3. By the end of this lecture you
should understand:
Basic concepts: acid, base, buffer,
pH, Hendresson-Hasselbalch
equation,
why keeping acid-base balance is
important
Normal H+ concentration
Source of H+ in the body
Body systems regulating H+ conc;
Buffers, Respiratory system &
kidney
4. A delicate balance of fluids,
electrolytes, and acids and
bases is required to maintain
good health.
This balance is called
Homeostasis.
5. Body Fluids
Intracellular fluid (ICF)
◦ found within the cells of the body
◦ constitutes 2/3 of total body fluid
◦ major cation is potassium
Extracellular fluid (ECF)(interstitial and
intravascular)
◦ found outside the cells
◦ accounts of 1/3 of total body fluid
◦ major cation is sodium
6. Acid-Base balance is:
the regulation of
HYDROGEN ions.
◦Maintaining a normal pH is
necessary because
hydrogen ions are highly
reactive and are especially
likely to combine with
proteins, altering their
7. The [H+] in extracellular fluid is
expressed in nanoequivalents (nEq)
per liter.
A nanoequivalent is one-millionth of a
milliequivalent, so there are millions
more sodium,chloride, and other ions
measured in mEq than there are
hydrogen ions.
Because nanoequivalents represent
such a small amount, the [H+] is
routinely expressed in pH units.
H+ = 24 x pCO2
8. H+ ion has special
significance
because of the
narrow ranges that
it must be
maintained in order
to be compatible
with living systems.
H+ ion is inversely
related to PH
8
9. ACID-BASE BALANCE primarily
controlled by regulation of H+ ions in the
body fluids
◦ Especially extracellular fluids.
The more Hydrogen ions, the more acidic the
solution and the LOWER the pH
The lower Hydrogen concentration, the more
alkaline the solution and the HIGHER the pH
9
10. Range of ECF [H+] variation very small
pH Vs. [H+]
pH nanoeq [H+]/L
6.8-7.35 Acidemia 100-44
7.35-7.45 Normal 44-36
7.45- 8 Alkalemia 36-16
Relationship between pH and [H] at
physiologic pH
pH 7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70
[H+] (nM) 100 79 63 50 40 32 25 20
11. pH SCALE
pH refers to Potential Hydrogen
Expresses hydrogen ion concentration in
water solutions
Water ionizes to a limited extent to form
equal amounts of H+ ions and OH- ions
◦ H2O H+ + OH-
H+ ion is an acid
OH- ion is a base
11
12. pH SCALE
pH equals the logarithm (log) to the
base 10 of the reciprocal of the
hydrogen ion (H+) concentration
H+ concentration in extracellular fluid
(ECF)
12
pH = log 1 / H+ concentration
4 X 10 -8 (0.00000004)
13. pH SCALE
Low pH values = high H+ concentrations
◦ H+ concentration in denominator of formula
Unit changes in pH represent a tenfold
change in H+ concentrations
◦ Nature of logarithms
13
pH = log 1 / H+ concentration
4 X 10 -8 (0.00000004)
17. Why acid base balance is
important
Acid-base balance refers to the
complex mechanisms through
which the body strives to achieve
and maintain a homogenous
internal environment.
This environment is reflected in a
serum pH of 7.35 to 7.45.
18. Because only slight changes in H+
from the normal value can cause
significant alterations in all
physiological processes.
Delivery of oxygen to the cell, the
cellular use of oxygen, and the
hormonal regulation of metabolism are
all affected by the pH of the body.
19. The task imposed on the
mechanisms that maintain Acid-Base
homeostasis is large
◦ Metabolic pathways are
continuously consuming or
producing H+
◦ The daily load of waste products for
excretion in the form of volatile and
fixed acids is substantial
19
20. The body produces more acids than
bases
Non-Volatile Acids – 50-100 meq/day
of non-volatile acids produced daily.
Acids take in with foods
Acids produced by metabolism of
lipids and proteins
Cellular metabolism produces CO2.
CO2 + H20 ↔ H2CO3 ↔ H+ +
HCO3
-
20
21. Intracellular pH (pHi)
In contrast to the value in the extracellular fluid, the
pH within the cell is not uniform because of the
presence of multiple compartments, including
the cytoplasm, mitochondria, endoplasmic
reticulum, and nucleus
It is maintained at 7.2:
1. To keep important metabolic intermediates in
ionized state and limit tendency to move out of
cell
2. Most intracellular enzymes taking part in
cellular metabolism have pH optimum close to
this value
3. DNA, RNA & Protein synthesis at slightly
22. Blood(extracellular) pH
Maintanined at 7.4:
this represents about a fourfold
gradient favouring the exit of hydrogen
ion from the cell.
1.To keep pHi in optimal range
2.Enable optimal binding of hormones to
receptors
3.Enable optimal activity of enzymes
present in blood
23. In assessment of acid-base
disorders, the clinician is
always looking from the
outside in.
Why? For 2 reasons:
Ease of sampling: Arterial blood is
easy to sample. It is much more
difficult to obtain an intracellular
sample
Arterial blood gives results which can
be considered a sort of 'average
value'. It would be more difficult to find
an intracellular sample that could be
considered to be 'representative' of all
24. Several factors contribute to the
regulation of intracellular pH, including
the rate of metabolic activity, tissue
perfusion, and the extracellular pH.
Alterations in the pH of the
extracellular fluid produce parallel,
although lesser, changes within the
cells.
The more efficient maintenance of
intracellular pH is in part related to the
greater buffering capacity within the
cells
25. This relationship between the pH in the
two fluid compartments is extremely
important in the clinical setting.
The principal physiologic effect of
changes in pH is on protein function.
Since the cells are the functioning units
in the body, it is the intracellular pH that
is of primary importance, yet it is only the
extracellular (plasma) pH that can be
easily measured in patients.
Fortunately, this still permits an accurate
assessment of acid-base status,
because of the direct relationship
between these two parameters.
26. Minimal pH changes have dramatic
effects on normal cell function
◦ 1) Changes in excitability of nerve and
muscle cells.
◦ 2) Influences enzyme activity and
hormones.
◦ 3) Influences electrolyte levels.
◦ 4) Affect delivery of oxygen to the cell
◦ 5) Chronic, mild derangements in acid-
base status may interfere with normal
growth and development. 26
27. 1-CHANGES IN CELL
EXCITABILITY
pH decrease (more acidic) depresses
the central nervous system
◦ Can lead to loss of consciousness
pH increase (more basic) can cause
over-excitability
◦ Tingling sensations, nervousness,
muscle twitches
27
28. 2-INFLUENCES ON ENZYME
ACTIVITY
pH increases or decreases can alter the
shape of the enzyme rendering it non-
functional
Changes in enzyme structure can result in
accelerated or depressed metabolic actions
within the cell
28
29. 3-INFLUENCES ON ELECTROLYTE
LEVELS
When reabsorbing Na+ from the filtrate of the
renal tubules K+ or H+ is secreted
(exchanged)
Normally K+ is
secreted in much
greater amounts
than H+
29
K+
K+K+K+K+K+K+
Na+Na+Na+Na+Na+Na+
H+
30. If H+ concentrations are high (acidosis) than
H+ is secreted in greater amounts
This leaves less K+ than usual excreted
The resultant K+ retention can affect cardiac
function and other systems
Acidosis also shift K+ from intracellular to
extra.
Alkalosis decrease the level of ionized
Calcium and can cause signs of
hypocalcemia inspite of normal total serum
calcium level.
30
K+K+K+
Na+Na+Na+Na+Na+Na+
H+H+H+H+H+H+H+
K+K+K+K+K+
32. Acid base imbalance
Normal ratio of HCO3
- to H2CO3 is 20:1
Deviations from this ratio are used to identify
Acid-Base imbalances witch is primarily
concerned with two ions:
◦ Hydrogen (H+)
◦ Bicarbonate (HCO3
- )
32
BASE ACID
H2CO3
H+
HCO3
-
33. Definitions
Acid is substance containing one or more
H+ ions (protons)that can be liberated into
solution.
Two types of acids are formed by metabolic
processes
◦ Volatile acids: liquid ↔ gas. CO2 eliminated by lungs.
CO2 + H2O ↔H2CO3 ↔ H+ + HCO3
-
◦ Nonvolatile or fixed acids: cannot be converted to a gas
and subsequently must be converted or eliminated by the
kidneys
Examples: SO4, PO4, lactic acid, ketoacids
The non-volatile portion is trivial when compared to the
volatile H2co3.
34. ACIDS
Physiologically important acids include:
◦ Carbonic acid (H2CO3)
◦ Phosphoric acid (H3PO4)
◦ Pyruvic acid (C3H4O3)
◦ Lactic acid (C3H6O3)
These acids are dissolved in body fluids
34
Lactic acid
Pyruvic acid
Phosphoric acid
35. Definitions
BASE is substance that can capture or
combine with hydrogen ions to form a
salt
A proton acceptor
Example: HCO3
- (bicarbonate)
39. Definitions
Acidosis is a pathological process that causes
an inecrease in H+ ion concentration.
A decrease in a normal 20:1 base to
acid ratio
◦ An increase in the number of
hydrogen ions
(ex: ratio of 20:2 translated to 10:1)
◦ A decrease in the number of bicarbonate ions
(ex: ratio of 10:1)
Caused by too much acid or too little base
39
ACID BASE
40. The 3 principal sources of
hydrogen ions are:
1) dietary protein metabolism
2) incomplete metabolism of
carbohydrates and fat; Incomplete
glucose metabolism can produce
lactic acid, and incomplete
triglyceride metabolism can
produce keto acids.
3) stool losses of bicarbonate, for
each bicarbonate molecule lost in 40
42. Definitions
Alkalosis is a pathological process that
causes a decrease in H+ ion concentration.
An increase in the normal 20:1 base to acid
ratio
◦ A decrease in the number of hydrogen ions
(ex: ratio of 20:0.5 translated to 40:1)
◦ An increase in the number of bicarbonate
ions (ex: ratio of 40:1)
Caused by base excess or acid deficit
42
ACID BASE
43. Acidemia & Alkalemia
indicated the blood PH
abnormality
Acidosis & Alkalosis indicate
the pathological process that
is taking place
44. acidemia is always
accompanied by an acidosis,
but a patient can have an
acidosis and a low, normal,
or high pH.
For example, a patient may have a
mild metabolic acidosis but a
simultaneous, severe respiratory
alkalosis; the net result may be
alkalemia.
46. Definitions
The base excess is defined as the
base that must be added to restore a normal pH
Because the base excess is a calculated (not a
measured) value, it may be inaccurate and
misleading. Despite these problems it is important
to understand the concept.
It is a calculated figure which provides an estimate
of the metabolic component of the acid-base
balance.
Calculated by Siggaard-Anderson equation:
B.E. = 0.9287 [HCO3 - 24.4 + 14.83 (pH - 7.4)]
Normal Range: -4 to +4 meq/L
47. When interpreting blood gas results the following
heuristic is useful:
a base excess > +4 = metabolic alkalosis
a base excess < -4 = metabolic acidosis
Simple Logic Interpretation
Positive (Base Excess) Metabolic Alkalosis
Negative (Base Deficit) Metabolic Acidosis
In Severe Acidosis (Base Excess < -10 ) Calculate
Total Body Bicarbonate deficit Deficit =
(Base Deficit) x (Weight in kg) x 0.3
and administer 50% of bicarbonate deficit .
48. Definitions
•Standard base excessis the
amount of strong acid that must be added to
each liter of fully oxygenated blood to return the
pH to 7.40 at a temperature of 37°C and a pCO2
of 40 mmHg
•BE can be measured in the blood (BEb) or
extracelluar fluid (BEecf).
49. DEFINITIONS
Respiratory Acidosis
The primary change is an
increasing PCO2 due to not
promptly vented by the lungs
Metabolic Acidosis
The primary change in a decreasing
HCO3 occurs when a disorder
adds acid to the body or causes
alkali to be lost.
50. Definitions
• Respiratory Alkalosis
Occurs when the primary change is a
decreasing pCO2 due to
hyperventilation.
• Metabolic Alkalosis
Occurs when the primary disorder is an
increasing HCO3 due to acid is
excessively lost or alkali is excessively
retained.
51. Definitions
COMPENSATION
The normal response of
the respiratory system or
kidneys to change in pH induced
by a primary acid-base disorder.
Compensation means bringing
PH to normal, but not bringing
HCO3 or pCO2 to normal.
52. Definitions
SIMPLE VS. MIXED ACID-BASE
DISORDER
Simple acid-base disorder – a
single primary process of
acidosis or alkalosis
Mixed acid-base disorder –
presence of more than one acid
base disorder simultaneously
53. ACID-BASE REGULATION
Maintenance of an acceptable pH range in
the extracellular fluids is accomplished by
three mechanisms:
◦ 1) Chemical Buffers
React very rapidly
(seconds to minutes)
◦ 2) Respiratory Regulation
Reacts rapidly (minutes to hours)
◦ 3) Renal Regulation
Reacts slowly (hours to days)
53
55. 1) Buffering Systems in Body Fluids
Buffering systems provide an immediate
response to fluctuations in pH
A buffer is a combination of chemicals in
solution that resists any significant
change in pH
Able to bind or release free H+ ions
Chemical buffers are able to react
immediately (within milliseconds)
Chemical buffers are the first line of
defense for the body for fluctuations in
pH
57. There are four main buffer
systems in the body:
◦ Bicarbonate buffer system. (the MAIN
one) 64%
HCO3- + H+ H2CO3 H2O +CO2
◦ Hemoglobin buffer system. 29%
HbO2
- ↔ HHb
◦ Protein buffer system. 6%
Pr- ↔ HPr
◦ Phosphate buffer system. 1%
NaH2PO4 ↔ NaHPO4
58. 2-RESPIRATORY RESPONSE
◦ Carbon dioxide is an important by-product of
metabolism and is constantly produced by cells
◦ The blood carries carbon dioxide to the lungs
where it is exhaled
58
CO2CO2 CO2
CO2CO2
CO2
Cell
Metabolism
59. ◦ When breathing is increased,
the blood carbon dioxide level
decreases and the blood
becomes more Base
◦ When breathing is decreased,
the blood carbon dioxide level
increases and the blood becomes more Acidic
◦ By adjusting the speed and depth of breathing,
the respiratory control centers and lungs are able
to regulate the blood pH minute by minute
59
60. Respiratory Center
Neurons in the medulla oblongata and pons
constitute the Respiratory Center
Stimulation and limitation of respiratory rates
are controlled by the respiratory center
Control is
accomplished by
responding to CO2
and H+
concentrations in
the blood
60
61. Chemosenstive areas
Chemosensitive areas of the respiratory
center are able to detect blood concentration
levels of CO2 and H+
Increases in CO2 and H+ stimulate the
respiratory center
◦ The effect is to raise
respiration rates
But the effect
diminishes in minutes
61
CO2
CO
CO2
CO2
CO2
CO2
CO2
CO2
Click to increase CO2
62. The effect of stimulating the respiratory
centers by increased CO2 and H+ is
weakened in environmentally increased
CO2 levels
Symptoms may persist for several days
62
63. Chemoreceptors
Chemoreceptors are also present in the
carotid and aortic arteries which respond to
changes in partial pressures of O2 and CO2
or pH
Increased levels of
CO2 (low pH) or
decreased levels of
O2 stimulate
respiration rates
to increase
63
64. Overall compensatory response is:
◦ Hyperventilation in response to
increased CO2 or H+ (low pH)
◦ Hypoventilation in response to
decreased CO2 or H+ (high pH)
64
65. RESPIRATORY CONTROL OF pH
65
pH rises toward normal
rate and depth of breathing increase
CO2 eliminated in lungs
H+ stimulates respiratory center in medulla oblongata
H2CO3 H+ + HCO3
-
H+ acidosis; pH drops
CO2 + H2O H2CO3
cell production of CO2 increases
66. 3-Kidney Regulation
The kidneys have
some ability to
alter the amount of
acid or base that is
excreted, but this
generally takes
several days
66
67. The kidneys regulate the serum bicarbonate
concentration by modifying acid excretion in
the urine. This requires a 2-step process:
A-First, the renal tubules resorb the bicarbonate
that is filtered at the glomerulus.
1. Proximal tubule – 90%.
2. Distal tubule.
B-Second, there is tubular secretion of hydrogen
ions. 1. Free urinary H+ - minimal
contribution
2. Ammonia
3. Phosphorus
69. Rules of compensations
Compensatory responses are not
strong enough to keep the pH
constant (they do not correct the
acid-base derangement).
They only to limit the change in
pH that results from a primary
change in PCO2 or HCO3.
Compensation is never
overshooting.
71. 1-Compensation for Metabolic
Acidosis
The ventilatory response to a metabolic
acidosis will reduce the PaCO2 to a level that
is defined by:
Expected pCO2 = (1.5 × HCO3 ) + 8
± 2.
For example, if a metabolic acidosis results in
a serum HCO3 of 15 mEq/L, the expected
PaCO2 is (1.5 × 15) + 8 ± 2 = 30.5 ±2 - mm
72. If the measured PaCO2 is equivalent to the expected
PaCO2(28.5-32.5 in this example), then the
respiratory compensation is adequate, and the
condition is called a compensated metabolic
acidosis.
If the measured PaCO2 is higher than the expected
PaCO2 (>32.5 mm Hg in this example), the
respiratory compensation is not adequate, and there
is a respiratory acidosis in addition to the metabolic
acidosis. This acid-base disturbance is called a
primary metabolic acidosis with a superimposed
respiratory acidosis.
If the PCO2 is lower than expected (lower than 28.5
mm Hg in the example), there is a respiratory
alkalosis in addition to the compensated metabolic
73. expected
PaCO2 28.5 32.5 40 50
Compensated
metabolic
acidosis.
a primary metabolic acidosis
with a superimposed
respiratory acidosis
a primary metabolic acidosis
with a superimposed
respiratory alkalosis
75. 2-Compensation for Metabolic
Alkalosis
The ventilatory response to a metabolic
alkalosis will increase the PaCO2 to a level
that is defined by:
Expected pCO2 = (0.7 × HCO3 )
+ 21 ± 2.
For example, if a metabolic alkalosis
is associated with a plasma HCO3 of
40 mEq/L, the expected PCO2 is
(0.7 × 40) + 21 ± 2 = 49 ± 2 mm Hg.
76. If the measured PaCO2 is equivalent to the
expected PaCO2(47-51 in this example), then the
respiratory compensation is adequate, and the
condition is called a compensated metabolic
alkalosis.
If the measured PaCO2 is higher than the
expected PaCO2 (>51 mm Hg in this example),
the respiratory compensation is not adequate,
and there is a respiratory acidosis in addition to
the metabolic alkalosis. This condition is called a
primary metabolic alkalosis with a superimposed
respiratory acidosis.
If the PaCO2 is lower than expected(lower than
47 mm Hg in the example), there is an additional
respiratory alkalosis, and this condition is called a
primary metabolic alkalosis with a superimposed
77. expected
PaCO2 40 47 51
a
compensated
metabolic
alkalosis.
a primary metabolic alkalosis
with a superimposed
respiratory acidosis
a primary metabolic alkalosis
with a superimposed
respiratory alkalosis
78. Respiratory Acid-Base
Disorders
Because of the delay in renal
compensation, respiratory acid-base
disorders are classified as:
A-acute (before renal compensation
begins).
B- chronic (after renal compensation
is fully developed).
81. 3-Acute Respiratory Acid-Base
Disorders
Prior to the onset of renal compensation, a
change in PaCO2 of 1 mm Hg will produce a
change in pH of 0.008 pH units.
∆ pH = 0.008 × ∆ PaCO2 .
This relationship is incorporated into
Equation using 7.40 for the normal pH and
40 mm Hg for the normal PaCO2. This
equation then defines the expected pH for
an acute respiratory acidosis:
Expected PH = 7.4 - 0.008 × (CO2-
82. pHCO2+H20=H2CO3 = H + HCO3
+
HCO3HCO3
RESP. ACIDOSIS ALKALOSIS META.
ACUTE RISE : PCO2 10 : pH .08
CHRONIC RISE : PCO2 10 : pH .03
PCO2
HIGH
H
HIGH
HCO3
+
83. The expected arterial pH for an acute
respiratory alkalosis can be described in
the same manner using:
Expected PH = 7.4 + 0.008 × (40-
CO2).
For example, starting with a normal pH
of 7.40, an acute increase in PaCO2
from 40 to 60 mm Hg is expected to
result in an arterial pH of [7.40 - (0.008 ×
20)] 7.24 pH units, and a sudden drop in
PaCO2 from 40 to 25 mm Hg is
expected to result in an arterial pH
of[7.40 + (0.008 × 15)] 7.56 pH units.
84. CO2 + H20 = H2CO3 = H + HCO3+
pH
SERUM
HCO3LOW H IONS
…LOW HCO3
RESP. ALK. ACID. META.
CO2
+
Bicarbonate
85. 4-Chronic Respiratory Acid-
Base Disorders
When the compensatory response in the
kidneys is fully developed, the arterial pH
changes only 0.003 pH units for every 1
mm Hg change in PaCO2:
∆ pH = 0.003 × ∆ PaCO2.
This relationship is incorporated into
Equation using 7.40 as a normal arterial pH
and 40 mm Hg as a normal PaCO2.
86. This equation describes the expected
change in pH for a chronic (compensated)
respiratory acidosis:
Expected PH = 7.4 - 0.003 × (CO2-
40 ).
The expected arterial pH for a chronic
(compensated) respiratory alkalosis is
described in a similar fashion:
Expected PH = 7.4 + 0.003 × (40-
CO2).
87. For example, a patient with BPD and chronic
CO2 retention who usually has a PaCO2 of
60 mm Hg is expected to have the following
arterial pH (from Equation: 7.40 - (0.003 × 20)
= 7.34 pH units.
The expected pH for an acute rise in PaCO2
to 60 mm Hg (from Equation is: 7.40 - (0.008
× 20) = 7.24 pH units.
Therefore, the renal compensation for an
acute rise in PaCO2 to 60 mm Hg is expected
to increase the arterial pH by 0.1 pH units.
88. Compare the measured pH
to the expected pH to
determine if the condition is
acute, partially
compensated, or fully
compensated.
For respiratory acidosis, if the
measured pH is lower than the
expected pH (7.24)for the acute,
uncompensated condition, there is a
superimposed metabolic acidosis.
89. pH scale
7.24 7.34 7.4 7.5
partially
Compensated
a primary respiratory acidosis
with a superimposed
Metabolic alkalosis
a primary respiratory acidosis
with a superimposed metabolic
acidosis
acute chronic
90. And if the measured pH(7.34) is higher
than the expected pH for the chronic,
compensated condition, there is a
superimposed metabolic alkalosis.
For respiratory alkalosis, if the
measured pH is higher than the
expected pH for the acute,
uncompensated condition, there is a
superimposed metabolic alkalosis.
And if the measured pH is below the
expected pH for the chronic,
compensated condition, there is a
superimposed metabolic acidosis.
91. COMPENSIONLIMITS
Metabolic Acidosis
PaCO2 = up to 10
Metabolic Alkalosis
PaCO2 = maximum 6O
Respiratory Acidosis
Bicarb = maximum 40
Respiratory Alkalosis
Bicarb = up to 10
