Transcript Acid – Base Physiology

Acid – Base Physiology II
The pH of the body is controlled by three systems:
1. The chemical acid-base buffering by the body fluids
that immediately combine with acids or base to prevent
excessive changes in pH.
2. The respiratory center which regulates the removal of
volatile CO2 as a gas in the expired air from the plasma
and therefore also regulates bicarbonate (HCO3-) from
the body fluids via the pulmonary circulation. This
response occurs in minutes.
3. The kidneys which can excrete either acid or alkaline
urine, thereby adjusting the pH of the blood. This
response takes place over hours or even days, but
represent a more powerful regulatory system.
Start 2nd class here!!!
Acid-base Distrubances in the pH
The abnormal loss of acid (as in vomiting gastric HCl) or
addition of a weak base can lead to the condition of
Metabolic Alkalosis: increasing pH above 7.4.
In contrast, abnormal removal of HCO3- or another alkali or
addition of acids other than CO2 or H2CO3 (as can happen
in renal failure) can lead to Metabolic Acidosis: decreasing
pH below 7.4.
Since the pH of a CO2/HCO3- solution depends upon the
ratio of these tow buffer pairs, and because the lung control
CO2 but the kidney controls HCO3, the overall description of
their interaction might be described as
pH = k + KIDNEY / LUNG
(Not a real reaction equation, but rather a descriptive relationship
between the regulating components of ph in the body)
Respiratory Acidosis is the inability of the lung to
eliminate CO2 efficiently so the equilibrium shifts toward
increased H+ and HCO3- and Ph decreases.
Respiratory Alkalosis is excessive loss of CO2 through
ventilation driving the equilibrium to the left away from H+
and increasing pH.
Respiratory Acidosis:
CO2 + H2O  H+ + HCO3-
Respiratory Alkalosis:  CO2 + H2O  H+ + HCO3Normally, 1.2 M/L of CO2 is dissolved in plasma, which is a
partial pressure or pCO2 of 40 mmHg.
In biological systems, the total buffering of pH and the
effects of acid-base disturbances is due to a complex
interaction of many buffering systems, open and closed, with
differing buffering capacities.
all HB (n+1)   H+ + all B (n)
Predictions of the effects of these disturbances is done using
a
“Davenport Diagram.”
Combining chemical buffers with CO2/HCO3 such that
CO2 + H2O  HCO3- + H+
+
B(n)  HB(n+1)
Now, the final pH depends on two buffering pathways that
affect the [H+] with two different equilibria equations.
Davenport diagram: the blue curve is the pCO2 isobar
(isopleth) represents the relationship between pH and HCO3 at
a pCO2 of 40 mmHg. Orange line is in respiratory alkalosis
(pCO2 = 20). The green line is respiratory acidosis. These
occur due to changing pCO2 via altered respiratory function
In the right panel. The red lines represent the influence of non
CO2/HCO3 buffering systems. Point A1 would occur if these did not
exist. Point A if these exist at 25 mM/pH (normal for whole blood) ,
and A2 if these buffering systems were infinite. Note that this red line
to point A is shown in panel A and describes the changing buffer
capacity of the non CO2/HCO3 systems during each respiratory
disturbance.
The Davenport Diagram is a nomogram to predict
the different “disturbances” in acid base balance,
based on the blood pH and the amount of
bicarbonate HCO3- in solution.
Acidosis will shift the balance to the left, and
alkalosis will shift it to the right.
Since respiratory disturbances will shift the
amount of HCO3- in solution the opposite of CO2,
then respiratory acidosis will be in the top left, and
respiratory alkalosis in the lower right corner fo the
nomogram.
Partial pressures of CO2
Respiratory
responses occur
along this axis as
the pH will be
inversely related to
the lungs ability to
eliminate CO2
After the acute changes in buffering pH with chemical
acid-base buffering systems, the LUNGS represent the
second line of regulation of pH.
Increased pCO2 will lead to a decrease in pH. The lungs
ability to release CO2 from the blood allows it to regulate
pH, as increased ventilation will vent CO2, increase pH by
adjusting the hydrogen ion concentration.
CO2 + H2O  H+ + HCO3-
CO2 is constantly formed in the cells as the by-product of
metabolic processes. Therefore there is a constant need to
get rid of it. If the metabolic formation of CO2 increases,
the pCO2 increases, and the ventilation rate must increase
to accommodate this change to try and bring the
extracellular fluid into equilibrium.
Also, the hydrogen ion concentration can affect the
ventilation rate, since ventilation rate is directly stimulated
by the pO2 because the pH directly affects the solubility of
blood for oxygen. Increased pH decreases O2 and
reflexively increases ventilation rate to increase O2 intake,
thereby venting out CO2.
Negative feedback loop of
H+ and alveolar ventilation
The respiratory buffering system is a buffering system with
limited gain; ie, it can’t completely compensate for
changes in pH (only 50-75% compensation), but the
relative speed at which it can make significant changes in
pH makes it efficient, and helps buffer pH changes until
the renal excretion of acids and bases comes into play.
Abnormalities in respiratory function reduce the efficiency
of this buffering system (such as emphysema or a
smokers lung) , and drive the body toward a constant
state of respiratory acidosis. Cigarettes smoke also has a
high concentration of CO2, making things even worse.
Thus, in these conditions the body becomes heavily
dependent on the ability of the kidney to compensate for
the inability of the lungs to buffer excess H+.
RENAL CONTROL OF ACID-BASE BALANCE
The kidneys control acid-base balance by excreting either
an acidic or basic urine.
The kidney filters large volumes of bicarbonate and the
extent to which they are either excreted or reabsorbed
determines the removal of “base” from the blood.
The kidney secretes large numbers of H+ into the tubule
lumen, thus removing H+ from the blood.
The “gain” of the adjustment of pH by the kidney and the
acid base balance it regulates is nearly infinite, which
means that while it works relatively slowly, it can
COMPLETELY correct for abnormalities in pH.
The “metabolic” or renal regulation of the balance of H+ or
HCO3- excreted will determine if there is a net loss of H+ or
HCO3-, and will determine the pH of the urine.
CO2 + H2O  H+ + HCO3-
Filtered
Nephron
Secreted
Reabsorbed
Note: the renal regulation of the
equilibrium between H+ and CO2
takes place on the “right” side of
the equation
Urine (excreted)
Overall, the kidneys
must excrete H+ and
prevent the loss of
HCO3-.
Filtered bicarbonate
must react with secreted
H+ in order to be
reabsorbed as H2CO3
The nephrons must secrete a total of 4,320 mEq
of H+/day in order to complex with HCO3- to
reabsorb (almost all of) it.
In addition, an additional 80 mEq/day of H+ is
secreted to facilitate the excretion of non-volatile
acids (products of protein metabolism that can
not be expired via the lung).
Thus, the kidney must secrete a total of 4,400
mEq/day of H+ into the tubular fluid.
The kidneys regulate extracellular fluid pH by
secreting H+, reqbsorbing HCO3-, and producing
new HCO3During alkalosis, excess HCO3- is not bound by
H+, and is excreted, effectively increasing H+ in the
circulation and reversing the alkalosis.
In acidosis, the kidneys reabsorb all the
bicarbonate and produce additional bicarbonate
which is all added back to the circulation to reverse
the acidosis.
H+ is secreted and HCO3- reabsorbed in all
segments of the kidney except for the thin limbs of
the loop of Henle. (however, HCO3 is not readily
permeable through the luminal membrane).
PROXIMAL H+
H+ is secreted via a
Na-H countertransport process,
coupled to the
active movement of
na into the cell via
the basalateral Na-
K atpase.
Bicarbonate
reabsorption is
facilitated by the
enhanced
conversion of CO2
to H2CO3 (normally
slow) via the
enzyme carbonic
anhydrase
Reabsorbed as
CO2 +
H2O 
Complexed
Secreted
filtered
H2CO3
 H+ +
HCO3-
Once CO2 enters the cell, it can be quickly driven in the
reverse reaction to form carbonic acid (normally very slow)
due to the intracellular enzyme carbonic anhydrase) and
this pushes the reaction to form bicarbonate and H+ to be
taken back into the
Inside the cell;
Carbonic anhydrase
CO2 + H2O -------*--------> H2CO3  H+ + HCO3Secreted back
Into the lumen
Reabsorbed into
the circulation
Note; this process is all driven by the active transcellular movement of Na+
DISTAL H+
In the intercallated cells of the distal
tubule, a H/Cl co-transport is involved with
H+ secretion.
The formation of
H+ inside the cell
provides a gradient
for the secretion of
more H+ into the
lumen to complex
weith and reabsorb
more bicarbonate
This distal pathway
accounts for only
5% of secreted H+
but the H+ gradient
it can form is 900X
so it is a major site
for creating an
acidic urine pH 4.5
In general (under “normal” conditions), the amount of
bicarbonate filtered and the amount of H+ secreted are
similar (they are said to “titrate” each other), though there is a
slight excess of H+ secreted and excreted. This is not as H+,
but rather complexing with other buffers such as phosphate
or ammonia to be excreted.
In metabolic alkalosis, the filtered bicarbonate exceeds the
secreted H+, and therefore the bicarbonate is excreted in the
urine (making it more alkaline). This loss of excess base will
slowly correct the metabolic alkalosis.
In metabolic acidosis, the excess secreted H+ results in
total reabsorption of bicarbonate, and the excess H+ is
excreted in the urine (making it more acidic). This loss of
excess acid will slowly correct the acidosis.
The urine can only accommodate a small
percentage of free H+ protons in solution, so much
of the H+ to be excreted must complex with other
buffering bases to facilitate its excretion.
The major such buffers are phosphates and
ammonia, but other lesser buffers including urate
and citrate also combine with H+ to get it out into
the urine.
The buffering of H+ by phosphate and urea in the
tubular fluid also contribute to the generation of
new bicarbonate.
Phosphate
buffering
and
secretion
of H+
The process of
driving CO2 to
secrete a H+
produces HCO3
de-novo
AMMONIUM GENERATES HCO3-
**
Ammonium (NH4+)
is produced from
the cellular
metabolism of
glutamine in all
nephron segments.
Ammonium is
secreted into the
lumen, and 2 HCO3ions are formed
and reabsorbed **
Ammonia buffers secreted H+ in the collecting duct
Secreted H+
combines with
ammonia which
freely diffuses into
the lumen from cells
to complex with H+
in the lumen to form
NH4+ which is
trapped in the lumen
and excreted. Again,
the loss of a
hydrogen ion from
the cell creates denovo sythhesis of a
bicarbonate
molecule to be
reabsorbed.
Note that “metabolic
acidosis and
alkalosis move I an
axis related to the
ability of the kidney to
reabsorb HCO3.
Acidosis occurs when
plasma HCO3 is low,
while alkalosis occurs
when it is high and
there the ratio to H+
in the nephron is also
high.
Metabolic Acidosis occurs when the kidneys fail to
excrete acids formed in the body, or there is excess
ingestion of acids, or the loss of bases from the body.
Renal Tubular Acidosis: due to a defect in H+ secretion or
HCO3 reabsroption.
Diarrhea: Excess bicarbonate loss into the feces without
time to reabsorb (most common cause).
Diabetes mellitus: In the absence of normal glucose
metabolism the cells metabolize fats and form acetoacetic
acid, reducing pH, and inducing renal acid wasting.
Chronic renal failure: decreased renal function results in
acid build-up in the circulation and reduced HCO3reabsorption.
Acid ingestion: toxins such as aspirin or methyl alcohol
result in excess acid formation.
Metabolic Alkalosis: occurs when there is excess retention
of bicarbonate or excess loss of H+ from the body.
Diuretic therapy: many diuretics increase tubular flow,
resulting in increased sodium load, increased na reabsorption
and therefore increased bicarbonate reabsorption.
Excess Aldosterone: which promotes excess sodium
reabsorption and stimulates H+ secretion.
Vomiting: loss of the acidic contents of the stomach creates
a depletion of H+ which is compensated for by removing
more H+ from the circulation.
Ingestion of alkaline drugs such as sodium bicarbonate
used for upset stomachs and ulcers.
Analysis of simple acid base disorders and how they are
compensated for by the body.