ENVIRONMENTAL and

NUTRITIONAL DISEASE

dr. Yuliet sinanu

The Global Burden Of Disease

Efek Perubahan Iklim terhadap Kesehatan
Toksisitas agen fisik dan agen kimiawi
Polusi lingkungan
Resiko Penyakit akibat Pekerjaan
Efek Tembakau
Efek Alkohol
Cedera akibat Obat Terapeutik dan
Penyalahgunaan obat
Cedera akibat Agen Fisik
Penyakit Gangguan Nutrisi

Environmental disease = Penyakit lingkungan

Kondisi yang disebabkan oleh paparan bahan kimia,
atau fisik yang ada di lingkungan tempat kerja, dan
lingkungan pribadi, termasuk gangguan nutrisi.
Sejarah :
Minamata bay Jepang, 1960
Reaktor nuklir Chernobyl Rusia, 1986
Reaktor nuklir Fukushima Jepang, 2011

The GBD

Sistem standart pelaporan penyakit sehingga dapat

diketahui jumlah penyakit dengan angka kematian
terbanyak

Kesimpulan GBD;
Kekurangan gizi ( undernutrition)
Ischemic heart disease & cerbrovascular disease
Penyakit infeksi
Kematian anak < 5 thn sudah menurun
Emerging infectious disease

Figure 9-1 Worldwide mortality of children under 5 years of age. Note the more than 50-fold difference between areas with the lowest and highest mortality. Malnutrition
and infections are major causes of the high mortality in East, Central, and West Africa.
Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)
2005 Elsevier

Efek Perubahan Iklim terhadap

Kesehatan

GLOBAL WARMING !!!

Kenaikan suhu 0,6 C / thn, sejak 1960
Kenaikan permukaan laut 1 2 mm/thn
Penyebab :
CO2
Methan
Ozone

GREEN HOUSE EFFECT

Uap air
Bertindak seperti selubung / selimut yang menahan / menyerap

energi yang dikeluarkan dari permukaan bumi sehingga tidak

dapat dikembalikan ke atmosfer.

Figure 9-2 Sources and consequences of increased greenhouse gases. A, Predicted temperature increases during the twenty-first century. Different computer models plot
anticipated rises in temperature of 2&#176; to 5&#176;C by the year 2100. B, Release of carbon dioxide (CO2) from combustion sources in China, 1970 to 2005. China
has now surpassed the United States as the world's largest producer of CO2. C, Regions of the United States in which ozone levels are above existing accepted
standards (80 ppb during an 8-hour period). These areas include about 500 counties located predominantly in the East Coast corridor, the Los Angeles basin, and areas
with large coal-burning plants.
Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)
2005 Elsevier

Beberapa penyakit yg mungkin timbul;

Peny. Kardiovaskular, cerebrovaskular dan

sal.pernapasan
Gastroenteritis dan penyakit infeksi yg epidemik
Vector borne infectious disease
Malnutrisi

Toksisitas Agen Fisik dan Kimiawi

Toksikologi :
Ilmu yang mempelajari ttg distribusi, efek, cara kerja

dari agen toksik, termasuk radiasi dan panas

Efek pada manusia tergantung;

Variasi polutan
Umur
Predisposisi genetik
Sensitivitas jaringan yang terpapar

TOKSIN : semua zat adalah toksin , tergantung

pada dosisnya.

Xenobiotik : bahan kimia eksogen

yang ada di udara, air, makanan dan
tanah
Masuk ke dalam tubuh manusia
melalui inhalasi, tertelan atau kontak
kulit.

Figure 9-3 Human exposure to pollutants. Pollutants contained in air, water, and soil
are absorbed through the lungs, gastrointestinal tract, and skin. In the body they may
act at the site of absorption but are generally transported through the bloodstream to
various organs where they may be stored or metabolized. Metabolism of xenobiotics
may result in the formation of water-soluble compounds that are excreted, or in
activation of the agent, creating a toxic metabolite.
Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)
2005 Elsevier

Figure 9-4 Xenobiotic metabolism. A, Xenobiotics can be metabolized to nontoxic metabolites and eliminated from the body (detoxification). B, Xenobiotic metabolism
may also result in the formation of a reactive metabolite that is toxic to cellular components. If repair is not effective, short- and long-term effects develop. (Based on
Hodgson E: A Textbook of Modern Toxicology, 3rd ed. Hoboken, NJ, Wiley, 2004.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Polusi Udara

Luar ruangan ( outdoor)

Partikel

Sulfur
dioksisa

Aerosol

Nitrogen
dioksida

Ozone

Smog

CO

CO :
Tidak berbau, tidak berwarna, tidak berasa, tidak

mengiritasi
Oksidasi karbon yang tidak sempurna
Sumber : asap kendaraan, mesin mesin dengan
bahan bakar kayu atau batubara
Asfiksia depresi SSP kematian
Mengikat Hb 200x > O2
CO-Hb 20 30% hipoksia sistemik
CO-Hb 60 70% kesadaran & kematian

Ozone (O3)
UV + O2
Di lap stratosfer ( 20 30 mil)
F melindungi bumi dari radiasi UV yg
berbahaya
Dalam 30 thn terakhir menipis dan berlubang

Ground level ozone

Nitrogen oksida + bahan organik
Sumber : emisi gas industri , kendaraan
Radikal bebas
Merusak epitel saluran pernapasan & alveolar type 1

Sulfur dioksida
Sumber : pembakaran batubara dan minyak t.u

pada pabrik peleburan tembaga dan pabrik kertas

Dilepas ke udara asam sulfur dan sulfur trioksida
Rasa terbakar pada tenggorokan, sulit bernapas,
dan serangan asma

Partikel partikel halus

Sumber : industri yg memakai batubara dan minyak
< 10 m alveolus inflamasi mediator radang
> 10 m dikeluarkan / ditangkap o/. Epitel resp

Polusi udara.

Dalam ruang (indoor)

o.k ventilasi ruang kurang
Sumber :
asap tembakau (rokok),
asap kayu infeksi paru - Ca
Bioaerosol Rhinitis, iritasi mata, asma.
Radon gas dr uranium Ca
Formaldehyde

SICK BUILDING SYND

Pencemaran o/. Logam berat

TIMBAL (Pb)

Sumber : udara, air dan

tanah yang terkontaminasi
Pd Cat rumah , bensin dan
mainan anak anak.
Anak & org dewasa
80 85 % diserap oleh
tulang dan gigi, VS kalsium
Half life dalam tulang 20
30 thn
Anak kecil menyerap 50%
> banyak dari org dewasa.

Figure 9-6 Pathologic features of

lead poisoning in adults.

Figure 9-7 Lead poisoning. Impaired remodeling of calcified cartilage in the

epiphyses (arrows) of the wrist has caused a marked increase in their
radiodensity, so that they are as radiopaque as the cortical bone. (Courtesy
of Dr. G.W. Dietz, Department of Radiology, University of Texas
Southwestern Medical School, Dallas, TX.)

Mercury
Ada dalam cat, kosmetik, pengobatan sifilis,

komponen diuretic
Intoksikasi mercury tremor, ginggivitis, perilaku aneh.
Sumber intoksikasi:
Ikan yg tercemar
Amalgam gigi
Pekerja tambang emas
Penyakit MINAMATA ( Minamata bay Jepang)
cerebral palsy
Tuli, buta. Retardasi mental
Defek SSP

Arsen
Scr natural ada dalam tanah dan air.
Jg dalam herbisida ( racun tikus), obat obatan

herbal China dan India

Jika tertelan dalam jumlah besar intoksikasi
akut ggn gastrointestinal, ggn cardiovascular
dan ggn SSP
Arsen gangguan DNA repair Ca
The poison of kings and King of poison

Cadmium
Pada daerah pertambangan & peleburan
Digunakan sbg; pigmen cat, campuran logam,

solder, penyepuhan dan batterai

Efek :
obstruksi paru o.k nekrosis makrofag alveolar.
kerusakan ginjal ( tubular damage)
Skeletal abnormalities o.k hilangnya kalsium

Penyakit Itai itai di Jepang

Osteoporosis + osteomalacia + penyakit ginjal

Resiko Kesehatan : Eksposur

Industri dan Pertanian

Lebih dari 10 juta luka-luka dan sekitar

100.000 kematian terjadi setiap tahun di
Amerika Serikat sebagai konsekuensi
dari kecelakaan kerja dan penyakit.
Kecelakaan kerja merupakan masalah
terbesar di negara-negara berkembang,
sedangkan penyakit yang berhubungan
dengan kerja lebih sering terjadi di
negara-negara industri.

Fraksi penyakit global dikaitkan dengan

paparan kerja mencakup 13% dari
semua kasus penyakit paru obstruktif
kronik, 9% dari kanker paru-paru, dan
2% dari leukemia.

Pelarut organik banyak digunakan dalam

jumlah besar di seluruh dunia.
Beberapa diantaranya chloroform dan karbon
tetraklorida, ditemukan dalam pembersih dan
pengering dan penghilang cat.
Pemaparan akut tingkat tinggi dari agent ini
menyebabkan pusing dan kebingungan,
depresi sistem saraf pusat, bahkan koma.
Pada tingkat yang lebih rendah menyebabkan
toksik pada hati dan ginjal.

Hidrokarbon polisiklik
dapat dilepaskan selama pembakaran

bahan bakar fosil, terutama ketika batu bara

dan gas dibakar pada suhu tinggi (seperti
dalam peleburan baja), dan juga hadir di tar
dan jelaga.
Termasuk karsinogen yang paling kuat, dan

exposure industri terlibat dalam

perkembangan kanker paru dan kandung
kemih.

Organoklorin, ( dan halogenasi senyawa

organik secara umum ) adalah produk
lipofilik sintetis yang tahan degradasi.
Digunakan sebagai pestisida termasuk DDT,

Lindane, Aldrin dan Dieldrin.

Organoklorin non-peptisida termasuk
polychlorinated biphenyls (PCBs) dan dioxin .
DDT dilarang di Amerika Serikat pada tahun
1973, tetapi lebih dari setengah penduduk AS
terdeteksi p,p-DDE, metabolit DDT yang panjang.

Dioxin dan PCB dapat menyebabkan gangguan kulit

seperti folikulitis dan dermatosis yang dikenal

sebagai chloracne, yang ditandai dengan jerawat,
pembentukan kista, hiperpigmentasi dan
hiperkeratosis, umumnya disekitar wajah dan
belakang telinga.
Racun ini juga dapat menyebabkan kelainan pada
hati dan sistem saraf pusat.
Karena PCB menginduksi CYPspekerja yang
terpapar zat ini mungkin menunjukkan metabolisme
yang abnormal

Bencana lingkungan di Jepang dan China pada

akhir tahun 1960, disebabkan oleh konsumsi

minyak beras terkontaminasi dengan PCB selama
produksi meracuni sekitar 2000 orang.
Manifestasi utama dari penyakit ini adalah
chloracne dan hiperpigmentasi pada kulit dan kuku.
Sebuah kasus aneh keracunan dioxin yang
disengaja, yang membuat berita utama
internasional dan merupakan halaman depan
ilustrasi chloracne melibatkan presiden masa
depan Ukraina.

Menghirup debu mineral penyakit paru kronik

non-neoplastik dikenal sebagai nonpneumoconiosis.
Istilah ini juga termasuk penyakit-penyakit yang
disebabkan oleh partikel organik dan anorganik,
dan asap kimia menginduksi terjadinya
penyakit paru non-neoplastic.
Yang paling umum pneumoconiosis disebabkan
oleh eksposur terhadap debu batubara, silika,
asbes, dan berilium.

Paparan vinil klorida yang digunakan dalam sintesa

resin polyvinyl mengarah ke pengembangan
angiosarcoma hati, tipe jarang dari tumor hati.

Paparan dari phthalates pada hewan laboratorium

menyebabkan gangguan endokrin dan sindrom
disgenesis testis melibatkan hipospadia,
kriptorkismus, dan kelainan sel testis yang mirip
dengan kondisi yang tidak diketahui asalnya.
Phthalates banyak ditemukan dalam plastik fleksibel (
seperti kantung pembungkus makanan) dan dalam
wadah medis seperti kantong darah dan serum.

EFEK ASAP TEMBAKAU

angka kejadian kanker

paru semakin
meningkat
perokok pasif sama
bahayanya dengan
perokok aktif

CEDERA AKIBAT AGEN

FISIK

TRAUMA MEKANIS

abrasi
kontusio
laserasi
luka insisi
luka tusuk

TRAUMA TERMAL
luka bakar
Hipertermia

heat cramps
- heat
exhaustion
- heat stroke
-

Hipotermia

Figure 9-16 A, Contusion resulting from blunt trauma. The skin is intact, but there is hemorrhage of subcutaneous vessels, producing extensive discoloration. B,
Laceration of the scalp; the bridging strands of fibrous tissues are evident. (From the Department of Pathology, Southwestern Medical School, Dallas, TX.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

CEDERA LISTRIK

e/. Arus listrik tegangan rendah ( mis,

rumah ) & tegangan tinggi ( mis, kabel
tegangan tinggi & petir )
terjadi 2 jenis cedera :

luka bakar evaluasi luka bakar

fibrilasi ventrikel - kematian

PENYAKIT GIZI

Malnutrisi energi protein;

- Marasmus
- Kwashiorkor

Anoreksia nervosa & Bulimia ; dilakukan

dengan sengaja
Defisiensi vitamin ; A,B,C,D,E,K
Obesitas ; peningkatan BB akibat
penimbunan jaringan lemak yg dapat
menyebabkan gangguan kesehatan, ( 20 %
)

Figure 9-23 Childhood malnutrition. A, Marasmus. Note the loss of muscle mass and subcutaneous fat; the head appears to be too large for the emaciated body. B,
Kwashiorkor. The infant shows generalized edema, seen as ascites and puffiness of the face, hands, and legs. (A, From Clinic Barak, Reisebericht Kenya.)

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-25 Vitamin A metabolism.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-26 Vitamin A deficiency: its major consequences in the eye and in the production of keratinizing metaplasia of specialized epithelial surfaces, and its possible
role in epithelial metaplasia. Not depicted are night blindness and immune deficiency.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-29 Vitamin D deficiency. There is inadequate substrate for the renal 1&alpha;-hydroxylase (1), yielding a deficiency of 1,25(OH)2D (2), and deficient absorption of
calcium and phosphorus from the gut (3), with consequently depressed serum levels of both (4). The hypocalcemia activates the parathyroid glands (5), causing
mobilization of calcium and phosphorus from bone (6a). Simultaneously, the parathyroid hormone (PTH) induces wasting of phosphate in the urine (6b) and calcium
retention. As a result, the serum levels of calcium are normal or nearly normal, but phosphate levels are low; hence, mineralization is impaired (7).

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-30 Anti-microbial effect of vitamin D. Pathogens and lipopolysaccharides (LPS) stimulate Toll-like receptors (TLRs) in macrophages, causing the transcription of
vitamin D receptor (VDR) and an increase in CYP27B activity in mitochondria. This causes the production of 1,25(OH)2D (1,25-dihydroxyvitamin D), which stimulates the
synthesis of cathelicidin, an antimicrobial peptide that is particularly active against Mycobacterium tuberculosis.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-31 Major consequences of vitamin C deficiency caused by impaired formation of collagen.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Metabolisme alkohol

Figure 9-12 Metabolism of ethanol: oxidation of ethanol to acetaldehyde by three different routes, and the generation of acetic acid. Note that oxidation by ADH (alcohol
dehydrogenase) takes place in the cytosol; the cytochrome P-450 system and its CYP2E1 isoform are located in the endoplasmic reticulum (microsomes), and catalase
is located in peroxisomes. Oxidation of acetaldehyde by ALDH (aldehyde dehydrogenase) oc-curs in mitochondria. ADH oxidation is the most important route; catalase is
involved in only 5% of ethanol metabolism. Oxidation through CYPs may also generate reactive oxygen species (not shown). (From Parkinson A: Biotransformation of
xenobiotics. In Klassen CD [ed]: Casarett and Doull's Toxicology: The Basic Science of Poisons, 6th ed. New York, McGraw-Hill, 2001, p 133.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-13 Adverse drug reaction. Skin pigmentation caused by minocycline, a long-acting tetracycline derivative. A, Diffuse blue-gray pigmentation of the forearm; B,
Deposition of drug metabolite/iron/melanin pigment particles in the dermis. (Courtesy of Dr. Zsolt Argenyi, Department of Pathology, University of Washington, Seattle,
WA.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-14 Acetaminophen metabolism and toxicity. (See text for details.) (Courtesy of Dr. Xavier Vaquero, Department of Pathology, University of Washington, Seattle,
WA.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-15 The effect of cocaine on neurotransmission. The drug inhibits reuptake
of the neurotransmitters dopamine and norepinephrine in the central and peripheral
nervous systems.

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Radiation injury

Figure 9-17 Effects of ionizing radiation on DNA and its consequences. The effects on DNA can be direct, or most importantly, indirect, through free radical formation.

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-19 Overview of the major morphologic consequences of radiation injury. Early changes occur in hours to weeks; late changes occur in months to years. ARDS,
acute respiratory distress syndrome.

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-20 Fibrosis and vascular changes in salivary glands produced by radiation therapy of the neck region. A, Normal salivary gland; B, fibrosis caused by radiation;
C, fibrosis and vascular changes consisting of fibrointimal thickening and arteriolar sclerosis. V, vessel lumen; I, thickened intima. (Courtesy of Dr. Melissa Upton,
Department of Pathology, University of Washington, Seattle, WA.)

Downloaded from: StudentConsult (on 6 February 2010 10:48 AM)

2005 Elsevier

Figure 9-21 Chronic radiation dermatitis with atrophy of epidermis, dermal fibrosis, and telangiectasia of the subcutaneous blood vessels. (American Registry of
Pathology &#169; 1990.)

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-22 Extensive mediastinal fibrosis after radiotherapy for carcinoma of the lung. Note the markedly thickened cardium. (From the teaching collection of the
Department Pathology, Southwestern Medical School, Dallas, TX.)

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-24 Mechanisms of cancer cachexia. The figure illustrates three mechanisms that cause muscle atrophy and muscle degradation leading to cachexia. (1)
Proteolysis-inducing factor (PIF) produced by tumors degrades myosin heavy chain through the proteasome, causing muscle atrophy; (2) TNF and other cytokines
produced by tumors and the host activate NF-&#954;B and initiate the transcription of the ubiquitin ligases MAFBx and MuRF1, contributing to protein breakdown; (3)
alterations in the dystrophin-glycoprotein complex leading to dystrophin-degradation by the proteasome also participate in the muscle atrophy of cachexia.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-32 Regulation of energy balance. Adipose tissues generate afferent signals that influence the activity of the hypothalamus, which is the central regulator of
appetite and satiety. These signals decrease food intake by inhibiting anabolic circuits, and enhance energy expenditure through the activation of catabolic circuits. PYY,
peptide YY. See text for details.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-33 Neurohumoral circuits in the hypothalamus that regulate energy balance. Shown are POMC/CART anorexigenic neurons and NPY/AgRP orexigenic neurons
in the arcuate nucleus of the hypothalamus, and their pathways. See text for details.

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Figure 9-34 Obesity, metabolic syndrome, and cancer. Obesity and excessive weight are precursors of the metabolic syndrome, which is associated with insulin
resistance, type 2 diabetes, and hormonal changes. Increases in insulin and IGF-1 (insulin-like growth factor-1) stimulate cell proliferation and inhibit apoptosis and may
contribute to tumor development. IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; SHBG, sex hormone-binding globulin. (Modified from
Renehan AG et al.: Obesity and cancer risk: the role of the insulin-I6F axis. Trends Endocrinol Metab 17:328, 2006.)

Downloaded from: StudentConsult (on 6 February 2010 10:49 AM)

2005 Elsevier

Terima kasih