intoxicating, bronchopulmonary, as well as indications of injuries of other organs.

At laboratory examination, expressed pathologic changes of haemogram are typical. MBT are often revealed in sputum. Mantoux test with 2 TU is positive, however, at the patient’s grave state it may be negative.

Roentgenologically nidi are large in size, symmetrically located, of medium and small intensity, with vague contours, inclined to confluence (the “falling snow” picture) and the formation of decay cavities, from which “stamped caverns” are formed (fig.2).

Fig. 2. Disseminated lung tuberculosis (subacute). Observation roentgenogram.

 

Differential diagnostics is performed with lung illnesses, similar by roentgenologic symptoms, accompanied by dissemination syndrome, stagnation phenomena in lungs (they are over 200). They are, first of all, bilateral nidus pneumonia, sarcoidosis (II stage), carcinomatosis, silicosis, lung stagnation phenomena, idiopathic fibrosing alveolite, Goodpasturer’s syndrome, mucoviscidosis, lung toxoplasmosis etc.

Treatment. The principal method of treating patients with lung subacute dis-seminated tuberculosis is antimycobacterial therapy, lasting for 8-12 months, the first 2-3 months – 4, and then 3 antituberculous preparations, up to decay cavities closure. The further treatment is done with isoniazidum and rifampicinum (or ethambutolum).

 

Chronic Disseminated Lung Tuberculosis

It is the most frequent form of lung disseminated tuberculosis, first of all of haematogenous genesis, and more often develops as an independent form or on the background of ineffective treatment of lung subacute disseminated tuberculosis. It is characterized by apicocaudal spreading of the process (fig. 3).

fig. 3. Chronic disseminated lung tuberculosis (pathomorphological picture)

 

 

Successive injury of various organs and systems is possible. Chronic disseminated tuberculosis has an undulatory course, at which intoxication symptoms at the remission period are partially extinct, and at the process outbreak they increase with the appearance of fresh lung and extra-lung local injuries. Roentgenologically polymorphic nidus shades are revealed in the lungs on the background of deformed lung picture, fibrosis and emphysema.

 

 At any stage of the disease caverns may arise in one or both lungs. Thus, in time at durable progress of disseminated tuberculosis, as a result of periodic outbreaks and remissions of the process, repeated waves of dissemination, formation of pneumosclerosis and emphysema, chronic lung heart develops. 

Data about the present contact with a person secreting bacteria, primary tuberculosis, pleurisy, extra-lung tuberculosis, suffered in the past, protracted undulatory progress of illness are of great importance at the diagnostics of chronic disseminated tuberculosis.

 Roentgenologically: polymorphous nidus shades predominantly in the upper and middle sections on the background of deformed lung picture and fibrosis, not seldom with decay cavities of irregular form. MBT revealing is the confirmation of the specific nature of illness(fig. 4 ).

 

Fig. 4.  Disseminated lung tuberculosis (chronic). Observation  roentgenogram.

 

Differential diagnostics at disseminated lung tuberculosis

Differential diagnostics of chronic disseminated tuberculosis is performed with illnesses like the differential diagnostics of subacute disseminated tuberculosis and, first of all, with those that are characterized by a protracted course (bilateral nidus pneumonia, sarcoidosis (II stage), carcinomatosis, silicosis, lung stagnation phenomena, idiopathic fibrosing alveolite, Goodpasturer’s syndrome, mucoviscidosis, lung toxoplasmosis etc.) (fig.5,6,7) (table1).

 

fig.5. Bilateral nidus pneumonia

 

fig.6. Carcinomatosis

fig.7. Lung stagnation phenomena

 

Differential diagnosis of disseminated lung tuberculosis                            table1

Main signs	Disseminated tuberculosis	Bilateral focus pneumonia	Carcinomatosis	Sarcoidosis II degree	Pneumoconiosis II degree
History	Contact with tuberculosis patients is possible, history of tuberculosis.	Common cold, infection of the upper respiratory tract, pharyngitis.	History of surgery, primary tumour in the lungs or other organs	History not relevant	Working in dusty conditions (coal minings, etc.)
Course	Slow progression, sometimes tuberculosis of other organs is present; slow resolution in case of specific treatment	The beginning is sudden, severe condition, quick resolution with antibiotics	The condition is worsening progressively	Scarcely symptomatic, antimycobacterial trerapy is not effective	Slowly progressive dyspnea
Symptoms	Subfebrility, cough, dullness of the percussion sound, rarely- moist rales in the upper and middle parts of the lungs	High temperature, dyspnea, cough, herpes, many various rales in the middle and lower parts of the lungs	Progressive dyspnea, dry cough, body weight loss.	Mild dyspnea, cough, sometimes arthralgias.	Cough, dyspnea, sometimes chest pain , sings of bronchitis and emphysema.
Radiographic findings	Symmetrical foci with ill-defined borders, prone to confluence and destruction, mainly in the upper and middle parts of the lungs	Unintensive foci without well-defined borders, often in the middle and lower parts of the lungs, no clear symmetry	Well-defined foci, growing in  volume and number in the apico-caudal direction	Small or medium foci in the middle medial parts of the lungs. Enlarged hilar lymphatic nodes.	Well-defined foci in the middle-lateral parts of the lungs, pneumosclerosis, “cut-off” of hili.
Laboratory findings	Leucocytosis <15·109/l, lymphopenia, increase of ESR, frequently MBT(+)	High leucocytosis, shift of formula to the left, increase of ESR, MBT (-)	High ESR, anemia, leucocytosis, sometimes there are tumour cells  in the sputum, MBT(-)	Sometimes leucopenia,  lymphopenia, monocytosis. Hypergammaglobulinemia, increased blood and urine calcium levels, MBT(-)	Hemogram is normal.
Other methods of investigation	Tuberculin test is positive. Bronchoscopy – sometimes shows specific endobronchitis.	Bronchoscopy –unspecific shows endobronchitis.	Mantoux test often is dubious or negative. Primary tumour should be searched for.	Mantoux test is negative. Bronchoscopy – reveals dilated vessels of the bronchial mucous, histologically – epithelioid granuloma without caseosis	Mantoux test is ofteormal, Koch test – negative. Bronchoscopy –  reveals deformation and narrowing of bronchi, signs of  endobronchitis.

MILIARY TUBERCULOSIS

 

Acute disseminated tuberculosis of haematogenous genesis is the most often manifested as miliary (from Latin milae – millet), separated into an individual clinical form due to its rising frequency under present-day conditions as well as its diverse clinical manifestations

Miliary tuberculosis is predominantly generalized with forming nidi in lungs, liver, spleen, intestine, brain tunics. It is rarelier that only lungs are injured at this form (fig. 8).

Miliary tuberculosis is characterized by an acute course and appearance in interstitial tissue of various organs of tubercles or their conglomerates – tiny tuberculous nidi. It arises as a result of haematogenous spreading of MBT at sharply reduced body resistance. More often with children and teenagers.

 

fig. 8. Miliary tuberculosis

Organ (% involved):
Spleen	86%
Liver	91
Lungs	100
Bone marrow	24
Kidneys	62
Adrenals	14
Eye	—
Thyroid	19

                  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

    Bacilli may be discharged into micro­scopic vessels within caseous lesions which, in turn, seeded large vessels. This type of dissemina­tion may lead to histology in which acute “soft” lesions are admixed with “hard” tubercles show­ing more cellular organization, fibrosis, and an absence of stainable organisms.

      Miliary lesions in HIV-positive cases may present the same pathologic features as in HlV-negative subjects. In general, however, the lesions demonstrate more necrosis and less cellular reac­tion. Acid-fast bacilli are usually more numerous than in lesions from HIV-negative cases. Granulomas tend to be poorly formed and giant cells infrequent. In advanced AIDS cases, miliary le­sions may consist of foci of necrosis teeming with tubercle bacilli but with little or no surrounding cellular reaction. Hill and associates described lesions in some patients with AIDS at autopsy who had foci of acute tuberculous pneumonia in the airspaces rather than in the interstitium. The lesions consisted of necrotic alveolar septa sur­rounded by a few monocytes and neutrophils.

 

        

As to clinical progress miliary tuberculosis is conditionally divided into lung, typhoid, meningeal and septic (Landuzi disease) forms.

At lung form of miliary tuberculosis eruption of tubercles occurs predominantly in lungs, in addition to sharply expressed intoxication, pant, dry cough and cyanosis prevail. Respiration rate is over 40 per minute, tachycardia is expressed.

Data of physical examination are scanty. At percussion, as a result of an acute emphysema, tympanitic percussioote. Breathing may be weakened or rough, with dry and tiny-bladdery rales.

No pathologic changes are observed on the roentgenogram on the first days of the illness or they are manifested in the form of a tender net as a result of a more intensive blood supply of the lung vessels; it is only in 7-14 days of the illness that bilateral total millet-like lung eruption is revealed (fig.9,10).

 

Fig. 9. Chest radiograph of a patient with miliary tuberculosis.

 Note the extensive, symmetrical distribution of  2- to 3-mm lesions throughout both lungs.

 

Fig.10.  Close-up view of the chest radiograph in Figure 9.

Note the uniform distribution of nodules throughout the lung parenchyma.

 

 

Typhoid form of miliary tuberculosis. Tiny-nidal eruption is observed in all organs and tissues. The clinical course of the illness is similar to typhoid fever. Ho-wever, typhoid fever begins gradually, while miliary tuberculosis sharply. The body temperature at typhoid fever is more stable, and at tuberculosis it is of irregular type, remittent. Typhoid fever patients may develop bradycardia, meteorism, diarrhea, which are not typical for miliary tuberculosis. Typhoid fever is accompanied by leucopenia and relative lymphocytosis, and miliary tuber-culosis – by inconsiderable leucocytosis and lymphopenia. Psychic depression is characteristic for typhoid fever, as well as relative bradycardia, positive Vidal reaction and roseola eruption on the abdomen skin.

At meningeal form of miliary tuberculosis cerebrum and spinal cord and, first of all, their meninges are injured. This form of tuberculosis is diagnosed first and foremost according to meningitis symptoms and then lesions of other localisations are revealed.

For acute miliary sepsis, as for the preceding forms, peculiar is haematogenous dissemination of highly virulent MBT with generalized tiny-nidal lesion of all organs and tissues of a weakened human body. Besides that, from the very beginning of the illness, specific tiny tubercles rapidly undergo purulent-caseous necrosis, where a great number of tuberculous mycobacteria can be revealed. The patient’s general state is extremely severe. The illness is hard to discern from sepsis of nontuberculous etiology, with what high lethality of patients is connected. Surely, sepsis is connected with purulent processes of other organs, an abrupt outbreak, high hectic body temperature, rigors. Substantial leucocytosis (over 20х10⁹/l with a considerable shift of the formula to the left). The diagnosis is confirmed by the blood culture for sterility, the growth of staphylococci or streptococci is revealed on the 2nd-3rd day, while the MBT on the nutrient media grow slowly, on the average, in 2-4 weeks.

Treatment of miliary tuberculosis patients consists in administering of 4 an-timycobacterial preparations in optimum doses: isoniazidum and rifampycinum – 0,6 g per day, streptomycini 1,0 g intramuscularly and pyrazinamidum – 1,0 g twice a day or ethambutolum 1,6 g once a day, during 2-3 months. Afterwards streptomycini is cancelled. The duration of continual chemotherapy is 9-12 months. Simultaneously with antimycobacterial preparations vitamins B₁, B₆, C are administered; desensitizing and general restorative preparations; a course of glucocorticoids (1,5-2 months) in the first months of the treatment.

 

 

TUBERCULOSIS OF CENTRAL NERVOUS SYSTEM AND CEREBRAL MEMBRANES. TUBERCULOUS PLEURISY.  TUBERCULOSIS  IN  COMBINATION  WITH  OTHER  ILLNESSES  AND  PREGNANCY

 

TUBERCULOSIS OF CENTRAL NERVOUS SYSTEM AND CEREBRAL MEMBRANES

 

Tuberculous meningitis is the inflammation of the membranes of cerebrum and (or) spinal cord, caused by tuberculous mycobacteria. Specific lesion of cerebral membranes and substances is tuberculous meningoencephalitis.

In Ukraine during the ninetines of the 20^th century statistics of tuberculous meningitis sickness was stably low and comprised 0,08-0,13 per 100 thousand population, and the death-rate was relatively high (0,053-0,086 per 100 thousand population). In recent years these indices are getting worse.

Pathogenesis. Tuberculous meningitis may be primary (in 20 %) and secondary (in 80 %), as children and teenagers primary tuberculosis complication and predominantly disseminated lung tuberculosis in adults. MBT penetrate into submembranous space of cerebrum and (or) spinal cord by haematogenous, lymphogenous and rarely – by perineural way.

Pathological anatomy. The specific process is predominantly localized in the soft membrane of cerebral base, in which connection cranial nerves, located here, are injured. The illness may progress as meningoencephalitis (64-70 %) – inflammation of cerebral membranes and substance, as basal meningitis (20-30 %) – inflammation of cerebral membranes and as spinal meningitis (4-6 %) – inflammation of spinal cord membranes.

Exudate, tubercles, tender fibrin threads appear on soft cerebral membrane at tuberculous meningitis. Pathologic changes are also observed on the vessel membrane of cerebral ventricles (fig.11).

fig.11. Exudate, tubercles, tender fibrin of cerebral base

 

Clinic. Tuberculous meningitis usually begins gradually, with a prodromic period of the duration from 1 to 4 weeks. Patients feel general weakness, irritability, sleeplessness, lability, unstable headache, often subfebrile body temperature, predisposition to stopping of diarrhoea. Later on, obvious clinical manifestations of soft cerebral membrane inflammation set in; the body temperature rises to febrile, the headache of sharp intensity, joined by vomiting and meningeal syptoms develop gradually: rigidity of cervical muscles, Kernig’s and Brudzinsky’s symptoms. At the inflammation of the soft membrane of cerebral base, eye motional and drain cranial nerves are injured. Oedema of cerebral substance causes pareses according to the central type of the VII, IX, X, XII pairs of cranial nerves. Owing to the injure of diencephalic section, vegetovascular disturbances in the form of vasomotor reactions develop, stable red dermographism, Trusso spots, relative bradycardia, disturbance of sleep and appetite. The illness may develop as meningoencephalitis and in these cases nidal sings of cerebral lesion – hemipareses, hemiplegias are observed. At the involving into the process of membranes of the spinal cord and its roots, pain appears in thoracic, lumber cords of the spinal column, peripheral pareses and paralyses. Further on, at meningitis progressing, the low paraparesis appears, disturbances of the function of pelvic organs, accompanied by hampered excretion of urine, stopping of diarrhoea, irretention of urine and excrement.

 

In the third, terminal period of tuberculous meningitis (the period of pareses and paralyses) an expressed adynamy is peculiar, apathy to all surrounding, consciousness blank, later on soporose state develops, coma. And all this may be accompanied by a patient’s recumbent position on a side with his head recumbent and his legs close to his stomach.

In general, 5 components (syndromes) are discriminated in the clinical picture of tuberculous meningitis:

I. Intoxicating syndrome.

II. Meningeal syndrome: headache, vomoting, hyperestasis.

Meningeal symptoms: rigidity of cervical muscles; Kernig’s, Brudzinsky’s, Gylene’s, Lessage’s positive signs; boat-shaped abdomen, ‘‘trigger’’ position.

III. Symptoms of cranial nerves lesions (III, VI, VII, XII) and the spinal cord roots (fig.12,13,14).

fig.12. Lesions of III pairs of cranial nerves

 

fig.13. Lesions of VII pairs of cranial nerves

 

 

fig.14. Lesions of XII pairs of cranial nerves

 

Lowered tendinous and periosteal, as well as disproportionate from both sides abdominal reflexes.

IV. Changes of spinal fluid: liquor is usually transparent or opalescent, flows under increased pressure (at norm up to 60 drops per minute); greater number of cells (100-300 in 1 ml, at norm – up to 10), increased protein content (0,6 -1,0 g/L and more, norm – 0,2-0,4 g/L), lowered sugar concentration (1,5 mmol/L and less, norm – 2,22-3,88 mmol/L), lowered chlorides concentration (110 mmol/L and less, norm 120-130 mmol/L), Pandi and None-Apelta’s positive reactions, in liquor a weblike film is formed in 24 hours, in which in 10-20 % of cases MBT are revealed.

To the point, on the first days of illness neutrophil granulae prevail in the liquor, however pleocytosis rapidly changes into lymphocytic.

V. Symptoms of irritation and prolapse of functions owing to cerebral tissue lesion: pareses and paralyses of central origin, violation of pronunciation (aphasia, alalia), disturbance of psychics (black out, sopor and coma).

Depending on the site of predominant lesion of cerebral membranes three forms of tuberculous meningitis are discriminated: basal, spinal and meningoencephalitis.

Basal meningitis is characterized by meningeal symptoms and often by signs of cranial nerve lesions, first and foremost eye-motional, drain, facial and sublinqual. At spinal form of tuberculous meningitis the first manifestations are the symptoms of lesion of spinal cord membranes and roots, in particular – pain in lumber and thoracic spine, disturbances of the functions of pelvic organs, paresthesia and pareses of the lower extremities and later on a picture of typical meningitis develops. Meningoencephalitis is characterized by meningeal symptom complex, signs of lesion of cranial nerves and nidal cerebral lesion, central hemipareses and paralyses.

Diagnostics. The most important method of diagnostics of tuberculous meningitis is the examination of liquor. Normalization of spinal fluid during treatment occurs not earlier than in 2-4 months. If its normalization occurs during a month, so the tuberculous etiology of meningitis becomes doubtful, in other words it is not tuberculous meningitis. In case that a doubt appears as to the etiology of meningitis and at the slightest suspicion of tuberculous meningitis, the question is always solved in favour of tuberculosis and treatment with 3-4 antituberculous preparations is administered, herewith two of them are obligatory rifampicinum and streptomycin.

Differential diagnostics of tuberculous meningitis is more often performed with meningococcal, viral, secondary purulent meningitis and “meningism”, developing at illnesses with sharply expressed intoxication.          

The meningococcic meningitis starts and progresses acutely. It is accompanied with the pronounced intoxication, loss of consciousness, sometimes with herpetic eruptions, high leukocytosis in peripheral blood. Cerebral nerves are seldom affected. Spinal liquor is turbid, cytosis – 1000 and more in 1 ml, mainly neutrophilic, sedimentation results in the formation of thick film, albumen content is increased, glucose level is decreased. The diagnosis is being confirmed at bacteriologic examination of the spinal liquor, where meningococci are found. Under the influence of intensive antibiotics therapy the sanation  of the liquor and the clinical recovery take place quickly.

         The secondary purulent meningitis is often caused by metastasation of purulent processes, most often from ears (otitis), circumnasal cavities (maxillary sinusitis, frontitis), by septimia development (pneumonia, abscess, osteomyelitis, carbuncle, etc.). The etiology of the secondary purulent meningitis is staphylococcous or pneumococcous. History and total examination are very important from the differential-diagnostic point of view. The absence of the primary purulent focus does not exclude the diagnosis of the secondary purulent meningitis. The start of the meningitis is acute, in 1-2 days appear focal affections of the central nervous system. Frequent are loss of consciousness, generalized clonic-tonic cramps, affection of cerebral nerves, frequent are also hemiparesis and paraparesis. The diagnosis is being confirmed at the bacteriologic examination of the liquor.

         At leptospirosis meningitis, the meningeal syndrome more frequently appears at the 3^d-6^th day of the disease at the background of the clinical symptoms characteristic for this illness (pain in the lumbar area, in sacrum, shin muscles, enlargement of liver and spleen, high temperature within 5-7 days, leukocyteosis in peripheral blood). Also the body temperature rises repeatedly, the headache intensifies, vomiting, general hyperestesia, skin and sclera ictericity appear. Anamnesis stimulates the in-time identification of the leptospirosis meningitis (contact with animals, bathing in rivers, swamped water places, fishing, etc.). Leptospirosis meningitis may proceed both with purulent and serous inflammation of the meninges. The liquor is mainly opacitated, pleocytosis is in the range of 800-4000 cells in 1 mm³ neutrophilic or mixed. The etiology of the illness is confirmed in the first day of the disease by leptospira identification in blood, urine and spinal liquor.

         Cetrtain difficulties may happen at the differential diagnosis of the tuberculous meningoencephalitis with serous meningoencephalitis. Among the primary serous meningoencephalitis, the most frequent are lymphocytic serous choriomeningitis, and rare – meningitis of other virus etiology. Acute serous lymphocytic choriomeningitis is characterized with the acute start without any prodromal symptoms. The headache is abrupt, sometimes vomiting is present, shivering, sometimes pain in the extremities, the waist, the back, temperature rise in the first days up to 40°C. Sharply pronounced meningeal symptoms. Fever duration is from 5-7 up to 10-12 days. There are moderately pronounced alterations of inflammatory character in the spinal liquor, sometimes the deposition of fibrinal film and sugar level drop, cytosis from 50 up to 1000 cells in 1 ml, the lymphocytic one. The illness course is favourable. Meningeal symptoms disappear within several days. Spinal liquor normalizes within 15-30 days.

Secondary serous meningitis and meningoencephalitis may occur at various infections, such as flu, epidemic parotitis, poliomyelitis, infectional jaundice, chickenpox, shingles, typhoids, etc. In practice the most common is influenzal meningitis or meningoencephalitis and meningitis at epidemic parotitis. The clinical picture has got the signs of the main illness with meningal syndrome features and pathologic changes of the liquor resembling those occurring at the primary serous meningitis.

         In some cases meningism occurs as a result of toxic irritation of brain membranes, caused by poisoning with medical preparations, by kidneys illnesses, by worm invasion, various intercurrent infections. At meningism, the lumbar puncture may intensify the signs of brain membranes irritation, however at the tuberculous meningoencephalitis it brings the patient the release. The liquor flows out under the elevated pressure, the albumen-cellular composition of the liquor is without any changes or the changes are minor. The phenomena of meningism quickly disappear after a toxic stimulator stops its action.

The treatment is performed in a specialized hospital till the liquidation of clinical symptoms and liquor sanation, but not less than 6 months. 4 antimycobacterial preparations (isoniazidum, rifampicinum, streptomycin, pyrazinamidum) are administered in optimum maximal daily doses. At the disturbance of swallowing the preparations are introduced parenterally, intrarectally. At the grave course of tuberculous meningitis, endolumbar infusion of calcium chloride complex of streptomycin (0,1-0,2 g daily during 10-14 days), as well as glucocorticosteroids (25-30 mg/day during 1,5-2 months) are applied. To decrease cerebral oedema and hydrocephaly patients are administered dehydrating therapy (lazyx, hypothiazid, 10 % solution of manit, albumin). At cramps – chloralhydrate in enemas, 25 % solution of magnesium sulfate intramuscularly, depakin, sibazon. Vitamins B₁, B₆, C. After the extinction of a sharp period of meningitis, in case of pareses, paralyses, dibazol 1-3 ml 1 % subcutaneously, prozerin  1ml 0,05 % solution subcutaneously 1-2 times/day or 0,015 g orally 2-3 times/day are administered.

After clinical treatment patients are sent to an antituberculous sanatorium, where they continue chemotherapy with two antimycobacterial preparations, as well as rehabilitation measures not less than 4 months. Later patients are under the observation at antituberculous dispensaries and during 2-3 years they are administered prophylactic treatment course with isoniazidum.