WATER, ELECTROLYTE, AND

DISTURBANCE
Alfi Muntafiah
Laboratorium Biokimia FK USOED
 WATER
Water is the most abundant body
constituent; it comprises 45 60% of
total body weight.
In a lean person, it accounts for a larger
fraction of the body mass than in an
overweight person.
most biochemical reactions take place
in an aqueous environment the
control of water balance is an important
requirement for homeostasis.
Total cairan tubuh beragam menurut jenis kelamin, umur dan
kadar lemak

in adult person: male & female Changes in Water Content with Age
Body water compartments
2/3 of total body water : ICF
1/3 of total body water : ECF
interstitial fluid (15% body weight)
Exchange with vascular fluid via
lymph system
Plasma/intravascular (3% body
weight),
transcellular fluids
Present in gastrointestinal fluid,
urine, intraocular fluid,
cerebrospinal fluid/CSF, synovial
(joint)
Ions present in the plasma
and in the intracellular fluid.

In Plasma (extracellular fluid) :

Sodium chloride is the main ionic
Glucose and urea also contribute to
plasma osmolality.
Rich in protein

In intracellular fluid:
Potassium & magnesiumthe are
predominant cation
the main anions are phosphates and
proteins.
 Fluid compartments are separated by
membranes that are freely permeable to
water but impermeable to solutes.

Movement of fluids is due to:

hydrostatic pressure differentials
osmotic pressure differentials

7
 Movements of water occur mainly via aquaporins
affected by osmosis and filtration

In osmosis water moves

to the area of highest
solute concentration.
active movement of salts
into an area creates a
concentration gradient
down which water flows
passively.
 Movements of water occur mainly via aquaporins
affected by osmosis and filtration

In filtration, hydrostatic pressure in

arterial blood moves water &
nonprotein solutes through specialized
membranes to produce an almost
protein-free filtrate: occurs in the renal
glomerular filtrate.
The kidneys are the major organs that
regulate extracellular fluid composition
and volume via their functional units
known a nephrons .
Principal transport processes in the renal nephron.

ADH antidiuretic hormone

 Filtration also accounts for
movement of water from
the vascular space into the
interstitial compartment,
which is opposed by the
osmotic (oncotic) pressure
of plasma proteins.
 Cells move ions (especially Na and K ) against a
concentration gradient by Na+/K+-ATPase
maintains the sodium and potassium
gradients across the cell membrane.
as an ion transporter (sodium pump)
or as an enzyme (ATPase).
It hydrolyzes one ATP molecule, and
the released energy drives the
transfer of 3 sodium ions from the
cell to the outside, and 2 potassium
ions from the outside into cell
Vid
Distribution of body water, sodium and potassium
The gradient of sodium and potassium
concentrations is maintained across cell
membranes by the Na+/K+-ATPase.
major contributor to the osmolality of the
ECF is sodium determinant of the
distribution of water between ECF and ICF.
Distribution of water between plasma and
interstitial fluid is determined by the
oncotic pressure exerted by plasma
proteins.
Two barriers are important :
the cell membrane and
the wall of the capillary vessel.
 Extracellular space Intracellular space
Intravascular Interstitial space
space

Water

Electrolytes

Colloids

Capillary wall Cell membrane

Oncotic pressure Osmotic pressure

Capillary vessel wall separates plasma from the
surrounding interstitial fluid
The capillary wall :
separates plasma from the interstitial fluid
is freely permeable to water and
electrolytes but not to proteins.
Ions and low-molecular-weight
molecules are present in similar
concentrations in the ECF and plasma.
protein concentration is 45 times
greater in plasma than in the interstitial
fluid.
Cell membrane separates the intracellular
and extracellular fluid
In the ICF :
the main cation is potassium
The main anions are proteins and
phosphate.
In the ECF :
the situation is reversed the main
cation is sodium
Water diffuses freely across most cell
membranes but the movement of ions
and neutral molecules is restricted
 Water diffuses freely across most cell membranes but the
movement of ions and neutral molecules is restricted

Small molecules are transported

across cell membranes by specific
transport proteins : the ion pumps
The most important is the sodium-
potassium ATPase (Na+/K+-
ATPase), also referred to as the
sodiumpotassium pump.
The Na+/K+-ATPase
is the major determinant of cytoplasmic sodium concentration
It also has an important role in regulating cell volume,
cytoplasmic pH and calcium levels through the Na+/H+ and
Na+/Ca2+exchangers.
One of the primary requirements for continuous sodium-
pump-driven adaptation comes from changes in dietary
sodium and potassium.
Hormones that control the volume and ionic composition of
the ECF often act directly on the sodium pump in the kidney
and intestine.
Na+/K+-ATPase activity is subject regulation by a
number of hormones
The Na+/K+-ATPase is activated by sodium and ATP at cytoplasmic
sites.
Some hormones appear to alter the Na+/K+-ATPase activity by
changing its apparent affinity for sodium (for instance, angiotensin II
and insulin increase the affinity).
The Na+/K+-ATPase is subject to regulation by a number of
hormones, including aldosterone.
Peptide hormones such as vasopressin and PTH affect the activity of
Na+/K+-ATPase
 Passive movement of electrolytes through ion
channels is driven by the electrochemical gradient
membrane potential : 50 to 90 mV, negative inside the cell.
The electrochemical gradient :
source of energy for transport of many substances such as the co-transport of the
sodium ions with glucose, amino acids, and phosphate.
promotes an increase in intracellular calcium by activating voltage-dependent
Ca2+channels.
water and sodium transport on the luminal side of the epithelial cells (in the
intestine and the kidneys) is linked to the ion gradient generated by the
Na+/K+-ATPase, so this enzyme is critical to water absorption in the intestine
and its reabsorption in the kidneys.
The impairment of the sodium pump function in the kidney and small
intestine is linked to pathophysiology of hypertension and chronic diarrhea
Molecules dissolved in body water contribute to
the osmotic pressure
Osmolality depends on the
concentration of molecules in
water
osmotic pressure is
proportional to the molal
concentration of a solution.
 A solution that has the same effective osmolality as plasma is said to
be isotonic , e.g., 0.9% saline, 5% glucose, and Ringer s and Locke s
solutions.
If a solute can permeate a membrane freely, then a solution of that
solute will behave like pure water with respect to the membrane.
Thus, a solution of urea will cause red cells to swell and burst as pure
water does, because urea moves freely across erythrocyte
membranes.
 Osmolalitas larutan merupakan fungsi dari jumlah partikel larutan
atau osmolar per unit volume. Satuan osmolalitas diukur dengan
mOsm/L.
Harga normal osmolalitas serum 265 sampai 285 dipertahankan oleh
fungsi ginjal, zat yang terlarut atau konsentrasi dari urin.
Differences in osmolality cause movement of water
between ICF and ECF

A change in the concentration of

osmotically active ions in either ECF
or ICF creates a gradient of osmotic
pressure and, consequently, causes
the movement of water.

Water always diffuses from lower

osmolality to higher to equalize
osmotic pressures
Water redistribution caused by
changes in osmolality

Osmotic pressure controls the

movement of water between
compartments.
An increase in ECF osmolality
draws water from the cells, and
leads to cellular dehydration.
On the other hand, when ECF
osmolality decreases, water
moves into the cells and this
may cause cell edema.
Balance between the oncotic and hydrostatic pressure changes
across the vascular bed and is fundamental for the circulation
of substrates and nutrients

The movement of water between the plasma and interstitial fluid

depends on the plasma protein concentration.
Proteins (particularly albumin) exert osmotic pressure in the plasma.
This is known as the oncotic pressure
it retains water in the vascular bed.
A reduction in plasma oncotic pressure, which occurs, for instance, as a
consequence of a decrease in the plasma albumin concentration, results in
the movement of fluid into the extravascular space and in the development of
edema
 Cells protect themselves against changes of
osmolality and volume
An increase in the intracellular concentration of sodium :
stimulates the Na+/K+-ATPase, which extrudes sodium from the cell.
This is followed by the egress of water and protects the cell from volume changes.
Another protective mechanism : generation of osmotically active
substances.
the brain cells adapt to increased ECF osmolality by increasing their amino acid concentration.
cells in the renal medulla exposed to a hyperosmotic environment produce an osmotically
active : alcohol, sorbitol, and increase the concentration of the amino acid taurine.
The body constantly exchanges water with
the environment

In a steady state, the intake of water equals

its loss.
The main source of water : oral intake
Water is lost through :
urine excretion
insensible loss : the lungs, sweat and
feces
500 mL daily)
can increase substantially in high
temperatures, during intensive
exercise, and also as a result of fever.
Daily water balance in an adult person
Water is obtained from :
diet (food & drink)
oxidative metabolism of lipid &
carbohidrat
Water is lost by expiration of air, in
feces and in urine
Note how much water enters and
leaves the gastrointestinal tract daily;
severe diarrhea quickly leads to
dehydration
ELECTROLYTE BALANCE
The major electrolytes are Na+ , K+ , Cl- , and HCO3-
sodium
The average Na content of the human body is 60 mEq/kg :
50% extracellular fluid, 40% bone, and 10% intracellular Na
The chief dietary source of sodium is salt added in cooking.
Excess sodium is largely excreted in the urine, although some is lost in
perspiration.
Gastrointestinal losses are small except in diarrhea.
Sodium balance is integrated with the regulation of extracellular fluid
volume
Hypernatremia
results from :
loss of hypo-osmotic fluid
e.g in burns, fevers, high environmental
temperature,exercise, kidney disease, diabetes
insipidus)
Increased Na intake
e.g., administration of hypertonic NaCl solutions,
ingestion of NaHCO 3.
Potassium
mainly in the intracellular spaces.
Required for carbohydrate metabolism,
increased cellular uptake of K occurs during glucose catabolism.
widely distributed in plant and animal foods.
Insulin and catecholamines promote a shift of K into the cells.
Excess K is excreted in the urine, a process regulated by aldosterone.
 Plasma K plays a role in the irritability of excitable tissue.
A high concentration of plasma K leads to electrocardiographic (ECG)
abnormalities and possibly to cardiac arrhythmia, which may be due
to the lowering of the membrane potential.
Low concentration of plasma K increases the membrane potential,
decreases irritability, and produces other ECG abnormalities and
muscle paralysis.
 Potassium
Normal serum concentration of
potassium is 3.55 mmol/L.
Rasio kalium intra & ekstraseluler
mrpk faktor penentu potensial listrik
di sel membrane berperan dalam
aktifitas potensial jaringan saraf dan
otot
Serum potassium concentration
below 2.5 mmol/L or above
6.0 mmol/L is dangerous life-
threatening : affect the cardiac
muscle
Chloride

is the major extracellular anion (about 70% is in the extracellular

fluid).
The average Cl content of the human body is 35 mEq/kg.
Chloride in food is almost completely absorbed.
Plasma levels of Na and Cl in general undergo parallel alterations.
in metabolic alkalosis, chloride concentration increases
Clinical box :
Body fluids differ in ionic composition
Clinical abnormalities that may develop
after fluid loss depend on the
composition of what is lost:
Sodium in sweat < ECF,
excessive sweating leads to a predominant
loss of water and concentrates sodium in the
extracellular fluid, causing hypernatremia.
sodium content of the intestinal fluid
plasma but contains considerable amounts
of potassium.
its loss (for instance, in severe diarrhea)
would result in dehydration and
hypokalemia, but may not change plasma
sodium concentration
Homeostasic Controls
The composition and
volume of extracellular
fluid are regulated by
complex hormonal and
nervous mechanisms
interact to control its
osmolality, volume, and
pH.
 The osmolality of extracellular fluid is due mainly to Na and
accompanying anions. It is kept within narrow limits (285 295
mosm/kg) by regulation of water intake (via a thirst center) and water
excretion by the kidney through the action of ADH.
The volume is kept relatively constant. Volume receptors sense the
effective circulating blood volume which, when decreased, stimulates
the renin angiotensin aldosterone system and results in retention
of Na
The pH of extracellular fluid is kept within very narrow limits (7.35
7.45) by buffering mechanisms, the lungs, and the kidneys. These
three systems do not act independently. For example, in acute blood
loss release of ADH and aldosterone restores the blood volume, and
renal regulation of the pH leads to shifts in K and Na levels.
 Extracellular fluid volume in a normal adult is kept constant; body weight
does not vary by more than a pound per day despite fluctuations in food
and fluid intake.
A decrease in extracellular fluid volume lowers the effective blood volume
and compromises the circulatory system.
An increase may lead to hypertension, edema, or both.
Volume control centers on renal regulation of Na balance.
When the extracellular fluid volume decreases, less Na is excreted; when it
increases, more Na is lost.
Na retention leads to expansion of extracellular fluid volume, since Na is confined to
this region and causes increased water retention.
Renal Na flux is controlled by the aldosterone angiotensin renin system
and natriuretic peptides.
 WATER AND OSMOLALITY CONTROLS
Water balance is regulated to maintain the
constant osmolality of body fluids.
This osmolality is directly related to the
number of particles present per unit
weight of solvent.

Regulation of osmolality in the body

 water passes freely through most biological membranes, all body
fluids are in osmotic equilibrium so that the osmolality of plasma is
representative of the osmolality of other body fluids.
The osmotic pressure of extracellular fluid is due primarily to its
principal cation Na and the anions Cl and HCO3 .
Renin-Angiotensin system
controls blood pressure and
the vascular tone
Renin is an enzyme produced
in the juxtaglomerular
apparatus of the kidney
released in response to a
decreased renal perfusion
pressure (decreased delivery
of Na+ to the macula densa)
and increased sympathetic
tone.
Reninangiotensin system.
Renin converts angiotensinogen into angiotensin I.
Angiotensin I is further converted into angiotensin II by the
angiotensin-converting enzyme (ACE).
It also yields other angiotensin peptides.
Cellular actions of angiotensins are mediated by angiotensin
receptors type 1 (AT1), type 2 (AT2) and MAS receptors that bind
angiotensin.
The reninangiotensin system is a target for two major classes of
hypotensive drugs: ACE blockers (e.g. ramipril, enalapril) and AT1
receptor antagonists (e.g. losartan).
Angiotensin receptors are important in the
pathogenesis of cardiovascular disease
Angiotensin II constricts vascular
smooth muscle, thereby increasing
blood pressure and reducing renal
blood flow and glomerular filtration
rate.
It also promotes aldosterone
release and vascular smooth
muscle proliferation.
Serum sodium concentration is a marker of fluid and electrolyte
disorders

Water and electrolyte disturbances result from an imbalance between

the intake of fluids and electrolytes and their loss, and from the
movement of water and electrolytes between body compartments.
A decreased sodium concentration (hyponatremia) usually indicates
that the extracellular fluid is being diluted (due to an excess of
water), whereas an increased sodium concentration (hypernatremia)
means that the extracellular fluid is being concentrated (due to
water loss).
Hyponatremia may also result from loss of sodium but this is rare.
GANGGUAN KESEIMBANGAN
CAIRAN DAN ELEKTROLIT
PADA KASUS PENYAKIT SALURAN
CERNA
 WATER
Water is the most abundant body
constituent; it comprises 45 60% of
total body weight.

most biochemical reactions take place

in an aqueous environment the
control of water balance is an important
requirement for homeostasis.
Ions present in the plasma
and in the intracellular fluid.

In Plasma (extracellular fluid) :

Sodium chloride is the main ionic
Glucose and urea also contribute to
plasma osmolality.
Rich in protein

In intracellular fluid:
Potassium & magnesium are
predominant cation
the main anions are phosphates and
proteins.
The body constantly exchanges water
with the environment

In a steady state, the intake of water equals

its loss.
The main source of water : oral intake
Water is lost through :
urine excretion
insensible loss : the lungs, sweat and
feces
500 mL daily)
can increase substantially in high
temperatures, during intensive
exercise, and also as a result of fever.
 Effect of water status on cell size
>>> water sel bengkak
<<<<water sel
mengkerut dan dehidrasi
Gangguan keseimbangan cairan
Overhidrasi intake >>> loss
Dehidrasi intake <<< loss
Homeostasis:
Berbagai pengaturan fisiologis
untuk mengembalikan ke
kondisi normal state, ketika
mengalami gangguan.
diatur oleh berbagai
mekanisme :
hormonal,
adaptasi vaskuler.
ginjal,
mengendalikan volume maupun
osmolalitas plasma.
Contoh kasus : penyakit saluran cerna (diare)
Perubahan komposisi dan volume cairan tubuh
gangguan keseimbangan cairan dan elektrolit
Kekurangan cairan dan elektrolit disebabkan oleh :
Kehilangan >>>
Intake <<<
Anamnesis dan pemeriksaan fisik diperlukan untuk memperkirakan
apakah ada perkembangan ke arah dehidrasi
diare
Dehidrasi = kekurangan cairan tubuh
Penyebab : kehilangan cairan >>>> (feces, muntah) dan atau intake cairan <<
cairan yang diekskresikan lebih banyak dari kapasitas absorpsi (kegagalan absorpsi)
kehilangan elektrolit
Diare + kehilangan cairan dan elektrolit dehidrasi isotonik
Sign of dehydration
 Dehidrasi hipernatremik dan hipernatremia
jumlah cairan yang keluar >>> larutannya
(Na+).
Hipernatemia menyebabkan plasma menjadi
hipertonik.
Hipertonik ekstraseluler menyebabkan air
keluar dari sel, sehingga sel lebih kecil
ukurannya.
Di otak menyebabkan berkerutnya jaringan
arachnoid hingga perdarahan subarahnoid,
intradural dan subdural.
 Dehidrasi hiponatremik dan hiponatremia
Hiponatremia (hypovolemia, euvolemia atau
hypervolemia)
untuk menyatakan apakah rendahnya kadar Na
benar benar diikuti kadar Na tubuh yang rendah.
Hiponatremi hypovolemia karena diare dan
muntah
kehilangan cairan dan hiponatremia
menyebabkan kegagalan sirkulasi karena
pengurangan volume cairan ekstraseluler.
osmolalitas serum turun, air masuk ke dalam sel
disfungsi muskuloskleletal & udem sel otak
Regulasi hormonal
Renin-Angiotensin system controls blood
pressure and the vascular tone
vid
Ginjal merupakan organ utama yang meregulasi
volume dan komposisi cairan ekstraseluler
melalui unit fungsionalnya yang disebut sbg
nefron

Filtrasi, reabsorbsi dan sekresi

tubuler bertujuan bertujuan
mengendalikan keseimbangan air
dan elektrolit
Filtrasi pada glomerular
menghasilkan filtrate yg free
protein
Hyponatremia

sodium loss greater than water loss

result from :
inadequate Na intake,
excessive fluid loss from vomiting or diarrhea,
diuretic abuse,
adrenal insufficiency.

Hyponatremia represents an abnormal ratio of total body sodium to water and is

commonly defined as a plasma sodium concentration <135 mEq/L (1 mEq/L = 1
mmol/L).
Hyponatremia is the most common electrolyte abnormality in hospitalized patients :
mild hyponatremia (plasma sodium < 135 mEq/L)
moderate hyponatremia (< 130 mEq/L)
severe hyponatremia (< 120 mEq/L)
hyponatremia
affects extracellular fluid volume, as it occurs in congestive heart
failure, uncontrolled diabetes, cirrhosis, nephrosis, and inappropriate
ADH secretion.
Severe hyponatremia, an hypo-osmolar condition can cause cerebral
edema resulting in neurocognitive dysfunction.
The treatment may require therapy with hypertonic saline and ADH
receptor antagonists
Hypernatremia
results from :
loss of hypo-osmotic fluid
e.g in burns, fevers, high environmental
temperature,exercise, kidney disease, diabetes
insipidus)
Increased Na intake
e.g., administration of hypertonic NaCl solutions,
ingestion of NaHCO 3.
Hyperkalemia
occur in:
chronic renal disease,
adrenal insufficiency, and either in the
disorders of drugs that inhibit renin-angiotensinogen-aldosterone axis.
Treatment :
promotion of cellular uptake of K by administration of insulin with glucose
and 2 adrenergic agonists.
In severe cases, ion exchange resins given orally which bind K in intestinal
secretions and hemodialysis are used to correct hyperkalemia
Hypokalemia
occur with :
loss of gastrointestinal secretions (which contain significant amounts of K )
excessive loss in the urine because of increased aldosterone secretion or
diuretic therapy.
usually associated with alkalosis.
Keseimbangan asam basa
pH cairan tubuh normal :7,35 7,45
Untuk menilai adanya gangguan asam basa, diperlukan pemeriksaan gas darah
arteri atau vena serta kadar elektrolit.
Gangguan asam basa terjadi karena gangguan pada CO2 maupun HCO3.
Perubahan pada HCO3 menyebabkan alkalosis atau asidosis metabolic
Perubahan pada pCO2 menyebabkan alkalosis atau asidosis respiratorik.
 Disorders of Acid Base Balance

Classification, characteristics,
and compensation of simple
acid base disorders.
Asidosis metabolik
akibat bertambahnya asam atau
berkurang/hilangnya basa dari
cairan tubuh.
Memacu respon kompensasi
berupa meningkatnya ventilasi
alveolar (alkalosis respiratorik)
dan turunnya pCO2.
 Buffer cairan ekstraseluler sebagian besar ditentukan oleh HCO3-
(NaHCO3) dan anion gap (anion lain yang sulit diukur : protein, fosfat,
sulfat, anion organic)
Pada asidosis, anion gap bisa naik/normal
Pada diare yg banyak kehilangan HCO3 akan terjadi asidosis metabolic
dengan anion gap normal (hiperkloremia)
Ketika HCO3 hilang dari tubuh, maka Cl- mrpk satu-satunya anion yg
siap mengkompensasi volume cairan. Cl- banyak diabsorpsi
dibanding Na+ shg terjadi hiperkloremia.
Alkalosis metabolik
Akibat meningkatnya basa atau hilangnya asam.
Menyebabkan hipoksia, iritabilitas otot, kejang dan aritmia.
Pada kasus penyakit saluran cerna (muntah), alkalosis biasanya terjadi
karena kehilangan klorida dan asam
Asidosis respiratorik
Karena meningkatnya pCO2 dan menurunnya pH plasma scr cepat.
Biasanya terjadi karena penyakit obstruksi jalan napas, bukan karena
penyakit saluran cerna.
Alkalosis respiratorik
Disebabkan oleh menurunnya pCO2 karena hiperventilasi
Tidak disebabkan oleh penyakit saluran cerna
TERIMAKASIH