1. Respiratory Failure Causes of Respiratory Failure
Medicine 2
Noel V. Bautista Organ/System Examples
December 20, 2007 Central Nervous Stroke, Drug overdose, Trauma, Myxedema
System
Peripheral Guillain-Barre syndrome, Spinal cord
Respiration Nervous System compression, Poliomyelitis
- The exchange of gases between the organism and the Neuromuscular Myasthenia gravis, Tetanus, Hypokalemic
environment System paralysis, Multiple sclerosis, Botulism,
Remember that respiration not only involved the lungs but all Organophosphate poisoning, Antibiotics
the organs (Kanamycin, Polymyxin), Curariform drugs
Thorax and Severe kyphoscoliosis, Flail chest, Massive
Respiratory Failure Pleura pneumothorax or pleural effusion
- Respiratory failure is a condition in which the respiratory system Upper Airway Epiglotitis, Tracheobronchitis, Vocal cord
is unable to perform its gas-exchange function i.e. oxygenation paralysis
and/or carbon dioxide elimination Lower Airway Pneumonia, COPD, Asthma, ARDS
and Alveoli
Extended Concept of Respiration Cardiovascular Heart failure
System
Blood Anemia, Polycythemia
Cell/Tissue Sepsis, Cyanide poisoning
We could therefore investigate causes of respiratory failure
according to the structures involved in respiration
Hemoglobin → carries 98% of oxygen to be delivered to body cells
Types of Respiratory Failure
Type 1 (Normocapnic Respiratory Failure) → Hypoxemia with
eucapnia or hypocapnia
- Pure oxygen problem
Type 2 (Hypercapnic Respiratory Failure) → Hypoxemia with
hypercapnia
- Oxygenation and ventilation (e.g. involving CO2) problem
The respiratory system is a pump that facilitates gas exchange → Respiratory Failure
main function: maintain metabolic function
- Ventilation and perfusion of organs should be properly matched
for ideal oxygenation of blood which delivers oxygen to
Hypoxemia Hypercapnia
individual organ systems to maintain optimum metabolic activity
and homeostasis
- Oxygen is important in aerobic glycolysation
- Carbon dioxide should also be effectively eliminiated → or Oxygenation Failure Ventilatory Failure
would lead to acidosis
External Respiration → exchange of gas between environment and
respiratory system
Internal Respiration → exchange of gas at cellular level Respiratory System Ventilatory Pump
Cellular metabolism → driving force of ventilation Disorders Disorders
Aiways Nervous System
Better Definition of Respiratory Failure Lungs Thorax
- Respiratory failure is present when the pulmonary system is Respiratory Muscles
unable to meet the metabolic demands of the body Respiratory System
RF will always produce acidosis. Thus it is important to know
Respiratory Failure oxygenation status (by looking at ABG) and ventilation status (by
looking at CO2 status)
- ABG involves
Acute Acute - Oxygenation status
- Ventilatory status
- Acid-base disturbance
Ventilation failure usually involves CNS, thorax, respiratory muscles;
most of time lungs not affected.
Develops in Develops over Oxygenation failure usually parenchyma of lungs
Minutes to a several hours or
few hours longer Ventilation and PaCO2
Kidneys Ficke equation:
compensate for PaCo2 = VCO2 x 0.863
the respiratory VA
acidosis ↑PaCO2 ~ ↓ VA
Classification of acute and chronic is very arbitrary → there is no - the lower the ventilation, the more CO2 accumulates
defining line
Acute respiratory failure → subcellular level has not yet been able to VE = V A + V D VE – minute ventilation
adapt to the disturbance VE = V T x f VA – alveolar ventilation
Major adaptation in gas exchange is achieved by kidneys → VA = (VT x f) – VD VD – dead space ventilation
however before the kidney participates, a buffer system first tries to VT – tidal volume
compensate f – respiratory rate
Chronic respiratory failure → kidneys have already adapted; kidney
adaptation could happen in a matter of hours or days → which is why
classification into acute or chronic is arbitrary CO2 elimination is usually 250 mL/min
How do get an idea of the status of alveolar ventilation: check
PaCO2
1

2. Minute ventilation affected by: Dalton’s Law:
Tidal volume, respiratory rate, and dead space ventilation PB (barometric pressure) = PN2 + PO2 + PCO2 + PH2O
↑ Respiratory rate (tachypneic) does not assure you adequacy of = 760 mmHg (at sea level)
ventilation normal atmospheric
pressure
Ventilatory Pump Failure Barometric pressure is the sum of all the partial
- Central nervous system pressures of the most important gases in atmosphere
- Peripheral nervous system Nitrogen is an inert gas; we breathe it without any
- Thorax & Pleura physiological consequence
- Respiratory muscles → myasthenia gravis Gas that we inhale is humidified
Hypercapnia results from disturbance in ventilatory pump
PiO2 = FiO2 x PB
Causes of Hypoventilation (Hypercapnia) FiO2 = PiO2/PB = 160/760 = 21%
- Brainstem PiO2 → fraction contributed by O2
- brainstem injury due to trauma, hemorrhage, infarction, FiO2 → available oxygen
hypoxia, infection etc
- metabolic encephalopathy Effects of Altitude on Barometric Pressure
- depressant drugs
- Spinal cord Altitude (Feet) PB (mmHg) PiO2 (mmHg)
- trauma, tumor, transverse myelitis 0 760 159
- Nerve root injury 10,000 523 110
- Nerve 20,000 349 73
- trauma 30,000 226 47
- neuropathy eg Guillain Barre 40,000 141 29
- motor neuron disease 50,000 87 18
- Neuromuscular junction In the urban setting, decreased FiO2 is rarely the reason for
- myasthenia gravis respiratory failure, except in cases of fire, CO poisoning
- neuromuscular blockers
- Respiratory muscles Alveolar Gases
- fatigue - amount O2 that reaches alveoli
- disuse atrophy
- myopathy
- malnutrition
- Respiratory system
- airway obstruction (upper or lower)
- decreased lung, pleural or chest wall compliance Alveolar Air Saturated
O2 100 mmHg (13%)
N2 573mmHg (76%)
Causes of Ventilatory Failure CO2 5mmHg (40%)
H2O 47mmHg (6%)
Increased VCO2 Fever, hypermetabolism
Increased VD and Lung parenchyma disorders e.g. COPD,
Decreased VA asthma, ARDS, pulmonary embolism Alveolar air equation:
Decreased VA Decreased ventilatory drive e.g. sedation or PAO2 = (PB – PH2O) x FiO2 – (PaCO2/RQ)
“Pump” failure e.g. neuromuscular disease = (760 – 47) x FiO2 – (PaCO2/RQ)
If blood gases reveal hypercapnea, try to categorize them into the = 713 x FiO2 – (PaCO2/RQ)
above three pathophysiological processes: = 713 x 0.21 – (40/0.8) = 99.7 mmHg
1. Increased CO2 production; rarely the cause, but can be an
additional factor that adds to hypercapnea Alveolar Capillary Membrane
More important factor is still diminished alveolar ventilation, not - When O2 reaches alveoli, next step is perfusion
increase CO2 production so can forget about this, usually it is - Fick’s law: involves diffusion of gas on surface
only co-conspirator however by itself will not cause hypercapnia
2. Increase in dead space (Minute ventilation is sum of alveolar
ventilation and dead space ventilation) which will decrease
alveolar ventilation. CO2 accumulates. Seen in obstructive
airway diseases
3. Decreased alveolar ventilation
Respiratory System Oxygenation
- Inspired gases (PiO2, PiCO2)
- Alveolar ventilation (Va, PAO2, PACO2)
- Diffusion of gas through the respiratory membrane (DmO2)
- Perfusion of pulmonary capillaries
- Ventilation-perfusion matching (V/Q) Fick’s Law of Diffusion:
Whenever there is hypercapnea, find reason. Do not rely on VO2 = DmO2 x ( PAO2 – PCO2)
respiratory rate → request for PaCO2 Dm = Diffusing Capacity
oxygenation failure – so many causes (Note: D is directly proportional to Area and Diffusion Coefficient for
the gas and inversely proportional to diffusion Distance ~ D = [A x
Inspired Air Dc]/T)
*No need to memorize or apply equation → what is important is that
Inspired Air: dry alveolar membrane should be in tip-top shape for the respiratory gases
O2 160 mmHg (21%) to diffuse through
Tracheal Air: Diffusion is fast → takes only a quarter of a second for desaturated
N2 600 mmHg (79%)
Saturated
CO2 0 mmHg (0%) gas to be completely oxygenated
O2 150 mmHg (20%)
H2O 0 mmHg (0%) So even if you exercise → diffusion or the respiratory system is
N2 563 mmHg (74%)
CO2 0 mmHg (0%) usually not the problem but the cardiovascular system
H2O 47 mmHg (6%) Exercise can improve the cardiovascular system improve oxygen
delivery from 10-15x, but the reserve capacity of the cardiovascular
system is even more (20-25x) in a normal resting physiologic bodies
Bottomline: Diffusion is not a usual cause of hypoxemia
2

3. Ventilation-Perfusion Matching
- The usual cause of hypoxemia Effect of Hypoventilation on Hypoxemia
↓Va → ↓PAO2 → ↓PaO2
↓Va → ↑PaCO2 → ↓PaO2
1mmHg ~ 1.25mmHg
Fixed Variable
PB = PN2 + PH2O + PCO2 + PO2
760 573 47 40 100 mmHg
Example:
Dead space High V/Q Low V/Q Shunt
Ventilation Ventilation Ventilation
PaCO2 = 55 mmHg (change = 55 – 40 = 15)
Expected PaO2 = 80 mmHg (80 – 15 x 1.25) = 61.25
If actual < expected → hypoventilation (plus other)
Normal V/Q ratio = 0.8 Actual PaO2 = 60 mmHg Hypoventilation
VQ matching or mismatching comes in a spectrum of physiologic Ventilation-Perfusion Mismatching
events - Causes:
A → complete ventilation but no perfusion; physiologic dead - Airway disorders
space - Lung parenchymal disorders
B → ideal VQ; ventilation is matched by perfusion. Most common cause of V/Q mismatch: Obstructive airway
Normal VQ → slightly more perfusion than ventilation; some of disease
blood flow goes back to heart unoxygenated.
D→ no ventialtion but complete perfusion; shunt Shunt Defect
Hard to determine A and D from one another; often lumped together Shunt Equation:
Qs = CcO2 – CaO2 = 5-8%
Alveolar-Arterial Oxygen Gradient QT CcO2 – CvO2
Causes:
- Intracardiac
PAO2 = 100 – 115 mmHg
- Right to left shunt e.g. Fallot's tetralogy, Eisenmenger's
syndrome
P(A-a)O2 = 15=20 mmHg
- Pulmonary
- Pneumonia
PaO2 = 80 – 100 mmHg
- Pulmonary edema
- Atelectasis
Mechanisms of Hypoxemia - Pulmonary haemorrhage
- Decreased inspired oxygen tension (FiO2) - Pulmonary contusion
- Hypoventilation*
- Ventilation – Perfusion (V/Q) mismatching* Dead Space Ventilation
- Shunt defect* Ventilation
- Diffusion defect - Causes
*The more common causes of hypoxemia - Pulmonary embolism
- Thrombus
Normal Gas Exchange
Va = 5L/min - Fat
Perfusion - Tumor
- Air
- Septic
Q = 0L/min
- Pulmonary vasculitis
Ventilation
Diffusion Defect
- Causes:
Diffusion - Acute Respiratory Distress Syndrome
- Interstitial lung disease
- Fibrotic lung disease
Tracheobronchial Tree
Perfusion
Hypoventilation
- Hypoventilation can also lead to decrese in arterial oxygen,
even if there’s no problem in parenchyma involved in gas
exchange. Thus hypoxygenation can lead to hypoxemia.
Airways divide dichotomously
Airway decreases in size → ↑ surface area 70m2
80-120mL blood in capillaries for gas exchange
↓Va → ↓PAO2 → ↓PaO2
3

4. Diffusion Time
Factors Affecting O2 Dissociation Curve
Carbon Dioxide Dissociation Curve
Extended Definition of Respiratory Failure
Condition Definition
Ventilatory Failure Abnormality of CO2 elimination by the
lungs
Failure of arterial Abnormality of O2 uptake by the lungs
oxygenation
Failure of O2 transport Limitation of O2 delivery to peripheral As PCO2 increases, oxygen carrying capacity diminishes. As PO2
tissues so that aerobic metabolism increases (especially in venous blood) there is decrease in CO2
cannot be maintained carrying capacity → Bohr effect
Failure of O2 uptake Inability of tissues to extract O2 from
and/or utilization blood and use it for aerobic metabolism Oxygen Consumption
O2 Consumption (VO2)
Oxygen Transport VO2 = Q x (CaO2 – CvO2) = 5 L/min x 5 mL/dL
O2 transport (or delivery) (DO2) = 250 ml/min
DO2 = Q x CaO2 = 5 L/min x 20 mL/dL x 10 CvO2 → oxygen content (venous)
= 1,000 ml/min O2 Extraction ratio
Q → cardiac output O2 ER = VO2 / DO2 = 250 mL/min / 1,000 mL/min
O2 content (CaO2) = 0.25 (25%)
CaO2 = (1.39 x Hb x %Sat) + (0.003 x PaO2) Safety mechanism at subcellular level has good application for
= 1.39 x 15 x 0.98 + 0.003 x 98 = 20 ml/dl (vol%) cardiac arrest → must be able to resuscitate within 3-5 min → still
be able to avoid brain damage/death/organ failure
Oxygenation Dissociation Curve
Clinical Manifestations of Respiratory Failure
- Apnea → respiratory failure
- Cyanosis → 5 mg of desaturated Hb already; only 20% of
patients with respiratory failure will present with cyanosis → not
a good parameter to measure
- Altered level of consciousness
- Dyspnea
- Signs of respiratory distress
- Signs/symptoms of hypoxemia
- Signs/symptoms of hypercapnea
- Signs/symptoms of underlying pathology
Manifestations of Respiratory Distress and Respiratory Failure
- Tachypnea and tachycardia
- Flaring of ala nasae
- Use of accessory muscles of respiration
- Supraclavicular fossa excavation
Note points - “Pump” handle breathing
PO2 = 40 mmHg g Saturation → 75% (PvO2 for a normal - Tracheal tug and decreased tracheal length
person at rest) - External jugular venous distension in expiration
PO2 = 60 mmHg g Saturation → 90% - Costal paradox
PO2 = 100 mmHg g Saturation → 97.5% (PaO2 for a normal - Pulsus paradoxus
person at rest and in exercise) - Abdominal paradox and asynchrony Respirator distress; but
P50 = 26 mmHg g Saturation → 50% (for normal Hb - Respiratory alternans there is impending
In sepsis, may have no hypoxemia, but hypoxia - Cyanosis apnea → ventilation
Hypoxemia → <50 mmHg - Altered level of consciousness failure in the next 15min
Respiratory failure is not synonymous with respiratory distress.
If there’s respiratory distress, investigate if there is RF
4

5. Evaluation of Hypoxemia
Signs of Respiratory Distress - Normal P(A-a)O2
- Tachypnea and tachycardia - Decreased FiO2
- Flaring of ala nasae - Hypoventilation
- Use of accessory muscles of respiration - Increased P(A-a)O2
- Intercostal muscle retraction - Ventilation-Perfusion mismatching
- Sternocleidomastoid muscle contraction - Shunt defect
- Costal paradox (Hoover’s sign) - Diffusion defect
- “Pump” handle breathing Most common cause of hypoxemia: hypoventilation, V/Q
- Supraclavicular fossae excavation mismatch & shunt
- External jugular venous distension in expiration If with hypoxemia → calculate first P(A-a)O2 gradient
- Tracheal tug and decreased tracheal length - Normal gradient → no problem in respiratory membrane &
- Abdominal paradox and asynchrony V/Q, it will still go to arterial system
- Respiratory alternans
Indices of Oxygenation
Signs and Symptoms of Hypercapnea
- Symptoms Indices Normal Values
Headache Pa O 2 80 – 100 mmHg
Mild sedation → Drowsiness → Coma Sa O 2 95 – 100 vol%
- Signs P(A-a)O2 25 – 65 mmHg
Vasodilation → redness of skin, sclera and conjunctiva PaO2/PAO2 0.75
secondary to increased cutaneous blood flow; sweating PaO2/FiO2 350 – 450
Sympathetic response → hypertension tachycardia QS/QT <5%
”Antok” PAO2 = (PB – PH2O) x FiO2 – (PaCO2/RQ)
= (760 – 47) x FiO2 – (PaCO2/RQ)
Signs and Symptoms of Hypoxia = 713 x FiO2 – (PaCO2/RQ)
- Symptoms PaO2/PAO2 = 0.15 → severe respiratory failure
Ethanol-like symptoms → confusion, loss of judgment, There are many oxygenation parameters. It is not adequate to look
paranoia, restlessness, dizziness at just PaO2. Must look at other oxygenation parameters
- Signs
Sympathetic response → tachycardia, mild hypertension, Algorithm of Hypoxemia
peripheral vasoconstriction
Non-sympathetic response → bradycardia, hypotension
”Lasing” P(A-a)O2
- Inhibitions depressed
COPD → chronic hypoxemia, irritable
Normal Increased
Diagnosis of Respiratory Failure
- Patient is in respiratory distress
- Hypoxemia (PaO2 < 60 mmHg)
- Hypercapnia (PaCO2 > 50 mmHg)
PaCO2 Challenge with
- Arterial pH shows significant acidemia (respiratory acidosis)
100% FiO2
*At least 2 of the 4 criteria should be fulfilled
Only way to diagnose RF is to do ABG. It is a laboratory
diagnosis, not a clinical diagnosis Increased Normal or Corrected Uncorrected
Decreased PaO2 PaO2
Other Diagnostic Modalities
- Laboratory
Hypo - Decreased V/Q mismatch Shunt
- CBC
ventialtion FiO2 Shunt <10% >10%
- Electrolytes
- Imaging studies Diffusion defect
- Chest x-ray
- CT scan Principles of Treatment
- Ventilation-perfusion scan - Maintain adequate oxygenation
- Support ventilation with mechanical ventilation when needed
Evaluation of Causes of Hypercapnia - Treat underlying illness or pathophysiologic derangements
- Maintain fluid and electrolyte balance
Minute Ventilation (VE) - Provide adequate nutrition
- Avoid complications
Transcribed by: Fred Monteverde
Increased VE Decreased VE
Notes from: Cecile Ong
Lecture recorded by: Lala Nieto
Increased VCO2 Increased VD & Decreased VA
Decreased VA Fred Monteverde Mae Olivarez
Emy Onishi Lala Nieto
Cecile Ong Chok Porciuncula
Airway or Lung Decreased “Pump” Mitzel Mata Section C 2009!
parenchyma ventilatory Regina Luz
disorders
disorders drive
Fever COPD, Sedation Neuromuscular
Hypermetabolism ARDS, Stroke disorder
Asthma, PE Pleural effusion
5