Respiratory regulation of Acid-Base
Balance
DR. SUMREENA MANSOOR
ASSISTANT PROF OF BIOCHEMISTRY
DEPT OF BIOCHEMISTRY & MOLECULAR BIOLOGY
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pH Review
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The Body and pH
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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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Types of Acids in the Body
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Volatile acids:
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Can leave solution and enter the
atmosphere.
H2C03 (carbonic acid).
Pco2 is most important factor in pH of body
tissues.
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Types of Acids in the Body
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Fixed Acids:
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Acids that do not leave solution.
Sulfuric and phosphoric acid.
Catabolism of amino acids, nucleic acids,
and phospholipids.
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Types of Acids in the Body
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Organic Acids:
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Byproducts of aerobic metabolism, during
anaerobic metabolism and during
starvation, diabetes.
Lactic acid, ketones.
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Small changes in pH can
produce major disturbances
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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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The body produces more acids
than bases
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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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Henderson-Hasselbalch
Equation
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APPLICATIONS OF HH EQUATION
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Analysis of dissociation of the alanine in
the same way as described for acetic
acid
Use to calculate how pH of a
physiologic solution responds to
changes in the concentration of a week
acid and/or it’s corresponding salt form.
Example Bicarbonate buffer system
(How HCO3 and CO2 Influence pH)
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APPLICATIONS OF HH EQUATION
 Useful for calculating ionic forms of
acidic and basic drugs.
 Acidic drug
HA
H++AExample: Aspirin
 Basic drug
BH+
B+H+
Example: Morphine

Drug can readily pass through the membrane
if it is uncharged
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APPLICATIONS OF HH EQUATION

How much drug is found on either side
of a membrane that separates two
compartments that differ in pH, for
example, the stomach (pH 1.0-1.5) and
blood plasma (pH 7.4)
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Buffer Systems
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Provide or remove H+ and stabilize the
pH.
Include weak acids that can donate H+
and weak bases that can absorb H+.
Change in pH, after addition of acid, is
less than it would be in the absence of
buffer.
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Chemical Buffers
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Act within fraction of a second.
Protein.
HCO3-.
Phosphate.
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Proteins
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COOH or NH2.
Largest pool of buffers in the body.
pKa close to plasma.
Albumin, globulins such as Hb.
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Protein Buffers
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Includes hemoglobin, work in blood
Carboxyl group gives up H+
Amino Group accepts H+
Glutamate, aspartate, histidine, arginine, lysine
Additional potentially charged groups in side chain
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Bicarbonate buffer
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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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HCO3
pk= 6.1
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Most important ECF buffer.
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Present in large quantities.
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Respiratory and renal systems act on
this buffer system.
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Phosphate buffer
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Major intracellular buffer
H+ + HPO42- ↔ H2PO4-
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OH- + H2PO4- ↔ H2O + HPO42-
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pk = 6.8
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Better buffer in ICF (kidneys and bone)
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Rates of correction
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Buffers function almost instantaneously

Respiratory mechanisms take several
minutes to hours

Renal mechanisms may take several
hours to days
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Respiratory System
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2nd line of defense.
Acts within min. maximal in 12-24 hrs.
H2CO3 produced converted to CO2, and
excreted by the lungs.
Powerful, but works with volatile acids
Exhalation of carbon dioxide.
CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3Body pH can be adjusted by changing rate
and depth of breathing
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Renal system
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Can eliminate large amounts of acid
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Can conserve and produce bicarbonate
ions
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Most effective regulator of pH

If kidneys fail pH balance fails
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Urinary Buffers
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Urine pH = 4.5
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H+ secreted into the urine tubule and
combines with HPO4-2 or NH3.

HPO4-2 + H+

NH3 + H+
H2PO4-2
NH4+
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Acid-Base Imbalances

pH< 7.35 acidosis
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pH > 7.45 alkalosis
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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
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If underlying problem is metabolic,
hyperventilation or hypoventilation can
help : respiratory compensation
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If
problem
mechanisms
is
can
respiratory,
bring
metabolic compensation
renal
about
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Acidosis
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Principal effect of acidosis is depression of the
CNS through ↓ in synaptic transmission
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Generalized weakness
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Deranged CNS function the greatest threat
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Severe acidosis causes
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Disorientation
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Coma
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Death
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Alkalosis
Alkalosis can cause
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It can cause :
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Nervousness
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Muscle spasms or tetany
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Convulsions
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Loss of consciousness
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Death
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Respiratory Acidosis
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Carbonic acid excess caused by
blood levels of CO2 above 45 mm Hg
Hypercapnia – High levels of CO2 in
blood
Chronic conditions:
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Depression of respiratory center in brain
that controls breathing rate – drugs or
head trauma
Paralysis of respiratory or chest muscles
Emphysema
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Respiratory Acidosis
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Acute conditions:
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Adult Respiratory Distress Syndrome
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Pulmonary edema
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Pneumothorax
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Compensation for Respiratory
Acidosis
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Kidneys eliminate hydrogen ion and retain
bicarbonate ion
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Acute respiratory failure:
pH low,[HCO-3] high normal, or slightly raised
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Chronic respiratory failure:
pH
normal
or
low
chronicity,[HCO-3] raised
depending
upon
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Signs and Symptoms of
Respiratory Acidosis
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Breathlessness
Restlessness
Lethargy and disorientation
Tremors, convulsions, coma
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Respiratory rate rapid then gradually
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depressed
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Skin
warm
and
flushed
due
vasodilatation caused by excess CO2
to
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Treatment of Respiratory Acidosis
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Restore ventilation
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Treat underlying dysfunction or disease
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Respiratory Alkalosis
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Carbonic acid deficit
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pCO2 less than 35 mm Hg (hypocapnea)
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Primary cause is hyperventilation
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Respiratory Alkalosis
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Conditions that stimulate respiratory center:
Hysterical over breathing (overrides normal
respiratory control)
Raised ICP (Which stimulate respiratory centre)
Hypoxia
Pulmonary edema
Lobar pneumonia
Pulmonary collapse or fibrosis
Excessive artificial ventilation
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Compensation of Respiratory
Alkalosis
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Compensatory fall in plasma [HCO-3] tends to
correct the pH
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Pco2 always reduced
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[HCO-3] low normal or low

pH
raised
(uncompensated
or
partly
compensated) or normal (fully compensated)
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Treatment of Respiratory Alkalosis

Treat underlying cause
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IV Chloride containing solution – Cl- ions
replace lost bicarbonate ions
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