1. Acid-Base

2. Definitions Acid: substance that can donate hydrogen ions
Base: substance that can accept hydrogen ions

3. Types of acids
Carbonic acid (volatile acid, carbon dioxide,~ mmol/d). Eliminated by the lungs
Non-carbonic acids (nonvolatile acids such as phosphoric and sulfuric acids, meq/d). Combine with buffers and subsequently excreted by the kidney

6. Clinical pH range
pH between 7.80 and 6.80 (H+concentrations between neq/l) are the extremes of pH compatible with life
Clinical laboratories measured pH, carbon dioxide, and oxygen in arterial samples
Bicarbonate concentration can be calculated from the Henderson equation
Laboratories measure total CO2 concentration (dissolved CO2 plus bicarbonate concentration, ~25-26 meq/l) in venous samples

7. Plasma bicarbonate concentration
Laboratories measure total CO2 concentration (dissolved carbon dioxide plus bicarbonate concentration, ~25-26 meq/l)
As a result, total CO2 concentration exceeds plasma bicarbonate concentration by 1.0 to 1.5 meq/l
Normal plasma bicarbonate concentration is approximately 24 mEq/l

8. Definitions
Reduced pH (elevated hydrogen ion concentration) equals acidemia
Increased pH (reduced hydrogen ion concentration equals alkalemia)
Process that lowers pH = acidosis
Process that increases pH = alkalosis

9. Bicarbonate buffer system
CO2 + H20  H2CO3  H+ + HCO3-
If a closed system, pKa = 6.1 (normal pH= 7.40)
We are an open system via the lungs excreting CO2 making this system a highly efficient buffer

11. Determinants of pH (pH) H+ = 24 ( CO2) (HCO3)
pH must be converted to H+ (nEq/L). pH = 7.40 = 40 nEq/L
7.40 = 40 = 24 (40/24)

12. pH vs. [H+]
[H+]
100 80 64 50 40 32 25 20 16 pH
7.0
7.1
7.2
7.3
7.4
7.5
7.6
7.7
7.8
[H+] = 80 – decimal digits of pH

13. Normals Normal pH Normal pCO2 Normal HCO3- 7.35-7.45 (7.40)
(7.40)
pH = -log[H+]
[H+] = 24 x pCO2/[HCO3-]
Normal pCO2
36-44 mm Hg (40 mmHg)
Normal HCO3-
22-26 meq/L (24 meq/l)

14. Metabolic Disorders
Processes that directly alter bicarbonate concentration
Metabolic acidosis: decreased bicarbonate
Metabolic alkalosis: increased bicarbonate

15. Respiratory Disorders
Processes that directly alter CO2
Respiratory acidosis: increased CO2
Respiratory alkalosis: decreased CO2
Buffer effect: slightly increased HCO3 with respiratory acidosis. Slightly decreased HCO3 with respiratory alkalosis.

16. Buffering
Prevent wide changes in pH in response to the addition of base or acid
Bicarbonate is the major extracellular buffer (can be easily measured)
There are also intracellular buffers

17. Effects of Buffers on pH
Bicarbonate is the major extracellular buffer. There are also intracellular buffers.
The presence of buffers attenuates changes in pH in response to acid-base disorders.
Immediate onset
Isohydric principle (all buffers change in the same direction)

18. Purpose of Acid-Base Balance
Maintain normal pH by buffer systems
Buffer Pair
H+ Acceptor
H+ Donor
Bicarbonate (ECFV)
HCO3-
H2CO3
Phosphate (urine)
H2PO42-
H2PO4
Ammonia (urine)
NH3
NH4+
Protein

19. Secondary(Compensatory) Mechanisms
In addition to buffering mechanisms, additional secondary (compensatory) physiologic responses occur in response to changes in pH.
Invariably present in simple acid-base disorders (if not present, it is a mixed disorder)

20. Compensatory mechanisms
The respiratory system compensates for metabolic disorders by altering CO2 (via the lungs, rapid onset, minutes)
Compensation for respiratory disorders occurs by alterations in bicarbonate concentration (via the kidney, slower onset 1-2 days)

21. Mechanisms that Buffer an Acid Load
Buffer systems
(primarily bicarbonate)
Extracellular fluid
Immediate
(HCO3- + H+ ↔ H2CO3 ↔ CO2 + H20)
Increased rate and depth of breathing to decrease CO2
Lungs
Minutes to hours
Buffer systems (phosphate, bicarbonate, protein)
Intracellular fluid
2-4 hours
Hydrogen ion excretion, bicarb reabsorption, & bicarb generation
Kidneys
Hours to days

22. Summary Disorder pH HCO3- pCO2 Comment Metabolic acidosis ↓
↓ (primary)
↓(compensatory)
All 3 markers go in same direction
Metabolic alkalosis 
 (primary)
 (compensatory)
Resp. acidosis
 (compensatory)
 (primary)
pH goes opp. other 2 markers
Resp. alkalosis
↓ (compensatory)

23. Golden rules: Simple acid-base disorders
1) PCO2 and HCO3 always change in the same direction.
2) The secondary physiologic compensatory mechanisms must be present.
3) The compensatory mechanisms never fully correct pH.

24. Metabolic acidosis
Process that reduces plasma bicarbonate concentration
Etiology:
Decreased renal acid excretion
Direct bicarbonate losses (GI tract or urine)
Increased acid generation (exogenous or endogenous)

25. Causes of metabolic acidosis
1) increased acid generation
Lactic acidosis, Ketoacidosis, ingestion of acids (aspirin, ethylene glycol, methanol), dietary protein intake (animal source)
2) loss of bicarbonate
Gastrointestinal (diarrhea, intestinal fistulas)
Renal: type 2 proximal renal tubular acidosis

26. Causes of metabolic acidosis
1) decreased acid excretion (impaired NH4+ excretion)
Renal failure (reduced GFR) decreased ammonium excretion
Type I (distal) renal tubular acidosis
Type 4 renal tubular acidosis (hypoaldosteronism)

27. Respiratory acidosis
Induced by hypercapnia (decreased alveolar ventilation)
Buffering mechanisms raise plasma bicarbonate concentration (rapid but limited response, ~1-2 meq/l)
Kidney minimizes the change in extracellular pH by increasing acid excretion (NH4+) generating new bicarbonate ions (delayed response, 2-3 days).

29. Respiratory alkalosis
Reduced carbon dioxide due to increased alveolar ventilation
Buffering processes lower plasma bicarbonate concentration (rapid but limited response, ~1-2 meq/l)
Kidney response is to reduce net acid excretion (eliminate bicarbonate into the urine or decrease ammonium excretion). Delayed response, 1-2 days)

31. Respiratory disorders
Acute respiratory acid base disorders always have a greater change in pH than chronic disorders
Plasma Cl changes equally and inversely with plasma HCO3.
Plasma anion gap does not change with respiratory disorders
Plasma sodium is not directly altered by acid base disorders

32. Metabolic alkalosis
Processes that raise plasma bicarbonate concentration
Etiology: Loss of hydrogen ion from the GI tract (vomiting) or into the urine (diuretic therapy)
Excessive urinary net acid excretion (primary hyperaldosteronism)

35. Metabolic alkalosis Urine chloride concentration:
Cl responsive: urine Cl <20 meq/l (usually <10 meq/l
Cl resistant: urine Cl > 20 meq/l (usuallly >50 meq/l)

36. Expected pH Changes for Respiratory Disorders
Acute Respiratory Acidosis:
HCO3- increases 1 mEq for each 10 mm increase in PCO2
Chronic Respiratory Acidosis:
HCO3- increases 4 mEq for each 10 mm increase in PCO2
Acute Respiratory Alkalosis:
HCO3- decreases 2 mEq for each 10 mm decrease in PCO2
Chronic Respiratory Alkalosis:
HCO3- decreases 5 mEq for each 10 mm decrease in PCO2

42. Plasma anion gap
Strong acids (HA) fully dissociate at physiologic pH (7.40) into H+ and A-
H+ is buffered by HC03-
A- is either excreted into the urine (normal plasma anion gap, increased plasma chloride concentration)
Or, A- is reabsorbed by the kidney and retained in plasma, as an unmeasured anion (increased plasma anion gap, minimal change in plasma chloride concentration)

47. Renal acid excretion
All of the filter of bicarbonate must be reabsorbed (primarily in the proximal tubule and loop of Henle)
Final excretion of the daily acid load occurs primarily in the collecting duct (approximately meq/d)

48. Titratable acidity
Phosphate homeostasis is maintained by urinary excretion of dietary phosphate
Monobasic phosphate is an effective urinary buffer, esp. at lower urinary pH
Accounts for excretion of 10 to 40 mEq of hydrogen ion daily
Cannot be increased beyond this due to the fixed amount of phosphate in urine

49. Ammonium excretion
Contributes the major adaptive response to an acid load
Can be increased in response to physiologic needs
Normally mEq/d and maximal excretion is approximately 300 mEq/d
NH4+ is lipid soluble and therefore trapped in the urinary lumen

50. Urine anion gap An indirect estimate of urinary NH4+ excretion
Urine Na + K minus urine Cl
Normally, ~ 10 meq/l
Becomes less positive and may even become neg with incr urinary NH4 excretion (Cl- must accomany NH4+)

53. Sodium and Chloride relationship
Law of electroneutrality:
Sodium concentration is not directly altered by acid base disorders
Plasma Cl is altered in all acid base disorders (except increased plasma anion gap metaboic acidosis)
Conclusion: If sodium concetration stays constant but chloride conc changes, an acid base disorder is present

54. Mixed Acid-base disorders
The presence of more than one simple acid-base disorder simultaneously:
Respiratory acidosis and metabolic acidosis (profound acidemia)
Respiratory alkalosis and metabolic alkalosis (profound alkalemia)
Metabolic alkalosis and respiratory acidosis
Metabolic acidosis and respiratory alkalosis

55. Examination/quiz
For this course, only simple acid-base disorders will be included in quizzes and examinations.
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