Acid base balance for medical, dental students

Basics of Acid Base Balance

1.  Acid Base Balance Dr. Apeksha Niraula Assistant Professor Department of Biochemistry Institute of Medicine Maharajgunj

2. pH, Buffers: Types Respiratory Acidosis, Respiratory Alkalosis, Metabolic Acidosis, Metabolic Alkalosis Compensated And Non-compensated Imbalances Delta Ratio, Anion gap and its significance OBJECTIVES

3. 3 pH Review pH = - Log [H + ] Range Is From 0 - 14 If [H + ] Is High, The Solution Is Acidic; pH < 7 If [H + ] Is Low, The Solution Is Basic Or Alkaline ; pH > 7

4. Acids are H + donors HCl H + + Cl - Bases are H + acceptors, or give up OH - in solution. KOH K + + OH - Acids and bases can be: Strong – dissociate completely in solution HCl, NaOH Weak – dissociate only partially in solution Lactic acid, carbonic acid H 2 CO 3 H + + HCO 3 - Acid and Base

5. 5 K a is an equilibrium constant. For an acid-base equilibrium between a generic acid, HA, and its conjugate base, A − , HA A − + H + , K a is defined as The negative logarithm of the acid dissociation constant ( Ka ) is the ionisation exponent ( pKa ) of the acid pKa = -log Ka For base, pKb = -log Kb Therefore, stronger the acid, greater is its ionisation, higher its Ka and lower its pKa

6. 6 Or H+ = Ka [HA] [A-] Or, -log [H+] = -log Ka -log [HA] [A-] Since, pH is negative logarithm of molar concentration of H+ ion to the base 10 and –log Ka=pKa pH = pKa + log [A-] [HA] THE HENDERSON-HASSELBALCH EQUATION When ratio of dissociated and undissociated particle is same i.e. [A-]=[HA] , pH= pKa

7. Acid Base Physiology Metabolic reactions: Influenced by the hydrogen concentration of the body fluid Any marked change in H + ion concentration: Distort the protein structure, adversely affects the enzyme activity pH of blood tightly regulated to 7.35-7.45 Blood pH compatible to life: 6.8-7.8

8. S o urces of H + Ions CarbonDioxide: Major Source Other organic and inorganic acids Glycolysis: Lactic Acid Lipolysis: Free Fatty Acid Ureagenesis: Urea Synthesis Ketogenesis: Ketoacids Renal excretion of buffered acids H +

9. Hydrogen Ion Homeostasis Three lines of defense operative in maintaining the blood pH Buffer Systems Respiratory Mechanism Renal Regulation

10. Body pH Homeostasis

11. Buffers are solution which resist any change of pH Types Mixture of weak acid with their salt and a strong base or, Mixture of weak base with their salt and a strong acid E.g.: CH 3 COOH/CH 3 COO-, H 2 CO3/HCO 3 , and NH 3 /NH 4 + Buffering capacity: of a buffer is defined as the ability of the buffer to resist change in pH when an acid or base is added How does buffer act? BUFFERS

12. pH = pKa + log [salt/base] [acid] HENDERSON HESSELBALCH equation gives relationship between pH, pKa, conc. of acid and conjugate base (or salt), thus when [base/salt]=[acid] ;then pH=pKa Application of the equation: 1. Determination of pH of buffer solution on addition of salt or acid 2. Measurement of the concentration of salt and acid by measuring pH Most effective when pH= pKa, range 1 pH unit higher or lower than pKa

13. 14 The body and pH Homeostasis of pH is tightly controlled Extracellular fluid = 7.4 Blood = 7.35 – 7.45 < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45

14. 15 Take up H + or release H + as conditions change Buffer pairs – weak acid and a base Exchange a strong acid or base for a weak one Results in a much smaller pH change Buffer Systems

15. Alkali Reserve Plasma Bicarbonate represents the Alkali reserve Should be sufficiently high to meet the acid load Normal ratio of 20:1 (HCO 3 : H 2 CO 3 ) Ensures high buffering efficiency against acids

16. 17 Bicarbonate buffer Sodium Bicarbonate (NaHCO 3 ) and Carbonic acid (H 2 CO 3 ) Buffer system of plasma accounts 65% of buffering capacity Average normal value of HCO 3 - is 24mmol/lit, H 2 CO 3 is 1.2mmol/lit pKa for H 2 CO 3 is 6.1 Substituting in HH eq. pH = pKa + log[HCO 3 - / H 2 CO 3 ] 7.4=6.1+ log 24/1.2 Maintain a 20:1 ratio : HCO 3 - : H 2 CO 3

17. Bicarbonate system is most important :  Predominates in extracellular fluid (ECF) High Concentration (40-50%) II. Concentration of both components can be regulated Carbonic acid by the respiratory system Bicarbonate by the renal system III. Have Alkali reserve (Ratio of HCO 3 : H 2 CO 3 = 20:1)

18. 19 Phosphate buffer Major Intracellular buffer Alternately switches Na + with H + pKa value is 6.8 H + + HPO 4 2- ↔ H 2 PO4 - OH - + H 2 PO 4 - ↔ H 2 O + H 2 PO 4 2-  Normal ratio of Na 2 HPO 4 and NaH 2 PO 4 in plasma is 4:1 Kept constant with the help of kidneys

19. Regulates pH within the cells and the urine Phosphate concentrations are higher intracellularly and within the kidney tubules More phosphate ions in tubular fluids More powerful than bicarbonate buffer system

20. 21 Protein Buffers Includes hemoglobin, work in blood, and ISF Proteins are excellent buffers: Contain both acid and base groups that can give up or take up H+ Carboxyl group gives up H + Amino Group accepts H + Proteins are extremely abundant in the cell The more limited number of proteins in the plasma reinforces the bicarbonate system in the ECF Side chains that can buffer H + are present on 27 amino acids

21. Hemoglobin as a buffer Hemoglobin buffers H+ from metabolically produced CO 2 in the plasma only As hemoglobin releases O 2 it gains a great affinity for H+ H+ generated at the tissue level from the dissociation of H2CO3 produced by the addition of CO2 Bound H+ to Hb (Hemoglobin) does not contribute to the acidity of blood Hb

22. 1. COOH 2. NH₂ 3. Gaunido group differential ionization of groups 4. Imidazole group 38 Imidazole groups (from 38 Histidine present in Hb ) In alkaline medium –imidazole N₂ donates H⁺ (behaves as a acid ) In acidity medium - imidazole N₂ accepts H⁺ (behaves as a base ) Differential ionization of groups based upon pH of the compartments

23. As H+Hb picks up O 2 from the lungs the Hb which has a higher affinity for O 2 releases H + and picks up O 2 Liberated H + from H 2 O combines with HCO 3 -

24. Respiratory Mechanism Second Line of Defense Ach ie ved by regulating the concentration of carbonic acid in the blood and other body fluids by the lungs Respiratory centre regulates the removal or retention of CO 2 and thereby H 2 CO 3 from the extracellular fluid by the lungs Thus, L u ngs functions by maintaining one component of the Bicarbonate buffer

25. Chemosensitive areas They are able to detect the blood concentration levels of CO 2 and H + Increased in CO 2 and H + Effect: Raised respiration rates Effect diminshes : 1-2 minutes

26. Cell Production of CO2 increases CO 2 +H 2 O H 2 CO 3 H 2 CO 3 H + + HCO 3 H + Acidosis, pH drops H+ stimulates respiratory centre in medulla oblongata Increased rate and depth of breathing CO 2 eliminated via lungs pH rises towards normal R espiratory Mechanism for acid base balance

27. Respiratory Mechanism Second Line of Defense Ach ie ved by regulating the concentration of carbonic acid in the blood and other body fluids by the lungs The respiratory center regulates the removal or retention of CO 2 and thereby H 2 CO 3 from the extracellular fluid by the lungs Thus, the l u ngs function by maintaining one component of the Bicarbonate buffer

28. Chemosensitive areas They are able to detect the blood concentration levels of CO 2 and H + Increased in CO 2 and H + Effect: Raised respiration rates Effect diminishes : 1-2 minutes

29. Cell Production of CO2 increases CO 2 +H 2 O H 2 CO 3 H 2 CO 3 H + + HCO 3 H + Acidosis, pH drops H+ stimulates respiratory centre in medulla oblongata Increased rate and depth of breathing CO 2 eliminated via lungs pH rises towards normal R espiratory Mechanism for acid base balance

30. Chloride S h ift H. Jacob Hamburger: Hamburger’s Phenomenon In Erythrocytes, the plasma carbon dioxide diffuses into the cell along a concentration gradient, where it generates bicarbonate ions through the carbonate dehydratase system The other product, H + is buffered by hemoglobin As the concentration of bicarbonate ions rises intracellularly, it diffuses into the extracellular fluid along a concentration gradient To maintain electroneutrality, diffusion of chloride ions occurs in the opposite direction, i.e. Chloride shift

31. Chloride S h ift

32. Radial Artery - 45 insertion angle Brachial Artery - 60 - 90 insertion angle Femoral Artery - 90 insertion angle Site Selection Arterial Blood Gas Analysis

33. pH = 7.35 - 7.45 PaCO 2 = 35-45 mmHg PaO 2 = 80-100 mmHg HCO3 = 22-26 mEq/L O 2 Saturation = 95-100% Base Excess = +/-2 m Eq/L  % met Hb = <2% % CO Hb = <3% Normal ABG Values Many blood gas analyzers also measures electrolytes in the arterial sample (Na + , K + , Cl - , HCO 3 - & Ca ++ Mg ++ ) Electrolytes measurement acts as an aid to understanding Acid-Base status

34. ABG INTERPRETATION NORMAL VALUES

35. Acid base status Oxygenation Dissolved O 2 (pO 2 ) Saturation of hemoglobin CO 2 elimination Levels of carboxyhemoglobin and methemoglobin Information Obtained from an ABG:

36. Procedure I

37. Remove any air bubbles from sample and cap syringe Dispose of needle in sharps container Roll syringe to mix heparin with sample Immerse in ice Deliver to lab Post puncture procedure

38. Sample should be analyzed as soon as possible – If iced sample, can be stored » Glass syringe – 1 hour » Plastic syringe – 15 minutes Remember: Blood is living tissue that continues to consume O2 and produce CO 2 Sample handling

39. ABG Analyzer Principle of ABG Analyzer pO 2 pCO 2 pH sensitive glass electrode

40. Acidemia –pH less than 7.35 Acidosis – A process that would cause acidemia, if not compensated Alkalemia–pH greater than 7.45 Alkalosis – A process that would cause alkalemia if not compensated Acid base disorders

41. Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis Four primary acid-base disorders

42. Simple acid-base disorder – a single primary process of acidosis or alkalosis Mixed acid-base disorder – presence of more than one acid base disorder simultaneously SIMPLE VS. MIXED ACID-BASE DISORDER

43. In the presence of acidosis or alkalosis, regulatory mechanisms occur which try to maintain arterial pH Disturbances in HCO 3 - result in respiratory compensation Changes in CO 2 are counteracted by renal compensation COMPENSATION The normal response of the respiratory system or kidneys to change in pH induced by a primary acid-base disorder

44. a. Renal compensation Kidneys adapt to alterations in pH by changing the amount of HCO 3 - generated/excreted Full renal compensation takes 2-5 days b. Respiratory compensation Alteration in ventilation allow immediate compensation for metabolic acidbase disorders

45. Characteristics of Primary Acid Base Disorders

46. Anion gap used to assess acid-base status in D/D of metabolic acidosis Anion gap based on principle of electroneutrality: Total Serum Cations = Total Serum Anions Na – (HCO 3 + Cl) = Anion gap Normal Anion gap – 10 +/- 2meq/L Anion Gap

47. Albumin is the major unmeasured anion The anion gap should be corrected if there are gross changes in serum albumin levels. AG (CORRECTED) = AG + 2.5 (4- Albumin)

48. The delta ratio (or the equivalent delta gap) are diagnostic and analytical tool used to determine the contribution from extra anions to the acidemia of any given acidosis A much more detailed overview of the delta ratio is available in a dedicated chapter from the Acid-Base Disturbance series Even though the calculation of a delta ratio is expected in every ABG interpretation question, the college has never asked any questions regarding its validity, or its limitations as a diagnostic instrument Calculation of the delta ratio is performed using the following equation: Delta ratio= (change in anion gap) / (change in bicarbonate) DELTA RATIO

49. Applied to metabolic acidosis to determine the contribution to acidosis from the unmeasured anions, the delta ratio suggests the following distinctions: Less than 0.4 = Pure normal anion gap acidosis 0.4-0.8 = Mixed high and normal anion gap acidosis 0.8-2.0 = Pure high anion gap acidosis More than 2.0 = High anion gap acidosis  and  a pre-existing metabolic alkalosis

50. C heck delta ratio in the presence of a high anion gap metabolic acidosis (HAGMA) to determine if it is a ‘pure’ HAGMA or if there is coexistent normal anion gap metabolic acidosis (NAGMA) or metabolic alkalosis When to Use??

51. I. CENTRAL : Drugs( anesthetics, morphine , sedatives) Stroke Infection II. AIRWAY : Obstruction Asthma RESPIRATORY ACIDOSIS III. PARENCHYMA : Emphysema Pneumoconiosis Bronchitis ARDS Barotrauma IV. NEUROMUSCULAR : Poliomyelitis Kyphoscoliosis 5. MISCELLANEOUS Obesity Hypoventilation  Respiratory acidosis is due to a primary rise in CO 2 Hypercapnia almost always results from alveolar hypoventilation due to one of the following causes

52. RESPIRATORY ALKALOSIS A respiratory alkalosis is due to decrease in PaCO 2 It results from hyperventilation leading to decrease in CO 2 Causes of respiratory alkalosis: 1. Hypoxemia from any causes 2. Respiratory center stimulation 3. Mechanical hyperventilation 4. Sepsis, pain

53. Rules for Acute Respiratory acidosis Rule : For Acute respiratory acidosis The [HCO 3 - ] will increase by 1 mmol/l for every 10 mm Hg elevation in pCo2 above 40 mm Hg Expected [HCO 3 - ]= 24 + {(Actual pCO 2 -40)/10}

54. Rule for Chronic Respiratory acidosis The [HCO 3 -] will increase by 4 mmol/L for every 10 mm Hg elevation in pCO 2 above 40 mm Hg Expected [HCO 3 - ]= 24 + 4 {(Actual pCO 2 -40)/10} With chronic acidosis, kidneys respond by retaining HCO 3 -, [ Renal Compensation]

55.  Step 1: Acidemic, alkalemic, or normal? Step 2: Is the primary disturbance respiratory or metabolic? Step 3: For a primary respiratory disturbance, is it acute or chronic? Step 4: For a metabolic disturbance, is the respiratory system compensating OK? Step 5: For a metabolic acidosis, is there an increased anion gap? Step 6: For an increased anion gap metabolic acidosis, are there other derangements? Six Step Approach for Acid base disorder

56. Comparison of different types of Acid Base disorders

57. Primary Compensatory Mechanism in Metabolic and Respiratory Acidosis

58. Primary Compensatory Mechanism in Metabolic and Respiratory Alkalosis

59. Arterial Blood Gas Analysis pH= 7.27 pCO2= 55.4 mm Hg pO2= 144 mm Hg HCO 3 - = 24.3 mmol/l Na+= 138 mmol/L; K+= 4.7 mmol/l; Cl-= 103 mmol/L; Urea= 64 and Creatinine= 2.3 Interpret the findings Calculate the anion gap

60. Thank You Life is a struggle, not against sin, not against Money Power . . but against hydrogen ions.. H.L. Mencken