Acid-base Balance

Acids:
 Acid is a substance whose dissociation in water releases
hydrogen ions (H+)
 Addition of an acid to a solution, increases concentration
of free H+ in the solution. This produces more acidic
solution & decrease in pH.
HCL H+ + Cl-
Bases:
 A base releases hydroxyl ions (OH-) in aqueous solution &
decreases its H+ concentration by accepting or by binding
with free H+. This results in increase in pH of the solution.
NaOH Na+ + OH-
 The OH-, accepts H+ & results in the formation of water.
Amphoteric Substances
Some substances, such as amino acids & proteins, act
acids as well as bases. These substances are referred
to as Amphoteric substances.
Production of acids by the body
The metabolism of the body is accompanied by an
overall production of acids. These include:
Volatile Acids:
Volatile acids like carbonic acid Produced by oxidative
metabolism of carbohydrates, Fat and Protein is most
predominant acid produced in body.
Average production is 15,000-20,000 mEq/day.
Excreted through Lungs as CO₂ gas.
Nonvolatile acids or Fixed acids
Acids that do not leave solution, once produced they
remain in body fluids until eliminated by Kidneys. (1
mEq/kg/day) or (about 80 mEq/day)
These include: lactic acid, sulfuric acid, phosphoric acid
etc. Produced by catabolism of:
– Amino acids (oxidation of sulfhydryl groups of cystine,
methionine)
– Phospholipids (hydrolysis)
– Nucleic acids
All these acids add up H+ ions to the blood. A diet rich in
animal proteins results in more acid production by the
body that ultimately leads to the excretion of acidic urine.
Production of Bases by the body
 The formation of basic compounds in the body,
in the normal circumstances is negligible.
 Some amount of bicarbonate is generated from
the organic acids such as lactate and citrate.
 A vegetarian diet has a tendency for a net
production of bases.
 For this reason, a vegetarian diet has an
alkalizing effect on the body. This is reflected by
the excretion of neutral or slightly alkaline
urine by these subjects.
Maintenance of Blood pH
 Maintenance of blood pH is an important
homeostatic mechanism of the body.
 The normal pH of the blood is maintained in the
narrow range of 7.35 - 7.45 (slightly alkaline).
 In normal circumstances, the regulation is so
effective that the blood pH varies very little.
Changes in blood pH will alter the intracellular
pH which, in turn, influence the metabolism.
 lt is estimated that the blood pH compatible to
life is 6.8-7.8.
Acid-base Balance
 pH is a measurement of the acidity or alkalinity of
the blood. It is inversely proportional to the no. of
(H+) in the blood. The normal pH range is 7.35-7.45.
 Significant changes in the blood pH above 7.8 or
below 6.8 causes various abnormalities.
 The body constantly produces acids through
metabolism. These acids must be constantly
eliminated from the body.
 Acid–base balance refers to the balance between
input (intake and production) and output
(elimination) of hydrogen ion and maintenance of
blood pH.
Acid–Base Balance
Normal Range in Blood
 Normal pH : 7.35-7.45
 Acidosis: Physiological state resulting from
abnormally low plasma pH.
 Alkalosis: Physiological state resulting from
abnormally high plasma pH.
 Acidemia: plasma pH < 7.35
 Alkalemia: plasma pH > 7.45
 The body is an open system
in equilibrium with the alveolar air where the
partial pressure of carbon dioxide pCO2 is
identical to the carbon dioxide tension in the
blood.
 The body has developed three lines of defense
to regulate the body's acid-base balance and
maintain the blood pH around 7.4.
1. Physiological buffers : First line of defence
2.Respiratory regulation: Second line of
defence
3. Renal regulation : Third line of defence
 The buffer systems in the human body are
extremely efficient, and different systems work at
different rates.
 It takes only seconds for the chemical buffers in
the blood to make adjustments to pH.
 The respiratory mechanism can adjust the blood
pH upward in minutes by exhaling CO2 from the
body.
 The renal system can also adjust blood pH
through the excretion of hydrogen ions (H+) and
the conservation of bicarbonate, but this process
takes hours to days to have an effect.
Acid Base Balance
Physiological Buffers
 Buffers are the first line of defense against acid load.
The buffer systems in the human body are extremely
efficient.
 It takes only seconds for the chemical buffers in the
blood to make adjustments to pH.
 The blood buffers temporarily acts as a shock
absorbent to reduce the free H+ ion but can not
remove H+ ions from the body permanently.
 The buffers are effective as long as the acid load is
not excessive, and the alkali reserve is not exhausted.
 Once the base is utilized in this reaction, it is to be
replenished to meet further challenge.
These buffer systems are enumerated in Table
below. Detail explanation of blood buffers was
done in previous class.
Respiratory Mechanism For Acid-base Balance
 Respiratory system provides a rapid mechanism
for the maintenance of acid-base balance.
 This is achieved by regulating the concentration
of carbonic acid (H2CO3) in the blood.
 The large volumes of CO2 produced by the
cellular metabolic activity endanger the acid
base equilibrium of the body.
 All of this CO2 is eliminated from the body in the
expired air via the lungs.
 The rate of respiration is controlled by a
respiratory centre, located in the medulla of
the brain.
 This centre is highly sensitive to changes in the
pH of blood.
 Decrease in blood pH causes hyperventilation
to blow off CO2 & reducing the H2CO3
concentration. H+ ions are eliminated as H2O.
 Respiratory control of blood pH is rapid but
only a short term regulatory process, since
hyperventilation cannot proceed for long.
Figure: Respiratory
Regulation of Blood pH.
The respiratory system
can reduce blood pH by
removing CO2 from the
blood.
Generation of HCO3- by RBCs and Chloride Shift
 Due to lack of aerobic metabolic pathways, RBC
produce very little CO2. The plasma CO2 diffuses
into RBC and combines with water to form
H2CO3 by Carbonic anhydrase.
 In RBC, H2CO3 dissociates to produce H+ &
HCO3-. The H+ ions are buffered by
Hemoglobin.
 As the concentration of HCO3- increases in the
RBC, it diffuses into plasma along with
concentration gradient, in exchange for Cl⁻-ions,
to maintain electrical neutrality.
This is referred to as chloride shift, helps to
generate HCO3- .
 Renal Regulation of Acid Base
Balance is achieved by following
mechanisms:

1. Excretion of H+ ions

2. Reabsorption of Bicarbonate

3. Excretion of titratable acid

4. Excretion of ammonium ions

Excretion of H⁺-Ions
 Kidney is the only route through which the H+
can be eliminated from the body.
 H+ excretion occurs in the proximal convoluted
tubules & is coupled with generation of HCO3.
 Carbonic anhydrase catalyses the production of
carbonic acid (H2CO3) from CO2 & H2O in renal
tubular cells. H2CO3 then dissociates to H+ &
HCO3⁻.
 H+ ions are secreted into tubular lumen in
exchange for Na+. Na+ in association with
HCO3- is reabsorbed into blood.
Bicarbonate Reabsorption
 The blood HCO3- is conserved with simultaneous
excretion of H+ ions. Bicarbonate freely diffuses from
plasma into tubular lumen where HCO3- combines
with H+, secreted by tubular cells, to form H2CO3.
 H2CO3 is then cleaved to form CO2 and H2O. In the
tubular lumen, CO2 diffuses into the tubular cells and
combines with H2O to form H2CO3 which then
dissociates into H+ & HCO3-.
 The H+ is secreted into the lumen in exchange for
Na+. The HCO3 - is reabsorbed into plasma in
association with Na+. Re-absorption of HCO3 - is a
cyclic process with the net excretion of H+ or
generation of new HCO3-.
Excretion of Titratable Acid
 Titratable acidity is a measure of acid excreted into
urine by the kidney.
 Titratable acidity refers to the number of milliliters of
N/10 NaOH required to titrate 1liter of urine to pH 7.4.
 Titratable acidity reflects the H+ ions excreted into
urine. H+ ions are secreted into the tubular lumen in
exchange for Na+ ion.
 This Na+ is obtained from the base, disodium
hydrogen phosphate (Na2HPO4).
 This combines with H+ to produce the acid, sodium
dihydrogen phosphate (NaH2PO4), in which form the
major quantity of titratable acid in urine is present.
 Tubular fluid moves down the renal tubules,
more and more H+ ions are added, resulting in
the acidification of urine. This causes a fall in
the pH of urine as low as 4.5.
Excretion of Ammonium Ions
 The H+ ion combines with NH3 to form
ammonium ion (NH4+).
 The renal tubular cells deaminate glutamine to
glutamate and NH3 by the action of enzyme
glutaminase.
 The liberated NH3 diffuses into the tubular
lumen where it combines with H+ to form NH4+.
 Ammonium ions cannot diffuse back into
tubular cells and excreted into urine.
Acid/Base Disorders
The acid-base disorders are mainly two types: Acidosis and
Alkalosis.
Acidosis: A decline in blood pH is known as acidosis. It is of
two types:
1. Metabolic acidosis- Due to a decrease in bicarbonate
concentration.
2. Respiratory acidosis- Due to an increase in carbonic acid
concentration.
Alkalosis : A rise in blood pH is known as alkalosis. It is of
two types:
3. Metabolic alkalosis - Due to an increase in bicarbonate
concentration.
4. Respiratory alkalosis - Due to decrease in carbonic acid
concentration.
ANION GAP
 The sum of cations and anions in ECF is always equal, so
as to maintain the electrical neutrality.
 The commonly measured electrolytes are Na+, K+ (95%),
Cl- & HCO3- (80%). The remaining unmeasured anion in
the plasma constitutes the anion gap. This is due to
presence of protein anions, sulphate , phosphate and
organic acids.
 Anion gap (A⁻) is defined as the difference between the
total concentration of measured cations (Na+ & K+) and
that of measured anion (Cl- & HCO3-).
 The anion gap (A⁻) may be calculated as follows:
Anion gap = (Na⁺ + k⁺) - ( HCO3⁻ + Cl⁻ )
 Normally anion gap is about 15 mEq/l. Normal range = 8-
18 mEq/l.
Clinical Significance of Anion Gap
High anion gap acidosis:
I. Renal failure
II. Diabetic ketoacidosis
III. Lactic acidosis
Normal anion gap acidosis:
I. Diarrhoea
II. Hyperchloremic acidosis
Low anion gap:
I. Multiple myeloma
Metabolic Acidosis
 Reduction in bicarbonate leads to fall in blood
pH.
 This is due to excessive production of organic
acids which can combine with NaHCO3- and
deplete the alkali reserve.
 Commonly seen in severe uncontrolled diabetes
mellitus (ketoacidosis)- production of organic
acids, Renal failure, Lactic acidosis, Severe
diarrhoea and Renal tubular acidosis.
Anion gap and Metabolic Acidosis
 Increased production and accumulation of
organic acid causes an elevation in anion
gap.
 This type is seen in ketoacidosis
COMPENSATION
 Hyperventilation of lungs (elimination of
CO2).
 Renal compensation-(3-4days): H+ ions
excreted as NH4+.
Respiratory Acidosis
 This is primarily due to excess of carbonic acid.
(Increased H2CO3). This lead to fall in pH.
Causes of Respiratory Acidosis
Severe asthma
Pneumonia
Cardiac arrest
Depression of respiratory centre
COPD
Breathing air with high content of CO2
Metabolic Alkalosis
 This is due to increase in HCO3- concentration/
primary excess of bicarbonate..
 Causes of Metabolic Acidosis
Severe vomiting
Hypokalemia
Intravenous administration of bicarbonate.
Cushing syndrome
 Respiratory mechanism initiates compensation
by hypoventilation to retain CO2, this is taken
over by renal mechanism which excrete more
HCO3- and retain H+.
Respiratory Alkalosis
 This is due to decrease in H2CO3
concentration/Primary deficit of carbonic acid.
 This is due to prolonged hyperventilation
resulting in increased exhalation of CO2 by the
lungs.
 Renal mechanism tries to compensate by
increasing the urinary excretion of HCO3-.
Causes of Respiratory Alkalosis
 Hyperventilation
 High altitude
 Salicylate poisoning
Acid Base Disorder and Potassium Ion

 Plasma potassium concentration (normal

3.5 - 5.0 mEq/l) is very important as it
affects the contractility of the heart.
 Hyperkalemia (high plasma K+) or
hypokalemia (low plasma K+) can be life
threatening.
Potassium and Diabetic Ketoacidosis
 Insulin increases K+ uptake by cells.
 The patient of severe uncontrolled diabetes
(i.e. with metabolic acidosis) is usually with
hypokalemia.
 When such a patient is given insulin, it
stimulates K+ entry into cells.
 The result is that plasma K+ level is further
depleted.
 Hypokalemia affects heart functioning and is
life threatening.
Potassium and Alkalosis
 Low plasma concentration of K+
(hypokalemia) leads to an increased
excretion of hydrogen ions, and thus may
cause metabolic alkalosis.
 Conversely, metabolic alkalosis is
associatedwith increased renal excretion
of K+.
 Blood Gas Analysis

Arterial Mixed venous

Ph 7.37-7.45 7.35-7,43

Pco2 hgmm(kpa) 35-46(4,6-6,1) 37-50 (4,9-6,6)

Bicarbonate (mmol/l) 21-26/21-26 21-26/21-26

Be (mmol/l) -2,5 - +2,5 -2,5 - +2,5

Anion gap (mmol/l) 10-14 10-14

THANK YOU SO MUCH FOR
YOUR ATTENTION