i

KARYA TULIS AKHIR

PENGARUH PAPARAN BENZENA PERINHALASI TERHADAP

EVALUASI HAPUSAN DARAH TIKUS PUTIH JANTAN (Rattus

norvegicus) STRAIN WISTAR

Oleh:

Wahyu Estu Septyah Margowati

201610330311080

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2020

ii

HASIL PENELITIAN

PENGARUH PAPARAN BENZENA PERINHALASI TERHADAP

EVALUASI HAPUSAN DARAH TIKUS PUTIH JANTAN (Rattus

norvegicus) STRAIN WISTAR

KARYA TULIS AKHIR

Diajukan kepada

Universitas Muhammadiyah Malang untuk memenuhi

salah satu persyaratan dalam menyelesaikan

Program Sarjana Fakultas Kedokteran

Oleh:

Wahyu Estu Septyah Margowati

201610330311080

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2020

iii

iv

v

vi

KATA PENGANTAR

Assalamu’alaikum Warahmatullahi Wabarakatuh

Puji syukur kehadirat Allah SWT karena atas rahmat dan hidayah-Nya,

penulisan tugas akhir ini dapat diselesaikan dengan baik dan tepat waktu. Shalawat

serta salam selalu tercurahkan kepada Rasulullah Muhammad SAW, keluarga, para

sahabat, dan pengikut beliau yang telah membawa duni ini dari zaman kegelapan

emunju zaman yang terang benderang.

Penelitian tugas akhir ini berjudul “Pengaruh Paparan Benzena Perinhalasi

Terhadap Evaluasi Hapusan Darah Tikus Putih Jantan (Rattus norvergicus) Strain

Wistar”. Tugas akhir ini diajukan untuk memenuhi persyaratan Pendidikan Sarjana

Fakultas Kedokteran Universitas Muhammadiyah Malang.

Penulis menyadari tugas akhir ini masih jauh dari kata sempurna, oleh

karena itu, penulis sangat mengharapkan saran dan masukan yang membangun.

Semoga karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi

semua pihak.

Wassalamu’alaikum Warahmatullahi Wabarakatuh

Malang, 14 Juni 2020

Penulis

xii

DAFTAR ISI

HALAMAN JUDUL ............................................................................................ i

HALAMAN PERSYARATAN GELAR .............................................................. ii

LEMBAR PENGESAHAN ................................................................................. iii

SURAT PERNYATAAN ORISINILITAS .......................................................... iv

LEMBAR PENGUJIAN ...................................................................................... v

KATA PENGANTAR ........................................................................................ vi

UCAPAN TERIMA KASIH .............................................................................. vii

ABSTRAK .......................................................................................................... x

ABSTRACT ......................................................................................................... xi

DAFTAR ISI ..................................................................................................... xii

DAFTAR TABEL ............................................................................................. xv

DAFTAR GAMBAR ........................................................................................ xvi

DAFTAR SINGKATAN ................................................................................. xvii

DAFTAR LAMPIRAN ................................................................................... xviii

BAB I PENDAHULUAN .................................................................................... 1

1.1. Latar Belakang ...................................................................................... 1

1.2. Rumusan Masalah ................................................................................. 3

1.3. Tujuan Penelitian ................................................................................... 3

1.3.1 Tujuan Umum ............................................................................... 3

1.3.2 Tujuan Khusus............................................................................... 3

1.4. Manfaat Penelitian.................................................................................. 3

1.4.1 Manfaat Akademik ........................................................................ 3

1.4.2 Manfaat Masyarakat ...................................................................... 4

BAB II TINJAUAN PUSTAKA .......................................................................... 5

2.1. Benzena ................................................................................................. 5

2.1.1. Benzena Secara Umum ................................................................. 5

2.1.2. Sifat Fisika dan Kimia Benzena .................................................... 6

2.1.3 Sumber Benzena di Lingkungan .................................................... 6

2.1.4 Toksikokinetika Benzena dalam Tubuh Manusia .......................... 8

xiii

2.1.5 Toksisitas Benzena ...................................................................... 10

2.1.6 Mekanisme Hematotoksisitas Benzena ........................................ 12

2.2. Proses Pembentukan Sel Darah (Hematopoiesis) .................................. 13

2.2.1 Sel Darah Merah (Eritrosit) ......................................................... 15

2.2.2 Sel Darah Putih (Leukosit) .......................................................... 18

2.2.3 Trombosit .................................................................................... 20

2.3. Anemia Aplastik .................................................................................. 21

2.3.1 Definisi Anemia Aplastik ........................................................... 21

2.3.2 Etiologi Anemia Aplastik ........................................................... 21

2.3.3 Patofisiologi Anemia Aplasstik ................................................... 22

2.3.4 Gejala Klinis Anemia Aplastik ................................................... 23

2.3.5 Kriteria Diagnosis Anemia Aplastik ............................................ 24

2.4. Evaluasi Hapusan Darah Tepi ............................................................... 25

2.4.1 Definisi........................................................................................ 25

2.4.2 Indikasi Dilakukan Evaluasi Hapusan Darah Tepi ....................... 26

2.5. Tikus .................................................................................................... 26

2.6. Hematopoiesis Tikus ............................................................................ 27

2.6.1 Eritrosit ....................................................................................... 28

2.6.2 Leukosit....................................................................................... 28

2.6.3 Trombosit .................................................................................... 28

BAB III KERANGKA KONSEP DAN HIPOTESIS.......................................... 29

3.1. Kerangka Konsep ................................................................................. 29

3.2. Hipotesis .............................................................................................. 30

BAB IV METODE PENELITIAN ..................................................................... 31

4.1. Jenis Penelitian ..................................................................................... 31

4.2. Tempat dan Waktu Penelitian ............................................................... 31

4.3. Populasi dan Sampel ............................................................................ 31

4.3.1 Populasi ....................................................................................... 31

4.3.2 Sampel ........................................................................................ 31

4.3.3 Besar Sampel ............................................................................... 31

xiv

4.3.4 Teknik Pengambilan Sampling .................................................... 32

4.3.5 Karakteristik Sampel Penelitian ................................................... 33

4.3.6 Variabel Penelitian ...................................................................... 33

4.3.7 Definisi Operasional .................................................................... 34

4.4. Alat dan Bahan Penelitian .................................................................... 35

4.4.1 Alat Penelitian ............................................................................. 35

4.4.2 Bahan Penelitian .......................................................................... 37

4.5. Prosedur Penelitian ............................................................................... 37

4.5.1 Proses Adaptasi ........................................................................... 37

4.5.2 Pembagian Kelompok Tikus ........................................................ 37

4.5.3 Pemaparan Benzena ..................................................................... 38

4.5.4 Proses Anestesi dan Pengambilan Darah ...................................... 38

4.5.5 Pembuatan Sediaan Hapusan Darah ............................................. 39

4.5.6 Penanganan Hewan Coba Setelah Pengambilan Sampel ............... 39

4.6. Alur Penelitian .................................................................................... 40

4.7. Analisis Data ........................................................................................ 41

4.8 Jadwal Penelitian ................................................................................... 41

BAB V HASIL PENELITIAN DAN ANALISIS DATA ................................... 42

5.1. Hasil Penelitian .................................................................................... 42

5.2. Analisis Data ........................................................................................ 44

5.2.1 Uji One Way ANOVA................................................................... 44

5.2.2 Uji Post Hoc ................................................................................ 46

BAB VI PEMBAHASAN .................................................................................. 48

BAB VII KESIMPULAN DAN SARAN ........................................................... 54

7.1. Kesimpulan .......................................................................................... 54

7.2. Saran .................................................................................................... 54

DAFTAR PUSTAKA ........................................................................................ 55

LAMPIRAN ...................................................................................................... 60

xv

DAFTAR TABEL

Nomor Judul Tabel Halaman

Tabel 2.1 Sifat Fisika dan Kimia Benzena 6

Tabel 2.2 Bentuk Eritrosit Abnormal 16

Tabel 2.3 Klasifikasi Etiologi Anemia Aplastik 22

Tabel 2.4 Keluhan Pasien Anemia Aplastik 24

Tabel 2.5 Klasifikasi Anemia Aplastik 25

Tabel 2.6 Karakteristik Hematologi Tikus dan Manusia 27

Tabel 4.1 Definis Operasional 34

Tabel 4.2 Jadwal Penelitian 41

Tabel 5.1 Hasil Uji Post Hoc Nutrofil Segmen 46

Tabel 5.2 Hasil Uji Post Hoc Limfosit 47

Tabel 5.3 Hasil Uji Post Hoc Monosit 47

xvi

DAFTAR GAMBAR

Nomor Judul Gambar Halaman

Gambar 2.1 Struktur Benzena 5

Gambar 2.2 Metabolisme Benzena 9

Gambar 2.3 Mekanisme Hematotoksisitas Benzena 12

Gambar 2.4 Skema Hematopoiesis di Sumsum Tulang 14

Gambar 2.5 Langkah-Langkah Utama Dalam Produksi Eritrosit 15

Gambar 2.6 Sickled Red Cell, Nucleated red cell (orthochromatic

erythroblast)

17

Gambar 2.7 Sel Target 17

Gambar 2.8 Tear Drop Red Cells, Fragmented Red Cell 17

Gambar 2.9 Nilai Normal Leukosit 20

Gambar 2.10 Platelet Normal 21

Gambar 2.11 Tikus Putih Rattus norvegicus 27

Gambar 4.1 Design Kandang Perlakuan 35

Gambar 5.1 Grafik Rerata differential counting Tiap Kelompok 41

xvii

DAFTAR SINGKATAN

APD : Alat Pelindung Diri

BR-1 : Broiler Starter-1

CYP2E1 : Cytochrome P450 2E1

DNA : Deoxyribonucleic Acid

EDTA : Ethylenediaminetetraacetic Acid

Hb : Hemoglobin

HSC : Hematopoetic Stem Cells

MCV : Mean Corpuscular Volume

NAB : Nilai Ambang Batas

NIOSH : National Institute of Occupational Safety and Health

OSHA : Occupational Safety and Health Administration

PAK : Penyakit Akibat Kerja

Ppm : Part per million

ROS : Reactive Oxygen Species

SPBU : Stasiun Pengisian Bahan Bakar Umum

t,t-MA : t,t muconal acid

xviii

DAFTAR LAMPIRAN

Nomor Judul Lampiran Halaman

Lampiran 1 Uji Normalitas dan Homogenitas 60

Lampiran 2 Uji One Way ANOVA 62

Lampiran 3 Uji Kruskal-Wallis 63

Lampiran 4 Uji Post Hoc Bonferroni 64

Lampiran 5 Uji Post Hoc Mann-Whitney 65

Lampiran 6 Sertifikat Layak Etik 67

Lampiran 7 Surat Ijin Penelitian 68

Lampiran 8 Hasil Plagiasi 69

Lampiran 9 Dokumentasi Kegiatan Penelitian 70

55

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