Transcript Acid Base Balance

The Renal Role in
Acid Base Balance
Dr. Dave Johnson
Associate Professor
Dept. Physiology
UNECOM
Review of Basics

Acid/Base refers to anything having to do with the
concentrations of free H+ ions in aqueous solutions

pH = - log [H+]

Therefore, the ‘normal’ pH of 7.40 means there are
10-7.40 moles of free H+ ions in a liter of plasma.

This is equivalent to about 40 nMol / L
Acid Base Pairs

An acid is a compound that
can donate a proton to a
solution.

An base is a compound that
can take up a proton from a
solution.

When an acid loses it’s
proton, it becomes the
conjugate base of that acid.
Biological Buffers

The 3 major buffering systems of
biological fluids are:
1.
2.
3.
Bicarbonate buffering system
Protein buffering system
Phosphate buffering system
Isohydric Principle

The isohydric principle simply denotes the fact
that, even though there are 3 principle types of
buffering systems in biological fluids, in an
acid/base crisis, they all work together.
This is because the H+ ion is common
to all of them.
Bicarbonate Buffer

The major components of the bicarbonate buffering system are carbon dioxide (C02), which
serves as the conjugate acid, and bicarbonate ion (HCO3-), which serves as the conjugate
base.

This acid/base pair is unusual, since C02 has no proton associated with it - therefore it is
usually described as a ‘potential’ acid, since increases in C02 can potentially increase free H+
ion concentrations, and thus lower pH.


C02 + H2O  H2CO3  H+ + HCO3-
The concentration of H2CO3 is about 340 times LESS than dissolved C02 and 6800 times
LESS than HCO3- at normal pH, so it is usually ignored and the equation is written as:


C02 + H2O  H+ + HCO3-
This reaction is greatly accelerated by the presence of carbonic anhydrase!
Dissolved CO2

CO2 is a gas, and only CO2 dissolved in the ECF is available to
participate in acid base reactions.

It is known that the ‘normal’ partial pressure exerted by CO2 in
plasma is 40 mm Hg (ie, pCO2 = 40).

It is also known that the solubility constant of C02 (ie, how much C02 gas
dissolves for each mm Hg of partial pressure exerted by the gas in solution)
is 0.03. Therefore:
0.03 mMol CO2 / L / mm Hg

Thus, at normal pCO2 of 40 mmHg, there is 1.2 mMol/L plasma of
dissolved CO2 in the ECF, that can participate in acid base reactions (40 x
.03 = 1.2)
Henderson-Hasselbalch
Equation

It is important to recognize that it is the RATIO of the log of the conjugate base
to the log of the conjugate acid of ANY buffering system in solution that
determines the pH of that solution:
pH = pK + log [A-] / [HA]
Plugging in the values for the plasma concentration of ANY buffering pair in the
ECF would give you the pH of the ECF (isohydric principle). For the bicarbonate
buffering system, it is written as follows:
pH = 6.1 + log [HCO3-] / 0.03 x PC02
pH = 6.1 + log [24] / 0.03 x 40
pH = 6.1 + log (24 / 1.2)
pH = 6.1 + log 20
pH = 6.1 + 1.3
pH = 7.4
Role of the Kidneys

There are 3 major roles the kidneys play in maintaining
acid base balance:
1.
They must recapture the daily filtered load of HCO3- ions by
reabsorbing them.
2.
They must excrete into the urine any excess free H+ ions
which are added to the body fluids daily
3.
The kidneys must also replace any HCO3- used up titrating
these excess acids produced daily.

“Life is a struggle, not against sin, not against
the Money Power, not against malicious animal
magnetism, but against hydrogen ions". H.L.
Mencken
Recapturing Filtered HCO3
HCO3- is readily filtered into
Bowman’s space, but normally
very little escapes into the urine.

Around 85% of the HCO3- filtered
load of is reabsorbed in the
proximal tubules, 10-15% in
Henle’s loop, and only 3-5% at
more distal sites.

Note the mechanism utilized:
secreted protons combine with the
filtered HCO3-.
Recapturing Filtered HCO3
It is important to recognize that the
loss of any free HCO3- into the
urine is equivalent to the addition
of free H+ ions to the ECF:
C02 + H2O  H+ + HCO3
The loss of HCO3- from the ECF
lowers the ratio of base (HCO3-) to
acid (CO2) in the ECF, and will
therefore result in an increase the
free H+ ion concentration (and
thus a decrease the pH!)
Generating New HCO3CO2 + H20  H+ + HCO3
During a metabolic acidemia, free H+ ions are added to the
ECF for some reason, which “uses up” HCO3- in the buffering
process.

The equation above shifts to the LEFT, generating CO2.

This HCO3- that buffered the excess H+ ions is lost for good,
and MUST BE REPLACED to bring plasma HCO3- levels
back up to approximately 24 mMol/ L.
HCO3- Generation in the Proximal
Tubules using Titratable Acids

PROXIMAL TUBULE:
Similar to what you saw
previously for HCO3REABSORBTION here,
except now a H+ is excreted
into the urine, generating a
new HCO3- .

In this scenerio, filtered
sodium monohydrogen
phosphate (Na2HPO4)
serves as a proton acceptor
(base), and is converted to
the acid, Na2H2PO4.
HCO3- Generation in Distal Tubules and
Collecting Ducts using Titratable Acids

DISTAL TUBULE AND
COLLECTING DUCTS: Similar
to what you saw here previously
for HCO3- REABSORBTION
here, except now a H+ is excreted
into the urine, generating a new
HCO3-

As you just saw in the proximal
tubule, a filtered Na2HPO4 serves
as the proton acceptor, and is
converted to Na2H2PO4.
What is Titratable Acidity?

The amount of strong base (such as NaOH) that it takes to titrate a patient’s
urine that is acidic back to normal pH (~7.42) is approximately equal to the
amount of titratable acids that were in the urine (ie, if 45 mMol of NaOH
were required to titrate urine pH up to 7.42, the assumption can be made
that 45 mMol of H+ ion were buffered by titratable acids, and 45 mMol of
‘new’ HCO3- were generated).

Dihydrogen phosphate is the major titratable acid measured in urine.

A healthy individual can easily generate some 50 to 100 mEq’s of H+ ions
daily, However, titratable acidity normally can account for the excretion of
only about 10 to 40 mEq of H+ ion per day.
Limitations of Titratable Acids

As the filtrate passes from
Bowman’s space to the collecting
tubules, the pH can drop all the
way to about 4.50. This is an
important concept, because
urinary pH cannot drop below
approximately 4.50.

Unfortunately almost all titratable
acids will be fully protonated
when the urine pH reaches about
5.20.
Importance of Urinary Acid Buffering…..

Assumption: individual has to excrete 100 mEq (mMol) of H+ ion a
day to stay in acid / base balance (this is about average).

As noted, the minimum pH that can be achieved by the urine is
about 4.50. Although urine with a pH of 4.50 has a H+ concentration
about 1000 times greater than healthy plasma (7.42 vs
4.50…..about 3 log units), the H+ ion concentration of this urine with
a pH of 4.5 is still only about 40 uMol/L (normal plasma is 40
nMol/L).

Thus, to get 100 mMol’s of unbuffered H+ ion into the urine each day
you would have to produce about 2500 liters of this urine !!
(2500 L x 40 uMol H+ ion/L = 100,000 uMol H+ ion = 100 mMol of H+
ion )
Ammonia Buffering

Many years ago, it was observed that in those patients
experiencing metabolic acidemia, there was not only
a rise in urinary titratable acid’s, but also in urinary
ammonium ion (NH4+).

We now know that ammonium ion is a very
important renal buffer, because the amount available
is not directly dependant on diet or filtration, like
titratable acids such as monohydrogen phosphate.
Ammonia Buffering

Ammonium ion can actually be produced in the cells
lining the nephron, predominately in the proximal
tubule, mostly (but not exclusively) from the
deamination of of the amino acid glutamine.

The synthesis of ammonium ion in the proximal
tubule occurs as follows:
Glutamine----> 2NH4+ + -ketoglutarate
How Does This Help?

The subsequent metabolism of  -ketoglutarate in the proximal tubular cell
results in the CONSUMPTION OF TWO H+ ions. Removal of two H+ ions
is equivalent to the GENERATION OF TWO NEW HCO3- ions in these
cells. These two new HCO3- ions are transported across the basolateral
membrane of the cell via a Na+/ HCO3- symporter, and returned to the
general circulation.

The ammonium ion (NH4+) is transported into the luminal fluid, mostly by
substituting for H+ on the Na+/H+ antiporter, and passed out into the urine.
Once in the tubule, it cannot diffuse back in due to it’s charge, and is thus
lost in the urine.

The urinary excretion of NH4+ plays NO DIRECT ROLE in removing
protons: NH4+ is merely a side product - or marker - of the formation of ketoglutarate in renal proximal tubular cells.
It Works

Therefore, proximal tubular secretion and
subsequent urinary excretion of each NH4+ ion
is linked to the generation of a new HCO3- ion
in proximal tubular cells, which will then be
returned to the circulation to replace HCO3lost buffering excess plasma H+ ions.
Graphic Proof

Notice that AKG metabolism to
C02 and H20 in proximal tubule
cells consumes two H+ ions.

Now, an intracellular HCO3- in
equilibrium with a H+ becomes a
‘free’ HCO3-

NH4+ MUST be excreted in the
urine after it is secreted from the
cell. If it were reabsorbed, it
would eventually be converted to
urea in the liver, a process which
generates two H+ ions (which
would then consume two HCO3ions).