ACID-BASE BALANCE & DISORDERS

 Water is the solvent of life.
 Functions of Water:
 Provides aqueous medium to organisms.
 Water directly participates as a reactant in
several metabolic reactions.

 Vehicle for transport of solutes.
 Associated with regulation of body
temperature.
 Distribution of Water:
 Adult human body contains about 60% (42
litres) water.

 Distributed in intracellular (28L) & extra
cellular (14L) compartments.
 Water turnover and Balance:
 Water intake:
 Water is supplied to the body by
 Exogenous Water.
 Endogenous Water.

 Ingested water & water content of solid
foods constitute the exogenous source of
water.
 Ingestion of water is mainly controlled by
thirst centre located in the hypothalamus.

 The metabolic water produced within the
body is the endogenous water.
 This water (300-350 ml/day) is derived from the
oxidation of foodstuffs.

 The elimination of water from the body
occurs through
 Urine
 Skin,
 Lungs
 Feces.

 Electrolytes are the compounds which readily
dissociate in solution & exist as ions i.e.
positively & negatively charged particles.

 Electrolytes are well distributed in the body
fluids in order to maintain the osmotic
equilibrium and water balance.

 Cations:
Na+ =142
K+ =5
Ca2+ =5
Mg2+ =3
Total =155
 Anions:
Cl- =103
HCO3
- =27
HPO4
2- =2
SO4
2- =1
Proteins =16
Organic acids =6
Total =155

 Cations
 K+ =150
 Na+ =10
 Mg2+ =40
 Ca2+ =2
Total =202
 Anions
HPO4
2- =140
HCO3
- =10
Cl- =2
SO4
2- =5
Proteins =40
Organic acids =5
Total =202

 Na+ is the principal extracellular cation.
 K+ is the intracellular cation.
 Osmolarity:
 The number of moles per liter of solution.
 Osmolality:
 The number of moles per kg of solvent.

 Electrolyte & water balance are regulated
together.
 Kidneys plays an important role.
 Role of Hormones:
 Aldosterone:
 It is a mineralocorticoid produced by
adrenal cortex.

 Aldosterone increases Na+ reabsorption by
renal tubules at the expense of K+ and H+
ions.
 The net effect is the retention of Na+ to the
body.

 An increase in the plasma osmolality
stimulates hypothalamus to release ADH.
 ADH increases water reabsorption by renal
tubules.

 The secretion of aldosterone is controlled by
renin-angiotensin system
 Decrease in blood pressure is sensed by
juxtaglomerular apparatus of the nephron
which secrete renin.
 Renin acts on angiotensinogen to produce
angiotensin I.

 Angiotensin I is converted to Angiotensin II
which stimulates the release of aldosterone.
 Aldosterone & ADH coordinate with each
other to maintain the normal fluid and
electrolyte balance.

 Characterized by water depletion in the body.
 It may be due to insufficient intake or
excessive water loss or both.
 Causes of dehydration:
 Occur as a result of diarrhea, vomiting,
excessive sweating, fluid loss in burns,
adrenocortical dysfunction, kidney diseases &
deficiency of ADH.

 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.
 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.

 Some substances, such as amino acids &
proteins, act acids as well as bases.
 These substances are referred to as
Amphoteric substances.

 The normal pH of the blood is maintained in
the narrow range of 7.35 - 7.45 (slightly
alkaline).
 The body has developed three lines of
defense to regulate the body’s acid-base
balance.

 Blood buffers
 Respiratory mechanism
 Renal mechanism
 Blood buffers:
 A buffer may be defined as a solution of a
weak acid & its salt with a strong base.

 The buffer resists the change in the pH by the
addition of acid or alkali & the buffering
capacity is dependent on the absolute
concentration of salt & acid.
 The buffer cannot remove H+ ions from the
body but it temporarily acts as a shock
absorbant to reduce free H+ ions.

 Bicarbonate buffer
 Phosphate buffer
 Protein buffer
 Bicarbonate buffer system:
 Sodium bicarbonate & carbonic acid (NaHCO3-
H2CO3) is the most predominant buffer system
of ECF (plasma).

 Carbonic acid dissociates into hydrogen and
bicarbonate ions.
H2CO3 H+ + HCO3
-
 By the law of mass action
Ka= -------(1)
 Ka=Dissociation constant of H2CO3.
(H+) (HCO3
-)
H2CO3

 The equation may be rewritten as follows
= Ka -------(2)
pH=log1/H+
 By taking the reciprocals & logarithms.
 log1/H+ = log1/Ka + log -------(3)
(H+)
(H2CO3)
(HCO3
-)
HCO3-
(H2CO3)

 Log1/Ka = pKa
 The equation 3 may now written as
pH = pKa + log --------(4)
 The above equation is referred as Henderson
– Hasselbalch equation for any buffer.
 pH = pKa + log
(H2CO3)
(HCO3-)
(Acid)
(Base)

 The plasma bicarbonate (HCO3-) concentration
is around 24 mmol/l (range 22-26 mmol/l).
 Carbonic acid is a solution of CO2 in water.
 Its concentration is given by the product of
pco2 (arterial partial pressure of CO2 = 40 mm
Hg) & the solubility constant of CO2 (0.03).

 Thus H2CO3 = 40 x 0.03 = 1.2 mmol/l.
 The Henderson-Hasselbalch equation for
bicarbonate buffer is
(H2CO3)
(HCO3-)
pH = pKa + log

 Substituting the values (blood pH = 7.4, pKa
for H2CO3 = 6.1; HCO3- = 24 mmol/l; H2CO3- = 1.2
mmol/l.
7.4 = 6.1 + log 24/1.2
= 6.1 + log 20
= 6.1 + 1.3
= 7.4

 The blood pH 7.4, the ratio of bicarbonate to
carbonic acid is 20 : 1
 The bicarbonate concentration is much higher
(20 times) than carbonic acid in the blood.
 This is referred to as alkali reserve.

 Sodium dihydrogen phosphate and
disodium hydrogen phosphate (NaH2PO4
-
Na2HPO4) constitute the phosphate buffer
 It is mostly an Intracellular buffer.

 The plasma proteins & hemoglobin, constitute
the protein buffer.
 The buffering capacity of proteins is
dependent on the pK of ionizable groups of
amino acids.
 The imidazole group of histidine (pK=6.7) is
the most effective contributor of protein
buffer.

 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
H2CO3 CO2 + H2O
Carbonic anhydrase

 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.

 Hemoglobin binds to H+ ions & helps to
transport CO2 as HCO3
- with a minimum change
in pH.
 In the lungs, hemoglobin combines with O2, H+
ions are removed which combine with HCO3
- to
form H2CO3 & is dissociates to release CO2 to be
exhaled.

 Due to lack of aerobic metabolic pathways,
RBC produce very little CO2.
 The plasma CO2 diffuses into RBC along the
concentration gradient, it 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
- .

Erythrocyte
CO2 + H2O
CA
H2CO3
HHb
HCO3- + H+ Hb
Cl-
Plasma
CO2
HCO3-
Cl-

 The kidneys plays an important role in the
regulation of pH
 Normal urine has a pH around 6.
 The pH of the urine vary from 4.5 to 9.8.

 Excretion of H+ ions
 Reabsorption of Bicarbonate
 Excretion of titratable acid
 Excretion of ammonium 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
 An effective mechanism to eliminate acids (H+)
from the body with a simultaneous generation of
HCO3
-
 H+ combines with non-carbonate base & excreted.

Renal Tubular Cell
Na+
HCO3
- + H+
CA
H2CO3
CA
CO2 + H2O
Blood
Na+
HCO3-
Na+
H+ + B-
HB
Excreted
Tubular lumen

 This mechanism is responsible to conserve blood
HCO3
-, with simultaneous excretion of H+ ions.
 Bicarbonate freely diffuses from plasma into
tubular lumen.
 HCO3
- combines with H+, secreted by tubular cells,
to form H2CO3.
 H2CO3 is then cleaved to form CO2 and H2O.

 As the CO2 concentration builds up in the
lumen, it diffuses into the tubular cells along
the concentration gradient.
 In the tubular cell, CO2 again 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+.
 Reabsorption of HCO3
- is a cyclic process with
the net excretion of H+ or generation of new
HCO3
-
 This mechanism helps to maintain the steady
state & will not be effective for the elimination
of H+ or generation of new HCO3
- .

Renal Tubular Cell
Na+
HCO3- + H+
H2CO3
CA
H2O + CO2
Blood
Na+
HCO3-
Na+
Tubular lumen
H+
HCO3-
Plasma
H2CO3
CO2 + H2O

 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.
 Causes a fall in the pH of urine as low as 4.5.

Renal Tubular Cell
Na+
HCO3- + H+
H2CO3
CA
H2O + CO2
Blood
Na+
HCO3-
Na+
Tubular lumen
H+
Na2HPO4
NaHPO4-
NaH2PO4
Excreted

 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.

Renal Tubular Cell
Glutamine
NH3
Glutamate
Na+
HCO3- + H+
H2CO3
CA
H2O + CO2
Blood
Na+
HCO3-
Na+
Tubular lumen
H+
Excreted
NH3
NH4+

 The acid-base disorders are mainly two
types
 Acidosis-a decline in blood pH.
 Metabolic acidosis-due to a decrease in
bicarbonate
 Respiratory acidosis-Due to an increase in
carbonic acid.

 Alkalosis-a rise in blood pH.
 Metabolic alkalosis-due to an increase in
bicarbonate.
 Respiratory alkalosis-due to a decrease in
carbonic acid.

 Metabolic acidosis:
 Occur due to DM (ketoacidosis).
 Lactic acidosis & renal failure.
 Respiratory acidosis:
 Severe asthama
 Cardiac arrest

 Metabolic alkalosis:
 Vomiting
 Hypokalemia
 Respiratory alkalosis- due to
 Hyperventilation
 Severe anemia

 The total concentration of cations & anions is
equal in the body fluids.
 It is required to maintain electrical neutrality.
 The commonly measured electrolytes are Na+,
K+, Cl- & HCO3-.
 Na+ & K+ together constitute about 95% of the
plasma cations.

 Cl- & HCO3- are the major anions, contributing
to about 80% of plasma anions.
 The remaining 20% of plasma anions include
proteins, phosphate, sulfate, urate and
organic acids.

 Anion gap 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-) in fact represents the
unmeasured anions in the plasma which may
be calculated as follows, by substituting the
normal concentration of electrolytes (mEq/l).

Na+ + K+ = Cl- + HCO3- + A-
136 + 4 = 100 + 25- + A-
A- = 15 mEq/l
• Anion gap in healthy individual is 15 mEq/l.
• Acid-Base disorders associated with alteration in
anion gap.

 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
 NaHCO3
- + Organic acid Na salts of
organic acids + CO2
 Commonly seen in DM.

 The primary defect is due to a retention of CO2
(Increased H2CO3)
 Causes for respiratory acidosis are
depression of respiratory centre, pulmonary
disorders & breathing air with high content of
CO2

 This is due to increase in HCO3
- concentration
 Occur due to excessive vomiting or an
excessive intake of sodium bicarbonate for
therapeutic purposes.
 Respiratory mechanism initiates
compensation by hypoventilation to retain
CO2, this is taken over by renal mechanism
which excrete more HCO3
- and retain H+

 This is due to decrease in H2CO3
concentration.
 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
-

 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.

 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.

 Low plasma concentration of K+
(hypokalemia) leads to an increased
excretion of hydrogen ions, and thus may
cause metabolic alkalosis.
 Conversely, metabolic alkalosis is associated
with increased renal excretion of K+.

 Textbook of Biochemistry – U Satyanarayana

ACID-BASE BALANCE & DISORDERS

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ACID-BASE BALANCE & DISORDERS