Download PUL.-TUBERCULOSIS

PULMONARY
TUBERCULOSIS
Definition
Chronic inflammatory response of
prolonged duration
(weeks,months,years) provoked by the
persistence of the causative organism
Mycobacterium tuberculosis
accompanied by tissue destruction and
repair of lung tissue.
Pulmonary Tuberculosis
• Tuberculosis (abbreviated as
TB for tubercle bacillus or
Tuberculosis) is a common
and often deadly infectious
disease caused by
mycobacteria, mainly
Mycobacterium tuberculosis.
Tuberculosis usually attacks
the lungs (as pulmonary TB).
TB Transmission
What is TB?
TB is a disease caused by infection with a
bacteria called Mycobacterium
tuberculosis.
Causative organism:
Mycobacterium tuberculosis
Morphology :
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Slender
Aerobic
Weakly Gram + Rod
Grows in straight or branching chains
Unique waxy cell wall
Acid Fast due to MYCOLIC ACID in the
cell wall
AFB smear
Mycobacterium tuberculosis (stained red) in sputum
Pulmonary Tuberculosis
• Scanning electron
micrograph of
Mycobacterium
tuberculosis
Characteristics of Mycobacterial
infection
• Infiltration of mononuclear cells
• Tissue destruction
• Healing with scar formation and fibrosis
Other Characteristics:
• Mode of transmission – Person to person by
air born organisms
• Reservoir – Humans with active disease of the
lung
• Primary infection – Usually asymptomatic
• Secondary infection - Reactivation of primary
focus
• Tissue destruction by inflammatory cells
• Attempts at repair with granuloma formation and
fibrosis
TB Transmission
How can you catch TB?
TB is spread through tiny
drops sprayed into the air
when an infected person
coughs, sneezes, or
speaks, or another person
breathes the air into their
lungs containing the TB
bacteria.
Epidemiology of Tuberculosis
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Affect 1.7 billion people worldwide
8-10 million new cases every year
1.6 million deaths every year
Over 10 million people infected with both
HIV and M. tuberculosis
• 14000 new cases in USA every year
Predisposing factors
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Poverty
Overcrowding
Any chronic debilitating illness
Certain disease states:
- Diabetes mellitus
- Hodgkins lymphoma
- Chronic lung disease (esp. silicosis)
- Chronic renal failure
Other predisposing conditions:
• Malnutrition
• Alcoholism
• Immunosupression
TB - Infection & Disease
Categories of TB - Latent & Active
TB disease varies with age and
the ability of your body to fight off
bacteria.
HIV is the strongest risk factor
for the progression of Latent TB
to Active TB infection.
Immunology
• Delayed hypersensitivity reaction
• Mantoux Test :
- Intradermal inj. of PPD
- Visible/palpable induration >10 mm after
72 hrs
- Signifies T-cell mediated immunity to
mycobacterial antigen
Diagnostics
• Inject intradermally
0.1 ml of 5TU PPD
tuberculin
• Produce wheal 6 mm
to 10 mm in diameter
• Represent DTH
(delayed type
hypersensitivity)
Reading of Mantoux test
• Read reaction 48-72
hours after injection
• Measure only
induration
• Record reaction in
mm
Even if a Skin Test is Negative…..
Coughing
up Blood
Chills
Chiclls
Fatigue
Difficulty
in
Breathing
THINK TB!
FFever
Anorexia
Loss
of Appetite
Night sweats
• False negative; certain viral inf.,
sarcoidosis, malnutrition, hodgkins
lymphoma, immunosupression, miliary
tuberculosis.
• False positive; atypical mycobacterial inf.,
BCG vaccination
Pathogenesis :The Players
(mononuclear phagocyte system)
• Macrophages
– Scattered all over (microglia, Kupffer cells,
sinus histiocytes, alveolar macrophages, etc.)
– Circulate as monocytes and reach site of
injury within 24 – 48 hrs and transform
– Become activated by T cell-derived cytokines,
endotoxins, and other products of
inflammation
Macrophages serve to eliminate injurious agents and initiate repairhowever, they are as well responsible for much of the tissue injury that
occurs
Tissue macrophage
Activated T cell or NK cell
Non Immune activation:
Endotoxins,
fibronectin,
chemical mediators
IFN-g
Activated macrophage
Fibrosis (Scaring)
Tissue injury
Toxic oxygen metabolites
Metallo-proteases
Coagulation factors
AA metabolites and NO
Growth factors involved
in fibroblast proliferation
(PDGF,TGFb,FGF)
Angiogenesis factors
(FGF,VEGF)
Collagen deposition
(IL-13 and TGFb)
The Players….
• T and B lymphocytes
– Antigen-activated (via macrophages and
dendritic cells)
– Release macrophage-activating cytokines (in
turn, macrophages release lymphocyteactivating cytokines until inflammatory
stimulus is removed)
• Plasma cells
– Terminally differentiated B cells
– Produce antibodies
The dominant cellular player in pulmonary tuberculosis
is the tissue macrophage
Blood monocyte
Tissue macrophage (RES)
migrate into tissue
within 48 hours
after injury
Kupffer cell
(liver)
Microglia (CNS)
Histiocytes
(spleen)
and differentiate
Alveolar macs
(lung)
It is joined by lymphocytes and plasma cells,
however mast cells and eosinophils are as well involved in
chronic allergic diseases
Lymphocyte
Plasma cell
Pathogenesis
Pathogenesis
• A-Primary Pulmonary Tuberculosis
(0-3 weeks):
inhalation of Mycobacteria---enter alveolar
macrophages---replication in phagosome--bacteremia---seeding of multiple sites
Pathogenesis
• B -Primary pulmonary tuberculosis
(>3 weeks):
Alveolar macrophages---IL-2---T Cells--- Thelper cells---Activated macrophages (i)--TNF,Chemokines—Hypersensitivity
(epith. granulomas) and (ii)---Nitric
oxide,reactive O2 sp.---Immunity
(bactericidal activity)
Primary Tuberculosis
• Develops in unexposed, unsensitized
persons
• Mostly(95%) asymptomatic; Infection
contained
• In 5 % symptomatic; Primary progressive
tuberculosis
• Source of organism; Exogenous
• Difficult to diagnose
Primary Tuberculosis
Presentation :
• Lung consolidation;
Lower and middle lobes
• Hilar lymphadenopathy
• Pleural effusion
• In majority organism remain dormant
• In severe immunosupression
- TB Meningitis
- Miliary Tuberculosis
Secondary Tuberculosis
• Arises in previously sensitized host
• Many years after primary infection
• Reactivation of latent infection or
overwhelming exogenous infection
• Involves apex of upper lobes
• Cavitation more prominant
Secondary Tuberculosis
• In majority symptomatic; insidious onset of
malaise, anorexia, weightloss, fever,
productive cough (mucoid, purulent,
hemoptysis) , pleuritic pain.
• Extrapulmonary manifestations
• May be asymptomatic when localised
TB Infection & Disease
There are 2 Categories of TB: Latent & Active
TB infection of the lungs can
fall into 2 categories of
disease: Latent TB or Active
TB.
Latent TB means a person is
infected by TB bacteria, but
cannot infect others, and is not
coughing or appearing sick.
Latent TB means the body’s
immune system has contained
the infection.
TB - Infection & Disease
Categories of TB - Latent
Persons with latent TB are
identified by a positive skin
test (PPD).
Persons who are not
infected with
Mycobacterium
tuberculosis have a
negative skin test (PPD).
In Pulmonary Tuberculosis
macrophage accumulation persists by different
mechanisms:
• Continued recruitment of monocytes from
the circulation
• Local proliferation
• Prolonged survival and immobilization
Outcome of Tuberculous infection
• Ulcers
• Fistulas
• Granulomatous diseases
• Fibrotic diseases
• and combinations of the above
Diagnosis
• History
• Physical examination
• X-Rays ;Consolidation/ cavitation in lung
apices
• Sputum for AFB :
- Z.N Stain
- > 10000 organisms in clinical specimen
Diagnosis
• Sputum Culture :
- conventional ---upto 10 weeks
- liquid --- within 2 weeks
• P.C.R :
- 10 org. in clinical specimen
Chest radiography
• No chest X-ray pattern is absolutely typical
of TB
• 10-15% of culture-positive TB patients not
diagnosed by X-ray
• 40% of patients diagnosed as having TB
on the basis of x-ray alone do not have
active TB
Number of sputum samples required
• overall diagnostic yield for sputum examination
related to
– the quantity of sputum (at least 5 mL)
– the quality of sputum
– multiple samples obtained at different times to the
laboratory for processing
• 3 samples obtained at least eight hours apart with at least
one sample obtained in the early morning
Cultures
Morphology
A-Primary Tuberculosis :
• Ghon complex
- subpleural parenchymal lesion (lower
part of upper lobe)
- hilar lymphadenopathy
• Progressive fibrosis
• Calcification
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Histology :
Epithelioid cell granulomas
epithelioid cells
lymphocytes
plasma cells
multinucleated langhan’s type giant cells
with or without central caseation
Granulomatous Inflammation
• Clusters of T cell-activated macrophages,
which engulf and surround indigestible
foreign bodies (mycobacteria, H.
capsulatum, silica, suture material)
• Resemble squamous cells, therefore
called “epithelioid” granulomas
Morphology
B – Secondary Tuberculosis :
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Focus of consolidation, < 2 cm
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Within 1-2 cm of apical pleura
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Histology :
Caseating granulomas
Morphology
C – Progressive Pulmonary Tuberculosis:
• Elderly/ immunosupressed
• Apical lesion---Spreads to adjacent lung tissue--Involves : a) Bronchi b) Blood vessels
• Irregular cavity , poorly walled off by fibrosis
Morphology
D – Miliary Pulmonary Tuberculosis :
• Organisms draining through lymphatics enter
venous blood and circulate back into the lung
and involving most of the parenchymal tissue.
• Microscopic or small visible yellowish white foci
resembling “millet” seeds
• Coalesce to form larger cavity
Pleural cavity :
Involvement of Pleural cavity in Progressive
pulmonary tuberculosis;
• Serous pleural effusion
• Tuberculous empyema
• Obliterative fibrous pleuritis
E – Endobroncheal,Endotracheal or
Laryngeal Tuberculosis :
• Spread via lymphatics or
• Expectoration of infected material
• Histology :
- Mucosal lining studded with tiny
granulomas
TB Infection and Disease
The lungs are the most
common place for TB.
This is known as
pulmonary TB.
TB of the voice box is
the second most
common and is usually
called laryngeal TB.
F – Systemic Miliary Tuberculosis :
• Bacteremia--- Involvement of Systemic Arterial System--Any organ :
- Liver
- Bone marrow
- Spleen
- Adrenals
- Meninges
- Kidneys
- Fallopian tubes
- Epididymus
• G – Isolated Tuberculosis :
• Any organ or tissue can be involved in isolation ;
hematogenous spread ;
- Meninges
- Kidneys
- Adrenals (Addison’s Disease)
- Bone
- Fallopian tubes
- Vertebra (Pott’s Disease)
. Paraspinal Cold Abscess track along tissue planes
( Abdominal or pelvic mass)
H – Intestinal Tuberculosis :
• Drinking contaminated unpasteurised milk
or
• Swallowing of coughed - up infected
material in patients with advanced
pulmonary tuberculosis
• Organism invade lymphoid aggregates--Granulomatous inflammation--- Mucosal
ulceration (usually illeum)
I- Lymphadenopathy :
• Most common presentation of
Extrapulmonary Tuberculosis
• Usually in Cervical region (“Scrofula”)
• Unifocal or localised
• Multifocal in HIV patients
Lymph Nodes and Lymphatics
• Lymphatics drain tissues
– Flow increased in inflammation
– Antigen to the lymph node
– Toxins, infectious agents also to the node
• Lymphadenitis, lymphangitis
• Usually contained there, otherwise bacteremia
ensues
• Tissue-resident macrophages must then prevent
overwhelming infection
Systemic effects
• Fever
– One of the easily recognized cytokinemediated (esp. IL-1, IL-6, TNF) acute-phase
reactions including
• Anorexia
• Skeletal muscle protein degradation
• Hypotension
• Leukocytosis
– Elevated white blood cell count
Systemic effects (cont’d)
– Bacterial infection (neutrophilia)
– Parasitic infection (eosinophilia)
– Viral infection (lymphocytosis)
Granulomatous inflammation
Granulomas are millimeter size nodules of
chronic inflammatory cells that can be isolated
or confluent.
Granuloma formation is the result of dealing
with indigestible substances or pathogens
and walls them off
The essential component are modified
macrophages named epithelioid cell (because
of shape).
Epithelioid cells can form multinucleated giant
cells.
Epithelioid cells are surrounded by a collar of
lymphocytes and occasionally plasma cells.
Fibrous connective tissue often surrounds
granulomas (remodeling of tissue)
Areas within the granuloma can undergo
necrosis (prototype: caseous necrosis in
tuberculosis). Necrosis can lead to
calcification or liquefaction and formation of a
cavern if drained.
Microscopic and macroscopic appearance of
tuberculosis
Characteristic tubercle with
caseating necrosis in center
Cavity formation due to
liquefaction and drainage of TBC
lesion
Macroscopic lesion
in TBC
Differential Diagnosis :
• LEPROSY
-Mycobacterium Leprae
Tuberculoid Form:
Granulomas with acid fast bacilli
in macrophages and epitheloid cells.
• CAT SCRATCH DISEASE
-Gram positive bacilli
Rounded or stellate granulomas
containing central granular debris with
neutrophils.
• SCHISTOSOMIASIS
-S.Mansoni,S hematobium,S.japonicum
Granulomas around eggs with
numerous eosinophils .
• FUNGAL
Cryptococcus neoformans
Organism yeast like, budding, 5-10 mm
clear capsule.
Coccidioides immitis
Organism appears as 30 – 80 mm cyst
containing spores of 3 – 5 mm each.
• IN ORGANIC METALS , DUSTS
Silicosis :
Beryliosis :
Involvement of lungs ,fibrosis .
• SARCOIDOSIS
Unknown Etiology :
Noncaseating granulomas ,langhan
and foreign body type giant cells.
Treatment
Treatment for Active TB
The CDC recommends that infections due
to Mycobacterium tuberculosis be treated
with several drugs in addition to INH:
Rifampin, Ethambutol, Streptomycin, and
Pyrazinamide.
Tuberculosis treatment
• The standard "short" course treatment for
tuberculosis (TB), is isoniazid, rifampicin,
pyrazinamide, and ethambutol for two months,
then isoniazid and rifampicin alone for a further
four months. The patient is considered cured at
six months (although there is still a relapse rate
of 2 to 3%). For latent tuberculosis, the standard
treatment is six to nine months of isoniazid
alone.
• If the organism is known to be fully sensitive,
then treatment is with isoniazid, rifampicin, and
pyrazinamide for two months, followed by
isoniazid and rifampicin for four months.
Ethambutol need not be used.
Drugs
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All first-line anti-tuberculous drug names have
a standard three-letter and a single-letter
abbreviation:
ethambutol is EMB or E,
isoniazid is INH or H,
pyrazinamide is PZA or Z,
rifampicin is RMP or R,
Streptomycin is STM or S.
Drugs
• There are six classes of second-line drugs
(SLDs) used for the treatment of TB. A drug may
be classed as second-line instead of first-line : it
may be less effective than the first-line drugs.
1. aminoglycosides: e.g., amikacin (AMK),
kanamycin (KM);
2. polypeptides: e.g., capreomycin, viomycin,
enviomycin;
3. fluoroquinolones: e.g., ciprofloxacin (CIP),
levofloxacin, moxifloxacin (MXF);
4. thioamides: e.g. ethionamide, prothionamide
5. cycloserine (the only antibiotic in its class);
6. p-aminosalicylic acid (PAS or P).
Drugs
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“Third-line drugs"
Not very effective or because their efficacy has not been
proven .
Rifabutin is effective, but is not included on the WHO list
because for most developing countries, it is impractically
expensive.
rifabutin
macrolides: e.g., clarithromycin (CLR);
linezolid (LZD);
thioacetazone (T);
thioridazinea;
arginine;
vitamin D;
R207910.
Drugs
• Multi-drug resistant TB (MDR-TB) is defined as
resistance to the two most effective first-line TB
drugs: rifampicin and isoniazid.
• Extensively drug-resistant TB (XDR-TB) is also
resistant to three or more of the six classes of
second-line drugs.
Treatment for Active TB
Multidrug-resistant TB (MDR)
Multidrug-resistant TB is on the rise.
MDR TB means that some TB bacteria
have developed resistance, so that
traditional antibiotics, like INH, no
longer kill the bacteria. “This is due to
people not taking their medication
properly; new strains of the bacteria
evolve.”
Monitoring and DOTS
• DOTS stands for "Directly Observed Therapy,
Short-course" and is a major plan in the WHO
global TB eradication programme.
• The DOTS strategy focuses on five main points
of action.
1. These include government commitment to
control TB,
2. diagnosis based on sputum-smear microscopy
tests done on patients who actively report TB
symptoms,
3. direct observation short-course chemotherapy
treatments,
4. a definite supply of drugs, and
5. standardized reporting and recording of cases
and treatment outcomes.
Treatment for Active TB….
TB is curable, IF it is
diagnosed early and
appropriate treatment is
started promptly.
Active TB can be spread to
other people if the person is
not taking medication to kill
the bacteria!
Treatment for Active TB
When a person with active TB is
diagnosed, they should be isolated
from other people until the medication
begins to kill the bacteria-usually 2
weeks, but sometimes longer.
Prevention
• TB prevention and control takes two parallel
approaches :
• In the first, people with TB and their contacts are
identified and then treated.
• Identification of infections often involves testing
high-risk groups for TB.
• In the second approach, children are vaccinated
to protect them from TB.
Current Surgical Intervention
• Patients with hemoptysis first received Bronchial
Artery Embolization because of the recurrent
hemoptysis.
• Current indication of Lung Resection for pulmonary
tuberculosis includes MDR-TB with a poor response
to medical therapy, hemoptysis due to bronchiectasis
or Aspergillus superinfection, and destroyed lung as
previously reported, which are consistent with our
indications.
• Surgery remains a crucial adjunct to medical therapy
for the treatment of MDR-TB and medical failure
lesions.
Fundamentals of TB
Infection Control Practices
Identify persons with active TB
early.
Initiate effective and appropriate
isolation of known or suspected
TB cases.
Initiate effective anti-TB
treatment promptly.
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As a healthcare worker, how can I protect
myself from being exposed?
Instruct your patients to cover their mouth
when coughing and do not transport
patients with TB throughout the hospital
unless they are wearing a mask.