Acid -base Balance

1
 Basic Principles of Acid-Base
Chemistry

Definition of an Acid and a base

Acid dissociation constant
Strong acids /bases vs Weak acids /bases
PKa, pH,
The Henderson–Hasselbalch equation
Buffer

2
 The term acid–base balance
- refers to the precise regulation of free
(that is, unbound) hydrogen-ion (H)
concentration in the body fluids.

3
 Basic Principles…
Acid = a substance that can release, or
donate, H+
Base = a substance that can combine with, or
accept, H+.

Acid Base/ Conjugate

base

4
 Acid Dissociation constant
(pka)

At equilibrium, the rate of dissociation and the

rate of association are equal.
Ka = equilibrium constant/ionization constant

Ka shows the strength of an acid

Ka = strong acid
 Ka = weak acid

5
 Acid-base strength
 Strong acid
 dissociate completely, with high Ka
 E.g. HCl, H SO4 , HNO
2 3
Weak acid
dissociate partially, with low Ka
E.g. H CO , C H O , NH4+ H PO –
2 3 3 6 3 2 4
Strong base
accepts all the H+
Weak base
Accepts only some of the H+
HCO3- , HPO 2- NH Acetate
4 3,

6
 pKa

each acid has a characteristic pKa

strong acid
high Ka and a low pKa.
weak acid
low Ka and a high pKa.

7
 Concept of pH
pH = a unit used to
measure the concentration
free H+ in solution

H+ pH  acidity.

 H+  pH  acidity

8
 pH…

ECF [H+] = 0.00000004 Eq/L (40 x 10-9

Eq/L).

pH = –log [40 x 10-9 ]

pH = 7.4

9
 The Henderson-Hasselbalch
Equation

10
 Buffer
an agent that minimizes the change in pH
produced when an acid or base is added
A mixture of a weak acid and its conjugate
base

11
 Buffer
 equilibrium expression for a buffer pair

 For H2CO3/HCO3-

 good buffer = high concentrations + pKa close to

the desired pH.

12
 pH of fluid compartments
plasma pH
7.4 or 7.35 – 7.45
pH compatible with life
6.8 – 7.8
Gastric juice = 1.0
Urine = 4.5-8

13
 Acid production

1. volatile acid - Carbonic acid (H2CO3)

CO2 + H2O  H2CO3  H+ + HCO3-
removed as CO2 through the lung
10,000 -15,000 mM of H2CO3 / day

2. Non volatile/fixed acids

Acids Excreted through urine
All the other Acids - Sulfuric acid, Lactic acid,
Pyruvic acid
80 meq/day

14
 Acid Production -
physiological

15
16
 Body alkaline loss and gain
Alkaline (HCO3- ) gain
metabolism of organic anions (e.g., citrate)
Aspartate and glutamate  HCO3-

Alkaline loss
HCO3- - in feces

17
 Effect of pH
Body pH affects
Enzymes
Rate of metabolic reactions
Acidosis stimulate aerobic respiration
Alkalosis inhibit aerobic resp. and stimulate
anaerobic glycolysis.
Electrolyte balance
Acidosis  Hyperkalemia
Alkalosis  Hypokalemia
Nerve excitability
alkalosisexcitability
Acidosis  CNS depression

18
 ECF pH regulation
Three mechanisms

1. Chemical buffers

2. the respiratory Acid base balance

3. the urinary (Renal) acid base

balance

19
 H+ and pH
balance in
the body

20
 Chemical buffers
Buffer = a substance that minimizes pH
changes
the first line of defense
Major ECF buffers
1. Carbonic acid/bicarbonate
2. Inorganic Phosphate
3. Protein
ICF buffers
 Organic phosphates
 Protein
 Hemoglobin

21
 1. Carbonic Acid/Bicarbonate
Buffer

Most import ECF buffer

Abundant
 Plasma [HCO3-] =24 mEq/L
 Plasma [CO2] = 1.2mmol/L
“Open” Buffer System
 Can be added or removed at controlled rates
controlled by both lungs and kidneys.

22
 1. Carbonic Acid/Bicarbonate
Buffer

Henderson–Hasselbalch equation

23
 The concentration of undissociated H2CO3
cannot be measured in solution because it
rapidly dissociates into CO2 and H2O or to H+
and HCO3
 However, the CO2 dissolved in the blood is
directly proportional to the amount of
undissociated H2CO3.

24
 Effect of the kidney and respiratory system on
H2CO3/HCO3-buffer and pH

25
 Cont…

26
 . Phosphate Buffer

pKa = 6.8
[ Pi ]ECF = 0.66 mmol/L
Important intracellular
High concentration = 6 mmol/l
ICF pH(7.0) is close to the pKa of
phosphate(6.8)

27
 3. Protein buffer

Example
 Albumin
 Globulins
 Hemoglobin

28
 Hemoglobin buffer

29
30
 Respiratory control of pH
Reflex changes in ventilation to
conserve/eliminate CO2

∆PaCO2 + ∆ plasma pH  depth+

frequency of ventilationnormal PaCO2 and
pH

2nd line of defense

Begin within minutes
maximum -12-24 hrs

31
 Cont’d…
Central
chemoreceptors
Stimulated by Increases in
blood CO2 and H+ in CSF
effect – respiration rates

Peripheral
chemoreceptors
Carotid body and Aortic
CO body
CO
CO2
2 2
CO
Stimulated by CO2 (pH)
pH
CO 2 or
CO 2
CO
2
CO
CO2
O2 respiration rates 2 2

32
33
 Renal Control of pH
Allow the elimination of fixed acids
Slow to act – 1-3 hrs
1.Excrete excess H+
 Free H+
 Titritable acid
the amount of hydrogen ions that are excreted
combined with urinary buffers - phosphate,
creatinine and other bases
 NH +
4

2.Reabsorption filtered HCO3-

3.Generation of new HCO3-

34
Each day the kidneys filter about 4320 mEq of
HCO3
(180 L/day × 24 mEq/L); under normal conditions
almost all this is reabsorbed from the tubules
Because HCO3 must react with a secreted H+ to
form H2CO3 before it can be reabsorbed, 4320
mEq of H+ must be secreted each day just to
reabsorb the filtered HCO3
−. Then an additional 80 mEq of H+ must be
secreted to rid the body of the nonvolatile acids
produced each day
-a total of 4400 mEq of H+ secreted into the
tubular fluid each day.
35
 Renal control of pH
the kidney can not excrete all the fixed
acids as H+ -----why?
Urine pH = 4.5 – 8
Max urine acidification = 4.5 (0.03 mEq/L of
H+)
Total amount of fixed acid must be excreted
= 80 mEq

36
 Renal Net Acid Excretion
 net acid excretion by the kidneys = the net rate
of H+ addition to the body

Urinary Urinary
 = Titratable urinary
+ HCO3--
Acid NH4+ Excretion
(24 (48 (2
mEq/day) mEq/day) mEq/day)
 = 70 mEq/day

37
Acidification along nephron
 LH.
 Na/H exchanger
 pH in Descending limb = 7.4
 pH in ascending limb =6.7
 Distal nephrone
 Secretes fewer H+
 H-ATPase or H/K-ATPase
 pH = 4.5-6

38
 Acidification along the nephron
Acidification = H+ secretion in to the renal
tubules

39
 Acidification in the PCT
 Na/H exchanger
 H-ATPase
 Used to reabsorb
bicarbonate
 Combine with
 HPO4- = H2PO4 2-

(Titritable acid)
 NH3  NH4+

40
 Acidification In collecting duct
(intercalated cells )

41
 Fate of Secreted H+
1. Used to reabsorb HCO3-
2. Titrated with urinary
buffer
 H+ + HPO42-  H2PO4-

3. Combine with NH3

 H+ + NH3  NH4+

42
Renal Excretion of H+ as
titratabe acid
Titratable acid
the amount of H ions that are excreted, combined
with urinary buffers
phosphate, creatinine, and other bases.
The largest component = phosphate (HPO42-)
Coupled with Generating “New” Bicarbonate
Ions
The major site of formation is in PCT

43
44
 Excretion of H+ as Renal Ammonia
NH4+ is formed from deamination of Gln
Actively secreted into the lumen and excreted
in the urine

45
46
 Renal HCO3 Reabsorption

47
 Renal Bicarbonate
handling
The reabsorption process involves
Apical Na-H+ antiporter
Apical H+ ATPase
Luminal and cellular carbonic anydrase
Basal Cl- - HCO - antiporter
3
Basal Na--HCO transporter
-
3
excretion = 2 mEq/day

48
H+ secretion & HCO3- reabsorption in the
proximal tubule

49
 H+ secretion & HCO3- Reabsorption by
intercalated cells of the collecting duct

50
Acid base disturbances and compensations

Tolerable pH range

6.8 – 7.8 or (160 nanomoless – 16 nanomoles

of H+)

pH w/n normal range = Euphemia

pH < 7.35 = Acidosis/acidemia

pH > 7.45 = Alkalosis/alkalemia

51
52
When disturbances of acid-base balance result from a

primary change in extracellular fluid HCO3 −

concentration

-referred to as metabolic acid-base disorders.

-Decrease in HCO3 −concentration is termed metabolic

acidosis Primary increase in HCO3 − concentration---
metabolic alkalosis

-Increase in PCO2 is called respiratory acidosis,

-a decrease in PCO2 is termed respiratory alkalosis.

53
 Simple acid base
disturbances

Respiratory disorders
Due to too much or tool little CO 2
 PaCO2 > 45 mm Hg = respiratory acidosis.
 PaCO2 < 35 mm Hg = respiratory alkalosis.

Metabolic disorders
Due to too much or too little HCO3−
 HCO < 22 mEq/L = metabolic acidosis.
3–

 HCO > 28 mEq/L = metabolic alkalosis.

3–

54
 Acid base compensations
Compensations
A set of physiological process that
adjust plasma pH with in the normal
range.
If the primary problem is a change in [HCO3]
or PCO2, the pH can be brought closer to
normal by changing the other member of the
buffer pair in the same direction
the lungs adjust the blood PCO2 and the
kidneys adjust the plasma [HCO3]
do not bring about normal blood pH.

55
 Acid base disturbances and
compensations

56
 Respiratory Acidosis
an abnormal process characterized by Pa
CO2
Causes
impaired elimination of CO2
Impairment of alveolar ventilation
Impairment of respiratory centers (Narcotic
overdose)
Lung diseases
Chest deformities
Weakness of respiratory muscles
Airway obstruction

57
 Respiratory acidosis
Compensation
 renal
Increased H+ secretion
H+ is excreted as titratable acid and
NH4+
Reabsorption filtered HCO3-
Generation of new HCO3-
Respiratory
hyperventilation

58
 Respiratory Alkalosis
Alkalosis due to loss of
too much CO2
Features :  pCO2 , pH
Cause -
Hyperventilation
hypoxia
Stimulation of the brain
stem (meningitis, fever,
aspirin intoxication)
Head injury
Some Medications
anxiety

59
 Respiratory alkalosis

Compensation

1. Chemical buffering
95% within cells.
Cell proteins and organic phosphates liberate
H+ added to the ECF and lower the plasma
[HCO3-]  pH
2. Respiratory compensation
Hypoventilation (PCO2pH)

3. Renal compensation
reduces H+ secretion
excreting HCO3- in the urine

60
 Metabolic Acidosis
acidosis due to gain of non carbonic acid or
Loss of HCO3-
 Features
 HCO3- , [H+] ( pH), HCO3- / CO2 < 20

 Causes
renal failure
uncontrolled diabetes mellitus
Lactic acidosis
ingestion of acidifying agents- NH4Cl
abnormal renal excretion of HCO3
Diarrhea
Hyperkalemia

61
62
 Metabolic Acidosis

Compensation
respiratory
 Hyperventilation Plasma PCO2.
Renal compensation
 Excreting H+
 Reabsorbtion of filtered HCO3-
 New HCO3- generation

63
 Metabolic Alkalosis
Alkalosis due to gain of a strong base or HCO3-
or a loss of fixed acids
Characteristics
pH, Plasma [HCO3]
Causes
Ingestion of too much bicarbonate
 baking soda, Bicarbonate containing antiacids
Vomiting of stomach contents
Hypokalemia
hyperaldosteronism

64
 Metabolic Alkalosis

Compensation
respiratory
hypoventilation.
raises the blood PCO2 and [H 2CO3]
Renal
HCO3- is secreted in the collecting ducts
 urinary [HCO3-] excretion
 plasma [HCO3-].

65
66
 Anion Gap
The cation normally measured is Na+, and the
anions are usually Cl− and HCO3
The cation normally measured is Na+, and the
anions are usually Cl− and HCO3−.

67
 The anion gap will increase if unmeasured
anions rise or if unmeasured cations fall.
The most important unmeasured cations
include calcium, magnesium, and
potassium,
- major unmeasured anions are albumin,
phosphate,
sulfate, and other organic anions.
Usually the unmeasured anions exceed the
unmeasured cations, and the anion gap
ranges between 8 and 16 mEq/L.
68
 SUMMARY
IMPORTANT POINTS
CASE STUDY
 Example-1
A 56-year-old man suffered a panic
attack while awaiting surgery. The
results of arterial blood gas analysis
showed the following abnormalities:
Po2 = 112 mm Hg (normal 80–100 mm Hg)
PCO2 = 24 mm Hg
[HCO3−] = 23 mEq/L (normal = 22–28
mEq/L)
pH = 7.60 (normal = 7.35–7.45)

70
 The acid-base disorder described is
respiratory alkalosis (low arterial Pco2) with
no metabolic component (normal plasma
[HCO3−]), which is producing an alkalemia
(high plasma pH).
Comment The patient’s panic attack
resulted in acute hyperventilation and
respiratory alkalosis. The acid-base
abnormality will be readily corrected when
breathing returns to normal.

71
 Example 2
A 24-year-old man who is a known
heroin addict was found unresponsive
with a hypodermic needle in his arm.The
results of arterial blood gas analysis
showed the following abnormalities:
Po2 = 50 mm Hg (normal = 80–100 mm
Hg)
PCO2 = 80 mm Hg
[HCO3−] = 23 mEq/L (normal = 22–28
mEq/L)
pH = 7.08 (normal = 7.35–7.45)
72
 The acid-base disorder
respiratory acidosis (high arterial PCO2) with
no metabolic component (normal [HCO3−]),
which is producing a severe acidemia (low
plasma pH).
Comment
The patient overdosed on a narcotic
that caused respiratory depression, alveolar
hypoventilation, and respiratory acidosis.

73
 Example 3
A 2-year-old child who is lethargic and
dehydrated has a 3-day history of
vomiting. The results of arterial blood gas
analysis show the following abnormalities:
Po2 = 90 mm Hg
PCO2 = 44 mm Hg
[HCO3−] = 37 mEq/L (normal = 22–28
mEq/L)
pH = 7.56 (normal = 7.35–7.45)

74
 The acid-base disorder
metabolic alkalosis (high [HCO3 −]) with no
respiratory component (normal arterial
PCO2), which is producing an alkalemia (high
plasma pH). Treatment of the

75
 Complex Acid-Base Disorders
acid-base disorders are not accompanied by
appropriate compensatory responses
abnormality is referred to as a mixed acid-base disorder
there are two or more underlying causes for the acid-
base disturbance.
eg if the low plasma pH and low HCO3 concentration
are associated with elevated PCO2, one would suspect
a respiratory component to the acidosis, as well as a
metabolic component.
Therefore, this disorder would be categorized as a mixed
acidosis.
for example, in a patient with acute HCO3 loss from the
gastrointestinal tract because of diarrhea (metabolic
acidosis) and emphysema (respiratory acidosis).

76
77