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Fluids and Electrolytes
Water constitutes 50% to 70% of the total body weight or about 40 liters
In males the ratio is ~ 65%
In females the ratio is less as they have more adipose tissue with lower
water content
Body water is distributed between two major compartments
Intracellular (ICF) that makes 40% of total body water
Extracellular (ECF) making 60% of total body water , divided between
Interstitial fluid (IF) (80% of ECF) that bathes the tissue cells
Plasma (20% of ECF) that circulates
The difference between IF and plasma is largely the high plasma
protein content
Total body water and its distribution between different compartments
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Shift of body fluids through different compartments
Saladin’s Anatomy & Physiology fourth edition McGraw Hill
Water intake and output
Saladin’s Anatomy & Physiology fourth edition McGraw Hill
Hydration and dehydration
Saladin’s Anatomy & Physiology fourth edition McGraw Hill
Fluids and Electrolytes
Body water acts as a solvent for two types of particles
Electrolytes: particles that can dissociate in solution from other partciles
and exist as electrically charged ions or compounds
Examples: Na+, K+, HCO3-,
Nonelectrolytes: particles that do not dissociate in solution, they are
mostly organic
Examples: glucose, urea, amino acids, lipids
Fluids and Electrolytes
Definitions*
Units of measuring solute concentration
Mole = 6 x 106 molecules of a substance. This is a constant figure
Millimole = 1 / 1000 = 1 / 10-3 of a mole
Equivalent = amount of ionized solute = moles x valence of solute
Example: 1 mmol/L of CaCl2 concentration dissociates into 2 Cland one Ca++ therefore the Ca++ concentration is
1 mmol x 2 (Ca++ valency) = 2 meq/ L
Osmole: one osmole = number of particles in a solution in which a solute
dissociates
Osmolarity = concentration of particles in solution expressed as osmoles
Electrolyte as well as nonelectrolyte particles contribute to the
osmolarity of a solution
*
Modified from Costanzo Physiology second edition Saunders
Fluids and Electrolytes
Acid and Base
An acid is a chemical compound that releases H in a solution
The more the H+ released the stronger the acid and the lower the pH
An example of a strong acid is HCl
An example of a weak acid is H2 CO3
A base is a compound that accepts H+
An example of a strong base is NaOH
An examople of a weak base is HCO3-
Fluids and Electrolytes
pH
pH is a measure of H+ concentration in body fluids
It is expressed in a logarithmic term because of it is a very small number
pH is the negative of H+ tenth logarithm
pH = - log10 (H+)
Fluids and Electrolytes
Compartment Volume Shifts
Normally there is a free interchange of water between the different
compartments e.g. exchange between intravascular and interstitial
compartments at the capillary level
Loss of blood results in a shift of water from the interstitial to the vascular
compartments
Excessive loss of interstitial fluid results in its shrinkage and a shift of
intracellular fluid to interstitial compartment
Burns, hemorrhage, vomiting, diarrhea, excessive sweating, lack of water
intake are all examples
Excessive hydration of ECF leads to water shift into the cells
Fluids and Electrolytes
Water Balance
To a large extent, the amount of body water is constant
This is achieved my balancing water intake and loss from the body
About 2500 ml of water is taken (or produced) and the same amount
is lost
Intake: Drinking (60%)
Water in solid food (30%)
Internally produced water (10%)
Output: Urine (60%)
Loss through the lungs and skin (insensible loss) (30%)
Sweating (7%)
Feces (3%)
Fluids and Electrolytes
Composition of ICF and ECF
Na+ and Cl-, and HCO- make the bulk of ECF ions
K+ and Mg++ are the main intracellular ions balanced by proteins and
organic phosphates
Ca++ is overwhelmingly in the ECF
The IC pH is ~ 7.1, while the EC is ~7.4
The osmolarity of EC and IC is the same (290 mosm/L) since water moves
freely across the cell membrane
Plasma proteins do not pass into ECF because of their large size
Composition of extracellular and intracellular fluids, notice that
the osmolarity is more or less the same
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Fluids and Electrolytes
Electroneutrality
Each body fluid compartment must have an equal number of anions
and cations
That is the same concentration in meq/L of the positively charged as
the negatively charged molecules
The plasma membrane has a negative intracellular and
a positive extracellular surface
Fluids and Electrolytes
Creation of Concentration Differences
Across Cell Membrane
Maintaining a different concentration of the same ion across the cell
membrane is crucial to cell function
Without this difference neural transmission, muscle contraction, and
absorption of nutrient from the GI tract and renal tubular function
become impossible
The sodium potassium pump activated by ATP
It is responsible for the difference between the intracellular and extracellular
concentrations of the two ions
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Fluids and Electrolytes
Ion Channels and Mediated Transporters
Both are membrane integral proteins
Both are specific allowing one ion or a specific class of particles through
Ion channels are permanently open to the specific ions
Mediated transporters undergo conformational changes on either
side of the membrane, opening on one side and closing on the other
then reversing this movement to allow larger molecules to pass
The result is that ion channels are faster than mediated transporters
Mediated transport is of two types
Facilitated diffusion
Active transport
Types of transport across cell membrane
Facilitated diffusion uses a transporter to move particles from higher to lower concentration.
It stops when the concentration is equal on both sides of the membrane
Active transport occurs against electrochemical gradient and consumes energy (ATP)
Active transport is of two types: primary and secondary
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Ions need open channels to diffuse
They can not diffuse through the bilayerd cell membrane
They move ions several hundred times faster than transporters
Vander Physiology eighth edition McGraw Hill
Fluids and Electrolytes
Creation of Concentration Differences
Across Cell Membrane
The Na+ – K+ pump keeps Na+ concentration higher and K+ concentration
lower outside the cell than inside it
This is an energy consuming process
Energy is derived from adenosine triphospahte (ATP)
The transporter acts as an enzyme that extracts energy from
ATP and converts it to ADP, the energy is used to move particles
across a gradient
Na+ - K+ ATPase is responsible for creating the large concentration
gradient across the cell membrane
Typically for each 3 Na+ out 2 K+ get in resulting in an electrical gradient
with ECF positive and ICF negative
Primary active transport
Phosphorilation leads to ↑affinity of transporter to the particle
Random oscillations of the transporter opens it to intracellular and
extracellular sides alternately
The transporter is an ATPase
Vander Physiology eighth edition McGraw Hill
Fluids and Electrolytes
Creation of Concentration Differences
Across Cell Membrane
Calcium has its Ca++ ATPase that keeps extracellular Ca++ concentration
higher than its intracellular concentration
Ca++ ATPase is present in cell wall, organelle membranes and
endoplasmic reticulum
In addition to the ATP consuming transporters, some molecules establish
concentration gradients utilizing the Na+ gradient established by
Na+ – K+ ATPase
Amino acids, glucose, Ca++ and H+ are transported this way
This is referred to as “secondary active transport”
Fluids and Electrolytes
Creation of Concentration Differences
Across Cell Membrane
Secondary Active Transport*
The secondarily transported solute can move in the same direction
(into the cell) as the primary (Na+) ion as with glucose molecules
In this case the process is identified as “cotransport”
If the secondarily transported solute goes in the opposite direction as
the primarily transported ion (Na+), that is outside the cell then
the process is termed “countertransport”
*Notice that the primary transport
Na+ always moves from ECF to the cell inside
Secondary active transport – Cotransport
Notice that the ion (Na+ in this case) is moving downhill while the
co-transported solute is moving against a high gradient
If the solute moves in an opposite direction than the Na+ the process is
called countertransport (not shown in this figure)
Vander Physiology tenth edition McGraw Hill
Movement of different solutes across cell membrane
Vander Physiology eighth edition McGraw Hill
Fluids and Electrolytes
Regulation of Water Intake
Low water intake will lead to ↑plasma osmolality
Low blood volume or blood pressure activate angiotensin II
Both stimuli stimulate hypothalamic thirst center to secrete ADH
High plasma osmolality leads to ↓salivary secretion → thirst → water intake
Once wet, the buccal mucosa eliminates the feeling of thirst
Stretch receptors in the GI tract act on to inhibit thirst center and avoid
excessive water intake and ↓plasma osmolality*
Fluids and Electrolytes
Water intake by the Cell
Water is a polar molecule
It passes through the cell membrane rapidly
Aquaporins are cell membrane proteins that facilitate the passing of water
into the cell
The permeability of the cell membrane to water depends on the number
of aquaporins
The number of aquaporins differ from cell type to the other and in the
same cell in response to different cignals
Fluids and Electrolytes
Water Output
The kidneys have to excrete metabolic by products dissolved in water
This mounts to about 500 cc*
Skin and lungs loose about 700 cc/day
Water is lost with the stools
The above represent obligatory water loss that needs to be replaced
The amount lost in the urine and sweat depend on the amount of
water ingested in drinks and food and the amount of sweat secreted
ADH resorbs water from renal collecting ducts only if the blood volume is
low
ADH secretion is controlled by hypothalamic osmoreceptors and by
significant changes in blood pressure
Fluids and Electrolytes
Sodium
Sodium is the very valuable ion, it maintains total body water and blood
volume
Sodium is important in maintaining the resting cell membrane potential
Sodium gradiants across cell membrane provides the energy for cotransport
of glucose, amino acids, potassium and calcium
Sodium bicarbonate is a major ECF buffer
Sodium/potassium pump is important in generating body heat
The adult needs 0.5 Gm of sodium/day
Fluids and Electrolytes
Sodium Regulation
The adult needs 0.5 Gm of sodium/day
Sixty five percent of filtered Na is resorbed by renal PCT
Another 25% is resorbed by HL
High aldosterone levels resorb the rest in the DCT and CD, otherwise
no Na+ resorption occurs beyond DCT
Water may or may not follow aldosterone Na+ resorbed
Water resorption depends on ADH aquaporins inserted in CD principal cells
Aldosterone is secreted in response to ↓BP or ↓Na+ in the JGA perfusate
Baroreceptors respond to ↓BP → vasoconstriction and activation of
renin/angiotensin/aldosterone mechanism
Fluids and Electrolytes
Sodium Regulation
Atrial Natriuretic Peptide (ANP): produces diuresis reducing blood volume
Promotes Na+ renal CD resorption, inhibits ADH and renin secretion
and causes vasodilatation
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Fluids and Electrolytes
Potassium
The most abundant ion in the ICF
Determines intracellular osmolarity
Part of the sodium potassium pump
Essential for protein synthesis
Fluids and Electrolytes
Potassium Regulation
The kidneys main function usually is to excrete potassium
Normally 60% - 80% of potassium is resorbed through renal PCT
Additional 10% resorbed through HL ascending limb
The rest is usually lost in the urine
If interstitial K+ is low, K+ will move from cells to interstitial space
CD principal cells reduce K+ loss to a minimum
Adrenal cortex cells are sensitive to K+ level, an increase will lead
to aldosterone secretion
High dietary K+ intake leads to K+ loss in the urine
The relation between potassium and hydrogen ions in the plasma
Saladin’s Anatomy & Physiology fourth edition McGraw Hill
Potassium balance in the body
Costanzo Physiology second edition Saunders
Fluids and Electrolytes
Calcium
Component of the skeleton
Essential for the activation of muscle contraction, including the heart
Intracellular secondary messenger for hormones and neurotransmitters
Part of the coagulation mechanism
Must be kept outside the cells to avoid precipitation with phosphate
Fluids and Electrolytes
Phosphorus
Concentrated intracellularly as mon. di and triphosphates
Part of the nucleic acids, lipophosphates, ATP, GTP and cAMP
Activate many metabolic reactions
Help maintain body fluid pH
Fluids and Electrolytes
Acid-Base Balance
Cell function is possible only in a very tight range of H+ concentration (pH)
H+ changes the shape of proteins including the enzymes
The body produces two types of acid
Fixed: SO4, PO4 , lactic acid, fatty acids, ketone bodies, etc.
Volatile: H2CO3
Normal arterial pH is 7.40, venous pH is 7.35, ICF 7.00
Acidosis is a tendency towards ↓pH
Acidemia is a drop in pH below 7.35
Alkalosis is a tendency towards a ↑pH
Alkalemia is a rise of pH above 7.45
Fluids and Electrolytes
Hydrogen Ion Metabolism
H+ is produced from the metabolism of proteins and other organic molecules
Cell metabolism results in the formation CO2 which reacts with water
CO2 + H2 O= H+ + HCO3The loss of HCO3- in urine and stools constitutes a gain in H+
H+ is lost in vomitus and urine, and is incorporated in organic compounds
H+ is also lost in hyperventilation with the excessive loss of CO2
Fluids and Electrolytes
Acid-Base Balance
Blood pH is regulated by three mechanisms
Chemical buffers: act immediately
Respiratory rate and depth: intermediate speed
Renal correction: slow but most potent
Fluids and Electrolytes
Acid-Base Balance
Chemical buffers
A buffer is a mixture of a weak acid and its base or a weak base and its acid
A buffered solution resists change in its pH when a strong acid or a
strong base is added to it
Chemical buffers can “hide” change in pH temporarily until renal control
takes effect
H2CO3 / HCO3- system
HCl + NaHCO3 → NaCL + H2CO3 (weak acid)
NaOH + H2CO3 → NaHCO3 (weak base) + H2O
Plasma HCO3- levels are referred to as “alkaline reserve” (25 mEq/L)
Fluids and Electrolytes
Acid-Base Balance
Chemical buffers
Carbonic acid – Bicarbonate System:
H2CO3 / HCO3HCl + NaHCO3 → NaCL + H2CO3 (weak acid)
NaOH + H2CO3 → NaHCO3 (weak base) + H2O
Plasma HCO3- levels are referred to as “alkaline reserve” (25 mEq/L)
Normally a 20:1 HCO3- to H2 CO3 maintains a plasma pH at the range of 7.35 – 7.45
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Fluids and Electrolytes
Acid-Base Balance
Chemical Buffers
Phosphate system:
Because of its ICF presence, it is more important as an IC than plasma
buffer
Na2HPO4 (weak base) and NaH2PO4 (weak acid)
HCL + Na2HPO4 → NaCl + NaH2PO4
NaOH + NaH2PO4 → Na2HPO4 + H2O
Fluids and Electrolytes
Acid-Base Balance
Chemical Buffers
Ammonia/Ammonium System:
NH3 / NH4+
NH3 is generated in tubular cells absorbs H+
NH3 reacts with ClNH3 + H+ → NH4+ + Cl- → NH4 Cl
Fluids and Electrolytes
Acid-Base Balance
Chemical Buffers
Protein system:
Intracellular proteins can expose NH2 or COOH ends (amphoteric)
In acidic medium absorbing H+ as in R-NH2 + H+ → R-NH3+
In an alkaline medium releasing H+ as in R-COOH → H+ + R-COOHemoglobin is an excellent intracellular buffer, reduced Hgb binds H+
Fluids and Electrolytes
Acid-Base Balance
Respiratory Regulation
CO2 + H2O →← H2CO3 →← H+ + HCO3CO2 is easily expelled from the lungs
The addition of acid will cause the conversion of H2CO3 to H2O and CO2
which is easily expelled from the lungs by ↑ RR
The addition of alkali depresses the respiratory center → ↓ RR → ↑ CO2
→ H2CO3 → ↓pH
Respiratory control has a large reserve capacity
It addresses “volatile acid”
Can affect change in pH within a very short time (minutes)
Fluids and Electrolytes
Acid-Base Balance
Renal Regulation
Addresses “fixed acid”, they actually eliminate H+ from the body
Corrects the greatest quantity of excesses in acid or base
Correct imbalance slower than other two systems
Conserves some chemical buffers (HCO3- )
Generates some buffers (HCO3-, NH4+ from amino acid glutamine)
Secretes H+ in the urine in PCT and CD
H+ is obtained from dissociation of H2CO3 created by CO2 and H2O
For this, carbonic anhydrase is present in the renal cells
Fluids and Electrolytes
Acid-Base Balance
Renal Regulation
The renal tubules convert CO2 and H2O to H2CO3
H2CO3 dissociates into H+ and HCO3- in a reversible reaction
The enzyme carbonic anhydrase facilitates the two sides of the reaction
In case of excess H+ the kidney excretes H+ in the urine and CO2 is
sent back to the PCT cell where it is converted to HCO3- and
sent back to the ECF elevating the pH
In case of alkalosis HCO3- is secreted in the urine and more H+ is
reabsorbed into the ECF
HCO3- reclaim from the filtrate
Bicarb left after Na+ resorption is converted to carbonic acid, carbonic anhydrase (CA) splits
carbonic acid to H2O and CO2, H2O is passed in the urine, CO2 enters the cell where it is
converted to H2CO3 then HCO3- . This exits to ECF through secondary active transport with Na+
Marieb Human Anatomy and Physiology seventh edition Pearson Benjamin Cummings
Buffering of H+ by the kidney
Saladin’s Anatomy & Physiology fourth edition McGraw Hill