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Acid Base Balance and Primary Disturbances - basic concepts

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basic concepts in acid-base physiology and pathophysiology. For basic science students in medical and allied health sciences

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Acid Base Balance and Primary Disturbances - basic concepts

  1. 1. Acid-base Balance Remember pH α [HCo3 - ] PCO2 Acidosis 7.35-7.45 Alkalosis Respiratory acid component PCO2 Metabolic alkaline component HCO3 - victor.nwai@gmail.com 2013
  2. 2. Learning outcomes 1. Define acid, base, buffer, acidaemia vs acidosis; alkalaemia vs alkalosis. 2. Explain why the arterial pH needs to be maintained within a narrow range 3. List the buffer systems available in the human body. 4. Describe the interrelationships between the pH, the PCO2 of the blood, and the plasma bicarbonate concentration, and state the Henderson-Hasselbalch equation. 5. Explain how the Henderson-Hasselbalch equation for bicarbonate/carbonic acid buffer system plays a crucial role in explaining the primary acid base disorders and the respective compensatory responses 6. State the role of the buffer system, the respiratory system and the kidneys in maintaining acid base balance and describe the mechanism of each in H+ ion homeostasis 7. State the potential causes of respiratory acidosis and alkalosis and metabolic acidosis and alkalosis, and deduce the effects of acidosis and alkalosis on body functions 8. Read Davenport diagrams for four primary disturbances and respective compensations
  3. 3. Some key concepts
  4. 4. Focus on the Acid and H+ ions. Forget the threat of base (alkali) • It’s the acids that are threatening us all the time – there is continuous metabolic production of • CO2 (becomes a volatile acid, H2CO3 - ,when dissolved) • nonvolatile or fixed acids (mainly from protein metabolism) • Forget the bases. Their threat is negligible compared with that of acids.
  5. 5. Where is the threat coming from? Endogenous • CO2 transport from tissues to lungs: – Dissolved carbonic acid is buffered in the plasma by plasma proteins, and in the RBC by haemoglobin (“Physiological buffering”) • Lactic acid production by hypoxic muscle cells • Ketoacid production by liver (in diabetes) • Retention of CO2 and carbonic acid in hypoventilation and H+ ions in renal failure Exogenous : food rich in acids (meat), ingestion of acids (salicylic acid, NH4Cl); intravenous infusion
  6. 6. Summary: Gain or loss of H+ ions H+ sources/gain: Metabolic production (CO2= 12,500 mEq/d) (H2SO4, H3PO4= 50 mEq/d) Extra acid loads Ketone bodies (diabetes mellitus); ingestion of acidifying salts or aspirin lactic acidosis (exercise, hypoxia) Failure to excrete: respiratory/renal failure Loss of alkali (bicarbonate): diarrhoea Base gain Ingestion (vegetables, NaHCO3, antacids) Infusion H+ loss vomiting (loss of HCl) Hyperventilation (CO2 wash-out) Primary aldosteronism
  7. 7. It’s the H+ ion and not the acid per se that is deadly • Physiologically, acid as such is quite harmless in the internal environment (it’s just a small molecule in the vast internal sea of body fluids) • Only when an acid dissociates and liberates H+ ions, does it become deadly
  8. 8. H+ ions are deadly. Why? • Because H+ ions can affect the cell function by altering the charge of functional proteins including enzymes – H+ ions are very reactive cations, – Proteins are anions (carry –ve charge) at body pH – H+ ions at higher concentrations can bind strongly to negatively charged proteins, including enzymes, and impair their activity and hence the cell function
  9. 9. Cell function Chemical reactions Activity of enzymes Temperature pH [H+ conc.] Other factors Acidosis Cell function depressed Alkalosis Cell function depressed Optimal pH = 7.4pH = -log10[H+ ] Note the inverse relationship
  10. 10. 7.00 7.36 7.4 7.44 7.7 100 44 40 36 20 Plasma pH [H+ ] nmol/L Normal range Extreme Acidosis Extreme Alkalosis
  11. 11. 7.00 7.36 7.4 7.44 7.7 100 44 40 36 20 Plasma pH [H+ ] nmol/L Normal range
  12. 12. 7.00 7.36 7.4 7.44 7.7 100 44 40 36 20 Plasma pH [H+ ] nmol/L Normal range
  13. 13. What then is Acid BaseWhat then is Acid Base Balance?Balance? • Acid-base balance is the maintenance within a relatively narrow range of the H+ concentration in the extracellular fluid. i.e. H+ ion homeostasis. • This is both a formidable and a critical physiologic function--formidable because the body must deal with and defend itself against about 15,000 meq of organic acid each day and critical because the H+ concentration in the extracellular fluid compatible with life covers a relatively narrow range, from about a pH of 7.0 to about 7.7.
  14. 14. Why control pH or [H+ ]? • Metabolic reactions are highly sensitive to changes in pH due to its effect on protein conformation and biological activity e.g. enzyme activity
  15. 15. • Acid Substance that contains H+ ions that can be released Carbonic acid (H2CO3) releases H+ ions • Base Substance that can accept H+ ions Bicarbonate (HCO3 - accepts H+ ions The stronger the acid, the greater it dissociates into H+ ions
  16. 16. H2CO3 - CO2 + H2O In a reversible reaction, the concentration of the reactants on either side of the equation determines the direction of the reaction ( The Law of Mass Action ) H2CO3 - CO2 + H2O H2CO3 - CO2 + H2O H2CO3 - CO2 + H2O H2CO3 - CO2 + H2O Reaction stops when the concentrations of the reactants on either side become equal
  17. 17. Buffering • All buffers are weak acids or bases • Buffers limit change in hydrogen ion concentration (and so pH) when hydrogen ions are added or removed from the solution. •A buffer is like a sponge. When hydrogen ions are in excess, the sponge mops up the extra ions. When in short supply, the sponge can be squeezed out to release more hydrogen ions! H+ H+ H+ H+ are tied up in undissociated HA molecule
  18. 18. Weaker acid buffers the stronger acid • H2SO4 and other strong acids are buffered by H2CO3 • H2CO3 is buffered (during CO2 transport in blood) by – plasma proteins (HPr- ) in the plasma – Haemoglobin (HHb- ) in RBCs so that RBC function may not be impaired • Of course plasma proteins (HPr- ) and haemoglobin (HHb- ) can also buffer acids stronger than H2CO3
  19. 19. Weaker acid buffers the stronger acid Physiological buffering
  20. 20. Principal Buffers in Body Fluids Blood H2 CO3 H⇆ + + HCO3 – HProt H⇆ + + Prot– HHb H⇆ + + Hb– Interstitial fluid H2 CO3 H⇆ + + HCO3 – Intracellular fluid HProt H⇆ + + Prot– H2 PO4 – H⇆ + + HPO4 2–
  21. 21. Buffer Systems • Bicarbonate buffer - most important Active in ECF and intracellular fluid ICF • Phosphate buffer Active in (ICF) • Protein buffer - Largest buffer store Albumins and globulins (ECF) Hemoglobin and protein anions in tissue cells(ICF)
  22. 22. The blood buffers 1. Carbonic acid/bicarbonate system 2. Oxyhaemoglobin/deoxyhaemoglobin system 3. Plasma protein system 4. Monosodium phosphate/ disodium phosphate system 53% 35% 7%
  23. 23. Henderson-Hesselbalch equation pH = 6.1 + log [HCO3- ] 0.03 x pCO2 pH = pK + log [salt]/ [acid] CO2 + H2O → H2CO3 → H+ + HCO3 - = 6.1 + log [ HCO3 - ] [HHCO3] = 6.1 + 1.3 = 7.4 = 6.1 + log [20/1] Regulated by kidneys Regulated by lungs pK = ionization constant 24 mEq/L 1.2 mEq/L
  24. 24. • Since pH is determined by a ratio of HCO3 - to PaCO2, the Henderson-Hasselbalch equation may be conveniently reduced for clinical use to • The kidneys are responsible for maintaining HCO3-, and the lungs are responsible for maintaining PaCO2 . Thus
  25. 25. Carbonic acid / bicarbonate system
  26. 26. Bicarbonate-Carbonic Acid • Body’s major buffer • Carbonic acid - H2CO3 (Acid) • Bicarbonate - HCO3 - (Base) 1 20 pH = 7.4 H2CO3 ……………… HCO3 24 mEq/L1.2 mEq/L
  27. 27. Bicarbonate-Carbonic Acid • Ratio important • Not absolute values • Person with COPD 1 20 7.4 H2CO3 ……………… HCO3 48 mEq/L2.4 mEq/L
  28. 28. The 3 major homeostatic mechanisms maintain acid-base balance: • Buffering by extracellular and intracellular buffers - 1st line emergency defence (rapid) • Lungs: Alveolar ventilation, which controls PaCO2 (and increases efficiency of H2CO3 - /NaHCO3 - buffer system) • Renal H+ excretion, which controls plasma [HCO3 - ] (and conserves Na+ and excretes anion of the H2CO3…..HCO3
  29. 29. acid production in cells e.g. lactic acid production in hypoxic muscle cells Not due to respiratory(ventilatory) cause Nonrespiratory or Metabolic Acidosis Intracellular buffers in the muscles try to reduce the intracellular pH changes Then extracellular buffers in ISF and blood will act
  30. 30. Intracellular or tissue buffers • Proteins • Phosphates • Carbonic acid/KHCO3 buffer • Bone : hydration shell of hydroxyapatite crystals
  31. 31. H+H2CO3 - HCO3 - +CO2 +H2O The Key Reaction Remember: The Law of Mass Action
  32. 32. H+H2CO3 - HCO3 - +CO2 +H2O When nonvolatile acid , H+ is buffered by HCO3 - HA  H+ + A-
  33. 33. H+H2CO3 - HCO3 - +CO2 +H2O When nonvolatile acid , H+ is buffered by HCO3 - HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Buffer pair
  34. 34. H+H2CO3 - HCO3 - +CO2 +H2O When nonvolatile acid , H+ is buffered by HCO3 - HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes HCO3 -Metabolic acidosis
  35. 35. H+H2CO3 - HCO3 - +CO2 +H2O When HCO3 - NaHCO3 -  Na+ + HCO3 - replenishes Metabolic alkalosis H+
  36. 36. H+H2CO3 - HCO3 - +CO2 +H2O PaCO2 NaHCO3 -  Na+ + HCO3 - replenishes Respiratory alkalosis H+ Hyperventilation:
  37. 37. H+H2CO3 - HCO3 - +CO2 +H2O PaCO2 HCO3 - Respiratory acidosis H+ Hypoventilation:
  38. 38. H+H2CO3 - HCO3 - +CO2 +H2O HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Metabolic acidosis HCO3 -
  39. 39. H+H2CO3 - HCO3 - +CO2 +H2O HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Respiratory centre in medullaHyperventilation washoutCO2 arterial chemoreceptors HCO3 -
  40. 40. H+H2CO3 - HCO3 - +CO2 +H2O HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Hyperventilation washoutCO2 Respiratory centre in medulla arterial chemoreceptors HCO3 -PaCO2
  41. 41. H+H2CO3 - HCO3 - +CO2 +H2O HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Hyperventilation washoutCO2 Respiratory centre in medulla arterial chemoreceptors Continued buffering
  42. 42. Respiratory Control of plasma[H+ ] The respiratory center in the medulla oblongata, through chemoreceptors, is sensitive to blood levels of pCO2 and [H+ ].  When plasma [H+ ] rises, the respiratory centre activity increases  The resultant hyperventilation increases CO2 excretion (washout)  The fall in PCO2 shifts the reaction to the left, facilitating the buffering power of the H2CO3/NaHCO3 system
  43. 43. Role of Respiratory System in Regulation of pH
  44. 44. H+H2CO3 - HCO3 - +CO2 +H2O When H+ it is buffered by HCO3 - HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes NaA Na+ , the cation of NaHCO3 (buffer) should be conserved; the anion A- of offending acid should be eliminated
  45. 45. CO2 [H+ ] CO2 [H+ ] [H+ ] [H+ ] secretion by renal tubular cells Plasma [H+ ] as such is not taken up by the renal tubular cells; it is in the form of CO2 which the tubular cells take up and convert back to [H+ ] and secreted
  46. 46. Filtered CO2 Secretion of H+ by
  47. 47. Filtered CO2 K+
  48. 48. Distal nephron ATPase K+ HCO3 - regeneration Proton pump Almost all HCO3 – has been reabsorbed in proximal tubule CO2
  49. 49. Proximal and distal nephron
  50. 50. Renal handling of acid • Excretion of the daily acid load (50-100 mEq of H+ ) occurs principally through H+ secretion by the apical proton pump (H+ -K+ -ATPase) in A-type intercalated cells of the collecting duct. • Hydrogen ions secreted by the kidneys can be excreted as free ions but, at the lowest achievable urine pH of 4.5, would require excretion of 5000- 10,000 L of urine a day. • Urine pH cannot be lowered much below 4.5 because the gradient against which H+ -ATPase has to pump protons (intracellular pH 7.5 to luminal pH 4.5) becomes too steep. The “limiting pH” = 4.5
  51. 51. Distal nephron ATPase K+ Proton pump CO2 pH 7.3 pH 4.5 The “limiting pH”
  52. 52. The role of Urinary buffers • By binding or transforming secreted [H+ ], keep the tubular fluid [H+ ] low • limiting pH 4.5 is not reached • So that proton pump can continue secreting [H+ ] ions • Help in renal secretion of H+
  53. 53. Accumulation of nonvolatile acids and the subsequent depleting effect on HCO3 - content can be offset only by the renal ability to exchange sodium ions for hydrogen ions and the production of an acid urine. Renal Control of Acid-Base Balance Final correction but takes time
  54. 54. Renal Control of Acid-Base Balance As nonvolatile acid anions are filtered, they are accompanied by an equivalent number of cations (e.g., Na+ ) (maintenance of electrical neutrality). Through the activity of carbonic anhydrase, renal tubule cells combine CO2 (from their own metabolic activities) with water to make H2CO3 which dissociates to H+ and HCO3 - ions.
  55. 55. Renal Control of Acid-Base Balance The [H+ ] ions pass into the tubule and an equivalent amount of Na+ is returned accompanied by an equivalent amount of HCO3 - thus, Buffer cations (Na+ ) are conserved HCO3 - ions are replaced (replenished), – [H+ ] ions are excreted and acid urine is produced. – nonvolatile acid anions are excreted
  56. 56. H+H2CO3 - HCO3 - +CO2 +H2O When H+ it is buffered by HCO3 - HA  H+ + A- NaHCO3 -  Na+ + HCO3 - replenishes Na+ A- H+ A-
  57. 57. Renal Control of Acid-Base Balance The overall effect: restoration of the blood bicarbonate ion: carbonic acid ratio with a resultant correction of pH. and final elimination of the offending acid (HA) from the body pH = 6.1 + log [HCO3- ] 0.03 x pCO2 Regulated by kidneys
  58. 58. Definitions of Acid-base Terms • Disorders in the Blood Acidemia. A low blood pH (less than 7.36) Alkalemia. A high blood pH (greater than 7.44) Hypocapnia. A low PaCO2 (less than 36 mm Hg) Hypercapnia. A high PaCO2 (greater than 44 mm Hg) • Disorders in the Patient Metabolic acidosis. A primary disorder that causes a decrease in the plasma bicarbonate and lowers the blood pH. Metabolic alkalosis. A primary disorder that causes an increase in the serum bicarbonate and, raises the blood pH. Respiratory acidosis. A primary disorder that leads to an increased PaCO2 and, lowers the blood pH. Respiratory alkalosis. A primary disorder process that leads to a decreased PaCO2 and raises the blood pH. Compensatory process. Not a primary acid-base 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.
  59. 59. Acidosis • Acidosis- any situation in which the H+ concentration of arterial plasma is elevated. • (a) Respiratory acidosis- respiratory system fails to eliminate CO2 as fast as it is produced. Hallmark is an elevation in arterial pCO2 and H+ . Causes include lung damage and hypoventilation • (b) Metabolic acidosis- all situations where the primary problem is other than respiratory e.g. – excessive production of lactic acid (exercise/hypoxia), – production of ketone bodies (diabetes/fasting) – Retention of H+ in renal failure – loss of bicarbonate through diarrhea.
  60. 60. Alkalosis • Alkalosis- any situation resulting in a reduction in arterial H + concentration • Two categories: (a) Respiratory alkalosis- occurs when respiratory system eliminates CO2 faster than it is produced. Hallmark is a reduction in pCO2 and H+ concentration. • (b) Metabolic alkalosis- other than respiratory- based lowering of arterial H + concentration eg persistent vomiting  loss of H + from gastric HCl
  61. 61. Primary event and compensatory response for acid-base disorders Acid-base disorder Primary event (disorder) Compensatory (physiologic) response Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis hyperventilation hypoventilation Increased renal bicarb. reabsorption decreased renal bicarb. reabsorption lesser fall in pH lesser rise in pH lesser rise in pH lesser fall in pH
  62. 62. In compensated acidosis or alkalosis, absolute concentrations of bicarbonate ions and carbonic acid may be changed, but as long as the ratio remains in the range of approximately 20:1, the pH may be in the normal range.
  63. 63. Graphic versions (Davenport graphs) • The blood-buffer line, shown above, illustrates the changes in pH and bicarbonate of normal blood that occur when PCO2 is varied.
  64. 64. Note: the primary disorder as well as the compensatory mechanism produces the changes in plasma HCO3 - in the same direction Respiratory acidosis and renal compensation since CO2 + H2O → H2CO3 → H+ + HCO3 - since kidney reabsorbs more HCO3 - as more CO2 is available to tubular cells
  65. 65. Note: the primary disorder as well as the compensatory mechanism produces the changes in plasma HCO3 - in the same direction Respiratory acidosis and alkalosis You should be able to work out for the other 3 acid-base disturbances Metabolic acidosis and alkalosis
  66. 66. Partial pressures of CO2 Respiratory responses occur along this axis as the pH will be inversely related to the lungs ability to eliminate CO2
  67. 67. Analysis of simple acid base disorders and how they are compensated for by the body.
  68. 68. References 1. Ganong’s Review of Medical Physiology. 23rd ed. MacGraw Hill. 2. Textbook of Medical Physiology, 11th edition. Guyton AC and JE. Hall. 3. http://www.health.adelaide.edu.au/paed- anaes/javaman/Respiratory/a-b/AcidBase.html 44 

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