The document discusses acid-base balance and regulation in the human body. It covers: 1) Chemical compounds can act as proton donors (acids) or acceptors (bases), and acids and bases react to form salts. The body maintains blood pH through buffers like bicarbonate and proteins. 2) The lungs, kidneys, buffers and liver all play roles in regulating arterial pH. The lungs excrete carbon dioxide through respiration as compensation for metabolic acidosis or alkalosis. The kidneys reclaim bicarbonate and generate new bicarbonate through secretion of hydrogen ions. 3) Disturbances to acid-base balance result in acidosis or alkalosis,

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- C.S.N.Vittal

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ACIDS, BASES AND SALTS
• CHEMICAL COMPOUNDS
CAN BE PROTON DONORS
OR ACCEPTORS
• PROTON DONORS ARE ACIDS
• PROTON ACCEPTORS ARE
BASES
• ACIDS AND BASES REACT TO
NEUTRALIZE EACH OTHER
FORMING SALTS

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H+ ion & pH SCALE
• H+ ion conc. of plasma:
0.000 000 04 mol/L
or
40 nmol/L
• pH is the negative logarithm
of hydrogen ion conc.
Normal : 7.35 – 7.45

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Acid Base Balance
Introduction
Metabolic processes continually
produce acid and, to a lesser
degree, base.
H+ :

can attach to negatively charged
proteins &

in high concentrations, alter their
overall charge, configuration, and
function.

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Acid Base Balance
Introduction
To maintain cellular function, the body has
elaborate mechanisms that maintain blood
H+ concentration within a narrow range—


typically
: 37 to 43 nmol/L
(pH 7.35 to 7.45), &
ideally : 40 nmol/L
(pH = 7.4)
Disturbances of these mechanisms can have
serious clinical consequences.

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Types of acids in the body
Volatile acid
– Can leave solution and enter the atmosphere (e.g. carbonic
acid)
– Produced by aerobic metabolism
Fixed acids
– Acids that do not leave solution (e.g. sulfuric and phosphoric
acids)
– Generated during catabolism of amino acids
Organic acids
– Participants in or by-products of aerobic and anaerobic
metabolism
– Metabolic byproducts such as lactic acid, ketone bodies

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Acid-Base Physiology

Most acid comes from carbohydrate and fat
metabolism (15,000 to 20,000 mmol of CO2 daily)

CO2 combines with water (H2O) in the blood to
create carbonic acid (H2CO3), which in the presence
of the enzyme carbonic anhydrase dissociates into
H+ and HCO3−.

The H+ binds with Hb in the blood and is released
with oxygenation in the alveoli, the above reaction is
reversed, creating H2O and CO2, which is exhaled

Very little metabolic acid is produced - which is
eliminated by kidney and liver.

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Acid-Base Physiology

Most base comes from metabolism of anionic
amino acids (glutamate and aspartate) and

from oxidation and consumption of organic
anions such as lactate and citrate, which
produce HCO3−

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pH
pH : the negative logarithm of the
hydrogen ion concentration
o a "decrease" in pH means an "increase" in acidity.
Standard pH: (Hasselbalch, 1916)
the pH under standard conditions:
o PCO2=40 mmHg, and 37oC, and saturated with oxygen
Arterial pH = 7.4
Venous pH = 7.36

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PaCO 2
PaCO 2 :
the partial pressure of carbon dioxide.
The normal value in arterial blood is
40 mm Hg (or 5.33 kPa)
PaCO2 ∝ CO 2 production + inspired CO 2
Low PaCO2 reflects the rate of CO2 elimination
Principal physiological cause of hypocapnia is
hyperventilation Intentional, incidental (HFV, ECMO)

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Bicarbonate
HCO 3 - : concentration (in mEq/L) of the
bicarbonate ion is not measured, it is calculated
from the PCO2 and pH
Standard Bicarbonate : (Jorgensen and Astrup, 1957)
bicarbonate concentration under standard
conditions: PCO2=40 mmHg, and 37oC, and
saturated with oxygen.
an excellent measurement of the metabolic
component.
= 21-27 mmol/l

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Base Escess
(Astrup and Siggard-Andersen, 1958)
a better method of measuring the metabolic
component.
In essence the method calculated the
quantity of Acid or Alkali required to return
the plasma in-vitro to a normal pH under
standard conditions.

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Base Excess & Base Deficit
(Astrup and Siggard-Andersen, 1958)
Amount of strong acid or base that has to
be added to a sample of blood to produce
a pH of 7.4 under the specified conditions
fro standard bicarbonate.
a more accurate in assessing metabolic
component of acid-base status.
Normal Buffer Base = 48mMol/L
(41.8 + 0.4 X Hb in g/dL)

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Base Excess & Base Deficit
Base excess – 3 mmol/l :
means 3 mmol of strong acid had to be added
to each litre of original sample to get a pH of
7.4 while kept at 370C and a PaCO2 of 40 mm
Hg.
Base deficit – 3 mmol/l :
means 3 mmol of strong base had to be added
to each litre of original sample to get a pH of
7.4 while kept at 370C and a PaCO2 of 40 mm
Hg.

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Base Excess & Base Deficit
Normal
A base excess below -2.0 mmol/l : Metabolic acidosis
A base excess above +2.0 mmol/l : Metabolic alkalosis
Range

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Anion Gap
the difference between major plasma cations and
major plasma anions.
Anion gap = ([Na+] +[K+]) - ([Cl--] +[HCO3-])
Gap = Na+ + K+ - Cl- - HCO3[ 15 = 140 + 5 - 105 - 25
mMol/L]
Normal Anion Gap
Children
: 9mo. 19 yrs = 8 + 2 mMol /L
Adults : 12 + 2 mMol /L

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Metabolic Acidosis:
Types “Normal Anion Gap”, “ Anion
Gap”
≡ [Na+] - ([Cl-] + [HCO3-])
Alb-
AlbHCO3-
AlbHCO3A-
HCO3-
Na+
Na+
Cl-
Na+
Cl-
No Anion gap
M acidosis
Cl-
High Anion gap
M acidosis

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ACID/BASE BALANCE AND THE BLOOD
[OH -]
[H+]
Acidic
Alkaline (Basic)
Neutral
pH
0
Venous Blood
Acidosis
6.8
7
7.4
Normal
7.35-7.45
14
Arterial Blood
Alkalosis
8.0

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
Abnormal acid-base balance
Acid-base imbalances can be defined
as acidosis or alkalosis.
Acidosis is a state of excess H+
Acidemia results when the blood pH is < 7.35

Alkalosis is a state of excess HCO3Alkalemia results when the blood pH is > 7.45
You can have acidosis without acidemia but
You can not have acidemia without an acidosis!

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Re gulation of ar terial pH
Respir ator y
Buf fer System
Renal

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Acid-Base Homeostasis
Lungs
Metabolism
Input
Output
Maintenance of
Normal [H+]
Buffers
Kidneys

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CHEMICAL BUFFER SYSTEMS
Unbuffered Salt Solution
Na+
Add
HCl
ClCl-
Protons taken up as Carbonic Acid
H2CO3: HCO3- Buffer
HCO3H+
H+
Na+
Cl-
H2CO3
All protons are free
Add
HCl
H2CO3
HCO3-
+
H+

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Buffer

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CHEMICAL BUFFER SYSTEMS
Weak acid/salt systems act as a
“sponge” for protons
As acidity tends to increase they take
protons up
As acidity tends to decrease they
release protons

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CHEMICAL BUFFER SYSTEMS
Extracellular Buffers :
Carbonic acid/Bicarbonate: Primary buffer against
non-carbonic acid changes
Serum Proteins (albumin)
Ammonia ( in renal tubules)
Intracellular Buffers :
Hemoglobin
Intracellular proteins
Phosphates

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Handerson Hasselbalch Equation
pH = 6.1 + log
pK
HCO3PaCO2 X 0.0301

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Kassirer and Bleich Equation
(Handerson Equation)
H + = 24 X
pCO2
HCO3-
With this formula, any 2 values (usually H+ and Pco2)
can be used to calculate the other (usually HCO3 −).

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Saturation of
carbonic acid – bicarbonate
buffer does not occur
because
carbonic acid
is continuously
breaking down into
carbon dioxide
and
water.

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Re gulation of ar terial pH
•• Respiratory
Respiratory
•• Buffer System
Buffer System
•• Renal
Renal
Respiratory Control:
•The power of the lungs to excrete large quantities of carbon
dioxide enables them to compensate rapidly, i.e. metabolic
acidosis and metabolic alkalosis normally elicit characteristic
partial respiratory compensation almost immediately.
• Not so efficient (50%)
• Less in preterm babies
• Control of respiratory centre
• A CO2 conc. of > 9% depresses centers and causes CO2 narcosis

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Re gulation of ar terial pH
•• Respiratory
Respiratory
•• Buffer System
Buffer System
•• Renal
Renal
Buffer System:
• Act within seconds
• Act at cellular level
• ¾ of body’s buffering system
from intracellular proteins and
phosphates.

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Re gulation of ar terial pH
•• Respiratory
Respiratory
•• Buffer System
Buffer System
•• Renal
Renal
Renal Control:
 HCO3-
 Reclamation of almost (80%) all the filtered HCO3- (5000 mEq)
Substantial task: 180 L x 24 mmol/L = 4320 mmol bicarbonate filtered/day
 Generation of new HCO3- with net secretion of H+
(energy dependant)
 H+
(1 - 1.5 mmol/kg/day)
 Increased excretion of acid as phosphate buffer and as ammonia
 Na+ re-absorption during the formation of H+

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Proximal Convoluted Tube

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Convection

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Distal Convoluted Tube

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Distal Convoluted Tube

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Acid-Base in the G-I Tract
CO2
+
H + HCO
3

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Acid-base and the Liver
Dominant site of lactate metabolism
Only site of urea synthesis

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Severe Liver Failure
NH4+ + oxo-glutarate ---X--> glutamine
NH4+ + CO2 --X--> Urea + H+
• metabolic alkalosis
• NH4+ toxicity

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Response of body to increase in acid load
Overview
1. Induces extra-cellular buffering by HCO32. Within minutes Respiratory Compensation
with decrease in pCO2 and H2CO3 [to
maintain a ratio of HCO3- : H2CO3 ] of 20 : 1
3. Intracellular buffering – in 1 to 4 hours
4. Renal acid excretion and production of new
HCO3- formation : in hours to days

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Acid-base disturbance
• Simple
Disorder type
Primary change in HCO3 -
→
Primary change in blood pCO2 →
Respiratory disorder
• Mixed
Metabolic disorder

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Abnormal acid-base
balances
Acid-base
imbalance
Respiratory acidosis
Respiratory alkalosis
Metabolic acidosis-
Metabolic alkalosis-
Plasma pH
Primary
disturbance
Compensation

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Abnormal acid-base
balances
Acid-base
imbalance
Plasma pH
Primary
disturbance
Respiratory acidosis
Low
Increased pCO2
Increased renal net acid
excretion with resulting
increase in serum
bicarbonate
Respiratory alkalosis
High
Decreased pCO2
Decreased renal net acid
excretion with resulting
decrease in serum
bicarbonate
Metabolic acidosis-
Low
Metabolic alkalosis-
High
Decreased HCO3
Increased HCO3
-
-
Compensation
Hyperventilation with
resulting low pCO2
Hypoventilation with
resulting increase in
pCO2

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Conclusions
Acid Base Homeostasis is a Dynamic Process
Buffers form the first line of Defence
Bicarbonate buffers are by far the most important
Lungs, Kidneys and Liver play important role in
Acid Base Homeostasis

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