Cellular Respiration

Acid and Base Balance and Imbalance

Cellular Respiration

Oxygen Transport

Haemoglobin

Oxyhaemoglobin dissociation curve

relates oxygen saturation (sO2) and partial pressure of oxygen in the blood (pO2),
and is determined by what is called "Haemoglobin affinity for oxygen"; that is, how
readily haemoglobin acquires and releases oxygen molecules

CO2 transport
10

CO2 is carried in blood in three different ways:

Most of it (about 70% to 80%) is converted to
bicarbonate ions HCO3-, by the enzyme carbonic
anhydrase in the red blood cells, by the reaction
CO2 + H2O H2CO3 H+ + HCO3
5% 10% is dissolved in the plasma,
and 5% 10% is bound to hemoglobin as carbamino
compounds

Arterial blood gas

pH Review
13

pH = - log [H+]
H+ is really a proton
Range is from 0 - 14
If [H+] is high, the solution is acidic; pH < 7
If [H+] is low, the solution is basic or alkaline ;

pH > 7

ACID AND BASE

14

Acids are H+ donors.

HCl
H+ + Cl Bases are H+ acceptors, or give up OH- in solution.
KOH
K+ + OH Acids and bases can be:
Strong dissociate completely in solution

HCl, NaOH

Weak dissociate only partially in solution

Lactic acid, carbonic acid

Ka is an equilibrium constant. For an acid-base equilibrium

between a generic acid, HA, and its conjugate base, A,
HA

A + H+, Ka is defined as

The negative logarithm of the acid dissociation constant (Ka) is

the ionisation exponent (pKa) of the acid
pKa = -log Ka
For base,
pKb = -log Kb
Therefore stronger the acid, greater is its ionisation, higher
its Ka and lower its pKa.
15

Or

H+ =

or

-log [H+] =

Ka [HA]
[A-]
-log Ka -log

[HA]
[A-]

Since, pH is negative logarithm of molar concentration of H+

ion to the base 10 and log Ka=pKa
pH = pKa + log [A-]
[HA]
THE HENDERSON-HASSELBALCH EQUATION
When ratio of dissociated and undissociated particle is same
i.e. [A-]=[HA] , pH= pKa

16

BUFFERS
~ buffers are solution which resist any change of pH
~ types
mixture of weak acid with their salt and a strong base
or mixture of weak base with their salt and a strong acid
~

H2CO3/NaHCO3 (BICARBONATE BUFFER)

CH3COOH/CH3COONa (ACETATE BUFFER)

~ buffering capacity of a buffer is defined as the ability of the

buffer to resist change in pH when an acid or base is added.
~ How does buffer act?

17

pH = pKa + log [salt/base]

[acid]
~ HENDERSON HESSELBALCH equation gives relationship
between pH, pKa, concentration of acid and conjugate base (or
salt), thus when [base/salt]=[acid] ; then pH=pKa.
~ application of the equation
1. determination of pH of buffer solution on addition of
salt or acid
2. measurement of concentration of salt and acid by
measuring pH.
~ most effective buffers when pH=pKa, range 1 pH unit
higher or lower than pKa.

18

The Body and pH

19

Homeostasis of pH is tightly controlled

Extracellular fluid = 7.4
Blood = 7.35 7.45
< 6.8 or > 8.0 death occurs
Acidosis (acidemia) below 7.35
Alkalosis (alkalemia) above 7.45

20

Small changes in pH can produce major disturbances

21

Most enzymes function only with narrow pH ranges

Acid-base balance can also affect electrolytes (Na+,

K+, Cl-)
Can also affect hormones

Acid-Base Biochemistry
Physiology
Sources of acid

Metabolism of food
Metabolism of drugs
Inborn errors of metabolism

The body produces more acids than bases

23

Acids take in with foods

Acids produced by metabolism of foods

- sulphuric acid from protein

Lactic acid from sugars

Ketoacids from fats

Cellular metabolism produces CO2

CO2 + H20 H2CO3

H+ + HCO3-

Acid-Base Biochemistry
Physiology
Greatest potential source of acid:
Carbon dioxide
(1) CO2 + H2O <=> H2CO3
(2) H2CO3 <=> H+ + HCO3Potentially 15,000 mmol/24 hours

26

27

Acid-Base Biochemistry
Physiology
Buffering systems in blood

Bicarbonate ions-most important

Proteins including intracellular proteins
Haemoglobin

Bicarbonate buffer
29

Sodium Bicarbonate (NaHCO3) and carbonic acid

(H2CO3)
Buffer system of plasma accounts 65% of
buffering capacity
Average normal value of HCO3- is 24mmol/liter,
H2CO3 is 1.2mmol/liter, pKa for H2CO3 is 6.1
Substituting in HH eq.
pH = pKa + log [HCO3-/H2CO3]
7.4=6.1+ log 24/1.2
ratio of 20
Maintain a 20:1 ratio : HCO3- : H2CO3

Acid-Base Biochemistry
Physiology

The bicarbonate system is enhanced by the fact

that carbonic acid can be formed from CO2 or
disposed of by conversion to CO2
CO2 + H2O <=> H2CO3

Acid-Base Biochemistry
Physiology
For every hydrogen ion buffered by bicarbonate a

bicarbonate ion is consumed.

To maintain the capacity of the buffer system, the
bicarbonate must be regenerated
However, when bicarbonate is formed from
carbonic acid (CO2 and H2O) equimolar amounts of
[H+] are formed

Acid-Base Biochemistry
Physiology
Bicarbonate formation can only continue if these

hydrogen ions are removed

This process occurs in the cells of the renal tubules
where hydrogen ions are secreted into the urine
and where bicarbonate is generated and retained in
the body

Acid-Base Biochemistry
Physiology
2 different processes:
Bicarbonate regeneration (incorrectly
reabsorption)
Hydrogen ion excretion

Protein Buffers
34

Includes hemoglobin, work in blood and interstitial fluid

Carboxyl group gives up H+
Amino Group accepts H+
Side chains that can buffer H+ are present on 27 amino

acids.

Phosphate buffer
36

Major intracellular & in urine

Na2HPO4/NaH2PO4
pKa value is 6.8
H+ + HPO42- H2PO4OH- + H2PO4- H2O + H2PO42-

Buffering systems of the body

ACID BASE
REGULATION

38

RENAL MECHANISM FOR REGULATION OF ACID BASE

BALANCE

~ Buffer system: temporary solution

~ Respiratory mechanism provide short time regulation
~ Renal mechanism: permanent solution

39

Events in lungs and tissue

lung

tissue
HCO3-

HCO3HHb

HHb

O2

O2
H+
H2CO3
H2O

H+
HbO2

HbO2

CO2

EXPIRED AIR

H2CO3
CO2 H2O

Isohydric transport
of CO2
40

METABOLISM

Acid-Base Imbalances
41

The body response to acid-base imbalance is called

compensation
May be complete if brought back within normal limits
Partial compensation if range is still outside norms.
Compensation
If underlying problem is metabolic, hyperventilation or
hypoventilation can help: respiratory compensation.
If problem is respiratory, renal mechanisms can bring about
metabolic compensation.

Acidosis
42

Principal effect of acidosis is depression of the CNS

through in synaptic transmission.

Generalized weakness
Deranged CNS function the greatest threat
Severe acidosis causes
Disorientation
coma

Alkalosis
43

Alkalosis causes over excitability of the central and

peripheral nervous systems.

Numbness
Lightheadedness
It can cause :
muscle spasms or tetany
Convulsions
Loss of consciousness

4 types of primary acid-base disorders

44

Name

Change

Respiratory acidosis

PCO2

Respiratory alkalosis

PCO2

Metabolic acidosis

HCO3

Metabolic alkalosis

HCO3

Acid-base disorders
Respiratory
acidosis/alkalosis:
change in pCO2

Respiratory Acidosis
46

Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg.

Hypercapnia high levels of CO2 in blood
Ratio of bicarbonate/carbonic acid decreased
Chronic conditions:

Depression of respiratory center in brain that controls breathing rate

drugs or head trauma
Paralysis of respiratory or chest muscles
Emphysema

Acute conditons:
Adult

Respiratory Distress Syndrome

Pulmonary edema
Pneumothorax

Compensation for Respiratory Acidosis

47

Kidneys eliminate hydrogen ion and retain

bicarbonate ion
Increase NH3 formation
Hyperventilation sets in but removal of CO2 is

partial as pathogenesis is involved

Compensation for Respiratory Acidosis

49

Respiratory Alkalosis
50

Carbonic acid deficit

pCO2 less than 35 mm Hg (hypocapnea)
Ratio of bicarbonate/carbonic acid increased
Most common acid-base imbalance
Primary cause is hyperventilation

Respiratory Alkalosis
51

Compensation of Respiratory Alkalosis

Kidneys conserve hydrogen ion
Excrete bicarbonate ion
Decreased excreation of NH3,retention of Cl-

52

Acid-base disorders
Metabolic
acidosis/alkalosis:
change in bicarbonate
concentration

Metabolic Acidosis
54

Bicarbonate deficit - blood concentrations of

bicarbonate drop below 22mEq/L

Causes:

Loss of bicarbonate through diarrhea or renal dysfunction

Accumulation of acids (lactic acid or ketones) which may
occur in DM, starvation, high fever.
Failure of kidneys to excrete H+

Symptoms of Metabolic Acidosis

55

Headache, lethargy
Nausea, vomiting, diarrhea

Compensation for Metabolic Acidosis

Increased ventilation
Renal excretion of hydrogen ions if possible
K+ exchanges with excess H+ in ECF

(H+ into cells, K+ out of cells)

Compensation for Metabolic Acidosis

56

57

Metabolic Alkalosis
58

Bicarbonate excess - concentration in blood is

greater than 26 mEq/L

Causes:

Excess vomiting = loss of stomach acid

Endocrine disorders
Heavy ingestion of antacids
Severe dehydration

Compensation for Metabolic Alkalosis

59

Decreased pulmonary respiration

Increased alkali excretion
Decreased acid excretion
Decreased NH3 formation

Symptoms of Metabolic Alkalosis

Respiration slow and shallow
Hyperactive reflexes ; tetany
Often related to depletion of electrolytes
Atrial tachycardia
Dysrhythmias

Compensation for Metabolic Alkalosis

60

61

Remember!!
62

When you see respiratory, think PCO2

When you see metabolic, think [HCO3]

65

THANK YOU