1. Acid-Base Balance
AnS 536
Spring 2014

2. 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+

3. Water as an Electric Dipole
                                 

4. Structure of Liquid Water (H2O)280

5. 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

6. Dissolving macromolecules (e.g., proteins):
Water of hydration

7. Dissolving molecules with polar covalent bonds:
NH3 d-
Figure: 2.15ab
Caption:
(a) Because of oxygen’s high electronegativity, the electrons that are shared when hydrogen and oxygen form a covalent bond are pulled toward the oxygen nucleus. The electrons spend more time close to the oxygen nucleus, so the oxygen atom has a slight negative charge and the hydrogen atom a partial positive charge. (b) The electrical attraction that occurs between the partial positive and negative charges on water molecules forms a hydrogen bond.  Exercise Label the hydrogen bond in part (b).

8. Dissolving ionic compounds:
Ionic solids dissolve readily in water d+ d- d- d+
Na+
Cl- d+ d- d+
Figure: 2.18d
Caption:
(d) Ionic solids dissolve readily in water. Why?  Exercise Ionic bonding can be thought of in terms of reduction and oxidation.

9. The incomplete ionization of water:+ O H - O H + OH
hydroxide
ion
hydronium
ion
or,
HOH
H OH + -
proton
hydroxide
ion

10. A pH of 7.0 is defined as neutral
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

11. 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)

12. Na/K ATPase Pump
Lehninger, 1993

14. 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)

15. 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+

16. Stewart (1981)
Balance of SID is maintained by the dissociation and reassociation of water

17. The incomplete ionization of water:+ O H - O H + OH
hydroxide
ion
hydronium
ion
or,
HOH
H OH + -
proton
hydroxide
ion

18. Dissociation of Salt in Water
                                                                           

19. Acids and bases ionize in water:
HCl
NaOH
Cl-
Na+ H+
OH-
Dissolved in
positively charged
water (H+), thus
lowering pH
Dissolved in negatively charged water (OH-), thus raising pH

20. Dissociation of Electrolytes
                                                                                                                                                                                                              

21. 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

22. 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

23. 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

24. Newborn Acid-Base Balance
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

25. Altering Acid Base Balance
DCAD diets
Sodium bicarbonate administration
IV vs GI
effect of other sodium forms

26. 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)

27. Weight or Equivalents…?
Dietary electrolyte balance (dEB) is expressed in equivalents, why not weight or percent of diet?
Eq = Molecular weight  valence
g/mol mmol/g mEq/g Na Mg K Ca
Cl –
Element MW Valence Weight equivalents

28. 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

29. Classical Approaches to Renal Acid-Base Balance
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