Renal Control of Acid-Base Balance
• The kidneys control acid-base balance by
excreting either acidic or basic urine
• Excreting acidic urine reduces the amount of
acid in extracellular fluid
• Excreting basic urine removes base from the
extracellular fluid
• The kidneys regulate extracellular fluid H+
concentration through three fundamental
mechanisms:
(1) secretion of H+
(2) reabsorption of filtered HCO3
(3) production of new HCO3
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pH Review
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pH = - log [H+]
H+ is really a proton
Range is from 0 - 14
If [H+] is high, the solution is acidic; pH < 7
If [H+] is low, the solution is basic or alkaline
; pH > 7
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• Acids are H+ donors.
• Bases are H+ acceptors, or give up OH- in
solution.
• Acids and bases can be:
– Strong – dissociate completely in solution
• HCl, NaOH
– Weak – dissociate only partially in
solution
• Lactic acid, carbonic acid
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Small changes in pH can produce
major disturbances
• Most enzymes function only with narrow pH
ranges
• Acid-base balance can also affect
electrolytes (Na+, K+, Cl-)
• Can also affect hormones
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Titration curve for the bicarbonate buffer system
The Body and pH
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Homeostasis of pH is tightly controlled
Extracellular fluid = 7.4
Blood = 7.35 – 7.45
< 6.8 or > 8.0 death occurs
Acidosis (acidemia) below 7.35
Alkalosis (alkalemia) above 7.45
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Law of Mass Action
CO2 + H2O
CA
H2CO3
AT EQUILIBRIUM,
K
=
=
+
H + HCO3
+
[H ] x [HCO3 ]
[H2CO3]
+
[H ] x [HCO3 ]
SOLUBILITY x PCO2
K
=
[H+] x [HCO3-]
0.03 x PCO2
WHICH, AFTER TAKING LOGS, BECOMES:
[HCO3 ]
pH = pK + Log(
0.03 x PCO2
)
- THE HENDERSON - HASSELBALCH EQUATION
Derivation of normal pH
The body produces more acids than
bases
• Acids take in with foods
• Acids produced by metabolism of lipids and
proteins
• Cellular metabolism produces CO2.
• CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3-
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Control of Acids
1. Buffer systems
Take up H+ or release H+ as conditions
change
Buffer pairs – weak acid and a base
Exchange a strong acid or base for a weak
one
Results in a much smaller pH change
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Bicarbonate buffer
• Sodium Bicarbonate (NaHCO3) and
carbonic acid (H2CO3)
• Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
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Phosphate buffer
• Major intracellular buffer
• H+ + HPO42- ↔ H2PO4• OH- + H2PO4- ↔ H2O + H2PO42-
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Protein Buffers
Includes hemoglobin, work in blood and ISF
Carboxyl group gives up H+
Amino Group accepts H+
Side chains that can buffer H+ are present on 27
amino acids.
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2. Respiratory mechanisms
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Exhalation of carbon dioxide
Powerful, but only works with volatile acids
Doesn’t affect fixed acids like lactic acid
CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3Body pH can be adjusted by changing rate
and depth of breathing
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3. Kidney excretion
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Can eliminate large amounts of acid
Can also excrete base
Can conserve and produce bicarb ions
Most effective regulator of pH
If kidneys fail, pH balance fails
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Rates of correction
• Buffers function almost instantaneously
• Respiratory mechanisms take several
minutes to hours
• Renal mechanisms may take several hours
to days
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Acid-Base Imbalances
• pH< 7.35 acidosis
• pH > 7.45 alkalosis
• The body response to acid-base imbalance
is called compensation
• May be complete if brought back within
normal limits
• Partial compensation if range is still outside
norms.
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Compensation
• If underlying problem is metabolic,
hyperventilation or hypoventilation can help
: respiratory compensation.
• If problem is respiratory, renal mechanisms
can bring about metabolic compensation.
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Acidosis
• Principal effect of acidosis is depression of the
CNS through ↓ in synaptic transmission.
• Generalized weakness
• Deranged CNS function the greatest threat
• Severe acidosis causes
– Disorientation
– coma
– death
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Alkalosis
• Alkalosis causes over excitability of the central
and peripheral nervous systems.
• Numbness
• Lightheadedness
• It can cause :
– Nervousness
– muscle spasms or tetany
– Convulsions
– Loss of consciousness
– Death
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• In acidosis, the kidneys do not excrete HCO3
into the urine but reabsorb all the filtered
HCO3 and produce new HCO3 which is added
back to the extracellular fluid
• This reduces the extracellular fluid H+
concentration back toward normal
• In alkalosis the kidneys fail to reabsorb all the
filtered HCO3 thus increasing the excretion of
HCO3
• Because HCO3 normally buffers H+ in the
extracellular fluid, this loss of HCO3 is the
same as adding H+ to the extracellular fluid.
• In alkalosis the removal of HCO3 raises the
extracellular fluid H+ concentration back
towards normal
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Secretion of H+ and Reabsorption of
Bicarbonate by the Renal Tubules
• About 80 to 90 percent of the bicarbonate
reabsorption and H+ secretion occurs in the
proximal tubule
Mechanism of Hydrogen ion secretion and
Bicarbonate Reabsorption
Primary Active Secretion of H+ in the Intercalated
Cells of Late Distal and Collecting Tubules
Buffering of Secreted Hydrogen Ions by
Filtered Phosphate
Excretion of Excess H+ and Generation of New
Bicarbonate by the Ammonia Buffer System
Buffering of hydrogen ion secretion by ammonia (NH3) in
the collecting tubules
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Renal Correction of Acidosis-Increased Excretion
of H+ and Addition of Bicarbonate to the ECF
• Acidosis decreases the ratio of Bicarbonate/Hydrogen
ion in Renal Tubular Fluid
• As a result, there is excess H+ in the renal tubules,
causing complete reabsorption of bicarbonate
and still leaving additional H+ available to combine
with the urinary buffers (phosphate and ammonia)
• Thus, in acidosis, the kidneys reabsorb all the filtered
bicarbonate and contribute new bicarbonte
through the formation of ammonium ions and
titratable acid
Renal Correction of Alkalosis-Decreased Tubular Secretion of H+
and Increased Excretion of Bicarbonate
• Alkalosis increases the ratio of
bicarbonate/hydrogen ion in renal tubular fluid
• The compensatory response to a primary
reduction in PCO2 in respiratory alkalosis is a
reduction in plasma concentration, caused by
increased renal excretion of bicarbonate
.
• In metabolic alkalosis, there is also an increase in plasma pH and decrease
in H+ concentration
• The cause of metabolic alkalosis is a rise in the extracellular fluid
bicarbonate concentration
• This is partly compensated for by a reduction in the respiration rate, which
increases PCO2 and helps return the extracellular fluid pH toward normal
• In addition, the increase in bicarbonate concentration in the extracellular
fluid leads to an increase in the filtered load of bicarbonate which in turn
causes an excess of bicarbonate over H+ secreted in the renal tubular fluid
• The excess bicarbonate in the tubular fluid fails to be reabsorbed because
there is no H+ to react with, and it is excreted in the urine
• In metabolic alkalosis, the primary compensations are decreased
ventilation, which raises PCO2, and increased renal excretion of bicarbonate
which helps to compensate for the initial rise in extracellular fluid
bicarbonate concentration
H+
pH
PCO2
Bicarbonate
Normal
7.4
40 mEq/L
40 mm Hg
24 mEq/L
Respiratory acidosis
↓
↑
↑↑
↑
Respiratory alkalosis
↑
↓
↓↓
↓
Metabolic acidosis
↓
↑
↓
↓↓
Metabolic alkalosis
↑
↓
↑
↑↑
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