Sasaran Belajar

 Mahasiswa mampu menjelaskan reaksi

biokimiawi yang terjadi dalam tubuh
sebagai mekanisme mempertahankan
keseimbangan cairan dan elektrolit
 Mahasiswa mampu menjelaskan reaksi
biokimiawi yang terjadi dalam proses
pembentukan urin
 Mahasiswa mampu menjelaskan sistem
buffer yang menjaga keseimbangan pH
intrasel dan ekstrasel
 Body Fluid Compartments

• 2/3 (65%) of TBW is intracellular (ICF)

• 1/3 extracellular water
– 25 % interstitial fluid (ISF)
– 5- 8 % in plasma (IVF intravascular fluid)
– 1- 2 % in transcellular fluids – CSF,
intraocular fluids, serous membranes, and in
GI, respiratory and urinary tracts
(third space)

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 Major Compartments for Fluids

•INTRACELLULAR •EXTRACELLULAR FLUID

FLUID (ICF) (ECF)
•Inside cell •Outside cell
•Most of body fluid •Intravascular fluid - within
here - 63% weight blood vessels (5%)
•Decreased in •Interstitial fluid - between
elderly cells & blood vessels
(15%)
•Transcellular fluid -
cerebrospinal, pericardial ,
synovial

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 METHODS OF FLUID &
ELECTROLYTE MOVEMENT

• Diffusion
• Osmosis
• Active Transport
• Filtration

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 DIFFUSION

• Process by which a solute in solution moves

• Involves a gas or substance
• Movement of particles in a solution
• Molecules move from an area of higher
concentration to an area of lower concentration
• Evenly distributes the solute in the solution
• Passive transport & requires no energy*

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 OSMOSIS

• Movement of the solvent or water across a

membrane
• Involves solution or water
• Equalizes the concentration of ions on each
side of membrane
• Movement of solvent molecules across a
membrane to an area where there is a higher
concentration of solute that cannot pass
through the membrane

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 ACTIVE TRANSPORT SYSTEM
• Moves molecules or ions uphill against
concentration & osmotic pressure
• Hydrolysis of adenosine triphosphate
(ATP) provides energy needed
• Requires specific “carrier” molecule
as well as specific enzyme (ATPase)
• Sodium, potassium, calcium,
magnesium, plus some sugars, &
amino acids use it

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 FILTRATION
• Movement of fluid through a
selectively permeable membrane
from an area of higher hydrostatic
pressure to an area of lower hydrostatic
pressure
• Arterial end of capillary has
hydrostatic pressure > than osmotic
pressure so fluid & diffusible solutes
move out of capillary

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 ELECTROLYTES
• Substance when dissolved in solution
separates into ions & is able to carry
an electrical current
• CATION - positively charged electrolyte
• ANION - negatively charged electrolyte
• Commonly measured in
milliequivalents / liter (mEq/L)

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 ELECTROLYTES IN
BODY FLUID COMPARTMENTS

INTRACELLULAR EXTRACELLULAR

POTASSIUM SODIUM

MAGNESIUM CHLORIDE

PHOSPHOROUS BICARBONATE

ECF
• Plasma :
 kation : Na+, K+, Ca2+
 anion : HCO3-, Cl-, HPO42- , (protein)
• Intersitial :
 kation : Na+, K+
 anion : HCO3-, Cl-, HPO42- , SO42-
ICF
 Kation : Na+, K+, Mg2+
 Anion : HCO3-, Cl-, HPO42- , SO42-, (protein)

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 ELECTROLYTES
• Na+: most abundant electrolyte in the body

• K+: essential for normal membrane excitability for

nerve impulse

• Cl-: regulates osmotic pressure and assists in

regulating acid-base balance

• Ca2+: usually combined with phosphorus to form

the mineral salts of bones and teeth, promotes
nerve impulse and muscle contraction/relaxation

• Mg2+: plays role in carbohydrate and protein

metabolism, storage and use of intracellular
energy and neural transmission. Important in the
functioning of the heart, nerves, and muscles

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 SODIUM/CHLORIDE IMBALANCES
• Regulated by the kidneys
• Influenced by the hormone
aldosterone
• Na is responsible for water
retention and serum osmolarity
level
• Chloride ion frequently appears
with the sodium ion
• Normal Na = 135-145 mEq/L
• Chloride 95-108 mEq/L
• Na and CL are concentrated in ECF

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 Chloride
• Maintains serum osmolarity along
with Na
• Helps to maintain acid/base
balance
• Combines with other ions for
homeostasis; sodium, hydrochloric
acid, potassium, calcium
• Closely tied to Na
• Decreased level is most commonly
due to GI losses

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 Sodium Functions
• Transmission and conduction of
nerve impulses
• Responsible for osmolarity of
vascular fluids
• Regulation of body fluid levels
• Sodium shifts into cells and
potassium shifts out of the cells
(sodium pump)
• Assists with regulation of acid-base
balance by combining with Cl or
HCO3 to regulate the balance

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 Chloride Functions
• Found in ECF
• Changes the serum osmolarity
• Goes with Na in retention of water
• Assists with regulation of acid-base
balance
• Cl combines with hydrogen to form
hydrochloric acid in the stomach

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Water and sodium output
 Kidneys ~intestine  water and electrolytes
(filtered proximally, and reabsorbed)
 daily losses : 1.5–2 L of water and 100 mmol of
sodium in the urine, and 100 mL and 15 mmol in
the faeces.
 Fine adjustment of the relative amounts of water
and sodium excretion occurs in the distal nephron
and the large intestine, often under hormonal
control.
 ADH or vasopressin and the mineralocorticoid
hormone aldosterone on the kidney are the most
important physiologically (+natriuretic peptides).
Water and sodium output
 About 1 L of water is lost daily in sweat and expired
air, and less than 30 mmol of sodium a day is lost in
sweat.
 The volume of sweat is primarily controlled by skin
temperature, although ADH and aldosterone have
some effect on its composition.
 Water loss in expired air depends on the respiratory
rate.
 Normally, losses in sweat and expired air are rapidly
corrected by changes in renal and intestinal loss.
Control of water balance
 intake & loss  hypothalamic
osmoreceptor centres.
 these centres, control thirst and the
secretion of Antidiuretic hormone
(ADH = arginine vasopressin)
Air
 70% air yang terfiltrasi direabsorpsi pd tubulus proksimal, 20% distal,
dan 10 % duktus kolektivus
 Cairan di dalam tubulus distal hipoosmotik terhadap peritubular
 Saat cairan sampai ke duktus kolektivus, osmolaritas cairan luminal
selalu lebih rendah daripada cairan insterstisial medula 
meningkatkan gaya osmotik u/ cairan dalam lumen bergerak ke
insterstisial
 Setelah air dapat menembus dinding duktus kolektivus akan
selanjutnya diabsorbsi.
 Urea dapat dengan mudah menembus membran  terdisribusi
secara sama (intralumen & instertisial), namun pada duktus
kolektivus secara aktif ditransportkan keluar tubulus ≈ 40%
osmolaritas medula
Control of antidiuretic hormone
secretion
 extracellular osmolality
 Stretch receptors (atrium), baroreceptors (aortic arch dan
carotid sinus) response to the low intravascular pressure 
stimulating ADH release.
 The stress (nausea, vomiting and pain) ↑ADH secretion
 ADH meregulasi permeabilitas tubulas distal akhir dan duktus
kolektivus (tanpa ADH impermeable)
 ADH aquaporin 2 enhances water reabsorption in excess
of solute from the collecting ducts of the kidney and so
dilutes the extracellular osmolality
Tanpa ADH
Dengan adanya ADH
Sodium Ion

 Sodium penting karena: peran penting eksitasi sel, digunakan u/

transport terlarut lain, terlarut utama ekstraseluler
 Pengaturan resorpsi Na  tugas terpenting ginjal (97%)
 Mekanisme:
 pasif pd tubulus proksimal (junction between cells / paraseluler)
 Transport aktif bersama glukosa dan asam amino
 tubulus ascenden: Na+,K+, & 2Cl-  dependen terhadap aktivitas Na+/K+ATPase
 Aldosterone (mineralocorticoid hormone), secreted by zona
glomerulosa (adrenal cortex).
 Aldosterone  controls loss of sodium particularly in distal tubule
(1/3 akhir).
 Circulating aldosterone concentration ↑ urinary sodium
concentration ↓.
 Feedback control  local electrolyte concentration
 Aldosteron X atrial natriuretic peptide (ANP)
The renin–angiotensin system
 Renin  secreted by the juxtaglomerular apparatus.
 Secretion ↑  change mean pressure in the afferent
arterioles (and β-adrenergic stimulation) ↓ renal artery
blood flow
 Renin catalyzes the conversion angiotensinogen into a
decapeptide (angiotensin I) from a circulating α2-Globulin
(renin substrate)
 Proteolytic enzyme / ACE (predominantly in the lungs but is
also presentin other tissues such as the kidneys)  splits off a
further two amino acid residues.
 The remaining octapeptide, angiotensin II.
Mekanisme stimulasi renin
Actions of Angiotensin II
 capillary walls (directly)  vasoconstriction and so
probably helps to maintain blood pressure and alter
the glomerular filtration rate (GFR).
 sympathetic nervous stimulation
 stimulates the cells of the zona glomerulosa
(adrenal cortex) to synthesize and secrete
aldosterone.
 Aldosteron  stimulates the thirst centre  oral
fluid intake.
Vascular Direct Mechanism of Ang II
 The binding of Ang II to the AT1-R activates the heterotrimeric G
protein signaling pathway which leads to phospholipase C (PLC)
activation.
 This releases inositol-1,4,5-triphosphate (IP3) and diacylglycerol
(DAG) from phosphatidylinositol 4,5-bisphosphate (PIP2).
 IP3 binds to its receptor on the sarcoplasmic reticulum, allowing for
Ca2+ efflux.
 Ang II also promotes an influx of external Ca2+ via calcium release
activated calcium (CRAC) channels.
 Ca2+ binds to calmodulin and activates myosin light chain kinase
(MLCK), which phosphorylates the myosin light chain and enhances
the interaction between actin and myosin, resulting in enhanced
vasoconstriction.
Control of water and sodium homeostasis (
ADH, antidiuretic hormone)
Natriuretic peptides
 Peptide hormone (secreted from right atrial
or ventricular wall)
 Secreted in response to stimulation of
stretch receptors
 Cause high sodium excretion (natriuresis) by
increasing the GFR and by inhibiting renin
and aldosterone secretion.
POTASSIUM

 3000 mmol (98% intracellular)  plasma potassium

concentration is a poor indicator
 Consequently changes in water balance have little direct effect
on the plasma [K+], unlike plasma [Na+].
 The normal potassium intake is about 60–100 mmol/ day.
 Potassium enters and leaves the extracellular compartment by
three main routes:
 the intestine,
 the kidneys,
 the membranes of all other cells.
Intestine - Potassium
 Potassium is principally absorbed in the small intestine, replaces net
urinary and faecal loss.
 Meat, vegetables and fruit including bananas have about 6.2
mmol/100 g of potassium.
 Foods with a high content of potassium (more than 12.5 mmol/100
g): dried fruits (dates and prunes), nuts, avocados and bran/wheat
grain.
 Dried figs, molasses and seaweed are rich in potassium (more than
25 mmol/100 g)
 Leaves the extracellular compartment in all intestinal secretions,
usually at concentrations near to or a little above that in plasma
(total 60 mmol/day, reabsorbed, <10 mmol/day is present
in formed faeces)
Kidney - Potassium
 Filtered by the glomeruli, about 800 mmol (1/4
total body content) would be lost daily if there
were no tubular regulation.
 net loss = 10% of that filtered.
 normally almost completely reabsorbed in the
proximal tubules.
 secreted in the distal tubules and collecting ducts in
exchange for Na+; hydrogen ions (H+) compete with
potassium ions (K+).
 Aldosterone stimulates both exchange
mechanisms.
POTASSIUM LOSS IN THE URINE
Potassium loss in the urine depends on three factors:
1. The amount of sodium available for exchange: depends on the GFR,
filtered sodium load, and sodium reabsorption from the proximal
tubules and loops of Henle.
2. The circulating aldosterone concentration: this is increased
following fluid loss, with volume contrac tion, which usually
accompanies intestinal loss of potassium, and in most conditions
for which patients are receiving diuretic therapy. Hyperkalaemia
stimulates aldosterone release in synergy with angiotensin II, while
hypokalaemia inhibits it.
3. The relative amounts of H+ and K+ in the cells of the distal tubules
and collecting ducts, and the ability to secrete H+ in exchange for
Na+.
Cells Membran - Potassium
 Na+/K+ adenosine triphosphatase (ATPase) ‘pump’ on cell surfaces
maintains a high intracellular [K+].
 This exchanges three Na+ ions from cells in exchange for two K+ ions
in the extracellular fluid (ECF), thus establishing an electrochemical
gradient across the cell membrane, with a net positive charge in the
ECF.
 The loss of K+ from cells down the concentration gradient is opposed
by this electrochemical gradient.
 Potassium is also exchanged for H+.
 A small shift of K+ out of cells may cause a significant rise in plasma
concentrations
 Usually the shift of K+ across cell membranes is accompanied by a
shift of Na+ in the opposite direction.
 Insulin enhances the cellular uptake of glucose and potassium
(Catecholamines have a similar action).
 Hyperkalaemia stimulates insulin secretion and hypokalaemia
inhibits it.
 β-adrenergic stimulation increases cellular potassium uptake by
stimulating the Na+/K+-ATPase ‘pump’.
 Synthesis of Na+/K+-ATPase is stimulated by thyroxine,
Calcium and phosphate ions
 Almost completely resorbed from the primary urine by active
transport (99% and 80 - 90%)
 Regulated by parathyrin, calcitonin, and calcitriol
 Parathyrin (PTH) produced by the parathyroid gland  stimulates Ca
resorption in the kidneys & inhibits the resorption of phosphate ≈
intestine & bones
 Calcitonin, peptida diproduksi sel C kelenjar tiroid  inhibisi resorpsi
Ca dan PO4 (antagonis PTH relative to Ca)
 Calcitriol (kidney)  stimulasi resorpsi Ca dan PO4
Referensi
 CLINICAL BIOCHEMISTRY & METABOLIC MEDICINE 8th Edition