Acid–base homeostasis

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Acids and bases

 Acid
 Acid–base reaction
 Acid–base homeostasis
 Acid strength
 Acidity function
 Amphoterism
 Base
 Buffer solutions
 Dissociation constant
 Equilibrium chemistry
 Extraction
 Hammett acidity function
 pH
 Proton affinity
 Self-ionization of water
 Titration
 Lewis acid catalysis
 Frustrated Lewis pair
 Chiral Lewis acid

Acid types

 Brønsted–Lowry
 Lewis
 Acceptor
 Mineral
 Organic
 Oxide
  Strong
 Superacids
 Weak
 Solid

Base types

 Brønsted–Lowry
 Lewis
 Donor
 Organic
 Oxide
 Strong
 Superbases
 Non-nucleophilic
 Weak

 v
 t
 e

Acid–base homeostasis is the homeostatic regulation of the pH of

the body's extracellular fluid (ECF).[1] The proper balance between
the acids and bases (i.e. the pH) in the ECF is crucial for the
normal physiology of the body, and cellular metabolism.[1] The pH of
the intracellular fluid and the extracellular fluid need to be maintained at a
constant level.[2]
Many extracellular proteins such as the plasma proteins and membrane
proteins of the body's cells are very sensitive for their three dimensional
structures to the extracellular pH.[3][4] Stringent mechanisms therefore exist to
maintain the pH within very narrow limits. Outside the acceptable range of
pH, proteins are denatured (i.e. their 3-D structure is disrupted),
causing enzymes and ion channels (among others) to malfunction.
In humans and many other animals, acid–base homeostasis is maintained by
multiple mechanisms involved in three lines of defense: [5][6]
1. Chemical: The first lines of defense are immediate – the various
chemical buffers which minimize pH changes that would otherwise occur
in their absence. These buffers include the bicarbonate buffer system, the
phosphate buffer system, and the protein buffer system.[7]
2. Respiratory Component: The second line of defense of the
extracellular fluid pH is rapid, measured by PCO 2, and consists of
controlling the carbonic acid concentration in the ECF by changing the
rate and depth of breathing (i.e. by hyperventilation or hypoventilation).
This blows off or retains carbon dioxide (and thus carbonic acid) in the
blood plasma as required.[5][8].
3. Metabolic Component: The third line of defense is slow, best
measured by the Base Excess, and mostly depends on the renal
system which can add or remove bicarbonate ions to or from the ECF.
[5]
 The bicarbonate is derived from metabolic carbon dioxide which is
enzymatically converted to carbonic acid in the renal tubular cells.[5][9][10] The
carbonic acid spontaneously dissociates into hydrogen ions and
bicarbonate ions.[5] When the pH in the ECF tends to fall (i.e. become more
acidic) the hydrogen ions are excreted into the urine, while the
bicarbonate ions are secreted into the blood plasma, causing the plasma
pH to rise (correcting the initial fall).[11] The converse happens if the pH in
the ECF tends to rise: the bicarbonate ions are then excreted into the
urine and the hydrogen ions into the blood plasma.
The second and third lines of defense operate by making changes to
the buffers, each of which consists of two components: a weak acid
and its conjugate base.[5][12] It is the ratio concentration of the weak acid
to its conjugate base that determines the pH of the solution. [13] Thus, by
manipulating firstly the concentration of the weak acid, and secondly
that of its conjugate base, the pH of the extracellular fluid (ECF) can
be adjusted very accurately to the correct value. The bicarbonate
buffer, consisting of a mixture of carbonic acid (H2CO3) and
a bicarbonate (HCO−
3) salt in solution, is the most abundant buffer in the extracellular fluid,

and it is also the buffer whose acid to base ratio can be changed very
easily and rapidly.[14]
An acid–base imbalance is known as Acidemia when the pH is Acid,
or Alkalemia when the pH is Alkaline.

Contents

 1Acid–base balance
o 1.1Unfortunately, Hasselbalch entered:
o 1.2Compensation:
o 1.3Homeostatic Mechanisms:
 2Imbalance
 3References
 4External links

Acid–base balance[edit]
The pH of the extracellular fluid, including the blood plasma, is
normally tightly regulated between 7.32 and 7.42, [15] by the chemical
buffers, the respiratory system, and the renal system.[12][16][17][18]
 Aqueous buffer solutions will react with strong acids or strong
bases by absorbing excess hydrogen H+
 ions, or hydroxide OH−
 ions, replacing the strong acids and bases with weak acids and weak
bases.[12] This has the effect of damping the effect of pH changes, or
reducing the pH change that would otherwise have occurred. But
buffers cannot correct abnormal pH levels in a solution, be that
solution in a test tube or in the extracellular fluid. Buffers typically
consist of a pair of compounds in solution, one of which is a weak acid
and the other a weak base.[12] The most abundant buffer in the ECF
consists of a solution of carbonic acid (H2CO3), and the bicarbonate
(HCO−
3) salt of, usually, sodium (Na ).  Thus, when there is an excess of OH
+ [5] −

 ions in the solution carbonic acid partially neutralizes them by forming

H2O and bicarbonate (HCO−
3) ions.  Similarly an excess of H+ ions is partially neutralized by the
[5][14]

bicarbonate component of the buffer solution to form carbonic acid

(H2CO3), which, because it is a weak acid, remains largely in the
undissociated form, releasing far fewer H+ ions into the solution than
the original strong acid would have done.[5]
The pH of a buffer solution depends solely on the ratio of
the molar concentrations of the weak acid to the weak base. The
higher the concentration of the weak acid in the solution (compared to
the weak base) the lower the resulting pH of the solution. Similarly, if
the weak base predominates the higher the resulting pH.
This principle is exploited to regulate the pH of the extracellular fluids
(rather than just buffering the pH). For the carbonic acid-bicarbonate
buffer, a molar ratio of weak acid to weak base of 1:20 produces a pH
of 7.4; and vice versa - when the pH of the extracellular fluids is 7.4
then the ratio of carbonic acid to bicarbonate ions in that fluid is 1:20. [13]
This relationship is accurately defined by the simple Henderson
Equation [19]:
[H+] x [HCO3-] = K x [CO2] x [H2O]
which relates the concentrations of the four variables with K being the
dissociation constant of carbonic acid
However this can be further simplified because:
[H2O] is constant and the partial pressure of CO2 is more familiar which
leaves us:
[H+] x [HCO3-] = K x PCO2
Recognition of an acute change now becomes simple:
With a constant PCO2, an increase in [H+] must lower the [HCO3-]
And an increase in the PCO2 initially at least increases both [H+] and
[HCO3-]
For more chronic changes there is time for compensation – see below.
 Unfortunately, Hasselbalch entered:[edit]
This is not the equation most commonly taught.
With no benefit and a huge penalty in complexity the Henderson–
Hasselbalch is used.
The Logarithmic notation makes recognition much harder.
It is described here because it is customary, not because it is useful.
The Henderson–Hasselbalch equation when
applied to the carbonic acid-bicarbonate
buffer system in the extracellular fluids,
states that:[13]

where:

 pH is the negative logarithm (or cologarithm) of molar concentration of

hydrogen ions in the ECF. It indicates the acidity in the ECF in an
inverse manner: the lower the pH the greater the acidity of the
solution.
 pKa H CO  is the cologarithm of the acid dissociation constant of carbonic
2 3

acid. It is equal to 6.1.

 [HCO−
3] is the molar concentration of bicarbonate in the blood plasma

 [H2CO3] is the molar concentration of carbonic acid in the ECF.

However, since the carbonic acid concentration is directly proportional to

the partial pressure of carbon dioxide ( ) in the extracellular fluid, the

equation can be rewritten as follows:[5][13]

where:

 pH is the negative logarithm of molar concentration of hydrogen ions in

the ECF, as before.
 [HCO−
3] is the molar concentration of bicarbonate in the plasma

 PCO  is the partial pressure of carbon dioxide in the blood plasma.

2

The pH of the extracellular

fluids can thus be controlled
by the regulation of the
Respiratory Acid (PCO2), and
the Metabolic Acids (Every
other acid).
Compensation:[edit]
In general, metabolism
produces more waste acids
than bases.[5]. Respiratory
Acidosis tends to cause an
acid pH. When Acute, e.g.,
from poisoning or trauma,
there is no time for
compensation. There is
a Pure Respiratory
Acidosis and the change in
pH is Typical. However, lung
disease usually
causes Chronic Respiratory
Acidosis and Metabolic
Compensation returns the pH
roughly Half Way Back to
Normal. Metabolic
Acidosis also tends to cause
an acid pH but normal lungs
usually compensate promptly
to maintain the pH
roughly Half Way Back to
Normal.
Homeostatic
Mechanisms:[edit]
The homeostatic control can
change the PCO2 and hence
the pH of the arterial plasma
within a few seconds.
[5]
 The partial pressure of
carbon dioxide in the arterial
blood is monitored by
the central chemoreceptors of
the medulla oblongata, and so
are part of the central nervous
system.[5][20] These
chemoreceptors are sensitive
to the pH and levels of carbon
dioxide in the cerebrospinal
fluid.[13][11][20].
The central chemoreceptors
send their information to
the respiratory centres in the
medulla oblongata
and pons of the brainstem.
[11]
 The respiratory centres then
determine the average rate of
ventilation of the alveoli of
the lungs, to keep the partial
pressure carbon dioxide in the
arterial blood constant. The
respiratory center does so
via motor neurons which
activate the muscles of
respiration (in particular
the diaphragm).[5][21] A rise in
the partial pressure of carbon
dioxide in the arterial blood
plasma above 5.3 kPa
(40 mmHg) reflexly causes an
increase in the rate and depth
of breathing. Normal breathing
is resumed when the partial
pressure of carbon dioxide
has returned to 5.3 kPa.[8] The
converse happens if the
partial pressure of carbon
dioxide falls below the normal
range. Breathing may be
temporally halted, or slowed
down to allow carbon dioxide
to accumulate once more in
the lungs and arterial blood.
The sensor for the plasma
HCO−
3 concentration is not known

for certain. It is very probable

that the renal tubular cells of
the distal convoluted
tubules are themselves
sensitive to the pH of the
plasma. The metabolism of
these cells produces CO2,
which is rapidly converted to
H+ and HCO−
3 through the action

of carbonic anhydrase.[5][9]
[10]
 When the extracellular fluids
tend towards acidity, the renal
tubular cells secrete the
H+ ions into the tubular fluid
from where they exit the body
via the urine. The HCO−
3 ions are simultaneously

secreted into the blood

plasma, thus raising the
bicarbonate ion concentration
in the plasma, lowering the
carbonic acid/bicarbonate ion
ratio, and consequently raising
the pH of the plasma.[5][11] The
converse happens when the
plasma pH rises above
normal: bicarbonate ions are
excreted into the urine, and
hydrogen ions into the
plasma. These combine with
the bicarbonate ions in the
plasma to form carbonic acid
(H+ + HCO−
3 = H2CO3), thus raising the

carbonic acid:bicarbonate
ratio in the extracellular fluids,
and returning its pH to normal.
[5]

Urine is generally acid which,

to a certain extent, is usually
neutralized by the ammonia
(NH3) which is excreted into
the urine
when glutamate and glutamin
e (carriers of excess, no
longer needed, amino groups)
are deaminated by the distal
renal tubular epithelial cells.[5]
[10]
 Thus some of the "acid
content" of the urine resides in
the resulting ammonium ion
(NH4+) content of the urine,
though this has no effect on
pH homeostasis of the
extracellular fluids.[5][22]

Imbalance[edit]
An Acid Base Diagram for human
plasma, showing the effects on the
plasma pH when PCO2 in mmHg or
Standard Base Excess (SBE) occur in
excess or are deficient in the plasma[23]

Acid–base imbalance occurs
when a significant insult
causes the blood pH to shift
out of the normal range (7.32
to 7.42[15]). An abnormally low
pH in the ECF is called
an acidemia and an
abnormally high pH is called
an Alkalemia.
"Acidemia" and "alkalemia",
[24]
 refer unambiguously to the
actual change in the pH of the
ECF. Two other similar
sounding terms are used in
acid-base pathophysiology:
"acidosis" and "alkalosis".
They are useful and refer to
the customary effect of a
component, respiratory or
metabolic. Thus a respiratory
acidosis (high PCO2) causes
an acid pH (acidemia) unless
there is a stronger metabolic
alkalosis. Acidosis would on
its own (i.e. if left
"uncompensated" by an
alkalosis) cause an acidemia.
[24]
 Similarly an alkalosis
would on its own cause an
alkalemia.[24] The
terms acidosis and alkalosis s
hould always be qualified by
an adjective to indicate
the cause of the disturbance:
"respiratory" (indicating a
change in the partial pressure
of carbon dioxide),[25] or
"metabolic" (indicating a
change in the bicarbonate
concentration of the ECF).[5]
[26]
 There are therefore four
different acid-base
problems: metabolic
acidosis, respiratory
acidosis, metabolic alkalosis,
and respiratory alkalosis.
[5]
 One or a combination these
conditions may occur
simultaneously. For instance,
a metabolic acidosis (as in
uncontrolled diabetes mellitus)
is almost always partially
compensated by a respiratory
alkalosis (hyperventilation), or
a respiratory acidosis can be
completely or
partially corrected by a
metabolic alkalosis.
The normal pH in
the fetus differs from that in
the adult. In the fetus, the pH
in the umbilical vein pH is
normally 7.25 to 7.45 and that
in the umbilical artery is
normally 7.18 to 7.38.[27]

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External links[edit]
 Stewart's original text at
acidbase.org
 On-line text at
AnaesthesiaMCQ.com
 Overview at kumc.edu
 Acid-Base Tutorial
 Online acid–base
physiology text
 Diagnoses at
lakesidepress.com
 Interpretation at
nda.ox.ac.uk
 Acids and Bases -
definitions