ACID-BASE

BALANCE
Dr. Kenneth O. Inaku FMCPath
Lecturer/Consultant Chemical Pathologist
University of Calabar/University of Calabar Teaching Hospital
 Introduction
• Metabolic processes in the body lead to the
production of hydrogen ions
• They include substrate, by-products and end-
products of intermediary metabolism
• Also included are some therapeutic drugs and
xenobiotics
• If left to accumulate they will be injurious to
the body halting all metabolic processes
 Introduction
• The body is endowed with mechanisms that
regulate hydrogen ions [H+] and get rid of excess
acids
• In health, [H+] in various body fluids is kept within a
narrow range of approximately 36-44 nmol/L (pH
7.35-7.45) by important regulatory mechanisms
• Excessive production of acids or bases and/or
disorders of the regulatory systems lead to
acid/base disorders
 Definition of Terms
ACID
Any substance that can yield a hydrogen ion (H+)
or hydronium ion when dissolved in water
Release a proton as the only positive ion
Strong acids have little affinity for H+ and therefore
can readily give up H+ (e.g H2SO4, HCL)
Weak acids have high affinity for H+ and slowly
gives up same (e.g H2CO3 and most organic acids)
 Definition of Terms
BASE
Substance that can yield hydroxyl ions (OH-)
Accept protons of H+ ions
A strong base has high affinity for H+ and readily
accepts same
A weak base has low affinity for H+ and less readily
accepts same
 Definition of Terms
• Conjugate Base
– This is the dissociated anion of an acid
– An acid dissociates to give up H+ and a conjugate base
– Acid H+ + Conjugate Base
Example: H2CO3 (carbonic acid) dissociates thus:
H2CO3 H+ + HCO3- (strong base)
H2SO4 2H+ + SO4- (weak base)
The conjugate base of a weak acid is a strong base and
vice versa
 Definition of Terms
pK/pKa
Negative log of the ionization constant of an acid
The pK is the pH at which an acid is half dissociated,
existing as equal proportions of acid and conjugate base
Strong acids would have a pK <3
Strong bases would have a pK >9
pH
Negative log of the hydrogen ion concentration
pH = pK + log ([base]/[acid])
Represents the hydrogen ion concentration
 Definition of Terms
BUFFERS
A combination of a weak acid and/or a weak base
and its salt

What does it do
Resists changes in pH

Effectiveness depends on
pK of buffering system
pH of environment in which it is placed
 Definition of Terms
ACIDAEMIA
An arterial blood pH <7.35
ALKALAEMIA
An arterial blood pH >7.45
ACIDOSIS and ALKALOSIS refer to pathological
states that lead to acidaemia and alkalaemia

Note: Normal blood pH is 7.35 - 7.45

 Definition of Terms
• ACIDOSIS
– A clinical and pathological state associated with
acidaemia
– Results from accumulation of acids in the blood or
loss of base from the body
Acidosis = Pathology + Acidaemia + Clinical manifestations
E.g:
◦ DKA ◦ Alcoholic ketoacidosis
◦ Lactic acidosis ◦ Organic acidosis
 Definition of Terms
• ALKALOSIS
– Clinical and pathological state associated with
alkalaemia
– Results from accumulation of base (alkali) in the
blood or loss of acid from the body
Alkalosis = Pathology + Alkalemia + Clinical manifestations
Examples:
◊ Milk alkali syndrome
◊ Hypochloremic alkalosis
 Roles of Buffer systems
• The body’s first line of defence against extreme changes
in H+ conc. is the buffer systems present in all body fluids
• Generally all buffers consists of a weak acid and its
conjugate base
• Example, for the bicarbonate-carbonic acid buffer system,
the acid is H2CO3 and its salt or conjugate base is HCO3-
• Generally, buffers work best in the interval of ±1 pH unit
of its pK
• They are also more effective at higher concentrations
 Physiological Buffers
• They are named based on the names of their
conjugate bases
• Examples
– H2CO3/HCO3- Bicarbonate buffer
– NH4+/NH3- Ammonia buffer
– HHb/Hb- Haemoglobin buffer
– H2PO4-/HPO4- Phosphate buffer
 Physiological Buffers
Acid Proton Conjugate Buffer pair
Base
HA H+ A‑ HA/A-
H2CO3 H+ HCO3- H2CO3/ HCO3-

NH4+ H+ NH3 NH4+/ NH3

HHb H+ Hb- HHb/ Hb-
H2PO4- H+ HPO42- H2PO4-/
HPO42-
HPr H+ Pr- HPr/ Pr-
 Physiological Buffers
S/N Extracellular Intracellular Erythrocyte
fluid fluid fluid

1. NaHCO3 K2HPO4 K+Hb

H2CO3 KH2PO4 H+Hb
[Haemoglobin]
[Bicarbonate] [Phosphate]
2. Na2HPO4 K Protein
+
K2HPO4
NaH2PO4 H+Protein KH2PO4
[Protein buffer]
[Phosphate] [Phosphate]
3. Na Albumin
+
KHCO3 KHCO3
H+Albumin H2CO3 H2CO3
[Protein buffer]
[Bicarbonate] [Bicarbonate]
 Henderson/Hasselbalch Equation
• It expresses the relationship between pH and a
buffer pair
• In aqueous solution the pH is determined by the
concentration ratio of the acid and its conjugate
base
pH = pK + Log Conjugate base
Acid
pH = pK + Log A-
HA
 Bicarbonate/Carbonic Acid Buffer
• The most important buffer in plasma
• Has a pK of 6.1
• Ratio of base to acid is ≈20:1
• Its effectiveness is based on:
– its high concentration in plasma (>20 mmol/L)
– the ease with which the lungs dispose of or retain CO2
– The ease with which the renal tubules can increase
and decrease the rate of reclamation of bicarbonate
from the glomerular filtrate
 Haemoglobin Buffer
• This is the second most important blood buffer
for the following reasons
– Each Hb molecule contains 38 histidine residues
that are able to bind H+
– The imidazole groups of these histidine residues are
responsible for the buffering capacity of Hb
– It has a pK of 7.2 (close to the pH of plasma 7.4)
– There is high concentration of Hb (approx 140 g/L)
in an adult male
– Its a major component of non bicarbonate buffers
within ICF of RBC
 Phosphate Buffer
• Present in the ECF, ICF, and urinary buffer
• At the physiological plasma pH of 7.4, the ratio of
[HPO42-]/[H2PO4-] is approximately 4:1 or 4/1.
• The pK value for the PO4 buffer system is 6.8.
• Total concentration of PO4 buffer system in RBC & plasma is
far less than those of other major blood buffers
• PO4 buffer system consists of approximately 5% of non-
bicarbonate buffer value of plasma.
• However, organic PO4 in the form of 2,3-DPG is present at a
concentration of approximately 4.5mmol/L within RBCs and
accounts for 16% of nonbiocarbonate buffer value of
erythrocyte fluid
 Ammonia Buffer
• A prominent urinary buffer
• Non-existent in blood and ICF
• It has a pK of 9.8
• It dissociates as follows
NH4+ H+ + NH3

The Henderson Hasselbalch equation is

pH = 9.8 + log [NH3]
[NH4+]
 Regulation of Acid-Base Balance
Control of CO2 is by the lungs
 The lungs participates in the maintenance of H+ ion
when:
• Inspired oxygen is carried from the lungs to tissue by
haemoglobin
• The tissue (cells) use the oxygen for aerobic metabolism
and release CO2
• CO2 diffuses along a concentration gradient from the
cells into the extracellular fluid and is returned by the
blood to the lungs where it is eliminated in the expired
air
 Regulation of Acid-Base Balance
• The RBC contributes to the regulation of ABB by:
- by harbouring the Hb buffer system (an important blood buffer)
- by generation of bicarbonate.
• Hb buffer system works in conjunction with the HCO3- buffer system.
• The RBC under normal condition produces only small amount of CO2
from anaerobic glycolysis
• In most cases, plasma CO2 diffuses into RBC ICF where it reacts with
water to form H2CO3-. The H2CO3-dissociates into H+ and HCO3-
• The H+ is buffered by the Hb buffer system.
• The HCO3- diffuses into the plasma.
• In order to maintain electroneutrality, Cl- diffuses in the opposite
direction (Chloride shift).
 Regulation of Acid-Base Balance
HCO3- Generation by Erythrocytes
Chloride shift

Red Cell
 Regulation of Acid-Base Balance
Role of the Kidneys
• The kidneys play significant roles in the control of ABB
• They control the metabolic component of ABB
• They help in the maintenance of ABB via the following mechanisms:
-Na+/H+ exchanger system
-HCO3- Reclamation (HCO3- Reabsorption)
-HCO3- Regeneration (HCO3- Generation).
-Excretion of H+ as H2PO4 (Urinary PO4 Buffer)
-Excretion of H+ as NH4+ (Urinary Ammonia
Buffer)
-Excretion of other nonvolatile acids.
 Regulation of Acid-Base Balance
Bicarbonate Reclamation by the Kidneys
• Simply the reabsorption of filtered HCO3-
• Helps to maintain a steady state of ABB
• Associated with no net loss of H+
• No net loss of HCO3-
• A self-perpetuating cycle
• Helps to reclaim and maintain the buffering capacity
of HCO3-
• Lacks the capacity to correct acidosis.
 Regulation of Acid-Base Balance
Bicarbonate Reabsorption by the Kidneys

Result: No net gain of

HCO3, Most useful in
steady state
 Regulation of Acid-Base Balance
Bicarbonate Regeneration by the Kidneys
• Involves the de novo generation of HCO3- by the renal
tubular cells.
• There is net generation of HCO3-
• There is net loss of H+ as HB (B represents a non-
bicarbonate anion)
• The HCO3- is produced from cellular CO2.
• A well-positioned mechanism for correction of
acidosis.
 Regulation of Acid-Base Balance
HCO3- Generation by the Kidneys

There is net gain of HCO3

 Regulation of Acid-Base Balance
• The phosphate buffer is relatively the most important buffer in
urine.
• This is because its pK of 6.8 is close to pH of glomerular filtrate.
• Also, phosphate concentration in tubular fluid increases to
approximately 25mmol/L as water is being reabsorbed along the
renal tubules.
• As urine pH decreases with increase in [H+] secretion, most
filtered phosphate combine with it to form H2PO4- .
• This represents the buffer action of PO4- buffer system in urine.
• There is net gain of HCO3-
• There is net loss of H+.
Regulation of Acid-Base Balance
Excretion of Hydrogen Ion as H2PO4-
(Urinary Phosphate Buffer)
 Regulation of Acid-Base Balance
• The ammonia buffer system seems to be the final mechanism
of buffering H+ secreted into renal tubular lumen.
• It tends to enhance H+ secretion and in turn HCO3- generation
even when the buffering actions of other urinary buffers are
exhausted.
• Usually, the H+ combines with ammonia to form NH4+ which
eventually combines with anions e.g Cl- to form ammonia
chloride (NH4Cl)
• There is net gain of HCO3-
• There is net loss of H+.
Regulation of Acid-Base Balance
Excretion of H+ as NH4+ (Urinary Ammonia Buffer System)
 Anion Gap
• This is the difference between the measured
cations (Na+& K+) and the measured anions
(Chloride and Bicarbonate)
• Normally between 15-20 mmol/L
• Increases when unmeasured anions such as
phosphates and sulphates increase in the
blood and HCO3 falls in acidosis
• The converse occurs in metabolic alkalosis
 Metabolic Derangements
• ACIDOSIS (fall in pH)
– Respiratory acidosis: primary excess of carbonic acid
– Metabolic acidosis: primary deficit of bicarbonate

• Alkalosis (rise in pH)

– Respiratory alkalosis: primary deficit of carbonic acid
– Metabolic alkalosis: primary excess of bicarbonate
 Metabolic Acidosis
• Results from any process that lowers the
plasma bicarbonate concentration
• It may be a primary process or secondary to
compensatory respiratory alkalosis
• When bicarbonate is reduced, the equation:
pH = pK + log HCO-3
pCO2
• The pH will fall.
 Causes of Metabolic Acidosis
• Increased or excess H+ production: Ketoacidosis,
e.g., uncontrolled diabetes mellitus, starvation,
lactic acidosis, shock Poisoning e.g. salicylate
over-dosage
• Failure to excrete H+: Acute and chronic renal
failure , distal renal tubular acidosis
• Loss of HCO3- from GIT : Severe diarrhoea,
pancreatic fistula
• Loss of HCO3- in urine: Uretero-enterostomy,
proximal renal tubular acidosis, carbonic
anhydrase inhibitors
 Compensation for metabolic Acidosis

• Compensation for metabolic acidosis occurs

through the respiratory centre.
• There is stimulation of the respiratory centre
resulting in hyperventilation to ’wash out’ CO2,
and avoid a change in pH

pH =6.1 + log (HCO3-)

pCO2x 0.23
 Renal Tubular Acidosis (RTA)
• Usually an acquired disorder
• Could be inherited
• No 10 glomerular lesion, urea & creatinine are
normal
• Usually a tubular defect- 2-types
• Classical or Type 1,Distal RTA-abnormal
permeability of distal tubular cells to H+
• Proximal or type 2—defect of Carbonic
anhydrase
• Both result in metabolic acidosis
 Respiratory Acidosis
• This is characterized by an increase in pCO2 due to CO2
retention (hypercapnia)
• The increase blood pCO2 may be the primary process or it
may be secondary to compensatory metabolic alkalosis
• If pCO2 is increased in the equation:

pH = (HCO3-)
pCO2
pH will fall
 Causes of Respiratory Acidosis
• Pulmonary disease: Chronic obstructive
airway disease(COAD) e.g, chronic bronchitis,
emphysema, severe asthma, pulmonary
oedema
• Chest infection: Bronchopneumonia
• CNS depression :Anaesthetics, opiates
• CNS disease: Stroke, trauma
Compensation for Respiratory Acidosis

• Compensation (metabolic) occurs by the

acceleration of the carbonic anhydrase
mechanism in the erythrocytes and renal
tubular cells, resulting in high HCO3 which
could also lead to normal or no change in pH
 Metabolic Alkalosis
• This disorder is characterised primarily by an
increase in the concentration of bicarbonate
in the ECF, resulting in the reduction of
hydrogen ion concentration.
• When this occurs, bicarbonate reabsorption is
reduced, resulting in bicarbonate excretion in
urine.
 Causes of Metabolic Alkalosis
• Ingestion of large amount of bicarbonate to
treat indigestion
• Loss of unbuffered H+, e.g., Conn’s and
Cushing’s syndrome
• Loss of H+ from GI tract vomiting, e. g.,
nasogastric tube drainage pyloric stenosis
• Loss of H+ in urine thiazide diuretics
 Compensation of Metabolic Alkalosis

• Largely by induction of respiratory acidosis by

CO2 retention to avoid a shift in pH from the
equation:
• pH = pK + (HCO3-)
pCO2
pH will fall
 Respiratory Alkalosis
• This occurs when there is a fall in PCO2 which
reduces the ratio of pCO2 to bicarbonate
concentration in the pH equation.
• Causes are:
• Hysterical over breathing: Voluntary
hyperventilation, excessive artificial respiration
• Stimulation of Respiratory centre: Pain, fever,
hypoxia, Lobar pneumonia, hypoxia, pulmonary
oedema
• Raised intracranial pressure or brain stem lesions
Compensation for Respiratory Alkalosis

• There is a compensatory fall in the drive of

carbonic anhydrase system to reclaim
bicarbonate in both the kidneys and the
erythrocytes leading to a fall in HCO3- to
minimise the change in pH
 Assessment of Acid-Base Parameters
• The assessment of acid-base status is usually done by the
blood gas analyzer, which measures pH, PCO 2 and PO2
directly, by means of electrodes. Arterial blood is used to
measure the acid-base parameters.
• In the absence of a blood gas analyzer, venous blood may
be collected under paraffin (to eliminate contact with air).
Bicarbonate is estimated by titration to pH 7.4. From the
values of Na+, K+, CI- and HCO3-, the anion gap is calculated.
• Most of the critical care analyzers estimate the blood gas,
electrolytes and calculate the anion gap.
CLINICAL AND LABORATORY ASSESSMENT
OF HYDROGEN ION HOMOEOSTASIS

NORMAL VALUES

H+ 35 – 46 nmol/L (pH- 7.35 - 7.45)

HCO3- 22-26 mmol/L
PCO2 4-6 kP (36-46 mmHg)
PO2 11-15 kP (85-105 mmHg)
O2 saturation 95-100%
 ARTERIAL BLOOD GAS:
CRITICAL VALUES
pH < 7.25; > 7.55
pCO2 < 20; > 60
HCO3- <15; > 40
pO2 < 40
O2 saturation < 75%
 .

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You