Fluid, Electrolyte, and Acid-Base Balance

I. Body Fluids
A. Fluid Compartments

Water occupies three main locations within the human body:

Intracellular Fluid (ICF) compartments --> cytoplasm within a cell, accounts for 2/3 volume of body
fluids
Extracellular Fluid (ECF) compartments --> water outside cells (plasma & interstitial fluid)
Other - lymph, CSF, humors of eye, serous fluid, and GI secretions

B. Composition of Body Fluids

Water is a universal solvent and dissolves various ionic and covalent bonded compounds that are classified as
either an electrolyte or nonelectrolyte
Nonelectrolytes contain covalent bonds that prevent them form dissociating in solution and therefore have no
electrical charge (egs. glucose, lipids, and urea)
Electrolytes dissociate into ions (ionize) in water; ions are charged particles and conduct an electrical current
Electrolyte examples --> Mg+, Na+, Cl-, K+
Dissolved solutes increase osmotic activity of a fluid; electrolytes have higher osmotic power than
nonelectrolytes because each electrolyte molecule dissociates into at least two ions
NaCl ---------> Na+ + Cl MgCl2 ---------> Mg2+ + Cl- + Cl glucose ---------> glucose
Therefore electrolytes have a greater ability to cause fluid shift
NOTE: review the chemical properties of water and functions of ions covered previously (i.e. AP I)

D. Disorders of Water Balance

III. Electrolyte Balance

A. Role of Sodium in Fluid and Electrolyte Balance

Exchange of body fluids regulated by osmotic and/or hydrostatic pressures

Osmotic pressure - pressure resulting from the movement of water through a membrane and against its
concentration gradient (i.e. the process of osmosis)
Hydrostatic pressure - pressure exerted to counteract the process of osmosis
Solutes are unequally distributed because of molecular size, electrical charge, or dependence on active transport;
therefore changes in solute concentration cause net water flows
Exchanges between plasma and interstitial fluid occur across capillary membranes (driven by hydrostatic
pressure of blood); plasma filters into interstitial space, water is reabsorbed and any leakage is picked up by
lymphatic vessels
Exchanges between the interstitial and intracellular fluids depend upon selective permeability of the cell and
forms of transport (active transport)
Plasma servers as link between the external and internal environments

II. Water Balance

A. Overview

Water intake = Water output

Intake = 2500 ml/day, water ingested as fluids (60%), foods (30%), and produced from cell metabolism or also
called metabolic water (10%)
Water output - vapor in lungs/diffusion from the skin (28%), perspiration (8%), and feces (4%); rest is excreted
by kidneys as urine (60%)
Rise in plasma osmolarity (soute concetration) triggers:
Thirst, provoking water intake
ADH release, causing the kidneys to excrete concentrated urine

Thirst Mechanism
Decrease in plasma volume and increase in plasma osmolarity causes dry mouth, in stimulating the
hypothalamic thirst centers
Dry mouth results from a decrease in water filtered from the bloodstream (therefore increased
osmolarity) and therefore salivary gland receives less water, in turn producing less saliva
Hypothalamic stimulation occurs when water moves (due to hypertonic ECF) out of thirst center
osmoreceptors by osmosis, causing osmoreceptors to become irritable and depolarize (therefore
sensation of thirst)
Thirst is imperfect - osmoreceptors provide feedback and inhibit hypothalamic thirst centers BEFORE enabling
osmotic changes to occur (thereby prematurely stopping intake of water)

C. Regulation of Water Output

Obligatory water losses - insensible water loss from lungs and through skin, undigested food, feces, and urine
Kidneys can concentrate urine, but only a minimum of 500 ml of water is lost in urine/day and therefore
concentration and volume of urine excreted depends on fluid intake

75-80% of sodium (NaCl) in renal filtrate is reabsorbed in proximal tubules of kidneys

Aldosterone aids in actively reabsorbing remaining Na+Cl- in distal convoluted tubule/collecting tubule by
increasing tubule permeability; therefore aldosterone promotes both sodium and water retention
Mechanism:
increase in K or decease in Na in blood plasma renin-angiotensin Mechanism
stimulates adrenal cortex to release aldosterone
aldosterone targeted towards the kidney tubules
increase in Na reabsorption increase in K secretion
restores homeostatic plasma levels of Na and K
Influences on aldosterone synthesis and release:
Elevated potassium levels in ECF directly stimulates adrenal cells to secrete aldosterone
Juxtaglomerular apparatus of renal tubes release renin in response to:

1.
2.
3.

ii. Cardiovascular system

decreased stretch (due to decrease in blood pressure)

decreased filtrate osmolarity
sympathetic nervous system stimulation

As blood volume (and pressure) rises, the baroreceptors in the heart and in the large vessels of the neck and
thorax (carotid arteries and aorta) communicate to the hypothalamus
Sympathetic nervous system impulses to kidneys decrease, allowing afferent arterioles to dilate; as the
glomerular filtration rate rises, sodium and water output increases (causing pressure diuresis)
Reduced blood volume and pressure results

iii. Influence of ADH

B. Regulation of Water Intake (Thirst Mechanism)

Sodium most abundant cation in the ECF and is the only one exerting a significant osmotic pressure
Sodium does not easily cross cellular membranes, it must be pumped across; therefore, abundance, osmotic
effect, and transport of sodium are controlling factors of ECF volume and water distribution
While the sodium content of the body may be altered, its concentration in the ECF remains stable because of
immediate adjustments in water volume; WATER FOLLOWS SALT
Because all body fluids are in osmotic equilibrium, a change in plasma sodium levels affects not only the plasma
volume and blood pressure (intravascular compartment), but also the fluid volumes of the other two
compartments (ICF and ECF)

B. Regulation of Sodium Balance (and sodium-water balance, BP, and Blood Volume)
i. Influence of Aldosterone

C. Movement of Fluids Between Compartments

Dehydration - water loss exceeds water intake

Hypotonic hydration - ECF is diluted; sodium concentration is normal but there is an increase in water, causing
ECF sodium levels to lower (hyponatremia), increase in osmosis occurs and tissue cells swell (edema)

Amount of water reabsorbed in the distal segments of the kidney tubules is proportional to ADH release
(increase in ADH secretion = increase in water resorption)
Osmoreceptors of the hypothalamus sense the ECF solute concentrations and trigger or inhibit ADH release
from the pituitary
Mechanism:
decrease in sodium concentration in plasma (decreased osmolarity)
stimulates osmoreceptors in hypothalamus
stimulates posterior pituitary to release ADH
ADH targeted toward distal and collecting tubules of kidney
the effect is increased water resorption
plasma volume increases, osmolarity decreases
scant urine produced

iv. Influence of atrial natriuretic factor (ANF)

Reduces blood pressure and blood volume by inhibiting nearly all events that promote vasoconstriction and
sodium and water retention
In essence, inhibits ADH and Aldosterone production

Potassium is the chief intracellular cation

C. Regulation of Potassium Balance

Relative intracellular-extracellular potassium concentrations directly affects a cell's resting membrane potential,
therefore a slight change on either side of the membrane has profound effects (egs. on neurons and muscle
fibers)
Potassium is part of the body's buffer system, which resists changes in pH of body fluids; ECF potassium levels
rise with acidosis (decrease pH) as potassium leave cells and fall with alkalosis (increase pH) as potassium
moves into cells
Potassium balance is maintained primarily by renal mechanisms (i.e. influenced by Aldosterone)
Potassium reabsorption from the filtrate is constant - 10-15% is lost in urine regardless of need; because
potassium content of ECF is low (compared to sodium concentration), potassium balance os accomplished by
changing amount of potassium secreted into the filtrate; therefore regulated by collecting tubules

D. Regulation of Calcium Balance

99% of calcium found in bones as an apatite

Calcium needed for blood clotting, nerve transmission, enzyme activation, etc...
Calcium ion concentration is regulated by interaction of two hormones: parathyroid hormone and calcitonin
Calcium ion homeostasis: effects of PTH and calcitonin
PTH - released by the parathyroid cells, promotes increase in blood calcium levels by targeting...
Bones - PTH activates osteoclasts, which breakdown the matrix
Small intestines - PTH enhances intestinal absorption of calcium ions indirectly by
stimulating the kidneys to transform vitamin D to its active form which is a necessary
cofactor for calcium absorption
Kidneys - PTH increases calcium reabsorption by renal tubes while simultaneously
decreasing phosphate ion reabsorption
Calcitonin - targets bone to encourage deposition of calcium salts and inhibits bone reabsorption
(therefore an antagonist of PTH and decreases blood calcium levels)

E. Other Major Electrolytes: Magnesium and Chloride

Magnesium - cation, cofactor of many enzymes and is need for both sodium-potassium pump and calcium ion
channel function
Chloride - anion, part of hydrochloric acid (chemical digestion) and involved in chemical digestion and blood
chemistry (e.g. chloride shift in oxygen/carbon dioxide circulation)

IV. Acid-Base Balance

All biochemical reactions are influenced by pH of their fluid environment, therefore optimum conditions and
balance (acid-base) is required
Optimal pH of various body fluids differ but not by much (pH of body fluids: arterial blood = 7.4, venous blood
and interstitial fluid = 7.35, intracellular fluid = 7.0)
Changes in pH in blood: arterial blood >7.45 = alkalosis and <7.35 = physiologic acidosis
Body has buffer systems: Bicarbonate (blood ph), Phosphate (urine pH), and Protein buffers (e.gs., albumins,
amino acids, hemoglobin, regulation of blood pH)

V. Clinically Related Terms:

Hyper/hyper kalemia
Hypo/hyper natermia
Hypo/hyper calcemia
Hypo/hyper chloremia
Hypo/heper phosphatemia
Hypo/hyper magnesia

Sodium
in biology
Sodium ions are necessary in small amounts for some types of plants, but sodium as a nutrient is more generally

needed in larger amounts by animals, due to their use of it for generation of nerve impulses and for
maintenance of electrolyte balance and fluid balance. In animals, sodium ions are necessary for the
aforementioned functions and for heart activity and certain metabolic functions.[1] The health effects of
salt reflect what happens when the body has too much or too little sodium.

Sodium distribution in species

Plants

In C4 plants, sodium is a micronutrient that aids in metabolism, specifically in regeneration of phosphoenolpyruvate

(involved in the biosynthesis of various aromatic compounds, and in carbon fixation) and synthesis of chlorophyll.
[2] In others, it substitutes for potassium in several roles, such as maintaining turgor pressure and aiding in the
opening and closing of stomata.[3] Excess sodium in the soil limits the uptake of water due to decreased water
potential, which may result in wilting; similar concentrations in the cytoplasm can lead to enzyme inhibition, which
in turn causes necrosis and chlorosis.[4] To avoid these problems, plants developed mechanisms that limit sodium
uptake by roots, store them in cell vacuoles, and control them over long distances;[5] excess sodium may also be
stored in old plant tissue, limiting the damage to new growth.
Carbon fixationCarbon fixation or arbon assimilation refers to the conversion process of inorganic carbon
(carbon dioxide) to organic compounds by living organisms. The most prominent example is photosynthesis,
although chemosynthesis is another form of carbon fixation that can take place in the absence of sunlight. Organisms
that grow by fixing carbon are called autotrophs. Autotrophs include photoautotrophs, which synthesize organic
compounds using the energy of sunlight, and lithoautotrophs, which synthesize organic compounds using the energy
of inorganic oxidation. Heterotrophs are organisms that grow using the carbon fixed by autotrophs. The organic
compounds are used by heterotrophs to produce energy and to build body structures. "Fixed carbon", "reduced
carbon", and "organic carbon" are equivalent terms for various organic compounds.[1]

Net vs gross CO2 fixation

Graphic showing net annual amounts of CO 2 fixation by land and sea-based organisms.
It is estimated that approximately 258 billion tons of carbon dioxide are converted by photosynthesis annually. The
majority of the fixation occurs in marine environments, especially areas of high nutrients. The gross amount of
carbon dioxide fixed is much larger since approximately 40% is consumed by respiration following photosynthesis.
[1] Given the scale of this process, it is understandable that RuBisCO is the most abundant protein on earth.

Overview of pathways

Six autotrophic carbon fixation pathways are known as of 2011. The Calvin cycle fixes carbon in the chloroplasts of
plants and algae, and in the cyanobacteria. It also fixes carbon in the anoxygenic photosynthetic proteobacteria
called purple bacteria, and in some non-phototrophic proteobacteria.[2]

Oxygenic photosynthesis

In photosynthesis, energy from sunlight drives the carbon fixation pathway. Oxygenic photosynthesis is used by the
primary producersplants, algae, and cyanobacteria. They contain the pigment chlorophyll, and use the Calvin
cycle to fix carbon autotrophically.
The process works like this:
+
2H2O 4e + 4H
+ O2
+
CO2 + 4e + 4H CH2O + H2O
In the first step, water is dissociated into electrons, protons, and free oxygen. This allows the use of water, one of the
most abundant substances on Earth, as an electron donoras a source of reducing power. The release of free oxygen
is a side-effect of enormous consequence. The first step uses the energy of sunlight to oxidize water to O 2, and,
ultimately, to produce ATP
ADP + Pi
ATP + H2O
and the reductant, NADPH
+

NADP + 2e + 2H+
NADPH + H+
In the second step, called the Calvin cycle, the actual fixation of carbon dioxide is carried out. This process
consumes ATP and NADPH. The Calvin cycle in plants accounts for the preponderance of carbon fixation on land.
In algae and cyanobacteria, it accounts for the preponderance of carbon fixation in the oceans. The Calvin cycle
converts carbon dioxide into sugar, as triose phosphate (TP), which is glyceraldehyde 3-phosphate (GAP) together
with dihydroxyacetone phosphate
(DHAP):
3 CO2 + 12 e + 12 H+ + Pi TP + 4 H2O
An alternative perspective accounts for
NADPH (source of e ) and ATP: +
3 CO2 + 6 NADPH + 6 H+ + 9 ATP + 5 H
2O TP + 6 NADP + 9 ADP + 8 Pi
The formula for inorganic
phosphate (Pi) is HOPO32 + 2H+. Formulas for triose and TP are C2H3O2-CH2OH and
C2H3O2-CH2OPO32 + 2H+

Evolutionary considerations

Somewhere between 3.5 and 2.3 billion years ago, the ancestors of cyanobacteria evolved oxygenic photosynthesis,
enabling the use of the abundant yet relatively-oxidized molecule H2O as an electron donor to the electron tranport
chain of light-catalyzed proton-pumping responsible for efficient ATP synthesis.[3][4] When this evolutionary
breakthrough occurred, autotrophy (growth using inorganic carbon as the sole carbon source) is believed to have
already been developed. However, the proliferation of cyanobacteria, due to their novel ability to exploit water as a
source of electrons, radically altered the global environment by oxygenating the atmosphere and by achieving large
fluxes of CO2 consumption. [5]

Carbon concentrating mechanisms

Many photosynthetic organisms have acquired inorganic carbon concentrating mechanisms (CCM), which increase
the concentration of carbon dioxide available to the initial carboxylase of the Calvin cycle, the enzyme RuBisCO.
The benefits of CCM include increased tolerance to low external concentrations of inorganic carbon, and reduced
loses to photorespiration. CCM can make plants more tolerant of heat and water stress.
Carbon concentrating mechanisms use the enzyme carbonic anhydrase (CA), which catalyze both the dehydration of
bicarbonate to carbon dioxide and the hydration of carbon dioxide to bicarbonate
HCO3 + H+
CO2 + H2O
Lipid membranes are much less permeable to bicarbonate than to carbon dioxide. To capture inorganic carbon more
effectively, some plants+ have adapted the anaplerotic reactions
HCO3 + H + PEP OAA + Pi
catalyzed by PEP carboxylase (PEPC), to carboxylate phosphoenolpyruvate (PEP) to oxaloacetate (OAA) which is a
C4 dicarboxylic acid.
CAM plants
CAM plants that use Crassulacean acid metabolism as an adaptation for arid conditions. CO2 enters through the
stomata during the night and is converted into the 4-carbon compound, malic acid, which releases CO2 for use in the
Calvin cycle during the day, when the stomata are closed. The jade plant (Crassula ovata) and cacti are typical of
CAM plants. Sixteen thousand species of plants use CAM.[6] These plants have a carbon isotope signature of -20 to
-10 .[7]
C4 plants
C4 plants preface the Calvin cycle with reactions that incorporate CO2 into one of the 4-carbon compounds, malic
acid or aspartic acid. C4 plants have a distinctive internal leaf anatomy. Tropical grasses, such as sugar cane and
maize are C4 plants, but there are many broadleaf plants that are C4. Overall, 7600 species of terrestrial plants use C4
carbon fixation, representing around 3% of all species.[8] These plants have a carbon isotope signature of -16 to -10
.[7]
C3 plants
The large majority of plants are C3 plants. They are so-called to distinguish them from the CAM and C4 plants, and
because the carboxylation products of the Calvin cycle are 3-carbon compounds. They lack C 4 dicarboxylic acid
cycles, and therefore have higher carbon dioxide compensation points than CAM or C4 plants. C3 plants have a
carbon isotope signature of -24 to -33.[7]

Other autotrophic pathways

Of the five other autotrophic pathways, two are known only in bacteria, two only in archaea, and one in both bacteria
and archaea.

Reductive citric acid cycle

The reductive citric acid cycle is the oxidative citric acid cycle run in reverse. It has been found in anaerobic and
microaerobic bacteria. It was proposed in 1966 by Evans, Buchanan and Arnon who were working with the
anoxygenic photosynthetic green sulfur bacterium that they called Chlorobium thiosulfatophilum. The reductive
citric acid cycle is sometimes called the Arnon-Buchanan cycle.[9]

Reductive acetyl CoA pathway

The reductive acetyl CoA pathway operated in strictly anaerobic bacteria (acetogens) and archaea (methanogens).
The pathway was proposed in 1965 by Ljungdahl and Wood. They were working with the gram-positive acetic acid
producing bacterium Clostridium thermoaceticum, which is now named Moorella thermoacetica. Hydrogenotrophic
methanogenesis, which is only found in certain archaea and accounts fror 80% of global methanogenesis, is also
based on the reductive acetyl CoA pathway. The pathway is often referred to as the Wood-Ljungdahl pathway.[10]
[11]

3-Hydroxypropionate and two related cycles

PEP is formed from the decarboxylation of oxaloacetate and hydrolysis of one guanosine triphosphate molecule.
This reaction is catalyzed by the enzyme phosphoenolpyruvate carboxykinase (PEPCK). This reaction is a ratelimiting step in gluconeogenesis:[1]
GTP + oxaloacetate GDP + phosphoenolpyruvate + CO2

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [ 1]

[[File: |{{{bSize}}}px|alt=Glycolysis and Gluconeogenesis edit|]]
Glycolysis and Gluconeogenesis edit

1.

The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

In plants

PEP may be used for the synthesis of chorismate through the shikimate pathway.[2] Chorismate may then be
metabolized into the aromatic amino acids (phenylalanine, tryptophan and tyrosine) and other aromatic compounds.
The first step is when Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-Darabinoheptulosonate-7-phosphate (DAHP), in a reaction catalyzed by the enzyme DAHP synthase.

The 3-hydroxypropionate cycle is utilized only by green nonsulfur bacteria. It was proposed in 2002 for the
anoxygenic photosynthetic Chloroflexus aurantiacus. None of the enzymes that participate in the 3hydroxypropionate cycle are especially oxygen sensitive.[12][13]
A variant of the 3-hydroxypropionate pathway was found to operate in aerobic extreme thermoacidophile archaeon
Metallosphaera sedula. This pathway, called the 3-hydroxypropionate/4-hydroxybutyrate cycle .[14] And yet
another variant of the 3-hydroxypropionate pathway is the dicarboxylate/4-hydroxybutyrate cycle. It was discovered
in anaerobic archaea. It was proposed in 2008 for the hyperthermophile archeon Ignicoccus hospitalis.[15]

Chemosynthesis

Chemosynthesis is carbon fixation driven by the oxidation of inorganic substances (e.g., hydrogen gas or hydrogen
sulfide). Sulfur- and hydrogen-oxidizing bacteria often use the Calvin cycle or the reductive citric acid cycle.[16]

Non-autotrophic pathways

Although almost all heterotrophs cannot synthesize complete organic molecules from carbon dioxide, some carbon
dioxide is incorporated in their metabolism.[17] Notably pyruvate carboxylase consumes carbon dioxide (as
bicarbonate ions) as part of gluconeogenesis, and carbon dioxide is consumed in various anaplerotic reactions.

Carbon isotope discrimination

Some carboxylases, particularly RuBisCO, preferentially bind the lighter carbon stable isotope carbon-12 over the
heavier carbon-13. This is known as carbon isotope discrimination and results in carbon-12 to carbon-13 ratios in the
plant that are lower than in the free air. Measurement of this ratio is important in the evaluation of water use
efficiency in plants, and also in assessing the possible or likely sources of carbon in global carbon cycle studies.

Phosphoenolpyruvic
acid
Phosphoenolpyruvic acid (PEP), or phosphoenolpyruvate as the anion, is an important chemical compound in

biochemistry. It has the highest-energy phosphate bond found (-61.9 kJ/mol) in living organisms, and is involved in
glycolysis and gluconeogenesis. In plants, it is also involved in the biosynthesis of various aromatic compounds, and
in carbon fixation; in bacteria, it is also used as the source of energy for the phosphotransferase system.

In glycolysis

PEP is formed by the action of the enzyme enolase on 2-phosphoglycerate. Metabolism of PEP to pyruvate by
pyruvate kinase (PK) generates 1 molecule of adenosine triphosphate (ATP) via substrate-level phosphorylation.
ATP is one of the major currencies of chemical energy within cells.
2-phospho-D-glycerate
Enolase
phosphoenolpyruvate
Pyruvate kinase
pyruvate
H2O

ADP ATP

H2O
Enolase

Pyruvate kinase

Compound C00631 at KEGG Pathway Database. Enzyme 4.2.1.11 at KEGG Pathway Database. Compound C00074 at KEGG Pathway
Database. Enzyme 2.7.1.40 at KEGG Pathway Database. Compound C00022 at KEGG Pathway Database.

In gluconeogenesis

Biosynthesis of DAHP from phosphoenolpyruate and erythrose-4-phosphate

In addition, in C4 plants, PEP serves as an important substrate in carbon fixation. The chemical equation, as
catalyzed by phosphoenolpyruvate
carboxylase (PEP carboxylase), is:
PEP + HCO3 oxaloacetate

Animals

Since only some plants need sodium and those in small quantities, a completely plant-based diet will generally be
very low in sodium. This requires some herbivores to obtain their sodium from salt licks and other mineral sources.
The animal need for sodium is probably the reason for the highly conserved ability to taste the sodium ion as "salty."
Receptors
for the pure salty taste respond best to sodium, otherwise only to a few other small monovalent cations
(Li+, NH4+, and somewhat to K+). Calcium ion (Ca2+) also tastes salty and sometimes bitter to some people but, like
potassium, can trigger other tastes.
Sodium ions play a diverse and important role in many physiological processes. Sodium is an essential nutrient that
regulates blood volume, blood pressure, osmotic equilibrium and pH.[6]
Humans
The minimum physiological requirement for sodium is 500 milligrams per day.[6] Sodium chloride is the principal
source of sodium in the diet, and is used as seasoning and preservative, such as for pickling and jerky; most of it
comes from processed foods.[7] The Adequate Intake for sodium is 1.2 to 1.5 grams per day,[8] but on average
people in the United States consume 3.4 grams per day,[9] the minimum amount that promotes hypertension.[10]
(Note that salt contains about 39.3% sodium[11]the rest being chlorine and other trace chemicals; thus the UL of
2.3g sodium would be about 5.9g of saltabout 1 teaspoon[12])
Normal serum sodium levels are between approximately 135 and 145 mEq/liter (135 - 145 mmol/L). A serum
sodium level of less than 135 mEq/L qualifies as hyponatremia, which is considered severe when the serum sodium
level is below 125 mEq/L.[13][14]
The renin-angiotensin system and the atrial natriuretic peptide indirectly regulate the amount of signal transduction
in the human central nervous system, which depends on sodium ion motion across the nerve cell membrane, in all
nerves. Sodium is thus important in neuron function and osmoregulation
between cells and the extracellular fluid;
the distribution of sodium ions are mediated in all animals by Na+/K+-ATPase.[15] Hence, sodium is the most
prominent cation in extracellular fluid: the 15 liters of it in a 70 kg human have around 50 grams of sodium, 90% of
the body's total sodium content.
Some potent neurotoxins, such as batrachotoxin, increase the sodium ion permeability of the cell membranes in
nerves and muscles, causing a massive and irreversible depolarization of the membranes, with potentially fatal
consequences. However, drugs with smaller effects on sodium ion motion in nerves may have diverse
pharmacological effects which range from anti-depressant to anti-seizure actions.

Function of sodium ions

Whenever there is an increase in sodium concentration in the blood, the kidney releases most of it in order that there
will be enough water for use of the body. But when there is a decrease in its concentration, there is more release of
water to store more sodium which the body needs dearly. This process is known as osmo-regulation.
Sodium is the primary cation (positive ion) in extracellular fluids in animals and humans. These fluids, such as
blood plasma and extracellular fluids in other tissues, bathe cells and carry out transport functions for nutrients and
wastes. Sodium is also the principal cation in seawater, although the concentration there is about 3.8 times what it is
normally in extracellular body fluids.

Human water and salt balance

Main articles: hyponatremia, hypernatremia, diuretic and vasopressin

Although the system for maintaining optimal salt and water balance in the body is a complex one,[16] one of the
primary ways in which the human body keeps track of loss of body water is that osmoreceptors in the hypothalamus
sense a balance of sodium and water concentration in extracellular fluids. Relative loss of body water will cause
sodium concentration to rise higher than normal, a condition known as hypernatremia. This ordinarily results in
thirst. Conversely, an excess of body water caused by drinking will result in too little sodium in the blood
(hyponatremia), a condition which is again sensed by the hypothalamus, causing a decrease in vasopressin hormone
secretion from the anterior pituitary, and a consequent loss of water in the urine, which acts to restore blood sodium
concentrations to normal.
Severely dehydrated persons, such as people rescued from ocean or desert survival situations, usually have very high
blood sodium concentrations. These must be very carefully and slowly returned to normal, since too-rapid correction
of hypernatremia may result in brain damage from cellular swelling, as water moves suddenly into cells with high
osmolar content.

In humans, a high-salt intake was demonstrated to attenuate nitric oxide production. Nitric oxide (NO) contributes to
vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and
leukocyte adhesion to the endothelium [17]

Urinary sodium

Because the hypothalamus/osmoreceptor system ordinarily works well to cause drinking or urination to restore the
body's sodium concentrations to normal, this system can be used in medical treatment to regulate the body's total
fluid content, by first controlling the body's sodium content. Thus, when a powerful diuretic drug is given which
causes the kidneys to excrete sodium, the effect is accompanied by an excretion of body water (water loss
accompanies sodium loss). This happens because the kidney is unable to efficiently retain water while excreting
large amounts of sodium. In addition, after sodium excretion, the osmoreceptor system may sense lowered sodium
concentration in the blood and then direct compensatory urinary water loss in order to correct the hyponatremic (low
blood sodium) state.