Download PULMONARY TUBERCULOSIS

PULMONARY TUBERCULOSIS
Shao Li
The department of respiratory of Ren-ji hospital
General Considerations
 Tuberculosis
is a chronic infection,
potentially of lifelong duration, caused
by two species of mycobacteria
M.tuberculosis and, rarely, M.bovis
 It was isolated by Robert Koch in 1882
 The
morbidity and mortality of
tuberculosis are high in developing
countries.
General Considerations
 The
disease
is
confined to the lungs
in most patients but
may spread to almost
any part of the body
Etiology
 The
tubercle bacillus
(M.Tuberculosis) is
aerobie, non-motile,nonspore-forming, high
in lipid content, and acid
and alcohol-fast
 It grows slowly .
 It can’t tolerate heat, but
It can live in humid or
dry or cold surroundings.
epidemiology
A key link of epidemic
 The source of contagious
 The route of spread
 Peoples of easily affected

Tuberculosis is
transmitted by
airborne droplet
nuclei(containing
tubercle bacilli )

Many droplet nuclei are
capable of floating in the
immediate environment
for several hours
 Large particles may
be inhaled by a person
breathing
the same
air and impact on the
trachea or wall of the
upper airway
The transmission is determined

The probability of contact with a case of TB
 The intimacy and duration of that contact
 The degree of infectiouseness of case
 The shared environment of the contact
Pathogenesis
tubercle
bacillus
Human immunity
Human Immunity after infected tubercle
bacillus and tuberculin hypersensitivity

The natural immunity of human to TB is
nonspecific
 After infected or given BCG vaccine,
human will obtain specific immunity
 The immunity of tubercle bacillus is cellmediated immunity
Human Immunity after infected tubercle
bacillus and tuberculin hypersensitivity

The cellular immunity develops within 4 to 8
weeks after infected with bacillus
Many immunologic cells involve in the
formation of pulmonary tuberculosis.
Two types of cells are essential in the
formation of TB

Macrophages: directly phagocytize TB and
processing and presenting antigens to T
lymphocyte
 T lymphocytes(CD4+): induce protection through
the production of lymphokines
T lymphocytes(CD4+)





Many lymphokines are involved in tuberculosis,
the interplay of these cytokines determine the
hosts response for example
IL-1 is related to fever
IL-6 is related to hyperglobulinemia
TNF is related to the killing of mycobacteria
formation of granolomas
other cytokines including IL-4,IL-5,IL-10 can
promote humoral immunity


Genetic factors play a key role in innate
nonimmune resistance to infection with
M. Tuberculosis
These genes may have a role in determining
susceptibility to tuberculosis
Koch phenomenon
It refers that there is different reaction to TB
infection between primary and secondary
infection
During the course of TB, there are three
basic pathologic changes

Including infiltration, hyperplasia, ulceration
or calcification
 These changes happen in different stage of
tuberculosis
 When host defense is destroyed and there is
much more bacterias, caseating ulceration
will exist
 Otherwise, when host defense is predominant
and there is less bacteria,perhaps hyperplasia
and calcification will happen
The result of the tuberculosis
after infection




Absorption
Fibrosis
Calcification
Deterioration: enlargement of infected aeras
and appear newer infiltrated regions or
spreading.
There are five common clinical patterns of
tuberculosis
1. Primary pulmonary tuberculosis (Primary
Complex and
Bronchial Lymphnod-Tuberculosis)
2. Milliary Tuberculosis (acute, subacute and
chronic hematogenous pulmonary tuberculosis)
3. secondary pulmonary tuberculosis
Infiltrative pulmonary tuberculosis
Chronic fibrocavenous pulmonary
tuberculosis
4.Tuberculous pleuritis
5.Extrapulmonary tuberculosis
Clinical Manifestations


systemic signs:
Most patients present as cases of pulmonary tuberculosis
with fever, weight loss, anorexia, fatigue, night sweats wasting.
respiratory signs:
Cough may vary from mild to severe, and sputum may be
scant and mucoid or copious and purulent
Hemoptysis may be due to cough of a caseous lesion or
bronchial ulceration
chest pain, tachypenea ect.
Physical signs: nonspecific.
Specific Manifestations

Allergic reaction to TB
 Non-reaction pulmonary tuberculosis
Laboratory and physical examinations

Chest radiography
 Sputum examination
 Tuberculin testing
 PCR test to detect TB
 TB antibody testing
 bronchoscopy
Radiology

Chest radiography is the most important
method to detect TB
 TB’s characteristics of a chest radiograph
favor the diagnosis of tuberculosis
as following :
(1) shadows mainly in the upper zone
(2) patchy or nodular shadows
(3) the presence of a cavity or cavities, although these, of
course, can also occur in lung abscess, carcinoma, etc
(4) the presence of calcification. although a carcinoma or
pneumonia may occur in an areas of the lung where
there is calcification due to tuberculosis
(5) bilateral shadows, especially if these are in the
upper zones
(6) the persistence of the abnormal shadows without
alteration in an x-ray repeated after several weeks
this helps to exclude a diagnosis of pneumonia or
other acute infection
Primary complex
Milliary Tuberculosis
acute milliary
tuberculosis
secondary pulmonary tuberculosis
infiltrate
Tuberculoma
Chronic fibro-cavitary pulmonary tuberculosis
cavity
Tuberculous effusion
Sputum examination
There are direct smear and culture
Direct smear examination is only
positive when large numbers of
bacilli begin to be excreted
Sputum examination
A
negative smear by no means
excludes tuberculosis
 A negative smear in the presence of
extensive disease and cavitation makes
the diagnosis less likely.
 Particularly
if the negatives are
frequently repeated
Tuberculin
testing
A positive tuberculin
test although it is of
great use in children, but it
has limited
diagnostic
significance in older age
groups
•
A reaction of less than 5 mm is considered
negative
•
5-9 mm is considered positive (+)
•
10-19 mm is considered positive (++)
•
more than 20 mm is considered positive
(+++)
A positive tuberculin skin test indicates

tuberculous infection, with or without disease
PCR test to detect TB
Bronchoscopy examination
White blood count and ESR
 The white blood count is usually normal.

In practice the white blood count is only
useful in a minority of cases, When the
patient is less ill and the radiological
shadowing less extensive the count is
often normal or high normal
ESR is often elevate
Diagnosis
According to the history, clinical signs, chest X-ray
and some other examinations, we can diagnose TB
A patient with tuberculous pulmonary disease
will come to the physician for one of three
reasons:
(1) Suggestive symptoms
(2) A positive finding on routine tuberculin
testing
(3) A suspicious routine chest roentgenogram
How to write the diagnosis
correctly?
 Generally,
we write the diagnosis
according to the site of TB, clinical
patterns, the result of sputum
examination and the history of
chemotherapy.
Differential Diagnosis
1234
Bronchiectasis may confused with chronic
fibrocavenous pulmonary tuberculosis. They also
have chronic cough, sputum production and
hemoptysis. Usually we can use chest x-ray
examination and CT scan to distinguish them.
Differential Diagnosis
1234
Cavitary lung abscess often involves the
dorsal segments of the lower lobes and posterior
segments of the upper lobes. Typically lung
abscess causes litt1e in the way of physical
findings, may have a fluid level, and is not
associated with patchy bronchogenic infiltrates.
In contrast, physical findings are prominent
over tuberculous cavities, fluid levels are rare.
And patchy infiltrates elsewhere are the rule.
Differential Diagnosis
1234
Acute bacterial pneumonias may resemble
florid tuberculosis in all particulars except for
the sputum examination and response to
antimicrobial drugs.
Differential Diagnosis
1234
Neoplasm may resemble tuberculosis. As in
an isolated coin lesion. An obstructing and
inconspicuous endobronchial tumor causing
distal cbronic inflammation or a caviting
neoplastic mass. ( An irregular cavity wall
suggests necorotic neoplasm. )
Differential Diagnosis

12345
Fever caused by some other diseases
complications

Pneumothorax
 Bronchiectasis
 Empyema
 Extrapulmonary expansion
 Hemoptysis
 Chronic pulmonary heart disease
Therapy

Chemotherapy
 Support therapy
 Surgical therapy
The metabolic state of
tubercle bacilli
 A groups
B
groups
 C groups
 D groups
Treatment

The principles of antituberculous
chemotherapy involve earlier,
combination, appropriate , regularly
and durations.
Treatment

The critical issue in TB control is adopting
the
DOTS (1995) ( Directly Observed
Treatment,
Short-course therapy; DOTS Strategy is
recommended by the WHO TB Program.


medicines used to treat tuberculosis are
classified as first-line and second-line agents
First-line essential antituberculous agents are the
most effective and are necessary components of
any short-course therapeutic regimen

First-line medicines include
Isoniazid, rifampin,
pyraziniamide,streptomycine

Second-line medicines include
ethambutal, para-amino-salicylic acid,
kanamycin, amikacin and ects.

Newer antituberculous drugs include
rifapentine, rifabutin quinolones
Isoniazid (INH)
first-line drug
 Isoniazid is a principal agent used to treat
tuberculosis
 It is universally accepted for initial treatment
 Now considered the best antituberculous drug
 It should be included in all TB treatment
regmens unless the organism is resistant
Advantages included





Inexpensive
Readily synthesized
Availabe worldwide
Highly selective for mycobacteria
Well tolerated(about only 5% of patients
exhibiting adverse effects)
Dosage

Tuberculosis organization have recommended
5 mg/kg daily for both groups
 Generally, a 300mg daily oral dose is adopted
Adverse effects
The two most important adverse effects
of isoniazid therapy are hepatotoxicity
and periphral neuropathy
Hepatotoxity

Isoniazid associated hepatitis is idiosyncratic
and increase in incidence with age
 We must measure liver enzymes before
administrating and during treatment
periods(usually monthly measure)
 If the liver enzymes level is higher than
normal,the drug must be discontinued
Periphral neuritis
It’s associated with isonizad develops at a
dose-dependent rate of 2 to 20% and probably
relates to interference with pyridoxine metabolism


This rate can be reduced to 0.2% with the
prophylactic administration of 10 to 50 mg of
pyridoxine daily
Resistance

It is associated with loss of pyrazinamidase
activity

Pyrazinamidase activity is determined by
PNCA gene, if PNCA gene is mutated, its
activity is lost pyrazinamidase
Rifampin (RFP)

first-line drug
It is also considered the most important and
potent antituberculose agent
 Like isoniazid it is bactericidal and highly
effective
 Unlike isoniazid, it is also effective against
most other mycobacteria as well as other
organisms
Advantage include

It is absorbed after either oral or intravenous
administration

It has both intracellular and extracellular
anti-bacterial activity
•
Dosage
Generally, 10mg/kg, 600mg daily
or twice weekly
•
Adverse effects
The most common adverse event
included gastrointestinal upset,
hepatitis
Resistance
Results from sponteneous point
multations that alter the  subunit
of the RNA polymerase
Pyrazinamide (PZA)


first-line drug
Pyrazinamide is a major oral agent used
against mycobacteria
It is an important bactericidal drug used
in short-course therapy for tuberculosis
Advantage

It is well absorbed after oral administration
 The drug is used to kill intracellular tubercle
bacillus
 It is distributed throghout the body,
excellent in CSF
Dosage
15 to 30 mg/Kg

Adverse effect
At the high dosages, hepatotoxity
is a prominent side effect

Resistance
Due to loss of pyrazinamidase activity
Streptomycin (SM)
first-line drug
It is frequently used in developing
country for its lower cost
It is administered only parenterally,
intramuscular or intravenous
Dosage

The usual adult dose is 0.5-1.0 g ( 10 to 15 mg/kg)
daily or five times weekly
 The dosage must be lowered and the frequency
of administtation reduced(to only
two or three times per week) in most patients
over fifty years old and in any patient with
renal impairment
Adverse effects
Ototoxity
Renal toxicity
 Resistance
Gene mutation

Ethambutal





second-line drug
It is used most often to protect against the
emergency of drug resistance
Oral administration
The dosage is usually 25 mg/Kg
It will distributes throughout the body except
CSF
Retrobulbar optic neuritis is the most serious
adverse effect
Regimens of chemotherapy



123
INH and RFP are the central agent
of any regimen based on their superior
bactericidal activity and low toxicity
PZA has special utility in promoting
rapid, early reduction in bacillary
burden; in drug-susceptible cases
PZA need be given only for the initial 2
months to produce this effect
Regimens of chemotherapy

123
EMB is useful primarily to protect against
the emergence of drug resistance in cases
with unknown initial susceptibility patterns
and large mycobacterial burdens
 EMB may be terminated if susceptibility is
reported or be continued throughout the
duration of treatment if resistance is noted
Regimens of chemotherapy


123
Streptomycin (SM), parenteral agent, has
found a diminishing role in modern therapy
due to problems with regularly administering
intramuscular injections
However, for patients with very extensive
tuberculosis, SM may accelerate initial
bactericidal activity.
Routine chemotherapy
Based on the character of the disease, the
following drug regimens are recommended
for initiation of therapy:
INH+SM+PAS 12-18 month
But the regimen is too long. Patients are unlikely
to employ with treatment. In actual practice, the
short-term chemotherapy is usually adopted. The
therapeutic effect of the short-term chemotherapy
is as well as the routine chemotherapy.
Short-term chemotherapy
Two or three drugs killing of organisms + one
drug restraint of organisms, for example


In usual mild or moderate disease with small
infiltrates and thin wall cavities :
INH+RFP+SM(EMB) (PZA) 2 M or
INH+RFP 4 -7 M
In extensive and severe disease, particularly when
large areas of caseation or thick-walled cavities
are identified:
INH+RFP+SM+EMB(PZA) 2 M or
INH+RFP 4 -7 M
chemotherapy
 To
initial patients : we can select shortterm chemotherapy 2HRZS(E)/4HR, the
duration lasts 6 months.
 To retreatment patients:3HRZSE/5HRZ ,
the duration lasts 6-12 months.
chemotherapy

To MDR-TB: MDR-TB means that resistant to
both INH and rifampin. We can select five
kinds of antitubercule drugs in the stage of
extensive .these drugs include
aminoglycosides(amikacin, kanamycin,
capremycin), cycloserine, EMB,
quinolones(levofloxacin, ofloxacin), PZA,
ethionamide.
 In the stage of consecutive, we can select three
kinds of drugs,including ethionamide,
quinolones and EMB.
 The whole therapy lasts at least 18 months.
Retreatment of Tuberculosis

Surgical Intervention :cavity,
Tuberculoma, empyema, severe
hemoptysis, ects.
Prevention

Prevention of Tuberculosis :Vaccination
 BCG Vaccination can obtain immunity
acquired for tubercle bacillus. Therefore, it is
one of the most important tuberculosis
prevention
 Vaccination target: infants children and
youngster of tuberculin negative (vaccination is
of course of no use in tuberculin-positive
persons)
Prevention
 Finding
patients earlier
 Treatment and management of patients
 Prevention with medicines
 The systemic organization of prevention
Management of severe
hemoptysis
 General
measures: eliminate patient’s anxiety, rest
in bed
 Maintain the airways
 Use of medicines of hemastatic, antitussive, ects.
 Supportive measures: keep water, electrolytes and
acid-base balance.
 Electric bronchoscopy: investigating the site and
cause of hemoptysis.
 Bronchial artery thrombosis
 Surgery
Case report




患者,男性,65岁。
主诉：干咳三个月伴乏力、消瘦一月余
现病史：患者自三个月前开始无明显诱因下出现咳嗽，
主要为干咳，亦无痰血、胸痛、呼吸困难等其他症状，
当时未予以注意。自近一月以来，自觉明显乏力，并
出现体重减轻，咳嗽仍以干咳为主，亦无其他呼吸系
统症状。遂今日来就诊。
自发病以来胃纳尚可，二便正常,近一月来夜间盗汗明
显。
既往史：有糖尿病史5年，无肺结核和肝炎等传染病病
史。
实验室检查
 血常规：正常
 PPD试验：++
 痰涂片找抗酸杆菌：阴性
胸片
讨
 诊断
 鉴别诊断
 治疗
论
选择题

1．浸润性肺结核最好发的部位是：B
 A、上叶前段
 B、上叶尖后段
 C、下叶内基底段
 D、中叶内侧段
 E、中叶外侧段

2．控制肺结核流行的最具有决定性的措
施是：A
 A、建立和健全各级防痨组织
 B、加强卫生宣教
 C、合理化疗
 D、卡介苗接种
 E、作好痰的处理

3．肺结核病人发热的最典型热型是：E
 A、稽留热
 B、驰张热
 C、波浪热
 D、间歇热
 E、午后低热

4．肺结核空洞和肺脓肿空洞的最主要的
鉴别诊断方法是：D
 A、病史
 B、体征
 C、胸部 X 线检查
 D、痰细菌学检查
 E、血白细胞检查






5．肺结核患者，咯血痰 2 天，突然大咯血，
从鼻中涌出，因害怕，患者极力屏气随即出现
烦燥不安，挣 扎坐起，极度呼吸困难，颤面青
紫，大汗淋漓，双眼上翻，立即应采取的抢救
措施是：D
A、鼻导管给氧、注射呼吸兴奋剂
B、进行人工呼吸
C、胸穿抽气
D、清除血块或气管切开
E、输液、输血、注射止血剂
6．成人结核菌素试验有：1：2000 阳性，
此结果最可能提示： E
 A、现在正患活动性肺结核
 B、可排除结核病
 C、非典型分枝杆菌感染
 D、结核病已经治愈
 E、曾有结核菌感染


7．干酪性肺炎属于下列疾病？C
 A、杆菌性肺炎
 B、肌炎球菌肺炎
 C、浸润型肺结核
 D、军团菌肺炎
 E、支原体肺炎






8．女性，63 岁，患肺结核 10 年，近一周来痰
中带血，10 分钟前大咯血约 600 毫升，突然血
中断，颜面 青紫，牙关紧闭，此时应立即采取
的抢救措施是：E
A、进行人工呼吸
B、使用呼吸兴奋剂
C、行导管吸氧
D、输血补液
E、解除呼吸道梗阻






9．男，20 岁，咳嗽半年，有血丝痰，易汗，
乏力，发热 1 个月，体温 37.5—38 度，胸片示
右上肺片状 阴影，密度不均可疑小透亮区，血
WBC：11＊10^9/L，诊断首先考虑：E
A、肺炎
B、肺癌
C、肺脓肿
D、支气管扩张症
E、肺结核






10．女，19 岁，乏力，低热三个月，咳嗽、咯
痰带血一周，X 线胸片示右肺上叶片状阴影，
大咯血一小时， BP：90/60mmHg，P：96 次每
分，采取下列哪种治疗措施最恰当？E
A、输血、补液
B、左侧卧位+青霉素静滴
C、吸氧+脑垂体后叶素静滴
D、止血芳酸静滴
E、右侧卧位+脑垂体后叶素静滴

11．结核病灶中常有生长速度不同的结
核菌群，其中致病力最强、传染性最大
的是： D
 A、耐药菌
 B、休眠菌
 C、细胞内酸性环境中的菌
 D、不断生长繁殖菌
 E、偶然繁殖菌

12.在结核病的化疗中坚持联合用药的最
主要目的是:B
 A.局部病灶内药物浓度高
 B.防止耐药菌的产生
 C.减少药物的不良反应
 D.缩短疗程,减少药物用量
 E.降低复发率

13.卡介苗是属哪种菌苗A
 A.活的无毒力的牛型结核菌苗
 B.灭活的牛型结核菌苗
 C.活的有毒力牛型结核菌苗
 D.活的无毒力人型结核菌苗
 E.活的有毒力人型结核菌苗

14.男性,30岁,乏力咳嗽1月余,伴低热,盗汗
和痰中带血1周,胸片示左上肺尖段炎症伴
有空洞形成,最可能的诊断是C
 A.肺囊肿继发感染
 B.癌性空洞伴感染
 C.肺结核伴空洞
 D.金黄色葡萄球菌肺炎
 E.慢性肺脓疡