Pemicu 5 Cessy Christy

Pemicu 5
Cessy Christy
LO 1
TB Paru pada Anak dan Dewasa
Tuberculosis
• Tuberculosis (TB) a multisystemic disease with myriad presentations and
manifestations, is the most common cause of infectious disease–related mortality
worldwide.
• Mycobacterium tuberculosis, a tubercle bacillus, is the causative agent of TB. It
belongs to a group of closely related organisms—including M africanum, M bovis,
and M microti —in the M tuberculosis complex.
Emedicine.medscape.com
TB Dewasa
Notifikasi kasus, 2012 WHO.int: GLOBAL TUBERCULOSIS REPORT 2013
Penyebab utama meningkatnya TB
• Kemiskinan pd negara berkembang
• Sanitasi, papan, sandang, pangan buruk
• Beban determinan sosial berat (pengangguran, pendidikan kurang, pendapatan rendah)
• Kegagalan proram TB
• Tdk memadai komitmen politik & pendanaan
• Organisasi pelayanan TB tdk memadai
• Tatalaksana kasus tdk memadai
• Salah persepsi thd manfaat & efektifitas BCG
• Infrastruktur kesehatan buruk
• Tdk ada sistem jaminan kesehatan merata
• Perubahan demografik krn meningkat penduduk dunia
• Gizi buruk, merokok, diabetes
• Pandemi HIV
• Kekebalan ganda kuman TB thd OAT (MDR)
Patogenesis
• Mycobacterium tuberculosis
• Bbrp spesies: M.tuberculosis, M.africanum, M.bovis,M.leprae
Dikenal sbg BTA (Bakteri Tahan Asam)
• Sifat umum kuman TB
• Batang, tahan asam dg pewarnaan ziehl Neelsen
• Media biakan khusus: Lowenstein Jensen, Ogawa
• Batang merah (mikroskopis)
• Tahan thd suhu rendah (4- -70 derajat celcius)
• Peka thd panas, sinar matahari & UV
• Paparan lgsg sinar UV  mati bbrp menit
• Dahak (30-37o) mati dlm ~ 1 mgg
• Dpt bersifat dormant
Emedicine.medscape
Patofisiologi
Patofisiologi
• the infectious droplets inhaled  settle throughout the airways  The majority of the bacilli are trapped in the upper parts of the airways where the mucus-secreting goblet cells exist  The mucus
produced catches foreign substances  the cilia on the surface of the cells constantly beat the mucus and its entrapped particles upward for removal minitial physical defense that prevents
infection in most persons exposed to tuberculosis.
• Bacteria in droplets that bypass the mucociliary system  reach the alveoli  quickly surrounded and engulfed by alveolar macrophages with endocytosis
• The mycobacterial lipoarabinomannan is a key ligand for a macrophage receptor  bind to mannose receptor in macrophage
• The complement protein C3 binds to the cell wall  enhances recognition of the mycobacteria by macrophages  Opsonization by C3 is rapid, even in the air spaces of a host with no previous
exposure to M tuberculosis  phagocytosis by macrophages initiates a cascade of events that results in either successful control of the infection, followed by LATENT TUBERCULOSIS, or progression
to active disease, called PRIMARY PROGRESSIVE TUBERCULOSIS
• The outcome is essentially determined by the quality of the host defenses and the balance that occurs between host defenses and the invading mycobacteria.
• After being ingested by macrophages  the mycobacteria continue to multiply slowly with bacterial cell division occurring every 25 to 32 hours by blocking fusion of phagosome and lysosome 
blocking it by inhibiting Ca signals and the recruitement and assembly of proteins that mediate lysosome phagosome fusion
• Regardless of whether the infection becomes controlled or progresses  initial development involves production of proteolytic enzymes and cytokines by macrophages in an attempt to degrade the
bacteria  attract T lymphocytes (Th1) to the site  Macrophages then present mycobacterial antigens on their surface to the T cells  This initial immune process continues for 2 to 12 weeks 
the microorganisms continue to grow until they reach sufficient numbers to fully elicit the cell-mediated immune response, which can be detected by a skin test
• For persons with intact cell-mediated immunity  Th1 produce IFN gamma  activate macrophage  help control the infection by stimulating production of NO to destroy the bacteria constituent
from cell wall to DNA and creating a micro acidic-environment from the formation of phagolysosome in infected macrophage that limits replication and the spread of the mycobacteria  This
environment destroys macrophages  macrophage (activated by IFN gamma) differentiate into “EPITHELOID HISTIOCYTE” (granuloma mark in histophatology)  formation of granulomas around
the M tuberculosis organisms from an accumulation of activated T lymphocytes and macrophages  produces early solid necrosis at the center of the lesion
• Activated macrophage secrete TNF  recruitment of monocyte
• however, the bacilli are able to adapt to survive.In fact, M tuberculosis organisms can change their phenotypic expression, such as protein regulation, to enhance survival.
• By 2 or 3 weeks, the necrotic environment resembles soft cheese (CASEOUS NECROSIS) and is characterized by low oxygen levels, low pH, and limited nutrients  restricts further growth and
establishes latency
• Lesions in persons with an adequate immune system generally undergo fibrosis and calcification  successfully controlling the infection  the bacilli are contained in the dormant, healed lesions.
• Lesions in persons with less effective immune systems progress to primary progressive tuberculosis
• For less immunocompetent persons  granuloma formation is initiated  unsuccessful in containing the bacilli  The necrotic tissue undergoes liquefaction the fibrous wall loses structural
integrity  The semiliquid necrotic material can then drain into a bronchus or nearby blood vessel, leaving an air-filled cavity at the original site.
• In patients infected with M tuberculosis, droplets can be coughed up from the bronchus and infect other persons.
• If discharge into a vessel occurs, occurrence of EXTRAPULMONARY TUBERCULOSIS is likely.
• Bacilli can also drain into the lymphatic system and collect in the tracheobronchial lymph nodes of the affected lung, where the organisms CAN FORM NEW CASEOUS GRANULOMAS.
Cara penularan & perjalanan TB pd manusia
• Percik renik dahak yg dikeluarkan
• Batuk, bersin (droplet nuclei)  3000 percikan dahak sekali batuk
• Tdpt 4 tahapan:
• Paparan
• Infeksi
• Menderita sakit
• Meninggal dunia
http://ccn.aacnjournals.org/content/29/2/34/T1.expansion.html
Latent Tuberculosis
• LTBI = begins when ingested bacilli by macrophage and presented to other white blood cell  triggers
white blood cell to kill or encapsulate most of the bacilli  leads to granuloma formation
• no signs or symptoms of the disease, do not feel sick, and are not infectious.
• However, viable bacilli can persist in the necrotic material for years or even a lifetimeand  immune
system later becomes compromised  reactivated.
• factor for reactivation :
• HIV
• uncontrolled diabetes mellitus
• Sepsis
• renal failure
• Malnutrition
• Smoking
• Chemotherapy
• organ transplantation
• long-term corticosteroid usage
• 65 years or older
http://ccn.aacnjournals.org/content/29/2/34.full..
Primary Disease
• Asymptomatic  results of diagnostic tests are the only evidence of the
disease.
• Associated paratracheal lymphadenopathy may occur  the bacilli spread
from the lungs through the lymphatic system.
• If the primary lesion enlarges pleural effusion is a distinguishing finding.
• This effusion develops because the bacilli infiltrate the pleural space from an adjacent
area.
• The effusion may remain small and resolve spontaneously, or it may become large
enough to induce symptoms such as fever, pleuritic chest pain, and dyspnea.
• Dyspnea is due to poor gas exchange in the areas of affected lung tissue.
• Dullness to percussion and a lack of breath sounds are physical findings indicative of a pleural
effusion because excess fluid has entered the pleural space
http://ccn.aacnjournals.org/content/29/2/34/T2.expansion.html
Primary Progressive Tuberculosis
• patient progresses to active tuberculosis  early signs and symptoms are often nonspecific.
• Manifestations :
• progressive fatigue
• Malaise
• weight loss
• Wasting  a classic feature of tuberculosis  lack of appetite and the altered metabolism associated with the inflammatory and immune responses.
• involves the loss of both fat and lean tissue
• decreased muscle mass contributes to the fatigue
• a low-grade fever accompanied by chills and night sweats.
• Finger clubbing  a late sign of poor oxygenation
• A cough
• initially be non-productive  advances to a productive cough of purulent sputum.
• The sputum may also be streaked with blood (Hemoptysis)  due to destruction of a patent vessel located in the wall of the cavity, the rupture of a
dilated vessel in a cavity, or the formation of an aspergilloma in an old cavity.
• Pleuritic chest pain  The inflamed parenchyma
• dyspnea or orthopnea  increased interstitial volume leads to a decrease in lung diffusion capacity
• rales may be detected over involved areas during inspiration, particularly after a cough.
• Hematologic studies might reveal anemi  cause of the weakness and fatigue.
• Leukocytosis  the large increase in the number of leukocytes, or white blood cells, in response to the infection.
Extrapulmonary Tuberculosis
• occurs in more than 20% of immunocompetent patients, and the risk for
extrapulmonary disease increases with immunosuppression.
• central nervous system  meningitis or space-occupying tuberculomas  fatal
• infection of the bloodstream by mycobacteria  disseminated or miliary
tuberculosis  bacilli can then spread throughout the body, leading to
multiorgan involvement.
• progresses rapidly and difficult to diagnose because of its systemic and nonspecific signs
and symptoms, such as fever, weight loss, and weakness.
• Lymphatic tuberculosis
• cervical adenopathy
• bones, joints, pleura, and genitourinary system.
Diagnosing
• The Standard
• Definitive diagnosis  culture of a diagnostic specimen.
• The most frequent sample used from persistent and productive cough sputum.
• Most mycobacteria grow slowly  3 to 6 weeks may be required for detectable growth on solid media.
• Alternative method
• high-performance liquid chromatography is used to isolate and differentiate cell wall mycolic acids provides
confirmation of the disease in 4 to 14 days.
• Conventionally, 3 sputum samples were also used for culture diagnosis
• After medications are started, the effectiveness of the therapy is assessed by obtaining sputum
samples for smears.
• the traditional requirement of 3 sputum smears negative for M tuberculosis may be unnecessary when determining if
respiratory isolation can be discontinued.
• A patient is considered to have achieved culture conversion when a culture is negative for the
mycobacteria after a succession of cultures have been positive
• Culture conversion is the most important objective evaluation of response to treatment
Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient
infected with a tuberculosis can no longer produce tuberculosis cell cultures.Culture conversion is a
http://ccn.aacnjournals.org/content/29/2/34.full.. positive prognostic marker indicating that a patient is cured of, or is recovering from, tuberculosis.
• Alternatives
• not all patients with tuberculosis can be detected by culture of sputum specimens  can lead to delayed or missed
diagnosis.
• For patients who have difficulty generating sputum  inhalation of an aerosol of normal saline can be used to
induce sputum for collection
• However, if sputum specimens are still inadequate, or the index of suspicion for tuberculosis is still high despite
cultures negative for M tuberculosis, alternative approaches are available:
• Bronchoscopy with bronchial washings or bronchoalveolar lavage can provide sputum for diagnosis.
• In bronchial washing, a fiberoptic bronchoscope is inserted into the lungs, and fluid is squirted in and then collected, essentially
washing out a sample of cells and secretions from the alveolar and bronchial airspaces
• In patients with involvement of intrathoracic lymph nodes, as indicated by adenopathy suggestive of tuberculosis,
who have sputum smears negative for M tuberculosis  culture of specimens collected by transbronchial needle
aspiration can be used to accurately and immediately diagnose the disease.
• With this technique, specimens are collected by inserting a 19-gauge flexible histology needle through a bronchoscopy tube; patients
are sedated but conscious, and computed tomography scans are used for guidance.
• Technological Advancements
• Nucleic Acid Smplification Tests (NAAT).
• molecular biology methods are used to amplify DNA and RNA, facilitating rapid detection of microorganisms
• Polymerase Chain Reaction (PCR) assay
• to differentiate M tuberculosis from other mycobacteria on the basis of genetic information and provides results within hours.
• Limitation : high cost, low sensitivity, and low availability.
• A PCR assay positive for M tuberculosis in conjunction + a sputum smear positive for the organism = true tuberculosis,
• Sputum smear negative for the organism + the positive polymerase chain reaction assay = considered carefully along with clinical
indicators.
• The results of these assays can not be relied on as the sole guide for isolation or therapy
• Diagnosing Latency
• Once patients recover from a primary M tuberculosis infection and the infection becomes latent  sputum
specimens are negative for the organisms, and findings on chest radiographs are typically normal + These
patients also do not have signs or symptoms of infection + not infectious to others
• Tuberculin skin testing  to screen for latent M tuberculosis.
• performed by intradermally injecting 0.1 mL of intermediate-strength purified protein derivative (PPD) that contains 5 tuberculin
units.
• After 48 to 72 hours, the injection site is examined for induration but not redness
• Although the test is useful because the PPD elicits a skin reaction via cell-mediated immunity when injected in patients
previously infected with mycobacteria, it is limited because it is not specific for the species of mycobacteria.
• limited value in patients with active tuberculosis because of its low sensitivity and specificity.
• A reaction of ≥ 5 mm = positive  for close contacts of tuberculosis cases (immunosuppressed persons, in particular persons
with HIV infection, individuals with clinical or radiographic evidence of current or prior TB and persons receiving TNF blocking
agents.
• A reaction of ≥10 mm = positive  for other persons at increased risk of LTBI (eg, persons born in high TB incidence
countriesnand those with at risk of occupational exposure to TB) and for persons with medical risk factors that increase the
probability of progression from LTBI to TB
• A reaction of ≥ 15 mm = positive for all other persons.
• False-negatives  patients who are malnourished, in infants and young children, early (<6–8 weeks) after infection, in persons
having recently received viral vaccination, in persons with clinical conditions associated with immunosuppression (eg, HIV
infection) or overwhelming illness (including extensive or disseminated tuberculosis), after recent viral and bacterial infections,
and in association with treatment with immunosuppressive drugs (eg, high-dose corticosteroids, TNF inhibitors).  cannot
mount an immune response to the injection In 20% to 25% of patients who have active tuberculosis, because there is a time lag
of 2 to 10 weeks between infection and the T-lymphocyte response required for a positive skin reaction.
• False-positives  patients who have infections caused by mycobacteria other than M tuberculosis or who have been given BCG
vaccine. http://ccn.aacnjournals.org/content/29/2/34.full..
• Interferon Gamma Release assay/IGRA (QuantiFERON-TB
Gold test)
• the cell-mediated reactivity to M tuberculosis is determined by :
• incubating whole blood with an antigen and then using an enzyme-linked immunosorbent
assay to measure the amount of interferon-γ released from white blood cells.
• 2 synthetic antigenic proteins specific in PPD are used rather than a PPD admixture 
more sensitive
• results in less than 24 hours
• can be used to detect both active and latent tuberculosis.
• The QFT-GIT assay is considered positive if :
• the difference between the IFN-γ concentration in response to the Mtb antigens and
the IFN-γ response to the nil control is ≥0.35 IU.
• In addition, to control for high background in the nil control, the IFN-γ response to
antigen must be 25% greater than the IFN-γ concentration in the NIL control.
• An indeterminate response defined as either a lack of response in the PHA control well
(IFN-γ concentration ≤0.5 IU) or a nil control that has a very high background (IFN-γ
concentration >8 IU).
• Centers for Disease Control and Prevention now recommend that the QuantiFERON-TB
Gold test be used in all instances in which the tuberculin skin test formerly would have
been used.
Radiographic
Findings
• INFILTRATES WITH CAVITATION IN THE
UPPER AND MIDDLE LOBES OF THE LUNGS
• elderly and patients with advanced infection
by human immunodeficiency virus  may
not have these typical findings.
• classic cavitation less often and may have LOWER-
LOBE INFILTRATES AS A PROMINENT FINDING.
• NOT DIAGNOSTIC FOR THE DISEASE.
Chest radiographs in pulmonary tuberculosis. A, Infiltrates in left lung. B,

Bilateral advanced pulmonary tuberculosis and cavitation in apical area of right
http://ccn.aacnjournals.org/content/29/2/34.full.. lung.
http://crudem.org/tuberculosis-in-haiti/
Ghon's complex is a lesion seen in the
lung that is caused by tuberculosis. The
lesions consist of a calcified focus of
infection and an associated lymph
node.
https://www.studyblue.com/notes/note/n/l16a-b-add-from-charts-mycobacteria-not-as-much-has-to-be-added-
as-with-other-lecs-but-still-need-to/deck/1297919
Miliary tuberculosis
• widespread dissemination of Mycobacterium
tuberculosis via hematogenous spread.
• Classic miliary TB is defined as milletlike (mean, 2
mm; range, 1-5 mm) seeding of TB bacilli in the
lung, as evidenced on chest radiography. This
pattern is seen in 1-3% of all TB cases.
• Occur in an individual organ (very rare, < 5%), in
several organs, or throughout the entire body
(>90%), including the brain.
• The infection is characterized by a large amount of
TB bacilli, although it may easily be missed and is
fatal if left untreated.
• Up to 25% of patients with miliary TB may have
meningeal involvement. In addition, miliary TB may
mimic many diseases. In some case series, up to
50% of cases are undiagnosed antemortem.
Therefore, a high index of clinical suspicion is
important to obtain an early diagnosis and to
ensure improved clinical outcomes.
• Following exposure and inhalation of TB bacilli in the lung  a primary
pulmonary complex is established  development of pulmonary lymphangitis
and hilar lymphadenopathy.
• Mycobacteremia and hematogenous seeding occur after the primary
infection.
• After initial inhalation of TB bacilli, miliary tuberculosis may occur as primary
TB or may develop years after the initial infection.
• The disseminated nodules consist of central caseating necrosis and peripheral
epithelioid and fibrous tissue.
• Radiographically, they are not calcified (as opposed to the initial Ghon focus,
which is often visible on chest radiographs as a small calcified nodule).
Upaya pengendalian TB
• DOTS (Directly Observed Treatment Short-course), 5 komponen kunci:
• Komitmen politis (peningkatan & kesinambungan pendanaan)
• Penemuan kasus mll pemeriksaan dahak mikroskopis yg terjamin mutu
• Pengobatan standar + supervisi & dukungan bagi ps
• Sistem pengelolaan & ketersediaan OAT efektif
• Sistem monitoring, pencatatan, pelaporan  memberi penilaian thd hasil
pengobatan ps & kinerja program
Tatalaksana pasien TB
• Strategi penemuan
• Kelompok yg rentan atau risiko tinggi TB (HIV, DM, malnutrisi)
• Kelompok yg rentan krn lingkungan risiko tinggi tjd penularan (Lapas/Rutan,
tempat penampungan pengungsi, kumuh, tempat kerja, asrama, panti jompo)
• Anak <5 thn dg kontak ps TB
• Kontak erat dg ps TB & ps TB resisten obat
Gejala Utama
• Tahap awal menjaring:
• Batuk berdahak >=2 mgg
• Diikuti + dahak darah, batuk darah, sesak nafas, badan lemas, nafsu makan turun, BB
turun, malaise, berkeringat malam tnp kegiatan fisik, demam meriang >1 bln
Pemeriksaan dahak
• Mikroskopis langsung
• S (sewaktu): dahak ditampung pada saat terduga pasien TB datang
berkunjung pertama kali ke fasyankes. Pada saat pulang, terduga pasien
membawa sebuah pot dahak untuk menampung dahak pagi pada hari kedua.
• P (Pagi): dahak ditampung di rumah pada pagi hari kedua, segera setelah
bangun tidur. Pot dibawa dan diserahkan sendiri kepada petugas di fasyankes.
• S (sewaktu): dahak ditampung di fasyankes pada hari kedua, saat
menyerahkan dahak pagi.
• Biakan
• Uji kepekaan obat
http://ccn.aacnjournals.org/content/29/2/34/F4.expansion
Isolation
• Patients receiving mechanical ventilation should also be kept in a
negative-pressure room, and respiratory masks should still be used by
anyone who enters the room. A closed-system endotracheal suction
catheter should be used for suctioning whenever feasible. In order to
help reduce the risk of contaminating ventilation equipment or release
of M tuberculosis organisms into the room air, a bacterial filter should
be placed on the endotracheal tube or on the expiratory side of the
ventilation circuit. Good oral care and strict adherence to suctioning
infection control practices should be a priority, because ventilator-
associated pneumonia is already a predominant nosocomial infection
and would pose an enhanced threat to a patient with tuberculosis.
Tipe ps TB
• Pasien TB berdasarkan hasil konfirmasi pemeriksaan
Bakteriologis:
• pasien TB yang dikelompokkan berdasar hasil pemeriksaan
contoh uji biologinya dengan pemeriksaan mikroskopis
langsung, biakan atau tes diagnostik cepat
• Termasuk dalam kelompok pasien ini adalah:
a. Pasien TB paru BTA positif
b. Pasien TB paru hasil biakan M.tb positif
c. Pasien TB paru hasil tes cepat M.tb positif
d. Pasien TB ekstraparu terkonfirmasi secara bakteriologis, baik
dengan BTA, biakan maupun tes cepat dari contoh uji jaringan
yang terkena.
e. TB anak yang terdiagnosis dengan pemeriksaan bakteriologis.
Pasien TB terdiagnosis secara Klinis:
• pasien yang tidak memenuhi kriteria terdiagnosis secara
bakteriologis tetapi didiagnosis sebagai pasien TB aktif oleh
dokter, dan diputuskan untuk diberikan pengobatan TB.
• Termasuk dalam kelompok pasien ini adalah:
a. Pasien TB paru BTA negatif dengan hasil pemeriksaan foto
toraks mendukung TB.
b. Pasien TB ekstraparu yang terdiagnosis secara klinis
maupun laboratoris dan histopatologis tanpa konfirmasi
bakteriologis.
c. TB anak yang terdiagnosis dengan sistim skoring.
Klasifikasi Pasien TB
• Berdasarkan riwayat pengobatan
• Pasien baru TB
• Blm pernah dpt OAT sblmnya
• Sudah pernah menelan OAT <1 bln (< 28 dosis)
• Pasien yg pernah diobati
• Pasien kambuh
• Pernah dinyatakan sembuh/pengobatan lengkap didiagnosis TB berdasarkan hasil bakteriologi
atau klinis (kambuh atau reinfeksi)
• Pasien yg diobati kembali stlh gagal
• Pernah diobati & dinyatakan gagal pd pengobatan terakhir
• Ps yg diobati kembali stlh putus berobat (lost to follow-up)
• Pernah diobati dinyatakan lost to follow up (putus berobat/default)
• Pasien yg riwayat pengobatan belum diketahui
• Berdasarkan lokasi anatomi penyakit
• TB paru
• TB tjd pd parenkim (jaringan) paru
• Milir TB dianggap TB paru krn lesi pd jaringan paru
Limfadenitis TB rongga dada (hilus atau mediastinum) atau
efusi pleura tnp tdpt gambarang rad yg mendukung TB paru
 TB extraparu
TB paru + TB extraparu  TB paru
• TB extraparu
• Organ lain selain paru
• Pleura, kel limfe, abdomen, sal kencing, kulit, sendi, selaput otak &
tulang
• Diagnosis ditetapkan berdasarkan hasil pemeriksaan bakteriologis
atau klinis (penemuan M.tuberculosis)
• Berdasarkan hasil uji kepekaan obat
• Mono resistan (TB MR): resistan terhadap salah satu jenis OAT
lini pertama saja
• Poli resistan (TB PR): resistan terhadap lebih dari satu jenis OAT
lini pertama selain Isoniazid (H) dan Rifampisin (R) secara
bersamaan
• Multi drug resistan (TB MDR): resistan terhadap Isoniazid (H)
dan Rifampisin secara bersamaan
• Extensive drug resistan (TB XDR): adalah TB MDR yang sekaligus
juga resistan terhadap salah satu OAT golongan fluorokuinolon
dan minimal salah satu dari OAT lini kedua jenis suntikan
(Kanamisin, Kapreomisin dan Amikasin)
• Resistan Rifampisin (TB RR): resistan terhadap Rifampisin
dengan atau tanpa resistensi terhadap OAT lain yang terdeteksi
menggunakan metode genotip (tes cepat) atau metode fenotip
(konvensional).
• Berdasarkan status HIV
• TB + HIV(+) pasien koinfeksi TB/HIV
• HIV + sebelumnya atau sedang dpt ART atau
• HIV + saat didiagnosis TB
• TB + HIV(-)
• HIV – sebelumnya atau
• HIV – pd saat didiagnosis TB
Apabila pd pemeriksaan selanjutnya HIV +  sesuaikan
kembali klasifikasinya (HIV +)
• TB + HIV tdk diketahui
• Tanpa bukti pendukung hasil tes HIV saat diagnosis TB
Pedoman Nasional
Pengendalian Tuberkulosis
KemenKes RI 2014
TB Anak
TB pd anak
• Tjd pd usia 0-14 thn
• Cara penularan:
• TB paru BTA +ve dewasa atau anak
• Anak terkena TB tdk sll menularkan org sekitar kecuali BTA +ve atau adult type
TB
• FR: tgt tgkt penularan, lama pajanan, daya tahan tubuh anak
• TB Anak Indonesia 2010 9,4%  8,5% 2011  8,2 2012
Diagnosis TB Anak
• Anak yg kontak dg ps TB menular
• Tinggal serumah atau sering bertemu
• TB menular: TB + px dahak +ve BTA umumnya dewasa
• Mempunyai tanda & gejala klinis sesuai TB anak
Gejala TB anak
• Sistemik
• BB turun tnp sebab jelas atau tdk naik dg adekuat atau tdk naik dlm 1 bln stlh
upaya perbaikan gizi baik
• Demam lama >=2 mgg dan/atau berulang tnp sebab jelas (umumnya tdk
tinggi). Keringat malam (bkn merupakan gejala spesifik Tb anak bl tdk + gejala
sistemik lain)
• Batuk lama >=3 mgg, non-remitting (tdk pernah reda atau makin lama makin
parah) & sebab lain dr batuk sdh disingkirkan
• Nafsu makan tdk ada (anorexia) atau berkurang + gagal tumbuh
• Lesu, malaise, kurang aktif bermain
• Diare persisten (>2mgg) tdk sembuh dg pengobatan diare
• Gejala spesifik terkait organ
• TB kelenjar (leher atau colli)
• Pembesaran KGB multipel (>1 KGB) d >=1 cm kenyal, tdk nyeri kadang saling
melekat atau konfluens
• TB otak & selaput otak
• Meningitis TB
• Tuberkuloma otak
• TB sistem skeletal
• Spondilitis: penonjolan tulang belakang (gibbus)
• Koksitis: pincang, gg berjalan, tanda peradangan panggul
• Gonitis: pincang, bengkak lutut sebab tdk jelas
• Spina ventosa/daktilis: tulang kaki tangan
• Skrofulodema
• Ulkus disertai jembatan kulit antar tepi ulkus (skin bridge)
• TB mata
• Konjungtivitis fliktenularis
• Tuberkel koroid
• TB organ lain
• Peritonitis, ginjal
TB Primer
• Ghon complex  lesi makroskopik yg pathogmonic (khas) dr TB
primer pulmonal
• Infeksi inisial pd anak
• 3 elemen:
• Ghon focus: lesi nodular kecil (~1cm), kuning-putih-, sentral nekrosis kaseosa,
encapsulated, di 1/3 bawah lobus superior atau di bagian atas lobus inferior,
subpleural
• Limfadenitis: diseminasi limfatik dr bacil ke nodus hilar nodus limfe  sentral
nekrosis kaseosa putih kuning membesar, kaku
• Limfangitis: terlihat scr radiologik, opasitas linear jelas dg nodul milier.
Inflamasi tuberkel
• Miliary tuberculosis
• Diseminasi hematogen bacili Koch
• Menyerang paru & organ lain
• Lesi noduler multipel kecil 2-3 mm
• Berbatas tegas, kekuningan, tersebar diseluruh permukaan
organ terinfeksi (miliary tubercles)
Atlas of Pathology 3rd edition. http://www.pathologyatlas.ro/primary-pulmonary-tuberculosis-pathology.php

Nutrisi
• Malnutrisi & defisiensi mikronutrien spesifik  respon imun tergg 
infeksi TB  risiko meningkat u/ perkembangan ke penyakit yg aktif
• TB aktif terkait dg defisiensi mikronutrien
• Vit A, B complex, C, D, E, selenium
• Peran vit D pd TB:
• Sel imun (makrofag) produksi enzim yg mengubah 25-OH vit D disirkulasi 
bentuk aktif  regulasi peningkatan vit D reseptor (VDR)  induksi produksi
antimikobakterial peptide, cethelicidin
1. TBM
2. Pleura effusion
3. Pneumothorax
4. Endocarditis
5. Pleuritis
6. Pott’s disease
Emedicine.medscape
Tuberculosis Meningitis
Emedicine.me
Tuberculose Pleural effusion
• A pleural effusion is an abnormal collection of fluid in the pleural space resulting from
excess fluid production or decreased absorption or both.[1] It is the most common
manifestation of pleural disease, with etiologies ranging from cardiopulmonary
disorders to symptomatic inflammatory or malignant diseases requiring urgent
evaluation and treatment
• The normal pleural space contains approximately 1 mL of fluid, representing the
balance between (1) hydrostatic and oncotic forces in the visceral and parietal pleural
vessels and (2) extensive lymphatic drainage. Pleural effusions result from disruption
of this balance.
• Pleural effusions are generally classified as transudates or exudates, based on the
mechanism of fluid formation and pleural fluid chemistry. Transudates result from an
imbalance in oncotic and hydrostatic pressures, whereas exudates are the result of
inflammation of the pleura or decreased lymphatic drainage.
Ncbi.nlm.nih.gov
Ncbi.nlm.ni
Tuberculose pneumothorax
• Spontaneous pneumothorax (SP) is defined as the sudden

presence of air in the pleural cavity without apparent
external cause. Though spontaneous pneumothorax (SP) is a
well-known complication of pulmonary tuberculosis (TB).
• Pleural infection results from rupture of subpleural caseous
lesions, resulting in accumulation of a chronic empyema. A
bronchopleural fisutla may occur spontaneously during the
natural history of the disease, though it is more frequently
caused by trauma or attempted surgical intervention. Both
chronic empyema and bronchopleural fistula may result in
spontaneous (and subsequent tension) pneumothorax,Ncbi.nlm.nih.gov
Tuberculose endocarditis
• Granulomas caused by Mycobacterium Tuberculosis have been
observed at autopsy in the heart, pre-dominantly in the myocardium
and endocardium, but rarely involving the coronary vessels and
valvular structures.
• This is the first reported case of triple valve endocarditis by
Mycobacterium Tuberculosis in an immunocompetent host. Especially
important is the fact that the right heart is involved which has been
historically described in the setting of intravenous drug abuse.
Ncbi.nlm.nih.gov
Tuberculose pleurisy
• Pleurisy, also referred to as pleuritis, is an inflammation of the parietal
pleura in the lungs. Clinically recognized as pain that is sharp,
localized, and made worse by deep inspiration or coughing, pleurisy
has a diverse array of possible causes.
• Inflammation that occurs at the periphery of the lung parenchyma
can extend into the pleural space and involve the parietal pleura,
thereby activating the somatic pain receptors and resulting in pleuritic
pain. Parietal pleurae of the outer rib cage and lateral aspect of each
hemidiaphragm are innervated by intercostal nerves. Pain is localized
to the cutaneous distribution of those nerves.
Pott’s disease
• Pott disease is usually secondary to an extraspinal source of infection. Pott
disease manifests as a combination of osteomyelitis and arthritis that
usually involves more than 1 vertebra. The anterior aspect of the vertebral
body adjacent to the subchondral plate is usually affected. Tuberculosis
may spread from that area to adjacent intervertebral disks. In adults, disk
disease is secondary to the spread of infection from the vertebral body. In
children, the disk, because it is vascularized, can be the primary site.
• Progressive bone destruction leads to vertebral collapse and kyphosis.
The spinal canal can be narrowed by abscesses, granulation tissue, or
direct dural invasion, leading to spinal cord compression and
neurologic deficits.
• The kyphotic deformity is caused by collapse in the anterior spine.
Lesions in the thoracic spine are more likely to lead to kyphosis than
those in the lumbar spine. A cold abscess can occur if the infection
extends to adjacent ligaments and soft tissues. Abscesses in the
lumbar region may descend down the sheath of the psoas to the
femoral trigone region and eventually erode into the skin.
Gibbus deformity is a short- This angulation, coupled with epidural
segment structural thoracolumbar granulation tissue and bony fragments, can
kyphosis resulting in sharp lead to cord compression. Unlike pyogenic
infections, the discs can be preserved. In late-
angulation. There are a number of
stage spinal TB, large paraspinal
causes which can be divided into abscesses without severe pain or frank pus
congenital and acquired. are common, leading to the expression "cold
LO 2
TB dan HIV
Pathogenesis of TB + HIV
• Qualitative and quantitative defects of CD4+ T-lymphocytes  inability of HIV-infected individuals to contain
mycobacterial proliferation.
• Reactive CD4+ T-lymphocytes produce cytokines of the Th1 pattern and participate in MHC class II-restricted
killing of cells infected with M. tuberculosis.
• Th1 CD4+ cells produce interferon (IFN)-γ and IL-2 and promote cell mediated immunity cell mediated
immunity (CMI) while Th2 cells produce IL-4, IL-5 and IL-10 and promote humoral immunity. The interplay of
these various cytokines and their cross-regulation determine the host's response.
• HIV promotes the progression of LTBI to disease and TB accelerates the progression of HIV disease.
• In healthy people previously exposed to and infected by TB  host cell mediated immunity keeps LTBI
dormant.
• HIV infection interferes with CMI  increasing the risk of progression to active disease
• In people with HIV infection, the risk of TB disease is influenced by:
• the prevalence of TB in the local community
• the person's likelihood of exposure to infectious TB
• the person's degree of immunodeficiency and the use of preventive therapy for LTBI.
• HIV-positive patients have however been found to be less infective than HIV-negative patients and this may
partly be explained by lower bacillary load in the sputum.
http://www.ssajm.org/article.asp?issn=2384-5147;year=2014;volume=1;issue=1;spage=1;epage=14;aulast=Adeiza
Impact of HIV Infection on Pathogenesis of
TB
• HIV infection increases the risk of reactivation of LTBI and causes progression of new infection and re-infection to active disease.
• These accelerate the natural course of the disease with a more rapid spread of strains, including those that are drug resistant, in the
community.
• M. tuberculosis is an intracellular pathogen and macrophage activation, by the release of IFN-γ from activated CD4+ and CD8+ T-
lymphocytes, is the primary mechanism by which M. tuberculosis replication is inhibited and by which M. tuberculosis is ultimately
killed.
• HIV infects and kills CD4+ T-lymphocytes, the concentration of which declines as the HIV infection progresses increasing the risks of
TB disease and disseminated mycobacterial infection.
• Active TB has been associated with a higher HIV viral load, which might be expected to accelerate the loss of CD4+ T-lymphocytes
and promote HIV/AIDS disease progression.
• Granulomas are absent or poorly formed in people with poor immune responses, particularly those infected with HIV.
• Through several mechanisms, HIV-1 co-infection leads to functional and numeric depletion of M. tuberculosis-specific CD4+ T-
lymphocytes and Th1 cytokine production.
• The resulting dysfunction of the CD4+ T-lymphocyte-macrophage immune axis impairs the host's ability to orchestrate CMI responses
and form immunologically competent granulomas  uncontrolled M. tuberculosis replication with little evidence of a host cellular
response.
• Sites of TB disease and granulomas themselves provide the ideal microenvironment for the propagation of HIV-1, thereby maximizing
the adverse consequences of HIV-1 at the crucial interface between M. tuberculosis and the host.
Impact of TB Infection on the Pathogenesis
of HIV
• High levels of TNF-α which are known to increase HIV replication in T-
lymphocyte clones have been demonstrated in both HIV-1
seropositive and seronegative TB cases.
• Moreover, investigators have shown that M. tuberculosis or purified
protein derivative (PPD) can also increase viral replication in
infected T-lymphocytes and monocytes.
• In asymptomatic HIV infected highly active antiretroviral therapy
(HAART) naïve children  isoniazid prophylaxis showed a marked
reduction in TB incidence and death when compared to a placebo
group.
Clinical Feature
• Latent TB infection
• It is hypothesized that HIV co-infection has a fundamental impact on the
spectrum of the host-pathogen relationship with a general shift towards poor
immune control, high bacillary numbers and subsequent development of
active infection and symptomatic disease.
• Recurrent exogenous re-exposure to M. tuberculosis in high TB prevalence
settings is also very likely to play an important role, further increasing
bacillary numbers and increasing the likelihood of progression to disease.
Clinical Feature
• Active TB infection
• Active infection and disease with M. tuberculosis can occur at any CD4+ count.
• In patients with early HIV disease and a well-maintained CD4+ count, the clinical picture is essentially very similar to that in the HIV-negative
population and the classical presentation of cough, fever and weight loss is common.
• As the degree of immunosuppression increases, the clinical presentation becomes increasingly atypical and non-specific particularly in the late
stage of HIV infection, with non-cavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion and other extra-pulmonary
manifestations of the disease.
• The difficulty with diagnosis is compounded by the fact that fever and weight loss can be common symptoms of HIV disease alone or other
opportunistic infections.
• The risks of disseminated disease become higher as the CD4+ count falls.
• A clear association has been reported between low CD4+ count and an increased frequency of extrapulmonary TB (EPTB), positive blood cultures
for M. tuberculosis and intrathoracic adenopathy on chest X-ray. Infectiousness and transmission are less in TB-HIV co-infected patients compared
to HIV-negative patients.
The most common manifestation of TB is pulmonary (Koch's) disease manifesting as prolonged cough for more than 2 weeks, haemoptysis, fever,
weight loss and night sweats.
• Early initiation of ART restores pathogen-specific immunity, but also significantly increases the risk of the TB-associated immune reconstitution
inflammatory syndrome (TB-IRIS).
• Conversely, a delay in initiation of ART may allow additional AIDS-defining illnesses to manifest. Other reasons for clinical deterioration during
anti-TB treatment include antimicrobial resistance, suboptimal anti-TB drug concentrations, drug reactions and other opportunistic illnesses.
Diagnosis of LTBI in HIV
• tuberculin skin test (TST).
• ≥5 mm in HIV-seropositive patient is considered as positive.
• This criterion does not take into account the role of prior sensitization by Bacille Calmette
Guerin vaccine (BCG) and infection with environmental mycobacteria in developing
countries where >80% of the global TB cases occur.
• sensitivity of TST is limited in immunocompromised individuals due to anergy 
compromised the sensitivity and specificity of tuberculin skin test for the diagnosis of
LTBI.
• negative TST does not exclude infection or active disease and testing with tuberculin PPD
is dependent on the presence of an intact CMI response.
• In the setting of HIV infection, reduced CMI and decreasing CD4+ T-lymphocyte counts
can lead to decreased DTH responsiveness, resulting in false-negative skin tests.
• IFN-γ release assays (IGRAs)
Diagnosis of Active TB in HIV
• Microscopic detection
• microscopic detection of the acid-fast bacilli in clinical specimens has remained the gold standard for the diagnosis of TB disease.
• inexpensive, relatively easy to perform and specific in most settings
• However, to be smear positive a specimen needs to contain 10 5 mycobacteria/ml or more
• the sensitivity of sputum microscopy in HIV infection is less than 60%.
• Methods that improve speed or sensitivity include fluorescence microscopy and alternative specimen processing methods, such as
concentration and bleach sedimentation.
• Any procedure for digestion or liquefaction followed by centrifugation, prolonged gravity sedimentation, or filtration increases
sensitivity by 13% to 33% over direct microscopy when culture is used as the reference standard.
• Alternative technologies using light-emitting diode (LED) bulbs allow fluorescence microscopes at a much lower cost; field-level
evaluation has shown promising results.
• Furthermore, it has been demonstrated that 2 specimens collected on the same day (so-called front loading) give results equivalent
to the traditional 3 specimens  increasing convenience for the patient and potentially increasing the proportion of patients
treated appropriately.
• Frequent smear-negative disease exacerbates the difficulty of detecting HIV-associated TB, leading to additional delays while
diagnostic testing or antibiotic treatment trials are being carried out.
• Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy may be useful in the evaluation of an abnormal chest
radiograph when sputum smears are negative in these groups of patients.
• Culture-based detection
• Mycobacterial culture on selective media remains the most sensitive method for detecting M. tuberculosis bacilli
in clinical specimens and allows subsequent strain characterization, including drug sensitivity testing (DST).
• The slow replication time of M. tuberculosis requires that solid media cultures be incubated for 2-8 weeks
(depending on the inoculated bacterial concentration) for the growth of the millions of organisms necessary to
generate visible colonies.
• This process can be accelerated by microscopically detecting immature colonies, detecting products of bacterial replication, or using
bacteriophages as markers of mycobacterial viability.
• Automated liquid culture systems have been developed as alternatives to conventional solid media culture.
• These systems detect bacterial carbon dioxide production or oxygen consumption with radiometric sensors (BACTEC 460 TB; Becton
Dickinson Diagnostic Instruments Systems), fluorescent sensors (BACTEC Mycobacteria Growth Indicator Tube [MGIT] 960), or redox
reagents, such as Alamar blue.
• These techniques are now the gold standard for the diagnosis of tuberculosis; they are substantially faster, have a 10% greater
yield than solid media and allow continuous monitoring of growth, obviating the need for mature colony formation compared
with Lφwenstein-Jensen culture.
• The microscopic observation drug-susceptibility (MODS) assay is a simple, rapid, low-cost method for diagnosis of TB and MDR-TB.
• MODS provided high sensitivity and specificity for rapid diagnosis of TB and MDR-TB. With the exception of Brazil, the Russian
Federation and South Africa, culture facilities are not readily available in countries with a high TB burden.
• Molecular detection
• NUCLEIC ACID AMPLIFICATION TESTING (NAAT)
• These tests use oligonucleotide primers and enzymes to catalyze reiterative reactions
that amplify a target, probe or signal, yielding a result within minutes to hours. [
• provides a reliable way of increasing the specificity of diagnosis (ruling in disease), but
sensitivity is variable, especially in paucibacillary disease.
• Despite the clear advantages of NAAT over existing tests, their use in diagnosis is limited
in TB-endemic settings, primarily because of their cost and complexity.
• However, a molecular line probe assay (LPA) is being scaled up by TB programs for rapid
detection of rifampicin and isoniazid resistance and, in combination with liquid
culture, is expected to provide timely results that confirm TB and the presence of drug
resistance.
• Radiographic features of HIV-associated tuberculosis
• The radiographic appearance of TB in AIDS differs from that in immune
competent hosts and depends largely on the level of immunosuppression.
• In early HIV disease where patients have relatively high CD4+ T-lymphocyte
counts (>200 cells/μL), the typical pattern of pulmonary reactivation occurs
with the chest x-ray revealing cavitary apical disease of the upper lobes.
• In advanced disease where patients present with lower CD4+ T-lymphocyte
counts (<200 cells/μL), disseminated disease is more common  diffuse or
lower lobe bilateral reticulonodular infiltrates consistent with primary TB i.e
miliary spread, pleural effusions and hilar and/or mediastinal adenopathy.
• The chest x-ray may also be normal in appearance in some patients with HIV
and TB co-infection.
Treatment of HIV-Associated Tuberculosis
• Anti-tuberculous therapy
• The standard recommendation for the treatment of TB is a 6-month regimen of isoniazid, rifampicin, pyrazinamide
and ethambutol, irrespective of HIV status.
• extending treatment beyond 6 months to 9 months in HIV-infected patients, especially when there is delayed
sputum conversion or evidence of dissemination and low CD4+ cell count.
• They also recommend the routine use of mycobacterial culture and DST
• It recommends that rifampicin should now always be given throughout the 6 months duration (2HRZE/4HR) of the
first-line regimen with the use of directly observed treatment short course (DOTS).
• TB patients returning after defaulting or relapsing from their first treatment course can receive the retreatment
regimen containing first-line drugs 2HRZES/1HRZE/5HRE if country-specific data show low or medium levels of
MDR in these patients or if such data are not available
• Co-trimoxazole preventive therapy
• In all HIV-positive TB patients, co-trimoxazole preventive therapy (CPT) should be initiated as soon as possible
and given throughout TB treatment irrespective of CD4+ T-cell count but barriers to implementing CPT still exist in
TB/HIV programs.
• CPT substantially reduces hospitalization and mortality in HIV-positive TB patients.
• The exact mode of activity is not clear but co-trimoxazole is known to prevent Pneumocystis jirovecii pneumonia and
malaria and is likely to have an impact on a range of other bacterial infections in HIV-positive TB patients.
• Co-infected patients should be given co-trimoxazole 960 mg daily or thrice weekly while ATT is administered.
• Anti-retroviral therapy
• The first line ART regimens that are recommended by the WHO for the treatment of HIV disease include: combinations of 3 drugs: 2
nucleoside reverse-transcriptase inhibitors (NRTIs) and 1 non nucleoside reverse-transcriptase inhibitor (NNRTI).
• Rifampicin is a potent inducer of many genes controlling drug metabolism and transport, including cytochrome P450 isoenzymes (CYP3A4)
and the drug efflux pump p-glycoprotein. Rifampicin may therefore reduce plasma concentrations of concomitantly administered NNRTIs
and protease inhibitors (PIs), potentially resulting in inadequate ART plasma concentrations and inferior ART outcomes. [Although
rifampicin, through its induction of the cytochrome enzyme system, lowers levels of both the NNRTIs-efavirenz and nevirapine, the former is
less affected.
• Efavirenz is therefore the NNRTI of choice for patients with TB and HIV co-infection at the recommended dose of 600mg, which achieves
adequate blood levels and is associated with good outcomes, despite high intra-individual and inter-individual variability
• The use of nevirapine is not recommended routinely with rifampicin, unless there is a contraindication to efavirenz, such as pregnancy or
psychiatric illness.
• However, in resource poor settings, some studies suggest that virological outcomes with nevirapine are comparable to those with efavirenz
when used with rifampicin; if used, the lead-in phase is not required and full-dose nevirapine may be used from the start.
• Alternatively where nevirapine and PI's must be used, rifabutin, which is a less potent inducer of drug metabolism, is recommended as an
alternative to rifampicin in resource rich countries, but is currently unaffordable in resource poor settings and logistically difficult to implement
in TB control programmes which use rifampicin-based fixed dose combination formulations of TB drugs.
• Rifabutin showed similar efficacy to rifampicin in a single-blind randomized study of 50 HIV positive patients in Uganda.
• Among the first-line TB drugs pyrazinamide, isoniazid and rifampicin have all been associated with hepatotoxicity.
• There are concerns about increased hepatoxicity when NNRTIs, particularly nevirapine and PI's are prescribed with TB treatment.
• Other shared side effects include drug rashes (that may occur due to many of the TB drugs, co-trimoxazole, nevirapine and, less frequently,
efavirenz), peripheral neuropathy (especially with isoniazid, stavudine and didanosine) gastro-intestinal intolerance (especially with
zidovudine, didanosine, protease inhibitors, pyrazinamide, ethionamide and para-aminosalicylic acid) and neurospychiatric side effects
(especially with efavirenz, isoniazid, ethionamide and cycloserine).
• Aminoglycosides (for example amikacin and kanamycin) and capreomycin used in the treatment of drug-resistant TB may result in
nephrotoxicity and co-administration of tenofovir with Aminoglycoside, which may also result in nephrotoxicity, should be avoided as much as
possible.
• Reasons to delay the initiation of ART until after 2 months of ATT include drug interactions between rifampicin and NNRTIs, cumulative drug
toxic effects (especially hepatotoxicity), pill burden and IRIS. The current WHO guidelines recommend that all HIV-infected individuals with
active TB (regardless of CD4+ cell count) receive ART as soon as TB treatment is tolerated, generally within 2-8 weeks. [75]
Preventing active TB in HIV patients
• WHO recommends provision of combination ART (ART) and the Three I's for
HIV/TB:
• intensified case-finding of TB (ICF)
• infection control (IC)
• isoniazid preventive therapy (IPT) for TB.
• Isoniazid preventive therapy significantly reduces tuberculosis in these patients who have a
positive TST [but not in those with a negative test.
• Such preventive therapy, administered to patients who are positive on TST and infected with
HIV, in areas of high incidence also provides around 60% protection, although the duration of
protection is limited.
• The WHO recommended a 6-month course of isoniazid for people with HIV infection and a
positive TST after excluding active TB and extended this recommendation to patients living in
areas where tuberculin skin testing was not feasible if the prevalence of latent tuberculosis
infection was high.
MDR-TB and HIV
• HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin
resistance which may contribute to resistance.
• Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons and
delayed diagnosis, inadequate initial treatment and prolonged infectiousness contribute
to increased attack rates among contacts and high case fatality rates among patients.
• Lack of routine use of mycobacterial culture and DST as recommended by the WHO are
the main impediments to MDR-TB diagnosis.
• At least 4 effective drugs-including a fluoroquinolone, an injectable agent (capreomycin,
kanamycin, or amikacin) and at least 2 agents from the remaining second-line anti-TB
drug classes (cycloserine, thioamides [ethionamide or prothionamide] and p-
aminosalicyclic acid)-along with pyrazinamide and ethambutol, if still sensitive, should
be used.
XDR-TB and HIV
• XDR-TB can develop when the second-line drugs for MDR-TB
treatment are misused and therefore, become ineffective and lead to
amplified resistance.
• Treatment options are extremely limited and challenging, with high
frequencies of adverse events and death.
LO 3
Multi Drug Resistent TB
http://www.sajr.org.za/index.php/sajr/article/view/829/1154
LO 4
Bronkiektasis
BRONCHIECTASIS
• Merupakan penyakit kronis progresif yg ditandai dgn dilatasi bronkus
dan bronkiolus yg bersifat menetap serta penebalan dinding bronkus.
• Disebabkan oleh infeksi virus atau bakteri yg kronis, dan inflamasi yg
diikuti dengan pelepasan mediator
• Dpt berupa focal (melibatkan jalan nafas regio yg terbatas dr
parenkim paru) atau difus (melibatkan distribusi lebih luas)
• Dari 110.000 pasien bronkiektasis di US, 2/3  wanita
http://radiopaedia.org/articles/bronchiectasis
Patofisiologi
1. Traksi dari saluran respiratorik yg kolaps, penonjolan saluran respiratorik akibat sekresi
sisa, perubahan dinding bronkial akibat infeksi atau inflamasi, atau kombinasi ketiga
mekanisme tersebut.
• Sering pd tingkat bronkus segmental atau subsegmental.
• Inflamasi sal nafas biasanya dimediasi t/u oleh neutrofil & menghasilkan regulasi enzim (elastase, matrix
metalloproteinases).
• Struktur komponen normal dari dinding: kartilago, otot, jar elastik  hancur  diganti jar fibrosa
• Dilatasi sal nafas biasanya tdd pool materi purulen tebal
• Sal nafas yg lebih perifer teroklusi oleh sekresi atau hilang dan digantikan jar fibrosa
2. Infeksi akut atau berulang, obstruksi kronis akibat kelainan kongenital, tumor, fibrosis
kistik, asma kronis, atau imunodefisiensi merupakan faktor pendukung terjadinya
bronkiektasis
3. Jejas berulang saluran respiratorik akibat aspirasi kronis, dengan atau tanpa GER sebagai
salah satu faktor penyebab
Etiologi & Patogenesis
• Konsekuensi dari inflamasi & destruksi komponen struktural dinding
bronkial:
• Penyebab tersering: infeksi Pseudomonas aeruginosa & Haemophilus
influenza  produksi pigmen, protease, toxin  melukai epitel respirasi & 
fungsi klirens mukosilier
• Respon inflamasi host  epitel rusak krn mediator dari neutrofil
• Proteksi jalan nafas   susceptible thd kolonisasi & pertumbuhan bakteri
Penyebab infeksius
• Adenovirus & Influenza
• Organisme berpotensi nekrosis: S.aureus, Klebsiella, anaerob 
penyebab penting bronchiectasis jika AB th/ pneumonia ✗ diberikan
atau ditunda
• Infeksi Bordetella pertussis pd masa anak2  terkait dg pykt
supuratif kronik sal nafas
• Dilaporkan pd pasien HIV (krn infeksi bakteri rekuren)
• TB  penyebab major bronchiectasis  dpt produksi dilatasi sal
nafas dg efek nekrosis pd parenkim paru & scr indirek sbg
konsekuensi dr obstruksi dr bronkostenosis atau kompresi ekstrinsik
nodus limfa
• Non-TB ditemukan pd kultur sbg infeksi sekunder atau kolonisasi
• Mycobacterium avium complex dpt menjadi patogen primer terkait
dg perkembangan dan progresi bronchiectasis
Penyebab non-infeksius
• Bbrp bronkiektasis berhub dg paparan thd substansi toksik  respon
inflamasi berat
• Ammonia, aspirasi konten gastrik asam
• Respon imun  memicu inflamasi  perubahan destruktif  dilatasi
bronkial
• Mekanisme ini penting u/ bronkiektasis dg ABPA (allergic bronchopulmonary
aspergillosis)
• Defisiensi α1 antitripsin  panacinar emfisema, biasanya indv jg
bronkiektasis
• Yellow nail syndr  krn hipoplastik limfatik, triad lymphedema, pleural
effusion, yellow discoloration dari kuku + bronkiektasis pd 40% ps
Manifestasi klinis
• Pada anak biasanya ditemukan pada usia prasekolah dan usia awal sekolah
• Batuk pesisten atau rekuren
• Batuk produktif, terjadi pada siang hari, memberat pada malam hari
• Pengeluaran banyak sputum (jernih  kekuningan  kuning kehijauan) > 6minggu
• Infeksi traktus respi dg purulen berulang  curiga bronkiektasis
• Hemoptysis  50-70% kasus krn berdarah dr mukosa yg bengkak rapuh
• Perdarahan lebih parah krn rusak p.d bronkial
• Jari tabuh
• Demam, sesak napas
• Gejala sistemik: fatigue, BB, myalgia
PF
• Bervariasi
• Kombinasi rhonki + crackles + wheeze
PP
• Radiografik
• CXR sgt penting u/ evaluasi bronkiektasis
• Potongan longitudinal: Tram tracks appearance
• Potongan cross-sectional: Ring shadows
• Lumen lebih padat  opaque tubular atau bercabang
• CT: 1-1.5 mm  gambaran jelas sal yg terdilatasi (skrg merupakan
teknik stardar u/ deteksi & konfirmasi diagnosis bronkiektasis)
• PK
• Sputum   neutrofil & kolonisasi atau infeksi dr organisme
• Kultur & pewarnaan  u/ th/ AB
• Bronkiektasis focal  bronkoskopi memperlihatkan obstruksi
endobronchial
• Keterlibatan lobus superior  suspek TB atau ABPA
Signet Ring
TRAM TRACK APPEARANCE

http://bronchiectasis.com.au/bronchiectasis/diagnosis-2/radiology https://openi.nlm.nih.gov/detailedresult.php?img=PMC3393337_copd-7-383f1&req=4
Pemeriksaan lab
Harus dapat menyingkirkan etiologi yg mungkin dapat
menyebabkan bronkiektasi
1. Sweat chloride  utk fibrosis kistik
2. IgE, hitung eosinofil, presipitan serum  utk aspergilus
3. Kultur sputum  utk jamur
4. Uji kulit terhadap aspergilus  menyingkirkan adanya ABPA
5. Pemeriksaan darah rutin lengkap
6. IgG, IgM, IgA serum, IgG subklas
7. Uji HIV
8. Kultur sputum atau apus orofaring dalam, dilakukan pada anak
yg masih kecil
9. Antinuclear antibody dan rheumatoid factor
High resolution CT
Acid fast bacilli

Tatalaksana
• Tujuan utama:
• Th/ infeksi, tu saat eksaserbasi akut
•  klirens sekret trakeobronkial
•  inflamasi
• Th/ penyakit yg mendasari yg terdeteksi
• AB sesuai pewarnaan gram
• Empiric: amoxicillin, trimetrophin-sulfamethoxazole, levofloxacin
• Pseudomonas  th/ oral dg kuinolon atau th/ parenteral dg aminoglikosid, carbapenem, gen 3
sefalosporin
• ✗ petunjuk pasti tp biasa diberikan 10-14 hari atau lebih
• Drainase
• Hemoptysis masif  ✗ membaik dg th/ konservatif  reseksi atau embolisasi arteri bronkial
Pencegahan
• Imunisasi campak dan pertusis pada masa kanak-kanak, menurunkan angka kejadian
bronkiektasis
• Vaksin influenza berkala membantu mencegah kerusakan bronkus oleh virus flu.
• Vaksin pneumokok membantu mencegah komplikasi berat dari pneumonnia pneumokok.
• Minum antibiotik dini saat infeksi juga mencegah bronkiektasis atau memburuknya
penyakit.
• Pengobatan dengan imunoglobulin pada sindroma kekurangan imunoglobulin mencegah
infeksi berulang yang telah mengalami komplikasi.
• Penggunaan anti peradangan yang tepat
• Menghindari udara beracun, asap dan serbuk yang berbahaya
• Masuknya benda asing ke saluran pernafasan
Diagnosis banding
• Hemosiderosis
• Hipersensitivitas pneumonitis
• Obstructive sleep apnea syndrome (OSAS)
• Right middle-lobe syndrome
• Sarkoidosis
• trakleomalasia
Komplikasi
• Bronkitis kronis
• Pneumonia dengan atau tanpa ateletaksis
• Pleuritis
• Efusi pleura atau empiema
• Abses metastasis di otak
• Hemoptisis
• Sinusitis
• Kor pulmonal kronik
• Kegagalan pernapasan
• Amiloidosis
LO 5
Pertusis
• Merupakan infeksi traktus respiratorius akut
• Whooping cough
• Etiologi: Bordetella pertussis
• Batuk yg menahun (kadang paroxysmal) jg dpt disebabkan
oleh Mycoplasma, parainfluenza, influenza, enterovirus,
RSV, adenovirus
Patogenesis
Bordetella pertusis masuk mll
sal. nafas
Menempel di trakea dan Hemaglutinin

bronkus filamentosa
• Toksin adenilat siklase

Mengeluarkan toksin dan
• Toksin dermonekrotik
substansi • Toksin hemolisin
• Sitotoksin paratrakeal
Nekrosis epitelium
• Pertusis yg berat terjadi pada bayi muda yg belum pernah diberi
imunisasi
• Setelah masa inkubasi 7-10 hari, anak timbul demam, biasanya
disertai batuk dan keluar cairan hidung yg secara klinik sulit dibedakan
dari batuk dan pilek biasa.
• Pada minggu ke 2, timbul batuk paroksismal yg dapat dikenali sbg
pertusis
• Batuk dapat berlanjut sampai 3 bulan atau lebih
Manifestasi klinis
• Penyakit yg lama, dibagi menjadi tahap: • Gejala inisial: Batuk kering,
• Catarrhal intermitten, iritative 
• 1-2 mgg paroksismal & tdk dpt ditahan
• setelah masa inkubasi 3-12 hari • Terinterupsi dg batuk tiap tarikan
dg gejala yg tdk khas: nafas, dagu & dada tertarik
kedepan, lidah menjulur
• Kongesti, rhinorrhea, maksimal, eye buldging & berair,
demam ringan, lakrimasi, wajah keunguan hgg batuk
conjunctival suffusion, berhenti & whoop yg keras
coryzea, batuk mild to mengikuti inspirasi
severe
• Post-tussive emesis (muntah
• Paroxysmal setelah batuk) & kelelahan
• 2-6 mgg, bisa bertahan hingga • # & derajat keparahan
10mgg paroxismal naik dlm bbrp hari
hgg minggu, tetap plateau bbrp
hari – minggu. Pada puncak
tahap paroxysmal = >1 episode
/jam
• Convalescent
• 2 mgg
• #, keparahan, durasi episode
hilang
Nelson Textbook of Pediatrics

• Bayi <3 bln
• Fase catarrhal hilang bbrp hari atau tdk terlihat
• Bayi mulai tersedak, gasp, gag, wajah memerah & memukul-
mukul ekstremitasnya
• Batuk mgkn tidak menonjol pd fase awal
• Whooping jarang tjd
• Apnea & sianosis menyertai batuk paroxysmal
• Lebih umum ditemukan pd pertussis daripada infeksi viral
• apnea dpt tjd tanpa batuk
• Apnea  mgkn satu2nya gejala
• Fase paroxysmal & convalescent pd bayi panjang
• Pd bayi batuk yg keras & whooping lebih keras & klasik pd
fase convalescence
• Intermiten paroxysmal coughing 1 tahun pertama kehidupan +
eksaserbasi penyakit respi lainnya (bukan reaktivasi pertussis)

• Adolescents (remaja)
• Remaja & anak2 yg sebelumnya diimunisasi memiliki waktu
yg lebih pendek dari setiap fase pertussis
• Dewasa tdk ada fase yg jelas
• Remaja & dewasa  tiba2 merasa tercekik + batuk tak
terinterupsi, sesak nafas, sakit kepala hebat, kesadaran
berkurang, kemudian nafas terengah, biasanya tanpa
whoop
• Clue: post-tussive emesis & intermiten paroxysms terbagi bbrp jam
• 30% dewasa pertusis tdk memiliki batuk spesifik, hanya dibedakan
berdasarkan durasi, biasanya >21 hari
• Sering ditemukan hemorrhages & petechiae pd tubuh
bagian atas

https://www.cdc.gov/pertussis/clinical/diagnostic-testing/diagnosis-confirmation.html
Diagnosis
• Suspek setiap individu dg predominan atau murni keluhan batuk
• Kultur  spesifik
• Dari spesimen nasopharyngeal 2 mgg pertama
• > 2mgg  sensitivity is decreased and the risk of false-negatives increases.
• PCR  lack of sensitivity in previously immunized individual
• should be tested from NP specimens taken at 0 to 3 weeks following cough onset, but may provide accurate results for up to 4
weeks.
• After the fourth week of cough, the amount of bacterial DNA in the nasopharynx rapidly diminishes, which increases the risk of
obtaining falsely-negative results.
• Serologi  not useful for diagnosing acute infection but can be confirmatory in the convalescent phase of
illness,
• The white blood cell count may increase from 20,000 cells/mm3 to more than 50,000 cells/mm3, consisting
primarily of mature lymphocytes.
• Radiographic signs:
• segmental lung atelectasis  during the paroxysmal stage.
• Perihilar infiltrates are common and are similar to those seen in viral pneumonia.

Tatalaksana
• Oksigen
- Bila terjadi sianosis atau berhenti napas atau batuk paroksismal berat
- Terapi dilanjutkan sampai gejala tsb tidak ada lagi
• Selama batuk paroksismal, letakkan anak dengan posisi kepala lebih
rendah dalam posisi telungkup, atau miring untuk mencegah aspirasi
muntahan dan membantuk pengeluaran sekret
- Bila anak mengalami episode sianotik, isap lendir dari hidung dan
tenggorokan dengan hati-hati
- Bila apnea, segera bersihkan jalan napas, beri bantuan pernapasan manual
dengan pompa ventilasi atau berikan oksigen
Perawatan penunjang
• Hindarkan dari tindakan yg merangsang terjadinya batuk
• Jangan memberi penekan batuk, obat sedatif, mukolitik atau
antihistamin
• Obat antitusif dapat diberikan bila batuk amat menggangu
• Jika anak demam ≥ 39⁰C yg dianggap dapat menyebabkan distress,
berikan parasetamol
• Beri ASI atau cairan peroral, nutrisi yg adekuat dgn pemberian
makanan porsi kecil dan sering
• Erythromycin
• Azithromycin • Because relapses have been reported after completion of 7--10 days
• Side effects : of treatment with erythromycin, a 14-day course of erythromycin
• abdominal discomfort or pain is recommended for treatment of patients with pertussis or for
• Diarrhea postexposure prophylaxis of close contacts of pertussis patients
• Side effects:
• Nausea
• Gastrointestinal irritation (epigastric distress, abdominal
• Vomiting cramps, nausea, vomiting, and diarrhea)  ORAL
• Headache • Some formulations with enteric-coated tablets and the ester
• dizziness. derivatives (e.g., ethylsuccinate) can be taken with food to
• Azithromycin should be prescribed with caution to minimize these side effects.
patients with IMPAIRED HEPATIC FUNCTION. • Hypersensitivity reactions (e.g., skin rashes, drug fever, or
eosinophilia), cholestatic hepatitis, and sensorineural hearing
• All patients should be cautioned not to take
loss  after administration of macrolides
azithromycin and aluminum- or magnesium- • An increased risk for IHPS(infantile hypertrophic pyloric
containing antacids simultaneously  reduces the stenosis) has been reported in neonates during the month
rate of absorption of azithromycin. after erythromycin administration
• Monitoring of patients is advised when azithromycin • Kontraindikasi :
is used concomitantly with agents metabolized by • hypersensitivity to any macrolide agent.
the cytochrome P450 enzyme system and with other • should not be administered concomitantly with astemizole,
drugs for which the pharmacokinetics change (e.g., cisapride, pimazole, or terfenadine.
• Rare cases of serious cardiovascular adverse events, including
digoxin, triazolam, and ergot alkaloids).
electrocardiographic QT/QTc interval prolongation, cardiac
• Azithromycin is classified as an FDA Pregnancy arrest, torsades de pointes, and other ventricular
Category B drug (75). arrhythmias, have been observed after concomitant use of
erythromycin with these drugs.
• Erythromycin is classified as an FDA Pregnancy Category B drug
Category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-
controlled studies in pregnant women.
• Clarithromycin. • Alternate agent (TMP--SMZ).
• Side effect : • effective in eradicating B. pertussis from the nasopharynx
• epigastric distress, abdominal cramps, nausea, • TMP--SMZ is used as an alternative to a macrolide antibiotic in
vomiting, and diarrhea. patients aged >2 months who have contraindication to or
• Hypersensitivity reactions (e.g., skin rashes, drug cannot tolerate macrolide agents, or who are infected with a
fever, or eosinophilia), hepatotoxicity, and severe macrolide-resistant strain of B. pertussis. Macrolide-resistant B.
reactions such as anaphylaxis are rare. pertussis is rare.
• Because of its similarity to erythromycin, both • should not be administered to pregnant women, nursing
chemically and metabolically, clarithromycin should mothers, or infants aged <2 months.
not be administered to infants aged <1 month • Side effect :
because it is unknown if the drug can be similarly • gastrointestinal adverse effects, hypersensitivity skin
associated with IHPS. reactions, and rarely, Stevens-Johnson syndrome, toxic
• Kontraindikasi : epidermal necrolysis, blood dyscrasias, and hepatic
• history of hypersensitivity to any macrolide agent. necrosis.
• should not be administered concomitantly with • Kontraindikasi :
astemizole, cisapride, pimazole, or terfenadine. • hypersensitivity to trimethoprim or sulfonamides.
• can be administered without dosage adjustment in • prescribed with caution to patients with impaired hepatic
patients with impaired hepatic function and normal renal and renal functions, folate deficiency, blood dyscrasias,
function; however, drug dosage and interval between and in older adults because of the higher incidence of
doses should be reassessed in the presence of impaired severe adverse events.
renal function. • should be instructed to maintain an adequate fluid intake to
• Clarithromycin is classified by FDA as a Pregnancy Category prevent crystalluria and renal stones.
C drug. (Animal reproduction studies have shown an • TMP--SMZ is classified by FDA as a Pregnancy Category C.
adverse effect on the fetus; no adequate or well-controlled
studies in humans exist.)
Prevention
• Active immunity is induced with acellular pertussis components given as a vaccine in
combination with the tetanus and diphtheria toxoids (DTaP).
• The acellular pertussis vaccines contain two to five antigens of B. pertussis, including pertussis toxin,
pertactin, filamentous hemagglutinin, and fimbrial agglutinogens, FIM-2 and FIM-3.
• DTaP vaccine is recommendedat 2, 4, 6, and 15 to 18 months, with a booster at 4 to 6 years, and has
an efficacy of 70% to 90%.
• A single booster doseof Tdap vaccine is recommended at 11 to 12 years or once for all adults.
• Underimmunized close contacts under 7 years of age should receive a booster dose of DTaP (unless
a booster dose has been given within the preceding 3 years), whereas those 7 to 10 years of age
should receive Tdap.
• Macrolides are effective in preventing secondary cases in contacts exposed to pertussis.
• All close contacts should receive prophylactic antibiotics for 5 days (azithromycin) or 7 to
14 days (clarithromycin or erythromycin, duration based on age).
DTaP is a vaccine that helps children younger than age 7 develop immunity to three deadly diseases caused by
bacteria: diphtheria, tetanus, and whooping cough (pertussis).
Tdap is a booster immunization given at age 11 that offers continued protection from those diseases for adolescents
and adults. Nelson Textbook of Pediatrics
Komplikasi
• Komplikasi utama pertusis:
• Apnea, infeksi sekunder (otitis media, pneumonia), batuk forceful
• Peningkatan tekanan intrathoracic & intraabdominal saat batuk  sklera &
konjungtiva hemorrhage, petechiae, epistaxis, CNS & retina hemorrhage,
pneumothorax & emfisema subkutis, umbilical& inguinal hernia
• Hipertensi pulmonal
• Abnr CNS krn hypoxemia & hemorrhage krn batuk atau apnea
• Bronchiectasis
• <2 tahun  dewasa  fungsi pulmo abnr
• Gizi kurang  disebabkan oleh berkurangnya asupan makanan dan sering muntah

LO 6
Kanker Paru
Tumor Paru
• Small cell lung cancer (SCLC) is one of the fastest growing and
spreading of all cancers.
• Large cell neuroendocrine carcinoma (LCNEC) is a rare cancer. It is a
subtype of non-small cell lung cancer (NSCLC).
• Typical carcinoids tend to grow slowly and only rarely spread beyond
the lungs. About 9 out of 10 lung carcinoids are typical carcinoids.
• Atypical carcinoids grow a little faster and are somewhat more likely
to spread to other organs. They have more cells in the process of
dividing and look more like a fast-growing tumor. They are much less
common than typical carcinoids.
http://www.cancer.org/cancer/lungcarcinoidtumor/detailedguide/lung-carcinoid-tumor-signs-and-symptoms
• Merokok = penyebab utama ca paru
• >60% kasus kanker paru:
• Never smokers (<100 cigarettes/lifetime) or
• Former smokers (100 cigarettes/lifetime, quit or 1 year)
• 1/5 wanita & 1/12 pria dg Ca paru  never smoked
Faktor risiko
• Mayoritas 80-90% merokok
• 10x atau risiko tinggi
• 1 mutasi genetik tiap 15 batang rokok
• Merokok meingkatkan risiko semua tipe kanker paru mayor
• ETS (environmental tobacco smoke) atau secondhand smoke juga penyebab dr ca paru
• Rendahnya asupan buah dan sayur saat dewasa (cerotenoid, retinoid 
chemopreventive)
• Radiasi ion
• Penyakit paru terdahulu
Harrison’s Principles of Internal Medicine,18e

Occupational
risk
Predisposisi herediter
• Karsinogen lingkungan  induksi transformasi sel bronchoepithelial
ke fenotip malignan
• Polymorphism genetik p450 enzyme system (specific: CYP1A1) atau
fragilitas kromosome  perkembangan ca paru
• Mutasi pd RB gene (Retinoblastoma) & P53 (Li-Fraumeni syndrome)
• 3 lokus genetik u/ ca paru:
• 5p15
• 15q25 (nicotinic acetylcholine receptor subunits)
• 6p21
Patologi
• Kanker paru (term) digunakan u/ tumor yg muncul dari epitel respirasi
(bronchi, bronchioles, alveoli)
• 4 histologi yg 90% dari seluruh kanker sel epitel paru:
• Small Cell Lung Cancer (SCLC)
• Adenocarcinoma
• Pd wanita & dewasa muda (<60 thn), adenocarcinoma = paling sering
• Squamous cell carcinoma
• Large cell carcinoma
Small Cell Carcinoma
• Tumor neuroendokrin tdk terdiferensiasi
• Prevalensi tinggi pada perokok
• Laki2 > perempuan
• Massa central dg pertumbuhan endobronchial
Squamous Cell Carcinomas
• Mayoritas di mainstem, lobar atau segmental bronchi
• Infiltrasi sel tumor dg nekrosis sentral  kavitasi
• Terkait dg riwayat merokok
• Biasanya terlihat keratin
• Varian penting: pola papillary, basaloid
Adenocarcinomas
• Lokasi di perifer paru
• Terkait dg riwayat merokok
• Tumor malignan epitel dg diferensiasi glandular atau produksi mucin
• Histologis, jaringan terdiri dari:
• Kelenjar
• Struktur papillary
• Pola bronchioalveolar
• Mucin seluler
• Pola padat jika tdk terdiferensiasi
• Padat + pola mikropapillary  prognosis buruk
• Varian: signet-ring, clear cell, mucinous
Bronchioalveolar carcinoma (BAC)
• Subtipe dari adenocarcinoma
• Tumbuh pd alveoli tanpa invasi
• Radiograf: massa tunggal, lesi multinodul diffuse, infiltrat fluffy
• CT: ground glass opacity
Large Cell Carcinomas
• <10% kanker paru
• Perifer
• Tdk terdiferensiasi baik
• Sel malignan besar + nekrosis
• Sitologi: tersusun sbg kelompok
syncytial, sel tunggal
• Varian:
• Basaloid carcinoma
• Lymphoepithelioma-like carcinoma
• Terkait dg EBV
https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-chap1.pdf
http://www.cancer.org/cancer/lungcarcinoidtumor/detailedguide/lung-carcinoid-tumor-diagnosis
PP
• X-Ray
• CT-scan
• Somatostatin receptor scintigraphy
• Sputum cytology (PPP)
• Biopsy
• Blood & Urine Test
• Pulmonary Function test
LO 7
Pnumokoniasis
• Penyakit paru okupasi (occupational lung diseases)
disebabkan atau diperburuk paparan thd substansi
berbahaya di tempat kerja
• Pneumoconiosis = penyakit terkait dg inhalasi mineral
dusts
• Debu yg menyebabkan fibrosis = fibrogenic
• Klasifikasi pneumoconiosis
Patogenesis
Serat reticulin
Proliferasi serat
Inhalasi debu penyokong tumbuh
kolagen
antara sel
Makrofag alv Protrude ke ruang Debu menetap di

engulf alv atau obliterasi makrofag pd lesi ini
Jika menetap,
Sel mati sesuai life
# partikel >>> pneumocyte tipe 1
span
tumbuh melapisi
Makrofag dg debu
Partikel
berkumpul di Migrasi ke limfatik
Mekanisme dikeluarkan,
interstisium (t/u atau bronkiol u/
eliminasi gagal reingested oleh
perivascular & dieliminasi
makrofag lain
peribronkial)
Diagnosis
• Berdasarkan riwayat pekerjaan
• Temuan radiografik dada & fungsi pulmonal
• Banyak yg efeknya muncul bbrp tahun setelah paparan
• Riwayat merokok  risiko meningkat u/ silikosis & coal workers’ pneumoconiosis
• Nafas pendek, batuk, dada sesak, dan/atau wheezing
• Presentasi awal bs berupa hemoptisis & demam (TB pulmonal berkembang sbg
komplikasi dr paparan silica)
• Tdk sering presentasi berupa non-respi: scleroderma atau RA
• Tanda fisik absen pd awal penyakit.
• Clubbing of fingers & toes  jk keparahan meningkat
Siderosis
• Buffer’s lung / silver polisher’s lung
• Non-fibrogenic, benign
• Inhalasi partikel iron (besi)
• Mikroskopis:
• Lesi perivaskuler & peribronkial agregasi partikel iron oxide berpigmen gelap dlm makrofag & ruang
alv & dindingnya.
• Sedikit prolif reticulin (ada berkaitan dg merokok)
• CXR:
• # >> opacities nodular 0.5-2 mm d, fine linear opacities
• Kerley’s B line pd bbrp ps (akumulasi iron pd septa interlobular)
• Nodus hilus radioopaque krn [] iron (tdk membesar)
• HRCT:
• Widespread
• Ill defined, small centrilobular nodules
• Jarang: patchy areas of ground glass
• Emphysema
• Bbrp tahun  menghilang
Stannosis
• Tin oxide
• Makros:
• Macula hitam-abu kecil banyak 1-3mm
• Lembek
• Tdk lebih tinggi dr permukaan paru
• Tdk meng gg fgs paru, tdk ada gejala atau tanda abnr
• Radiologi:
• Opacities kecil, banyak, tersebar rata di lapang paru
• >2-4 mm diameter
• Lebih ireguler & fluffy dari siderosis
• Kerley’s line
• Opacities/keruh linear padat di zona paru atas
Baritosis
• Debu barium
• Partikel menetap di paru bertahuntahun tdk ada
gejala, tanda abnr, ggan pd paru
• Radiograf:
• Padat
• Keruh  hilang dlm tahunan
Aluminosis
• Jarang
• Paparan thd silica bebas & bkn aluminium oxide
• Desquamative interstitial pneumonia
• Rxsi paru granulomatous & proteinosis alv paru setelah
paparan aluminium fumes
• Histologi: fibrosis subpleural & interstitial dg scar emfisema &
granulomatous pneumonitis + giant cells
• Radiograf
• Fibrosis interstitial diffuse tu pd lobus superior & medius paru
• Advance: subpleural bullous emphysema dg risiko
pneumothorax spontan
• HRCT:
• Keruhan nodular, centrilobular, septa interlobular menebal
Talcosis
• Talc (mineral pd keramik, kertas, plastik, karet, cat, kosmetik)
• Inflamasi granulomatous paru
• Inhalasi atau intravena
• Sering dg gejala non spesifik progresive dyspnea atau batuk
• Histologis:
• Non-necrotizing granulomatous inflammation: pembentukan
foreign body granumolas (multinucleated giant cells)
• CXR:
• Mikronodular diffuse atau nodul berbatas tegas yg dpt fusi dg
progresi  opasitas meningkat pd regio periilar
• Penebalan interstisial & emfisema lower-lobe dpt tampak
Berylliosis
• Mirip sarkoidosis
• Hilar limfadenopato dg kenaikan interstitial
Silicosis
• Nodul jelas kecil, di zona atas paru predominan posterior
• Nodul bergabung  lesi fibrotik masif
• PMF: apikal, posterior dg distorsi parenkim perifer
• Hilar & mediastinal nodus limfa membesar & kalsifikasi pd bentuk eggshell, belang,
atau masif
• Keterkaitan silicosis & pulmo TB
• Bacilli dpt encapsulated di nodul silikotik  reaktivasi penyakit
• Terlihat kavitas pd silicosis (bs tnp TB)
• Menurun fgs paru
• Test tuberkulin dg purified prot derivatives PPD  indikasi pd smua ps silikosis
• +  th/ infeksi
complicated PMF
Coal Worker’s Pneumoconiosis
• Akumulasi debu coal pd paru & reaksi jaringan thdnya
• Kategori:
• Simple coal worker’s (SCWP)
• Complicated (CCWP) atau PMF
• Pneumoconiosis – RA
• Classic (Caplan’s syndrome)
• CXR:
• 12 points classification
• Opasitas nodular kecil bulat
• Risiko TB meningkat
• Inhalasi jg terkait dg perkembangan COPD
PMF - patofisiologi
• Inhalasi debu batubara menjadi masalah ketika mekanisme pertahanan tubuh untuk memproses debu
bekerja terlalu keras (kewalahan) dan lalu menjadi overreaktif
• N: Inhalasi debu mencapai bronkiolus terminalis  carbon ditelan oleh makrofag alveolar & insterstisial
 partikel debu yg terfagosit dibwa dengan gerakan mukosiliar dan dikeluarkan bersama mukus atau
melalui sistem limfatik
• AbN: Sistem kewalahan  makrofag kaya debu terakumulasi di alveoli  respons imun terpicu 
fibroblast mensekresi retikulin  makrofag terperangkap o/ retikulin  makrofag lisis (terutama
apabila debu kaya silica)  respons meningkat  lebih banyak retikulin
• Bila makrofag ini sempat bermigrasi ke sistem limfatik di hilus, arteriol bisa terjepit akibat fibrosis interstisial  lebih
byk fibroblast, retikulin, dan kolagen terdeposit di hilus  nekrosis iskemik
• AbN: Daerah fokus deposisi debu batubara & makrofag disebut “coal macules” (ciri khas histologik dari
CWP)  tiap macules bergabung membentuk fibrosis interstisial  kolagen byk  distensi bronkiolus
 area fokus enfisema  area emfisema menyebar
• Tuberculosis dapat berperan sbg rheumatoid factor yang mengeksaserbasi laju progresi nekrosis iskemik
& fibrosis
Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue[1] composed of type III collagen
secreted by reticular cells.[2] Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a Medscape: Coal Worker Pneumoconiosis
supporting mesh in soft tissues such as liver, bone marrow, and the tissues and organs of the lymphatic system.
faktor risiko
• Tipe debu: Lebih banyak silica, lebih tinggi risiko fibrosis
• Usia saat terpapar
• Durasi terpapar
• Merokok
• Ukuran partikel debu
• Tipe pekerjaan (mis berhadapan langsung memotong batubara memiliki risiko lebih tinggi)
Medscape: Coal Worker Pneumoconiosis

tanda gejala
• Simple PMF biasanya asimptomatik atau gejala spt batuk & produksi
sputum (biasanya sekunder akibat bronkitis industrial atau merokok)
• Complicated PMF: batuk, dyspnea, gg fungsi paru, (advanced:) cor
pulmonale dg RVH, hepatomegali, edema perifer
• Kerusakan struktur dan mekanik paru sbbkan demam, keringat
malam, dan gejala konstitusional lain yang menunjukkan proses
infektif sekunder

PP
• Lab: hitung darah lengkap & kultur sputum untuk mengeksklusi proses infektif
• Pencitraan: Radiograf hingga sekarang masih digunakan sbg main diagnositic tool:
• Simple CWP biasanya terlihat sbg lingkaran opak kecil di lobus atas paru dg densitas: P (d: ≤1.5
mm), Q (d: 1.5-3 mm), R (d: 3-10 mm)
• Zona paru: RUZ & LUZ, RMZ & LMR, RLZ & LLZ
• Nodus opak d >1 cm = complicated CWP: A (d: 1-5 cm), B (d: 5 cm memenuhi <1/3 paru), C (≥1
nodul dg d > 1/3 paru)

Asbestosis
• Perokok meningkatkan progresi asbestosis
• Rusaknya klirens mukosilier
• Gejala stlh 20 tahun atau lebih
• Laten 15-40 tahun (antara paparan  penyakit)
• Dyspnea paling sering
• Batuk non produktif
• Clubbing finger (32-42 %)
• Infiltrat retikulonodular pd basis paru
• HRCT: subpleural linear opacities parallel thd pleura
• Basillar lung fibrosis
• Honeycombing, pleural plaques
• The American College of Pathologists’ (severity of
asbestosis grades fibrosis)
• 1: fibrosis dinding respi bronkiol tanpa ekstensi ke alveoli
yg jauh
• 2 & 3: penyakit lebih ekstensif
• 4: fibrosis alveolar & septal dg ruang lbh besar drpd alveoli
~1 cm (mis: honeycombing)
Pneumoconioses. [Indian J Chest Dis Allied Sci 2013;55:25-34]. http://www.medind.nic.in/iae/t13/i1/iaet13i1p25.pdf

LO 8
Histoplasmosis
Histoplasmosis
• Secara superfisial mirip dg tuberculosis
• Sering menginfeksi inisial pd paru
• Patogen dpt menyebar mll darah & limfe  lesi ke organ lain
• Gejala tdk jelas & subklinikal, infeksi respiratori minor
• <0,1% berprogress  berat (inokulum berat atau reaktivasi saat
sistem imun menurun)
• Organisme kausatif: Histoplasma capsulatum
• Fungus dimorfik
• Pd perkembangan jaringan (370): morfologi seperti ragi
• Sering ditemukan pd intrasel makrofag, bertahan hidup &
multiplikasi
• Tanah atau media artifisial (suhu ruangan): miselium
filamen dg konidia reproduktif
• Manusia mendapatkan penyakit dari konidia airborne
t/u dr kotoran burung & kelelawar
• Burung tdk membawa penyakit krn temperatur tubuh
yg tinggi, namun kotorannya memberikan nutrien
(nitrogen) u/ jamur
• Kelelawar dg suhu tubuh lebih rendah membawa
jamur dalam feses  infeksi tempat baru di tanah
• Th/: itraconazole atau amphotericin B
Klasifikasi penyakit
• Acute pulmonary histoplasmosis
• Chronic-Cavitary pulmonary histoplasmosis
• Progressive disseminated histoplasmosis
Acute Pulmonary Histoplasmosis:
immunocompetent host
• Muncul 2 mgg setelah terpapar berat pd pasien imunokompeten
• Gejala nonspesifik:
• Demam, meriang, batuk, dyspnea, chest pain
• Pemeriksaan Ag Histoplasma pd urin & serum
• BAL u/ pemeriksaan sekresi respiratorik
• Berat  penyakit diseminasi
• Hepatosplenomegali, limfadenopati extrapulmonal, lesi kulit atau mulut, massa adrenal atau
intestinal
• Lab: trombositopeni, anemia, leukopeni, elevasi enzim hati, insufusiensi adrenal
• Inokulum kecil  self limited
• Serologi u/ diagnosis pulmo histoplasmosis
• Radiograf: lobar atau patchy infiltrat. Sering terlihat mediastinal adenopathy
Chronic Pulmonary Histoplasmosis:
immunocompromised host
• Pasien dg penyakit mendasari paru spt emfisema, PPOK  risiko
progressive chronic-cavitary pulmonary histoplasmosis
• Batuk, demam, keringat malam hari, BB turun
• Radiograf: fibrocavitary di lobus atas mirip reaktivasi TB
• Progresif & tdk self limiting
• Sputum fungal stain & kultur
• BAL u/ sitologi & kultur
• Ag Histoplasma deteksi pd BAL
Acute & Progressive disseminate histoplasmosis:
immunosuppressed host
• PDH (Progressive disseminated histoplasmosis) stlh paparan
inisial
• Imunokompeten  imunitas protektif 2 mgg pertama
terinfeksi
• Imunosupresi  tdk ada respon imun seluler
• Tipikal pasien: AIDS
• Test Ag pd urin & darah (+ 90% dg PDH)  initial test of choice
• DD PDH: histoplasmosis, pneymocystis pneumonia, invasive
fungal infection, mycobacterial, opportunistic pathogens
• BAL u/ sitologi & mikrobiologi
Kenneth S. Knox and Chadi A. Hage "Histoplasmosis", Proceedings of the American Thoracic Society, Vol. 7,
No. 3 (2010), pp. 169-172.
Culture of Histoplasma capsulatum. Histiocyte containing numerous yeast cells of
Histoplasma capsulatum. Tissue smear, Giemsa
http://www.mycology.adelaide.edu.au/M stain CDC
ycoses/Dimorphic_systemic/Histoplasmo
sis/
Thoracic histoplasmosis. A 36-year-
old man developed progressive
cough, fever, and dyspnea. Chest
radiograph shows multiple diffuse
tiny but discrete pulmonary
nodules. This miliary pattern may
be seen in miliary tuberculosis,
histoplasmosis, blastomycosis,
silicosis, berylliosis, miliary
sarcoidosis, and metastatic
malignancy.
Thoracic
histoplasmosis. CT
image at the lung
bases confirms
the diffuse nature
of the disease (a
miliary form of
disseminated
pulmonary
histoplasmosis
[DPH]).
a.Chest radiograph showing bilateral upper lobe shadowing that was diagnosed as chronic
cavitary pulmonary histoplasmosis. The right upper lobe shadowing is more pronounced than
the left, which is consistent also with chronic cavitary pulmonary aspergillosis or pumonary
tuberculosis or non-tuberculous Mycobacterial infection.
Daftar Pustaka
• http://www.ssajm.org/article.asp?issn=2384-5147;year=2014;volume
=1;issue=1;spage=1;epage=14;aulast=Adeiza
• https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5414a1.htm
• World Health Organization, Pedoman pelayanan kesehatan anak di
rumah sakit rujukan tingkat pertama di kabupaten/WHO ; alihbahasa,
Tim adaptasi indonesia – Jakarta: WHO Indonesia, 2008.
• http://emedicine.medscape.com/article/297887-treatment
• Buku Ajar Respirologi Anak: Edisi Pertama, Cetakan Kedua: 2010
• Nelson: Ilmu Kesehatan Anak, Edisi Keenam 2011; Saunders Elsevier

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• NOT DIAGNOSTIC FOR THE DISEASE.

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Medscape: Coal Worker Pneumoconiosis

Medscape: Coal Worker Pneumoconiosis

Medscape: Coal Worker Pneumoconiosis

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