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Acid-Base Balance. AnS 536 Spring 2014. The properties of water are essential to life The properties of water are based on its polar covalent structure and its ability to form H-bonds with itself and other molecules. d +. d +. d -. Water as an Electric Dipole.
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Acid-Base Balance AnS 536 Spring 2014
The properties of water are essential • to life • The properties of water are based on • its polar covalent structure and its • ability to form H-bonds with itself • and other molecules... d+ d+ d-
Its polar covalent structure makes water a good solvent... • for large molecules like proteins whose • surfaces are charged • for other molecules with polar covalent • bonds • for ionic compounds
Dissolving macromolecules (e.g., proteins): Water of hydration
Dissolving molecules with polar covalent bonds: d+ d+ d+ N NH3 d-
Dissolving ionic compounds: Ionic solids dissolve readily in water d+ d- d- d+ Cl- Na+ d+ d- d+
+ H H H H O O O H H H or, + - H + OH HOH proton hydroxide ion The incomplete ionization of water: - + OH hydroxide ion hydronium ion
The concentration of H+ ions (protons) in a solution is measured by its pH In pure water: [H+] = [H3O+] = [OH-] = 10-7M NOTE: a 1 M solution contains 1 mole of a substance dissolved in 1 liter of water; a mole of a substance is its molecular mass in grams pH = -log[H+] = -log10-7 = 7.0 A pH of 7.0 is defined as neutral 10-7M = 10-7 g/liter
Electrolytes • Anions and cations distributed throughout the fluid compartments • Maintain electrical neutrality (anions MUST EQUAL cations) • Cations: Na, K, Ca, Mg • Anions: Cl, HCO3, S04, proteins, lactic acid • Critical to maintenance of acid/base balance • Influence water retention and water dissociation (favoring either H+ or OH-) *electrolytes listed in red are most critical to consider in diet (dietary electrolyte balance)
Na/K ATPase Pump Lehninger, 1993
Acid–Base Balance • Anion-cation balance regulates acid-base balance • Cations: Ca2+, Mg2+, Na+, K+ • Alkalosis or basic (increased OH–, increased pH) • Anions: Cl–, SO42–, proteins, lactic acid (toxic) • Acidosis or acidic (increased H+, lowered pH)
Stewart (1981) • Concept of electrolytes as critical factors in acid/base balance • Strong ion difference (SID) • sum of all strong cations minus sum of all strong anions (NA, K, CL, SO42-) • anions greater = negative SID = H+ > OH- • cations greater = positive SID = OH- > H+
Stewart (1981) • Balance of SID is maintained by the dissociation and reassociation of water
+ H H H H O O O H H H or, + - H + OH HOH proton hydroxide ion The incomplete ionization of water: - + OH hydroxide ion hydronium ion
Cl- Na+ Dissolved in positively charged water (H+), thus lowering pH Dissolved in negatively charged water (OH-), thus raising pH Acids and bases ionize in water: acid base HCl NaOH H+ OH-
Peter Stewart’s Theories of Acid-Base Balance • Based upon three variables that contribute to hydrogen ion concentration [H+] • Strong ion difference • Total weak acids • Partial pressure of carbon dioxide • Theory was developed to determine renal contribution to acid-base homeostasis based upon strong ions regulated by the kidney • K+, Na+, Cl- • Equation specific to kidney’s contribution to homeostasis • Kidney does not regulate CO2 or weak acids
H+ = Dependent Variable • Three independent variables determine the value of H+: • SID • Pco2 • H increases as Pco2 increases • CO2 acts as an acid • Total concentration of weak acids (plasma proteins) • H increases as weak acids increase
Control of Acid/Base Balance • Short-term (rapid) control • Lungs • During acidosis, more carbon dioxide exhaled, affects bicarbonate concentrations (an anion) • Decrease bicarbonate, decrease H+, increase pH • Chronic (long-term) control • GI tract – altered absorption of anions and cations • Kidneys – altered excretion/resorption of anions and cations CO2 + H2O HCO3– + H+ H2CO3
Respiratory component Mismatch between CO2 production (tissue - decreasing) and excretion (lung - increasing) Carbonic anhydrase activity increases postnatally Bicarbonate increases while carbon dioxide decreases In acidotic neonates, bicarbonate significantly lower than unstressed newborn because decreased dissociation of carbonic acid to bicarbonate Metabolic component Lactate is high (above 10 mmol/L in stressed newborns) Gluconeogenesis from lactate does not occur prenatally; enzymes in liver triggered postnatally by increased oxyegn tension Ig uptake in domestic species slow resolution of acidosis (partial negative charge) Plasma expansion also occurs SID decreases initially (1st hour) and then slowly increases through first day Newborn Acid-Base Balance
Altering Acid Base Balance • DCAD diets • Sodium bicarbonate administration • IV vs GI • effect of other sodium forms
Dietary Electrolyte Balance • Dietary electrolyte balance (dEB) • Na+ + K+ – Cl– • Diet electrolyte balance can be used to affect acid-base balance in body • Acidic conditions increase affinity for receptors to bind PTH Dairy rations for dry cows are difficult to make acidic,because alfalfa is often used (high in potassium (a cation)
Element MW Valence Weight equivalents g/mol mmol/g mEq/g Na 22.99 +1 43.50 43.50 Mg 24.31 +2 41.14 82.27 K 39.10 +1 25.58 25.58 Ca 40.08 +2 24.95 49.90 Cl 35.45 –1 28.20 28.20 Weight or Equivalents…? • Dietary electrolyte balance (dEB) is expressed in equivalents, why not weight or percent of diet? • Eq = Molecular weight valence
Classical Approaches to Renal Acid-Base Balance • Metabolism produces [H+] bi-products • Hydrogen ions consume equal amounts of bicarbonate buffer • [H+] uptake by tubule epithelial cells • Kidney traps [H+] with ammonia to form ammonium (excreted as the salt ammonium chloride) • Kidney is the only organ that can restore bicarbonate buffer • Acid-base balance • Pulmonary component • Regulates amount of CO2 excretion • Renal system • Corrects acid-base imbalances
Classical Approaches to Renal Acid-Base Balance • Classical approach • Evaluates overall contribution to acid and base concentrations • Does not isolate specific components of hydrogen ions • Not compatible with Stewart’s definition • Neonates • Ammoniagenesis decreased • Urinary phosphate best reflects titratable acidity • Oral ammonium chloride loads excreted more slowly than adults