1. Chapter 13 Part 1 Acid-Base Balance

2. Learning Objectives
Describe how the lungs and kidneys regulate volatile and fixed acids.
Describe how an acid’s equilibrium constant is related to its ionization and strength.
State what constitutes open and closed buffer systems.
Explain why open and closed buffer systems differ in their ability to buffer fixed and volatile acids.
Explain how to use the Henderson- Hasselbalch equation in hypothetical clinical situations.

3. Learning Objectives (cont.)
Describe how the kidneys and lungs compensate for each other when the function of one is abnormal.
Explain how renal absorption and excretion of electrolytes affect acid-base balance.
Classify and interpret arterial blood acid-base results.
Explain how to use arterial acid-base information to decide on a clinical course of action.

4. Learning Objectives (cont.)
Explain why acute changes in the blood’s carbon dioxide level affect the blood’s bicarbonate ion concentration.
Calculate the anion gap and use it to determine the cause of metabolic acidosis.
Describe how standard bicarbonate and base excess measurements are used to identify the nonrespiratory component of acid-base imbalances.
State how Stewart’s strong ion difference approach to acid-base regulation differs from the Henderson-Hasselbalch approach.

5. Acid-Base Balance
First, a Review: A. To be in balance, the quantities of fluids and electrolytes (molecules that release ions in water) leaving the body should be equal to the amounts taken in. B. Anything that alters the concentrations of electrolytes will also alter the concentration of water, and vice versa.

6. Acid-Base Balance
A. Electrolytes that ionize in water and release hydrogen ions are acids; those that combine with hydrogen ions are bases.
B. Maintenance of homeostasis depends on the control of acids and bases in body fluids.

7. Acid-Base Balance C. Sources of Hydrogen Ions
1.Most hydrogen ions originate as by- products of metabolic processes, including the:
aerobic and anaerobic respiration of glucose,
incomplete oxidation of fatty acids,
oxidation of amino acids containing sulfur, and the
breakdown of phosphoproteins and nucleic acids.

8. Aerobic respiration of glucose Anaerobic respiration of glucose
Fig18.06
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Aerobic
respiration
of glucose
Anaerobic
respiration
of glucose
Incomplete
oxidation of
fatty acids
Oxidation of
sulfur-containing
amino acids
Hydrolysis of
phosphoproteins
and nucleic acids
Carbonic
acid
Lactic
acid
Acidic ketone
bodies
Sulfuric
acid
Phosphoric
acid H+
Internal environment

9. Hydrogen Ion Regulation in Body Fluids
Even small hydrogen ion [H+] concentration changes can cause vital metabolic processes to fail;
Normal metabolism continuously generates [H+];
[H+] regulation is of utmost biologic importance.
Various physiologic mechanisms work together to keep the [H+] of body fluids in a range compatible with life.

10. Hydrogen Ion Regulation in Body Fluids
Acid-base balance is what keeps [H+] in normal range
For best results, keeps pH 7.35–7.45
Tissue metabolism produces massive amounts of CO2, which is hydrolyzed into volatile acid H2CO3
Reaction is catalyzed in RBCs by carbonic anhydrase
Aerobic Metabolism 
CO2 + H2O  H2CO3  H+ + HCO3–
(within RBC: H+ + Hb  HHb)
The hemoglobin in the erythrocyte (RBC) immediately buffers the H+, causing no change in the pH: Isohydric buffering

11. Hydrogen Ion Regulation in Body Fluids (cont.)
Lungs eliminate CO2; falling CO2 reverses Reaction:
Ventilation ↑
CO2 + H2O  H2CO3  H+ + HCO3–
HHb → H+ + HCO3–

12. Fig16.22 Tissue cell Tissue PCO2 = 40 mm Hg Cellular CO2 CO2 dissolved
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Tissue cell
Tissue
PCO2 = 40 mm Hg
Cellular CO2
CO2 dissolved
in plasma
CO2 + H2O
CO2 combined with
hemoglobin to form
carbaminohemoglobin
H2CO3
PCO2 = 40 mm Hg
PCO2 = 45 mm Hg
HCO3− + H+
Blood
flow from
systemic
arteriole
Blood
flow to
systemic
venule
H+ combines
with hemoglobin
HCO3−
Plasma
Red blood cell
Capillary wall

13. Hydrogen Ion Regulation in Body Fluids (cont.)
Buffer solution characteristics
A solution that resists changes in pH when an acid or a base is added
Composed of a weak acid and its conjugate base
(i.e., carbonic acid/bicarbonate: in blood exists in reversible combination as NaHCO3 and H2CO3
Add strong acid HCl + NaHCO3 → NaCl + H2CO3; buffered with only small acidic pH change
Add base NaOH + H2CO3 → NaHCO3 + H2O; buffered with only slight alkaline pH change

14. Hydrogen Ion Regulation in Body Fluids (cont.)
Bicarbonate & NonBicarbonate buffer systems
Bicarbonate: composed of HCO3– and H2CO3
Open system as H2CO3 is hydrolyzed to CO2
Ventilation continuously removes CO2 preventing equilibration, driving reaction to the right:
HCO3– + H+ → H2CO3 → H2O + CO2
Removes vast amounts of acid from body per day

15. Cells increase production of CO2
Fig18.07
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cells increase production of CO2
CO2 reacts with H2O to produce H2CO3
H2CO3 releases H+
Respiratory center is stimulated
Rate and depth of breathing increase
More CO2 is eliminated through lungs

16. Hydrogen Ion Regulation in Body Fluids (cont.)
Bicarbonate & Nonbicarbonate buffer systems (cont.)
NonBicarbonate: composed of phosphate & proteins
Closed system: All the components remain in the system; no gas to remove acid by ventilation
Hbuffer/buffer– represents acid & conjugate base
H+ + buffer– ↔ Hbuf reach equilibrium, buffering stops
Both systems are important to buffering fixed & volatile acids
(a volatile acid is one that is in equilibrium with a dissolved gas.)

17. Buffer Systems .
Fig 13-1

18. pH of Buffer System: Henderson-Hasselbalch Equation
Describes [H+] as ratio of [H2CO3]/ [HCO3–]
pH is logarithmic expression of [H+].
6.1 is the log of the H2CO3 equilibrium constant
(PaCO2 × 0.03) is in equilibrium with, & directly proportional to blood [H2CO3]
Blood gas analyzers measure pH & PaCO2; then use H-H equation to calculate HCO3–

19. pH of Buffer System: Henderson-Hasselbalch Equation
The ratio between the plasma [HCO3-] and dissolved CO2 determines the blood pH, according to the H-H equation.
A 20:1 [HCO3-]/dissolved CO2 ratio always yields a normal arterial pH of 7.40

20. What is the role of proteins in the acid-base regulation process?
produces fixed (nonvolatile) acids
produces volatile acids
isohydric buffering
produces carbonic acid
Answer: A

21. . .
Catabolism of proteins produces fixed (nonvolatile) acids

22. Hydrogen Ion Regulation in Body Fluids (cont.)
Bicarbonate buffer system
HCO3– can continue to buffer H+ as long as ventilation is adequate to exhale CO2:
Ventilation 
H+ + HCO3– → H2CO3 → H2O + CO2
In hypoventilation, H2CO3 accumulates; only the NonBicarbonate system can serve as buffer

23. Hydrogen Ion Regulation in Body Fluids (cont.)
NonBicarbonate buffer system:
Hemoglobin is the most important buffer in this system, because it’s the most abundant;
Can buffer any fixed or volatile acid;
As closed system, products of buffering accumulate & buffering may slow or or reach equilibrium:
(H+ + Buf- ↔ HBuf).
HCO3– and buf– exist in same blood system
Ventilation 
Open: H+ + HCO3– → H2CO3 → H2O + CO2
Closed: Fixed acid → H+ + Buf- ↔ HBuf

24. Classification of Whole Blood Buffers
Open System
Bicarbonate:
Plasma
Erythrocyte
Closed System
NonBicarbonate:
Hemoglobin
Organic Phosphates
Nonorganic Phosphates
Plasma Proteins .
Classification of Whole Blood Buffers

25. Which one of the following blood buffers systems is classified as a bicarbonate buffer (open buffer system)?
Hemoglobin
Erythrocyte (RBC)
Organic phosphates
Plasma proteins
Answer: B

26. .
b. Erythrocyte (RBC)

27. Hydrogen Ion Regulation in Body Fluids (cont.)
Definitions:
Excretion: Elimination of substances from the body;
Secretion: The process by which substances are actively transported;
Reabsorption: Active or passive transport of substances back into the circulation.

28. Acid Excretion Excrete CO2, which is in equilibrium with H2CO3
Buffers are temporary measure; if acids were not excreted, life-threatening acidosis would follow.
Lungs:
Excrete CO2, which is in equilibrium with H2CO3
Crucial: body produces huge amounts of CO2 during aerobic metabolism (CO2 + H2O → H2CO3)
In addition, through HCO3– , fixed acids are eliminated indirectly as byproducts CO2 & H2O
(Remove ~24,000 mmol/L CO2 removed daily)

29. Acid Excretion (cont.) Physically remove H+ from body
Kidneys
Physically remove H+ from body
Excrete <100 mEq fixed acid per day
Also control excretion or retention of HCO3–
If blood is acidic, then more H+ are excreted & all HCO3– is retained.
If blood is alkaline, then more HCO3– are excreted & all H+ is retained.
While lungs can alter [CO2] in seconds, kidneys require hours/days to change HCO3– & affect pH

30. Acid Excretion (cont.) Basic kidney function
Renal glomerulus filters the blood by passing water, electrolytes, and nonproteins through semipermeable membrane.
Filtrate is modified as it flows through renal tubules
HCO3– is filtered through membrane, while CO2 diffuses into tubule cell, where it’s hydrolyzed into H+, which is then secreted into renal tubule
H+ secretion increases in the face of acidosis
therefore, hypoventilation or Ketoacidosis increases secretion

31. Acid Excretion (cont.) Basic kidney function (cont.)
Reabsorption of HCO3–
For every H+ secreted, an HCO3– is reabsorbed
Reacts in filtrate, forming H2CO3 which dissociates into H2O & CO2
CO2 immediately diffuses into cell, is hydrolyzed, & H+ is secreted into filtrate, HCO3– diffuses into blood
Thus, HCO3– has effectively been moved from filtrate to blood in exchange for H+
If there is excess HCO3– that does not react with H+, it will be excreted in urine

32. Acid Excretion (cont.) Renal response to respiratory acidosis: Filtrate HCO3– is reabsorbed by first reacting with secreted H+
Fig 13-2

33. Acid Excretion (cont.) Renal response to respiratory alkalosis: Excess HCO3– is excreted in the urine with a positive ion.

34. Acid Excretion (cont.) Basic kidney function (cont.)
Role of urinary buffers in excretion of excess H+
Once H+ has reacted with all available HCO3–, excess reacts with phosphate & ammonia
If all urinary buffers are consumed, further H+ filtration ends when pH falls to 4.5
Activation of ammonia buffer system enhances Cl– loss & HCO3– gain

35. Acid Excretion cont.
The lungs regulate the volatile acid content (CO2) of the blood, while the kidneys regulate the fixed acid concentration of the blood
In the OPEN bicarbonate buffer system, H+ is buffered to form the volatile acid H2CO3, which is exhaled as CO2 into the atmosphere.
In the CLOSED nonbicarbonate buffer system, H+ is buffered to formed fixed acids which accumulate in the body.

36. Acid-Base Disturbances
Normal acid-base balance
Kidneys maintain HCO3– of mEq/L
Lungs maintain CO2 of mm Hg
These produce pH of (H-H equation)
pH = log (24/(40 × 0.03) → pH = 7.40
Note pH determined by ratio of HCO3– to dissolved CO2
Ratio of 20:1 will provide normal pH (7.40)
Increased ratio results in alkalemia
Decreased ratio results in acidemia

37. Acid-Base Disturbances (cont.)
Primary respiratory disturbances
PaCO2 is controlled by the lung, changes in pH caused by PaCO2 are considered respiratory disturbances
Hyperventilation lowers PaCO2, which raises pH; referred to as respiratory alkalosis
Hypoventilation (PaCO2) decreases the pH; called respiratory acidosis

38. Acid-Base Disturbances (cont
Acid-Base Disturbances (cont.) The Phosphate Buffer system: After bicarbonate buffers are exhausted, the remaining H+ reacts with urinary phosphate buffers.

39. Acid-Base Disturbances (cont
Acid-Base Disturbances (cont.) Tubule cells secrete ammonia in response to low-filtrate pH: NH3 molecules buffer H+, forming NH4+, which is secreted with Cl-

40. Acid-Base Disturbances (cont.)
Primary metabolic disturbances
Involve gain or loss of fixed acids or HCO3–
Both appear as changes in HCO3– as changes in fixed acids will alter amount of HCO3– used in buffering

41. Excessive production of acidic ketones as in diabetes mellitus
Fig18.12
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Kidney failure
to excrete acids
Excessive production of acidic
ketones as in diabetes mellitus
Accumulation of nonrespiratory acids
Metabolic acidosis
Excessive loss of bases
Prolonged diarrhea
with loss of alkaline
intestinal secretions
Prolonged vomiting
with loss of intestinal
secretions

42. Acid-Base Disturbances (cont.)
Primary metabolic disturbances (cont.)
Decrease in HCO3– results in metabolic acidosis
Increase in HCO3– results in metabolic alkalosis
Compensation: Restoring pH to normal
Any primary disturbance immediately triggers compensatory response
Any respiratory disorder will be compensated for by kidneys (process takes hours to days)
Any metabolic disorder will be compensated for by lungs (rapid process, occurs within minutes)

43. Acid-Base Disturbances (cont.)
Compensation: Restoring pH to normal (cont.)
Respiratory acidosis (hypoventilation)
Renal retention HCO3– raises pH toward normal
Respiratory alkalosis
Renal elimination HCO3– lowers pH toward normal
Metabolic acidosis
Hyperventilation ↓CO2, raising pH toward normal
Metabolic alkalosis
Hypoventilation ↑CO2, lowering pH toward normal

44. .

45. Acid-Base Disturbances (cont.)
The CO2 hydration reaction’s effect on [HCO3–]
Large portion of CO2 is transported as HCO3–
As CO2 increases, it also increases HCO3–
In general, effect is increase of ~1 mEq/L HCO3– for every 10 mm Hg increase in PaCO2
An increase in CO2 of 30 would increase HCO3– by ~3 mEq/L

46. To maintain a normal pH range of 7. 35–7
To maintain a normal pH range of 7.35–7.45, the ratio of HCO3– to dissolved CO2 should be:
10:1
15:1
20:1
30:1
Answer: D

47. .
c. 20:1

48. Acid-Base Disturbances (cont
Acid-Base Disturbances (cont.) The pH- PCO2 diagram: Because of the hydration reaction between CO2 and H2O, acute increases in PCO2 raise the plasma [HCO3– ] along line CADB. An acute rise in PCO2 from 40 to 80mm Hg(A-D) increases the [HCO3– ] from 24 to approx. 29 mEq/L.

49. Clinical Acid-Base States

50. Clinical Acid-Base States (cont.)
Respiratory acidosis (alveolar hypoventilation):
Any process that raises PaCO2 > 45 mm Hg & lowers pH below 7.35
Increased PaCO2 produces more carbonic acid
Causes:
Anything that results in VA that fails to eliminate CO2 equal to VCO2 . .
VCO2 – CO2 production in ml/min

51. Clinical Acid-Base States (cont.)

52. Clinical Acid-Base States (cont.)
Respiratory acidosis (cont.)
Compensation is by renal Reabsorption of HCO3–
Partial compensation: pH improved but not normal
Full compensation: pH restored to normal
Correction (goal is to improve VA)
May include:
Improved bronchial hygiene & lung expansion
Non-invasive positive pressure ventilation, endotracheal intubation & mechanical ventilation
If chronic condition with renal compensation, lowering PaCO2 may be detrimental for patient .
VCO2 – CO2 production in ml/min

53. Clinical Acid-Base States (cont.)
Respiratory alkalosis (alveolar hyperventilation):
Lowers arterial PaCO2 decreases carbonic acid, thus increasing pH
Causes (see Box 13-4 in Egan)
Any process that increases VA so that CO2 is eliminated at rate higher than VCO2.
Most common cause is hypoxemia
Anxiety, fever, pain
Clinical signs: early Paresthesia; if severe, may have hyperactive reflexes, tetanic convulsions, dizziness . .
VCO2 – CO2 production in ml/min

54. Decrease in concentration of H2CO3
Fig18.13
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• Anxiety
• Fever
• Poisoning
• High altitude
Hyperventilation
Excessive loss of CO2
Decrease in concentration of H2CO3
Decrease in concentration of H+
Respiratory alkalosis

55. Clinical Acid-Base States (cont.)
Respiratory alkalosis (cont.)
Compensation is by renal excretion of HCO3–
Partial compensation returns pH toward normal
Full compensation returns pH to high normal range
Correction
Involves removing stimulus for hyperventilation
i.e., hypoxemia: give oxygen therapy
VCO2 – CO2 production in ml/min

56. .

57. Clinical Acid-Base States (cont.)
Alveolar hyperventilation superimposed on compensated respiratory acidosis (chronic ventilatory failure):
Typical ABG for chronic ventilatory failure:
pH 7.38, PaCO2 58 mm Hg, HCO3– 33 mEq/L
Severe hypoxia stimulates increased VA, lowers PaCO2, potentially raising pH on alkalotic side
i.e. pH 7.44, PaCO2 50 mm Hg, HCO3– 33 mEq/L
Appears to be compensated metabolic acidosis
Only medical history & knowledge of situation allow correct interpretation of this ABG .
VCO2 – CO2 production in ml/min