Acid-Base Balance

1. Acid-Base Balance 205b

2. Educational Objectives • Describe the relationship between the lungs and the kidneys in maintaining acid-base homeostasis (normalcy of the body) • Given values for carbonic acid and bicarbonate, calculate the pH using the Henderson-Hasselbalch equation

3. Educational Objectives • Define base excess/base deficit • Define buffer system and list the electrolytes commonly associated with buffering in the blood • List the components of non-bicarbonate buffer systems

4. Normal ABG values • pH 7.35-7.45 • PaO2 80-100 mmHg • PaCO2 35-45 mmHg • HCO3- 22-26 mEq/L • BE +/- 2 • When reading a ABG: • 7.36, 40, 25, 80

5. Acid Base Balance Introduction • To maintain homeostasis, the body tries to keep the hydrogen ion concentration ([H+]) at approximately 40 nmoles/L or the pH close to 7.40. Deviation from this [H+] is minimized by buffering systems, all of which are in equilibrium with one another; the largest is the bicarbonate buffer system. Any change in acid­base status is reflected in the components of the bicarbonate buffer system­the bicarbonate ion (HCO3- ) and the arterial partial pressure of carbon dioxide (PaCO2).

6. Energy Production • Three sub-pathways of metabolism • Glycolysis • Tricarboxylic acid (TCA) cycle • Cytochrome (oxidative phosphorylation) system

7. Energy Production • Glycolysisand the Krebs cycle both generate the high-energy compound adenosine triphosphate ( ATP ) directly, by substrate -level phosphorylation, but this represents only a small fraction of the energy in each glucose that passes through these pathways. • Much more of the energy in glucose is conserved in the form of high-energy electrons carried in pairs by the electron "shuttles" NADH and FADH 2 , which are generated in glycolysis and the Krebs cycle.

8. Energy Production • Glycolysis • Enzymes break down glucose into pyruvic acid, hydrogen ions, and adenosine triphosphate (energy) ATP • When no oxygen is present (anaerobic conditions), lactic acid is product • http://www.youtube.com/watch?v=3GTjQTqUuOw

9. Energy Production • Glycolysis • C6H12O62CH3 O COOH + 4 H+where C6H12O6 is glucose and CH3 is pyruvic acid • CH3CHOH COOH + energy (heat) lactic acid • http://www.youtube.com/watch?v=bz5-T4p8WEQ&feature=related

10. Energy Production • Tricarboxylic acid (TCA) cycle • Also known as Krebs cycle • In the presence of oxygen, pyruvic acid yields adenosine triphosphate (ATP) and carbon dioxide, and hydrogen molecules • 2 CH3 = C = COOH + O2 2 H2 + 2 CO2 + Acetyl CoA • http://www.youtube.com/watch?v=WcRm3MB3OKw

12. Energy Production • Cytochrome (oxidative phosphorylation) system • Proceeds from TCA cycle in presence of sufficient oxygen • Produces the most energy of the three pathways

13. Energy Production • Cytochrome (oxidative phosphorylation) system • Oxygen and hydrogen molecules produce water and energy • O2 + H2 H2O + ATP (energy)

14. Glucose Glycolysis Pyruvic Acid Acetyl CoA TCA Cycle Aerobic Anaerobic 2 ATP 2 ATP 4 CO2 Lactic acid 2 H2 2 H2 2 CO2 Cytochrome System + O2 6 H2O 34 ATP Final Products

15. Acid-Base Balance • The dynamic equilibrium that exists between the substances in the body that are proton (H+) donors and those that are proton acceptors • "Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions."H.L. MENCKEN

16. Acid-Base Balance • Hydrogen ions are protons and do not exist in the naked state in body fluids; instead they react with water (H20) to form hydronium ions, such as H30+ and H5O2+. For clinical purposes H+ can be used to represent these hydrated protons. Because [H+] is so critical to enzyme function yet the absolute concentration is small and difficult to manipulate, the concept of pH was developed and is now universally used to represent [H+].*

17. Acid-Base Balance • Normally maintained within very fine, but slightly alkaline range • Has two key mechanisms • Lungs – regulation of CO2. • Kidneys – regulation of HCO3ˉ

18. Acid-Base Balance Blood (H+) Non-Bicarbonate Buffer System (Closed) Bicarbonate Buffer System (Open) Eliminated Through Ventilation H+ + Buf ˉ Buf H+ + HCO3ˉ H2CO3 H+ + CO2

19. Acid-Base Balance Open= removed/ exhaled

20. Acid-Base Balance • Buffering System • A chemical solution consisting of a weak acid and its salt, which has the ability to minimize changes in pH when adding acid or alkali

21. Acid-Base Balance • Buffering System: • A buffer system counteracts the effects of adding acid or alkali to the blood. The resulting pH change is less than if the buffer were not present. • Blood contains two basic buffer systems: bicarbonate and nonbicarbonate. Each consists of a weak acid or acids and their conjugate base or bases.

22. Acid-Base Balance • The bicarbonate system buffers the effects of fixed acids and alkalies that are added to the blood; the acid component is H2CO3 and the base is HCO3- • The nonbicarbonate system consists mainly of proteins and phosphates and serves to buffer changes in carbon dioxide. • Since the nonbicarbonate system is a heterogeneous group of compounds, the acid component is represented by HBuf and the base by Buf. Note that carbon dioxide is part of an open system, since any buildup in plasma (aqueous or dissolved CO2) can be excreted by healthy lungs.

23. Acid-Base Balance • The bicarbonate and nonbicarbonate buffer systems are in equilibrium with each other. Measuring the components of either system will give the hydrogen ion concentration ([H+]) or the pH of the blood. • However, since the nonbicarbonate system is a heterogeneous group of molecules, it is easier to measure the bicarbonate buffer components in order to determine pH. An extremely small quantity of H2C03 is present in the blood compared with dissolved CO2 (approximately 1 to 400). Since H2CO3 is in equilibrium with dissolved CO2, the latter (measured as PaCO2) can be used as the acid component in calculating pH. Therefore measurement of HCO3- and PaCO2 will provide the pH.

24. Henderson-HasselbalchEquation • Describes the relationship between pH, bicarbonate, and PCO2 • pH = 6.1 + logHCO3 PCO2 X 0.03 • Blood gas analyzers measure pH and PaCO2, but calculate HCO3ˉ

25. Henderson-Hasselbalch Equation • carbonic acid has the value 6.1. • The pH of the blood is equal to the bicarbonate buffer system plus the logarithm of the following ratio bicarbonate concentration ([HCO3-]) over 0.03 times the arterial partial pressure of carbon dioxide (PaCO2). • The constant 0.03 converts PaCO2 from mm Hg to mmoles/L. Inserting normal values gives 7.4, the normal blood pH.

26. Henderson­Hasselbalch equation • It is not necessary to memorize the full Henderson­Hasselbalch equation to intelligently manage acid­base disorders. It is important to understand that pH reflects a ratio of HCO3- to PaCO2. • The bicarbonate buffer system is the most important of the body's buffer systems for several reasons. This system provides the major way to buffer the additions of fixed acid and alkali to the blood. Since one of its components is carbon dioxide, the system is open, i.e., the respiratory system allows for excretion of huge amounts of carbon dioxide. Also, since carbon dioxide is readily diffusible across all cell membranes, the results of buffering can be reflected quickly in intracellular compartments. • The body preferentially wants to maintain normal pH and does so by altering the numerator (HCO3-) or denominator (PaCO2) of the Henderson­Hasselbalch equation as necessary.

27. Short Cut • Rule of 8’s (a rule of thumb when determining what the HCO3 will be given an pH and CO2) • pH Factorexample: When pH is 7.40 and PCO2 is 40 the 7.60 8/8 PCO2 HCO3- will be? 7.50 6/8 PCO2 5/8 (40) = 25 meq/ml 7.40 5/8 PCO2 7.30 4/8 PCO2 7.20 3/8 PCO2

28. DOES THE PATIENT HAVE AN ACID­BASE DISORDER? • It is important to recognize when a patient has an acid­base disorder since that recognition is the first step toward diagnosis and therapy. If any of the three variables in the Henderson­Hasselbalch equation are abnormal, the answer to this question is yes. Any acid­base derangement will be reflected in one or more components of the bicarbonate system: pH, PaCO2, HCO3- • A single abnormal component, even without knowledge of the other two, always indicates an acid­base disorder.

29. DOES THE PATIENT HAVE AN ACID­BASE DISORDER? • This is particularly important since an abnormal HCO3- is often found in venous blood (as part of the serum electrolytes measurement) without a concomitant blood gas measurement. An abnormal HCO3- value alone cannot define or diagnose an acid­base disorder but nonetheless points to its presence. For example, an elevated HCO3- suggests either metabolic alkalosis or respiratory acidosis.

30. DOES THE PATIENT HAVE AN ACID­BASE DISORDER? • Assess your patients thoroughly to determine possible cause of acid base disturbance • Look for possible metabolic causes (Renal failure, liver failure, dehydration/hypotension, verse respiratory disorders: COPD)

31. CALCULATED VS. MEASURED HCO3- • Incorrect therapeutic decisions can occur if blood gas values are accepted at face value. They should always be examined for physiologic correctness, particularly when considering acid­base disorders, which seem prone to misdiagnosis. For example, a PaCO2 of 49 mm Hg, pH of 7.35, and HCO3- of 16 mEq/L may be interpreted as a metabolic acidosis (low pH and low HCO3-) when in fact there is a transcription error: the HCO3- should be 26 and cannot possibly be 16 if the pH is 7.35 and the PaCO2 is 49 mm Hg.

32. CALCULATED VS. MEASURED HCO3- • Such errors can be avoided if it is remembered that HCO3-, PaCO2, and pH must satisfy the Henderson­Hasselbalch equation. If PaCO2 and pH have been measured, arterial HCO3- can be calculated and does not have to be measured. The HCO3- is routinely measured as one of the serum electrolytes (on venous blood), and this measurement can pose a problem when a comparison is made with the blood gas HCO3-. Often, the measured venous HCO3- does not agree with the arterial HCO3- that has been calculated from the Henderson­Hasselbalch equation.

33. POSSIBLE REASONS FOR MEASURED VENOUS HCO3- NOT AGREEING WITH CALCULATED ARTERIAL HCO3- • PHYSIOLOGIC REASONS1. The venous HCO3- measurement is actually the total CO2 content and is not identical to the plasma HCO3- calculated from the Henderson­Hasselbalch equation. • Total CO2 content includes all the acid­labile forms of carbon dioxide, of which plasma HCO3- constitutes approximately 85%; hence the normal value for measured venous HCO3- (total CO2 content) is approximately 2 to 3 mEq/L higher than calculated arterial HCO3-

34. POSSIBLE REASONS FOR MEASURED VENOUS HCO3- NOT AGREEING WITH CALCULATED ARTERIAL HCO3- • PHYSIOLOGIC REASONS2. In critically ill or unstable patients, the pK of the bicarbonate buffer system may not be 6. 1, thus rendering calculation of HCO3- inaccurate 3. The venous sample may be drawn at a time different from that of the arterial sample used for blood gas analysis, and thus reflect a true change in acid­base status.

35. POSSIBLE REASONS FOR MEASURED VENOUS HCO3- NOT AGREEING WITH CALCULATED ARTERIAL HCO3- • TECHNICAL REASONS1. The blood­drawing technique may alter venous HCO3-, e.g., tourniquet placement may create a transient lactic acidosis, lowering the HCO3-. • 2. The blood gases are usually measured within minutes after the arterial sample is obtained, whereas the serum electrolytes may not be measured for an hour or more after the venous sample is drawn. The venous sample's HCO3-, may change if the blood is not stored anaerobically or if its measurement is delayed .

36. POSSIBLE REASONS FOR MEASURED VENOUS HCO3- NOT AGREEING WITH CALCULATED ARTERIAL HCO3- • TECHNICAL REASONS 3. If pH and PaCO2 are inaccurately measured, the calculation of HCO3- will be inaccurate as well.4. The venous HCO3- or the arterial HCO3- may be transcribed incorrectly.

37. ACIDEMIA AND ALKALEMIA • In terms of pH, the blood can reflect either acidemia or alkalemia. Acidemia indicates an acid pH (less than 7.35), and alkalemia indicates an alkaline pH (greater than 7.45). • The terms acidemia and alkalemia provide no specific information about acidosis vs. alkalosis, metabolic disorder vs. respiratory disorder, or the underlying clinical causes. To characterize a patient's blood as having acidemia or alkalemia, only one value is needed: pH.

38. ACIDEMIA AND ALKALEMIA • Since pH is determined by a ratio of HCO3- to PaCO2, the Henderson­Hasselbalch equation may be conveniently reduced for clinical use to

39. ACIDEMIA AND ALKALEMIA • The kidneys are responsible for maintaining HCO3-, and the lungs are responsible for maintaining PaCO2

40. ACIDEMIA AND ALKALEMIA • Since the kidneys affect HCO3- changes slowly (from hours to days) and since the lungs may affect changes in PaCO2 quickly (within minutes), the ratio determining pH is viewed as slow over fast • Important when considering the compensatory changes for acid­base disturbances. For example, a compensation that involves altering the HCO3- occurs relatively slowly. Understanding acid­base disorders depends on knowing how the kidneys and the lungs act and react to the acid­base disorder.

41. ACIDEMIA AND ALKALEMIA • DISORDERS IN THE BLOOD Acidemia. A low blood pH (less than 7.35)Alkalemia. A high blood pH (greater than 7.45)Hypocapnia. A low PaCO2 (less than 35 mm Hg)Hypercapnia. A high PaCO2 (greater than 45 mm Hg)

42. ACIDEMIA AND ALKALEMIA • DISORDERS IN THE PATIENT Metabolic acidosis. A primary physiologic process that causes a decrease in the serum bicarbonate and, when not complicated by other acid­base disorders, lowers the blood pH. Metabolic alkalosis. A primary physiologic process that causes an increase in the serum bicarbonate and, when not complicated by other acid­base disorders, raises the blood pH.

43. ACIDEMIA AND ALKALEMIA • DISORDERS IN THE PATIENTRespiratory acidosis. A primary physiologic process that leads to an increased PaCO2 and, when not complicated by other acid­base disorders, lowers the blood pH.Respiratory alkalosis. A primary physiologic process that leads to a decreased PaCO2 and, when not complicated by other acid­base disorders, raises the blood pH.Compensatory process. Not a primary acid­base disorder, but a change that follows a primary disorder. A compensatory process attempts to restore the blood pH to normal and is not appropriately termed acidosis or alkalosis.

44. Examples • Metabolic Alkalosis • 7.55, 40, 40 • Metabolic Acidosis • 7.25, 40, 16 • Respiratory Alkalosis • 7.55, 25, 22 • Respiratory Acidosis • 7.25, 55, 22 All of these are uncompensated blood gases

45. Uncompensated (ACUTE) • ABG’s that have one of the following variables which is in normal range (PaCO2 of HCO3) while the pH is out of range is considered uncompensated • Simple means the body has not yet attempted to correct the blood gas • Example: • 7.25, 60, 24 • This patient has a uncompensated respiratory acidosis since the HCO3 has not been increased to increase the pH

46. ACIDEMIA AND ALKALEMIA

47. Acidosis and Alkalosis • In contrast to acidemia and alkalemia, which refer to the in vitro determination of blood pH, acidosis and alkalosis refer to the physiologic processes occurring in the patient. Acidosis and alkalosis cannot be fully characterized without reference to the patient's history, physical examination, serum electrolyte values, and other relevant laboratory data. Acidosis and alkalosis cannot be defined by reference to blood changes only.

48. Acidosis and Alkalosis • The numerator of the Henderson­Hasselbalch equation, HCO3-, is called the metabolic component, and the denominator, PaCO2, is called the nonmetabolic or respiratory component (the term respiratory is used henceforth instead of nonmetabolic). • There may be both metabolic and respiratory causes of acid­base disorders. The primary change determines the type of disorder

49. http://www.youtube.com/watch?v=i_pTaTveCCo&feature=related • http://www.youtube.com/watch?v=eK2dBdBRvCU&feature=related • http://www.youtube.com/watch?v=HrUvft2d8Zo&feature=related

50. ABG Practice • http://www.vectors.cx/med/apps/abg.cgi