Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis complex (referred to as Mycobacterium tuberculosis or Mycobacterium tuberculosis), which can involve multiple organ systems throughout the body. It can also involve the liver, kidneys, brain, lymph nodes and other organs. The main routes of transmission are through the respiratory tract, gastrointestinal tract, skin and uterus, but mainly through the respiratory tract. When the sputum of a TB patient who excretes bacteria is dried, the bacteria fly with the dust and are inhaled by others and cause infection. Whether a human being gets sick from inhaling droplets containing Mycobacterium tuberculosis is mainly related to various factors such as the number of inhaled TB bacteria, virulence and human resistance.
Causes of disease
The Mycobacterium tuberculosis complex includes Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum and Mycobacterium vole. The size of Mycobacterium tuberculosis is 0.3-0.6um×1-4um, fine and slightly curved, with slightly blunt ends. Acid-resistant staining is an important characteristic, and clinically, once found in the specimen, the majority of bacteria with positive acid-resistant staining represent Mycobacterium tuberculosis, which still requires culture and further strain identification. Mycobacterium tuberculosis grows slowly, and it takes at least 2-4 weeks for visible colonies to appear.
The cell wall of M. tuberculosis is rich in lipids, accounting for about 60% of the cell wall, and the main components are mycobacterium acid and acidified alginate. The former is the material basis of the anti-acid coloration reaction; the latter includes alglucose-bis-mycobacterium acid and thioglycolic acid, which have the roles of mediating granuloma formation and promoting bacterial survival in phagocytes, respectively. The cell wall also contains lipopolysaccharides, of which lipoarabinomannan is widely immunogenic and can be produced in large quantities by growing tubercle bacilli, which is a class of antigenic substances used in serological diagnosis.
Pathogenesis
The presence of the bacteria in the cells and the host immune response triggered by their long-term survival are the decisive factors affecting the pathogenesis, disease process and regression.
I. Natural history of Mycobacterium tuberculosis infection
After 3-8 weeks of infection the skin test for tuberculin (referred to as nodulin) turns positive and 95% of healthy infected patients with normal immune mechanisms have a natural regression of the primary syndrome and become a latently infected population, and about 5% develop the disease later due to potential infection rekindling.
Second, the host response and biological process of M. tuberculosis infection
The host immune response to Mycobacterium tuberculosis after it enters the human body has special significance in its pathogenesis, clinical course and regression.
The TB bacilli inhaled via droplets are phagocytosed by macrophages, activated alveolar macrophages, and form early foci of infection. The initial growth of tubercle bacilli within macrophages forms foci of solid cheese necrosis in the center, which can limit the continued replication of tubercle bacilli. Cellular immunity and delayed metaplasia mediated by T cells are formed during this phase. This has a decisive impact on the evolution and regression of TB disease.
The symbiotic phase is characterized by the persistence of the tuberculosis bacilli in most infected patients, the symbiosis of bacteria and host, and the central foci of fibrous encapsulated necrosis with caseous foci are considered to be the main sites of bacterial persistence.
Cheese foci contain TB bacteria that are capable of growth but do not multiply, and once liquefied, they provide an ideal environment for the bacteria to multiply.
Pathological changes
The characteristic pathologic changes of tuberculosis are granulomatous lesions and tuberculous nodules. The basic pathologic changes are exudative, proliferative, and necrotic (metaplastic) lesions.
I. Exudative lesions appear in the early stages of tuberculous inflammation or when the body is immunocompromised and the metaplasia is strong, and manifest as plasmacytosis or plasmacytic fibrinitis.
Second, proliferative lesions are the more characteristic lesions of tuberculosis pathomorphology, mainly manifested as tuberculous granulomas, which appear as a predominantly proliferative reaction when the number of infected Mycobacterium tuberculosis is low, virulence is low, and immune response is strong. Granulomatous lesions are not unique to tuberculosis and can also occur in diseases such as fungal disease and nodular disease. Tuberculous granulomas are characterized by epithelioid cells, Langhans giant cells, and caseous necrosis. The center of the nodule is often caseous necrosis surrounded by epithelioid cells, scattered Langhans cells, and lymphocytes and a few reactive fibroblasts on the outer side of the nodule. The epithelioid cells were formed by the transformation of macrophages by the action of mycobacterial lipids of Mycobacterium tuberculosis, while the Langerhans cells were formed by the fusion of epithelioid cells with each other. Langerhans cells are large and vary in size, generally 100-500 um in diameter, with several to hundreds of nuclei arranged in a wreath or horseshoe-like pattern on one side of the cytoplasm.
Third, necrotic lesions when the number of Mycobacterium tuberculosis, strong virulence, low body resistance or strong metabolic reaction can appear coagulative necrosis, necrotic tissue contains the lipids of Mycobacterium tuberculosis and intracellular lipids produced by macrophages in degenerative necrosis, this necrotic tissue pale yellow, uniform and delicate, fine granular, resembling cheese, also known as cheese-like necrosis. Cheese necrotic tissue contains Mycobacterium tuberculosis and can exist in a hibernating form for a long time.
Disease classification
I. Primary tuberculosis
Mycobacterium tuberculosis enters the lung from the respiratory tract and produces primary exudative lesions, which are mostly located in the lower part of the upper lobe or the upper part of the lower lobe under the dirty layer of the pleura. The main lesions of primary pulmonary tuberculosis are primary lesions in the lungs, lymphangitis and hilar lymph nodes, also known as primary syndrome.
Second, blood-borne disseminated pulmonary tuberculosis
Mycobacterium tuberculosis in the primary lesions in the lungs can cause systemic disseminated tuberculosis by invading the blood stream. Acute disseminated tuberculosis in the blood stream is also known as cornual tuberculosis, and chest CT shows diffuse cornual nodular shadow in both lungs with uniform nodule size and distribution. When a small amount of tuberculosis bacteria repeatedly enter the bloodstream can cause subacute hematogenous disseminated tuberculosis pulmonary tuberculosis.
Secondary tuberculosis
Tuberculosis caused by re-infection of the body with Mycobacterium tuberculosis after primary tuberculosis has healed spontaneously or been cured. It is mostly seen in adults. There are two views on the pathogenesis of secondary tuberculosis, endogenous re-infestation and exogenous reinfection. Endogenous re-inflammation refers to active lesions caused by the re-proliferation of latent Mycobacterium tuberculosis in the body under suitable conditions, and exogenous reinfection refers to tuberculosis caused by the re-invasion of external Mycobacterium tuberculosis into the body after the primary tuberculosis has healed.
Fourth, tuberculous pleurisy.
Including tuberculous dry pleurisy, tuberculous exudative pleurisy, tuberculous abscess chest.
V. Other extrapulmonary tuberculosis
Other extrapulmonary tuberculosis is named according to the site and organ, such as: osteoarthritis, tuberculous meningitis, renal tuberculosis, intestinal tuberculosis, etc.
Clinical manifestations
The clinical manifestations of pulmonary tuberculosis are diverse, and there may be no symptoms in the early stage. Typical tuberculosis has a slow onset and a long course, and may include low-grade fever, lethargy, loss of appetite, cough and hemoptysis. However, most lesions are mild and can be asymptomatic and are occasionally detected during physical examination. A small percentage of patients have prominent toxic symptoms, most often seen in cornified tuberculosis or caseous pneumonia. Symptoms in elderly patients with TB are easily masked by the symptoms of long-standing chronic bronchitis.
Systemic symptoms of tuberculosis
1, weakness generalized weakness, not doing physical work also feel tired. It does not recover even after rest. It is accompanied by loss of appetite and insomnia.
2, fever manifested as afternoon low-grade fever, is the most significant fever characteristics of tuberculosis, mostly in the afternoon 4-8 pm body temperature rises, generally between 37-38 ℃, mostly seen in light tuberculosis. Some patients have a temperature of 39°C, mostly seen in patients with acute, severe TB, such as blood-borne TB or caseous pneumonia. Some patients have prolonged irregular fever with body temperature of 38-39℃, mostly seen in chronic detoxification patients.
3, night sweating sweating after going to sleep and stop sweating after waking up is called night sweating, which is caused by autonomic dysfunction and is also one of the toxic symptoms of tuberculosis.
4.Unexplained menstrual irregularities or amenorrhea.
5.Loss of appetite, emaciation and weight loss.
6.Tuberculosis hypersensitivity reaction: rheumatoid arthritis, erythema nodosum, etc.
Respiratory symptoms of tuberculosis
Cough and sputum are common symptoms, recurring, mostly white mucous sputum, which can be purulent when combined with infection. A few patients can cough up cheese-like material. In case of co-infection, coughing is aggravated and sputum is increased. Patients with bronchial tuberculosis may have a violent and frequent cough.
Hemoptysis is a common symptom of pulmonary tuberculosis, usually blood in sputum. Medium or large amount of hemoptysis may also occur.
Chest pain is generally more fixed and persistent, and it increases with deep breathing or loud laughter or coughing, indicating that the lesion is adjacent to or invades the pleura.
Shortness of breath may occur when the lung tissue is extensively and severely damaged or when there are extensive pleural adhesions, and may be aggravated by shortness of breath, especially after activity.
Physical signs of pulmonary tuberculosis
Early lesions or small lesions may have no positive signs, but when the lesions are large, there may be decreased respiratory mobility on the affected side, decreased breath sounds, and wet rales may be heard in some patients. When the lung lesion is extensively fibrotic or destroyed, there may be collapse of the thorax on one side, narrowing of the rib space, and compensatory emphysema on the opposite side.
Ancillary tests
Laboratory tests
A tuberculosis bacillus test is the most specific method to confirm the diagnosis of pulmonary tuberculosis.
1, sputum smear sputum smear antacid staining is fast and easy, and the diagnosis of tuberculosis can be basically established with a positive smear. However, with the increasing incidence of non-tuberculous mycobacteriosis in China, it needs to be excluded.
2, tuberculosis culture in addition to the ability to understand the growth and reproduction of tuberculosis bacteria, but also can be used for drug sensitivity testing and mycobacterial identification, tuberculosis bacteria grow slowly, the use of modified Roche medium generally takes 4-8 weeks to report. Culture is time-consuming, but accurate and reliable, and drug sensitivity testing of cultured strains is particularly important for re-treatment of tuberculosis or suspected drug-resistant tuberculosis.
3, TB genetic testing and identification: the application of polymerase chain reaction (PCR) to amplify the DNA contained in trace amounts, the method is fast and easy, and can identify the mycobacterial type.
Imaging examination
Chest X-ray and chest CT are very important to find out the location, scope and nature of lesions in the lung with or without cavities, especially chest CT is important to find tiny lesions or hidden lesions. It also allows dynamic monitoring of the recovery of lesions during treatment.
Tuberculin test is a reference indicator for the diagnosis of tuberculosis infection. PPD (PPD-C) made from human type tuberculosis bacilli and BCG-PPD made from BCG vaccine in China are of good purity and have been widely used in clinical practice. A strong positive reaction. A strong positive reaction often indicates active TB disease.
Other tests
Severe tuberculosis may be associated with anemia, and severe tuberculosis may present with leukopenia or leukemia-like reactions. Increased blood sedimentation is commonly associated with active TB but has no diagnostic value. In sputum-negative patients, specific antibodies in the serum are of diagnostic value as an aid. Fiberoptic bronchoscopy is important for detecting bronchial tuberculosis, aspirating secretions, or doing pathogenic bacteria or exfoliative cell examination and biopsy.
Diagnostic points
The diagnosis of tuberculosis requires a combination of clinical manifestations, imaging features, sputum tuberculosis bacilli and other information. Sputum-positive cases require further strain identification and drug-sensitivity testing, while sputum-negative cases require more ancillary tests, CT, fiberoptic bronchoscopy, serum antibodies, and even biopsy, and diagnostic treatment can be performed in a fashion if necessary.
Diagnosis of extrapulmonary tuberculosis
Diagnosis of various types of plasma cavity tuberculosis is made mainly by combining clinical manifestations with a comprehensive analysis of nocturnal exudate laboratory tests. Tuberculous meningitis is diagnosed based on a comprehensive analysis of features such as subacute or chronic nonsuppurative meningitis. For intestinal tuberculosis, gastrointestinal X-ray and fiberoptic colonoscopy are helpful for diagnosis. Diagnosis of osteoarticular and urological tuberculosis is based on clinical manifestations and imaging examinations. Tuberculosis of lymph nodes, liver, spleen, etc. depends on biopsy to confirm the diagnosis.
Differential diagnosis
The clinical and X-ray manifestations of pulmonary tuberculosis are similar to those of many non-tuberculous diseases, which can be easily misdiagnosed.
Lung cancer is mostly seen in middle and old age, smoking history is common, often without obvious symptoms of tuberculosis poisoning, irritating cough, chest pain, progressive wasting, tuberculosis lesions on X-ray mostly have satellite foci and calcification, lung cancer lesions often have cut marks and burrs at the edges, chest CT helps to differentiate the two, fiber bronchoscopy and lung biopsy can be done if necessary, if it is difficult to exclude lung cancer clinically, dissection of the chest can be considered if necessary.
Pneumonia with rapid progression of secondary tuberculosis forming caseous pneumonia is easily misdiagnosed as lobar pneumonia caused by pneumococci. Pneumonia mostly has an acute onset, high fever, chills, chest pain with rust-colored sputum, X-ray lesions are often limited to a single lobe, and antibiotic therapy is effective. Caseous pneumonia mostly has symptoms of tuberculosis toxicity, slow onset, yellow mucus sputum, X-ray lesions mostly located in the right upper lobe, may involve multiple lobes and segments, uneven density, may appear worm-like cavities, anti-tuberculosis treatment is effective.
In lung abscess, the cavity of lung abscess is mostly seen in the lower lobe of the lung, the inflammatory infiltration around the abscess is more serious, and there is often fluid level in the cavity, while in pulmonary tuberculosis cavity is mostly seen in the upper lobe, and there is less fluid level in the cavity. In addition, lung abscesses have an acute onset, high fever, large amount of pus sputum, no tuberculosis bacilli in the sputum, significant increase in total blood leukocytes and neutrophils, and effective antibiotic treatment.
Disease treatment
Drug therapy
Anti-tuberculosis chemotherapy plays a decisive role in controlling tuberculosis, and a reasonable chemotherapy can make the lesions destroyed and eventually cured. The World Health Organization has divided anti-tuberculosis drugs into five groups. The first group of drugs is usually used for primary treatment of tuberculosis, and other groups of drugs may be needed for drug-resistant tuberculosis or for those who cannot tolerate first-line drugs due to allergies or toxic side effects. The principles of anti-tuberculosis treatment can be summarized in 10 words: early, combination, appropriate dosage, regularity, and whole course.
Table 1 Grouping of anti-tuberculosis drugs
First-line oral antituberculosis drugs
isoniazid (H), rifampin (R), ethambutol (E)
pyrazinamide (Z), rifapentine (Rft), rifabutin (Rfb)
Anti-tuberculosis drugs for injection
Streptomycin (S), Kanamycin (Km)
Amikacin (Am), capreomycin (Cm)
Fluoroquinolones
Ofloxacin (Ofx), Levofloxacin (Lfx), Moxifloxacin (Mfx)
Second-line oral antibacterial anti-tuberculosis drugs
Ethioisonicotinamide (Eto), prothioisonicotinamide (Pto), cycloserine (Cs), terizidone (Trd), para-aminosalicylic acid (PAS), para-aminosalicylic acid isoniazid (Pa), aminothiourea (Thz)
Anti-tuberculosis drugs of uncertain efficacy in the treatment of multidrug-resistant tuberculosis
Clofazimine (Cfz), linezolid (Lzd), amoxicillin/potassium clavulanate (Amx/Clv), clarithromycin (Clr), imipenem (Ipm)
First, early tuberculosis early, alveolar infiltration of inflammatory cells and fibrin exudation, alveolar structure still remains intact, and reversibility is large. At the same time, bacterial reproduction is vigorous and phagocytes are active in the body, so anti-tuberculosis drugs can best inhibit and kill bacteria with active metabolism and growth. Early treatment can facilitate the absorption and dissipation of lesions without leaving traces.
Second, the combination of both primary and re-treatment patients should be combined with drugs, clinical treatment failure is often caused by a single drug. The combination of drugs must be combined with two or more kinds of drug therapy, so as to avoid or delay the emergence of drug resistance, but also to improve the bactericidal effect. Both intracellular bactericidal drugs and extracellular bactericidal drugs, so that the chemotherapy program to achieve the best efficacy, and can shorten the course of treatment, reducing unnecessary economic waste.
Third, the right amount of drugs for any disease treatment must have an appropriate dose, and does not bring toxic side effects to the human body. Almost all anti-tuberculosis drugs have toxic side effects, such as too large a dose, the drug concentration in the blood is too high, the digestive system, the nervous system, the urinary system, especially the liver and kidneys can produce toxic side effects. Insufficient dose and low blood concentration will not achieve the purpose of antibacterial and sterilization and will easily produce drug resistance. So be sure to use the appropriate dose, under the guidance of a specialist in medicine.
Fourth, the regularity of the drug must be under the guidance of a specialist. Because the tuberculosis bacillus is a kind of stubborn bacteria with long division cycle, slow growth and reproduction, which is difficult to kill. If you stop using the medication when the symptoms are relieved, it will easily lead to the occurrence of drug resistance, resulting in treatment failure.
Fifth, the whole so-called whole drug is the doctor according to the patient’s condition to determine the chemotherapy regimen. The time required to complete the chemotherapy regimen is about six months to a year for the full course of treatment, and longer for drug-resistant tuberculosis.
Therefore, in order to treat TB thoroughly, the above five principles must be followed: early, combination, appropriate amount, regularity, and full course, in order to ensure effective and thorough treatment.
Surgical treatment
Surgery can also be considered for tuberculosis balls larger than 3 cm that are difficult to distinguish from lung cancer, recurrent unilateral thick-walled fibrous cavities, persistently positive sputum bacteria with long-term medical treatment, or unilateral damaged lung with bronchial dilatation, or recurrent hemoptysis, bronchopleural fistula, or tuberculous pustule that has failed to respond to medical treatment.
Interventional treatment
Interventional treatment of tuberculosis includes thoracic injection of anti-tuberculosis drugs, fiberoptic bronchoscopy (local injection, freezing, balloon dilation, etc.), bronchial artery embolization, etc.
Other treatments
Adjunctive treatment for TB includes immunomodulatory therapy, nutritional support therapy. Chinese medicine treatment.
Prognosis of the disease
Clinical cure of tuberculosis is defined as complete disappearance of tuberculosis toxicity symptoms, stabilization of the lesion and cessation of bacillary excretion after treatment. The way of healing varies depending on the nature, scope, type of lesion, reasonable treatment and immune function of the body, but the TB bacilli are still alive in the lesion, and once the body’s resistance decreases, the TB bacilli may become active again and multiply, resulting in rekindling or spreading, which is not true healing.
As long as you adhere to regular and reasonable treatment as prescribed by the doctor, you may recover and reduce the chance of recurrence to the greatest extent.
Dietary attention
Tuberculosis is a chronic wasting infectious disease caused by Mycobacterium tuberculosis. Treatment should be holistic, using anti-tuberculosis drugs and at the same time must increase body resistance and strengthen nutrition, which can supplement patients with sufficient heat and nutrients to meet the needs of tuberculosis lesion repair and enhance body resistance.
Tuberculosis calorie needs more than normal people, generally required to reach 30 kcal per kilogram of body weight supply, the total daily intake of about 2000 kcal, light manual workers 40 kcal per kilogram of body weight, the whole day about 2400 kcal.
Because TB patients consume a lot of protein, and protein is an important nutrient for repairing tissues and is beneficial for healing of lesions and recovery of the disease. The daily protein intake of tuberculosis patients should be 1,2 to 1,5 grams per kilogram of body weight, with a total daily intake of 80 to 100 grams, of which high-quality protein, such as meat and poultry, aquatic products, eggs, milk and soybean products should account for 50% of the total protein intake.
Vitamin A enhances the immunity of the body, vitamin D promotes calcium absorption, vitamin C facilitates the healing of lesions and hemoglobin synthesis, and the B vitamins have the effect of improving appetite. Fresh vegetables and fruits are also the main source of vitamins. In addition, milk, eggs, offal and other foods are rich in vitamin A. Peanuts, beans, lean meat, etc. are rich in vitamin B.
Prohibit smoking and drinking alcohol. Smoking increases the irritation of the respiratory and digestive tracts, and drinking alcohol dilates blood vessels and aggravates the symptoms of coughing and hemoptysis.
In addition, the diet of TB patients should pay special attention to calcium and iron supplements, calcium is the raw material for calcification of TB lesions, and milk contains a lot of calcium and good quality. Patients should drink 250-500 grams of milk daily. Iron is a necessary raw material for the production of hemoglobin, so patients with hemoptysis and blood in stool should pay more attention to supplementation.
Disease care
Tuberculosis is a chronic infectious disease and its treatment is a long process. During the treatment process, attention should be paid to the protection of close contacts and personal care of patients.
It is best to let the patient live in a room alone and choose a room with a sunrise or good ventilation. The room should not be humid. Bedding and eating utensils should be used alone and disinfected regularly. It is better to spit in paper and then burn it, and avoid spitting anywhere. Patients should not come into contact with children and try not to go to public places to avoid spreading the infection and affecting the health of others. Cover the mouth and nose with a handkerchief when coughing and sneezing. Bedding should be frequently exposed to the sun, and dishes should be disinfected by boiling.
Patients with tuberculosis often have a poor appetite, so it is advisable to eat a light, easily digestible diet and pay attention to appropriate protein and vitamin supplements. When the patient’s appetite improves during the improvement period, he should eat more lean meat, fish, eggs, soy products and fresh vegetables. The diet should be regular and not partial in choice to ensure the intake of various nutrients. Patients should abstain from smoking and alcohol.
When a patient has a small amount of hemoptysis, the caregiver should first stabilize his emotions, because excessive tension and excitement can increase the amount of hemoptysis, and excessive fear of hemoptysis and desperate breath holding can easily cause asphyxia. The patient should be made to lie still and cold towels should be applied to the forehead or chest. You can also eat some cold drinks to help stop the bleeding. When hemoptysis has just stopped, it is not advisable to get up and move immediately.
Patients with sudden hemoptysis or sudden cessation of hemoptysis accompanied by chest tightness, shortness of breath, irritability, cold sweat, or even purple face, which is an omen of asphyxia, should be immediately put on their sides, encouraged and helped to hemoptysis out, and immediately sent to the hospital for resuscitation.
Patients suffering from infectious diseases may affect family life, work and interpersonal communication, so they will have stress and emotional disorders, and there will be many emotional side effects of taking drugs, including gastrointestinal reactions, drug hepatic and renal toxicity, insomnia, excitement or even depression, so it is necessary to strengthen psychological support and comfort and encourage. To establish confidence in overcoming the disease, eliminate anxiety, depression, loneliness, and carry out the necessary recreational and leisure activities to distract the attention to the disease, in order to eliminate the adverse psychological.