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 CO 2 ) –Most impt -- carbonic acid (H 2 CO 3 ) –Gives up H+ by reaction: H 2 CO 3  CO 2 + H 2 O 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 CO 2 + H 2 O  H 2 CO 3  H+ + HCO 3 - (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 [HCO 3 -]/[H 2 CO 3 ]

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: –[HCO 3 -]/[H 2 CO 3 ] = 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 CO 2 + H 2 O  H 2 CO 3  H+ + HCO 3 - –Resp component is left side of equation: CO 2 + H 2 O  H 2 CO 3 –H 2 CO 3 dependent on CO 2, which is expired through lung Lung can rapidly decrease [H 2 CO 3 ] in blood by excreting CO 2 Body uses respiratory system to maintain H 2 CO 3 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 [H 2 CO 3 ]  decr’d blood pH –Respiratory acidosis –Due to retained CO 2 Decr’d blood [H 2 CO 3 ]  incr’d blood pH –Called respiratory alkalosis –Due to too little CO 2 in blood Note: respiratory component disorders are based on the amount of one of the blood buffer components (H 2 CO 3 ).

13. Bicarb/Carbonic Acid Buffer – cont’d Renal component –HCO 3 - regulated by kidney, w/ H+ secreted to urine –From overall carbonic acid rxn CO 2 + H 2 O  H 2 CO 3  H+ + HCO 3 - –Renal component is right side of equation H 2 CO 3   H+ + HCO 3 - –Kidneys control excr’n H+ and HCO 3 - from blood Body uses renal system to manipulate HCO 3 - 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 [HCO 3 -]  incr’d blood pH –Metabolic alkalosis Decr’d blood [HCO 3 -]  decr’d blood pH –Metabolic acidosis Note: metabolic dysfunctions focus on amount of conjugate base part of the buffer system (HCO 3 -)

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 PaCO 2 (arterial pressure CO 2 ) Lung dysfunction  CO 2 improperly excr’d  Build-up of CO 2 in bloodstream Increased PaCO 2 = 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 [CO 2 ] in IVF –  Stim’n kidney to increase reabsorption HCO 3 - from renal tubules –Also incr’d [CO 2 ] 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 HCO 3 - (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 PaCO 2 (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 CO 2 excr’n so decr’d PaCO 2 »Now less CO 2 + H 2 O  H 2 CO 3, 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 CO 2 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 [HCO 3 -] in blood –With chronic diarrhea

25. Acid/Base Imbalances – cont’d Metabolic acidosis – cont’d –Compensation - incr'd serum [HCO 3 -]; K+ exch. Resp system responds to decr’d [H 2 CO 3 ] in blood by decreasing CO 2 in blood (or increasing excr’n CO 2 ) –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 HCO 3 - –So incr’s base available to bring buffer system ratio back to normal

28. Acid/Base Imbalances – cont’d Metabolic alkalosis –Increased relative [HCO 3 -] 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 HCO 3 - reabsorption Heavy ingestion of antiacids

29. Acid/Base Imbalances – cont’d Metabolic alkalosis – cont’d –Compensation Renal compensation difficult (HCO 3 - 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 PaCO 2 (  increased [H 2 CO 3 ]) –Patient must hypoventilate (to decrease excretion of CO 2 ) –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