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LAPORAN TUTORIAL

SKENARIO A BLOK 11 TAHUN 2017

Tutor: Phey Liana, SpPK

Nama : Adrina Esther Liaw


Nim : 04011381621232
Kelas : Gamma
Kelompok A 5
Dosen pembimbing : Dr PheyLiana, SpPK

FAKULTAS KEDOKTERAN
UNIVERSITAS SRIWIJAYA
TAHUN 2017

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DAFTAR ISI

LEARNING ISSUE…...............................................................................03

Tuberkulosis.......................................................................……….....03

Tuberkulosis ekstrapulmonal...............................................................07

Radang Granulomatosa……................................................................12

Nekrosis Kaseosa…………….............................................................16

Immunosenescence..............................................................................18

Antibiotics for Mycobacteria………………………………………...20

Scars.....................................................………………………...........20

Pemeriksaan laboratorium...................................................................23

Fixation………………………………………………………………29

Analisis masalah…………………………………………………….33

KONKLUSI………………………………………………………………34

DAFTAR PUSTAKA……………………………………………………34

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LEARNING ISSUE

Tuberkulosis

Definisi :

Tuberkulosis merupakan infeksi bakteri kronik yang disebabkan oleh Micobacterium


tuberculosis dan ditandai oleh pembentukan granuloma pada jaringan yang terinfeksi
dan oleh hipersensitivitas yang diperantai-sel (cell-mediated hypersensitivity).
Penyakit biasanya terletak di paru, tetapi dapat mengenai organ lain. Dengan tidak
adanya pengobatan yang efektif untuk penyakit yang aktif, biasanya terjadi perjalanan
penyakit yang kronik, dan berakhir dengan kematian.

Etiology :

Mycobacterium tuberculosis, basilus tuberkel, adalah satu di antara lebih dari 30


anggota genus Mycobacterium. Mycobacterium adalah bakteri berbentuk batang yang
tahan asam dibedakan dari lipid permukaannya(yaitu, bakteri tersebut memiliki
banyak kandungan lipid kompleks yang siap berikatan dengan pewarnaan
Ziehl-Neelsen, carbon fuchsin), yang membuatnya tahan-asam sehingga warnanya
tidak dapat dihilangkan dengan alkohol asam setelah diwarnai. Karena adanya lipid
ini, panas atau detergen biasanya diperlukan untuk pewarnaa primer. Pada patogenesis
M.tuberculosis, mengandung banyak zat imunoreaktif. Lipid permukaan pada
mikobakterium dan komponen peptidoglikan dinding sel yang larut-air merupakan
tambahan yang penting yang dapat menimbulkan efeknya melalui kerja primernya
pada makrofag penjamu. Mikobakterium mengandung suatu kesatuan antigen
polisakarida dan protein, sebagian mungkin spesifik spesies tetapi pada lainnya secara
nyata memiliki epitop yang luas di seluruh genus .

Penularan :

M.tuberculosis ditularkan dari orang ke orang melalui jalan pernafasan. Basilus


tuberkel di sekret pernafasan membentuk nuklei droplet cairan yang dikeluarkan
selama batuk, bersin, dan berbicara. Droplet keluar dalam jarak dekat dari mulut, dan
sesudah itu basilus yang ada tetap berada di udara untuk waktu yang lama. Infeksi pada
pejamu yang rentan terjadi bila terhirup sedikit basilus ini. Jumlah basilus yang
dikeluarkan oleh kebanyakan orang yang terinfeksi tidak banyak;khas diperlukan

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kontak rumah tangga selama beberapa bulan untuk penularannya. Mikobakerium
rentan terhadap penyinaran ultraviolet, dan penularan infeksi di rumah jarang terjadi
pada siang hari. Ventilasi yang memadai merupakan tindakan yang terpenting untuk
mengurangi tingkat infeksi linkungan.

Patogenesis :

Jalan masuk awal bagi basilus tuberkel ke dalam paru atau tempat lainnya pada
individu yang sebelumnya sehat menimbulan respons peradangan akut nonspesifik
yang jarang diperhatikan dan biasanya disertai dengan sedikit atau sama sekali tanpa
gejalan. Basilus kemudian ditelan oleh makrofag dan diangkut ke kelenjar limfe
regional. Bila penyebaran organisme tidak terjadi pada tingkat kelenjar limfe ragional,
lalu basilus tuberkel akan mencapai aliran darah dan terjadi diseminata menyembuh,
sebegaimana lesi paru primer, walaupun tetap ada fokus potensial untuk reaktivasi
selanjutnya.

Selama 2 hingga 8 minggu setelah infeksi primer, saat basilus terus berkembang biak
di linkungan intraselulernya, timbul hipersensitivitas pada pejamu yang terinfeksi.
Limfosit yang cakap secara imunologik memasuki daerah infeksi, di situ limfosit
menguraikan faktor kemotaktik, interleukin dan limfokin. Sebagai responsnya,
monosit masuk ke daerah tersebut dan mengalami perubahan bentuk menjadi
makrofag dan selanjutnya menjadi sel histiosit yang khusus, yang tersusun menjadi
granuloma. Mikrobakterium dapat bertahan dalam makrofag selama bertahun-tahun
walaupun terjadi peningkatan pembentukan lisozim dalam sel ini, namun muliplikasi
dan penyabaran selanjutnya biasanya terbatas. Kemudian terjadi penyembuhan,
seringkali dengan kalsifikasi granuloma yang lambat yang kadang meninggalkan lesi
sisa yang tampak pada foto rontgen paru. Kombinasi lesi paru perifer terkalsifikasi
dan kelenjar limfe hilus yang terkalsifikasi dienal sebagai kompleks Ghon.

Contoh foto rontgen tuberkulosis paru ;

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Namun pada kasus ini, rontgen pada paru normal. Jadi indikasi pasuen bukan
mengalami M.tuberkulosis paru.

Patogenesis tuberkulosis pada orang imunokompoten dan belum terpajan sebelumnya


berpusat ada pembentukan kekebalan yang dimediasi oleh sel dengan target tertentu
dan menimbulkan daya tahan pada organisme sehingga mengakibatkan terjadinya
hipersensitivitas jaringan terhadap antigen tuberkulosis. Gambaran patologis
tuberkulosis, seperti granuloma kaseosa dan kavitasi, adalah akibat destruksi jaringan
yang hipersensitif yang merupakan bagian dari respons imun pejamu. Karena sel
efektor untuk kedua proses tersebut sama, maka tampilan jaringan yang hipersensitif
juga memberi sinyal tambahan kekebalan terhadap organisme.

Begitu mycobacterium turunan virulen masuk ke dalam endosom makrofag (suatu


proses yang dimediasi oleh beberapa reseptor makrofag, termasuk reseptor manose
makrofag dan reseptor komplemen yang mengenali beberapa kompponen dinding sel
mycobacterium), organisme tersebut mampu menghambat respons mikrobisida
normal dengan cara mencegah fusi lisosom dengan vakuol fagositik. Pencegahan
formasi fagolisosom memungkinkan proliferasi mycobacterium tanpa terdeteksi.
Sehingga fase paling dini dari tuberkulosis primer (pada 3 minggu pertama) pada
pasien yang belum tersensitisasi yang ditandai oleh proliferasi basil di dalam
makrofag alveolus paru dan rongga udara, serta terjadi bakteremia yang selanjutnya
terjadi penyemaian pada berbagai tempat. Terlepas dari bakteremia, sebagian besar
pasien pada fase ini bersifat asimptomatik atau mengalami gejala mirip flu ringan.

Susunan gen pasien mungkin mempengaruhi perjalanan penyakit. Pada beberapa orang
dengan polimorfisme gen NRAMP1 (natural resistance-associated macrophage protein

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1), penyakit dapat berlanjut tanpa terbentuknya respons imun yang efektif. NRAMP1
adalah protein transpor ion transmembran yang ditemukan pada endosom dan lisosom
yang dipercaya berperan dalam membunuh mikroba.

Perkembangan imunitas yang dimediasi sel yang sekitar 3 minggu pasca pajanan.
Antigen mycobacterium yang telah diproses mencapai aliran kelenjar getah bening
dan dipresentasikan ke sel T CD4 + oleh dendritik dan makrofag. Di bawah pengaruh
IL-12 yang disekresikan makrofag, sel T CD4+ subset sel THl diproduksi dan mampu
mensekresi lFN-γ .

lFN-γ yang dilepaskan oleh sel T CD4+ subset THl penting dalam mengaktifkan
makrofag. Makrofag yang teraktif akan melepas berbagai mediator dan meningkatkan
regulasi gen dengan efek downstream yang penting, termasuk TNF; yang
bertanggungjawab untuk menarik monosit, yang kemudian menjadi aktif dan
berdiferensiasi menjadi “histiosit epiteloid” yang merupakan ciri dari reaksi
granulomatosa; ekspresi gen inducible nitric oxide synthase (iNOS), yang
mengakibatkan peningkatan kadar oksida nitrat pada tempat infeksi, dengan aktivitas
antibakteria yang baik; dan menghasilkan jenis oksigen reaktif, yang mempunyai sifat
antibakteri. Oksigen nitrat adalah zat oksidator kuat yang mendorong produksi
nitrogen reaktif dan radikal bebas lain yang mampu melakukan destruksi oksidatif
pada beberapa komponen mycobacterium, dari dinding sel hingga DNA-nya.

Defek pada setiap langkah respons sel THl (termasuk produksi IL-12, lFN-γ, TNF,
atau oksida nitrat) mengakibatkan tidak terbentuk granuloma yang baik, tidak adanya
daya tahan, dan penyakit akan berlanjutan. Orang dengan kelainan bawaan berupa
mutasi pada komponen manapun dari jalur THl, sangat rentan terhadap infeksi
mycobacterium.
2 jenis Tuberkulosis :

Tuberkulosis paru ; adalah tuberkulosis yang menyerang jaringan (parenkim) paru.


Tidak termasuk pleura (selaput paru) dan kelenjar pada hilus.

Tuberkulosis ekstra paru ; Adalah tuberkulosis yang menyerang organ tubuh lain
selain paru, misalnya pleura, selaput otak, selaput jantung (perikardium), kelenjar
limfe, tulang, persendian, kulit, usus, ginjal, saluran kencing, alat kelamin, dan
lain-lain.
Tuberkulosis Ekstrapulmonal

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Limfadenitis adalah bentuk tersering tuberkulosis di luar paru, biasanya terjadi pada
regio leher (Scrofula). Limfadenopati cenderung unifokal, dan pada sebagian besar
pasien tidak memiliki penyakit ekstranodal pada saat yang sama. Adenitus
Tuberkulosis Skrofula merupakan limfadenitis tuberkulosis kronok pada kelenjar
limfe leher. Beberapa kelenjar limfe leher mungkin terkena, tetapi tempat yang paling
sering adalah segitiga anterior leher tepat di bawah mandibula. Pembesaran kelenjar
tuberkulosis biasanya kenyal dan tidak nyeri tekan. Dengan perkembangan penyakit
pembesaran kelenjar ini menjadi lebih keras dan kasar. Bisa timbul fistula dengan
drainase kronik, namun jarangm dan perjalanan penyakit yang bentuk tuberkulosis ini
biasanya lambat.

Diagnosis biasanya ditegakkan dengan biopsi secara bedah. Spesimen biopsi kelenjar
limfe yang didapatkan untuk tujuan ini sebaiknyan selalu dilakukan pembiakan dan
pemeriksaan histologik.

Lymph node tuberculosis

Lymph node tuberculosis (LNTB) has been called the “King’s evil” referring to the
divine benediction which was presumed to be the treatment for it. It was also referred
to as “scrofula” meaning “glandular swelling” (Latin) and “full necked sow” (French).
Peripheral lymph nodes are most often affected and cervical involvement is the most.
In India and other developing countries LNTB continues to be the most common form
of EPTB and lymphadenitis due to non-tuberculous mycobacteria (NTM) is seldom
seen. On the other hand, NTM are the most common cause of lymphadenopathy in the
developed world. In patients with mycobacterial lymphadenitis in the USA, M.
tuberculosis has been the most common pathogen among adults whereas NTM were
the most common pathogens among children.

Tuberculous lymphadenitis usually presents as painless swelling of one or more lymph


nodes. Systemic symptoms are not common unless there is concomitant TB elsewhere.
The nodes usually involved are those of the posterior or anterior cervical chain or those
in the supraclavicular fossa. Rupture of the node can result in formation of a sinus tract,
which may be slow to heal. A sinus tract may also form after an excisional biopsy of the
tuberculous node. It is therefore best to begin the diagnostic evaluation with a fine
needle aspiration of the enlarged node. If the smear or culture confirms the presence of

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acid-fast bacilli (AFB), then an excisional biopsy is not needed and the node will heal
more rapidly.

Pathogenesis:

LNTB is considered to be the local manifestation of a systemic disease whereas NTM


lymphadenitis is thought to be a truly localised disease. M. tuberculosis gains entry
into the body via the respiratory tract and undergoes haematogenous and lymphatic
dissemination. Hilar and mediastinal lymph nodes are initially involved. This may
occur at the time of primary infection or may occur later in life due to reinfection or
reactivation of previous infection. Sometimes, tonsil is an important portal of entry.

The infection then spreads via the lymphatics to the draining cervical lymph nodes.
Initially, the nodes are discrete. Periadenitis results in matting and fixation of the
lymph nodes. The lymph nodes coalesce and break down due to formation of caseous
pus. This may perforate the deep fascia and present as a collar-stud abscess.
Overlying skin becomes indurated and breaks down, resulting in sinus formation
which may remain unhealed for years. Healing may occur from each of the stages
with calcification and scarring. In contrast NTM, gain entry into the lymph nodes
directly via oropharyngeal mucosa, salivary glands, tonsils, gingiva or conjunctiva
and lymph node involvement represents a localised disease.

Clinical presentation:

LNTB often affects children and young adults. Patients usually present with slowly
enlarging lymph nodes and may otherwise be asymptomatic. In HIV-negative
patients, isolated cervical lymphadenopathy is most often seen in about two-thirds of
the patients. Bem et al53 observed that among HIV-negative as well as HIV-positive
patients, cervical lymph nodes were most commonly affected followed by axillary and
inguinal lymph nodes. Multifocal involvement was observed in 39 and 90 percent
among HIV-negative and HIV-positive patients respectively.

Some patients with LNTB may manifest systemic symptoms and these include fever,
weight loss, fatigue and occasionally night sweats. Patients with mediastinal
lymphadenopathy (Fig.1a and 1b) may present with cough and dysphagia. With wider
availability of computerised tomographic (CT) scan, it is expected that more cases of
intrathoracic and intraabdominal lymphadenopathy and other associated lesions (Fig.1c

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and 1d) may be reported. Peripheral tuberculosis lymphadenopathy has been classified
into five stages. These include:

(i) stage 1, enlarged, firm mobile discrete nodes showing non-specific reactive
hyperplasia;

(ii) stage 2, large rubbery nodes fixed to surrounding tissue owing to periadenitis;

(iii) stage 3, central softening due to abscess formation;

(iv) stage 4, collar-stud abscess formation; and

(v) stage 5, sinus tract formation.

Physical findings depend upon the stage of the disease. The enlarged lymph nodes
may be of varying size, are usually firm and may be discrete or matted. If necrosis and
abscess formation have taken place they may become cystic in consistency. The
lymph nodes are usually not tender unless secondary bacterial infection has occurred.
Physical examination may be unremarkable but for palpable lymphadenopathy.

Occasionally, lymph node abscess may burst leading to a chronic non-healing sinus
and ulcer formation. Classically, tuberculosis sinuses have thin, bluish, undermined
edges with scanty watery discharge. Uncommon manifestations observed in patients
with mediastinal lymph node involvement include dysphagia, oesophagomediastinal
fistula, and tracheo-oesophageal fistula. Upper abdominal and mediastinal lymph
nodes may cause thoracic duct obstruction and chylothorax, chylous ascites or
chyluria. Rarely, biliary obstruction due to enlarged lymph nodes can result in
obstructive jaundice. Cardiac tamponade has also been reported due to mediastinal
lymph node tuberculosis. Nontuberculous mycobacterial lymphadenitis: Very little is
known regarding lymphadenitis due to NTM from India. In the western literature,
NTM lymphadenitis has often been described in children. Both sexes are equally
affected. Constitutional symptoms seldom develop and the disease generally remains
localised to the upper cervical area. If untreated, the nodes often progress to softening,
rupture, sinus formation, healing with fibrosis and calcification.

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https://radiopaedia.org/articles/tuberculous-cervical-lymphadenitis

Example of Lymph node tuberculosis

Diagnosis

Methodological issues

Definitive diagnosis of tuberculosis involves demonstration of M. tuberculosis by


microbiological, cytopathological or histopathological methods. Clinical presentation
of EPTB is atypical. Especially when the disease involves obscure occult sites, EPTB
may not even be considered in the initial list of differential diagnosis. Further,
invasive methods may have to be employed to secure tissue/body fluids for analysis.
Many times representative tissue/body fluid may not be accessible. Even when
adequate tissue is procured, the pathological findings may be suggestive of
“granulomatous infection” which encompasses a wide range of differential diagnoses
rather than “definitive tuberculosis”. Therefore, the clinicians more often rely upon
the clinical impression, radiological and endoscopic appearances and nonconventional
diagnsotic methods as evidence to diagnose EPTB.

A complete medical evaluation for TB includes a complete history and physical


examination, TST, chest radiograph, and any appropriate bacteriologic or histologic

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examinations. A positive skin test indicates previous or current infection, but as noted
above, a negative test does not exclude the diagnosis. The chest radiograph may
reveal typical upper lobe lesions; however, several studies have described atypical
lower lung field lesions in elderly patienta.

TB in an older tuberculin-negative individual may cause a nonspecific, nonresolving


pneumonitis in the lower or middle lobes, similar to primary infection in childhood
except with much less hilar and mediastinal adenopathy. Old healed TB usually
presents a different radiographic appearance from active TB. Dense pulmonary
nodules with or without visible calcification can be seen in the hilar area or upper
lobes. Alternatively, small nodules with or without fibrotic scars may be seen in the
upper lobes. Upper-lobe volume loss often accompanies these scars. Nodules and
fibrotic scars contain slowly multiplying tubercle bacilli with the potential for future
progression to active TB. Conversely, calcified nodular lesions (calcified granuloma)
pose a low risk for future progression to active TB.

Principles of diagnosis

When EPTB is suspected as a possible diagnosis, every attempt should be made to


procure tissue/relevant body fluid for diagnostic testing. Most accessible tissue should
be procured for histopathological, cytopathological and micrbiological diagnosis. For
example, when working up a patient with suspected lymph node tuberculosis, the
most easily accessible representative peripheral lymph node should be excised and
subjected to diagnostic testing. Similarly, cerebrospinal fluid (CSF) and ascitic fluid
examination provide most valuable diagnostic clue in patients with neurological and
peritoneal tuberculosis respectively.

With the advent of ultrasound scan and subsequently CT scan and the magnetic
resonance imaging (MRI) and widespread availability of upper gastrointestinal
endoscopy, colonoscopy, laparoscopy, cystoscopy and biopsy under visual guidance
and other invasive investigations such as hysterosalpingography and colposcopy,
tremendous progress has been achieved in precise anatomical localisation of the
lesions of EPTB antemortem. If no accessible tissue/fluid is available for analysis,

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radiologically guided fine needle aspiration and cytopathology (FNAC) or biopsy may
be required to secure tissue for diagnosis.

Tuberculin skin test: In countries like India where tuberculosis is higly endemic,
tuberculin skin test result alone is not sufficient evidence to diagnose EPTB in adult
patients.

Histopathological, cytopathological and microbiologial examination of tissue


specimens and body fluids

Fine needle aspiration cytopathology (FNAC), biopsy: In patients with lymph


node tuberculosis, FNAC, excision biopsy of the most accessible peripheral lymph
node confirms the diagnosis most of the times. CT scan is helpful in localising
intrathoracic and intraabdominal lymphadenopathy and radiologically guided FNAC
and biopsy. When available, video-assisted thoracoscopic surgery (VATS) can be a
valuable minimally invasive procedure to procure tissue for diagnostic testing in
patients with intrathoracic lymphadenopathy and pleural disease. Transporting the
collected lymph node specimen in Kirschner’s transport medium is helpful in
increasing the microbiological yield. In patients with DTB/MTB, various invasive
methods have been employed to ascertain the diagnosis their relative diagnostic yield
is shown in Table II.

Laparoscopy will facilitate visual inspection of the lesions and faciliatate


procurement of tissue for histopathological confirmation of the diagnosis. These
details are discussed in elsewhere in this issue

Radang Granulomatosa

Radang granulomatosa merupakan radang kronik dengan gambaran tertentu ditandai


oleh agregrasi makrofag yang teraktifkan dan dijumpai limfosit di antaranya.
Granuloma dapat terbentuk dari 3 keadaan :

 Adanya respons tetap sel T terhadap beberapa mikroba (misalnya Mycobacterium


tuberculosis), di mana sitokin yang berasal dari sel T berperan mengaktifkan
makrofag terus menerus. Tuberkulosis merupakan prototipe penyakit granuloma

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yang disebabkan oleh infeksi dan selalu harus disingkirkan sebagai penyebab
apabila penyebabnya sudah ditemukan.

 Granuloma juga dapat terjadi pada radang akibat gangguan kekebalan, misalnya
penyakit Crohn, yang merupakan suatu jenis penyakit radang usus.

 Juga dijumpai pada penyakit dengan etiologi yang tidak diketahui, yang disebut
sebagai sarkoidosis, yang terjadi karena respons terhadap benda asing inert (misal
sutura atau serpihan kayu), dan akan membentuk granuloma benda asing.

Pembentukan granuloma akan membentuk benteng mengelilingi agen perusak


sehingga menjadi mekanisme pertahanan yang berguna. Namun pembentukan
granuloma tidak selalu berhasil memusnahkan agen penyebab, yang biasanya resisten
terhadap kehancuran atau kematian, dan radang granulomatosa yang disertai fibrosism
dapat menjadi penyabab utama disfungsi organ, seperti yang terjadi pada tuberkulosa.

Morfologi :

Pada sediaan H&E normal, beberapa dari makrofag yang diaktifkan mempunyai
sitoplasma merah muda, granuler dengan batas sel tidak jelas, dan disebut sel
epiteloid karena mirip sel epitel. Secara khas kelompok makrofag epiteloid akan
dikelilingi oleh limfosit. Granuloma yang lebih tua mempunyai lingkaran batas
fibroblas dan jaringan ikat tipis. Sering dijumpai sel raksasa berintii banyak di
granuloma. Sel tersebut mempunyai sitoplasme lebar dan banyak ini. Terjadi karena
fusi beberapa makrofag yang teraktifkan. Pada beberapa granuloma yang
berhubungan dengan organisme infektif (contoh klasik ialah baksil tuberkulosa) suatu
kombinasi dari hipoksia dan jejas radikal bebas akan menyebabkan zona sentral
nekrosis. Pada pemeriksaan makroskopik, dijumpai gambaran granuler mirip keju
hingga disebut nekrosis perkijuan. Pada pemeriksaan mikroskopis, materi nekrotik
tampak sebagai benda amorf eosinofilik, tanpa bentuk, tanpa struktur, sisa bekas
granuler, dan detail sel seluruhnya menghilang.

Reaksi Jaringan pada penyakit Tuberkulosa (Mycobacterium tuberculosis)

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Gambaran; granuloma yang khas akibat infeksi Mycobacterium tuberculosis menunjukkan
nekrosis perkijuan daerah sentral, makrofag epiteloid yang teraktifkanm sel datia, dan
akumulasi perifer limfosit.

Gambaran; Granuloma formation in fine needle aspirate and granuloma loose


aggregrate of epitheloid histiocytes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891789/

Granuloma kaseosa (tuberkel); fokus dari makrofag yang teraktifkan (sel epiteloid),
dibatasi fibroblas, limfosit, histiosit, kadang-kadang sel datia Langhans; nekrosis
sentral dengan sisa-sisa granula amorfik; basil tahan asam.

The well-defined role of FNAC in the investigation of lymphadenopathy has


previously been studied. In the context of granulomatous disorders, the possible
aetiology is wide and the use of FNAC with other ancillary tests (microbiological,
immunohistochemical, radiological, biochemical and special staining techniques) is
useful for obtaining a definitive diagnosis. The algorithm shows a useful classification
of the aetiology of granulomatous lymphadenopathy.

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FNAC as a first line screening method has been recommended in suspected
malignancy. The presence of granulomata in an aspirate may indicate the presence of
a neoplastic process. The background cell population needs to be scrutinised if a
malignant lymphoma is suspected. Granulomata may be encountered in both

Hodgkin's disease and non-Hodgkin's lymphoma, particularly T-cell


lymphoma. Hodgkin's lymphoma is characterised by the classic Reed-Sternberg cells
in a background of sarcoid-like granulomata, reactive lymphoid cells and occasional
eosinophils.Occasionally, lymph nodes containing metastatic carcinoma may also
show features of granulomata. Previous reports have been described in metastatic
nasopharyngeal carcinoma, seminoma and malignant melanoma.Histologically,
non-caseating granulomata composed of epithelioid histiocytes with multinucleated
giant cells are seen, but these can be indistinguishable from granulomatous
inflammation from other causes. A series by Khurana et al highlighted the difficulties
encountered in making a definitive diagnosis of malignant neoplasm that mimics, or
occurs, in association with granulomata.

Granulomatous inflammation found in lymph nodes draining carcinomas is a


recognised phenomenon. Such phenomenon are reported in pulmonary small cell
carcinoma, malignant melanoma, papillary thyroid carcinoma,14 gastric carcinoma,
and rhabdomyosarcoma.This has been suggested to be either a response to necrotic
material or an immunological T-cell mediated hypersensitivity reaction to cell surface
antigens.However, the precise mechanism is largely speculative as the exact tumour
or host factors that enable such a response remain unknown. We agree with Lui et
al in their pragmatic approach of diligent examination of FNAC slides combined with
ancillary clinical, serological and imaging investigations in the drainage areas to
identify any occult malignancy.

A suspicious clinical history of TB (pyrexia, night sweats, recent travel to endemic


areas, no previous BCG vaccination) coupled with positive aspirate, blood, sputum or
urine tests for AFB and good response to anti-tuberculous therapy supports the
diagnosis of TB. One disadvantage is the inherent delay in culture result, but it is
anticipated that as polymerase chain reaction and other amplification techniques
become more common, detection time for the organism will shorten, improving the
value of FNA in clinical practice.The typical FNAC features of toxoplasmosis include

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the presence of follicular hyperplasia with secondary germinal centres rich in
macrophages, presence of groups of epithelioid cells and presence of monocytoid
histiocytes have been previously described. A combination of FNA features with
positive serological testing and history of animal contact, as in the two patients here,
gives the diagnosis of toxoplasmosis and thus avoids unnecessary surgical excision.

Nekrosis Kaseosa

Sering dijumpai pada infeksi tuberkulosa. Kaseosa berarti “mirip keju” menyatakan
gambaran putih kuning-kekuningan pada daerah nekrosis yang rapuh. Pada gambaran
mikroskopis fokus nekrotik menunjukkan kumpulan sel yang berfragmentasi dan sel
yang hancur dengan gambaran merah muda granuler pada pewarnaan jaringan H&E.
Berbeda dengan nekrosis koagulatif, asritektur jaringan dirusak secara menyeluruh
dan gambaran sel tidak dapat dikenal lagi. Daerah nekrosis kaseosa biasanya
dikelilingi oleh jaringan radang.

A granuloma can be defined as a focal, compact collection of inflammatory cells in


which mononuclear cells predominate. Granulomas usually form as a result of the
persistence of a nondegradable product or as the result of hypersensitivity responses.
An overlap ofthe two mechanisms occurs in most infectious diseases since
microorganisms can serve both as foreign bodies and as antigens for immunologic
responses. Normally granulomas are the result of protective mechanisms and form
when acute inflammatory processes cannot destroy invading agents.

16
A granuloma is a focus of chronic inflammation consisting of a microscopic
aggregation of macrophages that are surrounded by a collar of lymphocytes and
plasma cells.A granuloma is a focal compact collection of inflammatory cells,
mononuclear cells predominating, usually as a result of the persistence of a
nondegradable product and of active cell-mediated hypersensitivity. There is a
complex interplay between invading organisms or prolonged antigenemia,
macrophage activity, a Th1 cell response, B cell overactivity, and a vast array of
biological mediators.

In hematoxylin and eosin (H and E) sections, epitheloid cells have a pale pink
cytoplasm with indistinct cell boundaries and appear to be merging with one another.
These giant cells have a large mass of cytoplasm with 20 or more nuclei arranged
haphazardly or in a horseshoe pattern peripherally-the Langhans type. These giant
cells can be formed by cell fusion and nuclear division without cytoplasmic separation.
In Langhans giant cells, the nuclei are either arranged in a horseshoe pattern at the
periphery or clustered at the two poles of the giant cell.

In granulomatous inflammation, macrophages engulf the foreign body/material and


present some of it to the T-lymphocytes, thus activating them. These cells produce
cytokines like interleukin (IL)-2 in response. IL-2 activates other T cells, and
interferon (IFN) - gamma activates other macrophages, resulting in a continued
response. Macrophages are also converted into epitheloid and multinucleated giant
cells.

During the aging process there are alterations in the immune system that affect T cell
functions such as decreased cytokine production (IL-2 and IFNγ), cytotoxic activity,
and T cell proliferation. Animal models, more specifically the mouse model, have
clearly documented the relationship between age-related decreased T cell responses
and the increased risk of infection by M.tb, as well as the negative impact of
dysregulated immune responses during M.tb chronic infection (Turner et al.,
2001a,b; Turner and Orme, 2002). Other factors such as other diseases (e.g., diabetes
mellitus), poor nutrition, and immunosuppression also impact the protective
granulomatous response against M.tb infection during aging .

17
Immunosenescence

Immunosenescence refers to the aging process in humans. This process of course


occurs continuously in time for the lifespan of a host. Consequences of
immunosenescence are the accumulation of changes in various components of the
body, specifically including the immune system, often resulting in a reduced
protection against exogenous pathogens. Consequently, an increase in morbidity and
mortality is found in elderly individuals for both acute and persistent infectious
diseases.

The aging immune system is characterized by two key types of changes : primary
alterations, which appear as a direct effect of age on normal cell or tissue activity; and
secondary alterations, which derive from attempts by the organism to compensate for
these primary changes. For example, at the cell level, primary alterations manifest as
reduced and/or slowed functionality (e.g., antigen processing and presentation, cell
proliferation and activation and signaling pathways), due to the accumulation of
unrepaired mutations after DNA damage or oxidative stress. At the organ level, the
thymus undergoes involution with age, which results in reduced production of naive T
cells and consequently an unbalance in the relative proportions of lymphocyte
populations. A lack of naive T cells reduces the capability of the immune system to
amount an adaptive response to new infections. The immune system reacts to thymic
involution by a compensatory homeostatic expansion of circulating lymphocytes
(secondary response), in order to maintain constant systemic levels of naive T cells.
However, in the long run homeostatic proliferation produces dysfunction due to cell
aging. These complex mechanisms are reviewed in .

Immunosenescence also has a detrimental effect on the memory response: while recall
responses to infections acquired at young ages are not affected by the age of the host,
age does impair generation of a new memory response in the elderly. In particular,
memory T cells generated by an aging host function poorly in terms of cytokine
production and proliferating capacity .

Over the lifetime of an individual other events related to Mtb infection occur that are
important also from an epidemiological perspective. Endogenous reactivation of a
LTBI(persistence of the pathogen that appears to be a balance between host and
pathogen occurring within and constrained by structures that develop in lungs called

18
granulomas (latent TB infection, or LTBI), may occur with ageing or other
immunodeficiencies: in this case, infection within a granuloma is no longer
controlled, bacterial growth accelerates, and active disease occurs. Endogenous
reactivation may occur even several decades after primary infection and is by far the
most common form of TB in high-resource, low-incidence countrie. Immunological
studies and data suggest that impaired or delayed availability of TB-specific CD4+
cells at the site of infection is an important determinant of the increased susceptibility
to primary TB disease in elderly.

With age, the T-cell mediated immune response wanes allowing for latent TB to
become active.

Age related changes in organ systems

19
Antibiotics for Mycobacteria

Mycobacteria are susceptible to some antibiotics. For example, Mycobacterium


tuberculosis is usually treated with drugs like rifampin, ethambutol and isoniazid.
Mycobacterium leprae is treated with dapsone. Newer antibiotics, known as macrolide
antibiotics, are more effective against intracellular mycobacteria than standard
anti-tuberculosis drugs. One of these macrolide antibiotics, clarithromycin, has been
shown to be effective against Mycobacterium avium complex infection (known as
MAC) in AIDS patients.

Scars

Keloids and hypertrophic scars are skin abnormalities that are unique to humans and
are characterized by excessive deposition of collagen in the dermis and subcutaneous
tissues secondary to traumatic or surgical injuries. Contrary to the asymptomatic
fine-line scar characteristics of normal wound repair, the exuberant scarring of keloid
and hypertrophic scars results typically in disfigurement, contractures, pruritis and
pain. Hypertrophic scars, on the other hand, are raised scars that remain within the
boundaries of the wound and frequently regress spontaneously. Histologically,
collagen bundles in the dermis of normal skin, or normal scar tissues, appear relaxed
and are arranged in a random array. Keloids and hypertrophic scars have collagen
bundles that appear stretched and aligned in the same plane as the epidermis. These
collagen bundles are thicker and more abundant in keloid scars and form acellular
node-like structures in the deep dermal portion of the keloid lesion. The center of
keloid lesions contain relatively few cells compared with hypertrophic scars.
Apoptosis may be involved in the clearance of certain cell populations in keloid
lesions1 . In contrast, islands composed of aggregates of fibroblasts, small vessels and
collagen fibers are seen throughout the dermis of hypertrophic scars.

20
http://www.siteprotocolo.com.br/upload/Quelóide%20e%20formação%20de%20cicatriz%20
hipertrófica.pdf

Histological comparison between normal scar, hipertrophic scar and keloid tissues, and
example of scars.

Cellular and molecular mechanisms of normal injury repair

Tissue repair is accomplished through concerted events involving various cell types,
extracellular matrix (ECM) components, cytokines and other soluble mediators. Skin
repair begins with the formation of a fibrin-rich blood clot, which provides a
provisional matrix for reparative events to follow. This process ends with newly
synthesized scar tissue composed mainly of collagen, which restores the functional
integrity of the skin. Several vital sequential stages have been identified in the repair
process, namely inflammation, fibroplasia, formation of granulation tissue and scar
maturation. The dynamic interactions and feedback control mechanisms among
participating components in these different stages govern the direction of the repair.
Therefore, an aberration in the process can result in poorly healing chronic wounds at
one extreme and excessively healing hypertrophic scars and keloids at the other.

21
There are many compelling in vitro examples of the control of cellular gene
expression through the adhesive interaction of connective tissue cells with their
surrounding ECM. Many of these interactions are mediated through cell adhesion
receptors called integrins. Frequently, their expression is regulated by cytokines and
growth factors, such as transforming growth factor b(TGF-b), released from adjacent
cells or the surrounding ECM through limited proteolysis. Indeed, proteolytic
degradation of ECM is an essential feature of tissue repair and remodeling processes.

The serine proteinases, including plasminogen activator (PA)–plasmin and the matrix
metalloproteinases (MMPs), are the two major groups of ECM degrading enzymes
that interact and form a lytic cascade for ECM remodeling. The major function of PA
is to control the activation of plasminogen into plasmin. Plasmin is not only the
primary effective enzyme in fibrinolysis, but it also participates in the breakdown of
other ECM proteins, and activates procollagenase into collagenase (a member of the
MMP family). Thus, the initiation of the proteinase cascade by PA leads to a notable
amplification of proteolytic activity. The complexity of this regulatory system is
increased by the fact that plasmin can release active TGF-bfrom its latency-associated
protein.

Many other growth factors such as epidermal growth factor (EGF), fibroblast growth
factor (FGF) and platelet-derived growth factor (PDGF) also have substantial
influence on the growth and differentiation of keratinocytes, fibroblasts and
endothelial cells during wound repair .

22
Pemeriksaan Laboratorium

Cara mengambil sampel darah melalui vena

Hemoglobin (Hb)

Nilai normal :

Pria : 13 - 18 g/dL SI unit : 8,1 - 11,2 mmol/L

Wanita: 12 - 16 g/dL SI unit : 7,4 – 9,9 mmol/L

Deskripsi:

Hemoglobin adalah komponen yang berfungsi sebagai alat transportasi oksigen (O2)
dan karbon dioksida (CO2). Hb tersusun dari globin (empat rantai protein yang terdiri
dari dua unit alfa dan dua unit beta) dan heme (mengandung atom besi dan porphyrin:
suatu pigmen merah). Pigmen besi hemoglobin bergabung dengan oksigen.
Hemoglobin yang mengangkut oksigen darah (dalam arteri) berwarna merah terang
sedangkan hemoglobin yang kehilangan oksigen (dalam vena) berwarna merah tua.
Satu gram hemoglobin mengangkut 1,34 mL oksigen. Kapasitas angkut ini
berhubungan dengan kadar Hb bukan jumlah sel darah merah.

23
Penurunan protein Hb normal tipe A1, A2, F (fetal) dan S berhubungan dengan
anemia sel sabit. Hb juga berfungsi sebagai dapar melalui perpindahan klorida
kedalam dan keluar sel darah merah berdasarkan kadar O2 dalam plasma (untuk tiap
klorida yang masuk kedalam sel darah merah, dikeluarkan satu anion HCO3).

Penetapan anemia didasarkan pada nilai hemoglobin yang berbeda secara individual
karena berbagai adaptasi tubuh (misalnya ketinggian, penyakit paru-paru, olahraga).
Secara umum, jumlah hemoglobin kurang dari 12 gm/dL menunjukkan anemia. Pada
penentuan status anemia, jumlah total hemoglobin lebih penting daripada jumlah
eritrosit.

Implikasi klinik :

• Penurunan nilai Hb dapat terjadi pada anemia (terutama anemia karena kekurangan
zat besi), sirosis, hipertiroidisme, perdarahan, peningkatan asupan cairan dan
kehamilan.

• Peningkatan nilai Hb dapat terjadi pada hemokonsentrasi (polisitemia, luka bakar),


penyakit paru-paru kronik, gagal jantung kongestif dan pada orang yang hidup di
daerah dataran tinggi.

• Konsentrasi Hb berfl uktuasi pada pasien yang mengalami perdarahan dan luka
bakar.

• Konsentrasi Hb dapat digunakan untuk menilai tingkat keparahan anemia, respons


terhadap terapi anemia, atau perkembangan penyakit yang berhubungan dengan
anemia.

Cara pemeriksaan Hb:

1. Menurut Kadar Hemoglobin (Hb)

Prinsip : Hemoglobin darah + larutan HCl 0,1N berubah menjadi hematin asam, lalu
kadarnya diukur dengan membandingkan warnanya dengan warna standar secara
visual.

24
2. Menurut cara Sianmethemoglobin (HiCN)

Prinsip : Hb darah + larutan K3Fe(CN)6 = methemoglobin

Methemoglobin + larutan KCN = hemoglobin sianida (HiCN)

Cara ini hanya memerlukan waktu 3 menit, sangat muda dilakukan, mempunyai
standar yang stabil, dan dapat mengukur semua jenis Hb, kecuali sulf Hb.

Leukosit (sel darah putih)

Nilai normal : 5.000 – 10.000/mm3

Deskripsi:

Fungsi utama leukosit adalah melawan infeksi, melindungi tubuh dengan memfagosit
organisme asing dan memproduksi atau mengangkut/ mendistribusikan antibodi. Ada
dua tipe utama sel darah putih:

• Granulosit: neutrofi, eosinofi dan basofi

25
• Agranulosit: limfosit dan monosit Leukosit terbentuk di sumsum tulang
(myelogenous), disimpan dalam jaringan limfatikus (limfa, timus, dan tonsil) dan
diangkut oleh darah ke organ dan jaringan. Umur leukosit adalah 13-20 hari.

Vitamin, asam folat dan asam amino dibutuhkan dalam pembentukan leukosit. Sistem
endokrin mengatur produksi, penyimpanan dan pelepasan leukosit. Perkembangan
granulosit dimulai dengan myeloblast (sel yang belum dewasa di sumsum tulang),
kemudian berkembang menjadi promyelosit, myelosit (ditemukan di sumsum tulang),
metamyelosit dan bands (neutrofi pada tahap awal kedewasaan), dan akhirnya,
neutrofi . Perkembangan limfosit dimulai dengan limfoblast (belum dewasa)
kemudian berkembang menjadi prolimfoblast dan akhirnya menjadi limfosit (sel
dewasa). Perkembangan monosit dimulai dengan monoblast (belum dewasa)
kemudian tumbuh menjadi promonosit dan selanjutnya menjadi monosit (sel dewasa).

Implikasi klinik: :

• Nilai krisis leukositosis: 30.000/mm3. Lekositosis hingga 50.000/mm3,


mengindikasikan gangguan di luar sumsum tulang (bone marrow). Nilai leukosit yang
sangat tinggi (di atas 20.000/mm3) dapat disebabkan oleh leukemia. Penderita kanker
post-operasi (setelah menjalani operasi) menunjukkan pula peningkatan leukosit
walaupun tidak dapat dikatakan infeksi.

• Biasanya terjadi akibat peningkatan 1 tipe saja (neutrofi ). Bila tidak ditemukan
anemia dapat digunakan untuk membedakan antara infeksi dengan leukemia

• Waspada terhadap kemungkinan leukositosis akibat pemberian obat.

• Perdarahan, trauma, obat (mis: merkuri, epinefrin, kortikosteroid), nekrosis, toksin,


leukemia dan keganasan adalah penyebab lain leukositosis.

• Makanan, olahraga, emosi, menstruasi, stres, mandi air dingin dapat meningkatkan
jumlah sel darah putih .

Cara hitung leukosit

Bahan : darah kapiler/darah dengan antikoagulan EDTA, Pipet pengencer(pipet


leukosit), larutan pengencer (Larutan Turk)

26
Sel ang dihitung : semua sel dalam 4 bidang besar (cukup pembesaran 40x), sel yang
mennyinggung garis batas kiri dan atas.

LED (Laju Endapan Darah):

Nilai normal:

Pria <15mm/ 1 jam

Wanita <20mm/ 1 jam

Deskripsi:

LED atau juga biasa disebut Erithrocyte Sedimentation Rate (ESR) adalah ukuran
kecepatan endap eritrosit, menggambarkan komposisi plasma serta perbandingan
eritrosit dan plasma. LED dipengaruhi oleh berat sel darah dan luas permukaan sel
serta gravitasi bumi.

Implikasi klinik :

• nilai meningkat terjadi pada: kondisi infeksi akut dan kronis, misalnya tuberkulosis,
arthritis reumatoid, infark miokard akut, kanker, penyakit Hodkin’s, gout, Systemic
Lupus Erythematosus (SLE), penyakit tiroid, luka bakar, kehamilan trimester II dan
III. Peningkatan nilai LED > 50mm/ jam harus diinvestigasi lebih lanjut dengan
melakukan pemeriksaan terkait infeksi akut maupun kronis, yaitu: kadar protein
dalam serum dan protein, immunoglobulin, Anti Nuclear Antibody (ANA) Tes,
reumatoid factor. Sedangkan peningkatan nilai LED >100mm/jam selalu dihubungkan
dengan kondisi serius, misalnya: infeksi, malignansi, paraproteinemia, primary

27
macroglobulinaemia, hiperfi brinogenaemia, necrotizing vaskulitis, polymyalgia
rheumatic.

•nilai menurun terjadi pada: polisitemia, gagal jantung kongesti, anemia sel sabit,
Hipofi brinogenemia, serum protein rendah Interaksi obat dengan hasil laboratorium:
etambutol, kuinin, aspirin, dan kortison.

Cara pemeriksaan LED:

Metode yang dipakai dalam pengukuran LED ada dua cara yaitu secara makro dan
mikro. Secara makro yaitu metode crista (Hellige volmer) dan metode landau. Kedua
metode ini sangat kurang popular di Indonesia.

Metode westergren didapat nilai yang lebih tinggi, hal itu disebabkan karena pipet
westergren yang hampir dua kali panjang pipet wintrobe. Pembacaan metode
westergren dilihat dengan panjangnya kolom plasma di atas tiang eritrosit dengan
memperhatikan beberapa hal yaitu warna plasma di atas eritrosit, kejernihan plasma
misalnya menjadi keruh oleh karena hiperlipemia, lapisan leukosit pada kolom
eritrosit akan meningkat oleh leukositosa dan leukimia, tajamnya batas antara darah
dan plasma yang menjadi tidak tajam oleh anisositosa. Penting sekali untuk menaruh
pipet atau tabung LED dalam sikap tegak lurus, selisih kecil dari garis vertikal sudah
dapat berpengaruh banyak terhadap hasil LED.

Uji kultur Tuberkulosis

Deskripsi :

Untuk menentukan kepastian seseorang menderita tuberkulosis dapat dilakukan baik


dengan kultur, menggunakan metode terbaru seperti molecular line probe, maupun
biakan sputum bakteri tahan asam (pewarnaan Ziehl Neelsen).

Implikasi klinik :

• Penentuan TB dapat dilakukan dengan tes pewarnaan kultur dan tes kultur
mikobakteri, jika dibandingkan keduanya, yang pertama simpel, cepat dan tidak
mahal tetapi sensitifi tasnya lebih rendah. Sensitifi tas bakteri tahan asam lebih rendah
pada TB ekstrapulmonal, pasien yang menderita HIV dan pasien yang menderita

28
mikobakteria non tuberkulosis. Bakteri tahan asam tidak dapat membedakan
mikobakteria tuberkulosis dan mikobakteria non tuberkulosis.

• Kultur mikobakteri: berguna untuk mengidentifi kasi kebenaran diagnosis TB secara


defi nitif, tetapi biayanya lebih mahal, keuntungan lainnya dapat digunakan untuk
menetapkan kepekaan bakteri terhadap obat anti TB.

• Apusan sputum; diagnosis dinyatakan negatif bila paling ketiga apusan sputum
negatif (termasuk paling tidak satu spesimen sputum pagi). Pasien yang dicurigai
dianjurkan dilakukan pengambilan 3 kali sputum, yaitu sewaktu pagi.

• Semua pasien harus dimonitor respon terapinya terutama pasien dengan tuberkulosis
pulmoner, melalui pemeriksaan spesimen sputum paling tidak pada dua bulan
pertama, lima bulan dan pada akhir terapi. Pasien dengan sputum positif pada bulan
kelima terapi dianggap gagal terapi dan terapi harus dimodifi kasi. Respon terapi
pasien dengan tuberkulosis ektrapulmoner dan pasien anak paling baik dinilai secara
klinis.

Tissue handings for lymph nodes :

Submit all lymph nodes in a fresh and sterile condition. This is in order to make touch
imprint preparations, freeze for potential immunohistochemical procedures, obtain
fresh nodal tissue for flow cytometry, or perform tissue cultures. This “triaging” must
be performed immediately. Please deliver specimens to Histopathology ASAP. The
requisition should be marked with a priority of “fresh”.

Fixation

Fixation of Tissue involves submerging the sampled tissue in chemical substances


(i.e. fixatives) in order to prevent tissue digestion by enzymes or bacteria and to
preserve as much as possible of its morphologic and chemical characteristics.
Fixatives promote cross-links between proteins and form a gel that maintains the in
vivo relations of tissue components to each other. There are a number of reagents that
can be used for fixation, each of which has differing penetration rates. Formaldehyde
is the most commonly used agent for histopathology and when dissolved in water, it is
referred to as “formalin.” One part formalin is typically diluted with nine parts water
to produce a 10 % formalin solution, a concentration that is optimal for tissue fixation.

29
This solution penetrates tissue at about 1 mm an hour, therefore, biopsies are
generally submitted for processing the same day as received, while larger specimens
(e.g. a mastectomy) are not processed the same day as received as they require a
longer fixation period.

Definition:

It is a complex series of chemical events which brings about changes in the various
chemical constituents of cell like hardening, however the cell morphology and
structural detail is preserved. Unless a tissue is fixed soon after the removal from the
body it will undergo degenerative changes due to autolysis and putrefaction so that
the morphology of the individual cell will be lost. Mode of teaching - Overhead
projector and practical demonstration.

Principle of fixation

The fixative brings about crosslinking of proteins which produces denaturation or


coagulation of proteins so that the semifluid state is converted into semisolid state; so
that it maintains everything in vivo in relation to each other. Thus semisolid state
facilitate easy manipulation of tissue.

Aims and Effects of fixation

If a fresh tissue in kept as such at room, temperature it will become liquefied with a
foul odour mainly due to action of bacteria i.e. putrefaction and autolysis so the first
and fore most aim of fixation is

1. To preserve the tissue in as lf like manner as possible.

2. To prevent postmortem changes like autolysis and putrefaction. Autolysis is the


lysis or dissolution of cells by enzymatic action probably as a result of rupture of
lysosomes. Putrefaction The breakdown of tissue by bacterial action often
withformation of gas.

3. Preservation of chemical compounds and microanatomic constituents so that


further histochemistry is possible.

4. Hardening : the hardening effect of fixatives allows easy manipulation of soft tissue
like brain, intestines etc.

30
5. Solidification: Converts the normal semifluid consistency of cells (gel) to an
irreversible semisolid consistency (solid).

6. Optical differentiation - it alters to varying degrees the refractive indices of the


various components of cells and tissues so that unstained components are more easily
visualized than when unfixed.

7. Effects of staining - certain fixatives like formaldehyde intensifies the staining


character of tissue especially with haematoxylin.

Preparation of tissue for histology

Pemeriksaan Differential Count

Pengertian

Hitung jenis leukosit adalah penghitungan jenis leukosit yang ada dalam darah
berdasarkan proporsi (%) tiap jenis leukosit dari seluruh jumlah leukosit. Hasil
pemeriksaan ini dapat menggambarkan secara spesifik kejadian dan proses penyakit
dalam tubuh, terutama penyakit infeksi. Tipe leukosit yang dihitung ada 5 yaitu
neutrofil, eosinofil, basofil, monosit, dan limfosit. Salah satu jenis leukosit yang
cukup besar, yaitu 2x besarnya eritrosit (sel darah merah), dan mampu bergerak aktif
dalam pembuluh darah maupun di luar pembuluh darah. Neutrofil paling cepat
bereaksi terhadap radang dan luka dibanding leukosit yang lain dan merupakan
pertahanan selama fase infeksi akut.

31
Pengukuran

Differensial counting merupakan hitung jenis lekosit yang biasanya dilakukan


bersama-sama dengan pemeriksaan apus darah tepi. Pada hitung jenis lekosit yang
dihitung adalah jenis-jenis lekosit normal sekaligus memperhatikan kemungkinan
adanya sel lekosit abnormal dalam darah tepi atau perifer. Sel lekosit normal
merupakan sel lekosit yang sudah matur atau dewasa yang beredar pada darah perifer
dan terdiri dari basofil, eosinofil, netrofil batang, netrofil segmen, limposit dan
monosit. Sel lekosit abnormal merupakan sel lekosit yang masih muda secara normal
ada dalam sumsum tulang dan dalam beberapa kasus dijumpai pada darah perifer.
Untuk dapat melakukan hitung jenis lekosit diperlukan preparat apus darah tepi yang
baik. Kriteria preparat darah hapus yang baik adalah lebar dan panjangnya tidak
memenuhi seluruh kaca benda, secara gradual penebalannya berangsur-angsur
menipis dari kepala ke ekor, tidak berlubang, tidak terputus-putus, tidak terlalu tebal
dan mempunyai pengecatan yang baik. Morfologi preparat darah hapus dibagi tiga
bagian yaitu kepala, badan dan ekor. Pada bagian badan dibagi dalam enam zona
(daerah baca) yang dimulai dari zona 1 yang berada dekat kepala sampai zona VI
yang dekat dengan ekor.

Hitung jenis lekosit dimulai dari zona VI yang biasanya terdapat jenis lekosit yang
berukuran besar menuju ke zona IV yang terdapat konsentrasi seri limfosit tua
(ukuran lebih kecil). Hitung jenis lekosit dilakukan sampai jumlah lekosit terpenuhi
100 sel dengan catatan tidak ada indikasi abnormal. Akan tetapi seringkali
penghitungan sudah mencapai 100 sel sebelum sampai ke zona IV. Untuk mencapai
zona IV maka penghitungan diteruskan sehingga jumlah sel melebihi angka 100
selanjutnya diprosentase.

32
Analisis Masalah

1. Hasil pemeriksaan Lokalis Leher


a. Bagaimana interpretasi dari pemeriksaan lokalis leher?

2. Pemeriksaan Laboratorium :
Hb 13 g/dl. Leukosit : 8000 /mm3 . LED : 25 mm/jam. DC :
0/1/2/51/40/6
a. Bagaimana Nilai normal dari hasil pemeriksaan laboratorium?
(terutama untuk laki2 usia 69 tahun)

Hemoglobin (Hb)

Nilai normal : Pria : 13 - 18 g/dL SI unit : 8,1 - 11,2 mmol/L

Leukosit (sel darah putih)

Nilai normal : 3200 – 10.000/mm3 SI : 3,2 – 10,0 x 109/L

LED (Laju Endapan Darah):

Nilai normal: Pria <15mm/ 1 jam

b. Bagaimana interpretasi dari hasil pemeriksaan laboratorium?

Nilai Hb dan Leukosit pada pasien adalah normal, namun LED pasien tinggi akibat
infeksi dari bakteri M.tuberculosis.

33
Penularan melalui droplet cairan di udara
Kerangka
Konsep
Basilus di udara diinhalasi/dihirup, lalu
masuk ke dalam traktus respiratorius

Mycobakterium melalui jalan pernafasan


di faring

Immunosenescence (aging immune


system)

Tuberculosis Tuberculosis Paru, (tuberculosis yang


Extrapulmonal,(Tuberkulosis yang menyerang paru)
menyerang organ lain selain paru)

Proses heaomatogenous dan lymphatic M.tuberculosis tidak berdifferensiasi di


dissemination paru

M.tuberculosis masuk ke Lymphatic Tidak mempunyai gejala demam, penurunan


system nafsu makan dan berat badan, keringat malam
hari, perubahan suara, dan batuk

Infektion spreads to the draining cervical


lymph nodes

Matting and fixation of lymph nodes


causes periadenitis to occur

Lymph nodes coalesce and break down due to


formation of caseous pus

Perforate deep fascia and present as


collar-stud abscess

Overlying skin becomes indurated and Sinus formation, scrofuloderma


breaks down

34
Konklusi
Pak Badri usia 69 tahun dengan keluhan terdapat 2 buah benjolan pada leher kanan
sejak 6 bulan yang lalu mengalami limfadenitis tuberkulosis

Daftar Pustaka

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PEDOMAN INTERPRETASI DATA KLINIK KEMENTERIAN KESEHATAN


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