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ACID BASE BALANCE

Biochemistry & Clinical Disorders

7.35-7.45
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• 7.4 = 40
• 7.3 = 50

• 7.2 = 65
• 7.1 = 80
• 7.0 = 100

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HUGE
H +

LOAD

A huge
mountain
of hydrogen
is produced,
about,
60 million
nano-moles

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But…

a little mole-hill of
hydrogen being
maintained in plasma/cells,
about 45 nano-moles

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Equation of Life

60,000,000

35-45 45 21-25
1 : 20
1 : 20

Production of acid

• Normal metabolic processes result in

the production of large amounts of
carbonic acid and lesser amounts
of sulfuric, phosphoric, and other
acids.

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Lungs Kidneys dispose the acid but…

• For example, during a 24 hour period,

a person weighing 70 kg disposes of
about 20 mol of carbon dioxide (the
volatile form of carbonic acid) through
the lungs, and about 70 to 100
mmol (or ≈1 mmol/kg) of non-
volatile acids (mainly sulfuric and
phosphoric acids) through the kidneys.

Without change in pH…

• These products of metabolism are
transported to the lungs and kidneys
via the ECF and blood with
no appreciable change in the ECF
pH, and with only a minimal
difference between arterial (pH 7.35
to 7.45) and venous (pH 7.32 to
7.38) blood.

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Because of buffers

• This is accomplished by the buffering

capacity of blood and by respiratory
and renal regulatory mechanisms

pH

• The pH of a solution is defined as

the negative logarithm of the
hydrogen ion activity (pH = -log
aH+).

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• Thus pH is a dimensionless quantity, such

that a decrease in one pH unit
represents a tenfold increase in
H+ activity.

• Potentiometric determinations of blood

pH measure H+ activity and not H+
concentration, although the activity is
assumed to equal the concentration.

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• The pH of plasma may be considered

to be a function of two independent
variables: (1) the PCO2, which is
regulated by the lungs and represents
the acid component of the carbonic
acid/bicarbonate buffer system,

The concentration of titratable base

(base excess or deficit ) which is
regulated by the kidneys.

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• The plasma total CO2 (bicarbonate)

concentration generally is taken as a
measure of the base excess or
deficit in plasma and ECF, although
conditions exist in which it may
not accurately reflect the true base
excess or deficit

• Bicarbonate is the second largest

fraction (behind Cl-) of plasma
anions (≈25 mmol/L).

• Conventionally, it is defined to
include

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• (1) plasma bicarbonate ion (HCO3-),

• (2) carbonate ion (CO32 -), and (3)

CO2 bound in plasma carbamino
compounds

• Actual bicarbonate ion concentration

is not measured, but rather is
calculated from the Henderson-
Hasselbalch equation

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• The analyte usually measured in

plasma is total CO2 , which includes
bicarbonate and dissolved CO2 (d CO2).

• It is calculated from the solubility

coefficient of CO2 in blood at 37°C
(α = 0.0306 mmol/L per mm Hg)
multiplied by the measured P CO2 in
mm Hg.

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• Thus at a PCO2 of 40 mm Hg,

cd CO2 is 1.224 mmol/L (0.0306
mmol/L × 40 mm Hg).

• This cd CO2 value can then be

used, in the Henderson-Hasselbalch
equation, to calculate the total
bicarbonate concentration.

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Henderson-Hasselbalch Equation

Maintenance of PH

I Buffering Action
II. Excretion of the load

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Buffers

Intra-celluar & Extra-cellular

Intracellular:
Hb, Phosphate, Protein

Extracellular:
Bicarb, Phosphate,
Protein

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Protein buffer

• The buffer value (β) of the non

bicarbonate buffers of plasma
totals about 7.7 mmol/L at pH
7.40 and a normal plasma
protein concentration of 72 g/L.

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• The most important buffer groups

of proteins in the physiologic pH
range are the imidazole
groups of histidines (pK ≈7.3).

• Each albumin molecule contains 16

histidines.

• The buffer value of HHb is slightly lower than that

for O2Hb at pH ≈6.5 but higher at pH ≈7.8.

• This is due to a decrease in the pK

value of the “oxygen-linked” acid-base
groups of Hb (C-terminal histidine and
N-terminal valine) when HHb is
oxygenated.

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• For each mole O2 released, the hemoglobin

binds about 0.5 mol of H+ ion.

Protein Buffering Hb//Protein

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• The imidazole groups of hemoglobin

are quantitatively the most important
buffer groups.

• When oxygenated, H+ ions are

liberated from Hb—a phenomenon
called the Haldane effect

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Phosphate Buffer System

• The total concentration of this buffer

in both erythrocytes and plasma
accounts for about 5% of the non
bicarbonate buffer value of plasma.

• Organic phosphate, however, in

the form of 2,3-diphosphoglycerate,
accounts for about 16% of the
non-bicarbonate buffer value of
erythrocytes.

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Build-up of the bicarbonate load:

Kidney

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Reclamation of Bicarbonate

• Normally, ≈90% of filtered HCO3-

(or about 4500 mmol/d) is reclaimed
in the proximal tubule, which parallels
Na+ reabsorption. Thus for each mmol
H+ secreted into the tubular fluid,
1 mmol Na+ and 1 mmol HCO3
enter the tubular cell and return to
the general circulation.

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• When plasma HCO3- concentration

increases above ≈28 mmol/L, the
capacity of the proximal and distal
tubules to reclaim HCO3- is exceeded,
and HCO3- is excreted in the urine.
Type II RTA is caused by a decreased
ability to reabsorb HCO3- in the
proximal tubules, leading to a decrease
in blood pH.

Excretion of the load

Carbondioxide by lungs
Hydrogen ions by kidney

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Disorders

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Metabolic:

Respiratory:

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Anion Gap

Anion Gap

• High AG MA

• Normal AG MA

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Elevated AG means MA

The presence of an elevated anion gap is often

the first indication of a metabolic acidosis and
should be assessed in the electrolyte profiles of
all patients.

• This apparent gap is due to unmeasured

anions(e.g protein, lactate
present in plasma)

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NAGMA

Loss of bicarb
Is the
Primary
reason

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Compensatory Mechanisms in
Metabolic Acidosis

• The respiratory compensatory

mechanism responds to correct
the ratio with increased rate
and depth of respiration to
eliminate CO2.

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• The decrease in pH in
metabolic acidosis stimulates hyper-
ventilation (Kussmaul
respiration), which results in
the elimination of carbonic
acid as CO2, a decrease in
PCO2 (hypocapnia), and thus
a decrease in cdCO2.

The kidneys respond to restore the

normal pH through increased excretion
of acid and preservation of base
(increased rate of Na+-H+ exchange, increased
ammonia formation, and increased
reabsorption of bicarbonate).

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• When the renal compensating

mechanisms are functioning, urine
acidity and ammonia are increased.

Paradoxical Aciduria

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Over compensation clue

• Physiologically, a normal pH
suggests that the acidosis is
over-compensated.

Metabolic Alkalosis

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Compensatory Mechanisms in
Metabolic Alkalosis
1. Decreased Na+ – H+ exchange,
2. 2. Decreased formation of ammonia,
3. decreased reclamation of
bicarbonate.
This response is blunted, however, in
conditions of hypokalemia and
hypovolemia.

Metabolic Acidosis
• Hyperkalaemia

Metabolic Alcholosis
• Hypokalaemia
• Hypocalcaemia

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Respiratory:

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Respiratory:

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Compensatory Mechanisms in
Respiratory Acidosis
• Compensation for respiratory acidosis
occurs immediately via buffers, and
over time via the kidneys and, if
possible, the lungs. Excess carbonic
acid present in blood is buffered
to a great extent by the
hemoglobin and protein buffer
systems

• Buffering of CO2 causes a slight

rise in cHCO3-. Thus in the
immediate post-hypercapnic state,
this compensation may appear as a
metabolic alkalosis

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• The kidneys respond to respiratory

acidosis similarly to the way that
they respond to metabolic acidosis,
namely, with (1) increased Na+-H+
exchange, (2) increased ammonia
formation, and (3) increased
reclamation of bicarbonate

Acute Respiratory Acidosis

• Respiratory Acidosis develops very quickly, in
minutes

• Renal compensation takes 48 hrs to be fully

active

• Rapid death unless compensated//managed

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Respiratory Acidosis usually fatal in…

• Choking
• Acute Asthma
• Broncho-pneumonia

Chronic Respiratory Acidosis

• Compensation is fair
chronic bronchitis ,emphysema &
anaemia

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Respiratory Alkalosis

• Usually acute
• No time for compensation
Hysterical
Mechanical hyper-ventilation
Raised ICP & hypoxia

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Compensatory Mechanisms in
Respiratory Alkalosis

In the first stage, erythrocyte and tissue

buffers provide H+ ions that consume
a small amount of HCO3-. The second
stage becomes operational in prolonged
respiratory alkalosis and depends on renal
compensation as described for metabolic
alkalosis (decreased reclamation of
bicarbonate).

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Pulse-Oxymetry

• Non-invasive method of estimating oxy and

carboxy haemoglobin as different molecules
absorb light at different wavelength

Clinical History

• More important than the investigations

• Investigations are meant for monitoring

• History is the basis for treatment

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Gold Standard

Treat the cause

Caution

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Additional Information

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Tetany of Alkalosis
Above pH 7.55, tetany may develop,
even in the presence of a normal
serum total calcium concentration.
The cause of the tetany is a
decreased concentration of ionized
calcium due to increased binding
of calcium ions by albumin.

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To continue……

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• 7.4 = 40
• 7.3 = 50

• 7.2 = 65
• 7.1 = 80
• 7.0 = 100

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Equation of Life

60,000,000

35-45 45 21-25
1 : 20
1 : 20

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Henderson-Hasselbalch Equation

Compensation Clue: Meta Aci//Alk

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Compensation: Clue

Hco3 : Pco2

• In Res Acidosis 1 : 10

• In Res Alkalosis 2 : 10

Over compensation clue

• Physiologically, a normal pH
suggests that the acidosis is
over-compensated.

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Maintenance of PH

I Buffering Action
II. Excretion of the load

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Protein Buffering Hb//Protein

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Disorders

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Metabolic:

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Respiratory:

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Respiratory:

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Gold Standard

Treat the cause

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Tetany of Alkalosis
Above pH 7.55, tetany may develop,
even in the presence of a normal
serum total calcium concentration.
The cause of the tetany is a
decreased concentration of ionized
calcium due to increased binding
of calcium ions by albumin.

• For each mole O2 released, the hemoglobin

binds about 0.5 mol of H+ ion.

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Haldane effect.

CSF Lactate significance

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Paradoxical Aciduria

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