MAKALAH

Biokimia Pangan
Metabolisme Air

Dosen pengampu :
Dr. Dedin F. Rosida, STP, MKes

Disusun oleh :

Desita Isna Nuramy / 1633010055

Annisa Septianing P.H / 1633010058

Reny Dian Permata S / 1633010059

Ahmad Nuris Irham / 1633010069

PROGRAM STUDI TEKNOLOGI PANGAN

FAKULTAS TEKNIK
UNIVERSITAS PEMBANGUNAN NASIONAL "VETERAN"
JAWA TIMUR
2017
 KATA PENGANTAR

Puji syukur kami haturkan ke hadirat Tuhan YME, karena dengan karunia-
Nya kami dapat menyelesaiakan makalah ilmiah yang berjudul “Biokimia Pangan :
Metabolisme Air”. Meskipun banyak hambatan yang kami alami dalam proses
pengerjaannya, tapi kami berhasil menyelesaikan karya ilmiah ini tepat pada
waktunya.
Tidak lupa kami sampaikan terimakasih kepada dosen pembimbing Ibu Dr.
Dedin F. Rosida, STP, M.Kes, yang telah membantu dan membimbing kami dalam
mengerjakan makalah ilmiah ini. Kami juga mengucapkan terima kasih kepada
teman-teman mahasiswa yang juga sudah memberi kontribusi baik langsung maupun
tidak langsung dalam pembuatan makalah ilmiah ini.
Tentunya ada hal-hal yang ingin kami berikan kepada masyarakat dari hasil
makalah ilmiah ini. Karena itu kami berharap semoga makalah ilmiah ini dapat
menjadi sesuatu yang berguna bagi kita bersama.
Penulis menyadari bahwa dalam menyusun makalah tulis ini masih jauh dari
kesempurnaan, untuk itu penulis sangat mengharapkan kritik dan saran yang bersifat
membangun guna sempurnanya makalah ini.Penulis berharap semoga makalah tulis
ini bisa bermanfaat bagi penulis khususnya dan bagi pembaca pada umumnya.

Surabaya, 25 Agustus 2017

Penulis

ii
 DAFTAR ISI

I. KATA PENGANTAR ....................................................................................................... I

II. DAFTAR ISI .................................................................................................................... II
III. BAB 1 PENDAHULUAN .................................................................................................1
1. Latar Belakang ................................................................................................................1
2. Rumusan Masalah ...........................................................................................................1
3. Tujuan dan Manfaat ........................................................................................................1
IV. BAB 2 PEMBAHASAN ...................................................................................................2
V. BAB 3 KESIMPULAN ...................................................................................................44

DAFTAR PUSTAKA ......…………………...………………...........………………………45

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 BAB I
PENDAHULUAN
1.1 Latar Belakang

Air merupakan suatu zat yang sangat di butuhkan oleh tubuh manusia karena
setiap sel dalam tubuh manusia membutuhkan air untuk hidup sehat,
keseimbangan metabolisme pada tubuh pun sangat tergantung pada asupan cairan
ke dalam tubuh bila jumlah cairan yang masuk tidak seimbang dengan
pengeluaran maka tubuh akan mengalami gangguan atau dehidrasi.
Rata-rata setiap orang memiliki 60% kadar air dari berat tubuhnya semua
sistem dari tubuh sangat bergantung terhadap air, sebagai contoh air akan
membilas racun dari organ vital, membawa nutrisi penting ke sel-sel tubuh dan
juga menjaga kelembaban tenggorokan , telinga , dan juga hidung.

1.2 Rumusan Masalah

1. Apa pengertian metabolisme?
2. Bagaimana metabolisme air dalam tubuh manusia?

1.3 Tujuan
1. Mengetahui pengertian metabolism secara umum.
2. Mengetahui proses metabilisme air dalam tubuh manusia.

1.4. Manfaat
1. Dapat mengetahui pengertian metabolisme secara umum.
2. dapat mengetahui proses metabolisme air dalam tubuh manusia.

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 BAB II
PEMBAHASAN
2.1 Metabolisme
Metabolisme adalah segala proses reaksi kimia yang terjadi di dalam makhluk
hidup, mulai makhluk hidup bersel satu yang sangat sederhana seperti bakteri,
protozoa, jamur, tumbuhan, hewan; sampai mkhluk yang susunan tubuhnya kompleks
seperti manuasia. Di dalam proses ini, makhluk hidup mendapat, mengubah dan
memakai senyawa kimia dari sekitarnya untuk mempertahankan hidupnya.
Metabolisme meliputi proses sintesis (anabolisme) dan proses penguraian
(katabolisme) senyawa atau komponen dalam sel hidup. Semua reaksi metabolisme
dikatalis oleh enzim. Hal lain yang penting dalam metabolisme adalah peranannya
dalam penawar racun atau detoksifikasi, yaitu mekanisme reaksi pengubahan zat yang
beracun menjadi senyawa tak beracun yang dapat dikeluarkan dari tubuh.

2.2.1 Metabolisme air

Air adalah pelarut senyawa ionik dan netral, dapat mengalami ionisasi.
Mempengaruhi disosiasi makro molekul. Sebagian besar tubuh manusia kurang lebih
70% terdiri dari air. Hampir semua reaksi kimia di dalam tubuh terjadi pada medium
air. Secara umum air berfungsi sebagai bahan pelarut dalam tubuh. Air berguna untuk
melakukan proses metabolisme dalam tubuh seperti pencernaan, ekskresi, penguapan,
dan lain-lain.
Air merupakan komponen utama protoplasma, darah dan limfa, sehingga air
berfungsi juga untuk mengangkut sisa metabolisme dari jaringan ke luar tubuh, serta
mengangkut nutrisi ke seluruh tubuh. Kita memerlukan 2,5 liter air setiap harinya,
karena setiap hari badan kita kehilangan lebih dari 2,5 liter. Air keluar dari tubuh
melalui air kencing, bersama feses, keringat, dan berupa uap air dari paru-paru.
Kebutuhan air dalam tubuh dapat diperoleh dari air minum, makanan, buah, dan
sayuran.
Air Tubuh Total
a. Cairan ekstraseluler :
- Plasma terdapat di dalam darah
- Cairan interstitiel. Menggenangi sel dalam jaringan. Plasma dan cairan interstitiel
saling bercampur lewat pori kapiler pembuluh darah, difusi, prosesnya adalah
fisikokimia
- Cairan pada jaringan ikat padat, tulang kartilago, jaringan pengikat. Pertukaran air
& elektrolit lambat. Tulang itu terlihat padat tetapi sebenarnya ada pertukaran air dan
elektrolit.
b. Cairan interseluler :
Cairan transseluler, termasuk cairan interseluler. Cairan yang terbentuk aktivitas
sekretoris dari kelenjar ludah, pankreas, hati, empedu, dll.
- Asupan & Hilangnya air tubuhnya keduanya harus sama atau seimbang. Jika tidak
maka akan terjadi dehirasi dan overhidrasi
- Asupan air : Makanan (makanan yang mengandung air) & air metabolik (air yang
yang dihasilkan oleh oksidasi tubuh berasal dari proses katabolisme)

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c. Hilangnya air : kulit (menjaga suhu tubuh), paru, ginjal, usus. Masukan air 2.500
ml/hari, air minum 1.200-1.500 ml/hari, makanan 770-1.000 ml/hari, air metabolik
(air yang dihasilkan metabolisme dalam tubuh) tergantung pada laju metabolik
masing-masing. Jumlah masukan air tergantung pada aktifitas fisik seseorang.
Di dalam tubuh manusia, cairan akan terdistridusi ke dalam 2 kompartemen
utama yaitu cairan intraselular (ICF) dan cairan ekstrasellular (ECF). Cairan
intraselular adalah cairan yang terdapat di dalam sel sedangkan cairan ekstraselular
adalah cairan yang terdapat di luar sel. Kedua kompartemen ini dipisahkan oleh sel
membran yang memiliki permeabilitas tertentu. Hampir 67% dari total badan air
(Body’s Water) tubuh manusia terdapat di dalam cairan intrasellular dan 33% sisanya
akan berada pada cairan ekstrasellular. Air yang berada di dalam cairan ekstrasellular
ini kemudian akan terdistribusi kembali kedalam 2 Sub-Kompartemen yaitu pada
cairan interstisial (ISF) dan cairan intravaskular (plasma darah). 75% dari air pada
kompartemen cairan ekstraselular ini akan terdapat pada sela-sela sel (cairan
interstisial) dan 25%-nya akan berada pada plasma darah (cairan intravaskular).
Pendistribusian air di dalam 2 kompartemen utama (Cairan Intrasellular dan
Cairan Ekstrasellular) ini sangat bergantung pada jumlah elektrolit dan makromolekul
yang terdapat dalam kedua kompartemen tersebut. Karena sel membran yang
memisahkan kedua kompartemen ini memiliki permeabilitas yang berbeda untuk tiap
zat, maka konsentrasi larutan (osmolality) pada kedua kompartemen juga akan
berbeda.
Komposisi elektrolit cairan tubuh
Cairan interstisiel, elektrolit cairan interstisiel sama dengan plasma kecuali
protein. Protein plasma berfungsi mempertahankan tekanan osmosis terutama
albumin, sebagai pengangkut albumin. Jumlah air tubuh kira-kira tetap, distribusi
berubah-ubah. Gerakan/perpindahan diarahkan ke arah tekanan osmotik. Tekanan
osmotik dikarenakan ada perbedaan konsentrasi.
Bahan yg terdapat dlm cairan tubuh :
1. Elektrolit terutama K dan Na
Na dan K mempengaruhi retensi dan distribusi air tubuh. Gerakan dipengaruhi oleh
perubahan kadar elektrolit dan tekanan osmotik pada masing-masing sisi.
Na = tulang punggug cairan ekstraseluler
K = tulang punggug cairan intrsaseluler
2. Bahan organik dgn molekul besar (protein)
Penting dlm pertukaran air antara darah & cairan interstitiel. Terutama
pemindahan air dari kompartemen yg satu ke lainnya (bukan air tubuh total).
3. Senyawa organik bermolekul kecil (glukose, urea, dan asam amino)
Tidak penting dlm pengaturan distribusi. Mempengaruhi air tubuh total.
4. Senyawa organik lain

2.2.2Air
Air merupakan bagian terbesar pada tubuh manusia, persentasenya dapat
berubah tergantung pada umur, jenis kelamin dan derajat obesitas seseorang. Pada
bayi usia < 1 tahun cairan tubuh adalah sekitar 80-85% berat badan dan pada bayi
usia > 1 tahun mengandung air sebanyak 70-75 %. Seiring dengan pertumbuhan

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seseorang persentase jumlah cairan terhadap berat badan berangsur-angsur turun yaitu
pada laki-laki dewasa 50-60% berat badan, sedangkan pada wanita dewasa 50 %
berat badan. Hal ini terlihat pada tabel berikut :

Tabel.1 Perubahan cairan tubuh total sesuai usia

Usia Kilogram Berat (%)
Bayi premature 80
3 bulan 70
6 bulan 60
1-2 tahun 59
11-16 tahun 58
Dewasa 58-60
Dewasa dengan obesitas 40-50
Dewasa kurus 70-75
DDikutip dari : Gamer MW: Physiology and pathophysiology of the body fluid, St.
Louis, 1981. Mosby.

Karakteristik air dalam fisiologi

Air adalah senyawa esensial untuk semua makhluk hidup dan mempunyai
beberapa karakteristik fisiologik:
- Media utama pada reaksi intrasel
- Diperlukan oleh sel untuk mempertahankan kehidupan. Hampir semua reaksi
biokimia tubuh terjadi dalam media air, sehingga dapat dikatakan bahwa air
merupakan pelarut untuk kehidupan.
- Pelarut terbaik untuk solut polar dan ionik.
- Media transpor pada sistem sirkulasi, ruang di sekitar sel (ruang intravaskuler,
interstisium), dan intra sel
- Mempunyai panas jenis, panas penguapan, dan daya hantar panas yang tinggi
sehingga berperan penting dalam pengaturan suhu tubuh.

Jumlah Cairan Tubuh

Total body water (air tubuh total) dapat ditentukan melalui beberapa
perhitungan yang menerapkan teknik dilusi dengan menggunakan berbagai zat seperti
duterium, tritium, dan antipirin. Penentuan jumlah cairan ekstrasel biasanya diukur
secara langsung akan tetapi lebih sulit dibandingkan pengukuran air tubuh total. Hal
ini disebabkan bahan yang digunakan dalam proses dilusi harus hanya terdapat pada
cairan ekstrasel dan tersebar pada seluruh kompartemen ekstrasel.
Beberapa cara mengukur kompatemen cairan tubuh, yaitu:
a. Pengukuran cairan kompartemen tubuh berdasarkan konsentrasi suatu zat di
dalam kompartemen:

jumlah zat disuntikan

Konsentrasi zat = volume distribusi

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 b. Dalam melakukan pengukuran jumlah air di kompartemen, perlu dilakukan
perhitungan (koreksi) zat zat yang dieskresikan dalam kurun waktu yang
dibutuhkan oleh zat tersebut sejak disuntikkan dan terdistribusi ke dalam
kompatemen.

Jumlah zat disuntikan−Jumlah diekskresikan

Vd : Konsentrasi setelah ekuilibrium

c. Untuk mengukur volume cairan kompartemen, diperhitungkan zat tertentu yang

terdistribusi dengan sendirinya di dalam kompartemen. Sementara pengukuran
volume kompartemen yang tidak mengandung zat tertentu, dilakukan dengan
melakukan pengurangan.
- Untuk mengukur jumlah total air tubuh (total body water, TBW) dibubuhkan
zat deuterium atau disebut deuterated water (D2O), tritium atau disebut
tritiated water (THO), dan antipirin.
- Volume ekstraseluler (extracellular fluid volume, ECFV) diukur dengan
melakukan pemberian label dengan inulin, sukrosa, mannitol dan sulfat.
- Volume plasma (plasma volume, PV) diukur dengan melakukan pemberian
label radioaktif, yaitu radiolabeled albumin atau zat warna biru Evans (Evans
blue dye yang berikatan dengan albumin).
- Volume intraselular (intracellular fluid volume, ICFV) diukur dengan
melakukan substraksi :
ICF = TBW – ECFV
- Volume cairan interstisium (interstitial fluid volume, ISFV) diukur dengan
melakukan substraksi :
ISFV = ECFV - PV
Jumlah cairan tubuh total kurang lebih 55-60% dari berat badan dan
persentase ini berhubungan dengan jumlah lemak dalam tubuh, jenis kelamin dan
umur. Pengaruh terbesar berhubungan dengan jumlah lemak tubuh. Kandiungna air di
dalam sel lemak lebih rendah dibandingkan kandungan air dalam sel otot, sehingga
cairan tubuh total pada orang yang gemuk lebih rendah dari mereka yang tidak
gemuk. Pada bayi dan anak, persentase cairan tubuh total lbih besar dibanding dengan
orang dewasa dan akan menurun sesuai dengan pertambahan usia. Pada bayi
prematur jumlah cairan tubuh total sebesar 70-75% dari berat badan, sedangkan pada
bayi normal dan pada orang dewasa sebesar 55-60% dari berat badan. Kadar lemak
pada wanita umumnyalebih bayak dibadning dengan pria, sedangkan kadar air pada
pria lebih besar dari pada wanita. Makin tua seseorang, biasanya jumlah lemaknya
meningkat sedngkan jumlah airnya makin berkurang.
Bila diperkirakan sekitar 55% berat tubuh merupakan air, maka perhitungan
cairan tubuh total menggunakan rumus :

Jumlah total air tubuh (L) = Berat badan (Kg) x 55%

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 Perhitungan ini hanya berlaku untuk individu dalam keadaan keseimbagnan
air tubuh normal. Untuk orang dewasa obesitas hasil penghitungan rumus ini
dikurangi 10%, sedangkan untuk orang kurus ditambahkan 10%.
Pada keadan dehidrasi berat, air tubuh total berkurang sekitar 10% maka pada
keadaan dehidrasi berat air tubuh total dihitung dengan menggunakan rumus:

Jumlah air total tubuh (L) = 0,9 x Berat badan (Kg) x 55%

Perhitungan di atas tidak dapat digunakan pada keadaan edema karena

kemungkinan kesalahan sangat besar.
Distribusi Cairan Tubuh
Seluruh cairan tubuh didistribusikan ke dalam kompartemen intraselular dan
kompartemen ekstraselular. Lebih jauh kompartemen ekstraselular dibagi menjadi
cairanintravaskular dan intersisial.
 Cairan intraselular
Cairan yang terkandung di antara sel disebut cairan intraselular. Pada orang
dewasa, sekitar duapertiga dari cairan dalam tubuhnya terdapat di intraselular (sekitar
27 liter rata-rata untuk dewasa laki-laki dengan berat badan sekitar 70 kilogram),
sebaliknya pada bayi hanya setengah dari berat badannya merupakan cairan
intraselular.

 Cairan ekstraselular
Cairan yang berada di luar sel disebut cairan ekstraselular. Jumlah relatif cairan
ekstraselular berkurang seiring dengan usia. Pada bayi baru lahir, sekitar setengah
dari cairan tubuh terdapat di cairan ekstraselular. Setelah usia 1 tahun, jumlah cairan
ekstraselular menurun sampai sekitar sepertiga dari volume total. Ini sebanding
dengan sekitar 15 liter pada dewasa muda dengan berat rata-rata 70 kg.
Cairan ekstraselular dibagi menjadi :
 Cairan Interstitial
Cairan yang mengelilingi sel termasuk dalam cairan interstitial, sekitar 11- 12 liter
pada orang dewasa. Cairan limfe termasuk dalam volume interstitial. Relatif terhadap
ukuran tubuh, volume ISF adalah sekitar 2 kali lipat pada bayi baru lahir
dibandingkan orang dewasa.
 Cairan Intravaskular
Merupakan cairan yang terkandung dalam pembuluh darah (contohnya volume
plasma). Rata-rata volume darah orang dewasa sekitar 5-6L dimana 3 liternya
merupakan plasma, sisanya terdiri dari sel darah merah, sel darah putih dan platelet.
 Cairan transeluler
Merupakan cairan yang terkandung diantara rongga tubuh tertentu seperti
serebrospinal, perikardial, pleura, sendi sinovial, intraokular dan sekresi saluran
pencernaan. Pada keadaan sewaktu, volume cairan transeluler adalah sekitar 1 liter,
tetapi cairan dalam jumlah banyak dapat masuk dan keluar dari ruang transeluler.
Perubahan jumlah dan komposisi cairan tubuh, yang dapat terjadi pada
perdarahan, luka bakar, dehidrasi, muntah, diare, dan puasa preoperatif maupun

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perioperatif, dapat menyebabkan gangguan fisiologis yang berat. Jika gangguan
tersebut tidak dikoreksi secara adekuat sebelum tindakan anestesi dan bedah, maka
resiko penderita menjadi lebih besar.
Cairan ekstrasel berperan sebagai :
- Pengantar semua keperluan sel (nutrien, oksigen, berbagai ion, trace mierals,
dan regulator hormon/molekul).
- Pengangkut CO2 sisa metabolisme, bahan toksik atau bahan yang telah
mengalami detoksifikasi dari sekitar lingkungan sel.

Body 100%

Water 60 %
Tissue 40 %
(100)

Intracellular Extracellular
Space 40% (60) Space 20% (40)

Interstitial Intravascular
space 15% (30) space 5% (10)

Diagram 1. Distribusi cairan tubuh

Pergerakan Cairan Tubuh

Pergerakan cairan tubuh (hidrodinamik) mencakup penyerapan air di usus,
masuk ke pembuluh darah dan beredar ke seluruh tubuh. Pada pembuluh kapiler, air
mengalami filtrasi ke ruang interstisium dan selanjutnya masuk ke dalam sel melalui
proses difusi, sebaliknya air dari dalam sel keluar kembali ke ruang interstisium dan
masuk ke pembuluh darah.
Pergerakan air juga meliputi filtrasi air di ginjal (sebagian kecil dibuang sebagai
urin), ekskresi air ke saluran cerna sebagai liur pencernaan (umumnya diserap
kembali) serta pergerakan air ke kulit dan saluran nafas yang keluar sebagai kerinat
dan uap air. Pergerakan cairan tersebut bergantung kepada tekanan hidorostatik dan
osmotik.

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Perubahan cairan tubuh
Perubahan cairan tubuh dapat dikategorikan menjadi 3, yaitu :
1. Perubahan volume

a. Defisit volume
Defisit volume cairan ekstraselular merupakan perubahan cairan tubuh yang
paling umum terjadi pada pasien bedah. Penyebab paling umum adalah kehilangan
cairan di gastrointestinal akibat muntah, penyedot nasogastrik, diare dan drainase
fistula. Penyebab lainnya dapat berupa kehilangan cairan pada cedera jaringan lunak,
infeksi, inflamasi jaringan, peritonitis, obstruksi usus, dan luka bakar. Keadaan akut,
kehilangan cairan yang cepat akan menimbulkan tanda gangguan pada susunan saraf
pusat dan jantung. Pada kehilangan cairan yang lambat lebih dapat ditoleransi sampai
defisi volume cairan ekstraselular yang berat terjadi.

Dehidrasi
Dehidrasi sering dikategorikan sesuai dengan kadar konsentrasi serum dari
natrium menjadi isonatremik (130-150 mEq/L), hiponatremik (<139 mEq/L) atau
hipernatremik (>150 mEq/L). Dehidrasi isonatremik merupakan yang paling siring
terjadi (80%), sedangkan dehidrasi hipernatremik atau hiponatremik sekitar 5-10%
dari kasus.
Dehidrasi Isotonis (isonatremik) terjadi ketika kehilangan cairan hampir sama
dengan konsentrasi natrium terhadap darah. Kehilangan cairan dan natrium besarnya
relatif sama dalam kompartemen intravaskular maupun kompartemen ekstravaskular.

Dehidrasi hipotonis (hiponatremik) terjadi ketika kehilangan cairan dengan

kandungan natrium lebih banyak dari darah (kehilangan cairan hipertonis). Secara
garis besar terjadi kehilangan natrium yang lebih banyak dibandingkan air yang
hilang. Karena kadar natrium serum rendah, air di kompartemen intravaskular
berpindah ke kompartemen ekstravaskular, sehingga menyebabkan penurunan
volume intravaskular.
Dehidrasi hipertonis (hipernatremik) terjadi ketika kehilangan cairan dengan
kandungan natrium lebih sedikit dari darah (kehilangan cairan hipotonis). Secara
garis besar terjadi kehilangan air yang lebih banyak dibandingkan natrium yang

xi
hilang. Karena kadar natrium tinggi, air di kompartemen ekstraskular berpindah ke
kompartemen intravaskular, sehingga meminimalkan penurunan volume
intravaskular.

Tabel.2 Tanda-tanda klinis dehidrasi

Symptom/sign Mild Dehydration Moderate Severe

Dehydration Dehydration
Level of Alert Lethargic Obtunded
consciousness
Capillary refill* 2 seconds 2-4 Seconds Greater than 4
seconds, cool limbs
Mucous Normal Dry Parched, cracked
membranes*
Tears* Normal Decreased Absent
Heart rate Sligh increase Increased Very increased
Respiratory rate Normal Increased Increased and
hyperpnea
Blood pressure Normal Normal, but Decreased
orthostais
Pulse Normal Thready Faint or impalpable
Skin turgor Normal Slow Tenting
Fontanel Normal Depressed Sunken
Eyes Normal Sunken Very sunken
Urine output Decreased Oliguna Oliguria/anuna
*Best indicators of hydration status

Tabel. 3 Derajat dehidrasi

Dehidrasi Dewasa Anak
Ringan 4% 4%-5%
Sedang 6% 5%-10%
Berat 8% 10%-15%
Shock 15%-20% 15%-20%

Terapi untuk dehidrasi (rehidrasi) dilakukan dengan mempertimbangkan

kebutuhan cairan untuk rumatan, defisit cairan dan kehilangan cairan yang sedang
berlangsung. Beberapa pendekatan terangkum dalam tabel 5.

Tabel.4 Pendekatan pada masalah cairan dan elektrolit

Fluid (Amount of Water) Electrolytes (Composition)

Maintance Determined by a ‘system”: Holliday- DS 0.2ns +20 mEq/L K+
Segar formula, surface area, or basal
calorie Method

xii
 Deficit Determined by acute weight change
or clinical estimate
Ongoing Losses Determined by measuring
Determined by tables
(generally DS 0.45 NS +
20 mEq/L K+)
Determines by tables for
measuring

Tabel.5 Rumatan cairan menurut rumus Holliday-Segar

Weight (kg) Kcal/d or Ml/d Kcal/h or Ml/h

0 to 10 kg 100/kg per day 4/kg per hour
11 to 20 kg 1,000 + (50/kg per day)* 40 + (2/kg per hour)*
>20 kg 1,500 + (20/kg per day)* 60 + (1/kg per hour)*

*From each kg >10.

*For each kg >20.
From Holliday MG, Segar WE, The maintenance need for water parenteral fluid therapy.
Pediatria.1957;19:823-832

Strategi untuk rehidrasi adalah dengan memperhitungkan defisit cairan, cairan

rumatan yang diperlukan dan kehilangan cairan yang sedang berlangsung disesuaikan
. Cara rehidrasi :
1. Nilai status rehidrasi (sesuai tabel 4 di atas), banyak cairan yang diberikan
(D) = derajat dehidrasi (%) x BB x 1000 cc
2. Hitung cairan rumatan (M) yang diperlukan (untuk dewasa 40 cc/kgBB/24
jam atau rumus holliday-segar seperti untuk anak-anak)
3. Pemberian cairan :
a. 6 jam I = ½ D + ¼ M atau 8 jam I = ½ D + ½ M (menurut Guillot)
b. 18 jam II = ½ D + ¾ M atau 16 jam II = ½ D + ½ M (menurut
Guillot)

b. Kelebihan volume
Kelebihan volume cairan ekstraselular merupakan suatu kondisi akibat
iatrogenik (pemberian cairan intravena seperti NaCl yang menyebabkan kelebihan air
dan NaCl ataupun pemberian cairan intravena glukosayang menyebabkan kelebihan
air) ataupun dapat sekunder akibat insufisiensi renal (gangguan pada GFR), sirosis,
ataupun gagal jantung kongestif.9,10 Kelebihan cairan intaseluler dapat terjadi jika
terjadi kelebihan cairan tetapi jumlah NaCl tetap atau berkurang.

2. Perubahan konsentrasi
Hiponatremia
Jika < 120 mg/L maka akan timbul gejala disorientasi, gangguan mental,
letargi, iritabilitas, lemah dan henti pernafasan, sedangkan jika kadar < 110 mg/L
maka akan timbul gejala kejang, koma. Hiponatremia ini dapat disebabkan oleh

xiii
euvolemia (SIADH, polidipsi psikogenik), hipovolemia (disfungsi tubuli ginjal, diare,
muntah, third space losses, diuretika), hipervolemia (sirosis, nefrosis). Keadaan ini
dapat diterapi dengan restriksi cairan (Na+ ≥ 125 mg/L) atau NaCl 3% sebanyak
(140-X)xBBx0,6 mg dan untuk pediatrik 1,5-2,5 mg/kg.12 Koreksi hiponatremia
yang sudah berlangsung lama dilakukan scara perlahanlahan, sedangkan untuk
hiponatremia akut lebih agresif. Untuk menghitung Na serum yang dibutuhkan dapat
menggunakan rumus :

Na = Jumlah Na yang diperlukan untuk koreksi (mEq)

Na1 = 125 mEq/L atau Na serum yang diinginkan
Na0 = Na serum yang aktual
TBW = total body water = 0,6 x BB (kg) Na= Na1 – Na0 x TBW

Hipernatremia
Jika kadar natrium > 160 mg/L maka akan timbul gejala berupa perubahan
mental, letargi, kejang, koma, lemah. Hipernatremi dapat disebabkan oleh kehilangan
cairan (diare, muntah, diuresis, diabetes insipidus, keringat berlebihan), asupan air
kurang, asupan natrium berlebihan. Terapi keadaan ini adalah penggantian cairan
dengan 5% dekstrose dalam air sebanyak
{(X-140) x BB x 0,6}: 140.12

Hipokalemia
Jika kadar kalium < 3 mEq/L. Dapat terjadi akibat dari redistribusi akut
kalium dari cairan ekstraselular ke intraselular atau dari pengurangan kronis kadar
total kalium tubuh. Tanda dan gejala hipokalemia dapat berupa disritmik jantung,
perubahan EKG (QRS segmen melebar, ST segmen depresi, hipotensi postural,
kelemahan otot skeletal, poliuria, intoleransi glukosa. Terapi hipokalemia dapat
berupa koreksi faktor presipitasi (alkalosis, hipomagnesemia, obat-obatan), infus
potasium klorida sampai 10 mEq/jam (untuk mild hipokalemia ;>2 mEq/L) atau infus
potasium klorida sampai 40 mEq/jam dengan monitoring oleh EKG (untuk
hipokalemia berat;<2mEq/L disertai perubahan EKG, kelemahan otot yang hebat).
Rumus untuk menghitung defisit kalium :

K = K1 – K0 x 0,25 x BB

K = kalium yang dibutuhkan

K1 = serum kalium yang diinginkan
K0 = serum kalium yang terukur
BB = berat badan (kg)

Hiperkalemia
Terjadi jika kadar kalium > 5 mEq/L, sering terjadi karena insufisiensi renal
atau obat yang membatasi ekskresi kalium (NSAIDs, ACE-inhibitor, siklosporin,
diuretik). Tanda dan gejalanya terutama melibatkan susunan saraf pusat (parestesia,
kelemahan otot) dan sistem kardiovaskular (disritmik, perubahan EKG). Terapi untuk

xiv
hiperkalemia dapat berupa intravena kalsium klorida 10% dalam 10 menit, sodium
bikarbonat 50-100 mEq dalam 5-10 menit, atau diuretik, hemodialisis.

3. Perubahan komposisi
Asidosis respiratorik (pH< 3,75 dan PaCO2> 45 mmHg)
Kondisi ini berhubungan dengan retensi CO2 secara sekunder untuk
menurunkan ventilasi alveolar pada pasien bedah. Kejadian akut merupakan akibat
dari ventilasi yang tidak adekuat termasuk obstruksi jalan nafas, atelektasis,
pneumonia, efusi pleura, nyeri dari insisi abdomen atas, distensi abdomen dan
penggunaan narkose yang berlebihan. Manajemennya melibatkan koreksi yang
adekuat dari defek pulmonal, intubasi endotrakeal, dan ventilasi mekanis bila perlu.
Perhatian yang ketat terhadap higiene trakeobronkial saat post operatif adalah sangat
penting.

Alkalosis respiratorik (pH> 7,45 dan PaCO2 < 35 mmHg)

Kondisi ini disebabkan ketakutan, nyeri, hipoksia, cedera SSP, dan ventilasi
yang dibantu. Pada fase akut, konsentrasi bikarbonat serum normal, dan alkalosis
terjadi sebagai hasil dari penurunan PaCO2 yang cepat. Terapi ditujukan untuk
mengkoreksi masalah yang mendasari termasuk sedasi yang sesuai, analgesia,
penggunaan yang tepat dari ventilator mekanik, dan koreksi defisit potasium yang
terjadi.

Asidosis metabolik (pH<7,35 dan bikarbonat <21 mEq/L)

Kondisi ini disebabkan oleh retensi atau penambahan asam atau kehilangan
bikarbonat. Penyebab yang paling umum termasuk gagal ginjal, diare, fistula usus
kecil, diabetik ketoasidosis, dan asidosis laktat. Kompensasi awal yang terjadi adalah
peningkatan ventilasi dan depresi PaCO2. Penyebab paling umum adalah syok,
diabetik ketoasidosis, kelaparan, aspirin yang berlebihan dan keracunan metanol.
Terapi sebaiknya ditujukan terhadap koreksi kelainan yang mendasari. Terapi
bikarbonat hanya diperuntukkan bagi penanganan asidosis berat dan hanya setelah
kompensasi alkalosis respirasi digunakan.

Alkalosis metabolik (pH>7,45 dan bikarbonat >27 mEq/L)

Kelainan ini merupakan akibat dari kehilangan asam atau penambahan
bikarbonat dan diperburuk oleh hipokalemia. Masalah yang umum terjadi pada pasien
bedah adalah hipokloremik, hipokalemik akibat defisit volume ekstraselular. Terapi
yang digunakan adalah sodium klorida isotonik dan penggantian kekurangan
potasium. Koreksi alkalosis harus gradual selama perode 24 jam dengan pengukuran
pH, PaCO2 dan serum elektrolit yang sering.

xv
2.2.3 Kebutuhan Tubuh Akan Air
Komponen tubuh terbesar adalah air. Tubuh orang dewasa rata-rata tersusun atas63
persenair, 17 persen protein, 13 persen lemak, 6 persen mineral dan 1 persen
karbohidrat dan vitamin. Seseorang yang mengalami kehilangan lemak dan protein
sampai terjadi penurunan berat badan sekitar 40 persen, masih mampu bertahan
hidup. Akan tetapi, kehilangan 20 persen air dapat menyebabkan kematian.
Kekurangan air melebihi 5 persen dari nilai optimal dapat menyebabkan kematian.
Laju pertukaran (turnover) yang umum adalah berkisar dari 15 persen pada anak anak
sampai 6 persen pada orang dewasa (table 14.2). tubuh memiliki beberapa mekanisme
hemeostatik yang dapat mempertahankan jumlah air dan keseimbangan air/elektrolit.
Jumlah air yang dibutuhkan per hari dapat diduga dari jumlah air yang hilang.
Untuk orang dewasa, kehilangan tersebut meliputi:
1. Kehilangan melalui urin, berkisar antara 200-900 ml tergantung dari jumlah
solutnya (urea, natrium, kalium dan klorida).
2. “Stool loss” sekitar 100ml.
Tabel 14.2 Pertukaran air per hari rata-rata dari orang dewasa dengan berat badan 70
kg

Pemasukan air Pengeluaran air

“obligatory” “facultative” “obligatory” “facultative”

Minuman 650 1000 Urin 700 1000

Makanan 750 Kulit 500

Oksidatif 350 Paru-paru 400

Feses 150

Subtotal 1750 Subtotal 1750

Total 2750 2750

3. Kehilangan yang tidak disadari melalui paru-paru dan kulit yang tidak
berkeringat, yaitu sekitar 1300 ml.
4. Kehilangat melalui keringat, yaitu bervariasi dari 1 liter untuk pekerja yang
banyak duduk pada temperature sedang sampai lebih dari 10 liter pada pekerja
di lingkungan daerah panas.
Dalam kondisi normal (aktivitas fisik sedikit dan tidak berkerinagat), kehilangan
air diduga sekitar 1.5 liter/hari. Kebutuhan normal rata-rata sebanyak 2.8 liter.

xvi
Kebutuhan air per hari pada berbagai umur di bawah kondisi normal, dapat dilihat
pada tabel 14.3.
Cara lain untuk menduga kebutuhan air adalah berdasarkan pemasukan energy.
Nilai 1ml air untuk setiap 1 kkal energy dianjurkan bagi orang dewasa dan 1.5
ml/kkal bagi anak-anak. Jumlah air akan diperlukan lebih banyak untuk diet yang
mengandung protein tinggi, khususnya anak-anak, karena ekskresi ureanya tinggi.
Kondisi lain yang membutuhkan tambahan air adalah demam, coma, muntah-muntah,
diare, poliurea dan penggunaan diyretik.

Tabel 14.3 kebutuhan air per hari (ml/kg berat badan) pada berbagi umur di bawah
kondisi normal

Umur Rata-rata berat Dugaan jumlah air yang

dibutuhkan (ml/kg)
Badan (kg)

3 hari 3.0 80-100

10 hari 3.2 125-150

3 bulan 5.4 140-160

6 bulan 7.3 130-155

9 bulan 8.6 125-145

1 tahun 9.5 120-135

2 tahun 11.8 115-125

4 tahun 16.2 100-110

6 tahun 20.0 90-100

10 tahun 28.7 70-85

14 tahun 45.0 50-60

18 tahun 54.0 40-50

Dewasa 70.0 21-43

xvii
 Konsumsi air yang berlebih sangat penting untuk orang yang banyak
mengkonsumsi protein dan lemak. Penggunaan lemak sebagai sumbee energi akan
menghasilkan asam dan keton di dalam darah. Tanpa konsumsi air yang tinggi untuk
meingkatkan volume urin yang membawa senyawa-senyawa beracun hasil
metabolism tersebut keluar tubuh, akan terjadi ketosis. Jika protein yang digunakan
sebagai sumber energi, akan menyebabkan timbulnya uremia. Kedua Keadaan
tersebut terjadi karena produk-ptoduk metabolism di dalam darah melebihi keadaan
normalnya.
Matode lain untuk menghitung kebutuhan air adalah berdasarkan luas
permukaan tubuh seeorang. Kebutuhan minimal adalah 870 ml/m2, kebutuhan rata-
rata adalah 1500 ml/m2 dan maksimum adalah 2730 ml/m2 luas permukaan tanah.

2.3 Water Balance

In the normal adult organism, not undergoing changes in weight, the quantity
of water supplied daily is balanced by that eliminated, a state of equilibrium being
maintained.

Water Intake
Water is supplied to the body from the following source: (1) dietary liquids;
(2) solid food; (3) oxidation of organic foodstuffs.
Water comprises 70-90 per cent of the weight of the average diet of adults,
even apparently very solid foods consisting largely of water. Moreover, water is one
of the chief products of combustion of protein, fat, and carbohydrate in the body, the
quantities produced by oxidation of 1 gram of each of these substances being as
follows: protein, 0.34 ml.; fat, 1.07 ml.; carbohydrate, 0.56 ml. It may be calculated
that 10-15 ml. of water are formed per 100 calories of energy produced. An ordinary
300-calorie diet therefore contains about 450 ml. of water in the solid food and may
provide an additional 300-450 ml. of water of oxidation. The remainder of the water
intake is supplied by dietary liquids (Fig. 72).

Water Output
Water leaves the body in the (1) urine, (2) feces, (3) perspiration, and (4) so-
called insensible perspiration (evaporation from skin and lungs) (Fig. 72).
Faces
Under normal conditions, the 3000-8300 ml. of digestive fluids (p. 269)
entering the alimentary tract are almost completely reabsorbed in the intestine. On an
ordinary mixed diet, about 80-150ml. of water are excreted daily in the feces of
normal adults (p. 287). This may be increased considerably on a high vegetable diet
and particularly in the presence of diarrhea.

xviii
Insensible Perspiration
In the absence of active perspiration the body is continually losing water
vapor from the skin surface and lungs in inverse proportion to the relative humidity of
the atmosphere. Inasmuch as 0.58 calorie is absorbed in the vaporization of 1 ml. of
water, the heat lost by this process, termed “insensible perspiration,” at ordinary room
temperatures amounts to about 25 per cent of the total heat loss. The latter is
proportional to the quantity of water lost by insensible perspiration is therefore an
obligatory loss, determined by metabolic activity and, in a normal adult, may be
calculated as 500 ml. per square meter of body surface area per day. This amounts to
about 850 ml. for a 70-kg. man (1.73 sq. meters).
Perspiration
When the environmental temperature and/or humidity rises to excessively
high levels, the sweat glands become active. Obviously, the quantity of water lost by
this route varies enormously. Moreover, in contrast 30 to 39 mEq./liter of Na and of
Cl (Fig. 76, p. 341). It is a hypotonic solution, plasma containing about 140 mEq./liter
of Na. Sweating therefore removes from the body relatively more water then
electrolytes.
Urine
The urine is the important medium of elimination of water provided to the
body in excess of its fixed requirements. The kidneys have a remarkable capacity for
regulating urinary excretion of water, within wide limits, regardless of the
simultaneous requirement for excretion of solids in solution (p. 843). However, their
ability to concentrate is not unlimited, a certain minimal quantity of water being
required for excretion of given among of solute. On an average adequate died
(adults), providing about 50 grams of solids for daily urinary excretion, a minimum
of approximately 500 ml. of water (300 ml./sq. meter body surface) is required for
their solution. Failure to meet this obligatory urine volume requirement will result in
retention of certain urinary constituents, mainly urea, in the body fluids.
Equilibrium Requirements
As indicated above, in addition to the small amount excreted in the feces (80-
150 ml.), the minimal daily water requirement is fixed by curtain metabolic
requirement: (1) loss of head by insensible perspiration (normally about 850 ml.); (2)
renal excretion of excess solid material, mainly urea and NaCl, and therefore
determined largely by the protein and salt intake (normally about 500 ml. of water ).
Consequently on an average normal diet, approximately 1500 ml. of water must be
available for elimination by these routes in the body temperature and blood urea N
are to be maintained within normal limits. The “solid” portion of such a diet
contributes about 800 ml. of water, approximately one-half of which is pre-formed,
the remainder being produced in the course of oxidation of the organic foodstuffs in

xix
the body. The balance of the water requirement must be supplied by intake of liquids
if the body fluids are to be maintained at a normal level.

Volume Of Body Fluid Compartements

Water comprises 60 to 70 per cent of the adult body weight, values expressed in this
manner being somewhat lower in women than in men, and decreasing with advancing
age. These age and sex differences after puberty are probably due to differences in the
amount of body fat, which has a low water content (Table 30). Classically, the body
water has been regarded as existing in two main compartments, (1) intracellular
(approximately 50 per cent body), and (2) extracellular (approximately 20 per cent),
the latter being further subdivided into (a) blood plasma water (about 5 per cent body
weight) and (b) interstitial fluid (about 15 per cent ). Although segregation into these
anatomical compartments is useful from many standpoints, it cannot be applied
strictly to physiological considerations. This is particularly important in relation to
the distribution and exchanges of electrolytes between the various body fluids (p.
318). From the standpoint of volume alone it seem desirable to regard the
extracellular water as existing in four main subdivisions: (1) blood plasma (about 4.5
per cent body weight); (2) interstitial fluid and lymph (about 12 per cent); (3) dense
connective tissue, cartilage and bone (about 9 per cent); (4) transcellular fluids (about
1.5 per cent). The latter term is applied to extracellular fluids that are not simple
ultrafiltrates of the blood plasma and which are formed by the transport activity of
cells (e.g., secreations of the gastrointestinal tract, liver and skin; fluids in the
kidneys, eyes and subarachnoid space).
The anatomical fluid compartments are illustrated in Figure 72. Water
entering the organism, i.e., from the gastrointestinal tract, passes into the blood
stream, and equivalent amount leaving the latter by way of the urine, lungs, skin and
feces. The water of the plasma is in equilibrium with that of the interstitical fluid and
the latter with the intracellular water, across the boundaries between these
compartments, i.e,. the capillary walls and the cell membrans, respectively. The
interstitial fluid, serving as a sort of middleman for the order two fluids, acts also as a
buffer which prevents rather sudden changes in composition of the plasma, resulting
from absorption from the intestine, from being reflected directly in the intracellular
fluid. More over, being a rather elastic compartments , it can expand or contract
considerably, it conditions of excessive retention (edema) or loss (dehydration) or
fluid, without comparable alterations in the volume of plasma or intracellular fluid,
which must be maintained rather rigidly in the interest of normal circulation and cell
function.

xx
Average Water Content of Tissue

TISSUE WATER (PER

CENT)

Muscle 75-80

Connective Tissue 60

Adipose Tissue 20

Bone 25

Nervous Tissue

White Matter 70

Grey Matter 85

Erytrocytes 60

The volume of (1) the circulating blood, (2) the plasma, (3) total extracellular
fluid, and (4) total body water could be measured by introduction of a substance into
the body if that substance would fulfill the following requirements: (a) be retained
exclusively in the fluid compartment in question; (b) not leave that compartment
during the test period; (c0 distribute itself uniformly throughout that compartment;
(d) be capable of precise quantitative determination in the blood or plasma. A number
of methods have been proposed, none of which is entirely satisfactory; certain of
them, however, have proved useful.

xxi
Blood and Plasma Volume
(a) Carbon monoxide method. Carbon monoxide displace from hemoglobin,
volume of volume, and can be measured accurately in blood, either as CO
or as HbCO. The subject breathes a known amount of CO and the
concentration oh HbCO in the blood is determined after allowing,
sufficient time for missing. If the total hemoglobin concentration is
known, one can calculate how much CO would be required to saturate the
Hb to its full capacity and can arrive at the total blood volume. By
determining the hematocrit value (relative volumes of packed cells and of
plasma), the plasma volume can be derived.
(b) Radioactive iron method. Fe59 is administered to a normal or anemic
subject; it becomes incorporated in the Hb of the circulating erythrocytes.
A predetermined amount of the labeled red cells is injected intravenously
in the test subject (compatible blood). Measurement of radioactivity in
blood samples withdrawn after allowing time for mixing indicates the
extent of dilution of the injected cells and permits calculation of the
volumes of blood and plasma (from hematocrit value).
(c) Dye methods. The dye employed most commonly is Evans blue (T-1824),
which is adsorbed by plasma proteins. A known amount is injected
intravenously and, after allowing time for distribution throughout the
blood plasma, a sample oxalated blood is withdrawn, centrifuged, and the
concentration of dye in the plasma determined colorimetrically. The
extend of dilution of the quantity injected can be calculated (plasma
volume) and, the hematocrit value being known, the total blood volume
can be determined.
(d) I131 .labeled proteins. Serum proteins, labeled with I131, are injected
intravenously and the extent of dilution of the injected protein is

xxii
 determined by measurement of the radioactivity of withdrawn blood
samples.
The CO method requires cooperation of the subject, which cannot always be
secured under clinical conditions. Moreover, other technical difficulties
introduce the possibility of serious errors. Furthermore, the accuracy of this
procedure, as well as of the Fe59 method, depends upon uniformity of
distribution of all the “labeled” erythrocytes in the circulation. This cannot
always be assured, especially in disease states (e.g.,shock), in which variable
and undeterminable numbers of cell may be “segregated” in such organs as
the spleen or in the splanchnic bed. In addition, calculations of total blood
volume on the basic of factors measured in either cells or plasma are subject
to inaccuracies arising out of variations in the ratio of cells to plasma in
different portions of the circulation.
One source of inaccuracy with the use of dyes and isotope-tagged serum
proteins is the fact that these proteins normally cross the capillary wall in
amounts which vary in different tissues; they are removed from the interstitial
fluid mainly by the lymphatic circulation. Approximately 50 per cent of the
plasma protein pool is in the interstitial fluid-lymph compartment and,
following intravenous injection of tagged protein, the latter is evenly
distributed throughout the entire extracellular space in about 24 hours.
Although under normal conditions loss of protein from the intravascular
compartment under the test conditions is not so rapid as to vitiate the
usefulness of these procedures, it may become so in many disease states in
which capillary permeability is increased.
Generally acceptable average values for blood and plasma volume in normal
subjects are as follows: whole blood, 2500-3200 ml./sq. meter body surface ,
or 63-80 ml./kg.; plasma, 1300-1800 ml./sq. meter, or 35-45 ml./kg. Values
for whole blood are about 7 per cent higher for men than for women, but the
plasma values are approximately the same.

Total Extracellular Fluid Volume

Application of the dilution technique to the measurement of the total volume
of extracellular fluids theoretically requires the use of a substance which,
when injected intravenously, crosses the capillary walls readily and distributes
itself rapidly and uniformly throughout all extracellular fluids, does not enter
the cells, is not destroyed in the body, and is not excreated rapidly. Substances
that have been used fot this purpose include certain nonmetabolizable
carbohydrates (sucrose, mannitol, inulin) and electrolytes (thiocyanet,
radioactive sodium, radioactive chloride, sulfate, bromide). There are two
major sources of inaccuracy of results obtained with these procedures: (1)the

xxiii
heterogeneous character of the intracellular fluids with respect to composition
(p. 315); (2) certain of the substances employed, particularly electrolytes, are
not absolutely excluded from the intercellular compartment, but penetrate
different cells to different degrees under normal conditions and particularly in
pathological states.
There are marked differences in the rates of equilibration of extracellular
fluids in muscle, skin, loose and dense connective tissue, cartilage and bone.
In certain of these extracellular fluids equilibrate rapidly; in others, e.g., dense
connective tissue and cartilage and certain regions in bones, they equilibrate
very slowly. Furthermore, some of the tracer substances employed (e.g.,
inulin, mannitol) do not enter the transcellular fluids, the volumes of which
may vary enormously in certain disease states.
The major electrolytes of extracellular fluid, Na, and Cl are present in only
low concentrations in intracellular fluid generally under physiological
conditions. However, both Na and Cl enter different cells to a variable degree
and not always to the same extent, the Na:Cl ratio in certain tissues (bone,
cartilage, muscle) being higher and in others (erythrocytes, connective tissue,
gastrointestinal mucosa) lower than in an ultrafiltrate of blood plasma.
Moreover, there are marked differences in the rates at which equilibrium is
established between different phases of the extracellular pool of Na. For
example, in bone, which contain 35-40 per cent of the total body Na, only
about 30 per cent is rapidly exchangeable, 10 per cent slowly exchangeable
(incorporated in the bone crystal, p.650).
Values obtained by the use ogf the electrolytes tend to be too high and those
with saccharides too low. For the reasons indicated, it is preferable to use the
designations, “sodium space”, “chloride space”, “thiocynate space” and
“inulin space”, etc., rather than “extracellular fluid volume” . The inulin space
seems to correspond most closely to the extracellular fluid volume in most
cases. Employing these procedures, values have been obtained for total
extracellular fluid volume (adults) approximating about 20 per cent of the
body weight. Of this, about one-fourth is blood plasma and three-fourth is
interstitial fluid and lymph (5 amd 15 per cent, respectively, of body weight).
Total Body Water
There is no accurate method for determining total body water, inasmuchas no
measurable substances has yet been found which, on injection, is distributed
uniformly throughout the entire body water and undergoes no metabolic
change during the test period. Heavy water and antipyrine are most
satisfactory for clinical purposes.
The water content of several tissues (Table 30) has been determined by direct
measurement (animals and human biopsy or autopsy material).

xxiv
Composition Of Body Fluid Compartrments
Inasmuch as water serves chiefly as a relatively inert medium in which are
conducted the chemical reactions constituting living processes, its
significance must be considered in relation to the other components of the
body fluids which , in fact, largely determine its volume and distribution in
the organism. The marked differences in composition of the intracellular and
interstitial fluids and the less striking differences between the latter and the
blood plasma are due differences in permeability of the membranes separating
these compartments to the solutes which these fluids contain.
Milliequivalents (mEq.)
Elements which combine chemically with one another do so in fixed ratios,
which are functions of their atomic weight and valences . Thus, 1.008 grams
of hydrogen (at. Wt. 1.008) combines with 8 grams of oxygen (at. Wt. 16) to
form water, and with 35.457 grams of Cl (at.wt. 35.457) tp form HCl.
Similarly, 35. 457 grams of Cl combine with 22.997 grams of Na, 39.096
grams of K, and 20.04 grams of Ca (at. Wt. 40.08). These numerical values
are designed “equivalent weight”, because they are equivalent in their
combining power. An “equivalent weight” may be defined as the weight of a
molecule, or of an atom or radical (group of atoms reacting chemically as a
unit ), devided by its valence. A “miliequivalent: (i.e., milligram equivalen t)
is 1/1000 of the gram equivalent weight.
The concentrations of the solid constituents of the body fluids may be
expressed in terms of weight per unit volume (e.g., miliigrams per 100 ml) or
in terms of chemical combining power (e.g.,milliquivalents per lier)
(mEq./liter). The power may be converted to the latter according to the
following formula:
1
1 𝑚𝑔. (= 𝑚𝑔. 𝑚𝑙. 𝑥10 𝑥 𝑣𝑎𝑙𝑒𝑛𝑐𝑒
mEq. = 𝑙𝑖𝑡𝑒𝑟
liter 𝑎𝑡𝑜𝑚𝑖𝑐 𝑜𝑟 𝑟𝑎𝑑𝑖𝑐𝑢𝑙𝑎𝑟 𝑤𝑒𝑖𝑔ℎ𝑡

Osmolar Concentration
Although absolute osmotic equilibrium is probably never attained in living
tissues, all internal body fluids, ectracellular and intracellular, tend to have an
equal osmotic pressure. Osmotic pressure is a function of the concentration of
active chemical components in a solution, i.e., the number of ions and moles
(undissociated compounds). The designation “osmole” in a applied to one
chemically active mole or ion. Although all solutions of identical osmolarity
do not necessarily have the same osmotic pressure (e.g., solutions of

xxv
electrolytes vs. Non-electrolytes), under conditions existing in the body fluids
osmolarity may be regarded as a satisfactory equivalent for osmotic pressure.
A solution containing 1 osmole (expressed in grams) of solute per liter of
water depresses the freezing point of the water by 1.860C. The freezing point
of blood plasma is -0.560C. It must, therefore , contain osmotically active
solutes in a total concentration of 0.56/1.86 or 0.30 osmoles per liter (320
milliosmoles per liter of water). The other body fluids with equal osmotic
pressures also have the same osmolar concentration of solutes (320
milliosmoles/liter of water), of which non-electrolytes contribute about 10
milliosmoles.

ELEMENT OR VALENCE ATOMIC OR EQUIVALENT

ION RATICULAR WEIGHT
WEIGHT

H 1 1.008 1.008

Na 1 22.997 22.997

K 1 39.096 39.096

Cl 1 35.457 35.457

Ca 2 40.08 20.04

Mg 2 24.32 12.16

HCO3 1 61.018 61.018

HPO4 2 95.988 47.994

H2PO4 1 96.996 96.996

SO4 2 96.066 48.033

TOTAL EXTARCELLULAR

Na CATIONS
CATIONS
Cl HCO3 ANIONS
NS
TOTAL INTRACELLULAR

Mg K CATIONS
xxvi
HPO4
HCO3
PROT

ANIONS
In this connection, the components of the body fluids may be classified
conveniently as follows:
1. Compounds of very large molecular size, e.g., proteins, lipids, glycogen,
to which all but a few capillary and cell membranes are almost completely
impervious. Inasmuch as osmotic pressure is proportional to the number
of active chemical components per unit of water, these compounds,
because of their large molecular size, exert relatively little effect on
osmotic pressure in proportion to their concentration on a weight basis.
For example, the concentration of plasma proteins, about 7 grams per 100
ml of plasma, with molecular weights of about 70.000 to over 1.000.000
represents only about 2 milliosmoles per liter. Moreover, since these
larger compounds displace a large volume of water and the osmolar
concentration is expressed in terms of units per liter of water, correction
must be made for this displacement. In the case of plasma, this correction
factor is 0.93,the total osmolar concentration being 301 milliosmoles per
liter of plasma (320 milliosmoles per liter of plasma water), 10 contributed
by non electrolytes.
2. Electrolytes, which cross capillary walls freely, but to certain of which
various cell membranes exhibit a variable degree degree of impermeability
under different conditions. Electrolytes dissociate into ions and therefore
exert an osmotic pressure greater than their molar concentrations because
the ions be have as units. The osmolar concentration of NaCl is pratically
twice its molar concentration because it dissociates almost complately into
Na+ and Cl-. One millimole of CaCl2 represents three milliosmoles,
dissociating into Ca++ + 2Cl-. In the presence of large amounts of protein,
certain elements, e.g., Ca and K, may exist as relatively poorly dissociated
salts of protein, being osmotically active only to the extendt of the degree
of dissociation.
3. Organic compounds of a molecular size which permits their free diffusion
across capillary walls, e.g., urea, glucose, amino acids. Some cell

xxvii
 membranes many be relatively impermeable to certain of these, as to
certain electrolytes.

Extracellular Fluid
All body cells exist in an environment of fluids collectively designated
“extracellular fluid”. These include the blood plasma, interstitial fluid, lymph, and
peritoneal, pericardial, pleural and joint fluids. Transcellular fluids also belong in this
category (p. 312), i.e., fluids formed by the gastrointestinal mucosa and other
digestive glands, liver, kidneys, etc. These differ from other extracellular fluids in
that they are formed by active cellular mecanisms and therefore do not resemble
ultrafiltrates of the blood plasma. The heterogeneous character of the interstitial fluid
is reffered to elsewhere (p. 312); from a physiological standpoint, there are distinct
differences in this respect between muscle, skin, dense connective tissue and
cartilage,and bone. With these exceptions and reservations, most of the extracellular
fluids may be regarded as having an essentially uniform qualitative composition.
What quantitative differences exist are due chiefly to differences in the concentrations
of proteins, which range from about 7 per cent in plasma and but slightly less in
hepatic lymph, to about 0.1 per cent in the subcutaneous interstitial fluid. They are
solutions chiefly of NaCl and NaHCO3 with small amounts of Ca, Mg, K, H,
phosphate, sulfate, and organis acid ions, variable amounts of protein, some non-
electrolythes (glucose, urea, lipids, etc) and with Ph values ranging from 7.35 to 7.45
under normal conditions.
The total concentration of the ionic constituents is about 310 mEq per liter
of plasma (about
335 mEq per liter pf plasma water ). The difference is due mainly to the relatively
high protein content of the plasma . In accordance with the laws of electrical
neutrality, cations and anions each comprise half of the (gambar) total concentration,
expressed in terms of chemical equivalence. Proteins, being amphoteric (p. 65 ff. ),
act as anions in these slightly alkaline fluids, the chemical composition of which is
indicated in Figure 74. Attention should be drawn to the distinction between this
anionic function of these proteins and their buffering capacity. The former is a
reflection of the net over-all charger on the entire molecule at the existing pH of the
solution, whereas the latter is a function almost exclusively of the imidazole groups
of their histidine component (p. 69 ff.).
The milliequivalent value for protein is obtained by multiplying grams of
protein per liter by 0.243 (Van Slyke factor). Each millimole (mmole) of protein
represent about 8 milliequivalents (mEq.), which accounts chiefly for the discrepancy
between the ionic osmolar and equivalent values for plasma. At the pH of
extracellular fluid, 80 per cent of the phosphate radical carries two equivalents
(𝐵2HP𝑂4) and 20 per cent one equivalent of cation (𝐵2HP𝑂4). The valence of
phosphate is therefore calculated as 1.8. The commonly used designations of carbonic

xxviii
acid and bicarbonate values in term of “volumes per cent 𝐶𝑂2” (p. 338) may be
converted to milliequivalents per liter by dividing by 2.22.
The relative importance of the several components of the extracellular fluids
in preserving osmotic, anion-cation, and acid-base balance is indicated by their
osmolar and equivalent concentrations, respectively (Fig. 73; Fig. 74). However,
those components, particularly cations, which are present in comparatively low
concentrations, viz., 𝐾 + , 𝐶𝑎++ , 𝑀𝑔++ , and 𝐻 + , exert profound influences upon a
variety of physiological process. Therefore, relatively slight deviations from their
normal concentrations produce significant biological effects.
As illustrated in Figure 74, the chief general structural difference between the
two main compartments of extracellular fluid, i.e., blood plasma and interstitial fluid,
is the relatively large amount of protein in the former. The presence of this non-
diffusible component result in certain readjustments of the diffusible ions in order to
maintain anion-cation equivalence (Donnan equilibrium, p. 319). Consequently, the
interstitial fluid contains a somewhat higher total concentration of diffusible anion
and a lower concentration of cation than does the plasma.

xxix
xxx
Intracellular Fluid
In contrast to the rather complete and precise information available regarding
the composition of extracellular fluids, knowledge of the chemical structure of
intracellular fluids is fragmentary and incomplete. It seems obvious that differences
in structure and function of cells of various tissues might be reflected in differences in
their chemical constitution, in contradistinction to the comparatively uniform
composition of most extracellular fluids. Moreover, the previous concept of an
intracellular compartment separated from extracellular fluids by a cell membrane
must be revised in the light of present knowledge that various cell constituents may
be distributed unequally between the soluble phase of the cytoplasma and the
particulate components (nucleus, mitochondria, endoplasmic, microsomes), each of
which has a limiting membrane. Nevertheless, it is useful to describe the major
differences between typical extracellular fluids and the most abundant of the
intracellular fluids, i.e., that of skeletal muscle which may, with certain exceptions, be
regarded as typical of most cells.
Whereas Na is the major cation in the extracellular fluid (142 mEq./liter),
much smaller amounts are present in the intracellular fluids (0-40 mEq./liter), which
also contain little or no Ca. The chief cations of the latter fluids are K, about 140
mEq./liter in muscle, and Mg, about 40 mEq./liter in muscle(5 and 3 mEq./liter
respectively in plasma). As regards anions, the intracellular fluids contain much more
phosphate and sulfate ions and protein than do the extracellular fluids. Cl, the major
anion of the extracellular fluids, is practically absent from the intracellular fluids,
expect in the case of erythrocytes (Fig. 74), and cells of the kidney, stomach, and
intestines. Cells of the latter organs contain Na and Cl, since they are engaged in
reabsorption or secretion of these elements. However, in these situations, Na and Cl
are apparently not in diffusion equilibrium with the extracellular fluid. 𝐻𝐶𝑂3 − is the
only ion which exist in both fluids in concentrations of even approximately
comparable magnitude. Because of the large volume of intracellular fluid,
intracellular Na and Cl, despite their low concentrations, comprise about one-third of
the total exchangeable Na and Cl of the body.
The market differences in concentrations of Na and K in the extra- and
intracellular fluids indicate a certain degree of impermeability of the cell membranes
to these ions. This impermeability is, however, not absolute nor fixed, both ions being
able to cross the membrane more freely under certain physiological and pathological
conditions (p. 324). It would appear that as K leaves the cell in increased amounts, Na
and H enter, the total cationic concentration being thereby maintained approximately.
The bulk of the phosphate is in organic combination and the extent of
dissociation of these compounds is not known. Similarly, much of the Mg and
perhaps of the K is undoubtedly present as undissociated salt of protein and organic
phosphate and, therefore, is not in ionic form. Furthermore, the concentration of
protein ions has not been established accurately and the estimated 𝐻𝐶𝑂3 −
concentration is subject to correction for carbamino-𝐶𝑂2 (p. 306). These factual

xxxi
deficiencies contribute to the present uncertainty regarding the constitution of the
intracellular fluids on an osmolar and equivalent basis.

Exchanges Between Fluid Compartments

The continual entrance into the body of substances from without (oxygen,
water, organic and inorganic foodstuffs, etc.) and production by the cells of a great
variety of metabolites, many of which much be distributed to other tissues or be
excreted, imply a continual movement of various components of the body fluid
compartments across the boundary membranes (capillaries and cell walls). The most
important of these exchange systems may be outlined as follows:
1. Alveolar air : blood plasma (p. 287). This system provides for entrance of
oxygen into and loss of 𝐶𝑂2 and water from the body.
2. Plasma : erythrocyte (p. 304). This system provides for ready exchange of
oxygen, 𝐶𝑂2, water, and certain anions (particularly 𝐶𝑙 − and 𝐻𝐶𝑂3 −) in
both directions. Cations are exchanged very slowly.
3. Plasma : interstitial fluid. These two media are separated by the capillary
walls, which are perfectly permeable to water, inorganic ions, and small
organic molecules (e.g.., glucose, amino acids, urea, etc.) but not to large
organic molecules, such as proteins.
4. Interstitial fluid : intracellular fluid. These two compartments are separated
by the cell membranes, across which gases, water, and small, uncharged
molecules can diffuse readily, but across which certain electrolytes, under
normal conditions, cannot, at least not freely. These membranes are also
relatively impermeable to large molecules, such as proteins, except in special
situations, vi ., the liver.

The first two of these system are discussed in the section on

respiration (pp. 296-306)

since they are intimately concerned with the transport and exchanges of oxygen and
𝐶𝑂2.

Gilbbs-Donnan Equilibrium

If two solutions are separated by a membrane which is freely permeable to the

solvent and solutes, the concentrations of the latter will be identical when equilibrium
is established. Thus, both the chemical composition and the osmotic pressures of the
two solutions will be the same.
Na+ Na+ Na+

K+ K+ K+

I- I- I-

Cl- Cl- Cl-

(I)
xxxii (II)
 (I) (II)

If, on the other hand, one of the solutions contains an electrolyte, e.g., NaCl, to which
the membrane is permeable, and the other contains one, e.g., Na proteinate (NaR) in
which R is a monovalent anion too large to pass through the membrane, the
distribution of 𝑁𝑎 + and 𝐶𝑙 − at equilibrium will be unequal on opposite sides of the
membrane. If both electrolytes are completely dissociated, the situation of
equililibrium may be represented as follows:

Na+
Na+ Na+ Na+

R-
Cl-

R- Cl- Cl-
(I) (II) (I) (II)

𝑁𝑎+ and 𝐶𝑙 − ions diffuse in pairs, preserving electrical neutrality, from

solution (II), into solution (I), and subsequently in the reverse direction, until
equilibrium is established, the net result being loss of 𝑁𝑎 + and 𝐶𝑙 − from solution (III)
and their addition to solution (I). These changes in distribution can be expressed
quantitatively if one assumes that there are no volume changes, i.e., that only ions are
transferred, and not water.

Let x represent the number of 𝑁𝑎+ and 𝐶𝑙 − ions lost from (II) and added to
(I), a the original number of 𝑁𝑎 + and 𝑅 − ions in (I), and b the original number of
𝑁𝑎+ and 𝐶𝑙 − ions in (II). The ionic distribution at equilibrium may be represented
quantitatively as follows:

(a + x) Na+ Na+ (b – x)

(a) R- Cl- (b –x)

(b) Cl-

(I) (II)

Inasmuch as the total number of positive and negative charges must be equal
on a given side of the membrane, a 𝑁𝑎+ ion cannot move in either direction without a
𝐶𝑙 − ion. The probability of these two ions reaching and passing through the
membrane at the same instant is proportional to the product of their concentrations on
that side of the membrane. At equilibrium, therefore, when equal amounts of
diffusible electrolyte pass in opposite directions. These concentration products must
be equal.

xxxiii
 Na+(I). Cl-(I) = Na+(II). Cl-(II)

Or (a + x)x = (b – x) or (b – x)2

This is the fundamental Donnan equation, expressing the quantitative aspects of this
situation, referred to as the Gibbs-Donnan equilibrium. This equation may also be
written:

Ax + x2 = b2 – 2bx + x2

Or ax = b2- 2bx

Or ax + 2bx = b2

Or (a + 2b)x = b2
𝑏2
Or x=
𝑎+2𝑏

Since in solution (I) the cation 𝑁𝑎+ must balance two anions, 𝑅 − and 𝐶𝑙 − , the
concentration of 𝑁𝑎 + will exceed that of 𝐶𝑙 − , whereas they will be equal in solution
(II). Therefore, the product of the concentrations of 𝑁𝑎+ and 𝐶𝑙 − in solution (II)
represents a square, but not in solution (I). it follows, too, that whereas 𝑁𝑎 + in
solution (I) exceeds 𝑁𝑎+ in solution (II), 𝐶𝑙 − in solution (II) exceeds 𝐶𝑙 − in solution
(I).

The quantitative ionic relations for the Gibbs-Donnan equilibrium may be

state as follows: The concentration of a diffusible positive ion (cation) is higher and
that of a diffusible negative ion (e.g., protein), i.e.,

Na+(I) > Na+(II) and Cl-(I) < Cl-(II)

It must be understood that these consideration apply only when the volumes of the
solutions on the two sides of the membranes remain constant and only ion transfer
occurs.

It can also be shown that, in the presence of several different diffusible ions,
their distribution ratios will be as follows:
−
𝑁𝑎+ (𝐼) 𝐾 + (𝐼) √𝐶𝑎++ (𝐼) 𝐶𝑙 − (𝐼𝐼) 𝐻𝐶𝑂3 − (𝐼𝐼) √𝑆𝑂4 (𝐼𝐼)
+
= + = = −
= − = −
𝑁𝑎 (𝐼𝐼) 𝐾 (𝐼𝐼) ++
√𝐶𝑎 (𝐼𝐼) 𝐶𝑙 (𝐼) 𝐻𝐶𝑂3 (𝐼) √𝑆𝑂4 (𝐼)

Gibbs-Donnan Effect and Osmotic Pressure

xxxiv
 Certain additional facts arise out of the mathematical considerations outlined
above, incident to the presence of a non-diffusible ion on one side of the membrane.

1. At equilibrium, if the volume of the solvent is kept constant, the sum of the
concentrations of diffusible ions in solution (I) (containing the non-diffusible
ion) exceeds the sum of the concentrations of the same ions in solution II, the
sum of the factors in a square being less than the sum of the factors in the
same product which is not a square. If the value for a and for b is represented
𝑏2
as 1 mole, the value for x, according to the Donnan equation 𝑋 = , will
𝑎+2𝑏
be 0,33 mole, and the quantitative distribution of 𝑁𝑎 , 𝐶𝑙 and protein (𝑅 − )
+ −

will be as follows:

Na+ (a + x) = 1.33 Na+ (b – x) = 0.66

Cl- (x) = 0.33 Cl- (b – x) = 0.66
R- (a) = 1.0
(I) (II)

2. The total ionic concentration in solution (I) exceeds that in solution (II).
Consequently, the former will have a higher osmotic pressure than the latter,
determined not only by the concentration of the non-diffusible ion, but also
by the higher concentration of diffusible ions.
The Gibbs-Donnan effect is of physiological significance in biological
system involving

ion exchanges across permeable membranes, especially when the fluid on one side of
the membrane contains a non-diffusible component, e.g., protein, in high
concentration. It finds particular application in exchange of 𝐶𝑙 − and 𝐻𝐶𝑂3 −
between the blood plasma and erythrocyte and in water and ion exchanges between
the blood plasma and interstitial fluid (i.e., across the capillary wall).

Plasma : Interstitial Fluid Exchange

Exchange between the blood plasma and interstitial fluid occur across the
endothelial lining of the capillaries, which act as semipermeable membranes,
allowing free passage of water and crystalloid solutes, inorganic and organic, but not
off colloids of large molecular size, viz., proteins. This impermeability to proteins is
not absolute nor uniform, the concentration of protein in interstitial fluids varying
from 0.05-0.5 per cent in subcutaneous tissues and serous cavities to 4-6 per cent in
liver. The concentrations of diffusible electrolytes on the two sides of the capillary
will vary, their distribution depending upon the difference in protein concentration in
the two fluids (Gibbs-Donnan effect, p. 319). The osmotic pressure will be greater in

xxxv
the plasma than in the interstitial fluid, owing both to the higher protein concentration
(colloid osmotic pressure ; C.O.P.) and to the consequent higher concentration of
diffusible ions (p. 321). Such freely diffusible organic solutes as urea, glucose,
creatinine, etc., being non-ionized, are not subject to the Donnan effect and are
distributed equally throughout the body water. Their diffusion across semipermeable
membranes is therefore determined by their concentration gradients.

In the absence of opposing forces, water and crystalloid solution will tend to
pass from the interstitial fluid to the plasma, which contains protein in higher
concentration, thereby producing an osmotic pressure gradient. This tendency is
counterbalanced by the opposing force of the capillary blood pressure and is also
modified by the concentration gradients of the individual solutes.

The colloid osmotic pressure (C.O.P.) of the proteins of normal plasma is

about 22 mm. Hg (30 cm. 𝐻2 𝑜). The capillary blood pressure varies considerably in
different tissue, but is higher than the C.O.P. at the arterial end of the capillary and
lower than the C.O.P. at the venous end. Consequently, filtration from the plasma
occurs at the arterial end and reabsorption into it at the venous end of the capillary.
Moreover, the increasing concentration of non-diffusible colloids (viz., proteins)
which result from loss of plasma water, creates a relatively small but actual gradient
of C.O.P., which further favors reabsorption as the blood pressure falls in the distal
end of the capillary. This mechanism (Starling hypothesis) provide for a continual
circulation of fluid between the capillaries and than tissue spaces, a balance being
maintained between the quantity of water filtered and that reabsorbed. Exchanges of
diffusible solutes between these two fluid depend upon these circumstances and also,
independently of them, upon their individual concentration gradients. The factors
concerned with the transfer of materials across the capillary wall are therefore those
of diffusion, osmosis, and hydrostatic pressure.

Filtration from the capillaries is opposed by the tissue tention, which varies
considerably in different situations, being relatively low in loose areolar tissues (e.g.,
eyelids, external genitalia) and high in dense tissue (e.g., muscle,liver, etc). Fluid
leaves the tissue spaces not only by direct reabsorption into the blood plasma but also
by filtration across the lymph capillaries, ultimately reaching the venous blood by
way of the lymphatic circulation.

Interstitial Fluid: Intracellular Fluid Exchange

Exchange between these two compartments occur across cell membranes,
which are generally freely permeable to gases, water, and small uncharged molecules
( urea, glucose, etc.) but not to large colloidal molecules, such as proteins. The
enormously higher concentration of proteins and other colloids in the intracellular
than in the interstitial fluids would cause a much greater osmotic pressure within the
cells (Gibbs-Donnan effect, p. 321) were it not for the fact that the cell membranes
are generally not freely permeable to inorganic ions, especially certain cations.

xxxvi
Consequently, the electrolyte composition of cells is quite as distinctive as their
organic constitution (Fig. 74,p. 316). Because of this limited permeability to
inorganic ions, adjustment to deviations of osmotic pressure is usually accomplished
largely by transfers of water, not by exchanges of electrolytes, the freely diffusible
organic solutes (urea, creatinine) moving with the water.
Inasmuch as the concentrations of protein in the body fluids are more stable
than the concentrations of inorganic ions, the letter constitute the dominant factor in
determining the total osmotic pressure and the exchanges of water between the body
fluid compartments. The milliequivalent value of the extracellular fluids (310
mEq./liter) approximates their milliosmolar value (Fig. 73) because of the enormous
preponderance of univalent ions. This is not true, howeve, of the intracellular fluids,
the total milliosmolar value of which approximates that of extracellular fluids, but the
milliequivalent value of which is considerably greater (about 390), because of the
relatively high concentrations of multivalent ions (Mg++, SO4=, HPO4=, protein).
It is probable that exchanges of water across the outer cell membrane proceed
passively, in relation to changes in osmotic pressure, diffusion of various metabolites,
and active transport of other substances, which occur continually in actively
metabolizing tissues. However, it is probable, too, that under these circumstances a
state of absolute osmotic equilibrium, although constantly approached, is never
reached.
The much higher concentrations of Na+ and Cl- in interstitial fluid and of K+
in intracellular fluid are accompanied by a difference in electrical potential, that of
resting skeletal muscle cells being about 90 millivolts negative to the interstitial fluid.
It is believed that lipid-protein membrane plays an important role in determining and
maintaining these differences in concentration and potential. K+ ions tend to diffuse
out of and Cl- ions into the cell because of their concentrations gradients, but this is
almost exactly counterbalanced by a tendency to diffuse in the opposite direction due
to the difference in electrical potential, i.e., the relative negativity on the inside of the
cell tends to keep Cl- out and K+ in. in the case of Na+, however, diffusion into the
cells is favored by both concentration gradient and electrical potential. Under normal
conditions, there must be some mechanism for removing Na+ from the cell virtually
as rapidly as it enters. Since this is accomplished in opposition to forces of
concentration and electrical potential, it involves expenditure of energy, derived from
cellular metabolism. This process of active transport of Na+ out of the cell is referred
to as the “sodium pump,” which effectively excludes Na+ from the intracellular fluid
(resting muscle). It has been suggested that pyridoxal phosphate (p. 198), due to its
capacity for forming metal chelates, may serve as the carrier of cations across the cell
membrane. This is based on observations that passage of K+ into the cell is
accompanied by diminution in intracellular concentration of amino acids, whereas
increase of Na+ in the cell. Phosphatides, too, have been proposed as important
components of the transport system. The dependence of this function of the cell
membrane upon metabolic processes in the cell is illustrated by the fact that if cells

xxxvii
are incubated in a glucose-free medium, Na+ enters and K+ leaves the cell. These
changes are reversed upon addition of glucose to the medium.
The relative impermeability of cell membranes to inorganic ions is not
uniform or constant. HCO3- ions are generally freely diffusible; Cl- ions pass freely
into and out of erythrocytes (p.306) and the acid-secreting cells of the gastric mucosa.
Although permeability to Na+ is restricted, it may enter cells in increased amounts
when they lose K+ and the passage of K+ across cell membranes appears to be
related to metabolic activities of the cell. For example, there is acceleration of the
entrance of K+ onto cells during periods of administration of glucose od insulin (p.
456). Changes in the distribution of Na+ and K+ occur during excitation of nerve and
muscle cells, and can be produced by adrenocortical hormones (p. 726), and by
dehydration, anoxia, and changes in pH (p. 337), due to alterations in the properties
of the cell membrane. Loss of K+ from the cell, e.g., following administration for
aldosterone, is accompanied by entrance of Na+ and H+ from the interstitial fluid,
with consequent fall in intracellular pH and rise in extracellular pH(p. 639).
When Na is introduced into the blood plasma, it is distributed rapidly
throughout the extracellular fluids, but penetrates the cells only very slowly.
Consequently, an increase in Na concentration in the extracellular fluids causes water
to pass out of the cells, equalizing the osmotic pressure in the two fluid
compartments. Withdrawal of Na from the extracellular fluids cause passage of water
in the opposite direction, i.e., into the cells.
Shifts of water are also caused by changes in pH of the body fluids. The
explanation frequently given is that acids remove cations from the weakly dissociated
proteins, forming more completely dissociated salts and thereby increasing the
number of osmotically active components. Inasmuch as the protein content of
intracellular fluids is greater than that of extracellular fluids, acidification, according
to this view, results in greater increase in osmotic pressure within the cells than in the
extracellular fluids. Consequently, water passes into the cell under such
circumstances. This explanation is not entirely satisfactory.
Phosphate is present within cells in much larger amounts than in extracellular
fluids. Much of this is in organic combination, e.g., as hexose and triose phosphates
ATP and ADP, nucleic acids, phosphocreatine (muscles), etc. however, the
concentration of inorganic phosphate, too, is higher than in the extracellular fluids
and fluctuates continually in relation to the latter at different levels of cell metabolic
activity involving formation and splitting of phosphorylated metabolites. In contrast
to the case of K+, the rate of entrance of phosphate into muscle cells is not altered
significantly by muscular activity but is increased markedly during the recovery
period. It is increased also by administration of glucose and insulin.
The concentrations of K, Na, Mg, and phosphate in the cell can vary, within
limits, in accordance with the metabolic activity of the cell, without influencing
exchanges of water, because, presumably, considerable fractions of these substances

xxxviii
from undissociated or poorly dissociated combinations with cell proteins, nucleic
acids, polysaccharides, etc., and therefore oamotically inactive.
REGULATORY MECHANISMS
In health, the volume and composition of the various body fluid compartment
are maintained within physiological limits even in the face of wide variations in
intake of water and solutes. Isotope-labeled water becomes distributed throughout the
body fluids in two to three hours after administration; in the absence of increase
volume, this implies continual exchanges of water across compartment boundaries.
Fluid exchanges across the cell wall are conducted in a state of osmotic equilibrium
(p. 323). Assuming a “steady state” of cellular metabolic activity, the osmolarity of
intracellular fluids is determined mainly by their K concentration, while that of
extracellular fluids is determined by their Na concentration. If constancy of
osmolarity is to be maintained, the volume of intracellular fluid must be proportional
to its total K content, and that of extracellular fluid to its total Na content.
Consequently, if the volumes of these compartments are to be maintained at constant
levels, a mechanism must be provided for adjustments in excretion not only of water
but also of Na and K in response to variations in amounts of each supplied to the
organism.
These adjustments are accomplished mainly be the kidney. Normal renal
function provides a steady state with respect to: (1) the amount of water in the body;
(2) the amounts of Na and K, which determine the volume of extracellular and
intracellular fluids; (3) the osmolar concentration of these fluids, determined largely
by the concentration of Na and K, respectively. The kidney responds promptly to
deviations in osmolarity or individual ion concentration in extracellular fluid, e.g.,
produced by administration of excessive quantities of water or Na, by augmented
excretion of these substances in amounts required for preservation of osmotic
equilibrium. However, isosmotic expansion of extracellular fluid volume, e.g., by
intravenous infusion of isotonic solutions of salt or serum albumin, is followed
promptly by increased urinary excretion of water and salt. Homeostasis of body fluids
therefore involves a mechanism that responds to fluctuation in volume as well as
mechanisms responsive to changes in concentration of total solute or of individual
ions. Urinary excretion of water and salt is conditioned by a number of variations in
body fluids. These include such factors as: the volume or blood flow ; cardiac output;
pressure changes in various portions of the circulation; rental blood flow;
concentration of total or individual solutes in extracellular fluid. Certain of these
variables, which involve significant alteration in renal blood flow or pressure, or in
solute concentration in the blood plasma, may produce their effects by direct action
on the kidney. Others, however, can produce their effects in the absence of significant
changes in renal hemodynamics or in solute concentration in the plasma. These
effects on kidney function must therefore be mediated by extrarenal factors.
Current concepts of the nature of these regulatory mechanisms include the
existence of receptors sensitive to variations in osmolar (osmoreceptors) or individual

xxxix
ion (chemoreceptors) concentration in extracellular fluids, and to local or general
variations in intravascular pressure (baroreceptors) and/or plasma and/or extracellular
fluid volume (volume receptors, stretch receptors). The intrarenal mechanisms
concerned with excretion of water an solutes may be influenced by stimuli initiated in
these receptors either by direct neural connections or through the medium of humoral
factors, i.e., alterations in production or release of certain hormones. There is
evidence that there are pathways in the nervous system capable of mediating such
influences, but more precise information is available concerning the role of certain
hormones in this connection. Those involved most fundamentally are the antidiuretic
hormone (ADH) and aldosterone, the former regulating the excretion of water, the
letter of Na an K. Adrenal glucocorticoids also exertan influence that is not as well
defined. Details are presented elsewhere of the actions of these hormones in
promoting renal tubular reabsorption of water (pp.726, 826) and Na (pp. 726, 827),
and excretion of K (pp. 726, 829). The mechanisms of regulation of production and
release of these hormones are also considered elsewhere (pp. 721, 752). It will suffice
here to consider the manner in which these two independently controlled systems
may be coordinated in the interest of body fluid homeostasis.
The complexity of this regulatory system in indicated (1) by the great variety
of conditions to which it makes adjustments (e.g., water and salt intake; extracellular
fluid composition and volume; emotional states; blood flow an pressure, general or in
certain spesifuc regions) and (2) by the great diversity of its components (e.g., various
types of receptors; diencephalic centers; nervous pathways; neurohypophysis; adrenal
cortex; renal glomeruli and tubules), many of which have independent controlling
mechanisms. Perhaps the simplest concept, applicable to many circumstances but
certainly not to all, is that the end-effects of the action of one hormone, e.g., ADH,
influence the rate of production or discharge of another, e.g., aldosterone. In addition,
since adjustment may be made in either direction, the receptors of the initiating
stimuli must be in a state of tonic activity, capable therefore of either excitation or
depression.
Adjustment to increasing osmolarity of extracellular fluid may occur as
follows: (1) stimulation of osmoreceptors, presumably in the diencephalon; (2)
perhaps trough neuronal connections, this causes increased production (in
paraventricular and supraoptic nuclei) and discharge (from neurohypophysis) of
ADH; (3) this hormone, reaching the kidney in the systemic circulation, causes
increased reabsorption of water in the distal nephron; (4) normal osmolarity of the
extracellular fluid is restored but its volume is increased; (5) this, directly or
indirectly, depresses the activity of stretch receptors (volume receptors;
baroreceptors), perhaps in various locations; (6) by some as yet undetermined
mechanism, aldosterone production decreases; (7) renal tubular reabsorption of Na
diminishes and it is excreted, with water, in the urine in amounts required to restore
normal extracellular fluid volume and osmolarity.

xl
 The converse occurs in response to decreased osmolarity. Other relationships
are superimposed upon this basic pattern. Secretion of ADH is influenced by changes
not only in osmolarity but also in volume of extracellular fluids; secretion of
aldosterone is influenced by variations not only in volume of extracellular fluid but
also in the amount and concentration of Na and K (chemoreceptors), in some cases at
least operating independently of changes in volume.
The thirst mecanisms plays an important role in fluid homeostasis, regulating
water intake. It is activated by increasing osmolar concentration of extracellular fluids
(osmoreceptors), resulting either from a deficit in water or an excess of solute. It also
has a sensory component, mediated by the glossopharyngeal and vagus nerves,
stimulated by dryness of the mouth and throat.
The intracellular and extracellular fluids are in osmotic equilibrium. Consequently,
the volume of the former is determined largely by the osmolarity of the letter.
Ultimately, therefore, the kidneys regulate the intracellular fluid volume by adjusting
excretion of water in response to changes in osmolarity of the extracellular fluid. The
volume of circulating blood plasma is of much greater concern to the welfare of the
organism then is the volume of other extracellular fluids. It tends to be maintained
within normal limits, largely through the operation of cardiovascular mechanisms,
even in the presence of marked expansion or contraction of interstitial and
transcellular fluids. However, since the plasma proteins do not cross most normal
capillary walls readily (p. 322), an increase in plasma volume may follow intravenous
infusion of hypertonic albumin solutions. Conversely, reduction in plasma volume
may occur in conditions of severe plasma protein depletion.

Buffer
Figure 2-9 shows that titration curve of each acid has a relatively flat zone
extending about 1.0 Ph unit on either side of its midpoint. In this zone, the pH of the
system changes relatively little when small increments of H+ or OH- is added. At ph
values outside this zone there is less capacity to resist changes in ph. The buffering
power is maximum at the ph of the exact midpoint of the titration curve, at which the
concentration of the proton acceptor equals that of the proton donor and pH=Pk’
(Figure 2-9). Buffering power decreases as the ph is raised or lowered from this point,
a direct consequence of the change in ratio of the proton-acceptor and proton-donor
species. Each conjugate acid-base pair has a characteristic ph at which its buffering
capacity is greatest, namely, the point at which Ph=pk’.
Intracellular and extracellular fluids of living organism contain conjugate
acid-base pairs which act as buffers at the normal ph of these fluids. The major
intracellular buffer is the conjugate acid-base pair H2PO4—HPO42- (Pk’ = 7.2). organic
phosphates such as glucose 6-phosphate and ATP also contribute buffering power in
the cell. The major extracellular buffer in the blood and interstitial fluid of vertebrates
is the bicarbonate buffer system. The extraordinary buffering power of blood plasma
can be shown by the following comparison. If 1 ml of 10 N HCl is added to 1.0 l of

xli
neutral phsycologycal saline, i.e., about 0.15 M NaCl, the ph of the saline will fall to
ph 2.0, since NaCl solutions have no buffering power. However, if 1 ml of 10 N HCl
is added to 1 L of blood plasma the ph will decline only slightly, from ph 7.4 to about
ph 7.2. buffer action is best appreciated by solving problems with the Henderson-
Husselbalch equation.
The bicarbonate buffer system (H2CO3-HCO3) has some distinctive features.
While it function as a buffer in the same way as other acid-base pairs, the pK’ of
H2CO3, relatively strong acid, is about 3.8 (table 2-7), which is far lower than the
normal range of blood. The question therefore arises why an acid having such a long
pK’ is capable of serving as a physiologycal at ph near 7.0. in a bicarbonate buffer
system, the proton-donor species, carbonic acid, is in reversible equilibrium with
besolved CO2 :
H2CO3 ↔ CO2(aq) + H2O
If such an aqueous system is in contact with a gas phase, the dissolved CO2
will in turn equilibrate between the gaseous and aqueous phases;
CO2(aq) ↔ CO2(g)
Since by henry’s law the solubility of a gas in water is proportional to its
partial pressure, the ph of the bicarbonate buffer system is a function of the partial
pressure of CO2 pessure is increased, all other variables remaining constant, the ph of
the bicarbonate buffer decline, and vice versa. The bicarbonate system can buffer
blood plasma effectively near ph 7.0, at which the proton-acceptor/proton-donor ratio
is very high, because a small amount of proton donor H2CO3 is in labile equilibrium
with a relatively large reserve capacity of dissolved CO2 in the blood plasma and
gaseous CO2 in the lungs. When the blood must absorb excess OH-, the H2CO3,
which is used up and converted to HCO3-, is quickly replaced from this large pool of
CO2.
There is another distinctive features of the bicarbonate buffer system. CO2 is a
major end product of the aerobic combustion of well molecules and in mamals is
ultimately eliminated via the lungs. The steady state ratio of [HCO3-] / [H2CO3] in the
blood is a reflection of the rate of CO2 production during tissue oxidation and the rate
of loss of CO2 by expiration.
The ph of blood plasma in mamals is held at remarkably constant values. The
blood plasma of man normally has a ph of 7.40. should the ph regulating mechanisms
fail as may happen in disease, and the ph of the blood fall belong 7.0 or rise above
7.8, irreparable damage may ocecur. We may ask : what molecular mechanisms in
cells also extraordinarily sensitive that a change in hydrogen-ion concentration of as
3 X 10-8 M (approximately the difference between blood plasma at ph 7.4 and at ph
7.0) can be lethal ? although many aspects of cell structure and function are
influenced by ph, the catalytic activity of enzymes is especially sensitive. The typical

xlii
curves in figure 2-10 (see also page 196) show that enzymes have maximal activity at
a characteristic ph, called optimum ph. and that their activity decline sharply on either
side of the optimum. Thus biological control of the ph cells and body fluids is of
central importance in all aspects of intermediary metabolism and cellular function.

xliii
 BAB III
KESIMPULAN

1. Metabolisme adalah segala proses reaksi kimia yang terjadi di dalam makhluk
hidup.
2. Air adalah pelarut senyawa ionik dan netral, dapat mengalami ionisasi
3. Di dalam tubuh manusia, cairan akan terdistridusi ke dalam 2 kompartemen
utama yaitu cairan intraselullar (ICF) dan cairan ekstrasellular (ECF)
4. Pergerakan cairan tubuh mencakup penyerapan air di usus, masuk ke
pembuluh darah dan beredar ke seluruh tubuh.
5. Pergerakan air juga meliputi filtrasi air di ginjal (sebagian kecil dibuang
sebagai urin), ekskresi air ke saluran cerna sebagai liur pencernaan (umumnya
diserap kembali) serta pergerakan air ke kulit dan saluran nafas yang keluar
sebagai keringat dan uap air.

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New York : Cambridge University Press

Lehningher, Albert L. 1995. Dasar-dasar Biokimia. Jakarta : PT Gelora Aksara Pratama

Purnomo, dkk. 2009. Biologi Kelas XI untuk SMA/M. Jakarta : Pusat Perbukuan
Departemen Pendidikan Nasional

Irawan, M.A. 2007. Cairan Tubuh, Elektrolit dan Mineral. Pssplab

Gangguan Keseimbangan Air-Elektrolit dan Asam Basa, Fisiologi, Patofisiologi,

Diagnosis, dan Tatalaksana. Unit Pendidikan Kedokteran-Pengembangan
Keprofesioan Berkelanjutan. FKUI. 2007

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Heitz U, Horne MM. Fluid, electrolyte and acid base balance. 5th ed. Missouri: Elsevier-
mosby; 2005.p3-227

Leksana E. Terapi cairan dan elektrolit. Smf/bagian anestesi dan terapi intensif FK
Undip: Semarang; 2004: 1-60.

Holte K, Kehlet H. Compensatory fluid administration for preoperative dehydrationdoes

it improve outcome? Acta Anaesthesiol Scand. 2002; 46: 1089-93

Pandey CK, Singh RB. Fluid and electrolyte disorders. Indian J.Anaesh. 2003;47(5):380-
387.

Mayer H, Follin SA. Fluid and electrolyte made incredibly easy. 2nd ed. Pennsylvania:
Springhouse; 2002:3-189.

Barash PG, Cullen BF, Stoelting RK. Handbook of clinical anesthesia. 5th
ed.Philadelphia: Lippincot williams and wilkins; 2006: 74-97.

Graber MA. Terapi cairan, elektrolit dan metabolik. Ed.2. Farmedia; 2003: 17-40.

Schwartz SI, ed. Principles of surgery companion handbook. 7th ed. New york: McGraw-
Hill; 1999:53-70.

Fakultas Kedokteran Unpad. Protokol Tindakan Bedah. Bandung. 2003

Ellsbury DL, George CS. Dehydration. eMed J [serial online] 2006 Mar (Diakses tanggal
21 Januari 2009).

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