Medicine 2004/2005

Phase 1, Year 1
Respiratory Block, Week 2

Respiratory Mechanisms
in Acid-Base Homeostasis
Assoc. Prof. Faridah Abdul Rashid
Dept. of Chemical Pathology
School of Medical Sciences
USM Kubang Kerian, Kelantan
faridah@kb.usm.my

Saturday, 26 February 2005, 8:30 am – 9:30 am, DK4 1

 Part 1
Own reading

• Normal values for arterial blood gases

• Carbonic acid/bicarbonate buffer

system

• Henderson-Hasselbalch equation

2
Normal values for arterial blood gases
Memorise
Arterial Blood Gases (ABG)
Blood Gas Parameter Parameter Reported Normal Value
and Symbol Used
Carbon dioxide PCO2 35 – 45 mm Hg
tension* (average, 40)
Oxygen tension* PO2 80 – 100 mm Hg

Oxygen percent SO2 97

saturation
Hydrogen ion pH 7.35 – 7.45
concentration*
Bicarbonate HCO3- 22 – 26 mmol/L
* Indicates measured parameter Normal values may differ slightly in exams 3
 Gold trunk

Carbonic acid/bicarbonate buffer system

CO2 + H2O CA H2CO3  H+ + HCO3-

• Carbonic acid is formed when CO2 combines

with water. This reaction is catalysed by
carbonic anhydrase
• Carbonic acid dissociates spontaneously to form
a proton and a bicarbonate ion
• The above reactions are reversible:
– Write the reaction for buffering acids formed in tissues
– Write the reaction for CO2 release in the lungs

4
Carbonic acid/bicarbonate buffer system
pKa = 6.1
ECF: H2CO3  H+ + HCO3-
Carbonic acid Bicarbonate ion

• Carbonic acid is a weak acid

• Carbonic acid dissociates spontaneously to form
a proton and a bicarbonate ion
• The pKa of carbonic acid is 6.1
• Carbonic acid is the major buffer in ECF
• The pH of blood can be determined using the
Henderson-Hasselbalch equation
5
Henderson-Hasselbalch equation
Memorise
• pH = pKa + log [HCO3-]/[H2CO3]

• pH = pKa + log [HCO3-]/0.03 x PCO2

• pH = 6.1 + log [HCO3-]/0.03 x PCO2

• 7.4 = 6.1 + log 20/1

• 7.4 = 6.1 + 1.3

Gold trunk
• The solubility constant of CO2 is 0.03
• The pKa of carbonic acid is 6.1
• Plasma pH equals 7.4 when buffer ratio is 20/1
• Plasma pH may be affected by a change in either the bicarbonate
concentration or the PCO2
• The [HCO3-] and PCO2 values determine plasma pH 6
 Part 2
Own reading
• CO2 and PCO2
– Pulmonary function & CO2 homeostasis
– CO2 elimination

• Hyperventilation
– Lowering PCO2
– Alveolar hyperventilation
– Causes of alveolar hyperventilation

• Hypoventilation
– Raising PCO2
– Alveolar hypoventilation
– Causes of alveolar hypoventilation 7
 CO2 and PCO2
• The amount of CO2 in the blood is directly
related to the PCO2
• The CO2 dissociation curve is nearly linear
in the physiologic range of PCO2
• There is never any significant barrier to
CO2 diffusion; CO2 diffuses freely
• PCO2 provides a good index of the
adequacy of ventilation
8
 Pulmonary Ventilation
• Normal, unassisted breathing:
– An increase in arterial PCO2 acts through the
respiratory centre to increase the rate of
pulmonary ventilation
– A decrease in arterial PCO2 reduces the rate
of ventilation

• Assisted breathing:
– A respirator is used to assist breathing by
expelling CO2, thus reducing PCO2 in blood
9
Pulmonary function & CO2 homeostasis
• The acid-base balance of the body is greatly affected by
pulmonary function and CO2 homeostasis:

Normal acid-base balance; pH remains at 7.4

CO2 + H2O  H2CO3  H+ + HCO3-

Normal
pulmonary function CO2 homeostasis

[H2CO3] 1:20 [HCO3-]

Normal bicarbonate/carbonic acid ratio 10
 CO2 elimination
• CO2 elimination through the lungs must be
matched with CO2 production for adequate
ventilation
• CO2 is highly diffusible:
– CO2 tensions are equal in alveolar air and
arterial blood
– Thus, PCO2 is the direct and immediate
reflection of the alveolar ventilation in relation
to the metabolic rate
11
 Hyperventilation
• Hyperventilation (alveolar ventilation in excess of
metabolic needs) causes alkalosis ( in blood pH above
the normal 7.4) as a result of the excess excretion of CO2
from the lungs Acid-base disorder
Alkalosis
CO2 + H2O  H2CO3  H+ + HCO3-

CO2 homeostasis
Pulmonary function
Hyperventilation  CO2,  PCO2

[H2CO3] 1:>20 [HCO3-] 12

 Lowering PCO2
• Lowering the PCO2, as in hyperventilation, causes the
reaction to proceed to the left, with consequent lowering
of the H+ concentration (elevated pH)

Hyperventilation
Excess excretion of
Reaction shifts left
CO2 from the lungs
 [H+],  pH, alkalosis
 CO2,  PCO2

CO2 + H2O  H2CO3  H+ + HCO3-

Reaction shifts left

13
 Alveolar hyperventilation
• The direct cause of a lowered PCO2 is
always alveolar hyperventilation

• Hyperventilation causes respiratory

alkalosis and a rise in the pH of the blood

• Hyperventilation represents an effort to

raise the PO2 at the expense of excreting
excess CO2 from the lungs
14
 Gold trunk

Causes of alveolar hyperventilation

• Hyperventilation is common in:
– asthma
– pneumonia
• Hyperventilation may also be caused by:
– brain injury
– tumour
– aspirin poisoning
– anxiety
• Hyperventilation may be a compensation
for metabolic acidosis 15
 Hypoventilation
• Hypoventilation (alveolar ventilation insufficient to meet
metabolic needs) causes acidosis (decrease of the blood
pH below the normal 7.4) as a result of the retention of
CO2 by the lungs
Acid-base disorder
Acidosis
CO2 + H2O  H2CO3  H+ + HCO3-

CO2 homeostasis
Pulmonary function
Hypoventilation  CO2,  PCO2

[H2CO3] 1:<20 [HCO3-] 16

 Raising PCO2
• Raising the PCO2, as in hypoventilation, causes the
reaction to proceed to the right, producing an increase in
H+ concentration (decreased pH)

Hypoventilation
Retention of CO2 by Reaction shifts right
the lungs  [H+],  pH, acidosis
 CO2,  PCO2

CO2 + H2O  H2CO3  H+ + HCO3-

Reaction shifts right

17
 Alveolar hypoventilation
• When PCO2 rises, the direct cause is
always generalised alveolar
hypoventilation

• Hypoventilation causes respiratory

acidosis and a fall in the pH of the blood

• Alveolar hypoventilation may occur if the

respiratory rate is decreased
18
 Gold trunk

Causes of alveolar hypoventilation

• Hypoventilation occurs in many conditions that
affect the respiratory system
• CO2 retention is caused by trapped air in the
lungs as occurs in:
– emphysema
– chronic bronchitis
• Alveolar hypoventilation may occur in:
– narcotic
– barbiturate drug overdose
• The PCO2 may also rise to compensate for
metabolic alkalosis
19
SUMMARY

Alveolar hypoventilation
• To interpret the PCO2 correctly, one must
also consider the blood pH and
bicarbonate levels to determine whether a
change is caused by a primary respiratory
condition or is compensating for a
metabolic condition

20
SUMMARY
Gold trunk
Acid-base disorders
Alkalosis
Acidosis
CO2 + H2O  H2CO3  H+ + HCO3-

Pulmonary function CO2 homeostasis

Hyperventilation CO2,  PCO2
Hypoventilation  CO2,  PCO2

[H2CO3] 1:20 [HCO3-]

Bicarbonate/carbonic acid ratio

>20:1
<20:1

21
 Equivalences
Disorder Cause Mechanism

Respiratory Hypercapnia Alveolar

acidosis hypoventilation

 pH  PCO2 CO2 retention

Respiratory Hypocapnia Alveolar

alkalosis hyperventilation

 pH  PCO2 blow off CO2

22
 Part 3 Own reading

• Acid-base disturbances: Types of acid-base imbalance

1. Respiratory acidosis
2. Respiratory alkalosis
3. Metabolic acidosis
4. Metabolic alkalosis

• Acid-base changes in acidosis & alkalosis and

compensation
– Terms used for describing compensation
– Renal compensatory mechanisms in acid-base imbalance
– Metabolic and respiratory acid-base changes in blood
– Compensation in respiratory disorders
– Compensation in metabolic disorders
23
 Acid-base disturbances Memorise

• pH = 6.1 + log [HCO3-]/0.03 x PCO2

• Plasma pH may be affected by a change in

either the [bicarbonate] or the PCO2:
– When the primary change is in the PCO2, the disturbance
is called respiratory; when it is the [bicarbonate], it isGold trunk
called metabolic:
  PCO2 will decrease pH acidosis
  PCO2 will increase pH Respiratory
alkalosis
  HCO3- will decrease pH
acidosis
  HCO3- will increase pH Metabolic
alkalosis
24
 Types of acid-base imbalance
• Simple acid-base imbalance: (Phase 1 MD)
1. Respiratory acidosis
2. Respiratory alkalosis
3. Metabolic acidosis
4. Metabolic alkalosis

• Mixed acid-base imbalance (Phase 2 MD)

– Refer to:-
Interpretation of Diagnostic Tests. Seventh Edition, 2000
Jacques Wallach
Lippincott Williams & Wilkins, Philadelphia
Chapter 12 – Acid-Base Disorders, pages 489-500
25
 Acid-base changes in acidosis and alkalosis

Acid-base Disturbance pH HCO3- PCO2

Respiratory acidosis   
Respiratory alkalosis   
Metabolic acidosis   

Metabolic alkalosis 
 
Thicker arrows indicate primary disorder
26
Acid-base changes in acidosis and alkalosis

Memorise
Acid-base Disturbance pH HCO3- PCO2
pH, PCO2 in
Respiratory acidosis   
opposite
directions;
HCO3- will
Respiratory alkalosis    follow PCO2

pH, HCO3-
Metabolic acidosis    in same
direction;
PCO2
Metabolic alkalosis    will follow
HCO3-
Thicker arrows indicate primary disorder 27
 Gold trunk

Compensation
• The purpose of the compensation is to return the
blood pH to normal

• The change in the PCO2 in the metabolic

disorders represents the lung’s role in
compensation

• The change in the bicarbonate level represents

the kidney’s attempt to compensate for the
respiratory acidosis or alkalosis
28
Respiratory Compensation for
Preventing Change in pH
Cells/Tissue Blood
Acidosis
Acidaemia
CO2 
pH , PCO2 
H+ Hypoventilate
Lungs Slow or  CO2 removal
CO2 removal
Via respiration

Blood Normal or  CO2 removal

Hyperventilate
Normal pH

Acidosis may be accompanied by acidaemia.

The change in pH may be prevented by respiratory removal of CO2.
29
 Respiratory Compensation for
Preventing Change in pH
Cells/Tissue Blood
Alkalosis
Alkalaemia
CO2 
pH , PCO2 , HCO3-
HCO3-
Hyperventilate
Lungs Slow or  CO2 retention
CO2 retention
Via respiration

Blood Normal or  CO2 retention

Hypoventilate
Normal pH

Alkalosis will not be accompanied by alkalaemia

if enough CO2 has been retained to prevent the change in pH.
30
 Gold trunk

Compensation in respiratory disorders

• Compensation in respiratory disorders is a two-phase process:
(i) Acute response: initial 10 minutes
• Involves blood buffers
(ii) Chronic (renal) adaptation: for up to 4-8 days
• The change in the bicarbonate level represents the kidney’s
attempt to compensate for the respiratory acidosis or alkalosis
• pH returns towards normal but not pH 7.4:
10 min

pH 7.7 Acute response pH 7.77.6

pH 7.6 Chronic response pH 7.67.45
pH 7.5 10 min
pH 7.4
pH 7.3 4 days 8 days
pH 7.2 Chronic response pH 7.27.35 RESPIRATORY ALKALOSIS
pH 7.1 Acute response pH 7.17.2
31
RESPIRATORY ACIDOSIS
Changes in bicarbonate
Gold trunk

Compensation in respiratory disorders

1. Compensation in respiratory disorders is a two-phase process:
(i) Acute response occurs during initial 10 minutes
• This buffering by buffers in blood
• Changes in [HCO3-] occur within 10 minutes
(ii) Chronic (renal) adaptation occurs for up to 4-8 days
• The change in the bicarbonate level represents the kidney’s attempt to
compensate for the respiratory acidosis or alkalosis
• Changes in [HCO3-] occur up to:
» 4 days in respiratory acidosis
» 8 days in respiratory alkalosis

2. Changes in [HCO3-] and pH occur within 10 minutes, and up to:

4 days in respiratory acidosis
8 days in respiratory alkalosis

32
1. Summary of changes in pH
Gold trunk

Compensation in respiratory disorders

1. Compensation in respiratory disorders is a two-phase process:
(i) Acute response occurs during initial 10 minutes
• This buffering by buffers in blood
• Changes in pH occur within 10 minutes
(ii) Chronic (renal) adaptation occurs for up to 4-8 days
• Changes in pH occur up to:
» 4 days in respiratory acidosis
» 8 days in respiratory alkalosis
2. Changes in pH occur within 10 minutes, and up to:
4 days in respiratory acidosis
8 days in respiratory alkalosis

3. pH returns towards normal but not pH 7.4:

Final pH 7.35 in respiratory acidosis
33
Final pH 7.45 in respiratory alkalosis
2. Summary of changes in pH
Gold trunk

Compensation in respiratory disorders

1. Compensation in respiratory disorders is a two-phase process

2. Changes in pH occur within 10 minutes, and up to:

(i) 4 days in respiratory acidosis
(ii) 8 days in respiratory alkalosis

3. When fully compensated, pH returns towards normal but not pH 7.4

4. pH Changes in RESPIRATORY ACIDOSIS are:

(i) Acute response pH 7.17.2 (initial 10 minutes)
(ii) Chronic response pH 7.27.35 (lower normal limit within 4 days)

5. pH Changes in RESPIRATORY ALKALOSIS are:

(i) Acute response pH 7.77.6 (initial 10 minutes)
(ii) Chronic response pH 7.67.45 (upper normal limit within 8 days)
34
Respiratory acidosis Gold trunk

35
Respiratory alkalosis Gold trunk

36
 Respiratory Disturbance of pH
• The disturbances of pH caused by
hypoventilation and by hyperventilation are
known as ‘gaseous’ or ‘respiratory’
acidosis and alkalosis

• They indicate that the disturbances arise

from mishandling of the blood gases or
from an inappropriate rate of pulmonary
ventilation
37
 Please read

Compensation in Respiratory Acidosis

• Assisted breathing:
– A respirator is used to assist breathing by
expelling CO2, thus reducing PCO2 in blood
• Bicarbonate is generated and reabsorbed
by renal tubules
• Renal system excretes H+ in urine
• Renal bicarbonate is returned to blood to
bring up pH to normal
A respirator is a device (alat) to assist (help) a patient to breathe (bernafas).
38
 Please read
Compensatory response in
respiratory acidosis
• Berikut ialah di antara respons
kompensatori asidosis pernafasan:
A. Hiperventilasi tidak boleh berlaku sebab paru-
paru rosak/tersumbat dan tidak boleh berfungsi
B. Peningkatan ventilasi alveolar melalui respirator
mengurangkan PCO2 darah
C. Ion bikarbonat dijana serta diserap semula oleh
tubul renal
D. Sistem renal meningkatkan perkumuhan H+
dalam urin
E. Lebih banyak ion bikarbonat yang dihasilkan di
renal memasuki darah
39
Terms used for describing compensation
• Compensated
– The compensatory mechanisms have come into play
in a normal manner; does not necessarily imply that
the plasma pH is within the normal range
• Uncompensated
– Compensation cannot occur due to some abnormality;
patient may show no sign of compensation
• Partially compensated
– Intermediate state where compensation is occurring
but is not yet as complete as it should be

40
 Primary Conditions & Compensation

• Four primary conditions are possible:

1. Respiratory acidosis
+ acute blood response Rapid compensation (10 min)
+ chronic renal response Slow compensation (4 days)
Two-phase
2. Respiratory alkalosis process
+ acute blood response Rapid compensation (10 min)
+ chronic renal response Slow compensation (8 days)

3. Metabolic acidosis
+ respiratory response Fast compensation (24 h)
Single-phase
4. Metabolic alkalosis process
+ respiratory response Fast compensation (24 h)
41
 Metabolic and Respiratory Acid-
Base Changes in Blood
pH pCO2 HCO3-
Acidosis
1. Acute metabolic  N 
2. Compensated metabolic N  
3. Acute respiratory   N
4. Compensated respiratory N  
Alkalosis
1. Acute metabolic  N 
2. Chronic metabolic   
3. Acute respiratory   N
4. Compensated respiratory N   42
=decreased; =increased; N=normal
 Gold trunk

Compensation in respiratory disorders

• Compensation in respiratory disorders is a two-phase process:
– Acute response: initial 10 minutes
• Involves body buffers
– Chronic (renal) adaptation: for up to 4-8 days
• The change in the bicarbonate level represents the kidney’s
attempt to compensate for the respiratory acidosis or
alkalosis
– pH returns towards normal: 10 min

pH 7.7 Acute
pH 7.6
Chronic
pH 7.5 10 min
pH 7.4
pH 7.3 Chronic 8 days
4 days
pH 7.2
pH 7.1 Acute 43
Respiratory acidosis Respiratory alkalosis
 Gold trunk

Compensation in metabolic disorders

• The change in the PCO2 in the metabolic
disorders represents the lung’s role in
compensation
• Compensation may take up to 1 day (24 hours)
• pH returns towards normal:
pH 7.6 compensat
ion
pH 7.5
pH 7.4
pH 7.3 24 hr 24 hr
pH 7.2
pH 7.1 en sa tion
pH 7.0 comp
Metabolic acidosis Metabolic alkalosis 44
Respiratory acidosis Gold trunk

45
Respiratory alkalosis Gold trunk

46
Summary of changes in pH
Gold trunk

Compensation in respiratory disorders

1. Compensation in respiratory disorders is a two-phase process

2. Changes in pH occur within 10 minutes, and up to:

(i) 4 days in respiratory acidosis
(ii) 8 days in respiratory alkalosis

3. When partially compensated, pH has still not returned towards normal

4. When fully compensated, pH returns towards normal but not pH 7.4

5. pH Changes in RESPIRATORY ACIDOSIS are:

(i) Acute response pH 7.17.2 (initial 10 minutes)
(ii) Chronic response pH 7.27.35 (lower normal limit within 4 days)

6. pH Changes in RESPIRATORY ALKALOSIS are:

(i) Acute response pH 7.77.6 (initial 10 minutes)
(ii) Chronic response pH 7.67.45 (upper normal limit within 8 days)
47
 Please read

Compensation in Respiratory Acidosis

• Assisted breathing:
– A respirator is used to assist breathing by
expelling CO2, thus reducing PCO2 in blood
• Bicarbonate is generated and reabsorbed
by renal tubules
• Renal system excretes H+ in urine
• Renal bicarbonate is returned to blood to
bring up pH to normal
A respirator is a device (alat) to assist (help) a patient to breathe (bernafas).
48
 Please read
Compensatory response in
respiratory acidosis
• Berikut ialah di antara respons
kompensatori asidosis pernafasan:
A. Hiperventilasi tidak boleh berlaku sebab paru-
paru rosak/tersumbat dan tidak boleh berfungsi
B. Peningkatan ventilasi alveolar melalui respirator
mengurangkan PCO2 darah
C. Ion bikarbonat dijana serta diserap semula oleh
tubul renal
D. Sistem renal meningkatkan perkumuhan H+
dalam urin
E. Lebih banyak ion bikarbonat yang dihasilkan di
renal memasuki darah
49
Patients with Metabolic Acidosis
• Excess acid in blood
– removes HCO3- from the plasma, lowering pH and stimulating the
peripheral chemoreceptors to increase breathing
– lowers PCO2, making the CSF more alkaline, so that the central
chemoreceptors act at first to oppose the respiratory stimulation
– Consequently, the typical hyperventilation that accompanies a
sustained acidosis takes 1 to 2 days to develop, while the
[HCO3-] in the CSF is being reduced

• If the acidosis in the blood is suddenly relieved

– the hyperventilation may still continue because the patient is like
the acclimatised mountaineer who has come down quickly
– the [HCO3-] in his CSF is low, and he must continue to
hyperventilate until it rises to normal 50
 Metabolic Acidosis
Normal

[HCO3-]  [HCO3-]
(mmol/L) Bicarbonate is reduced in metabolic acidosis

Acid-base Disturbance pH HCO3- PCO2

Metabolic acidosis   
51
The primary lesion in metabolic acidosis is reduced [HCO3-]
 Metabolic Acidosis

 [PCO2-]
PCO w
2 ill follow
PCO2 HCO -
3
22.5
(mmHg)

Acid-base Disturbance pH HCO3- PCO2

Metabolic acidosis   
52
pH, HCO3- in same direction; PCO2 will follow HCO3-
 Metabolic Acidosis
pH, HCO3-
in same pH Observed During Compensation
direction

n or mal)
Partial compensation is n ever 7.25
pH al ( but
or m
wa rds n
e t u r ns to
pH r

(1 day)

Compensation in METABOLIC ACIDOSIS: Full compensation

pH returns towards normal (but is never normal)
pH  from pH 7.07.25 within 1 day 53
At full compensation, final pH reaches 7.25 (lower than in respiratory acidosis)
 Initial 1 Comp
Acid-base pH HCO3- PCO2
Disturbance
Metabolic
  
acidosis

• The primary lesion in

metabolic acidosis is
reduced [HCO3-] from
2510 mmol/L

• The compensatory
response to lowered
plasma bicarbonate is
decreased PCO2 from
4022.5 mmHg

Observe pH  from 7.07.25

54
Metabolic acidosis Gold trunk

55
 START
Compensation in
Metabolic Acidosis
• The primary lesion in
metabolic acidosis is BLOOD
reduced [HCO3-] from
2510 mmol/L

• The compensatory
response to lowered
plasma bicarbonate is
decreased PCO2 from
4022.5 mmHg
Observe pH  from
7.07.25

56
 Metabolic Alkalosis
Bicarbonate is increased in metabolic alkalosis

[HCO3-]  [HCO3-]
(mmol/L) Normal

Acid-base Disturbance pH HCO3- PCO2

Metabolic alkalosis   
57
The primary lesion in metabolic acidosis is increased [HCO3-]
 Metabolic Alkalosis

-
HCO 3 50
l lo w
PCO2 O w ill fo
PC 2
 [PCO2-]
(mmHg)
Normal

Acid-base Disturbance pH HCO3- PCO2

Metabolic alkalosis   
58
pH, HCO in same direction; PCO2 will follow HCO3
3
- -
 Metabolic Alkalosis
pH Observed During Compensation

pH, HCO3- pH  from

pH 7.67.
5
in same
pH direction
Partial compensation

(1 day)

Compensation in METABOLIC ALKALOSIS: Full compensation

pH returns towards normal (but is never normal)
pH  from pH 7.67.5 within 1 day 59
At full compensation, final pH is 7.5 (higher than in respiratory alkalosis)
 Initial 1 Comp
Acid-base pH HCO3- PCO2
Disturbance
Metabolic
  
alkalosis

• The primary lesion in

metabolic alkalosis is
increased [HCO3-] from
2540 mmol/L

• The compensatory
response to elevated
plasma bicarbonate is
increased PCO2 from
4050 mmHg

• Observe pH  from
7.67.5
60
Metabolic alkalosis Gold trunk

61
 START
Compensation in
Metabolic Alkalosis
• The primary lesion in BLOOD
metabolic alkalosis is
increased [HCO3-] from
2540 mmol/L

• The compensatory
response to elevated
plasma bicarbonate is
increased PCO2 from
4050 mmHg

• Observe pH  from
7.67.5
62
Summary of changes in pH
Gold trunk

Compensation in Metabolic Disorders

• The change in the PCO2 in the metabolic disorders represents the
lung’s role in compensation
• Compensation may take up to 1 day (24 hours)
• pH returns towards normal (but is never normal) in metabolic
disorders
• pH  in METABOLIC ACIDOSIS from pH 7.07.25 within 1 day.
Final pH is lower than in respiratory acidosis
• pH  in METABOLIC ALKALOSIS from pH 7.67.5 within 1 day.
pH 7.6 Final pH is higher than in respiratory alkalosis
compensat
ion
pH 7.5
pH 7.4
pH 7.3 24 hr 24 hr
pH 7.2
pH 7.1 n sa tion
e
pH 7.0 comp
pH 7.07.25 pH 7.67.5
63
METABOLIC ACIDOSIS METABOLIC ALKALOSIS
Summary of changes in PCO2
Gold trunk
Compensation in Metabolic Disorders
• The change in the PCO2 in the metabolic disorders represents the
lung’s role in compensation
• Compensation may take up to 1 day (24 hours)
• pCO2 returns towards normal (but is never normal)?
• pCO2  in METABOLIC ACIDOSIS from 4022.5 mmHg within 1 day.
Final pCO2 is lower than in respiratory acidosis
• pCO2  in METABOLIC ALKALOSIS from 4050 within 1 day.
Final pCO2 is higher than in respiratory alkalosis

64
METABOLIC ACIDOSIS METABOLIC ALKALOSIS
 Part 4
Own reading

• Indicators of hypoxaemia and hypoxia

• Hypercapnia
– Major causes of hypercapnia
– Clinical features of hypercapnia
– Hypoxemia and hypercapnia
• Hypocapnia
– Causes of hypocapnia
– Clinical features of hypocapnia
65
Indicators of hypoxaemia and hypoxia
Arterial blood gases Lab Findings
80-100 mm Hg (normal)
60-80 mm Hg (mild hypoxemia)
PO2 40-60 mm Hg (moderate hypoxemia)
<40 mm Hg (severe hypoxemia)
95%-97% (normal)
SO2 <90% (may indicate hypoxemia)

7.35-7.45 (normal)
pH <7.35 (acidemia)
>7.45 (alkalemia)
35-45 mm Hg (normal)
PCO2 >45 mm Hg (hypoventilation)
<35 mm Hg (hyperventilation)
66
Indicators of hypoxaemia and hypoxia
System Clinical Signs
Respiratory system Tachypnea, decreased tidal
volume, dyspnea, yawning, use of
accessory respiratory muscles,
flared nostrils
Central nervous system Headache (from cerebral
vasodilation), mental confusion,
bizarre behaviour, restlessness,
agitation, anxious facial
expression, sweating, drowsiness
progressing to coma when hypoxia
is severe
67
 Hypoxemia and hypercapnia
• By definition, hypoxemia is present in respiratory
failure – patient may need oxygen support

• Hypoxemic respiratory failure is characterised by

hypoxemia and either normocapnia or
hypocapnia

• Ventilatory failure is characterised by hypoxemia

and hypercapnia
68
Indicators of hypoxaemia and hypoxia

System Clinical Signs

Cardiovascular system Tachycardia early; bradycardia
later when the heart muscle is
not receiving adequate O2, rise
in BP followed by a drop when
hypoxia remains uncorrected;
dysrhythmias
Skin Cyanosis of lips, oral mucosa,
and nailbeds
69
 Major causes of hypercapnia
• The major causes of hypercapnia are
obstructive airways disease, respiratory
depressant drugs, weakness or paralysis
of the respiratory muscles, chest trauma or
abdominal surgery causing shallow
respirations, and loss of lung tissue – e.g.,
when diabetic patient lies in bed for too
long, lazy to get up to go to toilet, lazy to
do exercises, silly ideas, uncooperative …
70
 Clinical features of hypercapnia
• Clinical signs associated with hypercapnia
are mental confusion progressing to coma,
headache (as a result of cerebral
vasodilation), asterixis or flapping tremor
of the outstretched hands, and a pulse of
large volume with warm, sweaty
extremities (as a result of the peripheral
vasodilation caused by the hypercapnia) –
as the diabetic patient stretches her hand
71
 Clinical features of hypercapnia
• In chronic hypercapnia resulting from
chronic pulmonary disease, the patient
may become abnormally tolerant to the
high PCO2, so that the principal drive to
respiration is hypoxia
– E.g., the lazy diabetic patient who complaints
of difficulty breathing
– Danger! Under these circumstances, if O2 is
administered at a high concentration,
respiration is diminished and the hypercapnia
is increased
72
 Hypocapnia
• Excessive loss of CO2 from the lungs
(hypocapnia) occurs when there is
hyperventilation (ventilation in excess of
metabolic need to remove CO2)

73
 Causes of hypocapnia
• Common causes of hyperventilation
include brain injury/cerebral trauma,
tumour, aspirin poisoning, anxiety,
compensation for metabolic acidosis/
compensatory response to hypoxia, or
excessive mechanical ventilation - asthma
and pneumonia

74
 Clinical features of hypocapnia
• Signs and symptoms typically associated
with hypocapnia include frequent sighing
and yawning, dizziness, palpitations,
tingling and numbness in the extremeties,
and muscular twitches

• Danger! Severe hypocapnia (PCO2 <25

mm Hg) may cause convulsions
75
 Part 5
Own reading

• Serum values in acid-base disturbances

• Serum electrolytes values
• Upper limits of arterial blood pH and
bicarbonate
• Acid-base map
• Summary of pure acid-base disorders

76
Serum Values in Acid-Base Disturbances
Condition Na+ Cl- HCO3- pCO2 pH
mmol/L mmol/L mmol/L mmHg
Normal 140 105 25 40 7.40
Metabolic acidosis 140 115 15 31 7.30
Chronic respiratory alkalosis 136 102 25 40 7.44
Mixed metabolic acidosis and 136 108 14 24 7.39
chronic respiratory alkalosis
Metabolic alkalosis 140 92 36 48 7.49
Chronic respiratory acidosis 140 100-102 28 50 7.37

Mixed metabolic alkalosis and 140 90 40 67 7.40

77
chronic respiratory acidosis
 Serum Values in Acid-Base Disturbances
Condition Na+ Cl- HCO3- pCO2 pH
mmol/L mmol/L mmol/L mmHg
Normal 136-145 100-106 24-26 35-45 7.35-7.45
Metabolic alkalosis 139 89 35 47 7.49
Respiratory alkalosis 136 102 20 30 7.44
Mixed alkalosis, mild 139 92 32 39 7.53

Mixed alkalosis, severe 139 92 32 30 7.63

Mixed chronic respiratory 136 102 22 55 7.22
acidosis and acute
metabolic acidosis
Mixed metabolic acidosis 140 103 25 40 7.40 78
and metabolic alkalosis
 Mixed Metabolic Acidosis and
Chronic Respiratory Alkalosis
Examples:
• Sepsis
• Addition of respiratory alkalosis to
metabolic acidosis further decreases
HCO3- but pH may remain normal
• Lactic acidosis plus respiratory alkalosis
due to severe liver disease, pulmonary
emboli, or sepsis
79
 Mixed Metabolic Alkalosis and
Chronic Respiratory Acidosis
Examples:
• Patient with COPD receiving
glucocorticoids or diuretics
• pCO2 and HCO3- are increased by both
conditions, but pH is neutralized

80
 Mixed Alkalosis, Severe
Example:
• Postoperative patient with severe
hemorrhage stimulating hyperventilation
[respiratory alkalosis] plus massive
transfusion and nasogastric drainage
[metabolic alkalosis]

81
Mixed Chronic Respiratory Acidosis
and Acute Metabolic Acidosis
Examples:
• COPD [chronic respiratory acidosis] with
severe diarrhoea [metabolic acidosis]. pH
is too low for pCO2 of 55 mmHg in chronic
respiratory acidosis, indicating low pH due
to mixed acidosis, but HCO3- effect is
offset

82
 Mixed Metabolic Acidosis and
Metabolic Alkalosis
Examples:
• Gastroenteritis with vomiting [metabolic
alkalosis] and diarrhoea [metabolic
acidosis due to loss of HCO3-]; surprisingly
normal findings with marked volume
depletion

83
 Serum Electrolyte Values in
Various Conditions
Condition HCO3- K+ Na+ Cl-
pH
mmol/L mmol/L mmol/L mmol/L
Normal 7.35-7.45 24-26 3.5-5.0 136-145 100-106
Metabolic acidosis
Diabetic acidosis 7.2 10 5.6 122 80
Fasting 7.2 16 5.2 142 100
Severe diarhoea 7.2 12 3.2 128 96
Hyperchloremic acidosis 7.2 12 5.2 142 116
Addison’s disease 7.2 22 6.5 111 72
Nephritis 7.2 8 4.0 129 90
Nephrosis 7.2 20 5.5 138 11384
 Serum Electrolyte Values in
Various Conditions

Condition HCO3- K+ Na+ Cl-

pH
mmol/L mmol/L mmol/L mmol/L
Normal 7.35-7.45 24-26 3.5-5.0 136-145 100-106
Metabolic alkalosis
Vomiting 7.6 38 3.2 150 94
Pyloric obstruction 7.6 58 3.2 132 42
Duodenal obstruction 7.6 42 3.2 138 49
Respiratory acidosis 7.1 30 5.5 142 80
Respiratory alkalosis 7.6 14 5.5 136 112
85
Upper Limits of Arterial Blood pH and [HCO3-]
(Expected for Blood pCO2 Values)
Arterial Blood
Calculated
pCO2 HCO3-
pH
mmHg mmol/L

20 7.66 22.8
30 7.53 25.6
40 7.57 27.3
60 7.29 27.9
80 7.18 28.9
Values shown are the upper limits of the 95% confidence bands 86
Source: Coe FL, Metabolic alkalosis. JAMA 1977; 2238-2288
(Jacques Wallach,
7th edition, 2000;
Fig. 12-1, page
495 - Acid-Base
Map)

What are
normal ABG
values?

87
 Summary of Pure and Mixed Acid-
Base Disorders
Decreased pH Normal pH Increased pH

Normal Metabolic acidosis Normal Metabolic alkalosis

pCO2

 pCO2 Metabolic acidosis with Respiratory Respiratory alkalosis

incompletely compensated alkalosis and with or without
respiratory alkalosis or compensated incompletely
coexisting respiratory metabolic acidosis compensated
alkalosis metabolic acidosis or
coexisting metabolic
alkalosis
Source: Adapted from Friedman HH. Problem-oriented medical diagnosis, 3rd 88
ed. Boston: Little, Brown. 1983
Summary of Pure and Mixed Acid-
Base Disorders
Decreased Normal pH Increased
pH pH
 pCO2 Respiratory acidosis Respiratory Metabolic alkalosis
with or without acidosis and with incompletely
incompletely compensated compensated
compensated metabolic alkalosis respiratory acidosis
metabolic alkalosis or or coexisting
coexisting metabolic respiratory acidosis
acidosis
Normal Metabolic acidosis Normal Metabolic alkalosis

pCO2
Source: Adapted from Friedman HH. Problem-oriented medical diagnosis, 3rd
ed. Boston: Little, Brown. 1983 89
 Reference
Own reading

• Renal Block
– Renal compensatory mechanisms in acid-base
imbalance
• Reference:
– Biochemistry: A Comprehensive Review for Medical
Students. Essentials of Modern Biochemistry.
Rudolf Werner
QU4 W494 1983
Pages 339-341

90
 Reference
• An illustrated colour text. Clinical
Biochemistry.
Allan Gaw, Robert A. Cowan, Denis St. J.
O’Reilly, Michael J. Stewart, James
Shepherd
Churchill Livingstone, London
1995, pages 34-43
RM45 (Syarikat Kamal)

91
 Reference
• Interpretation of Diagnostic Tests
Jacques Wallach
Seventh Edition, 2000
Lippincott Williams & Wilkins, Philadelphia
Chapter 12 – Acid-Base Disorders, pages
489-500
RM100 (Syarikat Kamal)

92
 Reference
• Clinical Chemistry in Diagnosis and Treatment.
Philip D. Mayne
Sixth edition, 1994
Educational Low-Priced Books Scheme funded by
the British Government
RM15 (Koperasi UNIKEB)
Chapter 4
Hydrogen ion homeostasis, pages 79-90
Disturbances of hydrogen ion homeostasis, pages 90-104

93
 Reference
• A Primer of
Chemical Pathology.
1996
– Evelyn S.C. Koay
– Noel Walmsley

• World Scientific
Publishing Co. Pte. Ltd.
• Singapore

• QY4 K75 1996

94
 Study guide
Own reading

Acid-base:
• Identify the primary disorder (lesion)
• List possible causes
• Describe the causative mechanism
• Describe the compensatory mechanism
• Determine the level of compensation

95
 Acid-base algorithms
Own reading

• Online resources:
– Cecil Textbook of Medicine
– Harrison’s Principles of Internal Medicine
– Current Medical Diagnosis & Treatment Type acid-base
– www.amazon.com in the search box
– www.google.com

96