Acid-Base

Definitions
• Acid: substance that can donate hydrogen
ions
• Base: substance that can accept hydrogen
ions
 Types of acids
• Carbonic acid (volatile acid, carbon
dioxide,~ 15000 mmol/d). Eliminated by
the lungs
• Non-carbonic acids (nonvolatile acids such
as phosphoric and sulfuric acids, 50 -100
meq/d). Combine with buffers and
subsequently excreted by the kidney
 Clinical pH range
• pH between 7.80 and 6.80
(H+concentrations between 16 -160 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
 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
 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
 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
 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)
 pH vs. [H+]
• pH • [H+]
7.0 100
7.1 80
7.2 64
7.3 50
7.4 40
7.5 32
7.6
25
7.7
20
7.8
16

[H+] = 80 – decimal digits of pH

 Normals
• Normal pH
– 7.35-7.45 (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)
 Metabolic Disorders

• Processes that directly alter

bicarbonate concentration
Metabolic acidosis: decreased
bicarbonate
• Metabolic alkalosis: increased
bicarbonate
 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.
alkalosis
 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
 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)
Purpose of Acid-Base Balance
•Maintain normal pH by buffer
systems
Buffer Pair H+ Acceptor H+ Donor

Bicarbonate HCO3- H2CO3

(ECFV)
Phosphate H2PO42- H2PO4
(urine)
Ammonia NH3 NH4+
(urine)
Protein Protein Protein
 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)
 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)
Mechanisms that Buffer an Acid
Load
Buffer systems Extracellula Immediate
(primarily r fluid (HCO3- + H+ ↔ H2CO3 ↔ CO2
bicarbonate) + H20)

Increased rate and Lungs Minutes to hours

depth of breathing
to decrease CO2
Buffer systems Intracellular 2-4 hours
(phosphate, fluid
bicarbonate,
protein)
Hydrogen ion Kidneys Hours to days
excretion, bicarb
reabsorption, &
 Summary
Disorder p HCO3- pCO2 Comme
H nt
Metabolic ↓ ↓ (primary) ↓(compensatory) All 3
acidosis markers
go in same
direction

Metabolic (primary) (compensatory) All 3

alkalosis markers
go in same
direction

Resp. ↓ (primary) pH goes

acidosis (compensatory) opp. other
2 markers

Resp. ↓ ↓ (primary) pH goes

 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.
 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)
 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
 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)
 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).
 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)
 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
 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)
 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)
 Expected pH Changes for
Respiratory Disorders
• Acute Respiratory Acidosis:
HCO3- increases 1 mEq for each 10 mm increase in PCO 2

• Chronic Respiratory Acidosis:

HCO3- increases 4 mEq for each 10 mm increase in PCO 2

• Acute Respiratory Alkalosis:

HCO3- decreases 2 mEq for each 10 mm decrease in PCO 2

• Chronic Respiratory Alkalosis:

HCO3- decreases 5 mEq for each 10 mm decrease in PCO 2
 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)
 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 50-100 meq/d)
 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
 Ammonium excretion
• Contributes the major adaptive response
to an acid load
• Can be increased in response to
physiologic needs
• Normally 30-40 mEq/d and maximal
excretion is approximately 300 mEq/d
• NH4+ is lipid soluble and therefore trapped
in the urinary lumen
 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+)
 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
 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
 Examination/quiz
• For this course, only simple acid-base
disorders will be included in quizzes and
examinations.
• You have got to crawl before you walk!