Vittal

- C.S.N.Vittal
Vittal

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
Vittal

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
Vittal

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.
Vittal

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.
Vittal

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
Vittal

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.
Vittal

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−
Vittal
Vittal

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
Vittal

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)
Vittal

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
Vittal

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.
Vittal

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)
Vittal

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.
Vittal

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
Vittal

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
Vittal
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
Vittal

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
Vittal



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!
Vittal

Re gulation of ar terial pH

Respir ator y
Buf fer System
Renal
Vittal

Acid-Base Homeostasis
Lungs

Metabolism
Input

Output

Maintenance of
Normal [H+]
Buffers

Kidneys
Vittal

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+
Vittal

Buffer
Vittal

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
Vittal

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
Vittal
Vittal

Handerson Hasselbalch Equation

pH = 6.1 + log
pK

HCO3PaCO2 X 0.0301
Vittal

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 −).
Vittal

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

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
Vittal

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.
Vittal

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+
Vittal

Proximal Convoluted Tube
Vittal

Convection
Vittal
Vittal

Distal Convoluted Tube
Vittal

Distal Convoluted Tube
Vittal

Acid-Base in the G-I Tract
CO2

+

H + HCO

3
Vittal

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

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

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
Vittal

Acid-base disturbance 

• Simple

Disorder type

Primary change in HCO3 -

→

Primary change in blood pCO2 →

Respiratory disorder

• Mixed

Metabolic disorder
Vittal
Vittal
Vittal
Vittal
Vittal

Abnormal acid-base
balances
Acid-base
imbalance

Respiratory acidosis

Respiratory alkalosis

Metabolic acidosis-

Metabolic alkalosis-

Plasma pH

Primary
disturbance

Compensation
Vittal

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
Vittal

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
Vittal



Vittal

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Acid-Base Balance : Basics

  • 2. Vittal 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
  • 3. Vittal 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
  • 4. Vittal 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.
  • 5. Vittal 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.
  • 6. Vittal 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
  • 7. Vittal 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.
  • 8. Vittal 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−
  • 10. Vittal 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
  • 11. Vittal 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)
  • 12. Vittal 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
  • 13. Vittal 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.
  • 14. Vittal 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)
  • 15. Vittal 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.
  • 16. Vittal 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
  • 17. Vittal 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
  • 18. Vittal 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
  • 19. Vittal 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
  • 20. Vittal  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!
  • 21. Vittal Re gulation of ar terial pH Respir ator y Buf fer System Renal
  • 23. Vittal 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+
  • 25. Vittal 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
  • 26. Vittal 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
  • 28. Vittal Handerson Hasselbalch Equation pH = 6.1 + log pK HCO3PaCO2 X 0.0301
  • 29. Vittal 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 −).
  • 30. Vittal Saturation of carbonic acid – bicarbonate buffer does not occur because carbonic acid is continuously breaking down into carbon dioxide and water.
  • 31. Vittal 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
  • 32. Vittal 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.
  • 33. Vittal 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+
  • 39. Vittal Acid-Base in the G-I Tract CO2 + H + HCO 3
  • 40. Vittal Acid-base and the Liver Dominant site of lactate metabolism Only site of urea synthesis
  • 41. Vittal Severe Liver Failure NH4+ + oxo-glutarate ---X--> glutamine NH4+ + CO2 --X--> Urea + H+ • metabolic alkalosis • NH4+ toxicity
  • 42. Vittal 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
  • 43. Vittal Acid-base disturbance  • Simple Disorder type Primary change in HCO3 - → Primary change in blood pCO2 → Respiratory disorder • Mixed Metabolic disorder
  • 48. Vittal Abnormal acid-base balances Acid-base imbalance Respiratory acidosis Respiratory alkalosis Metabolic acidosis- Metabolic alkalosis- Plasma pH Primary disturbance Compensation
  • 49. Vittal 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
  • 50. Vittal 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