This document discusses acid-base balance and disorders. It covers 3 key mechanisms to maintain blood pH: 1) blood buffers, 2) respiratory regulation, and 3) renal regulation. The blood's bicarbonate buffer system uses carbonic acid, while tissues also use phosphate and protein buffers. Respiration controls pH by regulating CO2 exhalation. The kidneys compensate for acid-base imbalances over hours by regulating bicarbonate reabsorption and acid excretion. Acid-base disorders include respiratory and metabolic acidosis and alkalosis.

1. Moderator : Dr. M. S. Somannavar
Presenter : Jay prakash sah
Jawaharlal Nehru Medical college, Belgaum,Karnataka,India
Email:shahjayprakash978@gmail.com

2.  INTRODUCTION
 REGULATION OF ACID BASE BALANCE
 BLOOD BUFFERS
 RESPIRATORY MECHANISM
 RENAL MECHANISM
 ACID BASE DISORDERS
 ABG ANALYSIS

3.  Normal blood PH : 7.35-7.45
 Maintenance of blood pH - important
homeostatic mechanism of the body.
 PH less than 7.35 leads to acidosis and
pH more than 7.45 leads to alkalosis.

4.  Acids are proton donors.
HA ↔ H+ + A-
HCL ↔ H ++ CL -
 Bases are proton acceptors.
NH3+H+ ↔ NH4+
HCO3+H+ ↔ H2CO3
• Weak and strong acids :
HCL → H ++ CL - (COMPLETE) - Strong acid
H2CO3 → H+ + HCO3
- ( PARTIAL) - Weak acid
Acid Base

5.  Carbonic acid - Oxidation of c-compounds
 Sulphuric acid - Oxidation of sulphur containing amino acids.
 Phosphoric acid-metabolism of dietary phosphoproteins ,
nucleoproteins, phosphatides .
 Organic acid- oxidation of carbohydrates , fats and proteins.
e.g. pyruvic acid ,lactic acid , acetoacetic acid etc.
 Iatrogenic : - certain medicine like NH4Cl, mandelic acid etc.
NOTE:DIET RICH IN ANIMAL PROTEIN RESULTS IN MORE
ACID PRODUCTION.

6.  Vegetarian diet has an alkalizing effect.
Intestine Blood Cell
From diet
Acid
From foods ,fruits etc
Salts of potasium tartarate + water
Potasium citrate+water
NaHCO3 + H2O
Acetic acid
Lactic acid
Citric acid
Fatty acid
CARBONIC ACID
Lactic acid
Phosphoric acid
Sulphuric acid
TARTARIC ACID+KOH
CITRIC ACID + KOH
CARBONIC Acid+ NaOH
Carbohydrates ,fat,
proteins
H2O+ CO2
Glycogen breakdown
Nucleoprotein
Phosphoprotein
Phospholipid metabolism
Cysteine , cystine and
methionine metabolism

7.  Buffers - resist change in pH.
 Two types
a) Mixture of weak acids with their salt with a strong
base.
b) Mixture of weak bases with their salt with a strong
acid.
Example
1. Bicarbonate buffer (H2CO3 / NaHCO3 )
2. Acetate buffer (CH3COOH / CH3COONa)
3. Phosphate buffer (Na2HPO4 /NaH2PO4 )

8.  If you go running you build up lactic acid in
your muscles.
 Therefore your pH will decrease.
 Buffer will act to increase the pH.
 And vice versa.
So how does it work using chemistry ?

9.  H+ + A- → HA
 OH- + HA → A- + H2O
EX;
H+ + HCO3- → H2CO3
OH- + H2CO3 → HCO3- + H2O

10.  Acid add [ H+ ] therefore ↑ [ H+ ] - ↓ pH
 Base bind [ H+ ] therefore ↓ [ H+ ] - ↑ pH .
 Phosphate buffer
H2PO4 ↔ HPO4
2- + H+

11.  Protein buffer
Amino acid
 If pH ↓
In acidic medium amino acid (NH2) act as a base
and absorbs H+.
 If pH↑
In alkaline medium amino acid (COOH) act as a
acid and release H+.

12.  Acetate buffer
 When HCl is added to the acetate buffer, the salts
react with the acid forming the weak acid , acetic
acid and its salts.
CH3COONa + Hcl CH3COOH + Nacl
 When NaOH is added, the acid reacts with its
forming salt and water.
CH3COOH + NaoH CH3COONa +Nacl
Thus changes in pH is minimised.

13.  Bicarbonate buffer
H2O + CO2 ↔ H2CO3 ↔ H++ HCO3
-
RESPIRATORY RENAL
Le Chatelier’s principle

14. 1. Standard buffer solution are used with
indicator for determination of pH.
2. Buffer are used to check the performance of
electrode used for determination of pH.
3. Used for many chemical reactions including
those catalysed by enzymes.
4. Used in the pathological laboratory to control
pH of culture media for bacteria tissues.
5. Very important in regulating the pH of body
fluids e.g. blood, interstitial fluid ,lymph.

15.  Sodium monohydrogen phosphate (Na2HPO4 )
 Sodium dihydrogen phosphate ( NaH2PO4 )
 Sodium bicarbonate ( NaHCO3 )
 Hydrogen carbonate (H2CO3 )
 Sodium proteinate
 Hydrogen proteinate

16. .
’ ..
erythrocytes
• Potassium bicarbonate
• Carbonic acid
• K2HPO4
• kH2PO4
• Potasium proteinate
• Hydrogen proteinate
Tissue cell
• Potassium proteinate
• Hydrogen proteinate
• Potasium bicarbonate
• Hydrogen bicarbonate
• K2HPO4
• kH2PO4

17.  pH = - log [H+] , dimensionless quantity.
 [H+] means gm of hydrated H+ ion present as
H3O+ per litre of fluid .
 E.g. H2O contains 1/1000000gm of hydrogen ion
in 1 litre ,means [H+]=10-7.
 Decrease of one pH unit represents a ten fold
increase in the H+ activity.
 The pH 7.40 corresponds to a hydrogen ion
concentration of 40 nmol/L ( European centre).

18.  Represents the negative logarithm of the
ionization constant of a weak acid (ka).
 Pk is the pH at which an acid is half
dissociated.
 Acids have pk value less than 7 and bases
have have more than 7.
 Lower pk = stronger acid
 Higher pk = stronger base

19. 1. Enzyme activity
2. Action potential of myelinated nerve
3. Membrane permeability
4. Control of respiration
5. Heart activity
6. Plain muscle activity
7. Oxygen Hb dissociation curve
8. Nerve excitability

20.  3 mechanism
1. Blood buffers : first line of defence
2. Respiratory regulation :second line of defence
3. Renal regulation : third line of defence

21.  Can not remove H+ ions from the body.
 Temporarily acts as a shock absorbant to reduce
the free H+ ion.
 3 buffer system :
1. Bicarbonate buffer
2. Phosphate buffer
3. Protein buffer

22.  Extracellular buffer system of the body
 NaHCO3/H2CO3= [ SALT ] / [ACID]
 NORMAL RATIO= 20 : 1
 Base constituent (HCO3 ) - regulated by the kidney
(Metabolic component)
 Acid (H2CO3) - respiratory regulation
( Respiratory component ).

23.  Neutralization of strong acid and non- volatile
acid entering the ECF is achieved by bicarbonate
buffer ,such acid e.g. HCl , H2SO4,lactic acid etc.
 Strong acid react with NaHCO3 component .thus
lactic acid is buffered as follows:
 NaHCO3 H+ L-
Na L-
H2CO3 (weak acid) + Na Lactate (salt)
lungs(H2co3)
HCO3 H+

24.  H2CO3 H+ + HCO3-
 By the law of mass action, at equilibrium
 Ka = [H+] [HCO3] --------(1)
[H2CO3 ]
 [H+] =Ka [H2CO3 ] -------------(2)
HCO3-
By taking reciprocal and logarithm
 Log 1/[H+] = log 1/Ka +log [HCO3] --------(3)
[ H2CO3 ]
Ka = dissociation constant
Ka=log 1/[H+]

25. pH = pka + log [ HCO3 ] -------(4)
[H2CO3 ]
USES;
1. It determines the pH of blood.
2. Serve as an index to understand the
disturbance in acid base balance of the
body.

26. 1. High concentration
2. Alkali reserve
3. Very good physiological buffer and act as
front line of defence.

27.  Na2HPO4 /NaH2PO4
 Intracellular buffer , pka= 6.8 , 4:1.
 When a strong acid enters ,it is fixed up by the
alkaline po4(Na2hpo4) which is converted to acid po4
as follows
Hcl Na2HPO4
Cl- Na+
NaH2PO4 +NaCl
excreted through urine(kidney)
H+ NaHPO4

28.  When a alkali enters , buffered by acid PO4,
which is converted to alkaline PO4 and is
excreted in urine.
 NaH2PO4 NaOH
NaHPO4 Na+
H2O+Na2HPO4
excreted in urine
H+ OH-

29.  Advantage
 Very effective and better, as pka approaches
physiological ph.

30.  Plasma Protein and Hb - most important
 Buffering action of protein depends on pk of
ionizable group of amino acid
 Effective group- imidazole group of Histidine
 Pk - 6.7

31.  In acidic medium, protein acts as a base, NH2
group takes up H+ ions from the medium
forming NH3+, proteins becomes positively
charged.
 in alkaline medium , protein act as an acid,
COOH group dissociates and gives H+,
forming COO-. H + combines with OH- to
produce molecule of water , proteins become
negatively charged

32.  The respiratory system helps control the
acidity of the blood by regulating the
elimination of CO2 and H2O.
 These molecules are exhaled with every
breath.
H2CO3  H2O + CO2
carbonic acid
 The brain is sensitive to blood CO2 levels and
pH.

33. → Normal blood
pH
→
↑ ↓
Lower blood pH,
higher CO2 levels
↑ ↓
Decreased blood CO2,
increased blood pH
Respiratory
center
stimulated
↑ ↓
Faster, deeper
breathing
↑ ↓
← Increased
amount
of CO2 exhaled
←

34. A significant decrease in CO2 or increase in pH
- causes breathing to decrease
- results in hypoventilation
- less CO2 is exhaled
- increases CO2 - increases H2CO3 and H+ concentrations
- decreases pH back to normal
→→ Normal blood
pH
→→
↑ ↓
Higher blood pH,
lower CO2 levels
↑ ↓
Increased blood CO2,
decreased blood pH
Respiratory
center
stimulated
↑ ↓
Slower, shallower
breathing
↑ ↓
← Decreased
amount
of CO2 exhaled
←

35. • Third line of defense against change in
hydrogen ion concentration
• permanent solution to the acid base
disturbances.
• Kidneys require hours to days to
compensate for changes in body-fluid pH

36. 1. Excretion of H+.
2. Reabsorption of bicarbonate
3. Excretion of titratable acid
4. Excretion of ammonium (NH4+)

37. Plasma PCT CELL Tubular lumen
Na+
HCO3
-
( alkali is recovered )
Na+
HCO3
- + H+
H2CO3
CA
CO2 + H2O
Na+
H+
Excreted in urine

38. plasma PCT cell Tubular lumen
Na+
HCO3
-
Na+
HCO3
- + H+
H2CO3
CA
CO2 + H2O
NaHCO3 (filtered)
Na+ HCO3
-
H+
H2CO3
CA
CO2 + H2O

39. plasma DCT cell tubular lumen
Na+
HCO3
-
Na+
HCO3
- + H+
H2CO3
CA
CO2 + H2O
Na2HPO4 (ph-7.4)
Na+
H+
NaH2PO4 (ph-5.4)
Excreted in urine

40. Plasma DCT cell tubular lumen
Na+
HCO3
-
+H2O
Glutamine glutamate
glutaminase
NH3
Na+
HCO3
- + H+
H2CO3
CA
CO2 + H2O
NH3
Na+
H+
NH4+
( H+ trapped and
excreted)

41.  A 50 year old man came to emergency department after returning
from foreign travel. His symptom included persistent diarrhoea (over
the past 3 days) and rapid respiration . Blood gases were drawn with
following results :
 pH- 7.21 ( )
 pCO2 - 19 mmHg ( )
 pO2 - 96 mmHg
 HCO3- 7 mmol/l
Questions:
1. What is the patient acid base status?
2. Why is the HCO3 level is so low?
3. Why does the patient have rapid respiation?

42.  ACIDOSIS: PH <7.35
a ) METABOLIC ACIDOSIS
b ) RESPIRATORY ACIDOSIS
 ALKALOSIS : PH >7.45
a ) METABOLIC ALKALOSIS
b ) RESPIRATORY ALKALOSIS

44.  The sum of cations and anions in ECF is
always equal , so as to maintain the electrical
neutrality.
 Commonly measured electrolytes in plasma
are Na+, K+,Cl-,HCO3- .
 Unmeasured anion in the plasma constitutes
the anion gap.

45.  This is due to presence of protein anions ,
sulphate , phosphate and organic acids.
 Anion gap = (Na + k) - ( HCO3+ Cl- ) .
 Normally anion gap is about 15 mEq/l
 Normal range = 8-18 mEq/l.

46.  High anion gap acidosis
I. Renal failure
II. Diabetic ketoacidosis
III. Lactic acidosis
 Normal anion gap acidosis
I. Diarrhoea
II. Hyperchloremic acidosis
 Low anion gap
I. Multiple myeloma

47.  Primary deficit of bicarbonate.
 Due to its utilization in buffering H+ ions,
loss in urine or GIT .
 Important cause-excessive production of
organic acids which combine with sodium
bicarbonate and deplete alkali reserve .
NaHCO3+organic acids Na salts of
o organic acids + CO2

48.  Severe uncontrolled diabetes mellitus
(ketoacidosis)- production of organic acids
 Renal failure
 Lactic acidosis
 Severe diarrhoea
 Renal tubular acidosis

49.  Increased production and accumulation of
organic acid causes an elevation in anion gap.
 This type is seen in ketoacidosis
COMPENSATION
• Hyperventilation of lungs(elimination of co2)
• Renal compensation-(3-4days) H+ ions
excreted as NH4+

50.  Primary excess of carbonic acid .
 Causes
• Severe asthma
• Pneumonia
• Cardiac arrest
• Depression of respiratory centre
• COPD

51.  Compensation
H2O + CO2 ↔ H2CO3 ↔ H++ HCO3
-
renal mechanism-
• Increase in renal reabsorption of bicarbonate
• excretion of titrable acidity and NH4+ is
elevated in urine

52.  Primary excess of bicarbonate
Causes
• Severe vomiting
• Hypokalemia
• Intravenous administration of bicarbonate.
• Cushing syndrome

53.  M. alkalosis is commonly associated with
hypokalemia .
 In severe k+ deficiency ,H+ ions are retained
inside the cells to replace missing k+ ions.
 In the tubular cells, H+ions are exchanged
(instead of k+) with the reabsorbed Na+.
 Paradoxically , the patient excretes acid urine
despite alkalosis.

54.  COMPENSATION
H2O + CO2 ↔ H2CO3 ↔ H++ HCO3
-
HYPOVENTILATION- to retain co2
Renal mechanism-
excretes more bicarbonate and retains H+

55.  Primary deficit of carbonic acid
causes
• Hyperventilation
• High altitude
• Salicylate poisoning

56.  Compensation
H2O + CO2 ↔ H2CO3 ↔ H++ HCO3
-
Renal mechanism –
 by increasing excretion of bicarbonate by
decreasing reabsorption
secretion of H+ decreases

57.  Potassium- affects contractility of heart
 Hypokalaemia - life threatening
 Insulin – increases K+ uptake by cells
 Measurement of plasma k+ concentration
assumes significance in acid-base disorders.

58.  Patients with severe uncontrolled DM (M.
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 the heart functioning
and is life threatening.

59.  Therefore in the treatment of diabetic ketoacidosis,
k+ has to be given.
K+ and alkalosis
Hypokalemia leads to increased excretion of hydrogen
ions, and thus may cause M. alkalosis.

60.  Assessment of acid base status.
 Arterial blood
Radial artery – in the Wrist
Brachial artery - in the arm
Femoral artery - in the groin

62. parameter value
[H+] 35-43 mmol/l
pH 7.35-7.45
pco2 4.5-6.0 kpa
34-45 mmHg
1.02-1.35 mmol/l
po2 10.5-13.5 kpa
Bicarbonate 24-30 mmol/l

63. pH co2 Hco3- H+
Respiratory acidosis ⇩ ⇧* ⇧ ⇧
Respiratory alkalosis ⇧ ⇩* ⇩ ⇩
Metabolic acidosis ⇩ ⇩ ⇩* ⇩
Metabolic alkalosis ⇧ ⇧ ⇧* ⇩
Co2+H20 ↔ H2CO3 ↔ H+ +HCO3-

65. A) Arterial blood gas analysis
PH- 7.31 ( ↓) ,
Pco2-55 mmHg (↑) ,
HCO3-28 mmol/l (Normal)
 respiratory acidosis w/o compensation.
B)ABG
Ph-7.31
Pco2-55mmhg
Hco3-35mmol/l (abnormal)
 Respiratory acidosis with compensation

66.  TIETZ TEXT BOOK OF CLINICAL CHEMISTRY
 VARLEY’S CLINICAL CHEMISTRY
 MICHAEL L. BISHOP, CLINICAL CHEMISRY ,SEVENTH EDITION.
 DM VASUDEVAN TEXTBOOK OF BIOCHEMISTRY
 U. SATYANARAYANA TEXTBOOK OF BIOCHEMISTRY
 LAWERENCE A. KAPLAN A TEXT BOOK OF CLINICAL CHEMISTRY
 DR. R. N. ROY A TEXT BOOK OF BIOPHYSICS