ACID-BASE BALANCE

Dr Adrian G Miller PhD

Royal Liverpool Hospital

Aims of the Lecture

Introduce you to some basic concepts of

acid- base physiology
Introduce you to important buffer systems

Discuss the role of the main organs involved in

maintaining acid-base homeostasis

Describe assessment and causes of acidbase disorders

Apply knowledge to clinical scenarios (cases)

Important Notice

Acid-base homeostasis is a large, complex

subject. Use the references cited to expand
your knowledge.
Dont be phased by some of the concepts
and terminology itll all make sense
A good website to help you:
www.acid-base.com

(One day. Maybe.)

Life is a struggle. Not against sin, not against the money power, not against
malicious animal magnetism, but against hydrogen ions! Mencken, 1919.

The Basics

In physiology, when we discuss acid-base, we are essentially

describing the activity of hydrogen ions (H+)

Acids are H+ donors e.g. HCl (HCl

H+ + Cl-)
Bases are H+ acceptors e.g. OH- (OH- + H+
H2O)

Strong acids readily give up H+, strong bases readily accept H+

Hydrogen Ion Activity (pH)

The pH of a solution is defined as the negative logarithm of the

hydrogen ion activity/concentration or :

pH = -log [H+]

The average pH of blood is 7.4, which = 0.00000004 mol/L (40 nmol/L)

The relationship between [H+] and pH is illustrated thus:

If [H+] > 45 nmol/L the person

is said to be acidaemic
If [H+] < 35 nmol/L the person
is said to be alkalaemic

pKa

The pKa represents the negative logarithm of the ionisation constant

of an acid (Ka).
In English, the pKa is the pH at which a buffer exists in equal
proportions with its acid and conjugate base e.g.

Acids have pKa values < 7.0

Bases have pKa values > 7.0

The LOWER the pKa, the stronger the acid (and vice versa for
conjugate base)

Henderson-Hasselbalch Equation
Explains how acids and bases contribute to pH, ergo [H+]

In physiology, the [acid] is carbonic acid. We dont actually measure

carbonic acid but its concentration bears a linear relation to the amount
of dissolved carbon dioxide.
Well come back to this later but for now, remember this:

[dissolved carbon dioxide] is proportional to [H+]

Acid-Base Physiology

Metabolic processes result in large amounts of carbonic, sulphuric,

phosphoric (et al.) acids. During a 24-hour period, a 70 kg individual:

Exhales ~20 mol of carbon dioxide (the volatile form of carbonic

acid) through the lungs
Excretes 70-100 mmol of non-volatile acids through the kidneys

These products of metabolism are transported to the excretory

organs via the ECF without producing an appreciable change in
pH
Arterial pH 7.36 7.44
Venous pH 7.32 7.38

This transport and excretion is achieved by a

combination of efficient buffer systems and
respiratory and renal mechanisms

Physiological Buffering Systems

A buffer system consists of a weak (partly dissociated) acid

and its conjugate base (the anion that combines with a
hydrogen ion to form the acid).
Several buffer systems are used in physiology. These include:
Bicarbonate (HCO )
3
Phosphate (PO )
4
Haemoglobin (Hb )

Proteins (anionic)
Ammonia (NH3)
All designed to ensure H+ are transported and
excreted without causing damage to physiological
processes.

Renal Processes

Yucha C. Renal regulation of Acid-Base Balance. Nephrology Nursing

Journal (2004) 31 201-208

Bicarbonate
If you remember nothing else from todays lecture, remember this:

This equation is CENTRAL to acid-base balance. From it you can see:

When dissolved in blood, CO2 becomes an acid
The more carbon dioxide added to blood, the more carbonic acid (H2CO3) is
produced, which readily dissociates to release H+
Blood pH depends, not on absolute amounts of CO2 or HCO3-, but the RATIO of
the two.
Q. What will happen if the lungs cant expire sufficient CO2

Renal H+ Excretion and HCO3- Regeneration

Phosphate
Monohydrogen (H2PO42-) and Dihydrogen Phosphate (H2PO4-) form a buffer pair
with a pKa of 6.8

While this buffer system seems favourable, plasma concentrations of these

anions are too low. However, in the renal filtrate, they are present in higher
concentrations and are an important buffer in urine.
Renal Tubular Cell

http://www.nda.ox.ac.uk/wfsa/html/u13/u1312_02.htm

Ammonia

There are some myths surrounding the role of ammonia

in acid base balance.

The pKa of ammonium (NH4+) is ~100 x lower than the

physiological [H+], so almost all of ammonia in the body is already
in the ammonium form.

Ammonia comes to the fore in a urinary context as it

provides a route for urea synthesis that does not result in
the generation of H+.

Ammonia

Hye-Young Kim. Renal handling of ammonia and acid base regulation.

Electrolytes and Blood Pressure (2009) 7 9-13

Lung Processes

Haemoglobin
Hb buffering of hydrogen ions is an important process in acid-base balance. In the
deoxy- state, Hb is reduced to HHb

Oxygen Dissociation Curve

The role of proteins

Proteins contain weakly acidic and basic groups due to

their amino acid composition.
Albumin is the predominant plasma protein and is the
main protein buffer in this compartment
Intra-cellularly, other proteins act as buffers
Bone proteins play a major role in acid-base
Protein buffering within bone matrix
Increased H+ stimulates bone resorption (alkaline
minerals act as buffers)

S. New. The role of the skeleton in acid-base homeostasis.

Proc. Nutr. Soc. (2002) 61 p 151-164

Summary (I)

The key organs involved in acid-base

homeostasis are:

Lungs
Kidneys

In states of acid-base imbalance, other

systems contribute:

Liver
Bones
Intracellular proteins

Assessment of Acid-Base Status

Assessment (Clinical)

Clinical features of acidosis and alkalosis are nonspecific and may only present when disturbances are
severe

Alterations of consciousness
Breathing irregularities
Nausea and vomiting

Clues should be derived from the organ(s) trying to

correct the abnormality

Biochemical Investigations

These are vital to diagnose conditions, as well as

indicate their severity and management
The ABG may comprise:

Hydrogen ion concentration

Partial pressure of arterial carbon dioxide (PaCO2)
Partial pressure of oxygen (PaO2)
Standard bicarbonate
Anion gap
Electrolytes (optional)
Co-oximetry (optional)

What do the ABG machines measure?

Co-oximetry

Total Hb
sO2
O2 Hb
CO Hb
Met Hb
H Hb

Reference ranges

11.8-16.7 g/dL
>97%
94.0-97.0%
0-2.0%
0-1.5%
0-5.0%

Your mission, should you choose to accept it, is to find out the difference
between sO2 and O2 Hb!!

Hydrogen Ion Activity and PaCO2

Measured components (ion selective electrodes), usually

on arterial blood (ABG)
The 2 most important values to determine the TYPE of
disturbance
Respiratory acidosis
Respiratory alkalosis
Metabolic acidosis
Metabolic alkalosis
Mixed disorder

Standard Bicarbonate

Derived from the Van Slyke equation

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 37C
d = base excess concentration in blood /(mmol/L).

Must measure the pH, the pCO2, and the haemoglobin

concentration

Base Excess

Amount of strong acid/alkali that would have to be added per unit

volume of whole blood to titrate it to pH 7.4

Blood with a pH of 7.40, pCO2=5.33 kPa and Hb=15.0 g/dL at 37oC has a
BE of zero.

Calculated as follows:

BE = (HCO3- - 24.4 + [2.3 Hb + 7.7] [pH - 7.4]) (1 - 0.023 Hb)

Hb:

Assayed value from associated co-oximeter

Derived from a measured haematocrit
Assumed value entered into the analyser set-up

Anion Gap

In those analysers that measure electrolytes, the anion

gap represents the sum of the major cations in plasma
minus the major anions

Electroneutrality dictates that this should be equal and

gaps show the presence of unmeasured species
(usually proteins) e.g. lactate, ketones etc.

Disorders of Hydrogen Ion

Homeostasis

Reminder

The types of disturbance are:

Respiratory acidosis
Respiratory alkalosis
Metabolic acidosis
Metabolic alkalosis
Mixed disorder

The processes involved are

Generation of the disorder

Buffering
Physiological compensation
Correction (hopefully)

Respiratory Acidosis

A consequence of carbon dioxide retention (lungs)

pH

[H+]

PaCO2

HCO3-

N/

Buffering by haemoglobin limits the process

Compensation is achieved by

Hyperventilation
Increased renal H+ excretion
Increased bicarbonate regeneration (renal)

Causes of a Respiratory Acidosis

CNS disorders

Depression of respiratory centre

(e.g. opiates, sedatives,
anaesthetics)

CNS trauma, infarct, haemorrhage

or tumour

High central neural blockade

Poliomyelitis

Tetanus

Cardiac arrest with cerebral hypoxia

Nerve or Muscle Disorders

Guillain-Barre syndrome

Myasthenia gravis

Muscle relaxant drugs

Toxins e.g. organophosphates,

snake venom

Lung or Chest Wall Defects

COPD

Chest trauma haemothorax,

pneumothorax

Diaphragmatic paralysis

Pulmonary oedema

ARDS

Restrictive lung disease

Airway Disorders

Upper Airway obstruction

Laryngospasm

Bronchospasm/Asthma

External Factors

Inadequate mechanical ventilation

Respiratory Alkalosis

A consequence of increased carbon dioxide excretion through

the lungs

pH

[H+]

PaCO2

HCO3-

N/

Compensation is achieved by increased renal bicarbonate

excretion

Causes of a Respiratory Alkalosis

Central Causes (direct
action via respiratory centre)

Head Injury
Stroke
Anxiety-hyperventilation
syndrome (psychogenic)
Supra-tentorial' causes (e.g.
pain, fear)
Drugs (e.g. analeptics,
salicylate intoxication)
Endogenous compounds (e.g.
progesterone during
pregnancy, cytokines during
sepsis, toxins in patients with
chronic liver disease)

Pulmonary Causes (act via

intrapulmonary receptors)

Pulmonary Embolism
Pneumonia
Asthma
Pulmonary oedema (all types)

Iatrogenic (act directly on

ventilation)

Excessive controlled ventilation

Metabolic Acidosis

Can develop as a consequence of:

Increased acid formation
Decreased acid excretion
Decrease in buffering capacity
Increased acid ingestion

pH

[H+]

PaCO2

HCO3-

N /

Compensation is achieved by increasing carbon dioxide

excretion (lungs)

Causes of a Metabolic Acidosis

Raised Anion-Gap

Normal Anion-Gap

Ketoacidosis

Diabetic, alcoholic, starvation

Renal Causes

Lactic Acidosis

Impaired perfusion
Impaired carbohydrate metabolism

GI Causes

Severe diarrhoea
Drainage of pancreatic or biliary
secretions

Small bowel fistula

Renal Failure

Uraemic acidosis
Acidosis with acute renal failure

Toxins

Ethylene glycol
Methanol/ethanol
Salicylates

MUDPILES

Renal tubular acidosis

Carbonic anhydrase inhibitors

Other Causes

Recovery from ketoacidosis

Addition of HCl, NH4Cl

Metabolic Alkalosis

Can develop due to:

Loss of hydrogen ions
Decreased generation of hydrogen ions
Exogenous administration of alkali
Potassium losses

pH

[H+]

PaCO2

HCO3-

N/

Compensation is achieved by retaining carbon dioxide

Causes of a Metabolic Alkalosis

Addition of Base to ECF

Milk-alkali syndrome
Excessive NaHCO3 intake
Recovery phase from organic
acidosis (excess regeneration
of HCO3)

Potassium Depletion

Chloride Depletion

Loss of acidic gastric juice

Diuretics
Excess faecal loss (e.g. villous
adenoma)

Primary hyperaldosteronism
Cushings syndrome
Some drugs (e.g.
Carbenoxolone)
Kaliuretic diuretics
Excessive liquorice intake
(glycyrrhizic acid)
Bartter's syndrome
Severe potassium depletion

Other Disorders

Laxative abuse

Summary (II)

Respiratory disorders are compensated by

metabolic processes

Metabolic disorders are compensated by

respiratory processes

Over-compensation does not occur.

Clinical Cases

pH

pCO2

Base excess
Positive
(>2.5)

High (>6kPa)

Normal
(-2.5 to +2.5)

Interpretation
Primary respiratory
acidosis with renal
compensation
Primary respiratory
acidosis

Negative
(<-2.5)

Mixed respiratory
and metabolic
acidosis

Normal (4.5-6kPa)

Negative
(<-2.5)

Primary metabolic
acidosis

Low (<4.5kPa)

Negative
(<-2.5)

Primary metabolic
acidosis with
respiratory
compensation

Acidaemia
Low pH
(<7.35)

pH

pCO2

Base excess
Positive
(>2.5)

Low (<4.5kPa)

Normal
(-2.5 to +2.5)

Interpretation
Mixed respiratory
and metabolic
alkalosis
Primary respiratory
alkalosis

Negative
(<-2.5)

Primary respiratory
alkalosis with renal
compensation

Normal (4.5-6kPa)

Positive
(>2.5)

Primary metabolic
alkalosis

High (>6kPa)

Positive
(>2.5)

Primary metabolic
alkalosis with
respiratory
compensation

Alkalaemia
High pH
(>7.45)

Case 1
A 34 year old female, presents to her GP complaining of breathlessness
On metformin
BMI of 49

Parameter

Result

Range

H+

45

35 45 nmol/L

pH

7.35

7.35 7.45

PaCO2

7.3

4.7 6.0 kPa

PaO2

9.6

>10.6 kPa

Bicarbonate

29

22 28 mmol/L

Base Excess

-3.8

-2 to +2

O2 Sat

96%

>98%

Lactate

0.4 1.5 mmol/L

Hb

13

13 18 g/dL

Glucose

3.5 6 mmol/L

Case 1

Is it a respiratory acidosis with metabolic compensation?

Is it a metabolic alkalosis with respiratory compensation?

Remember, over-compensation does not occur.

Dx Compensated respiratory acidosis

Obesity hypoventilation syndrome (OHS) is a well-known cause of
hypoventilation. Abnormal central ventilatory drive and obesity contribute to
the development of OHS. OHS is defined as a combination of obesity,
body mass index greater than or equal to 30 kg/m2 with awake chronic
hypercapnia (PaCO2 >6 kPa) and sleep-disordered breathing.

Case 2
A 35 year old male is brought to A&E after being found unconscious at home by
his wife. She tells the Clinician her husband has:
PMH of Type 1 Diabetes Mellitus
Has not been eating well for the past 2 days due to vomiting bug
Has missed taking some insulin due to not eating
Patient was administered 10 L of O2 by mask in ambulance
O/E
Pulse 130 bpm
BP 100/60
Respiratory rate 22 breaths per minute

Case 2
Parameter

Result

Range

H+

90

35 45 nmol/L

pH

7.05

7.35 7.45

PaCO2

1.5

4.7 6.0 kPa

PaO2

28.5

>10.6 kPa

Bicarbonate

22 28 mmol/L

Base Excess

-25.2

-2 to +2

O2 Sat

99.8%

>98%

Lactate

0.4 1.5 mmol/L

Hb

12

13 18 g/dL

Glucose

35

3.5 6 mmol/L

Ketones

Positive

Case 2
Parameter

Result

Range

Sodium

141

135 145 mmol/L

Potassium

4.6

3.5 5.5 mmol/L

Chloride

96

95 105 mmolL

Ionised calcium

1.25

1 1.25 mmol/L

Glucose

35

3.5 6 mmol/L

Bicarbonate

22 28 mmol/L

What is the anion gap?

AG = (141 + 4.6) (96 + 6)
AG = 43.6 (normal 10 18)

Case 2

Uncompensated metabolic acidosis the lungs are trying to blow off

as much CO2 as possible but the degree of acidosis is such that the
patient is dangerously acidotic
Dx of Diabetic Ketoacidosis (DKA)

DKA
Lack of insulin stimulates
lipolysis
Results in generation of
ketones (weak acids but
accumulate in DKA)
Buffering system is
overwhelmed
Metabolic acidosis ensues
Management revolves
around fluid resuscitation
and insulin administration
Beware The Refeeding
Syndrome!!

Charfen & Fernandez-Freckleton. Diabetic ketoacidosis. Emerg Med Clin N Am

(2005) 23 609-628

Case 3
A 79 year old female presents to the General Surgery ward to have a
large bowel tumour removed

The tumour was found after the patient complained of 6/12 rectal
bleeding
Presented to the ward feeling tired and short of breath (SOB)

O/E
Pulse 100 bpm (tachycardic)
BP 100/80 (hypotensive)
Respiratory rate 26 breaths/min

Case 3
Parameter

Result

Range

H+

32.3

35 45 nmol/L

pH

7.49

7.35 7.45

PaCO2

3.31

4.7 6.0 kPa

PaO2

11.9

>10.6 kPa

Bicarbonate

22

22 28 mmol/L

Base Excess

+2

-2 to +2

O2 Sat

99.8%

>98%

Lactate

0.4 1.5 mmol/L

Hb

6.8

13 18 g/dL

Glucose

3.9

3.5 6 mmol/L

Case 3

What is the acid base disorder?

Uncompensated respiratory alkalosis caused by anaemia (probably
due to chronic blood loss)
In this patient, there is no impairment of oxygen transfer or
ventilation so the PaO2 and O2 Sat are normal. However, because of
the low Hb, her blood O2 content is low (hypoxaemic)
Hyperventilation is a normal response and will cause her to blow off
CO2, causing a respiratory alkalosis
Condition is treated with a blood transfusion
Why do we not give her more oxygen?

Summary

Acid-base can be difficult to master, use the many resources

available to help you.
Learning basic concepts will help (HH equation, acid-base disorders
and compensatory mechanisms etc.)
Practising ABG interpretation is an excellent way to improve your
understanding of the physiological mechanisms of acid-base
balance
Dont panic! People spend whole careers hating acid-base because
they dont get it make a friend of it and talk to those in your
department who do! (if they exist)