This document defines key terms related to acid-base homeostasis, including acids, bases, pH, buffers, and the mechanisms that regulate hydrogen ion concentration in the blood. It discusses how the major buffer systems, especially the bicarbonate-carbonic acid system, help maintain acid-base balance. Respiration and the kidneys work together to remove acids produced during metabolism and regulate the excretion of non-volatile acids and bicarbonate.

1. PREPARED BY
MARTIN SHAJI
PHARM D
ACID BASE
HOMEOSTASIS I

3. DEFINITION OF TERMS
ACID
A substance that dissociates in water to
produce hydrogen ions (H+).
A strong acid, e.g., hydrochloric acid,
dissociates almost completely:
A weak acid, e.g., acetic acid, shows poor
dissociation

4. DEFINITION OF TERMS
ALKALI
A substance that dissociates in water to produce
hydroxyl ions (OH-), e.g., sodium hydroxide.

6. DEFINITION OF TERMS
BASE
A base is a substance that can accept hydrogen ions,
e.g., C1-.
A strong base, e.g., CH,COO-, has a high affinity for
hydrogen ions.
A conjugate base is the dissociation anionic product
of an acid, e.g., the bicarbonate ion (HCO3
-) is the
conjugate base of carbonic acid (H2CO3)
H2CO3 ⇌ H+ + HCO3
- (conjugate base)

7. DEFINITION OF TERMS
Respiration: Process to supply cells with oxygen for
metabolic processes and remove the carbon dioxide
produced during metabolism.
Partial pressure: In a mixture of gases, partial
pressure is the amount of pressure contributed by
each gas to the total pressure exerted by the
mixture.
Acidaemia: A raised blood [H+], greater than 45
nmol/L; or a low blood pH, less than 7.35

8. DEFINITION OF TERMS
Alkalaemia: A low blood [H+], less than 35 nmol/L,
or a high blood pH, greater than 7.45.
Hypercapnia is increased blood PCO2
Hypocapnia is decreased blood PCO2.
Acidosis: A primary process that generates hydrogen
ions. Depending on the buffering and compensatory
processes it may, or may not, produce an acidaemia.

9. DEFINITION OF TERMS
Alkalosis: A primary disorder that produces excessive
hydroxyl ions. It need not always result in alkalaemia.
Concentration of dissolved carbon dioxide (cdCO2):
Includes undissociated carbonic acid (H2CO3) and
carbon dioxide dissolved in blood (represented by
PCO2)
Concentration of total carbon dioxide (ctCO2):
Includes bicarbonate (primary component), carbamino-
bound CO2, carbonic acid, and dissolved carbon dioxide

10. DEFINITION OF TERMS
• Respiratory component: The term defines the
PCO2 level as this parameter is ultimately controlled
by respiration. A high PCO2 (>45 mmHg) is a
respiratory acidosis and a low PCO2 (<35 mmHg),
is a respiratory alkalosis.

11. DEFINITION OF TERMS
Metabolic component: This describes the plasma
bicarbonate concentration. Metabolic acidosis is
defined by a low plasma [HCO3
-] (e.g.,<23 mmol/L)
and metabolic alkalosis, by a high plasma [HCO3
-]
(>33 mmol/L)..

12. DEFINITION OF TERMS
Compensation: During acid-base disturbances the
body's homeostatic mechanisms try to keep the pH
of the body fluids as near normal as possible. As the
pH is directly related to the ratio of the [HCO3
-] to
the PCO2, then during metabolic acidosis (low
[HCO3-]) the pH can be brought back to normal by
lowering the PCO2; i.e., the development of a
respiratory alkalosis compensates for the metabolic
acidosis.

13. DEFINITION OF TERMS

14. ANION GAP
 The number of millimoles (mmol) per litre of
cations in plasma is normally balanced by an equal
amount of millimoles per litre of anions (electrical
neutrality is maintained).
 This means that in plasma, the total amount in
mmol per litre of Na+ + K+ + Ca2+ + Mg2+ + other
cations will be equal to the total amount in mmol
per litre of Cl- + HCO3
- + HPO4
2- + SO4
2- +
proteinate + other anions.
 In most clinical laboratories, the routinely
measured electrolytes are Na+, K+, Cl- and HCO3
-

15. ANION GAP
 These four ions in plasma exert the greatest
influence on water balance and acid-base
relationships.
 The difference between the sum of the measured
cation concentrations (Na+ + K+) and the sum of
the measured anion concentrations (CI- + HCO3
-)
is called the anion gap (the correct term should be
unmeasured anions as there is no anion gap as
such).
 Anion gap is the total amount of unmeasured or
undetermined anions.

16. MAJOR PLASMA CATIONS AND ANIONS (in
mEq/L).

17. ANION GAP
 Anion gap is the difference between the usually
unmeasured cations and the usually unmeasured
anions.
 Anion gap is often calculated by subtracting the
measured anions (HCO3
- and Cl-) from the
measured cations (Na+ and K+)
Anion Gap = (Na+ + K+) – (HCO3
- + Cl-)
Anion Gap = Na+ – (HCO3
- + Cl-)
The normal anion gap is about 8 -16 mmol/l

19. USES OF ANION GAP
 It is used in the diagnosis of metabolic acidosis.
With few exceptions, the anion gap will be normal
in other acid-base disturbances
 The anion gap may also be used as a tool to
monitor response to therapy in those individuals
with increased anion gap, especially in diabetic
ketoacidosis.

20. pH
A measure of free H+ ion concentration.
This H+ ions come from acids produced as a result
of metabolism.
These acids could be volatile acids and non-
volatile
pH is variable in certain areas of the body (e.g.
saliva, stomach, CSF)
 Body pH = 7.35 – 7.45

21. pH
 A measure of the hydrogen ion concentration defined as
the logarithm of the reciprocal of the [ H+].
pH =log10 1/[ H+] = - log10 [H+]
 Blood normally has a slightly alkaline pH
 The normal range of the arterial blood pH of a healthy
resting individual at sea level is 7.35 to 7.45 (i.e. about 35
to 45 nmol/l of H+ ion concentration).
 The amount of H+ ion in the body is precisely regulated in
healthy individuals. This is because changes in blood H+
concentration affect the physiological functions of many
enzymes (effect on the conformation of proteins) and
hormones.

22. pH
 Slight changes in pH affect the shape and activity of
proteins.
 H+ ion concentration also influences neurologic functions
(may lead to depression and over-excitability of the
CNS). And the distribution of other ions (e.g. K+) in the
body

23. MECHANISMS FOR HYDROGEN
ION HOMEOSTASIS
 There are two major mechanisms for H+ homeostasis.
 These are respiratory and metabolic
 The lungs and kidneys are both involved in the excretion
of acids produced during metabolic processes in the body.
 Large amounts of carbon dioxide are formed in the body
from the oxidation of carbohydrates, proteins and fats.

24. MECHANISMS FOR HYDROGEN
ION HOMEOSTASIS
 Most of the organic acids formed during the metabolism
of fat, carbohydrate, and protein are converted to carbon
dioxide and water and do not accumulate in the body.
 These are largely converted to carbonic acid, a volatile
acid which is converted to carbon dioxide which is
excreted in the lungs during respiration

25. MECHANISMS FOR HYDROGEN
ION HOMEOSTASIS
 ATP hydrolysis, respiratory chain reactions, and the
reduction of nicotinamide nucleotides also generate H+
ions.
 Under normal circumstances these reactions are
reversible and do not result in a net H+ gain.
 However, some acids called non-volatile acids (fixed
acids) are produced by many processes in the body.

26. MECHANISMS FOR HYDROGEN ION
HOMEOSTASIS
These non-volatile acids which accumulate and have to be
excreted are formed as follows:
Dietary protein is the major source of non-volatile acid hydrogen ions.
They kidneys excrete or eliminate non-volatile acids as they can not be
excreted by the lungs
The kidneys also regulate the re-absorption of bicarbonate (HCO3
-).

27. PH OF A BUFFER SYSTEM
This may be calculated from the Henderson-Hasselbalch
equation which relates the pH to the concentrations of acid
and base.
pH = pK + log10 [base]/[acid] (K is overall dissociation
constant)
For the bicarbonate system pK is 6.10, thus
pH = 6.1 + log10 [HCO3
-]/[H2CO3]
This equation shows that the pH of this system is
proportional to the ratio of base to acid, i.e.,
pH = [HCO3
-]/[H2CO3] Equation (1)

28. PH OF A BUFFER SYSTEM
In solution, e.g., in the plasma, the [H2CO3] is directly
related to the PCO2 (partial pressure of CO2). The solubility
constant of this gas is 0.03, thus
PCO2 (mmHg) x 0.03 = [H2CO3] (mmol/L)

29. PH OF A BUFFER SYSTEM
Therefore Equation (1) can be recast as:
pH ∝ [HCO3
-]/PCO2 Equation (2)
The hydrogen ion concentration of the bicarbonate buffer
system can be calculated, using the Henderson- Hasselbalch
equation, as follows:
[H+](nmol/L) = 24 {PCO2(mmHg)/[HCO3
-](mmol/L)}

30. MAJOR BUFFER SYSTEMS
A buffer system is generally defined as
a weak acid and its conjugate base or
conversely as a weak base and its
conjugate acid.
A system that can resist change in pH;
composed of a weak acid or a weak base
and its corresponding salt

31. MAJOR BUFFER SYSTEMS
Bicarbonate system: H2CO3/HCO3
- (75%)
Protein system: protein+/protein- (20%)
Phosphate system: H2PO4
-/HPO4
2- (5%)

32. MAJOR BUFFER SYSTEMS
There are four buffer systems of clinical importance exist
in whole blood, namely;
 Bicarbonate/Carbonic acid
 Phosphate
 Haemoglobin
 Proteins
They can further be classified as: Extracellular buffers
(Bicarbonate/Carbonic acid and plasma proteins) and
intracellular buffers (Proteins, organic and inorganic
phosphates and haemoglobin).

33. MAJOR BUFFER SYSTEMS
a. The bicarbonate-carbonic acid buffer
system uses HCO3
− and H2CO3 to
minimize pH changes in plasma and
erythrocytes. It is the most important
buffer system in plasma.
b. The protein buffer system uses plasma
proteins to minimize pH changes in the
blood.

34. MAJOR BUFFER SYSTEMS
c. The phosphate buffer system uses
HPO4
2− and H2PO4 to minimize pH
changes in plasma and erythrocytes.
d. The haemoglobin buffer system uses
the haemoglobin in red blood cells to
minimize pH changes in the blood. It is
the most important intracellular buffer.

35. REFERENCE VALUES

36. THANK YOU