Download Egan Ch 13.1 Acid-Base Balance

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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 HendersonHasselbalch equation in hypothetical clinical
situations.
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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.
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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.
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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.
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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.
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C. Sources of Hydrogen Ions
1.Most hydrogen ions originate as byproducts of metabolic processes,
including the:
a. aerobic and anaerobic respiration of
glucose,
b. incomplete oxidation of fatty acids,
c. oxidation of amino acids containing
sulfur, and the
d. breakdown of phosphoproteins and
nucleic acids.
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Fig18.06
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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
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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.
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Acid-base balance is what keeps [H+] in normal range
◦ For best results, keeps pH 7.35–7.45
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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)
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The hemoglobin in the erythrocyte (RBC) immediately buffers the
H+, causing no change in the pH: Isohydric buffering
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◦ Lungs eliminate CO2; falling CO2 reverses
Reaction:
Ventilation
↑
CO2 + H2O  H2CO3  H+ + HCO3–
↑
HHb → H+ + HCO3–
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Fig16.22
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
PCO2 = 40 mm Hg
Blood
flow from
systemic
arteriole
CO2 + H2O
CO2 combined with
hemoglobin to form
carbaminohemoglobin
HCO3−
+
H2CO3
H+
H+ combines
with hemoglobin
HCO3−
Plasma
Red blood cell
PCO2 = 45 mm Hg
Blood
flow to
systemic
venule
Capillary wall
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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
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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
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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
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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.)
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.
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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]
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Blood gas analyzers
measure pH & PaCO2;
then use H-H equation to
calculate HCO3–
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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
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What is the role of proteins in the acid-base
regulation process?
a.
b.
c.
d.
produces fixed (nonvolatile) acids
produces volatile acids
isohydric buffering
produces carbonic acid
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.
a. Catabolism of proteins produces
fixed (nonvolatile) acids
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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
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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
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Open System
 Bicarbonate:
oPlasma
oErythrocyte
Closed System
 NonBicarbonate:
o Hemoglobin
o Organic Phosphates
o Nonorganic Phosphates
o Plasma Proteins
.
Classification of Whole Blood Buffers
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Which one of the following blood buffers systems
is classified as a bicarbonate buffer (open buffer
system)?
a.
b.
c.
d.
Hemoglobin
Erythrocyte (RBC)
Organic phosphates
Plasma proteins
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b. Erythrocyte (RBC)
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Definitions:
1.
2.
3.
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.
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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)
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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
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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
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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
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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
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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.
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Normal acid-base balance
◦ Kidneys maintain HCO3– of 22-26 mEq/L
◦ Lungs maintain CO2 of 35-45 mm Hg
◦ These produce pH of 35-45 (H-H equation)
pH = 6.1 + 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
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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
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 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
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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
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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)
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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
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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
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To maintain a normal pH range of 7.35–7.45, the
ratio of HCO3– to dissolved CO2 should be:
a.
b.
c.
d.
10:1
15:1
20:1
30:1
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c. 20:1
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48
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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
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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
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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
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Fig18.13
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• Anxiety
• Fever
• Poisoning
• High altitude
Hyperventilation
Excessive loss of CO2
Decrease in concentration of H2CO3
Decrease in concentration of H+
Respiratory alkalosis
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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
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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
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