Pathophysiology of Respiratory Failure

Gamal Rabie Agmy ,MD ,FCCP

Professor of Chest Diseases, Assiut University
ERS National Delegate of Egypt
 Non Respiratory Functions

Biologically Active Molecules:

*Vasoactive peptides
*Vasoactive amines
*Neuropeptides
*Hormones
*Lipoprotein complexes
*Eicosanoids
 Non Respiratory Functions

Haemostatic Functions

Lung defense :
*Complement activation
*Leucocyte recruitment
*Cytokines and growth factors
Protection
Vocal communication
Blood volume/ pressure and pH regulation
 Respiratory Functions

*Oxygenation

*CO2 Elimination
 Definition

*Failure in one or both gas exchange functions:

oxygenation and carbon dioxide elimination

*In practice:
PaO2<60mmHg or PaCO2>50mmHg

*Derangements in ABGs and acid-base status

 Definition

Respiratory failure is a syndrome of

inadequate gas exchange due to
dysfunction of one or more essential
components of the respiratory system
 Types of Respiratory Failure

Type 1 (Hypoxemic ): * PO2 < 60 mmHg on room air.

Type 2 (Hypercapnic / Ventilatory): *PCO2 > 50
mmHg
Type 3 (Peri-operative): *This is generally a subset of
type 1 failure but is sometimes considered
separately because it is so common.
Type 4 (Shock): * secondary to cardiovascular
instability.
 The respiratory System
Lungs Respiratory pump

Pulmonary Failure Ventilatory Failure

• PaO2 • PaO2
• PaCO2 N/ • PaCO2

Hypoxic Hypercapnic
Respiratory Respiratory
Failure Failure
 Cardiogenic pulmonary edema Atelectasis

Post surgery
Pneumonia
Hypoxic changes

pulmonary
ARDS
Respiratory Trauma

Failure Pulmonary
extra pulmonary fibrosis
ARDS

Infiltrates in Aspiration
immunsuppression
 Type 3 (Peri-operative)
Respiratory Failure

Residual anesthesia effects, post-

operative pain, and abnormal
abdominal mechanics contribute to
decreasing FRC and progressive
collapse of dependant lung units.
 Type 3 (Peri-operative)
Respiratory Failure
Causes of post-operative atelectasis include;
*Decreased FRC
*Supine/ obese/ ascites
*Anesthesia
*Upper abdominal incision
*Airway secretions
 Type 4 (Shock)

Type IV describes patients who are intubated and

ventilated in the process of resuscitation for
shock
• Goal of ventilation is to stabilize gas
exchange and to unload the respiratory
muscles, lowering their oxygen consumption
*cardiogenic
*hypovolemic
*septic
Hypoxemic Respiratory Failure (Type 1)

Causes of Hypoxemia

1. Low FiO2 (high altitude)

2. Hypoventilation
3. V/Q mismatch (low V/Q)
4. Shunt (Qs/Qt)
5. Diffusion abnormality
6. low mixed venous oxygen due to cardiac
desaturation with one of above mentioned
factors.
Hypoxemic Respiratory Failure (Type 1)

Physiologic Causes of
Hypoxemia
Low FiO2 is the primary cause
of ARF at high altitude and
toxic gas inhalation
 Hypoxemic Respiratory Failure (Type 1)

Physiologic Causes of Hypoxemia

However, the two most common causes of

hypoxemic respiratory failure in the ICU are
V/Q mismatch and shunt. These can be
distinguished from each other by their
response to oxygen. V/Q mismatch
responds very readily to oxygen whereas
shunt is very oxygen insensitive.
 V/Q: possibilities

0 ∞
1
V/Q =1 is “normal” or “ideal”

V/Q =0 defines “shunt”

V/Q =∞ defines “dead space” or “wasted ventilation”

Hypoxemic Respiratory Failure (Type 1)

V/Q Mismatch
V/Q>1 V/Q<1

V/Q=o V/Q=∞
 Why does “V/Q mismatch” cause
hypoxemia?
Low V/Q units contribute to
hypoxemia
High V/Q units cannot compensate
for the low V/Q units
Reason being the shape of the
oxygen dissociation curve which is
not linear
 Hypoxic respiratory failure

Gas exchange failure

Respiratory drive responds
Increased drive to breathe
– Increased respiratory rate
– Altered Vd /Vt (increased dead space etc)
– Often stiff lungs (oedema, pneumonia etc)
Increased load on the respiratory pump which
can push it into fatigue and precipitate
secondary pump failure and hypercapnia
Hypoxemic Respiratory Failure (Type 1)

Types of Shunt
1. Anatomical shunt
2. Pulmonary vascular shunt
3. Pulmonary parenchymal shunt
Hypoxemic Respiratory Failure (Type 1)

Common Causes for Shunt

1. Cardiogenic pulmonary edema
2. Non-cardiogenic pulmonary edema
(ARDS)
3. Pneumonia
4. Lung hemorrhage
5. Alveolar proteinosis
6. Alveolar cell carcinoma
7. Atelectasis
Causes of increased dead space ventilation

*Pulmonary embolism
*Hypovolemia
*Poor cardiac output, and
*Alveolar over distension.
 Ventilatory Capacity versus Demand

Ventilatory capacity is the maximal

spontaneous ventilation that can be
maintained without development of
respiratory muscle fatigue.

Ventilatory demand is the spontaneous minute

ventilation that results in a stable PaCO 2.
Normally, ventilatory capacity greatly
exceeds ventilatory demand.
Ventilatory Capacity versus Demand

Respiratory failure may result from either a

reduction in ventilatory capacity or an
increase in ventilatory demand (or both).

Ventilatory capacity can be decreased by a

disease process involving any of the
functional components of the respiratory
system and its controller. Ventilatory
demand is augmented by an increase in
minute ventilation and/or an increase in
the work of breathing.
 Components of Respiratory System

*CNS or Brain Stem *Nerves

*Chest wall (including pleura, diaphragm)
* Airways * Alveolar–capillary units
*Pulmonary circulation
 Type 2 ( Ventilatory /Hypercapnic
Respiratory Failure)

Causes of Hypercapnia
1. Increased CO2 production (fever,
sepsis, burns, overfeeding)
2. Decreased alveolar ventilation
 decreased RR
 decreased tidal volume (Vt)
 increased dead space (Vd)
 Hypercapnic Respiratory Failure
 Depressed drive: Drugs, Myxoedema,Brain stem lesions
and sleep disordered breathing
 Impaired neuromuscular transmision: phrenic nerve
injury, cord lesions, neuromuscular blokers,
aminoglycosides, Gallian Barre syndrome, myasthenia
gravis, amyotrophic lateral sclerosis, botulism
 Muscle weakness: fatigue, electrolyte Derangement
,malnutrition , hypoperfusion, myopathy, hypoxaemia
 Resistive loads; bronchospasm, airway edema
,secretions scarring ,upper airway obstruction,
obstructive sleep apnea
 Lung elastic loads:PEEPi, alveolar edema, infection,
atelectasis
 Chest wall elastic loads:pleural effusion, pneumothorax,
flail chest, obesity,ascites,abdominal distension
 Why does “V/Q mismatch” cause
hypoxemia?

• Low V/Q units contribute to

hypoxemia
• High V/Q units cannot compensate
for the low V/Q units
• Reason being the shape of the
oxygen dissociation curve which is
not linear
 Hypoxic respiratory failure
• Gas exchange failure
• Respiratory drive responds
• Increased drive to breathe
– Increased respiratory rate
– Altered Vd /Vt (increased dead space etc)
– Often stiff lungs (oedema, pneumonia etc)
Increased load on the respiratory pump which can
push it into fatigue and precipitate secondary
pump failure and hypercapnia
Hypoxemic Respiratory Failure (Type 1)

Types of Shunt
1. Anatomical shunt
2. Pulmonary vascular shunt
3. Pulmonary parenchymal shunt
Hypoxemic Respiratory Failure (Type 1)

Common Causes for Shunt

1. Cardiogenic pulmonary edema
2. Non-cardiogenic pulmonary edema
(ARDS)
3. Pneumonia
4. Lung hemorrhage
5. Alveolar proteinosis
6. Alveolar cell carcinoma
7. Atelectasis
 Causes of increased dead space
ventilation

*Pulmonary embolism
*Hypovolemia
*Poor cardiac output, and
*Alveolar over distension.
Ventilatory Capacity versus Demand

Ventilatory capacity is the maximal

spontaneous ventilation that can be
maintained without development of
respiratory muscle fatigue.

Ventilatory demand is the spontaneous minute

ventilation that results in a stable PaCO 2.
Normally, ventilatory capacity greatly
exceeds ventilatory demand.
Ventilatory Capacity versus Demand

Respiratory failure may result from either a

reduction in ventilatory capacity or an
increase in ventilatory demand (or both).

Ventilatory capacity can be decreased by a

disease process involving any of the
functional components of the respiratory
system and its controller. Ventilatory
demand is augmented by an increase in
minute ventilation and/or an increase in the
work of breathing.
 Components of Respiratory System

*CNS or Brain Stem *Nerves

*Chest wall (including pleura, diaphragm)
* Airways * Alveolar–capillary units
*Pulmonary circulation
 Type 2 ( Ventilatory /Hypercapnic
Respiratory Failure)

Causes of Hypercapnia
1. Increased CO2 production (fever,
sepsis, burns, overfeeding)
2. Decreased alveolar ventilation
• decreased RR
• decreased tidal volume (Vt)
• increased dead space (Vd)
 Hypercapnic Respiratory
Failure
• Depressed drive: Drugs, Myxoedema,Brain stem lesions
and sleep disordered breathing
• Impaired neuromuscular transmision: phrenic nerve
injury, cord lesions, neuromuscular blokers,
aminoglycosides, Gallian Barre syndrome, myasthenia
gravis, amyotrophic lateral sclerosis, botulism
• Muscle weakness: fatigue, electrolyte Derangement
,malnutrition , hypoperfusion, myopathy, hypoxaemia
• Resistive loads; bronchospasm, airway edema
,secretions scarring ,upper airway obstruction,
obstructive sleep apnea
• Lung elastic loads:PEEPi, alveolar edema, infection,
atelectasis
• Chest wall elastic loads:pleural effusion, pneumothorax,
flail chest, obesity,ascites,abdominal distension
 Hypercapnic Respiratory Failure
PaCO2 >50 mmHg
Not compensation for metabolic alkalosis

(PAO2 - PaO2)
normal increased

Alveolar V/Q abnormality

Hypoventilation

NNIF  P0.1 NIF N P0.1 N VCO2 VCO2

Central Neuromuscular V/Q Hypermetabolism

Hypoventilation Problem Abnormality Overfeeding
 Hypercapnic Respiratory Failure

Alveolar
N NIF Hypoventilation NIF

Central Neuromuscular
Hypoventilation Disorder

Brainstem respiratory depression Critical illness polyneuropathy

Drugs (opiates) Critical illness myopathy
Obesity-hypoventilation syndrome
Hypophosphatemia
Magnesium depletion

Myasthenia gravis
Guillain-Barre syndrome
 Evaluation of Hypercapnia

NIF (negative inspiratory force). This is a measure

of the patient's respiratory system muscle
strength.
It is obtained by having the patient fully exhale.
Occluding the patient's airway or endotracheal
tube for 20 seconds, then measuring the maximal
pressure the patient can generate upon
inspiration.
NIF's less than -20 to -25 cm H2O suggest that the
patient does not have adequate respiratory muscle
strength to support ventilation on his own.
 Evaluation of Hypercapnia

P0.1 max. is an estimate of the patient's

respiratory drive.
This measurement of the degree of pressure drop
during the first 100 milliseconds of a patient
initiated breath. A low P0.1 max suggests that the
patient has a low drive and a central
hypoventilation syndrome.
Central hypoventilation vs. Neuro-
muscular weakness
central = low P0.1 with normal NIF
Neuromuscular weakness = normal P0.1 with low
NIF
 A-a Gradient
n The P (A—a)O2 ranges from 10 mm Hg in young
patients to approximately 25mm Hg in the elderly while
breathing room air.

n P (A-a)O2 if greater than >300 on 100% =

Shunt < 300 = V/Q mismatch

• RULE OF THUMB
The mean alveolar-to-arterial difference [P(A—a)o2]
increases slightly with age and can be estimated ~ by the
following equation:

Mean age-specific P(A—a)O2 age/4 + 4

 Increased Work of Breathing
Work of breathing is due to physiological work and
imposed work.
Physiological work involves overcoming the elastic forces during
inspiration and overcoming the resistance of the airways and lung
tissue

Imposed Work of Breathing

In intubated patients, sources of imposed work of breathing include:

n the endotracheal tube,

n ventilator Circuit
n auto-PEEP due to dynamic hyperinflation with airflow obstruction, as is
commonly seen in the patient with COPD.
Increased Work of Breathing
n Tachypnea is the cardinal sign of increased work of breathing

n Overall workload is reflected in the minute volume needed to maintain

normocapnia.
 Rationale for ventilatory assistance

 Respiratory muscles
Abnormal
capacity
ventilatory drive

 Respiratory load

Alveolar hypoventilation
 PaO2 and  PaCO2
 Mechanical ventilation unloads the
respiratory muscles

Respiratory load Respiratory muscles

Mechanical
ventilation