Pulmonary Tuberculosis - Evolution and Clinical picture doc

¾ It consists of a collection of epithelioid cells surrounded by lymphocytes, fibroblasts and giant cells with bacilli in the center ¾ The primary tuberculous infection usually occurs

Pulmonary Tuberculosis

Evolution and Clinical picture

Global burden of TB

z In 1993 WHO declared TB a global emergency

z It is estimated that 9 million new cases of TB

occurred /year and 3 million TB deaths/year

z Tuberculosis poses a major problem for

developing countries

z 75% of TB cases in developing countries are in the economically productive age group ( 15-50 ys)

Why does the global burden of

TB increase?

z Improper management

z Impact of HIV pandemic

z Poverty, drug addiction and an increasing

number of homeless people

Mycobacterium tuberculosis

Three types can infect man:

1 The human type: the commonest type.

2 The bovine type.

3 The atypical or opportunistic

mycobacteria.

Mode of infection

z The disease is transmitted through

inhalation of infected sputum droplets or ingestion of infected milk

Primary Tuberculosis

z Occurs in the body when it is infected for

the first time

z Usually in children

z It can occur in adults who are exposed for

the first time

z Occasionally typical primary TB occur in

elderly people who lost their tuberculin sensitivity

¾ The characteristic lesion is the tubercle.

¾ It consists of a collection of epithelioid cells

surrounded by lymphocytes, fibroblasts

and giant cells with bacilli in the center

¾ The primary tuberculous infection usually

occurs in the lung but occasionally in the

tonsils or in the alimentary tract.

Lung 80%

Intestine (enteritis & tabes mesenterica) 10%

Throat (tonsillitis&cervical adenopathy) 5%

Skin, mucous membrane, conjunctiva,

Characteristics of primary tuberculous

lung lesion (primary complex):

1 Usually in the lower part of the upper lobe

or in the upper part of the lower lobe

commonly on right side (Ghon’s focus)

2 Coexisting endobronchitis and

lymphangitis.

¾ In children the nodal component is more obvious than lung component.

¾ In adulthood prim TB the lung component

is more evident & located more in upper

lobes, (that is why it is not easy to

distinguish between prim and postprim in adults unless recent tuberculin conversion has been documented).

macrophages so that it phagocytose & destroy

bacilli at a markedly enhanced rate compared to

nonstimulated cells

¾ Both hypersensitivity and immunity develop simultaneously

¾ Cell mediated type IV reaction is responsible for both phenomena.

Protective immunity (PI) Vs delayed

hypersensitivity (DH) in pathogenesis of TB

z The observation that advanced TB is associated with –ve tuberculin gave the questionable impression that +ve

tuberculin means good immunity.

z However, the current concept is that PI & DH are separate immunologic events

z In PI monocytes are recruited, activated to destroy

intracellular bacilli and differentiate into epithelioid cells forming the granuloma This is mediated by protective CD4

T cells (TH1)

z In DH non activated macrophages are killed, caseation

occurs followed by liquefaction , cavitation , extracellular bacillary multiplication morbidity & infectivity This is mediated through cytolytic CD4 cells (TH2)

z Blood born spread :

•Early in prim infection bacillemia occurs through lymph-hematogenous spread with seeding of bacilli

to all parts of the lungs and also other body organs.

•These dormant foci are reactivated later on with marked potential variability according to local and

general resistance.

I.Fate of primary focus (lung

component)

z (1)Good fate (regressive primary)

•Regression occurs when:

Low virulence of bacilli High host resistance

•Resolves & disappear completely by absorption

•Healing by fibrosis, calcification & even ossification

•Some bacilli may be imprisoned alive and become active again when resistance decreases

z (2)Bad fate (progressive primary – one type of postprim tuberculosis)

•Hematogenous dissemination

bronchial vein Rt side of Ht lungspulmonary vein Lt side of Ht allover the bodypulmonary artery one lung dissemination

II.Fate of primary focus (glandular

erosion Þ aspiration (2)Rupture in blood vessel Þ hematogenous spread

Clinical features:

• Symptomless,

• brief febrile illness at the time of tuberculin conversion that is indistinguishable from the many febrile illnesses of childhood Most children are symptom-free and are

discovered only when they are investigated as contacts of

an adult case,

• may occur in elderly people who have lost their

tuberculin sensitivity.

• In most cases there are no detectable physical signs.

• the child may be unwell with loss of appetite, fretfulness and failure to gain weight

• Cough is not usual but may occur, and may mimic the paroxysms of whooping cough when lymph nodes or

tuberculous granulation tissue impinge on the bronchial wall;

• wheeze.

• Sputum production is rare in children.

• Auscultation of the chest occasionally crepitations may

be heard over an extensive primary focus

• More obvious physical signs may be present if there is segmental or lobar exudation or collapse.

• This term is not used now

• It describes dense homogenous shadow in lung of children with tuberculosis

• This radiological appearance is due to

- hypersensitivity reaction to tubercle protein

- tuberculous pneumonitis (rarely caseating)

- collapse by

pressing lymph node pouring of caseous material caseous bronchitis and stenosis

- Erythema nodosa.

- Phlyctenular conjunctivitis.

- Allergic pleural effusion.

Other sequela of prim TB

• Broncholith

Calcified primary or lymph node extruded to bronchus hemoptysis

• Bronchiectasis mostly in upper lobe.

• Obstructive emphysema

external pressure or endobronchitis valve like mechanism

Radiological features

• Radiological changes are found at the time of tuberculin

conversion in 7-30% of young adults.

• Lymphadenopathy The hilar lymph node was most commonly involved but the paratracheal node was also frequently enlarged.

• Bilateral hilar adenopathy may be seen In adults the lung

component of the primary complex is usually more obvious and the nodal component may not be seen

• Radiological abnormality persists in a majority 6 months after

diagnosis but complete resolution is usual after 2 years.

Usually after a year or more but rarely, the lung or nodal

component of the primary complex or both may calcify

Calcification may occur in the absence of any chest radiographic changes in the acute stage.

POST PRIMARY TUBERCULOSIS

• Infection occurring after sometime from the primary infection.

• Tissue reaction is different from that in prim reaction because the ground has been changed by acquired immunity & hypersensitivity.

• Unlike prime disease, postprim bronchogenic TB is characterised

by increased local destruction caseation and cavity formation while lymph nodes enlarge rarely and lately (if suppressed immunity).

• This is because enhanced phagocytic activity prevents spread to lymph nodes aiming at localising infection and destroying bacilli.

Haematogenous Bronchogenic

acute TB septicaemia most common & most important

acute miliary TB 85% culture +ve

chronic hematogenous

dissemination

50% smear +ve

HEMATOGENOUS TB

A disease caused by dissemination of tubercle bacilli via blood to involve more than one organ not related to each other except by blood stream.

Source of bacillemia

- Progressive primary.

- During advanced bronchogenic TB

- Surgery on tuberculous origin (curettae of endometritis, massage

of arthritis)

so surgery should be under anti TB cover

-Tuberculous endangitis :

Seeding of bacilli into vessel walls may cause a

caseous vasculitis of the intima , with subsequent

discharge of bacilli into the blood stream leading to

miliary spread Usually solitary, caseating and

liquefying but can later heal by endothelial covering

Can occur in large veins & thoracic duct but less

commonly in arterial system.

acute :

Large no of bacilli + poor resistance

chronic:

small no of bacilli + good resistance

takes months or years to develop

Forms of dissemination

Acute Miliary TB

• Characterised by millet seed sized foci uniformly

distributed throughout the lung or other involved

Clinical features

Acute or classical miliary tuberculosis

• The disease is most common in infants and young children

• In children, the onset may be associated with an acute or

sub acute febrile illness

• In adults, the onset is insidious with gradual development

of vague ill-health, malaise, anorexia, weight loss and fever

• Cough, breathlessness, haemoptysis and night sweats are

less common

• Headache as a feature suggests associated tuberculous

meningitis, which is found in an appreciable proportion of cases.

• No physical signs.

• The chest is frequently normal on auscultation, although

crepitations may develop in the later stages

• Hepatomegaly, nuchal rigidity, lymphadenopathy and

splenomegaly may be found in a proportion of cases

• Choroidal tubercles are found in over 90% of children with

miliary tuberculosis but less commonly in adults

• Miliary lesions of the skin are very occasionally seen and may

take the form of macules, papules, vesicles or purpuric lesions.

Cryptic miliary or disseminated

tuberculosis

z A variant pathological type known as ‘non-reactive’

z The lesions are mainly necrotic, with no obvious

tuberculous histology, and are teeming with tubercle

bacilli The spleen and liver may be enlarged and

studded with irregular necrotic foci, usually less than 1

cm in diameter or only visible microscopically Any

organ may be affected.

z Increasingly being seen in the elderly, where it may be difficult to diagnose since the chest film may be normal, choroidal tubercles are absent and the tuberculin test may be negative

z The most common presentation is with the insidious onset of weight loss, malaise and a fever of unknown origin Anemia is usual and the ESR is often elevated

A variety of blood dyscrasias, including leucopenia, pancytopenia, aplastic anaemia, leukemoid reactions leucoerythroblastic anaemia and polycythemia, have been seen

z The liver function tests are commonly disturbed, with elevation of transaminases and alkaline phosphatase Hyponatremia and hypokalemia are also commonly seen.

• chest radiograph may be quite normal in the presence of

miliary tuberculosis, since the lesions are too small to be seen

• abnormal shadows are usually fairly evenly distributed and

may vary from faint shadows 1-2 mm in diameter to large

dense shadows up to 5 or 10 mm

• Usually the shadows are all a similar size but, as the

disease processes, larger coalescent shadows may

develop

• Evidence of a primary tuberculous complex, complicating

segmental lesion or a postprimary lesion may be seen

• Bilateral pleural effusion may occur

Radiology

Chronic haematogenous spread

Pathologically characterized by :

• tendency to fibrosis & calcification.

• caseation plays a minor role

• restriction of spread to certain areas (bronchi are rarely involved)

• presence of extra pulmonary lesions.

Radiologically :

• symmetrical distribution

• uniformity of size fo the lesions

• ± calcification or bilateral pleural effusion.**

Clinically :

• General toxemia

• Lack of local signs & symptoms (cough, expect, hemoptysis are not usual)

Pulmonary manifestations of chronic haematogenous TB

(1)Chronic miliary dissemination

sharply defined foci with typical tubercle structure connected with fibrotic strands

(2)Corticopleural dissemination

groups of foci are seen at the margin of one lobe beneath & implicating the pleura

(3)Disseminated emphysematous type

characterised by fibrosis alveolar dilatation emphysema & bullous formation (bullae alternating with fibrosing military nodules)

(4)Punched out cavities

•thin walled stamped out cavities

•no sputum as necrotic material is absorbed by blood rather than expectorated

•either heal or persist as thin walled spaces over years.

•differ from cavities of bronchogenic TB that show thick fibrosed walled

Extra Pulmonary manifestations of

1-urogenital 2-bone & joint 3-CNS tuberculomata 4-lymph nodes

5-serous membranes & meninges

• Postprimary pulmonary tuberculosis is by far the

most important type of tuberculosis, partly because it

is the most frequent and partly because

smear-positive sputum is the main source of infection

responsible for the persistence of disease in the

community.

• It is usually present in upper lobes and is often

bilateral as it starts in one lung and spread via

bronchi to other lung

Postprimary pulmonary tuberculosis

Bronchogenous TB

Postprimary pulmonary tuberculosis may arise in one of three ways:

(i) direct progression of a primary lesion;

(ii) reactivation of a quiescent primary or postprimary lesion;

(iii) exogenous reinfection.

Factors helping reactivation of TB lesion

• Bad housing, overcrowding ,Cigarette smoking , Alcoholism & addiction

• Fatigue, malnutrition & debility

• Silicosis through toxic effect on macrophage

• Health service professions

• Diabetes millets

• Steroids & immunosuppressants

• Lymphomas, leukaemia, AIDS

• Gastrectomy, peptic ulcer, vagotomy

• Hepatobiliary disease

• Pulmonary stenosis Æ oligemia ÆTB

(mitral stenosis decrease incidence due to plethora)

• Lung cancer developing in TB focus

Pathological picture depends on interrelationship between

• virulence of bacilli

• hypersensivity of the host

• local O2, CO2 & blood flow

2 forms may occur

1- apical reaction with fibrosis with or without calcification

living bacilli will be left in this focus & may cause bacillemia

later on.

2- chronic fibrocaseous TB

The Rt lung is more affected (usually subapically i.e post Seg Of UL & apex of LL)

Lower lobe TB is common in:

Diabetes Negroes pregnancy

• Cavitation occurs

• The pleura may be involved either as

TB pleurisy , Visceroparietal adhesion

• Hilar nodes not enlarged

• The majority of patients are middle-aged or elderly.

• no symptoms

• gradual onset of symptoms over weeks and months

• general symptoms, such as tiredness, malaise, loss of appetite,

weakness or loss of weight.

• febrile symptoms may be reported and night sweats

• Cough :

persisting for more than 3 weeks, should have a chest radiograph

• Sputum may be mucoid, purulent or blood-stained

• Haemoptysis is a classic symptom , massive haemoptysis is usually

due to erosion of a bronchial artery, which bleeds at systemic pressure .

Clinical features

Physical signs

• no physical signs in spite of extensive radiological changes.

• post-tussive crepitations in the upper zones or apices.

• There may be signs of consolidation

• In chronic disease, deviation of the trachea may occur due to

fibrosis

• The classical physical signs of a cavity are seldom found

even when large cavities are evident on the chest film

• Localized wheezes may occasionally be heard if the patient

has severe endobronchial tuberculosis.

In general, examination of the chest contributes relatively

little to the diagnosis or assessment of postprimary

tuberculosis Sputum examination and chest radiography are much more important However, it is essential to conduct a general examination of the patient as there may be additional tuberculous lesions outside the chest.