EKSKRESI

1. EKSKRESI

2. Ekskresi • TOKSIKAN  eliminasi potensi toksik turun (o.k. Peluang menumpuk & merusak sel2 penting berkurang) • Elimination –melalui metabolisme & ekskresi • Eksresi eliminasi melalui organ ekskretory khusus

3. Toxican yg polar  > mdh di ekskresikan dari tubuh lewat berbagai jalur kecuali paru • non polar  lewat paru • u/ bisa dikeluarkan dari tubuh bahan kimia harus melewati berlapis membran • Sifatkimia & fisikbhnygmenentukanbstidaknyabhnmelaluimembranjugaberlakudi organ ekskretory

4. JALUR EKSKRESI • berbagairute • Jalurutama : urine, feces & ekshalasi • organ utama u/ ekskresi: urinary system, gastrointestinal system & respiratory system. • Jalur lain (krgpenting) , kecualidlmhaltertentu

5. Jalurekskresi : a. GIT, sweat, & saliva b. ASI, Air mata (tears), & semen c. Urinary & Fecal excretion d. Ekshalasi

6. Urinary Excretion • Melalui ginjal urine • terpenting • Fgs utama ginjal : ekskkresi sisa metabolisme & bhn kimia bbhy • Unit fungsional ginjal : Nephron

7. Tiapginjalterdiriatas 1 jutanephrons. 3 daerahnephronygb’fgsekskresi: glomerulus, proximal tubule & the distal tubule.

9. 3 proses ekskresilewat urine: Filtrasi, sekresi, reabsorbsi • Filtrasi: • Prosespertama • Di glomerulus (the very vascular beginning of the nephron). • ± ¼ Curahjantungmelaluiginjal (organ ygmenerimaalirandarahterbesar) • Banyak plasma drhygdisaringdiglomeruluskarena : a. Banyakalirandarah b. pori berukuran besar (40 Å) c. tekanan hidrostatik darah

10. Molekulberukurankecil (termasuk air)  dapatsegeramelewati filter di nephron tubulus • Bahan Polar & Non Polardptlewat glomerulus  masuktubulussbgfiltrat • Juml. Filtrat sangat banyak ± 45 galon/hari (dws) • 99% fitralt yg larut air , molekul kecil, larut lemak diserab lagi di tubulus; yg jadi urin hanya 1%

11. Molekul berukuran besar >60.000 , ex: protein dan sel darah tak dapat menembus lubang kapiler  tetap berada dalam aliran darah • Adanya darah dan protein di urine pertanda ada kerusakan di glomerulus • Bahan yg polar tak terikat dg protein plasma  dapat lewat dan tersaring menuju tubulus • Bahan yg non polar akan tetap dalam darah

12. Sekresi • Terjadi di tubulus bagian atas/proximal  mengeluarkan molekul keluar dari darah menjadi urine) • Yg disekresi : ion K, H, bbrp, xenobiotic • Sekersi  terjadi dg transport aktif  dpt membedakan bahan berdasar polaritasnya • Ada 2 sistem sekresi : a. Yg mentransport asam lemah (ex: obat yg sdh terkonjugasi) b. Yg mentransport basa (ex: histamine & choline).

13. REABSORBSI • Terutama terjadi di proximal convoluted tubule • Hampir semua air, glukosa, K, AA yg telah menjadi filtrat masuk kembali ke darah melalui tubulus • Reabsorpsi terutama terjadi melalui transfer pasif (tgr gradient konsentrasi : tinggirendah ; dari tubulus proximal  kapiler di sekitarnya)

14. Faktor yg sangat berpenagruh pd Reabsorbsi & Ekskresi : pH urine. • Urine basa asam lemah terionisasi >>dikeluarkan • Urine asam asam lemah kurang terionisasi  reabsorbsi  ekskresi << • pH urine beragam  ekskresi elektrolit lemah juga beragam

15. Phenobarbital (asam)  terionisasi pd urine yg basa; • Amphetamine (basa)  terionisasi pd urine yg asam O.k.i: • Pada keracunan phenobarbital: urine diubah menjadi basa • Pd keracunan amphetamine urine dibuat asam (diet tinggi protein)

17. DAPAT DISIMPULKAN : • E liminasi melalui GINJAL –sangat dipengaruhi o/ : - SIFAT FISIK (terutama ukuran molekul) dan - POLARITAS filtrat • Racun yg ukuran molekul KECIL (polar maupun non polar)  dg MUDAH disaring Glomerulus • Pd bbrp kasus, Molekul yg BESAR (termasuk yg terikat protein)  dpt disekresi dg TRANSFER PASIF (darah sel endotel kapiler & membran tubulus  urine) • POLARITAS merupakan Faktor utama dlm ELIMINASI • Bahan yg TERIONISASI  dikeluarkan mel URINE • Bahan yg non polar  reabsorbsi  masuk kembali ke sirkulasi  memperpanjang T ½  meningkatkan potensi toksik

18. Racun, infeksi, ketuaan kerusakan Ginjal kemampuan eliminasi toksin turun  lebih rentan thd racun) • Albuminuria tanda kerusakan sistem filtrasi glomerulus (alb. :molekul ukuran besar -dapat lewat) • Glucosuria tanda adanya kegagalan reabsorbsi

19. For Academics : • The reason that much of the blood plasma filters into the renal tubule is due to: a. the large amount of blood, under relatively high pressure, that flows through kidney glomerulae whose capillaries have large pores b. its high lipid content c. the high binding content of plasma

20. A considerable amount of the blood plasma filters through the glomerulus into the nephron tubule. This results from the large amount of blood flow through the glomerulus, the large pores (40 Å) in the glomerular capillaries, and the hydrostatic pressure of the blood. (a)

21. For Academics : • In which area of the nephron does active secretion take place? a. the collecting duct of b. the nephron c. the proximal tubule of the nephron d. the glomerulus of the nephron

22. Secretion occurs in the proximal tubule section of the nephron and is responsible for the transport of certain molecules out of the blood and into the urine. (c)

23. For Academics : • Most of the material filtered through the glomerulus is reabsorbed in the proximal convoluted tubule of the nephron. The primary property of a xenobiotic that determines whether it will be reabsorbed is: a. protein binding b. molecular size c. its polarity

24. The ultimate fate of a substance filtered into the renal tubule is governed by its polarity. Those substances that are ionized remain in the urine and leave the body. (c)

25. Fecal Excretion • Eliminasi toksikan mel. feces terjadi dg 2 proses : a. Ekskresi di empedu masuk kembali ke usus b. Ekskresi langung ke lumen usus

26. Rute Billiar • Mekanisme penting pd ekskresi fecal xenobiotik • > penting dari ekskresi metabolit • Rute ini > banyak SEKRESI AKTIF daripada DIFUSI PASIF

27. Bahan kimia tertentu (basa organik, asam organic, bahan yang netral keasamannya)  mengalami transport khusus • Logam berat yang diekskresikan lewat empedu : e.g., arsenic, lead, and mercury • ekskresi melalui empedu terutama untuk - Molekul Terionisasi, - Ukuran besar (>300), - Terkonjugasi

28. Begitu suatu bahan diekskresi o/liver  empedu usus eliminasi melalui feces reabsorbed.

29. Krn hampir semua bhn yg diekskresikan di empedu LARUT AIR  tdk diserab kembali • Namun , ada enzym di usus yg dpt mengHIDROLISIS konjugat glukoronat & sulfat  sehingga bahan menjadi < POLAR  DISERAB kembali • Proses ekskresi ke usus melalui empedu & reabsorbsi  kembali ke liver melalui sirkulasi portal : sirkulasi enterohepatik /enterohepatic circulation memperpanjang T ½ menambah peluang toksik

30. Jika terjadi bioaktifasi metabolit > toksik dibanding konjugat • Sirkulasi enterohepatik  T1/2 memanjang  racun sulit keluar  perlu obat lewat oral untuk binding bahan yg diekskresi empedu AGAR CEPAT KELUAR • Ex: Keracunan dimethylmercury  diberi RESIN binding racun tdk diserap kembali lewat sirkulasi enterohepatik

31. EFEK GANGGUAN LIVER • efisiensi ekskresi empedu dipengaruhi oleh produksi dan aliran cairan empedu • Sakit liver aliran empedu turun • Phenobarbital  dpt meningkatkan aliran empedu • Pemberian phenobarbital meningkatkan pengeluaran methyl mercury

33. Direct intestinal excretion • >> bhnygdptdiekskresilewatususdandikskresikanlewat feces • TERUTAMA yg “poorly ionized” dlm plasma (ex: asam & basalemah) dptlewatdindingkapiler  menembus sub mukosa  masuk lumen usus - dieliminasilewat feces

34. Ekskresilewatusus –lambat rutepenting  proseseliminasiygpenting u/ xenobiotics yglambatbiotransformasinyaatauyglambatdikeluarkanlewaturin / empedu • Jikakandunganlemakdiususditingkatkan ekskresilewatususdptlebihcepat u/ mengeluarkanracun –diet mineral oil  lgskeluarlewatusus

35. For Academics : • Substances excreted in the bile are primarily: a. small, lipid soluble molecules b. comparatively large, ionized molecules c. large lipid soluble molecules

36. The most likely substances to be excreted via the bile are comparatively large, ionized molecules, such as large molecular weight (greater than 300) conjugates. (b)

37. For Academics : • Many substances excreted in bile undergo enterohepatic circulation, which involves: a. excretion of substances into the circulating system rather than into the intestine b. excretion into the intestinal tract and reabsorption and return to the liver by the portal circulation c. the recycling of xenobiotics between the liver and gall bladder

38. The process of excretion into the intestinal tract via the bile and reabsorption and return to the liver by the portal circulation is known as the enterohepatic circulation. The effect of this enterohepatic circulation is to prolong the life of the xenobiotic in the body.(b)

39. Exhaled Air • Paru rutepentingekskresixenobiotics (& metabolites) ygbentuknya gas dlmdarah • Blood gases  ekskresipasifdaridarah alveolus- mengikutigradienkonsentrasi • (terjadijikakadar gas dlmdarah > di alveoli) • Gas ygkkuranglarut dl darah (jadilarutlemak)  > cepatdieliminasidibandingygsangatlarut air

40. Cairanygmdhmenguap (Volatile liquids ) yglarutdlmdarahjugacepatdikeluarkanlewatekshalasi • Jumlahlikuidaygdikeluarkanlewatekshalasi tgt tekananuapnya (vapor pressure) • Ekshalasi mrpruteygefisien u/ bhnuglarutlemak • Kapilersangatbanyak di alveoli +membram alveoli tipismdhterjadipertukaran gas

41. For Academics : • Xenobiotics are eliminated in exhaled air by: a. passive diffusion b. active transport c. facilitated transport

42. Blood gases are excreted by passive diffusion from the blood into the alveolus, following a concentration gradient. This occurs when the concentration of the xenobiotic dissolved in capillary blood is greater than the concentration of the substance in the alveolar air.(a)

43. Other Routes ofExcretion • Several minor routes of excretion exist, primarily via: a. mother's milk, d. tears b. sweat, e. semen c. saliva, • Excretion into milk can be important since toxicants can be passed with milk to the nursing offspring. • In addition, toxic substances may be passed from cow's milk to people. • Toxic substances are excreted into milk by simple diffusion.

44. Bahan yang BASA & NON POLAR  dpt diekskresi lewat ASI • Bahan BASA – mdh terkonsentrasi di air susu karena air susu > ASAM (pH ~ 6.5) dibanding plasma • Karena SUSU mengandung 3-4% LEMAK  xenobiotik yg LARUT LEMAK --dapat terdifusi bersama lemak plasma  kelenjar mammae  ada pada ASI • Bahan yg sifat kimianya mirip Calsium  dpt dekeluarkan lewat ASI bersama kalsium • Contoh yg dpt keluarlewat ASI: - DDT, polybrominated biphenyls, & Pb (which follows calcium kinetics).

45. Ekskresi lewat rute lain (saliva, sweat, tears, hair, and skin)  kurang penting • Pada produksi keringat yg ber>an  ekskresi menjadi penting (bisa signifikan) • Beberapa logam (cadmium, copper, iron, lead, nickel, and zinc)  dpt dieliminasi lewat keringat • Xenobiotics yg terdifusi pasif lewat liur (saliva)  dpt tertelan absorbsi lewat GIT • Ekskresi lewat saliva RASA tak enak di mulut (EX: Rasa Logam)

46. For Academics : • The following are minor routes of excretion: a. sweat and saliva b. urinary excretion, fecal excretion, and exhaled air

47. Several minor routes of excretion exist, primarily via mother's milk, sweat, saliva, tears, and semen.