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Acid base balance

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physiology,
acid base balance
acid base homeostasis
acid base regulation in the body
acid base regulation

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Acid base balance

  1. 1. ACID - BASE Balance PHYSIOLOGY
  2. 2. ACID BASE HOMEOSTASIS  Acid-Base homeostasis involves chemical and physiologic processes responsible for the maintenance of the acidity of body fluids at levels that allow optimal function of the whole individual 2
  3. 3. ACID BASE HOMEOSTASIS  The chemical processes represent the first line of defense to an acid or base load and include the extracellular and intracellular buffers  The physiologic processes modulate acid-base composition by changes in cellular metabolism and by adaptive responses in the excretion of volatile acids by the lungs and fixed acids by the kidneys 3
  4. 4. ACID BASE HOMEOSTASIS  The need for the existence of multiple mechanisms involved in Acid-Base regulation stems from the critical importance of the hydrogen ion (H+) concentration on the operation of many cellular enzymes and function of vital organs, most prominently the brain and the heart 4
  5. 5. ACID BASE HOMEOSTASIS ◦Metabolic pathways are continuously consuming or producing H+ ◦The daily load of waste products for excretion in the form of volatile and fixed acids is substantial 5
  6. 6. EFFECTS OF pH  The most general effect of pH changes are on enzyme function ◦ Also affect excitability of nerve and muscle cells 6 pH pH Excitability Excitability
  7. 7. ACID-BASE BALANCE 7
  8. 8. ACID-BASE BALANCE  Acid - Base balance is primarily concerned with two ions: ◦Hydrogen (H+) ◦Bicarbonate (HCO- ) 3 8 - H+ HCO3
  9. 9. ACID-BASE BALANCE  Derangements of hydrogen and bicarbonate concentrations in body fluids are common in disease processes 9
  10. 10. ACID-BASE BALANCE H+ ion has special significance because of the narrow ranges that it must be maintained in order to be compatible with living systems 10
  11. 11. ACID-BASE BALANCE  Primarily controlled by regulation of H+ ions in the body fluids ◦ Especially extracellular fluids 11
  12. 12. ACID-BASE REGULATION 12
  13. 13. ACID-BASE REGULATION  Maintenance of an acceptable pH range in the extracellular fluids is accomplished by three mechanisms: ◦1) Chemical Buffers React very rapidly (less than a second) ◦2) Respiratory Regulation Reacts rapidly (seconds to minutes) ◦3) Renal Regulation Reacts slowly (minutes to hours) 13
  14. 14. ACID-BASE REGULATION  Chemical Buffers ◦ The body uses pH buffers in the blood to guard against sudden changes in acidity ◦ A pH buffer works chemically to minimize changes in the pH of a solution 14 Buffer
  15. 15. ACID-BASE REGULATION  Respiratory Regulation ◦ Carbon dioxide is an important by-product of metabolism and is constantly produced by cells ◦ The blood carries carbon dioxide to the lungs where it is exhaled 15 Cell Metabolism CO2CO2 CO2 CO CO2 2 CO2
  16. 16. ACID-BASE REGULATION  Respiratory Regulation ◦ When breathing is increased, the blood carbon dioxide level decreases and the blood becomes more Base ◦ When breathing is decreased, the blood carbon dioxide level increases and the blood becomes more Acidic ◦ By adjusting the speed and depth of breathing, the respiratory control centers and lungs are able to regulate the blood pH minute by minute 16
  17. 17. ACID-BASE REGULATION  Kidney Regulation ◦ Excess acid is excreted by the kidneys, largely in the form of ammonia ◦ The kidneys have some ability to alter the amount of acid or base that is excreted, but this generally takes several days 17
  18. 18. ACID-BASE REGULATION  Enzymes, hormones and ion distribution are all affected by Hydrogen ion concentrations 18
  19. 19. ACIDS 19
  20. 20. 20 ACIDS  Acids can be defined as a proton (H+) donor  Hydrogen containing substances which dissociate in solution to release H+  Many other substance (carbohydrates) also contain hydrogen but they are not classified as acids because the hydrogen is tightly bound within their molecular structure and it is never liberated as free H+
  21. 21. 21 ACIDS  Physiologically important acids include: ◦Carbonic acid (H2CO3) ◦Phosphoric acid (H3PO4) ◦Pyruvic acid (C3H4O3) ◦ Lactic acid (C3H6O3)  These acids are dissolved in body fluids Lactic acid Pyruvic acid Phosphoric acid
  22. 22. BASES 22
  23. 23. BASES  Bases can be defined as: ◦ A proton (H+) acceptor ◦ Molecules capable of accepting a hydrogen ion (OH-) 23
  24. 24. BASES  Physiologically important bases include: ◦Bicarbonate (HCO- ) 3 ◦Biphosphate (HPO4 -2 ) 24 Biphosphate
  25. 25. pH SCALE 25
  26. 26. pH SCALE  pH refers to Potential Hydrogen  Expresses hydrogen ion concentration in water solutions  Water ionizes to a limited extent to form equal amounts of H+ ions and OH- ions ◦H2O H+ + OH- H+ ion is an acid OH- ion is a base 26
  27. 27. pH SCALE  Pure water is Neutral ◦ ( H+ = OH- )  pH = 7  Acid ◦ ( H+ > OH- )  pH < 7  Base ◦ ( H+ < OH- )  pH > 7 ACIDS, BASES OR NEUTRAL??? OH-OH-OH-OH H+ H+  Normal blood pH is 7.35 - 7.45  pH range compatible with life is 6.8 - 8.0 27 OH-OH-OH-OH-OH-OH-H+ H+ H+ H+ OH- - H+ H+ OH-OH-OH-H+ H+ H+ H+ H+ H+ H+ 1 2 3
  28. 28. pH SCALE  pH = 4 is more acidic than pH = 6  pH = 4 has 10 times more free H+ concentration than pH = 5 and 100 times more free H+ concentration than pH = 6 6.8 7.3 7.4 7.5 8.0 28 ACIDOSIS NORMAL ALKALOSIS DEATH DEATH Venous Blood Arterial Blood
  29. 29. ACIDOSIS / ALKALOSIS 29
  30. 30. ACIDOSIS / ALKALOSIS  An abnormality in one or more of the pH control mechanisms can cause one of two major disturbances in Acid-Base balance ◦ Acidosis ◦ Alkalosis 30
  31. 31. ACIDOSIS / ALKALOSIS  Acidosis and alkalosis are not diseases but rather are the results of a wide variety of disorders  The presence of acidosis or alkalosis provides an important clue to physicians that a serious metabolic problem exists 31
  32. 32. ACIDOSIS / ALKALOSIS 32  Acidosis ◦ A condition in which the blood has too much acid (or too little base), frequently resulting in a decrease in blood pH  Alkalosis ACID BASE ◦ A condition in which the blood has too much base (or too little acid), occasionally resulting in an increase in blood pH ACID BASE
  33. 33. ACIDOSIS / ALKALOSIS  pH changes have dramatic effects on normal cell function ◦1) Changes in excitability of nerve and muscle cells ◦2) Influences enzyme activity ◦3) Influences K+ levels 33
  34. 34. CHANGES IN CELL EXCITABILITY  pH decrease (more acidic) depresses the central nervous system ◦Can lead to loss of consciousness  pH increase (more basic) can cause over-excitability ◦ Tingling sensations, nervousness, muscle twitches 34
  35. 35. INFLUENCES ON ENZYME ACTIVITY  pH increases or decreases can alter the shape of the enzyme rendering it non-functional  Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell 35
  36. 36. INFLUENCES ON K+ LEVELS  When reabsorbing Na+ from the filtrate of the renal tubules K+ or H+ is secreted (exchanged)  Normally K+ is secreted in much greater amounts than H+ 36 K+ K+ Na+ H+
  37. 37. INFLUENCES ON K+ LEVELS  If H+ concentrations are high (acidosis) H+ is secreted in greater amounts  This leaves less K+ than usual excreted  The resultant K+ retention can affect cardiac function and other systems 37 K+ Na+ H+
  38. 38. ACIDOSIS / ALKALOSIS Normal values of bicarbonate (arterial) ◦pH = 7.4 ◦PCO= 40 mm Hg 2 ◦HCO- = 24 meq/L 3 38
  39. 39. RESPONSES TO: ACIDOSIS AND ALKALOSIS Mechanisms protect the body against life-threatening changes in hydrogen ion concentration ◦1) Buffering Systems in Body Fluids ◦2) Respiratory Responses ◦3) Renal Responses ◦4) Intracellular Shifts of Ions 39
  40. 40. 1) Buffer Systems 2) Respiratory Responses 3) Renal Responses 4) Intracellular Shifts of Ions 40
  41. 41. BUFFERS  Buffering systems provide an immediate response to fluctuations in pH ◦1) Phosphate ◦2) Protein ◦3) Bicarbonate Buffer System 41
  42. 42. BUFFERS  A buffer is a combination of chemicals in solution that resists any significant change in pH  Able to bind or release free H+ ions 42
  43. 43. 43 BUFFERS  Chemical buffers are able to react immediately (within milliseconds)  Chemical buffers are the first line of defense for the body for fluctuations in pH
  44. 44. PHOSPHATE BUFFER SYSTEM  1) Phosphate buffer system Na2HPO4 + H+ NaH2PO4 + Na+ ◦ Most important in the intracellular system ◦ Alternately switches Na+ with H+ Disodium hydrogen phosphate H+ Na2HPO4 + +Na+ Click to NaH2PO4 animate 44
  45. 45. PHOSPHATE BUFFER SYSTEM Na2HPO4 + H+ NaH2PO4 + Na+  Phosphates are more abundant within the cell and are rivaled as a buffer in the ICF by even more abundant protein 45 Na2HPO4 Na2HPO4 Na2HPO4
  46. 46. PHOSPHATE BUFFER SYSTEM  Regulates pH within the cells and the urine ◦Phosphate concentrations are higher intracellularly and within the kidney tubules ◦Too low of a concentration in extracellular fluid to have much importance as an ECF buffer system 46 HPO4 -2
  47. 47. PROTEIN BUFFER SYSTEM  2) Protein Buffer System ◦Behaves as a buffer in both plasma and cells ◦Hemoglobin is by far the most important protein buffer 47
  48. 48. PROTEIN BUFFER SYSTEM 48  Most important intracellular buffer (ICF)  The most plentiful buffer of the body
  49. 49. PROTEIN BUFFER SYSTEM  Proteins are excellent buffers because they contain both acid and base groups that can give up or take up H+  Proteins are extremely abundant in the cell  The more limited number of proteins in the plasma reinforce the bicarbonate system in the ECF 49
  50. 50. PROTEIN BUFFER SYSTEM  Hemoglobin buffers H+ from metabolically produced CO2 in the plasma only  As hemoglobin releases O2 it gains a great affinity for H+ 50 Hb O2 O2 O2 O2
  51. 51. PROTEIN BUFFER SYSTEM  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 51 Hb O2 O2 O2 O2
  52. 52. PROTEIN BUFFER SYSTEM  As H+Hb picks up O2 from the lungs the Hb which has a higher affinity for O2 releases H+ and picks up O2  Liberated H+ from H2O combines with HCO3 - H2CO3 CO2 52 - HCO3 (exhaled) Hb O2 H+ O2 O2
  53. 53. PROTEIN BUFFER SYSTEM  Venous blood is only slightly more acidic than arterial blood because of the tremendous buffering capacity of Hb  Even in spite of the large volume of H+ generating CO2 carried in venous blood 53
  54. 54. PROTEIN BUFFER SYSTEM  Proteins can act as a buffer for both acids and bases  Protein buffer system works instantaneously making it the most powerful in the body  75% of the body’s buffer capacity is controlled by protein ◦ Bicarbonate and phosphate buffer systems require several hours to be effective Pr - added H+ + Pr - 54
  55. 55. PROTEIN BUFFER SYSTEM  Proteins are very large, complex molecules in comparison to the size and complexities of acids or bases  Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule ++ + + + 55 - - + + + + ++ + + + - - - - - - - - - - - - - - - - - - - - - - - - - - - + ++ + + - - -- + ++ + + +
  56. 56. PROTEIN BUFFER SYSTEM  H+ ions are attracted to and held from chemical interaction by the negative charges ++ + 56 - - ++ + + + + + + + ++ + + + - - - - - - - - - - - - - - - - - - - - - - - - - - - + + - - -- + ++ + + + H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H H+ H+ H+ H+ H+ H+ +
  57. 57. PROTEIN BUFFER SYSTEM OH- ions which are the basis of alkalosis are attracted by the positive charges in the crevices of the protein + ++ + 57 - - ++ + + + + + + + ++ + + + - - - - - - - - - - - - - - - - - - - - - - - - - - - + - - -- + ++ + + + OH-OH-OH-OH-OH-OH-OH-OH-OH-OH OH- - OH-
  58. 58. PROTEIN BUFFER SYSTEM + ++ + 58 - - ++ + + + + + + + + ++ + + + - - - - - - - - - - - - - - - - - - - - - - - - - - - + - - -- + ++ + + OH-OH-OH-OH-OH-OH-OH-OH-OH- OH-OH-OH- H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H H+ H+ H+ H+ H+ H+ +
  59. 59. BICARBONATE BUFFER SYSTEM  3) Bicarbonate Buffer System ◦ Predominates in extracellular fluid (ECF) HCO- + added H+ HCO3 23 HCO3 - H2CO3 59
  60. 60. BICARBONATE BUFFER SYSTEM  This system is most important because the concentration of both components can be regulated: ◦Carbonic acid by the respiratory system ◦ Bicarbonate by the renal system 60
  61. 61. BICARBONATE BUFFER SYSTEM H2CO3 H+ + HCO3 61 - ◦ Hydrogen ions generated by metabolism or by ingestion react with bicarbonate base to form more carbonic acid HCO3 - H2CO3
  62. 62. BICARBONATE BUFFER SYSTEM  Equilibrium shifts toward the formation of acid ◦ Hydrogen ions that are lost (vomiting) causes carbonic acid to dissociate yielding replacement H+ and bicarbonate H2CO3 H+ HCO3 - 62
  63. 63. BICARBONATE BUFFER SYSTEM Addition of lactic acid 63 Loss of HCl H+ HCO3 - CO H2O H2CO3 2+ + Exercise Vomiting
  64. 64. 64 1) Buffer Systems 2) Respiratory Responses 3) Renal Responses 4) Intracellular Shifts of Ions
  65. 65. RESPIRATORY RESPONSE  Neurons in the medulla oblongata and pons constitute the Respiratory Center  Stimulation and limitation of respiratory rates are controlled by the respiratory center  Control is accomplished by responding to CO2 and H+ concentrations in the blood 65
  66. 66. 66 RESPIRATORY CENTER Pons Respiratory centers Medulla oblongata
  67. 67. CHEMOSENSITIVE AREAS  Chemosensitive areas of the respiratory center are able to detect blood concentration levels of CO2 and H+  Increases in CO2 and H+ stimulate the respiratory center ◦ The effect is to raise 67 respiration rates But the effect diminishes in 1 - 2 minutes CO2 CO2 CO2 CO2 CO2 Click to increase CO2 CO2 CO2 CO2 CO2
  68. 68. CHEMOSENSITIVE AREAS 68  The effect of stimulating the respiratory centers by increased CO2 and H+ is weakened in environmentally increased CO2 levels  Symptoms may persist for several days
  69. 69. 69 CHEMORECEPTORS  Chemoreceptors are also present in the carotid and aortic arteries which respond to changes in partial pressures of O2 and CO2 or pH  Increased levels of CO2 (low pH) or decreased levels of O2 stimulate respiration rates to increase
  70. 70. 70 CHEMORECEPTORS  Overall compensatory response is: ◦Hyperventilation in response to increased CO2 or H+ (low pH) ◦Hypoventilation in response to decreased CO2 or H+ (high pH)
  71. 71. RESPIRATORY CONTROL OF pH cell production of CO2 increases CO2 + H2O H2CO3 H2CO3 H+ + HCO3 H+ stimulates respiratory center in medulla oblongata rate and depth of breathing increase 71 CO2 eliminated in lungs pH rises toward normal - H+ acidosis; pH drops
  72. 72. 1) Buffer Systems 2) Respiratory Responses 3) Renal Responses 4) Intracellular Shifts of Ions 72
  73. 73. 73 RENAL RESPONSE  The kidney compensates for Acid - Base imbalance within 24 hours and is responsible for long term control  The kidney in response: ◦To Acidosis Retains bicarbonate ions and eliminates hydrogen ions ◦To Alkalosis Eliminates bicarbonate ions and retains hydrogen ions
  74. 74. ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA 74
  75. 75. ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA 75 Capillary Distal Tubule Cells Tubular urine to be excreted NH2 H+ NH3 NH3 WHAT HAPPENS NEXT?
  76. 76. ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA NH3 Na + 76 Capillary Distal Tubule Cells + Cl- Tubular Urine HCO HCO2-+ 3 3 NaCl NaHCO3 Click Mouse to Start Animation NH3Cl- H+ NH4Cl Click Mouse to See Animation Again Notice the H+ - Na+ exchange to maintain electrical neutrality Dissociation of carbonic acid
  77. 77. RESPIRATORY / EXCRETORY RESPONSE CO2 + H2O H2CO3 H+ + HCO3 - 77 Hyperventilation removes H+ ion concentrations Hypoventilation increases H+ ion concentrations Kidneys eliminate or retain H+ or bicarbonate ions
  78. 78. 1) Buffer Systems 2) Respiratory Responses 3) Renal Responses 4) Intracellular Shifts of Ions 78
  79. 79. 79 HYPERKALEMIA  Hyperkalemia is generally associated with acidosis ◦Accompanied by a shift of H+ ions into cells and K+ ions out of the cell to maintain electrical neutrality H+ K+
  80. 80. 80 HYPERKALEMIA  Hyperkalemia is an elevated serum K+ ◦H+ ions are buffered in cell by proteins  Acidosis may cause Hyperkalemia and Hyperkalemia may cause Acidosis H+ K+
  81. 81. 81 HYPOKALEMIA  Hypokalemia is generally associated with reciprocal exchanges of H+ and K+ in the opposite direction ◦Associated with alkalosis  Hypokalemia is a depressed serum K+ H+ K+
  82. 82. Acidosis Compensatory Response Result Alkalosis Compensatory Response Result 82 ELECTROLYTE SHIFTS H+ cell K+ - H+ buffered intracellularly - Hyperkalemia H+ K+ cell - Tendency to correct alkalosis - Hypokalemia
  83. 83. 84

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