2. Pathophysiology of Respiratory Failure
Gamal Rabie Agmy ,MD ,FCCP
Professor of Chest Diseases, Assiut University

4. Non Respiratory Functions
Biologically Active Molecules:
*Vasoactive peptides
*Vasoactive amines
*Neuropeptides
*Hormones
*Lipoprotein complexes
*Eicosanoids

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

6. Respiratory Functions
*Oxygenation
*CO2 Elimination

8. 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

9. Definition
Respiratory failure is a syndrome of
inadequate gas exchange due to
dysfunction of one or more essential
components of the respiratory system

11. 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.

12. The respiratory System
Lungs
Respiratory pump
Pulmonary Failure
Ventilatory Failure
• PaO2
• PaO2
• PaCO2 N/
• PaCO2
Hypoxic
Respiratory
Failure
Hypercapnic
Respiratory
Failure

13. Cardiogenic pulmonary edema
Post surgery
changes
Hypoxic
Pneumonia
pulmonary
ARDS
Atelectasis
Respiratory
Failure
extra pulmonary
ARDS
Infiltrates in
immunsuppression
Trauma
Pulmonary
fibrosis
Aspiration

14. Brainstem
Airway
Lung
Spinal cord
Nerve root
Nerve
Pleura
Chest wall
Neuromuscular
junction
Respiratory
muscle
Sites at which disease may cause ventilatory disturbance

15. Type 3 (Peri-operative)
Respiratory Failure
Residual anesthesia effects, postoperative pain, and abnormal
abdominal mechanics contribute to
decreasing FRC and progressive
collapse of dependant lung units.

16. Type 3 (Peri-operative)
Respiratory Failure
Causes of post-operative atelectasis include;
*Decreased FRC
*Supine/ obese/ ascites
*Anesthesia
*Upper abdominal incision
*Airway secretions

17. 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

18. Hypoxemic Respiratory Failure (Type 1)
Causes of Hypoxemia
1.
2.
3.
4.
5.
6.
Low FiO2 (high altitude)
Hypoventilation
V/Q mismatch (low V/Q)
Shunt (Qs/Qt)
Diffusion abnormality
low mixed venous oxygen due to cardiac
desaturation with one of above mentioned
factors.

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

20. 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.

21. 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”

22. Hypoxemic Respiratory Failure (Type 1)
V/Q Mismatch
V/Q>1
V/Q<1
V/Q=o
V/Q=∞

23. Optimal V/Q matching

24. Dead Space

25. Shunt

26. 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

27. 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

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

29. 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

30. Causes of increased dead space
ventilation
*Pulmonary embolism
*Hypovolemia
*Poor cardiac output, and
*Alveolar over distension.

31. 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.

32. 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.

33. Components of Respiratory System
*CNS or Brain Stem
*Nerves
*Chest wall (including pleura, diaphragm)
* Airways
* Alveolar–capillary units
*Pulmonary circulation

34. 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)

35. 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

36. Hypercapnic Respiratory Failure
PaCO2 >50mmHg
Not compensation for metabolic alkalosis
(PAO2 - PaO2)
normal
Alveolar
Hypoventilation
NPI max
Central
Hypoventilation
PI max
Neuromuscular
Disorder
increased
V/Q abnormality
Nl VCO2
V/Q
Abnormality
VCO2
Hypermetabolism
Overfeeding

37. Hypercapnic Respiratory Failure
V/Q abnormality
Increased Aa gradient
VCO2
Nl VCO2
V/Q
Abnormality
Hypermetabolism
Overfeeding

38. Hypercapnic Respiratory Failure
V/Q abnormality
Increased Aa gradient
VCO2
Nl VCO2
V/Q
Abnormality
• Increased dead space ventilation
• advanced emphysema
• PaCO2 when Vd/Vt >0.5
• Late feature of shunt-type
• edema, infiltrates
Hypermetabolism
Overfeeding

39. Hypercapnic Respiratory Failure
V/Q abnormality
Increased Aa gradient
VCO2
Nl VCO2
V/Q
Abnormality
Hypermetabolism
Overfeeding
• VCO2 only an issue in pts with
ltd ability to eliminate CO2
• Overfeeding with carbohydrates
generates more CO2

40. Hypoxemic Respiratory Failure
Yes
Is PaCO2
increased?
(PAO2 - PaO2)?
Hypoventilation
(PAO2 - PaO2)
Hypoventilation
alone
No
Yes
Hypovent plus
another
mechanism
Respiratory drive
Neuromuscular dz
Is low PO2
correctable
with O2?
No
Shunt
Yes
No
Inspired
PO2
High altitude
FIO2
V/Q mismatch

41. Hypercapnic Respiratory Failure
PaCO2 >50 mmHg
Not compensation for metabolic alkalosis
(PAO2 - PaO2)
normal
Alveolar
Hypoventilation
PI max
Central
Hypoventilation
NPI max
Neuromuscular
Problem
increased
V/Q abnormality
N VCO2
V/Q
Abnormality
VCO2
Hypermetabolism
Overfeeding

42. Hypercapnic Respiratory Failure
Alveolar
Hypoventilation
PI max
Central
Hypoventilation
Brainstem respiratory depression
Drugs (opiates)
Obesity-hypoventilation syndrome
N PI max
Neuromuscular
Disorder
Critical illness polyneuropathy
Critical illness myopathy
Hypophosphatemia
Magnesium depletion
Myasthenia gravis
Guillain-Barre syndrome

43. 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.

44. 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.
Neuromuscular weakness
central = low P0.1 with normal NIF
Neuromuscular weakness = normal P0.1 with low
NIF

45. 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
Shunt
•
if
greater than >300
< 300 = V/Q mismatch
on
100%
=
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

46. 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
n
n
the endotracheal tube,
ventilator Circuit
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.

47. Pediatric considerations
The frequency of acute respiratory
failure is higher in infants and
young children than in adults for
several reasons.

48. Pediatric considerations
Neonates are obligate nose breathers.
This nose breathing occurs until the
age of 2-6 months because of the close
proximity of the epiglottis to the
nasopharynx. Nasal congestion can
lead to significant distress in this age
group.

49. Pediatric considerations
The airway size is smaller. Size is one
of the primary differences in infants
and children younger than 8 years
when compared with older patients.

50. Pediatric Consideration
The epiglottis is larger and
more
horizontal
to
the
pharyngeal wall. The cephalad
larynx and large epiglottis
makes
laryngoscopy
more
challenging.

51. Pediatric Consideration
Infants and young children have a
narrow subglottic area. In children, the
subglottic area is cone shaped, with
the narrowest area at the cricoid ring. A
small amount of subglottic edema can
lead to significant narrowing, increased
airway resistance, and increased work
of breathing. Older patients and adults
have a cylindrical airway that is
narrowest at the glottic opening.

52. Pediatric considerations
In slightly older children, adenoidal
and tonsillar lymphoid tissue is
prominent and can contribute to airway
obstruction.
The intrathoracic airways and lung
include the conducting airways and
alveoli, the interstitia, the pleura, lung
lymphatics,
and
the
pulmonary
circulation.

53. Pediatric considerations
Infants and young children have fewer
alveoli. The number dramatically
increases during childhood, from
approximately 20 million after birth to
300 million by 8 years of age.
Therefore, infants and young children
have less area for gas exchange.
The alveolus is smaller. Alveolar size
increases from 150-180 mcm to 250-300
mcm during childhood.

54. Pediatric considerations
Collateral ventilation is less developed, making
atelectasis more common. During childhood,
anatomic channels form to provide collateral
ventilation to alveoli. These pathways exist
between adjacent alveoli (pores of Kohn),
bronchiole and alveoli (Lambert channel), and
adjacent bronchioles. This important feature
allows alveoli to participate in gas exchange in
the presence of an obstructed distal airway.
Smaller intrathoracic airways are more easily
obstructed. With age, the airways enlarge in
diameter and length.

55. Pediatric considerations
Infants and young children have less
cartilaginous support of the airways. As
cartilaginous support increases, dynamic
compression during high expiratory flow
rates is prevented.
The respiratory pump includes the nervous
system with central control (ie, cerebrum,
brain stem, spinal cord, peripheral nerves),
respiratory muscles, and chest wall.
The respiratory center is immature in infants
and young children, which leads to irregular
respirations and the risk of apnea.

56. Pediatric considerations
The ribs are horizontally oriented.
During inspiration, less volume is
displaced, and the capacity to
increase tidal volume is limited
when compared with that in older
patients.
The surface area for the interaction
between the diaphragm and thorax
is small, which limits displacing
volume in the vertical direction.

57. Pediatric considerations
The musculature is less developed.
The slow-twitch fatigue-resistant
muscle fibers in the infant are
underdeveloped.
The soft compliant chest wall
provides little opposition to the
deflating tendency of the lungs.
This leads to a lower functional
residual capacity than in adults

59. Acute Type 1 RF
•
•
•
•
Cardiogenic pulmonary edema
Non cardiogenic pulmonary edema
Pneumonia
Acute pulmonary thromboembolic
disease
• Acute allergic alveolitis
• Severe bronchial asthma without
diaphragmatic fatigue
• Acute milliary TB and lymphagitis
tuberculosa reticularis

60. ChronicType 1 RF
•
•
•
•
Fibrosing alveolitis
Other causes of IPF
Chronic allergic alveolitis
Thromboembolic
pulmonary
hypertension
• Chronic pulmonary edema
• Lymphangitis carcinomatosis

61. Acute Type 2 RF
• Upper airway obstruction
• Acute
severe
asthma
diaphragmatic fatigue
• Acute CNS disorder
• Myathenia gravis
• polyneuritis
• AE of COPD
• Pneumothorax
with

62. Chronic Type 2 RF
•
•
•
•
•
•
Chronic bronchitis
Emphysema
Pickwikian syndrome
kyphoscoliosis
Chronic neuromuscular diseases
Progressive
respiratory
diseases
preterminally

64. Clinically
• Clinical picture of causative disease
• Manifestations of hypoxaemia.
1-Central cyanosis if reduced hemoglobin is
>5gram%.
2- Restlessness, irritability,, impaired
intellectual functions. Acute severe
hypoxaemia may cause convulsions,
coma and death.
3- Hyperventilation and tachypnae through
stimulation of chemoreceptors

65. Clinically
• 4-Tachycardia,arrythmias,increased COP
and dilatation of peripheral vessels
• 5-Pulmonary vasoconstriction with
pulmonary hypertension
• 6-Secondary polycythaemia with
predisposition to DVT and pulmonary
embolism

66. Clinically
Manifestations of hypercapnia:
•
1-Drowsines,flapping tremors, coma(CO2 narcosis)
and papillodema due to increased CSF formation
secondary to cerebral vasodilatation and increased
cerebral blood flow.
•
2-Paradoxical action on peripheral blood vessels:
Vasodilatation through direct action and
vasoconstriction through sympathetic stimulation and
the predominant action is the local one.
•
3-Tachycardia,sweating and generalized
vasodilatation with hypotension due to sympathetic
stimulation.
•
4-Gastric dilatation and may be paralytic ileus.

67. Investigations
• for the cause
• arterial
blood
gas
analysis.
• non-invasive methods

68. Investigations

70. • Treatment of the underlying
cause
• Correction of hypoxaemia
• Treatment of complications

71. Complications of RF:
• 1-Cardiac arrythmias due to severe
hypoxaemia and acidaemia secondary to
CO2 retention.
• 2-Pulmonary hypertension and cor
pulmonale due to pulmonary
vasoconstriction as aresult of hypoxaemia
and acidaemia.
• 3-DVT and pulmonary embolism due to
polycythaemia secondary to chronic
hypoxaemia.
• 4-Complications of oxygen therapy and
mechanical ventilation.

72. Oxygen Therapy
• Controlled O2 therapy
• Uncontrolled O2 therapy

73. Oxygen Therapy

74. Different equipments of oxygen supply::
A) Central oxygen in hospitals.
B) Home oxygen, includes :
1. Compressed gas cylinders.
2. Liquid oxygen cylinders.
3. Oxygen concentrators.
4. Small devices.

75. Compressed gas cylinders

76. Liquid oxygen cylinders
easier to refill, but of
higher cost

77. An oxygen concentrator works by taking in room air
which has an oxygen concentration of around 21% and
passing it through a series of molecular, bacterial and
dust filters to remove any dust particles and unwanted
gases. Purified oxygen with a concentration of up to
95% is then delivered to the patient via a flowmeter,
with mask or nasal cannulae.

78. Aquagen
Opure O2
Oxyshot
These three forms of oxygen in small devices
applied by ingestion in Aquagen, inhalation in
Opure O2, and spray in Oxyshot.

79. Indications for acute oxygen
therapy
• Respiratory failure(PaO2<60 mmHg;
SaO2<90%).
• Cardio-respiratory arrest.
• Hypotension and low cardiac output.
• Metabolic acidosis(HCO3<18 mmol/L).
• Respiratory distress.
• Myocardial infarction.
• Sickle cell crises.

83. Nasal cannula:
The most commonly used.
Simple inexpensive, easy.
The FiO2 from 24%-44%
increasing the flow more
than 6L/min doesn't raise
FiO2 than 44 %, and may
result in drying of mucous
secretions.

85. Simple face mask

86. Face mask with reservoir bag
and one way valve.

87. Venturi mask
Ideal for type II respiratory failure (hypercapnia)
as in COPD

88. Different colors of venturi control parts adjusted
to certain O2 flow to deliver different
concentrations of O2.

89. Treanstracheal oxygen catheter:
•Bypass the anatomical dead space of upper airway,using it as an
oxygen reservoir during respiration.
•Lack of nasal or facial irritation due to oxygen flow.
•Infrequency of catheter displacement during sleep.

90. Invasive ventilator
Endotracheal tube
Invasive ventilator with endotreacheal tube:
•Give up to 100% oxygen under positive pressure.
•Used in sever cases when there is deterioration of spontaneous
breathing with decreased pH, raised CO2, and persistent
hypoxaemia.

91. Non invasive ventilator with face
mask

92. Hyperparic Oxygen
A medical treatment in which the patient is entirely
enclosed in a pressure chamber breathing 100% O2
at > 1.4 times atmospheric pressure.
Hyperbaric oxygen (HBO) therapy uses a
monoplace (single-person) chamber pressurized
with pure O2 or a larger multiplace chamber
pressurized with compressed air in which the
patient receives pure O2 by mask, head tent, or
endotracheal tube.

95. Indications
• CARBON MONOXIDE POISONING .
•ARTERIAL
GAS
EMBOLISM
DECOMPRESSION SICKNESS.
AND
•Gas gangrene.
•Crush injury.
•Compromized skin grafts and flaps.
•Mixed aerobic anerobic soft tissue infections.
•Nonhealing ischaemic wounds.
•Burns.
•Smoke ionhalation.

98. Rationale for ventilatory assistance
Abnormal
ventilatory drive
 Respiratory load
Alveolar hypoventilation
 PaO2 and  PaCO2
 Respiratory muscles
capacity

99. Mechanical ventilation unloads the
respiratory muscles
Respiratory load
Mechanical
ventilation
Respiratory muscles