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Buffers in Blood.
Acidosis and Alkalosis.

     Chemistry Department of UB




                                  1
Buffers in the Blood
   The pH of blood is 7.35 – 7.45
   Changes in pH below 6.8 and above 8.0 may result in
    death
   The major buffer system in the body fluid is H2CO3/HCO3-
   Some CO2, the end product of cellular metabolism, is
    carried to the lungs for elimination, and the rest dissolves
    in body fluids, forming carbonic acid that dissociates to
    produce bicarbonate (HCO3-) and hydronium (H3O+) ions.
   More of the HCO3- is supplied by the kidneys.
   CO2 + H2O ↔ H2CO3
   H2CO3 + H2O ↔ H3O+ + HCO3-

                                                              2
Carbonate buffer
H2CO3 + H2O ↔ H3O+ + HCO3-
   Excess acid (H3O+) in the body is
    neutralized by HCO3-
   H2CO3 + H2O ← H3O+ + HCO3-
   Equilibrium shifts left
   Excess base (OH-) reacts with the carbonic
    acid (H2CO3)
   H2CO3 + OH- → H2O + HCO3-
   Equilibrium shifts right
                                             3
pH of the blood buffer
   The concentrations in the blood of H2CO3 and
    HCO3- are 0.0024M and 0.024 respectively
   H2CO3/ HCO3- = 1/10 is needed to maintain the
    normal blood pH (7.35 – 7.45)        −
                    [ H 3O + ][ HCO3 ]
               Ka =
                         [ H 2CO3 ]
                                  [ H 2CO3 ]
               [ H 3O + ] = K a          −
                                             =
                                  [ HCO3 ]
                          0.0024
               = 4.3 x10 −7 x       = 4.3 x10 −7 x0.10 = 4.3 x10 −8
                           0.024
               pH = − log(4.3 x10 −8 ) = 7.37



                                                                      4
The effectiveness of the blood buffer
   If the pH of 100 mL of distilled water is 7.35 and
    one drop of 0.05 M HCl is added, the pH will
    change to 7.00.
   To change 100 mL of “normal” blood from pH of
    7.35 to 7.00, approximately 25 mL of 0.05 M HCl
    is needed.
   With 5.5 L of blood in the average body, more
    than 1300 mL of HCl would be required to make
    the same change in pH.
                                                    5
Regulation of blood pH
   The lungs and kidneys play important role in
    regulating blood pH.
   The lungs regulate pH through retention or
    elimination of CO2 by changing the rate and
    volume of ventilation.
   The kidneys regulate pH by excreting acid,
    primarily in the ammonium ion (NH4+), and by
    reclaiming HCO3- from the glomerular filtrate (and
    adding it back to the blood).
                                                    6
Importance of the bicarbonate-
carbonic acid buffering system
1.   H2CO3 dissociates into CO2 and H2O,
     allowing H3O+ to be eliminated as CO2 by
     the lungs
2.   Changes in PCO2 modify the ventilation
     rate
3.   HCO3- concentration can be altered by
     kidneys

                                                7
Other important buffers
   The phosphate buffer system (HPO42-/H2PO4-) plays
    a role in plasma and erythrocytes.
   H2PO4- + H2O ↔ H3O+ + HPO42-
   Any acid reacts with monohydrogen phosphate to
    form dihydrogen phosphate
dihydrogen phosphate   monohydrogen phosphate
   H2PO4- + H2O ← HPO42- + H3O+
   The base is neutralized by dihydrogen phosphate
dihydrogen phosphate   monohydrogen phosphate
   H2PO4- + OH- → HPO42- + H3O+
                                                      8
Proteins act as a third type of blood
buffer
   Proteins contain – COO- groups, which, like acetate ions
    (CH3COO-), can act as proton acceptors.
   Proteins also contain – NH3+ groups, which, like
    ammonium ions (NH4+), can donate protons.
   If acid comes into blood, hydronium ions can be
    neutralized by the – COO- groups
   - COO- + H3O+ → - COOH + H2O
   If base is added, it can be neutralized by the – NH3+
    groups
   - NH3+ + OH- → - NH2 + H2O

                                                               9
Normal Values for Blood Buffer in
Arterial Blood.
   The following values are determined by
    blood gas analyzer:
   pH       7.35 – 7.45
   PCO    2 35 – 45 mm Hg
   H2CO3      2.4 mmoles/L of plasma
   HCO3-      24 mmoles/L of plasma
   PO 2       80 – 110 mm Hg

                                             10
Blood Gases
   In the body, cells use up O2 and give off CO2.
   O2 flows into the tissues because the partial
    pressure of O2 is higher (100 mm Hg) in
    oxygenated blood, and lower (<30 mm Hg) in
    the tissues.
   CO2 flows out of the tissues because the
    partial pressure of CO2 is higher (>50 mm
    Hg) in the tissues and lower (40 mm Hg) in
    the blood.
                                                     11
Blood Gases
   In the lungs, O2
    enters the blood,
    while CO2 from
    the blood is
    released.
   In the tissues, O2
    enters the cells,
    which release
    CO2 into the
    blood.               12
Interpretation of Clinical Blood Gas Data
                      H 2O
CO2 + H2O ↔ H2CO3 ↔ H3O+ + HCO3-



   The concentration of carbonic acid in the body is
    associated with the partial pressure of CO2.
   When CO2 level rises, producing more H2CO3, the
    equilibrium produces more H3O+, which lowers the
    pH – acidosis.
   Decreasing of CO2 level due to a hyperventilation,
    which expels large amounts of CO2, leads to a
    lowering in the partial pressure of CO2 below
    normal and the shift of the equilibrium from
    H2CO3 to CO2 and H2O. This shift decreases H3O+
    and raises blood pH – alkalosis.
                                                   13
Respiratory Acidosis: CO2 ↑ pH ↓
   Symptoms: Failue to ventilate, suppression of
    breathing, disorientation, weakness, coma
   Causes: Lung disease blocking gas diffusion (e.g.,
    emphysema, pneumonia, bronchitis, and asthma);
    depression of respiratory center by drugs,
    cardiopulmonary arrest, stroke, poliomyelitis, or
    nervous system disorders
   Treatment: Correction of disorder, infusion of
    bicarbonate
                                                   14
Respiratory Alkalosis: CO2 ↓ pH ↑
   Symptoms: Increased rate and depth of breathing,
    numbness, light-headedness, tetany
   Causes: hyperventilation due to anxiety, hysteria,
    fever, exercise; reaction to drugs such as
    salicylate, quinine, and antihistamines; conditions
    causing hypoxia (e.g., pneumonia, pulmonary
    edema, and heart disease)
   Treatment: Elimination of anxiety producing state,
    rebreathing into a paper bag
                                                    15
Metabolic (Nonrespiratory)
Acidosis: H+ ↑ pH ↓
   Symptoms: Increased ventilation, fatigue,
    confusion
   Causes: Renal disease, including hepatitis and
    cirrhosis; increased acid production in diabetes
    mellitus, hyperthyroidism, alcoholism, and
    starvation; loss of alkali in diarrhea; acid retention
    in renal failure
   Treatment: Sodium bicarbonate given orally,
    dialysis for renal failure, insulin treatment for
    diabetic ketosis
                                                       16
Metabolic (Nonrespiratory)
Alkalosis: H+ ↓ pH ↑
   Symptoms: Depressed breathing, apathy,
    confusion
   Causes: Vomiting, diseases of the adrenal
    glands, ingestions of access alkali
   Treatment: Infusion of saline solution,
    treatment of underlying diseases


                                            17

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Buffer in the blood

  • 1. Buffers in Blood. Acidosis and Alkalosis. Chemistry Department of UB 1
  • 2. Buffers in the Blood  The pH of blood is 7.35 – 7.45  Changes in pH below 6.8 and above 8.0 may result in death  The major buffer system in the body fluid is H2CO3/HCO3-  Some CO2, the end product of cellular metabolism, is carried to the lungs for elimination, and the rest dissolves in body fluids, forming carbonic acid that dissociates to produce bicarbonate (HCO3-) and hydronium (H3O+) ions.  More of the HCO3- is supplied by the kidneys.  CO2 + H2O ↔ H2CO3  H2CO3 + H2O ↔ H3O+ + HCO3- 2
  • 3. Carbonate buffer H2CO3 + H2O ↔ H3O+ + HCO3-  Excess acid (H3O+) in the body is neutralized by HCO3-  H2CO3 + H2O ← H3O+ + HCO3-  Equilibrium shifts left  Excess base (OH-) reacts with the carbonic acid (H2CO3)  H2CO3 + OH- → H2O + HCO3-  Equilibrium shifts right 3
  • 4. pH of the blood buffer  The concentrations in the blood of H2CO3 and HCO3- are 0.0024M and 0.024 respectively  H2CO3/ HCO3- = 1/10 is needed to maintain the normal blood pH (7.35 – 7.45) − [ H 3O + ][ HCO3 ] Ka = [ H 2CO3 ] [ H 2CO3 ] [ H 3O + ] = K a − = [ HCO3 ] 0.0024 = 4.3 x10 −7 x = 4.3 x10 −7 x0.10 = 4.3 x10 −8 0.024 pH = − log(4.3 x10 −8 ) = 7.37 4
  • 5. The effectiveness of the blood buffer  If the pH of 100 mL of distilled water is 7.35 and one drop of 0.05 M HCl is added, the pH will change to 7.00.  To change 100 mL of “normal” blood from pH of 7.35 to 7.00, approximately 25 mL of 0.05 M HCl is needed.  With 5.5 L of blood in the average body, more than 1300 mL of HCl would be required to make the same change in pH. 5
  • 6. Regulation of blood pH  The lungs and kidneys play important role in regulating blood pH.  The lungs regulate pH through retention or elimination of CO2 by changing the rate and volume of ventilation.  The kidneys regulate pH by excreting acid, primarily in the ammonium ion (NH4+), and by reclaiming HCO3- from the glomerular filtrate (and adding it back to the blood). 6
  • 7. Importance of the bicarbonate- carbonic acid buffering system 1. H2CO3 dissociates into CO2 and H2O, allowing H3O+ to be eliminated as CO2 by the lungs 2. Changes in PCO2 modify the ventilation rate 3. HCO3- concentration can be altered by kidneys 7
  • 8. Other important buffers  The phosphate buffer system (HPO42-/H2PO4-) plays a role in plasma and erythrocytes.  H2PO4- + H2O ↔ H3O+ + HPO42-  Any acid reacts with monohydrogen phosphate to form dihydrogen phosphate dihydrogen phosphate monohydrogen phosphate  H2PO4- + H2O ← HPO42- + H3O+  The base is neutralized by dihydrogen phosphate dihydrogen phosphate monohydrogen phosphate  H2PO4- + OH- → HPO42- + H3O+ 8
  • 9. Proteins act as a third type of blood buffer  Proteins contain – COO- groups, which, like acetate ions (CH3COO-), can act as proton acceptors.  Proteins also contain – NH3+ groups, which, like ammonium ions (NH4+), can donate protons.  If acid comes into blood, hydronium ions can be neutralized by the – COO- groups  - COO- + H3O+ → - COOH + H2O  If base is added, it can be neutralized by the – NH3+ groups  - NH3+ + OH- → - NH2 + H2O 9
  • 10. Normal Values for Blood Buffer in Arterial Blood.  The following values are determined by blood gas analyzer:  pH 7.35 – 7.45  PCO 2 35 – 45 mm Hg  H2CO3 2.4 mmoles/L of plasma  HCO3- 24 mmoles/L of plasma  PO 2 80 – 110 mm Hg 10
  • 11. Blood Gases  In the body, cells use up O2 and give off CO2.  O2 flows into the tissues because the partial pressure of O2 is higher (100 mm Hg) in oxygenated blood, and lower (<30 mm Hg) in the tissues.  CO2 flows out of the tissues because the partial pressure of CO2 is higher (>50 mm Hg) in the tissues and lower (40 mm Hg) in the blood. 11
  • 12. Blood Gases  In the lungs, O2 enters the blood, while CO2 from the blood is released.  In the tissues, O2 enters the cells, which release CO2 into the blood. 12
  • 13. Interpretation of Clinical Blood Gas Data H 2O CO2 + H2O ↔ H2CO3 ↔ H3O+ + HCO3-  The concentration of carbonic acid in the body is associated with the partial pressure of CO2.  When CO2 level rises, producing more H2CO3, the equilibrium produces more H3O+, which lowers the pH – acidosis.  Decreasing of CO2 level due to a hyperventilation, which expels large amounts of CO2, leads to a lowering in the partial pressure of CO2 below normal and the shift of the equilibrium from H2CO3 to CO2 and H2O. This shift decreases H3O+ and raises blood pH – alkalosis. 13
  • 14. Respiratory Acidosis: CO2 ↑ pH ↓  Symptoms: Failue to ventilate, suppression of breathing, disorientation, weakness, coma  Causes: Lung disease blocking gas diffusion (e.g., emphysema, pneumonia, bronchitis, and asthma); depression of respiratory center by drugs, cardiopulmonary arrest, stroke, poliomyelitis, or nervous system disorders  Treatment: Correction of disorder, infusion of bicarbonate 14
  • 15. Respiratory Alkalosis: CO2 ↓ pH ↑  Symptoms: Increased rate and depth of breathing, numbness, light-headedness, tetany  Causes: hyperventilation due to anxiety, hysteria, fever, exercise; reaction to drugs such as salicylate, quinine, and antihistamines; conditions causing hypoxia (e.g., pneumonia, pulmonary edema, and heart disease)  Treatment: Elimination of anxiety producing state, rebreathing into a paper bag 15
  • 16. Metabolic (Nonrespiratory) Acidosis: H+ ↑ pH ↓  Symptoms: Increased ventilation, fatigue, confusion  Causes: Renal disease, including hepatitis and cirrhosis; increased acid production in diabetes mellitus, hyperthyroidism, alcoholism, and starvation; loss of alkali in diarrhea; acid retention in renal failure  Treatment: Sodium bicarbonate given orally, dialysis for renal failure, insulin treatment for diabetic ketosis 16
  • 17. Metabolic (Nonrespiratory) Alkalosis: H+ ↓ pH ↑  Symptoms: Depressed breathing, apathy, confusion  Causes: Vomiting, diseases of the adrenal glands, ingestions of access alkali  Treatment: Infusion of saline solution, treatment of underlying diseases 17