Download Acids and Bases

Regulation of Acid-Base Balance
Objectives
To know
• Various mechanisms that contribute to the
regulation of H+ concentration
• The control of renal H+ secretion
• Renal reabsorption, production, and
excretion of bicarbonate ions (HCO3–)
• The key components of acid-base control
systems in the body fluids.
Hydrogen Ion
Precise H+ regulation is essential because:
The activities of almost all enzyme systems
in the body are influenced by H+
concentration changes in hydrogen
concentration alter virtually all cell and body
functions.
Normal concentration of H+, averages only
0.00004 mEq/L.
Because of this low concentration we
express H+ concentration on a logarithm
scale, using pH units.
pH is inversely related to the H+ conc. ;
therefore, a low pH corresponds to a high
H+ concentration, and a high pH
corresponds to a low H+ concentration
Acids and Bases
A hydrogen ion is a single free proton released from a
hydrogen atom.
Acids: molecules containing hydrogen atoms that can
release hydrogen ions in solutions eg:
((HCl ; (H2CO3).
Base: is an ion or a molecule that can accept an H+.
eg :HCO3–; HPO4= ; proteins ; protein hemoglobin
in the red blood cells and proteins in the other cells
of the body
Alkali is a molecule formed by the combination of one
or more of the alkaline metals-sodium, potassium,
and a highly basic ion such as a hydroxyl ion (OH–).
Acid
An acid is when hydrogen ions accumulate in a solution.
•
• It becomes more acidic
• [H+] increases = more acidity
• CO2 is an example of an acid.
HCl
2
H+
H+
H+
Cl-
Cl-
H+
7
pH
Cl-
ClH+
Cl-
As concentration of hydrogen ions
increases, pH drops
Base
• A base is chemical that will remove hydrogen ions
from the solution
• Bicarbonate is an example of a base.
NaOH
Na+ OH- H + ClH + ClNa+ OHH + ClH+
ClNa+
Na+ OHH + ClOH-
2
7
pH
Acids and basis
neutralize eachother
A change of 1 pH unit corresponds to a
10-fold change in hydrogen ion
concentration
2
Na+
ClNa+
H+
Na+
7
OH-
Na+
Cl-
ClH2O
Cl-
pH
Alkalosis
excess removal of H+ from the body fluids.
Acidosis
the excess addition of H+.
Normal pH
-arterial blood is 7.4
-venous blood and interstitial fluids is 7.35 Why?
-intracellular fluid range between 6.0 and 7.4.
-Hypoxia of the tissues and poor blood flow to the tissues
can cause acid accumulation and decreased intracellular
pH.
-The lower limit of pH at which a person can live more than a
few hours is about 6.8, and the upper limit is about 8.0
The pH of urine can range from 4.5 - 8.0,
depending on the acid-base status of the
ECF.
The kidneys play a major role in correcting
abnormalities of extracellular fluid H+
concentration by excreting acids or bases at
variable rates.
eg. of acidic body fluid is the HCl secreted
into the stomach by the oxyntic (parietal)
cells of the stomach mucosa, The H+
concentration in these cells is about 4
million times greater than the hydrogen
concentration in blood, with a pH of 0.8.
Systems that regulate the H+concentration in
the body fluids
(1) the chemical acid-base buffer systems of the body
fluids, which immediately combine with acid or base to
prevent excessive changes in H+ concentration;
(2) the respiratory center, which regulates the removal of
CO2 (and, therefore, H2CO3) from the ECF.
(3) the kidneys, which can excrete either acid or alkaline
urine, thereby readjusting the ECF H+ concentration
toward normal during acidosis or alkalosis.
Buffer systems of the body fluids react within a
fraction of a second to minimize these changes.
The second line of defense, the respiratory system,
also acts within a few minutes to eliminate CO2
and, therefore, H2CO3 from the body.
The kidneys are relatively slow to respond
over a period of hours to several days, they
are by far the most powerful of the acidbase regulatory systems.
A buffer is any substance that can reversibly
bind H+.
The general form of the buffering reaction is
Buffer + H
→
H Buffer
Phosphate: important intracellular and renal
tubular buffer
HPO4- + H+
H2PO4
Ammonia: important renal tubular buffer
NH3 + H+
NH4+
Proteins: important intracellular and plasma buffers
H+ + Hb
HHb
Bicarbonate: most important Extracellular buffer
H+ + HCO3 H2CO3
H2O + CO2
BICARBONATE BUFFER SYSTEM
• Most important buffer system in the plasma
• Accounts for 65% of the buffering capacity in
plasma
• Accounts for 40% of the buffering capacity in the
whole body
Bicarbonate as a Buffer
Bicarbonate Buffer System
(1) a weak acid,H2CO3, and
(2) a bicarbonate salt, such as NaHCO3.
H2CO3 is formed in the body by the reaction
of CO2 with H2O.
(3) the bicarbonate buffer system is the most
powerful extracellular buffer in the body.
Phosphate buffer system
The main elements of the phosphate buffer
system are H2PO‾ and HPO4 =.
The phosphate buffer system is also important
in buffering intracellular fluid it plays a major
role in buffering renal tubular fluid and
intracellular fluids.
The pH of intracellular fluid is lower than that
of extracellular fluid.
Proteins important intracellular buffers
In the red blood cell, hemoglobin (Hb) is an
important buffer, as follows
H+ + Hb → HHb
Approximately 60 to 70 per cent of the total chemical
buffering of the body fluids is inside the cells, and
most of this results from the intracellular proteins.
Respiratory Regulation
of Acid-Base Balance
The second line of defense against acid-base
disturbances
increase in ventilation eliminates CO2 from ECF,
which, reduces the H+ concentration.
Conversely, decreased ventilation increases
CO2, and increasing H+ concentration
CO2 is formed continually in the body by
intracellular metabolic processes &it
diffuses from the cells into the interstitial
fluids and blood
About 1.2 mol/ L of dissolved CO2 normally
is in the ECF, corresponding to a Pco2 of 40
mm Hg.
• If the rate of metabolic formation of CO2
increases, the PCO2 of the ECF is increased.
Conversely, a decreased metabolic rate lowers the
P CO2.
If the rate of pulmonary ventilation is increased,
CO2 is expired from the lungs, and the Pco2 in
the ECF decreases. Therefore, changes in either
pulmonary ventilation or the rate of CO2
formation by the tissues can change the ECF
Pco2.
• Increasing alveolar ventilation decreases EC F
Hydrogen ion concentration and raises pH
• If the metabolic formation of CO2 remains
constant, the only other factor that affects P CO2
in ECF is the rate of alveolar ventilation.
• when CO2 concentration increases, the H2CO3
concentration and H+ concentration also increase,
thereby lowering ECF pH
Alveolar ventilation rate influence H+ concentration
and H+ concentration affects the rate of alveolar
ventilation.
Because increased H+ concentration stimulates
respiration, and because increased alveolar
ventilation decreases the H+ concentration, the
respiratory system acts as a typical negative
feedback controller of H+ concentration.
Respiratory control cannot return the H+
concentration all the way back to normal.
The respiratory mechanism for controlling H+
concentration has an effectiveness between
50 - 75 %
Respiratory regulation of acid-base balance is
a physiologic type of buffer system because it
acts rapidly and keeps the H+ concentration
from changing too much until the slowly
responding kidneys can eliminate the
imbalance.
Abnormalities of respiration can also cause
changes in H+ concentration an impairment
of lung function, (severe emphysema)
decreases the ability of the lungs to eliminate
CO2; & causes a buildup of CO2 in the ECF
and a tendency toward respiratory acidosis
Renal Control of
Acid-Base Balance
The kidneys control acid-base balance by
excreting either an acidic or a basic urine.
Excreting an acidic urine reduces the
amount of acid in ECF, whereas excreting a
basic urine removes base from the ECF.
Large numbers of HCO3 – are filtered continuously
into the tubules, and if they are excreted into the
urine, this removes base from the blood. Large
numbers of H+ are also secreted into the tubular
lumen by the tubular epithelial cells, thus
removing acid from the blood.
If more H+ is secreted than HCO3 – is filtered, there
will be a net loss of acid from the ECF.
Conversely, if more HCO3 – is filtered than H+ is
secreted, there will be a net loss of base.
Nonvolatile acids, mainly from the
metabolism of proteins. (called nonvolatile
because they are not H2CO3 )and, therefore,
cannot be excreted by the lungs.
When there is a reduction in the ECF H+
concentration (alkalosis), the kidneys not
reabsorb all the filtered bicarbonate, and
increasing the excretion of bicarbonate.
Because HCO3 –normally buffers hydrogen
in the ECF, this loss of bicarbonate is the
same as adding an H+ to the ECF.
Therefore, in alkalosis, the removal of
HCO3 – raises the ECF H+ concentration
back toward normal.
In acidosis, the kidneys do not excrete
bicarbonate into the urine but reabsorb all
the filtered bicarbonate and produce new
bicarbonate, which is added back to the
ECFand reduces the ECF H+ concentration
back toward normal.
The kidneys regulate ECF H+ concentration
through three mechanisms:
(1) secretion of H+,
(2) reabsorption of filtered HCO3 -, and
(3) production of new HCO3 -.
Reabsorption of bicarbonate in different segments of the renal
tubule.
The percentages of the filtered load of bicarbonate absorbed by
the various tubular segments per day under normal conditions.
Each time an H+ is formed in the tubular epithelial
cells, an HCO3 - is also formed and released back
into the blood. The net effect of these reactions is
“reabsorption” of HCO3 – from the tubules,
although the HCO3 – that actually enters the ECF
is not the same as that filtered into the tubules.
The reabsorption of filtered HCO3 – does not
result in net secretion of H+ because the secreted
H+ combines with the filtered HCO3– and is
therefore not excreted.
Primary active secretion of hydrogen ions through the luminal membrane of
the intercalated epithelial cells of the late distal and collecting tubules.
Note that one bicarbonate ion is absorbed for each hydrogen ion
secreted, and a chloride ion is passively secreted along with the hydrogen
ion.
When H+ in the tubular fluid with HCO3‾, this
results in the reabsorption of one HCO3 ‾ for each
H+ secreted.
But when there are excess H+ in the urine, they
combine with buffers other than HCO3 ‾, and this
results in the generation of newHCO3 ‾ that can also
enter the blood.
Thus, when there is excess H+ in the ECF, the
kidneys not only reabsorb all the filtered HCO3 ‾ but
also generate new HCO3 ‾ thereby helping to
replenish the HCO3 ‾ lost from the ECF in acidosis.
Phosphate Buffer System
The phosphate buffer system is composed of
HPO4 = and H2PO4 ‾.
Both become concentrated in the tubular fluid
because of their relatively poor reabsorption
and because of the reabsorption of water from
the tubular fluid.
Therefore, is effective as a buffer in the tubular
fluid.
Buffering of secreted hydrogen ions by filtered
phosphate (NaHPO4 –). a new bicarbonate ion
is returned to the blood for each NaHPO4 – that
reacts with a secreted hydrogen ion.
Whenever an H+secreted into the tubular lumen
combines with a buffer other than HCO3-, the
net effect is addition of a newHCO3 - to the
blood.
This demonstrates one of the mechanisms by
which the kidneys are able to replenish the
ECF stores of HCO3–.
Under normal conditions, much of the filtered
phosphate is reabsorbed, and only about 30
to 40 mEq/day is available for buffering
H+. Therefore, much of the buffering of
excess H+ in the tubular fluid in acidosis
occurs through the ammonia buffer system.
A second buffer systemmore important quantitatively than the
phosphate is composed of ammonia (NH3) and the
ammonium ion (NH4 +). Ammonium ion is synthesized
from glutamine, which comes mainly from the metabolism
of amino acids in the liver. The glutamine delivered to the
kidneys is transported into the epithelialcells of the
proximal tubules, thick ascending limb of the loop of
Henle, and distal tubules
For each molecule of glutamine metabolized
in the proximal tubules, two NH4 + are
secreted into the urine and two HCO3 – are
reabsorbed into the blood. The HCO3 –
generated by this process constitutes new
bicarbonate.
Production and secretion of ammonium ion (NH4 +) by proximal tubular
cells. Glutamine is metabolized in the cell, yielding NH4 +and
bicarbonate. The NH4 + is secreted into the lumen by a sodium-NH4 +
pump. For each glutamine molecule metabolized, two NH4 + are
produced and secreted and two HCO3 – are returnedto the blood.
In the collecting
tubules, the addition of
NH4+ to the tubular
fluids occurs through a
different mechanism
Buffering of hydrogen ion secretion by ammonia (NH3) in the collecting tubules. Ammonia diffuses into
the tubular lumen, where reacts with secreted hydrogen ions to form NH4 +, which is then excreted. For
each NH4 + excreted, a new HCO3 – is formed in thetubular cells and returned to the blood.
Regulation of Renal Tubular
Hydrogen Ion Secretion
H+ secretion by the tubular epithelium is necessary for
both HCO3 ‾ reabsorption and generation of new HCO3
Under normal conditions, the kidney tubules
must secrete at least enough H+ to reabsorb almost all
the HCO3 ‾ that is filtered, and there must be enough
H+ left over to be excreted as titratable acid or NH4 +
to rid the body of the nonvolatile acids produced each
day from metabolism.
The most important stimuli for increasing H+
secretion by the tubules in acidosis are
(1) an increase in PCO2 of the ECF and
(2) an increase in H+ concentration of the
extracellular fluid (decreased pH).
Factors That Increase H+ Secretion and
HCO3 - Reabsorption by the Renal Tubules
↑ PCO2
↑ H+, ↓ HCO3–
↓ Extracellular fluid volume
↑ Angiotensin II
↑ Aldosterone (Conn’s syndrome)
Hypokalemia
Factors That Decrease H+ Secretion
and HCO3-Reabsorption by the Renal
Tubules
↓ PCO2
↓ H+,↑ HCO3 –
↑ Extracellular fluid volume
↓ Angiotensin II
↓ Aldosterone
Hyperkalemia
ECF volume depletion stimulates sodium
reabsorption by the renal tubules and increases H+
secretion and HCO3 ‾ reabsorption through multiple
mechanisms,
(1) Increased angiotensin II levels, which directly
stimulate the activity of the Na+-H+ exchanger in
the renal tubules,
(2) increased aldosterone levels, which stimulate H+
secretion by the intercalated cells of the cortical
collecting tubules. Therefore, ECF volume
depletion tends to cause alkalosis due to excess H+
secretion and HCO3 ‾ reabsorption.
Renal Correction of Alkalosis
In alkalosis,HCO3 ‾ is removed from the ECF
by renal excretion, which has the same
effect as adding an H+ to the ECF. This
helps return the H+ concentration and pH
back toward normal.
The cause of the alkalosis is a decrease in
plasma PCO2 , caused by hyperventilation.
Therefore, the compensatory response to a
primary reduction in PCO2 in respiratory
alkalosis is a reduction in plasma HCO3 ‾
concentration,caused by increased renal
excretion of HCO3 ‾.
In metabolic alkalosis, there is
• an increase in plasma pH
• a decrease in H+ concentration.
• a rise in the extracellular fluid HCO3 ‾
concentration
(In metabolic alkalosis, the primary compensations are
decreased ventilation, which raises PCO2 , and
increased renal HCO3 ‾ excretion, which helps
compensate for the initial rise in extracellular fluid
HCO3 ‾ concentration).
Clinical Causes of Acid-Base Disorders
Any factor that decreases the rate of pulmonary
ventilation increases the PCO2 of ECF .This
causes an increase in H2CO3 and H+
concentration, resulting in acidosis.
Because the acidosis is caused by an abnormality in
respiration, it is called respiratory acidosis.
In respiratory acidosis, the compensatory
responses available are
(1) the buffers of the body fluids and
(2) the kidneys, which require several days to
compensate for the disorder.
Respiratory alkalosis is caused by overventilation by the lungs.
A psychoneurosis can occasionally cause overbreathing to the
extent that a person becomes alkalotic.
A physiologic type of respiratory alkalosis occurs when a
person ascends to high altitude. The low oxygen content of
the air stimulates respiration, which causes excess loss of
CO2 and development of mild respiratory alkalosis. Again,
the major means for compensation are the chemical buffers
of the body fluids and the ability of the kidneys to increase
HCO3 ‾ excretion.
Metabolic acidosis refers to all types of acidosis besides those
caused by excess CO2 in the body fluids.
Metabolic acidosis can result from several general causes:
(1) failure of the kidneys to excrete metabolic acids normally
formed in the body,
(2) formation of excess quantities of metabolic acids in the
body,
(3) addition of metabolic acids to the body by ingestion or
infusion of acids, and
(4) loss of base from the body fluids, which has the same
effect as adding an acid to the body fluids.
Clinical Measurements and Analysis
of Acid-Base Disorders
Interpreting Arterial Blood Gases
(ABG)
• This blood test is from arterial blood, usually from the
radial artery.
• There are three critical questions to keep in mind when
attempting to interpret arterial blood gases (ABGs).
First Question: Does the patient exhibit acidosis or
alkalosis?
Second Question: What is the primary problem?
Metabolic? or Respiratory?
Third Question: Is the patient exhibiting a compensatory
state?