The document discusses acid-base balance and its regulation in the human body. It states that acid-base balance refers to precise regulation of hydrogen ion concentration in body fluids, which is important for homeostasis. The body produces both volatile acids from carbon dioxide metabolism and non-volatile acids from protein metabolism. Buffering systems and the respiratory and renal systems work to balance acid production and maintain pH within a narrow range. Disturbances in acid-base balance can occur from changes in bicarbonate levels or carbon dioxide partial pressure and are assessed using arterial blood gas analysis.

1.  The term acid–base balance refers to the precise regulation of free (that is, unbound)
hydrogen ion (H+) concentration in the body fluids.
 Acid-base balance is very important for the homeostasis of the body and almost all the
physiological activities depend upon the acid-base status of the body.
 Acids are constantly produced in the body.
 However, the acid production is balanced by the production of bases so that the acid-base
status of the body is maintained.
 In practice, the acidotic conditions are common than alkalotic ones, because the body tends
to produce more acid than alkali.
 Acid: is any proton donor (a molecule that releases a proton H+ in water).
 Strong acids: HCL.
 Weak acids: Carbonic acid (H2CO3), Lactic acids and sodium dihydrogen phosphate
(NaH2PO4).
 Base: is a proton acceptor (a substance accepts H+ often with the release of hydroxyl (OH-)
ions).
 Strong base: Hydroxyl ion (OH-).
 Weak base: Bicarbonate (HCO3).
 Hydrogen ion (H+) contains only a single proton
(positively charged particle).
 It is the smallest ionic particle, it is highly reactive.
 The normal H+ concentration in the extracellular fluid
(ECF) is 38 to 42 nM/L.
 The pH is another term for H+ concentration that is
generally used nowadays instead of „hydrogen ion
concentration‟.
 An increase in H+ ion concentration decreases the pH (acidosis) and a reduction in H+
concentration increases the pH (alkalosis).
 In a healthy person, the pH of the ECF is 7.40 and it varies between 7.38 and 7.42.
 The maintenance of acid-base status is very important for homeostasis, because even a slight
change in pH below 7.38 or above 7.42 will cause serious threats to many physiological
functions.
 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.

2.  Production of Acids by body:
Two types of acids are produced in the body:
1. Volatile Acids:
 Volatile acids are derived from CO2.
 Large quantity of CO2 is produced during the metabolism of carbohydrates and lipids.
 This CO2 is not a threat because it is almost totally removed through expired air by lungs.

3. 2. Non-volatile Acids (Fixed acids):
Non-volatile acids are produced during the metabolism of other nutritive substances such as
proteins.
 These acids are real threat to the acid-base status of the body.
 For example, sulfuric acid is produced during the metabolism of sulfur containing amino
acids such as cysteine and metheonine; hydrochloric acid is produced during the
metabolism of lysine, arginine and histidine.
3: Organic acids like Lactic acid, Acetic acid and β- hydroxybutyric acid. Uric acid produced in
the metabolism of nucleoproteins.
 Production of Bases by body:
 In a normal circumstance, a negligible amount of bases is formed in the body because:
 HCO3- produced by the metabolism of organic anions (e.g. citrate) offsets non-volatile
acid production to some degree.
 Ammonia produced in the amino acid metabolism is converted to urea; hence its
contribution as a base in the body is insignificant.
 The body has three different mechanisms to regulate acid-base status:
1- Acid-base buffer system:
 Which binds free H+
 Is the fastest one and it read just the pH within seconds.
2- Respiratory mechanism:
 Which eliminates CO2
 Adjust the pH in minutes.
3- Renal mechanism:
 Which excretes H+ and conserves bases (HCO3–)
 Slower and it takes few hours to few days to bring the pH back to normal.
 Is the most powerful mechanism than the other two in maintaining the acid-base balance of
the body fluids.
REGULATION OF ACID-BASE BALANCE:

4.  An acid-base buffer system is the combination of a weak acid (protonated substance) and a
base – the salt (unprotonated substance).
 A buffer is any substance that can reversibly bind H+. The general form of the buffering
reaction is:
Buffer + H+
H Buffer.
For example, about 80 milliequivalents of H+ is either ingested or produced each day by
metabolism, whereas the H+ concentration of the body fluids normally is only about 0.00004
mEq/L. Without buffering, the daily production and ingestion of acids would cause lethal
changes in body fluid H+ concentration.
 Types of Buffer Systems:
1- Bicarbonate buffer system.
2- Phosphate buffer system.
3- Protein buffer system.
 Bicarbonate buffer system is present in ECF (plasma).
 HCO3 – is in the form of salt, i.e. sodium bicarbonate (NaHCO3).
 Importance of bicarbonate buffer system:
 Concentration of HCO3 – is regulated by kidney and the concentration of CO2 is regulated
by the respiratory system.
 Mechanism of action of bicarbonate buffer system:
1- REGULATION OF ACID-BASE BALANCE BY ACID-BASE BUFFER SYSTEM:
Henderson-Hasselbalch equation, states that increase in HCO3- concentration causes the
pH to rise, shifting the acid-base balance toward alkalosis. An increase in PCO2 causes the pH to
decrease, shifting the acid-base balance toward acidosis.

5.  Phosphate buffer system is useful in the intracellular fluid (ICF), in red blood cells or other
cells, as the concentration of phosphate is more in ICF than in ECF.
 Importance of phosphate buffer system:
 Phosphate buffer is useful in tubular fluids of kidneys.
 The elements of phosphate buffer inside the red blood cells are in the form of potassium
dihydrogen phosphate (KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
 Mechanism of phosphate buffer system:
As you look the mechanism action of bicarbonate and phosphate buffer system are same except
the substance used for buffering system.
 Protein buffer systems are present both in the plasma and erythrocytes.
 Protein buffer systems in plasma:
 i. C-terminal carboxyl group, N-terminal amino group and side-chain carboxyl group of
glutamic acid.
 ii. Side-chain amino group of lysine
 iii. Imidazole group of histidine.
During Acidosis (pH less than7.45), the amino group of Amino acids takes the
excess H:

6.  Protein buffer system in erythrocytes (Hemoglobin):
 Hemoglobin has about six times more buffering capacity than the plasma proteins.
 When a hemoglobin molecule becomes deoxygenated in the capillaries, it easily binds with
H+, which is released when CO2 enters the capillaries.
During Alkalosis (pH more than7.45), the Carboxyl group of Amino acids
release the H:

7.  Respiration has a direct bearing on acid-base balance of the body because carbon dioxide is
eliminated from the body during expiration.
 Effect of pH on Respiration:
 Increased H+ concentration and decreased pH to 7.2 increases the pulmonary ventilation
(hyperventilation) by acting through the chemoreceptor by doing this the excess of CO2 is
removed from the body.
 When metabolic activities increase, more amount of CO2 is produced in the tissues and the
concentration of H+ increases.
 Steps of formations of H+ ions:
1. Carbon dioxide and water added together by enzyme called “CARBONIC ANHDRASE ” –
is a zinc containing enzyme.
2. Leads for the production of carbonic acid which is unstable and.
3. Immediately dissociate into H+ and bicarbonate.
 Effect of Respiration on pH:
 In some abnormal situations respiratory depression or pathological hyperventilation may lead
to an acid-base disturbance.
 When decreased carbon dioxide elimination from the body causing more H+ production so
there is a decrease in pH a condition known as “Acid _ Base disturbance” especially
respiratory acidosis.
 When increased carbon dioxide elimination from the body means less H+ production leads
increase in pH causes what we are called “Acid _ Base disturbance” especially respiratory
alkalosis.
Effect Of H+
on: Increased H+
Concentration: “less
secretion”
Decreased H+
Concentration: “high
secretion”
1. Nerve Cells Depression. Overexcitability.
2. Enzyme Alters the shape of the enzyme.
3. K+
Hypokalemia due to increased K+
secretion.
Hyperkalemia due to decreased K+
secretion.
2- REGULATION OF ACID-BASE BALANCE BY RESPIRATORY MECHANISM:

9.  Kidney maintains the acid-base balance of the body by the secretion of H+ and by the
retention of HCO3–. Or the kidneys control acid-base balance by excreting either acidic or
basic urine.
 The renal excretes the nonvolatile acid that produced from the metabolism of protein because
the lung cannot have the ability to excrete these substances.
 The kidneys regulate extracellular fluid H+ concentration through three fundamental
mechanisms:
(1) Secretion of H+
:
a) ATP- driven proton pump.
b) Na+
- H+
antiport pump.
c) Excretion of H+
in combination with phosphate ions.
d) Excretion of H+
in combination with ammonia ions.
e) K+
- H+
antiport pump.
f) Secretion of H+
as Titratable acid.
(2) Reabsorption of filtered HCO3
-
:
a) H+
and HCO3
-
are produced in the proximal tubule cells from CO2 and H2O. CO2
and H2O combine to form H2CO3, catalyzed by intracellular carbonic anhydrase;
H2CO3 dissociates into H+
and HCO3-. H+
is secreted into the lumen via the Na+
– H+
exchange mechanism in the luminal membrane. The HCO3
-
is reabsorbed.
b) In the lumen, the secreted H+
combines with filtered HCO3
-
to form H2CO3, which
dissociates into CO2 and H2O, catalyzed by brush border carbonic anhydrase. CO2
and H2O diffuse into the cell to start the cycle again.
c) The process results in net reabsorption of filtered HCO3
-
. However, it does not
result in net secretion of H+.
(3) Production of new HCO3
-
:
 When H+
is excreted as titratable acid and ammonia, new HCO3
-
is formed and is
added to the blood. New HCO3
-
replaces the HCO3
-
used to buffer the strong acids
produced by metabolism.
 Mechanism action of this process:
 H+
and HCO3
-
are produced in the intercalated cells from CO2 and H2O. The H+
is
secreted into the lumen by an H+
-ATPase, and the HCO3
-
is reabsorbed into the blood
2- REGULATION OF ACID-BASE BALANCE BY KIDNEY MECHANISM:

10. (“new” HCO3
-
). In the urine, the secreted H+
combines with filtered base phosphate
HPO4
-2
to form H2PO4-
, which is excreted as titratable acid. This process results in
net secretion of H+
and net reabsorption of newly synthesized HCO3
-
.
Intracellular pH:
 Cells are typically threatened by acidic metabolic end products and by the tendency for
H+ to diffuse into the cell down the electrical gradient.
 H+ is extruded by Na+/H+ exchangers ~ 8 different isoforms designated NHE1 (sodium-
hydrogen exchanger), NHE2, etc., which are present in nearly all body cells.
 These transporters exchange one H+ for one Na+
 Active extrusion of H+ keeps the internal pH within narrow limits.
 Many hormones and growth factors, via intracellular second messengers, activate various
protein kinases that stimulate or inhibit the Na+/H+ exchanger. In this way, they produce
changes in intracellular pH, which may lead to changes in cell activity.
 The cell can deal with acids and bases in other ways:
Various HCO3-
transporters (e.g., Na+
-dependent and Na+
-independent Cl-
/
HCO3
-
exchangers, electrogenic Na+
/ HCO3
-
cotransporters).
Various cells have large stores of protein and organic phosphate buffers, which can bind
or release H+
.
Various chemical reactions in cells can also use up or release H+
.
Various cell organelles may sequester H+
.
 Anion gap is an important measure in the
clinical evaluation of disturbances in acid-base
status.
 Only few cations and anions are measured

11. during routine clinical investigations.
 Commonly measured cation is sodium and the unmeasured cations are potassium, calcium
and magnesium.
 Usually measured anions are chloride and bicarbonate.
 The unmeasured anions are phosphate, sulfate, proteins in anionic form such as albumin and
other organic anions like lactate.
 Difference between concentrations of unmeasured anions and unmeasured cations is called
anion gap.
 Normal value of anion gap is 9 to 15 mEq/L.
 There are two type of Anion Gap:
 Plasma anion gap _ It is calculated as:
 Urine anion gap _ It is calculated as:
 It increases when concentration of unmeasured anion
increases and decreases when concentration of unmeasured cations decreases.
 Anion gap is a useful measure in the differential diagnosis (diagnosis of the different causes) of acid
- base disorders particularly the metabolic acidosis.
The most common causes of metabolic acidosis with an increased anion
gap are (MULEPAK ):
1. Methanol ingestion 2. Uremia

12. 3. Lactic acidosis
4. Ethylene glycol ingestion
5. Paraldehyde ingestion
6. Aspirin overdose
7. Ketoacidosis
DISTURBANCES OF ACID-BASE STATUS
 ACIDOSIS:
 Acidosis is the reduction in pH (increase in H+ concentration)
below normal range.
 Acidosis is produced by:
1. Increase in partial pressure of CO2 in the body fluids
particularly in arterial blood
2. Decrease in HCO3– concentration.
 ALKALOSIS:
 Alkalosis is the increase in pH (decrease in H+ concentration)
above the normal range.
 Alkalosis is produced by:
1. Decrease in partial pressure of CO2 in the arterial blood
2. Increase in HCO3 – concentration.
 Change in HCO3 – are called the metabolic disturbances.
 Types:
o Metabolic acidosis
o Metabolic alkalosis.
 Changes in arterial pCO2 are called the respiratory disturbances.
 Types:
o Respiratory acidosis.
o Respiratory alkalosis.

14. Assessment of a patient’s acid–base status requires data from an arterial blood gas sample
ANALYSIS AND CLINICAL EVALUATION OF ACID–BASE DISORDERS:
Three-step approach for analysis of acid–base disorders:
 Step I: Estimate pH to know acidosis (pH<7.4) or alkalosis (pH>7.4).
 Step II: Detect primary disturbance to know whether the disorder is metabolic (primary disturbance
of HCO3-) or respiratory (primary disturbance of pCO2).
 Step III: Analysis of compensatory response can be done from the values of plasma HCO3- and pCO2
THERE 3 GRAPHIC ANALYSIS OF CHANGES IN pH, pCO2 AND HCO3-
1- Acid–base nomogram:
 Useful in predicting compensatory
responses to simple acid–base disorder.
 There is normal range situated centrally in
this graph (pH=7.4, arterial plasma HCO3-
ml = 24, arterial blood H+ = 40nmol/L).


15. 2- Davenport diagram:
 Is the typical graphical display of true plasma
pH, HCO3- and pCO2 in uncompensated and
compensated metabolic acidosis and metabolic
alkalosis.
 Interpretation of acid–base abnormalities using
pH, HCO3- diagram is made as:
Point A, represents uncompensated respiratory
acidosis,
Point B, represents uncompensated respiratory alkalosis,
Point C, represents uncompensated metabolic acidosis,
Point D, represents uncompensated metabolic alkalosis,
Point E, represents respiratory acidosis + metabolic acidosis,
Point F, represents respiratory acidosis + metabolic
alkalosis,
Point G, represents respiratory alkalosis + metabolic acidosis and
Point H, represents respiratory alkalosis + metabolic
alkalosis.
3- Siggard–Anderson curve nomogram:
 Siggard–Anderson (SA) curve
nomogram has pCO2 plotted on a log
scales on the vertical axis and pH on
the horizontal.
 This nomogram is helpful in the
clinical situation to plot the acid–
base, a characteristic of arterial
blood.