ACIDS AND BASE S

1. ACIDS AND BASES

2. pH Review • ECF pH = 7.4 • Tightly regulated • Fatal if pH 7.25 > pH > 7.55 • Nec for proper enzyme activity • May  change protein shape (enzymes) • Enzymes catalyze rxns by holding substrates properly for rxn to occur at active site of certain shape • pH change   cell death

3. pH Review – cont’d • pH = - log [H+] • High [H+] = acidic sol’n = low pH (1-6) • Low [H+] = basic (alkaline) sol’n = high pH (8-14) • pH = 7 = neutral solution

4. Acids • H+ donors • Body acids classified as: • Volatile (eliminated from the body as CO2) • Most impt -- carbonic acid (H2CO3) • Gives up H+ by reaction: H2CO3 CO2 + H2O • Nonvolatile (eliminated through kidney tubules) • Ex: lactic acid, phosphoric acid, etc

5. Acids – cont’d • Another classification of acids: weak/strong • Strong – easily gives up H+ from molecular structure • Ex: HCl mostly (H+ + Cl-)Note: there are few strong acids in the body • Weak – most physiological acids – may or may not easily give up H+ in solution • Dissociation depends on molecular structure and conditions of solution

6. Carbonic Acid Important • CO2 + H2O  H2CO3 H+ + HCO3-(carbon (water) (carbonic (hydrogen (bicarbonate)dioxide) acid) ion)Both reversible reactions catalyzed by enzyme carbonic anhydrase

7. Bases, Buffers • Bases -- H+ acceptors • Overall negative (-) charge (ex: OH-) • Can also be weak or strong • Buffer – system of weak acid + conjugate base • Pairs of related molecules • Conjugate base – what’s left of a weak acid molecule, once H+ dissociated • React with either added base or added acid  no significant change in pH • Blood buffers -- first responders to changes in blood pH

8. Buffers – cont’d • Four important body buffers: • Bicarbonate/carbonic acid • Weak acid = carbonic acid • Conjugate base = bicarbonate ion • Hb/oxy-Hb • Phosphate system – works inside cells • Protein system – important in ISF

9. Bicarbonate/Carbonic Acid Buffer System • Henderson-Hasselbach equation (for any buffer): • pH = pKa + log [conjugate base]/[weak acid], where • pH can be measured • pKa is constant for any weak acid • If pKa is known, concentration of conjugate base and weak acid can be calculated • For carbonic acid buffer system: • pH = pKa + log [HCO3-]/[H2CO3]

10. Bicarb/Carbonic Acid Buffer – cont’d • Blood concentrations of base, acid in proper blood buffer (REMEMBER 20:1) • Substitute into H-H eq’n (pH = pKa + log [base]/[acid]): • Normal blood pH = 7.4 • pKa for carbonic acid = 6.1 • Solve for [base]/[acid] ratio: • [HCO3-]/[H2CO3] = 20 / 1 • For every 1 carbonic acid molecule in bloodstream, body strives to maintain 20 bicarbonate molecules • Actual concentrations in healthy blood: [HCO3-]=24 mEq/L, [H2CO3]=1.2 mEq/L

11. Bicarb/Carbonic Acid Buffer – cont’d • Respiratory component • From overall carbonic acid rxn • CO2 + H2O  H2CO3  H+ + HCO3- • Resp component is left side of equation: • CO2 + H2O  H2CO3 • H2CO3 dependent on CO2, which is expired through lung • Lung can rapidly decrease [H2CO3] in blood by excreting CO2 • Body uses respiratory system to maintain H2CO3 at proper amounts to maintain 20:1 buffer ratio • Fast mechanism • Minutes to hours

12. Bicarb/Carbonic Acid Buffer – cont’d • Respiratory component – cont’d • Acid/base disorders identified • Incr’d blood [H2CO3]  decr’d blood pH • Respiratory acidosis • Due to retained CO2 • Decr’d blood [H2CO3]  incr’d blood pH • Called respiratory alkalosis • Due to too little CO2 in blood • Note: respiratory component disorders are based on the amount of one of the blood buffer components (H2CO3).

13. Bicarb/Carbonic Acid Buffer – cont’d • Renal component • HCO3- regulated by kidney, w/ H+ secreted to urine • From overall carbonic acid rxn • CO2 + H2O  H2CO3  H+ + HCO3- • Renal component is right side of equation • H2CO3   H+ + HCO3- • Kidneys control excr’n H+ and HCO3- from blood • Body uses renal system to manipulate HCO3- part buffer system to maintain the 20:1 buffer ratio • Slow • Hours to days (so not sufficient in acute dysfunction or disease)

14. Bicarb/Carbonic Acid Buffer – cont’d • Renal component – cont’d • Acid/base disorders identified • Incr’d blood [HCO3-] incr’d blood pH • Metabolic alkalosis • Decr’d blood [HCO3-]  decr’d blood pH • Metabolic acidosis • Note: metabolic dysfunctions focus on amount of conjugate base part of the buffer system (HCO3-)

15. Importance of K+ -- It Can Exchange for H+ • If blood acidosis (high concentration of [H+] can’t be neutralized by blood buffer base) • H+ can leave IVF  ISF • If ISF [H+] high enough, H+ will enter the cell •  cell with too high + charge • To maintain neutral ICF charge, K+ leaves cell, enters ISF

16. K+ Exchange – cont’d • Opposite in alkalosis: • Too little H+ in ECF  H+ from cell moves into ECF • To maintain charge neutrality, ECF K+ moves into cell from ECF in exchange  ECF hypokalemia

17. Acid/Base Imbalances (Figs.4-10 – 4-13) • Respiratory Acidosis • Decr’d ventilation (breathing or gas exchange)  incr’d PaCO2 (arterial pressure CO2) • Lung dysfunction  CO2 improperly excr’d •  Build-up of CO2 in bloodstream • Increased PaCO2 = hypercapnia • Due to: • Chronic conditions • Depression of resp center of brain that controls breathing rate • Paralysis of respiratory or chest muscles • Acute conditions • Adult Respiratory Distress Syndrome (ARDS) • Occurs with trauma, acute infection  high amts biochems impt to inflammatory response  severe impact on the lungs  inhibited breathing • Pneumothorax (or collapsed lung)

18. Acid/Base Imbalances – cont’d • Respiratory acidosis – cont’d • Causes differ for chronic/acute • Acute – airway obstruction • Chronic – chronic pulmonary disease • Compensation differs for chronic/acute • Acute – compensation difficult • Can’t use resp system to adjust acid/base levels • Renal component too slow to accommodate acute difficulty • Chronic – renal mechanism compensates • Body senses increased [CO2] in IVF •  Stim’n kidney to increase reabsorption HCO3- from renal tubules • Also incr’d [CO2] sensed stimulates kidney to incr excr’n of H+ into urine • Taken together, blood now will have less H+ (so will be less acidic) and more HCO3- (neutralizes any excess H+ remaining)

19. Acid/Base Imbalances – cont’d • Respiratory acidosis – cont’d • Clinical • Neurological effects: if acidity increases enough, cerebrospinal fluid becomes acidic    tremors, coma • Treatment • Restore ventilation • Treat any underlying cause of chronic dysfunctions or diseases

21. Acid/Base Imbalances – cont’d • Respiratory Alkalosis • Most common acid/base imbalance • Primarily caused by hyperventilation  decr’d PaCO2 (hypocapnia) • Due to: • Pulmonary diseases • Congestive heart failure • Both  hypoxia sensed at chemoreceptors in vasculature • Chemoreceptors send signals to brain (respiratory center)  •  incr’d breathing to bring in more oxygen • BUT incr’d breathing  incr’d CO2 excr’n so decr’d PaCO2 • Now less CO2 + H2O  H2CO3, and too little acid defines alkalosis • Acute: anxiety  hyperventilation

22. Acid/Base Imbalances – cont’d • Clinical • Frequent yawning • Deep respirations • Treatment • Eliminate underlying disease • Breathe into a paper bag (to decrease CO2 lost with breathing)

24. Acid/Base Imbalances – cont’d • Metabolic acidosis • Due to: • Incr’d metabolic acids accumulating in blood • With metabolic disorders • With hypoxia • Greatly incr’d ingested acids • Decr’d excreted acids • With renal dysfunction • Decr’d [HCO3-] in blood • With chronic diarrhea

25. Acid/Base Imbalances – cont’d • Metabolic acidosis – cont’d • Compensation - incr'd serum [HCO3-]; K+ exch. • Resp system responds to decr’d [H2CO3] in blood by decreasing CO2 in blood (or increasing excr’n CO2) • So hyperventilation • Renal system must respond to incr’d excr’n H+ if possible • K+ exchanges with excess H+ in ECF • So K+ moves out of the cells into ECF as H+ moves out of ECF into the cells

26. Acid/Base Imbalances – cont’d • Metabolic acidosis – cont’d • Clinical • Headache, lethargy • CNS depression • Deep, rapid respirations • Dysrhythmias • Treatment • Treat underlying cause • Lactate solution IV • In liver, lactate converted to HCO3- • So incr’s base available to bring buffer system ratio back to normal

28. Acid/Base Imbalances – cont’d • Metabolic alkalosis • Increased relative [HCO3-] in the blood • Due to • Chronic vomiting, g.i. suction, diuresis • H+ lost to body fluids along with other electrolytes • Problematic if concurrent renal dysfunction that allows incr’d HCO3- reabsorption • Heavy ingestion of antiacids

29. Acid/Base Imbalances – cont’d • Metabolic alkalosis – cont’d • Compensation • Renal compensation difficult (HCO3- reabs'd) • Most commonly occurs with renal dysfunction, so patient can’t count on kidney to compensate • Resp. compensation difficult (limited hypovent'n) • Body needs to increase PaCO2 ( increased [H2CO3]) • Patient must hypoventilate (to decrease excretion of CO2) • BUT hypoventilation is only temporary (through breathing reflex at resp center) • So the patient can’t count on the respiratory system to compensate

30. Acid/Base Imbalances – cont’d • Metabolic alkalosis – cont’d • Clinical • Respirations slow, shallow • Symptoms often related to depletion of electrolytes (if cause is vomiting, etc.) • Atrial tachycardia • Dysrhythmias • Treatment • Electrolytes to replace those lost • Treat underlying renal disorder if possible