Fluids and Electrolytes

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 Marieb Human Anatomy and Physiology seventh edition Pearson Benjamin Cummings

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 Cl- and 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 Vander Physiology eighth edition McGraw Hill

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 Vander Physiology tenth edition McGraw Hill

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 Vander Physiology eighth edition McGraw Hill

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

Saladin’s Anatomy & Physiology fourth edition McGraw Hill

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+ + HCO3- The 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 / HCO3- HCl + 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 Saladin’s Anatomy & Physiology fourth edition McGraw Hill

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 Cl- NH3 + 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-COO- Hemoglobin is an excellent intracellular buffer, reduced Hgb binds H+

Fluids and Electrolytes Acid-Base Balance Respiratory Regulation CO2 + H2O →← H2CO3→← H+ + HCO3- CO2 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

Fluids and Electrolytes