Assessment And Disorders

Of Acid-Base Balance
Mrs Sarah Curtis DipRCPath
Royal Liverpool Hospital

Aims of the lecture
• Understand measurements used to
describe acid-base biochemistry

• Develop a logical approach to assessment
of acid-base disorders

• Apply knowledge to clinical cases
What do ‘Blood Gas’ machines measure?
Derived parameters
Base excess
Standard bicarbonate
Total CO2
Anion Gap
Co-oximetry
Total Hb
O2 saturation
Oxy-Hb
CO-Hb
Met-Hb
Metabolites
Glucose
Lactate
Electrolytes
Sodium
Potassium
Chloride
Calcium
Gases
PCO2
PO2
pH
Let’s take a look at the
Henderson-Hasselbalch
equation…
pH = pK
a
+ Log
10
[A-]
[AH]
Where has it come from?
Panic!
Panic!
Panic!
Panic!
Panic!
Panic!
What am I supposed to do with it?
Panic!
You may previously have seen two different ‘logs’ used:
Base ‘10’ (Log
10
often just written Log)
We are only concerned with Log
10

Base ‘e’ (Log
e
or Ln)
and the reverse of this, ‘antilog’, 10
x
The logarithm of 1000 to base 10 is 3…
Log
10
1000 = 3
The logarithm of a number is the exponent by which another fixed
value, the base, has to be raised to produce that number.
????????
And in reverse… the ‘antilog’ of 3 to base 10 is 1000
Antilog 3 = 10
3
= 1000
…because 1000 is 10
3
1000 = 10
3
= 10 × 10 × 10
Enough maths, time for
some Chemistry…
Acid Equilibria
Acids reversibly dissociate to release protons (H
+
)
AH
A
-
H
+
acid conjugate
base (salt)
proton
Acid Dissociation Constant
K
a
= [A
-
] x [H
+
]
[AH]
Strong acids (e.g. HCl) are more favourably dissociated: K
a
large
Weak acids (e.g. ethanol) are poorly dissociated: K
a
small
Describes the readiness with which an acid will dissociate
HCl
Cl
-
H
+
HCl Cl
-
Cl
-
Cl
-
H
+
H
+
H
+
H
+
Cl
-
EtOH
EtO
-
H
+
EtO
-
H
+
EtOH
EtOH
EtOH
EtOH
Bringing in the logarithms…
We all love ‘pH’, but what does it mean?

Even for strong acids, [H
+
] is still very small…

Logarithms make the numbers manageable (pre electronic calculators!)

pH = -Log
10
[H
+
]
[H+]
Blood
= 40 nmol/L
Blood pH = -Log
10
[0.00000040]
= 0.00000040 mol/L
= pH 7.0
The same trick is used for the rather less popular ‘pK
a


pK
a
= -Log
10
[K
a
]
Deep breath…
pK
a
= -Log
10
[K
a
]
Substituting for K
a
Since LogXY = LogX + LogY
pH = pK
a
+ Log
10
[A-]
[AH]
= -Log
10
[A
-
] [H
+
]
[AH]
= -Log
10
[A
-
] - Log
10
[H
+
]
[AH]
= -Log
10
[A-] + pH
[AH]
pK
a
= -Log
10
[K
a
] K
a
= [A
-
] [H
+
]
[AH]
We know:
Substituting for -Log
10
[H
+
]
Rearranging to put pH at the beginning
pH = -Log
10
[H
+
]
= -Log
10
[A
-
] x [H
+
]
[AH]
Henderson-Hasselbalch
Let’s take another look at the
Henderson-Hasselbalch
equation…
pH = pK
a
+ Log
10
[A
-
]
[AH]
Conjugate base (salt)
Acid
In blood there is a bicarbonate buffering system
Describes the relationship between pH and a buffering system
weak acid and its conjugate base (salt)
HCO
3
-
H
2
CO
3

+ H
+

Henderson-Hasselbalch
and the blood
pH = pK
a
+ Log
10
[HCO
3
-
]
[H
2
CO
3
]
Conjugate base (salt)
Acid
The lungs
excrete CO
2
,
increasing
the buffering
capacity
Bicarbonate buffering in
blood has a pK
a
’ = 6.1
H
2
O + CO
2
Carbonic
anhydrase
As H
2
CO
3
is in equilibrium with CO
2

we can replace this with PCO
2
(kPa)
multiplied by a solubility factor 0.225
HCO
3
-
H
2
CO
3

+ H
+

6.1
0.225 x PCO
2

How does this relate to laboratory
assessment of acid-base Biochemistry?
pH = 6.1 + Log
10
[HCO
3
-
]
0.225 x PCO
2

Normal blood pH = 7.35-7.45
[H
+
] > 45 nmol/L = acidaemia

[H
+
] < 35 nmol/L = alkalaemia
Normal [H
+
] = 35-45 nmol/L
What is the prevailing [H
+
]?
Measured using pH electrode on blood gas machine
pH
1
st
How does this relate to laboratory
assessment of acid-base Biochemistry?
pH = 6.1 + Log
10
[HCO
3
-
]
0.225 x PCO
2

Normal blood PCO
2
= 4.7-6.0 kPa
PCO
2
> 6.0 kPa = metabolic

PCO
2
< 4.7 kPa = respiratory
2
nd
PCO
2
> 6.0 kPa = respiratory

PCO
2
< 4.7 kPa = metabolic
Alkalosis Acidosis
Is the primary disorder metabolic or respiratory?
Measured using CO
2
electrode on blood gas machine
PCO
2
How does this relate to laboratory
assessment of acid-base Biochemistry?
pH = 6.1 + Log
10
[HCO
3
-
]
0.225 x PCO
2

Normal blood standard HCO
3
-
= 22-26 mmol/L
3
rd
Is there any compensation?
Derived by blood gas machine (Van Slyke equation) using pH, PCO
2
& Hb
Normal [HCO
3
-
]
standard
= all respiratory

Abnormal [HCO
3
-
]
standard
= metabolic component
‘Standard’ bicarbonate is one corrected for respiratory contribution (normalise PCO
2
)
a - 24.4 = - (2.3 ± b + 7.7) ± (c - 7.40) + d/(1 - 0.023 ± b)

a = bicarbonate concentration in plasma (mmol/L)
b = haemoglobin concentration in blood (mmol/L)
c = pH of plasma at 37 °C
d = base excess concentration in blood (mmol/L)
How does this relate to laboratory
assessment of acid-base Biochemistry?
pH = 6.1 + Log
10
[HCO
3
-
]
0.225 x PCO
2

Normal Total CO
2
(‘bicarbonate’) = 22-33 mmol/L
Measured enzymatically or derived by gas machine from Henderson-Hasselbalch
‘Total CO
2
’ is approximation of bicarbonate = HCO
3
-
+ CO
2
+ H
2
CO
3
+ CO
3
-
TCO
2
= Metabolic acidosis / Respiratory alkalosis
TCO
2
= Metabolic alkalosis / Respiratory acidosis
Base Excess
CO
2
cannot be buffered by bicarbonate…
Respiratory
alkalosis
relative base deficit
HPr
Pr
- H
+
Pr
-
HPr
H
+
Equilibration of CO
2
requires non-bicarbonate buffers
relative base excess
H
2
O + CO
2
Carbonic
anhydrase
HCO
3
-
H
2
CO
3

+ H
+

/ negative base excess
Derived by blood gas machine using pH, PCO
2
& Hb
Amount of strong acid/alkali needed to titrate whole blood to pH 7.4 at normal PCO
2
BE = (HCO
3
-
- 24.4 + [2.3 × Hb + 7.7] × [pH - 7.4]) × (1 - 0.023 × Hb)
Respiratory
acidosis
Anion Gap
‘Unmeasured’ Anions
• Proteins
• -Hydroxybutyrate
• Acetoacetate
• Lactate
• Sulphates
• Phosphates
• Formate
• Glycolate
• Oxalate
• Hippurate
• Salicylate
‘Unmeasured’ Cations
• Calcium
• Magnesium
• (Lithium)
• (Cationic Igs)
Difference between sum of measured anions and cations
Anion gap = [Na
+
] + [K
+
] – [Cl
-
] – [HCO
3
-
]
Normal individuals have excess measured cations, hence anion ‘gap’
Increased
anion gap in
metabolic
acidosis
(HCO
3
-
)
Absent gap is rare phenomenon
• Increased unmeasured cations
• Hypoalbuminaemia
• Bromide toxicity (spurious Cl
-
)
• Nitrates
(Osmolar gap indicates uncharged species)
Disorders of Hydrogen Ion
Homeostasis
Metabolic Acidosis
pH [H+] PCO
2
HCO
3
-
PO
2
  N /  
Metabolic Acidosis - Causes
Increased Acid Formation
Ketoacidosis: diabetic, alcoholic, starvation
Lactic acidosis
Type A: tissue hypoxia
Type B: drugs, liver disease, IEMs
D-lactic acidosis
Poisoning: salicyate, alcohols
Inherited organic acidoses
Decreased Acid Excretion
Uraemia
Distal renal tubular acidosis (1/4)
Acid Ingestion
Strong acid
Ammonium chloride
I.V. feeding with cationic amino acids
Loss Of Base
Gastrointestinal: diarrhoea, fistula
Renal
Proximal renal tubular acidosis (2)
Acetazolamide
Ureteroenterostomy
Which of these increase the anion gap?
Metabolic Acidosis – Response
Buffering
Acute H
+
resisted by bicarbonate buffering causing HCO
3
-
Tissue proteins and bone important in chronic acidosis
Respiratory Compensation
Peripheral chemoreceptors and respiratory centre stimulated – hyperventiliation
Self-limiting as generates additional CO
2
– lower limit for PCO
2
is 1.6 kPa
Develops rapidly but several hours to become maximal


Renal Compensation
Urine H+ excretion maximised (pH 4.2)
Glutaminase induced in chronic acidosis
Increased renal gluconeogenesis
Increased rate of regeneration of bicarbonate
Glutamine Glutamate
NH
3

H
2
O
Systemic Effects Of Acidosis
Cardiovascular
Negative inotropic effect
Arteriolar vasodilaton
Constriction of peripheral veins
Oxygen Delivery
Immediate right shift (Bohr) in oxyHb dissociation curve
Slow left shift in oxyHb dissociation curve (synthesis breakdown 2,3-BPG)
Potassium
K
+
movement from ICF to ECF causing hyperkalaemia
Decreased renal excretion
Frequently K-depleted; hypokalaemia common with correction
Bone
Decalcification with negative calcium balance
Osteodystrophy
Metabolic Acidosis - Management
Identify and treat cause

Administration of i.v. sodium bicarbonate (alkali)
Usually only given if [H
+
] > 100 nmol/L (pH 7.0)
Oral bicarbonate
CKD, RTA types 1 & 2

Rapid correction impairs O
2
delivery (until 2,3-BPG normal)

Rebound alkalosis possible
Respiratory Acidosis
pH [H+] PaCO
2
HCO
3
-
   N / 
Respiratory Acidosis - Causes
Defective Control Of Respiration
CNS depression
Anaesthetics
Narcotics
Severe hypoxia
CNS disease
Trauma
Stroke
Neurological disease
Spinal cord lesions
Poliomyelitis
Guillan-Barre syndrome
Motor neurone disease
Neurotoxins
Defective Respiratory Function
Mechanical
Myasthenic syndrome
Myopathies
Thoracic tumours and deformities
Pneumothorax
Pleural effusion
Airway disease
Restrictive defects
Fibrosis
Pulmonary oedema
Infiltrative tumours
Obstructive defects
Chronic bronchitis
Emphysema
Severe asthma
Laryngospasm
Impaired perfusion
Massive pulmonary embolism
Respiratory Acidosis – Response
Buffering
Limited buffering by haemoglobin

Intracellular buffers important in chronic acidosis
Respiratory Compensation
PCO
2
stimulates respiratory centre but disease prevents adequate response
Renal Compensation
Maximal bicarbonate reabsorption
Almost all phosphate excreted as H
2
PO
4
-
Marked increase in urinary ammonium

Respiratory Acidosis – Systemic Effects
Hypoxaemia:
Breathlessness, cyanosis, drowsiness
Hypercapnia:
Neurological, headache, papilloedema, extensor plantar responses, myoclonus
Effects of acidosis (as for metabolic)
Respiratory Acidosis – Management
Treat underlying cause if possible
Maintain adequate arterial PO
2
, avoid loss of hypoxic stimulus to respiration
Avoid rapid correction as risk of alkalosis due to persistence of compensation
Metabolic Alkalosis
pH [H+] PaCO
2
HCO
3
-
K
+
  N / 
(not > 8kPa)
 
Metabolic Alkalosis - Causes
Saline-Responsive

Gastrointestinal
Vomiting
Gastric drainage
Congenital Cl-losing diarrhoea

Exogenous alkali administration
Sodium bicarbonate
Lactate
Acetate (especially if GFR)

Urinary
Poorly reabsorpable anion therapy
Diuretic administration post PCO
2
Saline-Unresponsive

Association with hypertension
Primary hyperaldosteronism
Secondary hyperaldosteronism

Not usually associated with HT
Barter’s syndrome
Refeeding syndrome
Severe potassium depletion
Magnesium deficiency
Excessive loss / increased generation of H
+
, exogenous alkali
Metabolic Alkalosis – Response
Buffering
Release of buffered H
+
, with HCO
3
-
Respiratory Compensation
Decreased stimulation of chemoreceptors but self-limiting as PCO
2
stimulates
Hypoxic stimulus also overrides H
+

Renal Compensation
Inappropriate reabsorption of HCO
3
-
due to GFR and increased tubular function
If ECF volume associated with Cl
-
deficiency, obligatory HCO
3
-
reabsorption
Potassium deficiency contributes to persistence of alkalosis
Increased mineralocorticoid activity promotes distal tubular Na
+

Metabolic Alkalosis – Systemic Effects
Generally opposite to those of acidosis
Less pronounced CV effects, poor O
2
delivery, no apparent bone effects
Potassium depletion, which sustains alkalosis
Neuromuscular hyperexcitability: parasthesia, muscle cramps, tetany, convulsions
( Binding of H
+
to albumin increases Ca
2+
binding, lowering ionised calcium)
Metabolic Alkalosis – Management
Treat underlying cause
Treat factors that sustain alkalosis
Do not give saline if saline-unresponsive cause
(e.g. sodium excess)
Respiratory Alkalosis
pH [H+] PaCO
2
HCO
3
-
K
+
Phos

   N /   
Respiratory Alkalosis - Causes
Rate of excretion of CO
2
exceeds rate of production
Voluntary hyperventiliation

Mechanical hyperventilation

Reflex hyperventilation
Pulmonary compliance
Disease affecting chest wall
Irritative lesions of the air passages

Respiratory stimulation
Cortical influences : pain, fever, anxiety
Local disease: trauma, tumours
Toxins: salicylate, hepatic failure
Hypoxaemia: high altitude, right-to-left shunts, pulmonary disease, CO
Recovery from metabolic acidosis

Respiratory Alkalosis – Response
Buffering
Release of H
+
from non-bicarbonate buffers
New steady state achieved within 6 hours

Respiratory Compensation
Inhibitory effect of PCO
2
overwhelmed by primary cause
Renal Compensation
Decreased renal generation of bicarbonate (CO
2
is substrate)

Respiratory Alkalosis – Systemic Effects
Manifestations of underlying disease predominate
Acute hypocapnia decreases cerebral blood flow
Ionised calcium: perioral and peripheral parasthesia
Cardiovascular: increased heart rate, tightening of chest, angina
Mild hypokalaemia
Marked hypophosphataemia

Respiratory Alkalosis – Management
Treat underlying cause
Rapid symptomatic relief by re-breathing
Sedation or prevention of hyperventilation
by mechanical hyperventilation
Mixed Acid-Base Disorders
Mixed primary disorders are quite common if you look for them

Some examples of double disorders… triple etc. also occur!
Metabolic Acidosis Metabolic Alkalosis
Respiratory Acidosis Respiratory failure
Cardiac arrest
Ethanol
Methanol
Diuretics + COPD
Vomiting + COPD
Severe K
+
depletion
Respiratory Alkalosis Salicylate
Septicaemia
Fulminant hepatic failure
Ketoacidosis + pneumonia
Vomiting + CCF
Diuretics + pneumonia
Metabolic Alkalosis Vomiting + renal failure
Diuretics + DKA
Severe vomiting in ketoacidosis
Counterbalancing Additive
Conclusions
• Henderson-Hasselbalch is our friend!

• Respiratory disorders are compensated by
metabolic processes

• Metabolic disorders are compensated by
respiratory processes

• Over-compensation does not occur