Acid Base Balance and Primary Disturbances - basic concepts

Acid-base Balance
Remember pH α [HCo3
-
]
PCO2
Acidosis 7.35-7.45 Alkalosis
Respiratory acid component
PCO2
Metabolic alkaline component
HCO3
-
victor.nwai@gmail.com
2013

Learning outcomes
1. Define acid, base, buffer, acidaemia vs acidosis; alkalaemia vs
alkalosis.
2. Explain why the arterial pH needs to be maintained within a narrow
range
3. List the buffer systems available in the human body.
4. Describe the interrelationships between the pH, the PCO2 of the
blood, and the plasma bicarbonate concentration, and state the
Henderson-Hasselbalch equation.
5. Explain how the Henderson-Hasselbalch equation for
bicarbonate/carbonic acid buffer system plays a crucial role in
explaining the primary acid base disorders and the respective
compensatory responses
6. State the role of the buffer system, the respiratory system and
the kidneys in maintaining acid base balance and describe the
mechanism of each in H+
ion homeostasis
7. State the potential causes of respiratory acidosis and alkalosis and
metabolic acidosis and alkalosis, and deduce the effects of
acidosis and alkalosis on body functions
8. Read Davenport diagrams for four primary disturbances and
respective compensations

Focus on the Acid and H+
ions.
Forget the threat of base (alkali)
• It’s the acids that are threatening us all the
time
– there is continuous metabolic production of
• CO2 (becomes a volatile acid, H2CO3
-
,when
dissolved)
• nonvolatile or fixed acids (mainly from protein
metabolism)
• Forget the bases. Their threat is negligible
compared with that of acids.

Where is the threat coming from?
Endogenous
• CO2 transport from tissues to lungs:
– Dissolved carbonic acid is buffered in the plasma by
plasma proteins, and in the RBC by haemoglobin
(“Physiological buffering”)
• Lactic acid production by hypoxic muscle cells
• Ketoacid production by liver (in diabetes)
• Retention of CO2 and carbonic acid in
hypoventilation and H+
ions in renal failure
Exogenous :
food rich in acids (meat), ingestion of acids
(salicylic acid, NH4Cl); intravenous infusion

Summary: Gain or loss of H+ ions
H+
sources/gain:
Metabolic production
(CO2= 12,500 mEq/d)
(H2SO4, H3PO4= 50 mEq/d)
Extra acid loads
Ketone bodies (diabetes mellitus);
ingestion of acidifying salts or aspirin
lactic acidosis (exercise, hypoxia)
Failure to excrete:
respiratory/renal failure
Loss of alkali (bicarbonate):
diarrhoea
Base gain
Ingestion (vegetables, NaHCO3,
antacids)
Infusion
H+
loss
vomiting (loss of HCl)
Hyperventilation (CO2 wash-out)
Primary aldosteronism

It’s the H+
ion and not the acid per se
that is deadly
• Physiologically, acid as such is quite harmless in
the internal environment (it’s just a small
molecule in the vast internal sea of body fluids)
• Only when an acid dissociates and liberates
H+
ions, does it become deadly

H+
ions are deadly. Why?
• Because H+
ions can affect the cell function
by altering the charge of functional
proteins including enzymes
– H+
ions are very reactive cations,
– Proteins are anions (carry –ve charge) at body
pH
– H+ ions at higher concentrations can bind
strongly to negatively charged proteins,
including enzymes, and impair their activity
and hence the cell function

Cell function
Chemical reactions
Activity of enzymes
Temperature pH [H+
conc.]
Other factors
Acidosis
Cell function
depressed
Alkalosis
Cell function
depressed
Optimal pH
= 7.4pH = -log10[H+
]
Note the inverse relationship

7.00 7.36 7.4 7.44 7.7
100 44 40 36 20
Plasma pH
[H+
] nmol/L
Normal range
Extreme
Acidosis
Extreme
Alkalosis

7.00 7.36 7.4 7.44 7.7
100 44 40 36 20
Plasma pH
[H+
] nmol/L
Normal range

What then is Acid BaseWhat then is Acid Base
Balance?Balance?
• Acid-base balance is the maintenance within a
relatively narrow range of the H+
concentration in the
extracellular fluid. i.e. H+
ion homeostasis.
• This is both a formidable and a critical physiologic
function--formidable because the body must deal with
and defend itself against about 15,000 meq of organic
acid each day and critical because the H+
concentration in the extracellular fluid compatible with
life covers a relatively narrow range, from about a pH
of 7.0 to about 7.7.

Why control pH or [H+
]?
• Metabolic reactions are highly sensitive to
changes in pH due to its effect on protein
conformation and biological activity e.g.
enzyme activity

• Acid
Substance that
contains H+
ions
that can be
released
Carbonic acid
(H2CO3) releases H+
ions
• Base
Substance that
can accept H+
ions
Bicarbonate
(HCO3
-
accepts H+
ions
The stronger the acid,
the greater it
dissociates into H+
ions

H2CO3
-
CO2 + H2O
In a reversible reaction, the concentration of the
reactants on either side of the equation
determines the direction of the reaction
( The Law of Mass Action )
H2CO3
-
CO2 + H2O
H2CO3
-
CO2 + H2O
H2CO3
-
CO2 + H2O
H2CO3
-
CO2 + H2O
Reaction stops when the
concentrations of the reactants
on either side become equal

Buffering
• All buffers are weak acids or bases
• Buffers limit change in hydrogen ion
concentration (and so pH) when
hydrogen ions are added or removed
from the solution.
•A buffer is like a sponge. When
hydrogen ions are in excess, the
sponge mops up the extra ions. When
in short supply, the sponge can be
squeezed out to release more
hydrogen ions!
H+
H+
H+
H+
are tied up in
undissociated HA
molecule

Weaker acid buffers the stronger acid
• H2SO4 and other strong acids are buffered by H2CO3
• H2CO3 is buffered (during CO2 transport in blood) by
– plasma proteins (HPr-
) in the plasma
– Haemoglobin (HHb-
) in RBCs so that RBC function may
not be impaired
• Of course plasma proteins (HPr-
) and haemoglobin
(HHb-
) can also buffer acids stronger than H2CO3

Weaker acid buffers the stronger acid
Physiological
buffering

Principal Buffers in Body Fluids
Blood H2
CO3
H⇆ +
+ HCO3
–
HProt H⇆ +
+ Prot–
HHb H⇆ +
+ Hb–
Interstitial fluid H2
CO3
H⇆ +
+ HCO3
–
Intracellular fluid HProt H⇆ +
+ Prot–
H2
PO4
–
H⇆ +
+ HPO4
2–

Buffer Systems
• Bicarbonate buffer - most important
Active in ECF and intracellular fluid ICF
• Phosphate buffer
Active in (ICF)
• Protein buffer - Largest buffer store
Albumins and globulins (ECF)
Hemoglobin and protein anions in tissue
cells(ICF)

The blood buffers
1. Carbonic acid/bicarbonate system
2. Oxyhaemoglobin/deoxyhaemoglobin
system
3. Plasma protein system
4. Monosodium phosphate/ disodium
phosphate system
53%
35%
7%

Henderson-Hesselbalch equation
pH = 6.1 + log [HCO3-
]
0.03 x pCO2
pH = pK + log [salt]/ [acid]
CO2 + H2O → H2CO3 → H+
+
HCO3
-
= 6.1 + log [ HCO3
-
]
[HHCO3]
= 6.1 + 1.3
= 7.4
= 6.1 + log [20/1]
Regulated by
kidneys
Regulated by lungs
pK = ionization
constant
24 mEq/L
1.2 mEq/L

• Since pH is determined by a ratio of HCO3
-
to PaCO2,
the Henderson-Hasselbalch equation may be
conveniently reduced for clinical use to
• The kidneys are responsible for maintaining HCO3-,
and the lungs are responsible for maintaining PaCO2 .
Thus

Carbonic acid / bicarbonate system

Bicarbonate-Carbonic Acid
• Body’s major buffer
• Carbonic acid - H2CO3 (Acid)
• Bicarbonate - HCO3
-
(Base)
1 20
pH = 7.4
H2CO3 ……………… HCO3
24 mEq/L1.2 mEq/L

Bicarbonate-Carbonic Acid
• Ratio important
• Not absolute values
• Person with COPD
1 20
7.4
H2CO3 ……………… HCO3
48 mEq/L2.4 mEq/L

The 3 major homeostatic mechanisms
maintain acid-base balance:
• Buffering by extracellular and
intracellular buffers - 1st
line
emergency defence (rapid)
• Lungs: Alveolar ventilation, which
controls PaCO2 (and increases
efficiency of H2CO3
-
/NaHCO3
-
buffer
system)
• Renal H+
excretion, which controls
plasma [HCO3
-
] (and conserves Na+
and excretes anion of the
H2CO3…..HCO3

acid production in cells
e.g. lactic acid production in
hypoxic muscle cells
Not due to respiratory(ventilatory)
cause Nonrespiratory or
Metabolic Acidosis
Intracellular buffers in the muscles
try to reduce the intracellular pH
changes
Then extracellular buffers in ISF
and blood will act

Intracellular or tissue buffers
• Proteins
• Phosphates
• Carbonic acid/KHCO3 buffer
• Bone : hydration shell of
hydroxyapatite crystals

H+H2CO3
-
HCO3
-
+CO2 +H2O
The Key
Reaction
Remember:
The Law of Mass Action

H+H2CO3
-
HCO3
-
+CO2 +H2O
When nonvolatile
acid , H+
is buffered by HCO3
- HA  H+
+ A-

H+H2CO3
-
HCO3
-
+CO2 +H2O
When nonvolatile
acid , H+
is buffered by HCO3
- HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Buffer pair

H+H2CO3
-
HCO3
-
+CO2 +H2O
When nonvolatile
acid , H+
is buffered by HCO3
- HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
HCO3
-Metabolic acidosis

H+H2CO3
-
HCO3
-
+CO2 +H2O
When HCO3
-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Metabolic alkalosis H+

H+H2CO3
-
HCO3
-
+CO2 +H2O
PaCO2
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Respiratory alkalosis H+
Hyperventilation:

H+H2CO3
-
HCO3
-
+CO2 +H2O
PaCO2
HCO3
-
Respiratory acidosis H+
Hypoventilation:

H+H2CO3
-
HCO3
-
+CO2 +H2O
HA  H+
+ A-
NaHCO3
-
 Na+ + HCO3
-
replenishes
Metabolic acidosis
HCO3
-

H+H2CO3
-
HCO3
-
+CO2 +H2O
HA  H+
+ A-
NaHCO3
-
 Na+ + HCO3
-
replenishes
Respiratory centre in
medullaHyperventilation
washoutCO2
arterial chemoreceptors
HCO3
-

H+H2CO3
-
HCO3
-
+CO2 +H2O
HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Hyperventilation
washoutCO2
medulla
HCO3
-PaCO2

H+H2CO3
-
HCO3
-
+CO2 +H2O
HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Hyperventilation
washoutCO2
medulla
Continued buffering

Respiratory Control of
plasma[H+
]
The respiratory center in the medulla oblongata,
through chemoreceptors, is sensitive to blood
levels of pCO2 and [H+
].
 When plasma [H+
] rises, the respiratory centre activity
increases
 The resultant hyperventilation increases CO2
excretion (washout)
 The fall in PCO2 shifts the reaction to the left,
facilitating the buffering power of the H2CO3/NaHCO3
system

Role of Respiratory
System in Regulation of pH

H+H2CO3
-
HCO3
-
+CO2 +H2O
When H+
it is buffered by
HCO3
-
HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
NaA
Na+
, the cation of NaHCO3 (buffer) should be conserved;
the anion A-
of offending acid should be eliminated

CO2 [H+
]
CO2 [H+
] [H+
]
[H+
] secretion by renal
tubular cells
Plasma [H+
] as such is not taken
up by the renal tubular cells; it is in
the form of CO2 which the tubular
cells take up and convert back to
[H+
] and secreted

Filtered
CO2
Secretion of H+
by

Distal
nephron
ATPase
K+
HCO3
-
regeneration
Proton
pump
Almost all HCO3
–
has
been reabsorbed in
proximal tubule
CO2

Renal handling of acid
• Excretion of the daily acid load (50-100 mEq of H+
)
occurs principally through H+
secretion by the apical
proton pump (H+
-K+
-ATPase) in A-type intercalated
cells of the collecting duct.
• Hydrogen ions secreted by the kidneys can be
excreted as free ions but, at the lowest achievable
urine pH of 4.5, would require excretion of 5000-
10,000 L of urine a day.
• Urine pH cannot be lowered much below 4.5
because the gradient against which H+
-ATPase has
to pump protons (intracellular pH 7.5 to luminal pH
4.5) becomes too steep.
The “limiting pH” = 4.5

Distal
nephron
ATPase
K+
Proton
pump
CO2
pH 7.3 pH 4.5
The “limiting pH”

The role of Urinary buffers
• By binding or transforming secreted [H+
],
keep the tubular fluid [H+
] low
• limiting pH 4.5 is not reached
• So that proton pump can continue
secreting [H+
] ions
• Help in renal secretion of H+

Accumulation of nonvolatile acids and
the subsequent depleting effect on
HCO3
-
content can be offset only by
the renal ability to
exchange sodium ions for hydrogen
ions and
the production of an acid urine.
Renal Control of Acid-Base
Balance
Final correction but takes time

Renal Control of Acid-Base Balance
As nonvolatile acid anions are filtered, they are
accompanied by an equivalent number of
cations (e.g., Na+
) (maintenance of electrical
neutrality).
Through the activity of carbonic anhydrase,
renal tubule cells combine CO2 (from their
own metabolic activities) with water to make
H2CO3 which dissociates to H+
and HCO3
-
ions.

The [H+
] ions pass into the tubule and an
equivalent amount of Na+
is returned
accompanied by an equivalent amount of HCO3
-
thus,
Buffer cations (Na+
) are conserved
HCO3
-
ions are replaced (replenished),
– [H+
] ions are excreted and acid urine is
produced.
– nonvolatile acid anions are excreted

H+H2CO3
-
HCO3
-
+CO2 +H2O
When H+
it is buffered by
HCO3
-
HA  H+
+ A-
NaHCO3
-
 Na+
+ HCO3
-
replenishes
Na+
A-
H+ A-

The overall effect:
restoration of the blood bicarbonate ion:
carbonic acid ratio with a resultant
correction of pH.
and final elimination of the offending acid
(HA) from the body
pH = 6.1 + log [HCO3-
]
0.03 x pCO2
Regulated by
kidneys

Definitions of Acid-base Terms
• Disorders in the Blood
Acidemia. A low blood pH (less than 7.36)
Alkalemia. A high blood pH (greater than 7.44)
Hypocapnia. A low PaCO2 (less than 36 mm Hg)
Hypercapnia. A high PaCO2 (greater than 44 mm Hg)
• Disorders in the Patient
Metabolic acidosis. A primary disorder that causes a decrease in
the plasma bicarbonate and lowers the blood pH.
Metabolic alkalosis. A primary disorder that causes an increase in
the serum bicarbonate and, raises the blood pH.
Respiratory acidosis. A primary disorder that leads to an
increased PaCO2 and, lowers the blood pH.
Respiratory alkalosis. A primary disorder process that leads to a
decreased PaCO2 and raises the blood pH.
Compensatory process. Not a primary acid-base disorder, but a
change that follows a primary disorder. A compensatory process
attempts to restore the blood pH to normal and is not appropriately
termed acidosis or alkalosis.

Acidosis
• Acidosis- any situation in which the H+
concentration of arterial plasma is elevated.
• (a) Respiratory acidosis- respiratory system fails
to eliminate CO2 as fast as it is produced.
Hallmark is an elevation in arterial pCO2 and H+
.
Causes include lung damage and hypoventilation
• (b) Metabolic acidosis- all situations where the
primary problem is other than respiratory e.g.
– excessive production of lactic acid (exercise/hypoxia),
– production of ketone bodies (diabetes/fasting)
– Retention of H+
in renal failure
– loss of bicarbonate through diarrhea.

Alkalosis
• Alkalosis- any situation resulting in a reduction in
arterial H
+
concentration
• Two categories: (a) Respiratory alkalosis- occurs
when respiratory system eliminates CO2 faster
than it is produced. Hallmark is a reduction in
pCO2 and H+
concentration.
• (b) Metabolic alkalosis- other than respiratory-
based lowering of arterial H
+
concentration eg
persistent vomiting  loss of H
+
from gastric HCl

Primary event and compensatory response for acid-base disorders
Acid-base disorder Primary event (disorder)
Compensatory (physiologic)
response
Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis
Respiratory alkalosis
hyperventilation
hypoventilation
Increased renal bicarb. reabsorption
decreased renal bicarb. reabsorption
lesser fall in pH
lesser rise in pH
lesser rise in pH
lesser fall in pH

In compensated acidosis or alkalosis,
absolute concentrations of bicarbonate
ions and carbonic acid may be changed,
but as long as the ratio remains
in the range of approximately
20:1, the pH may be in the
normal range.

Graphic
versions
(Davenport
graphs)
• The blood-buffer line, shown above,
illustrates the changes in pH and
bicarbonate of normal blood that occur
when PCO2 is varied.

Note: the primary disorder as well as the compensatory mechanism
produces the changes in plasma HCO3
-
in the same direction
Respiratory acidosis and renal compensation
since CO2 + H2O → H2CO3 → H+
+ HCO3
-
since kidney reabsorbs more HCO3
-
as
more CO2 is available to tubular cells

Note: the primary disorder as well as the compensatory mechanism
produces the changes in plasma HCO3
-
in the same direction
Respiratory acidosis
and alkalosis
You should be able to work out for
the other 3 acid-base disturbances
Metabolic acidosis and
alkalosis

Partial pressures of CO2
Respiratory
responses occur
along this axis as
the pH will be
inversely related to
the lungs ability to
eliminate CO2

Analysis of simple acid base disorders and how they are compensated for by the body.

Acid Base Balance and Primary Disturbances - basic concepts

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