Acid Base Balance and Imbalance lecture. Simple to understand.

2. Acid Base

4. Hydrogen containing substances which dissociate in solution to
release H+
Any ionic or molecular substance that can act as a proton (H+) donor.
Strong acid：HCl, H2SO4, H3PO4.
Weak acid：H2CO3, CH3COOH.
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
SO4
H
H
H
H
H
H H
ACIDS

5. ▪ VOLATILE ACIDS (20,000mEq/day):
Produced by oxidative metabolism of CHO,Fat,Protein
Average 15000-20000 mmol of CO₂ per day
Excreted through LUNGS as CO₂ gas
• FIXED ACIDS (1 mEq/kg/day)
 Acids that do not leave solution, once produced they remain in
body fluids until eliminated by KIDNEYS
Eg: Sulfuric acid, Phosphoric acid, Organic acids
Are most important fixed acids in the body
Are generated during catabolism of:
amino acids(oxidation of sulfhydryl groups of cystine, methionine)
Phospholipids(hydrolysis)
nucleic acids
Metabolic Sources of Acids

6. ▪Physiologically important acids include:
▪ Carbonic acid (H2CO3)
▪ Phosphoric acid (H3PO4)
▪ Pyruvic acid (C3H4O3)
▪ Lactic acid (C3H6O3)
Lactic acid
Pyruvic acid
Phosphoric acid
ACIDS

7.  Bases can be defined as:
♥ A proton (H+) acceptor
♥Any ionic or molecular substance that can act as a proton
acceptor.
♥Strong alkali： NaOH, KOH.
♥Weak alkali：NaHCO3, NH3, CH3COONa.
CO3
Na
H
CO3
H
H
CO3
H
H
CO3
H
H
CO3
Na
H
CO3
H
Na
CO3
Na
H
CO3
H
H
CO3
H
Na
H
Na
H
Na
Na
Bases

8. ▪Physiologically important bases include:
▪ Bicarbonate (HCO3
- )
▪ Biphosphate (HPO4
-2 )
Biphosphate
Bases

9. ▪ Ability of an acid-base mixture to resist sudden changes in pH is
called its buffer.
▪ Buffer is a solution of weak acid and its corresponding salt.
▪ Buffer resists a change in pH when a small amount of acid or base
is added to it.
▪ By buffering mechanism a strong acid (or base) is replaced by a
weaker one.
Buffer

10. pH

11. ▪ pH is the negative log of hydrogen ion
concentration.
pH= -log[H+]
 If [H+] is high, the solution is acidic; pH
< 7
 If [H+] is low, the solution is basic or
alkaline ; pH > 7
pH

12. Acid Base

13. The Body and pH
▪ 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

15. ▪ Most enzymes function only with narrow pH ranges
▪ Acid-base balance can also affect electrolytes (Na+, K+, Cl-)
▪ Affects membrane functions, alter protein functions, etc.
▪ Can also affect hormones
Small changes in pH can produce
major disturbances

16. ▪ Two types of acids are produced in the body:
 Volatile acids : Carbonic acid formed from CO2
 Non-volatile acids: metabolism of protein, CHO, lipids
e.g. lactic acid, keto acid,
sulphuric acids

17. To maintain the blood pH at 7.35 –7.45, there are three
primary systems that regulate the hydrogen ion concentration
in the body fluids.
These are:
Renal Regulation
Respiratory Regulation
Buffers system
Regulation of blood pH.

19. ♣These are the first line of defense against pH change
♣React very rapidly within seconds.
♣The buffer systems of the blood, tissue fluids and cells;
immediately combine with acid or base to prevent
excessive changes in pH.
♣It do not eliminate hydrogen ions from the body or add
them to the body but only keep them tied up until balance
can be re-established.
♣Three major chemical buffer systems
 Bicarbonate buffer
 Phosphate buffer
 Protein buffer
Buffer system

20. Phosphate
buffer
Protein buffer
Bicarbonatebuf
fer
Hemoglobin
buffer
(RBCs only)
Plasma protein
buffer
Amino acid buffer
(all proteins)
ICFECF
Buffer Systems in Body Fluids

21. Bicarbonate Buffer System (NaHCO3
-/H2CO3)
▪ Bicarbonate Buffer is the most important extracellular fluid
buffer.
▪ Bicarbonate Buffer constitute, Sodium bicarbonate (NaHCO3-)
and carbonic acid (H2CO3).
▪ Carbonic acid dissociates into hydrogen and bicarbonate ions.
▪ Under normal circumstances there is much more bicarbonate
present than carbonic acid (the ratio is approximately 20:1).
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H+ HCO3
-
H2CO3
+

22. ♠Hydrogen ions generated by metabolism or by ingestion
react with bicarbonate base to form more carbonic acid
HCO3
-H2CO3
H2CO3H+ + HCO3
-
Mechanism of action of bicarbonate buffer
 When pH is rising….
CO2 + H2O

23. ♠Hydrogen ions generated by metabolism or by ingestion
react with bicarbonate base to form more carbonic acid
H+
HCO3
-
H2CO3
Mechanism of action of bicarbonate buffer
 When pH is falling….
H2CO3
H+ + HCO3
-

24. Importance of Bicarbonate Buffer
▪ Present in high concentration – (accounts 40-50%)
▪ Have alkali reserve – (ratio of HCO3
-
to H2CO3 is 20:1)
▪ Concentration of component can be regulated by
▪ The base constituent, bicarbonate (HCO3
–), is regulated by the kidney
▪ While the acid part, carbonic acid (H2CO3), is under respiratory regulation
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25. Alkali Reserve
▪ Plasma Bicarbonate (HCO3– ) represents the alkali reserve and it
has to be sufficiently high to meet the acid load.
▪ If it was too low to give a ratio of 1, all the HCO3– would have
been exhausted within a very short time; and buffering will not
be effective.
▪ So, under physiological circumstances, the ratio of 20:1 (a high
alkali reserve) ensures high buffering efficiency against acids.

26. PHOSPHATE BUFFER SYSTEM (Na2HPO4/ NaH2PO4)
It is not important as blood buffer.
It plays a major role in buffering renal tubular fluid and the
intracellular fluid.
The normal ratio of Na2HPO4 and NaH2PO4 in plasma is 4:1
and this is kept constant by the help of kidneys for which
phosphate buffer system is directly related to the kidneys.
H+ Na2HPO4+
NaH2PO4
Na++
Na2HPO4 + H+ NaH2PO4 + Na+

27. PHOSPHATE BUFFER SYSTEM
♠Regulates pH within the cells and the urine
♠Phosphate concentrations are higher intracellular and
within the kidney tubules.
♠More phosphate ions are found in
tubular fluids
♠More powerful than
bicarbonate buffer system
HPO4
-2

28. ▪In the blood, plasma proteins especially
albumin act as buffer because:
▪– It contain a large number of dissociable
▪ acidic (COOH) &
▪ basic (NH2) groups.
▪– In acid solution, NH2 accept excess H+
▪– In basic solutions, COOH give up H+
▪– Other important buffer groups of proteins in
the physiological pH range, are the imidazole
groups of histidine.
PROTEIN BUFFER SYSTEM

29. Hemoglobin buffer
Hemoglobin buffers in RBC plays an important role in
respiratory regulation of pH.
It helps in transport of metabolically produced CO2
from cell to lungs for excretion.
As hemoglobin releases O2 it gains a great affinity for
H+

30. RBC
H2CO3H2OCO2 +
H+ HCO3
-
H2CO3 +
H+ Hb+ HHb
HbO2
H2O
O2+
H2CO3
HHb H+
+
H+ HCO3
-+
H2CO3 +CO2
CO2
RBC
Lungs
Tissues

32. Respiratory Mechanism
▪ Respiratory mechanism is called second line of defence.
▪ It is achieved by regulating the concentration of carbonic acid
(H2CO3) in the blood and other body fluids by the lungs.
• The respiratory center regulates the removal or retention of CO2
and thereby H2CO3 from the extracellular fluid by the lungs.
• Thus lungs, function by maintaining one component (H2CO3) of
the bicarbonate buffer

33. 5/1/2015ACID BASE BALANCE BY ASHOK KATTA 35
RESPIRATORY CENTRE
Respiratory centers
Medulla oblongata
Pons
• The rate of respiration is controlled by chemoreceptors present in
respiratory centre of brain which is sensitive to change in pH.

34. 5/1/2015ACID BASE BALANCE BY ASHOK KATTA 36
CHEMOSENSITIVE AREAS
Increases in CO2 & H+ stimulate the
respiratory center
♣The effect is to raise respiration
rates
♣ But the effect diminishes
in 1 - 2 minutes
H+
H+
H+
H+
H+
H+
H+
H+
H+
Chemo sensitive areas of the respiratory center are
able to detect blood concentration levels of CO2 and
H+

35. RESPIRATORY CONTROL OF pH
pH rises toward normal
rate and depth of breathing increase
CO2 eliminated in lungs
H+ stimulates respiratory center in medulla oblongata
cell production of CO2 increases
CO2 + H2O H2CO3
H2CO3 H+ + HCO3
-
H+ acidosis; pH drops

36. RBC
H2CO3H2OCO2 +
H+ HCO3
-
H2CO3 +
H+ Hb+ HHb
HCO3
-
Cl-Cl-
Chloride shift

38. ▪ The role of kidneys in the maintenance of acid-base balance of
the body (blood pH) is highly significant.
▪ The renal mechanism tries to provide a permanent solution to
the acid-base disturbances.
▪ This is in contrast to the temporary buffering system and a
short term respiratory mechanism.
▪ The kidneys regulate the blood pH by maintaining the alkali
reserve
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Renal Mechanism

39. Urine pH normally lower than blood pH
▪ The pH of urine is normally acidic (6.0). This clearly indicates
that the kidneys have contributed to the acidification of urine,
when it is formed from the blood plasma (pH 7.4).
▪ In other words, the H+ ions generated in the body in the normal
circumstances are eliminated by acidified urine.
▪ Hence the pH of urine is normally acidic (6.0), while that of
blood is alkaline (7.4). Urine pH, however, is variable and may
range between 4.5-9.5, depending on the concentration of H+
ions.
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40. Renal Mechanism
▪The renal mechanism of acid base balance is
achieved by…
Excretion of H+ ions
Reabsorption of bicarbonate
Excretion of titratable acid
Excretion of ammonium ions.
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41. Excretion of H+ ions
Na+ Na+ Na+
H+
HCO3
+B-
HB
Excreted
CO2+H2O
HCO3
-H+
+
H2CO3
CA

42. Reabsorption of
bicarbonate
Na+Na+Na+
H+HCO3
-
Plasma
HCO3
-
H2CO3
CO2 + H2O
CA
CO2+H2O
HCO3
-
H+
+
H2CO3
CA

43. Excretion of
titratable acid
Na+
Na+ Na+
H+
HCO3
Excreted
Na2HPO4
NaHPO4
-
NaH2PO4
CO2+H2O
HCO3
-H+
+
H2CO3
CA

44. Excretion of
ammonium ions
Na+
Na+
Na+
H+
Excreted
NH3
Glutamine
Glutamine
NH3
NH4
+
HCO3
CO2+H2O
HCO3
-H+
+
H2CO3
CA

46. ▪ The body has developed an efficient system for the
maintenance of acid-base equilibrium with a result that
the pH of blood is almost constant (7.4)

47. The response to Acid–Base Imbalance
Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory
Mechanisms in the Regulation of Plasma pH.
 Respiratory
rate lowers PCO2
H2CO3 +
(Carbonic acid) (Bicarbonate
Ion)
Addition
of H+
HCO3
-H2OCO2 + (Sodium
bicarbonate)
NaHCO3
HCO3
-
Na+
Other
buffer
systems
absorb H+
Generation
of HCO3
-
The response to acidosis
Secretion
of H+
BICARBONATE RESERVE
H+
LUNGS

48. Interactions among the Carbonic Acid–Bicarbonate Buffer System and
Compensatory Mechanisms in the Regulation of Plasma pH.
The response to Acid–Base Imbalance
 Respiratory
rate lowers PCO2
H2CO3 +
Removal
of H+
HCO3
-H2OCO2 + NaHCO3
HCO3
-
Na+
Other buffer
systems
releases H+
The response to alkalosis
Secretion
of HCO3
-
BICARBONATE RESERVE
H+
LUNGS

49. Steps to the Clinical Assessment of
Acid-Base Disturbances
1. Assess pH (normal 7.4);
pH <7.38 is academia and >7.42 is alkalemia
2. Serum bicarbonate level
3. Assess arterial pCO2
4. Check compensatory response:
Compensation never overcorrects the pH.
i. If pH is <7.4, acidosis is the primary disorder.
ii. If pH is >7.4, alkalosis is primary.
5. Assess anion gap.
6. Assess the change in serum anion gap/change in
bicarbonate.
7. Assess if there is any underlying cause.

52. Acidosis
• 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
– death

53. Alkalosis
• Alkalosis causes over excitability of the central and
peripheral nervous systems.
• Numbness
• Lightheadedness
• It can cause :
– Nervousness
– muscle spasms or tetany
– Convulsions
– Loss of consciousness
– Death

54. ▪ The acid-base disorders are mainly classified as
Metabolic acidosis
(due to  in bicarbonate)
Respiratory alkalosis
(due to  in carbonic acid)
Respiratory acidosis
(due to  in carbonic acid)
Metabolic alkalosis
(due to  in bicarbonate)
Acidosis
Alkalosis

55. Acid-Base Imbalances
• pH< 7.35 acidosis
• pH > 7.45 alkalosis
• 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.

56. Compensation
• If underlying problem is
metabolic, hyperventilation or
hypoventilation can help :
respiratory compensation.
• If problem is respiratory, renal
mechanisms can bring about
metabolic compensation.

60. The total concentration of cations and anions (expressed as
mEq/l) is equal in the body fluids.
 This is required to maintain electrical neutrality.
The commonly measured electrolytes in the plasma are Na+, K+,
Cl- and HCO3
-.
Sodium and potassium together account for 95% of the cations
whereas chloride and bicarbonate account for only 86% of the
anions.
Hence there is always a difference between the measured
cations and the anions.
This is due to the presence of protein anions, sulphate,
phosphate and organic acids.
Anion Gap

61. Anion gap is defined as the difference between the total
concentration of measured cations (Na+ and K +) and that of
measured anion (Cl- and HCO3
-).
The anion gap (A-) in fact represents the unmeasured anions in
the plasma which may be calculated as follows…
The anion gap in a healthy individual is around 15 mEq/l (range
8-18 mEq/l)
Na+ K + Cl- HCO3
-
136 4 100 25
A-
A-
A- 15 mEq/l

62. Clinical Significance of Anion Gap
The anion gap is a biochemical tool which sometimes helps in
assessing acid-base problems. It is used for the diagnosis of different
causes of metabolic acidosis.

63. Disorder pH [H+]
Primary
disturbance
Secondary
response
Metabolic
acidosis    [HCO3
-]  pCO2
Metabolic
alkalosis    [HCO3
-]  pCO2
Respiratory
acidosis    pCO2  [HCO3
-]
Respiratory
alkalosis    pCO2  [HCO3
-]

64. Metabolic Acidosis

65. METABOLIC ACIDOSIS
Causes:
• Lethargy
• Nausea,
Vomiting,
Diarrhea
• Death
• Coma
•  BP
• Hyperkalemia
• Warm
Flushed
Skin
(Vasodilation)
Symptoms:
• Headache
• Renal Tubular
acidosis
• Diabetes mellitus
(ketoacidosis)
• Renal failure
• Lactic acidosis
• Severe
Diarrhea

66. Compensation of metabolic
acidosis
▪ Decrease in pH in metabolic acidosis stimulates the respiratory
compensatory mechanism and produces hyperventilation—
Kussmaul respiration
▪ This leads to an increased elimination of CO2 from the body
(hence H2CO3).
▪ But respiratory compensation is only short-lived.
▪ Renal compensation sets in within 3-4 days and the H+ ions are
excreted as NH4 ions

67. ▪ Increased production and accumulation of organic acids
causes an elevation in the anion gap.
▪ This type of picture is seen in metabolic acidosis associated
with diabetes (ketoacidosis)
Anion gap and Metabolic Acidosis

69. Acidosis causes hyperkalemia. Why?
♣Potassium is the major intracellular cation.
♣In acidosis, there is an increase in H+ conc in ECF.
♣This leads to exchange of H+ with intracellular K+
♣Net effect is an increase in ECF potassium
(hyperkalemia)

70. ▪ It results from an increase in concentration of carbonic
acid (H2CO3) in plasma.
▪ It is due to a retention of CO2.
▪ An increase in concentration of H2CO3 is due to decrease
in alveolar ventilation, and that leads to retention of CO2.
Respiratory Acidosis

72. RESPIRATORY ACIDOSIS
Causes:
• Death
Symptoms:
• Pulmonary
edema
• asthma
• Chronic obstructive
lung disease
• Depression of
respiratory
center
• Breathlessness
• Restlessness
• Rapid, Shallow
Respiratory
• Lethargy and
disorientation
• Tremors,
convulsions,
coma
• Drowsiness,
Dizziness,
Disorientation
• pneumonia
• emphysema

73. ▪ Increase in renal reabsorption of bicarbonate.
▪ Rise in urinary acid (H2PO4
–) and ammonia.
Compensation of metabolic
acidosis

74. ▪ A rise in blood pH due to rise in the
bicarbonate levels of plasma is called
metabolic alkalosis.
METABOLIC
ALKALOSIS
I can’t control the pH!
There is too much base and I
have lost my H+. I’m alkalotic
I’m coming to
help!

76. ▪ The respiratory mechanism initiates the compensation by
hypoventilation to retain CO2 (hence H2CO3
-
).
▪ This is slowly taken over by renal mechanism which
excretes more HCO3
-
and retains H
+
.
Compensation of Metabolic
Alkalosis

77. ▪ A rise in blood pH due to decreased concentration of CO2 or
H2CO3, due to hyperventilation.
RESPIRATORY
ALKALOSIS

79. ▪The renal mechanism tries to compensate by
increasing the urinary excretion of HCO3.
▪Reduction of urinary ammonia formation
Compensation of Respiratory
alkalosis

80. 84 of 62
Contact no. – 07418831766
E mail – ashokkt@gmail.com
For more presentation visit - http://www.slideshare.net/ashokktt
Ashok Katta
Dept. of Biochemistry,
Dhanalakshmi Srinivasan Medical College,
Perambalur
Thankyou