Mechanisms of Hypoxia and

Types of Respiratory Failure

By Amanuel

Moderator: Dr Selam (MD, Consultant Internist)

October 2021
Outline
 Introduction

 Measurements of oxygenation

 Causes of hypoxia

 Stages of hypoxia

 Mechanisms of hypoxia

 Types of respiratory failure

Introduction

 Major purpose of the cardiorespiratory system

 To deliver O2 and nutrients to cells

 To remove CO2 and other metabolic products

 Proper maintenance of this function depends on

 Intact cardiovascular and respiratory systems

 Adequate number of RBCs and hemoglobin

 Adequate O2 supply from the inspired gas

Introduction: Terms

 Anoxia: Absence of oxygen supply. No oxygen.

 Asphyxia: Absence of O2 and accumulation of CO2

 Hypoxia: Low oxygen in the body (general hypoxia)

or specific: tissue hypoxia, alveolar hypoxia

 Hypoxemia: Low oxygen in the blood ► Insufficient

oxygenation

 Hypoxemia is determined by measuring the

partial pressure of oxygen in the arterial blood
[PaO2] on ABG analysis.
Introduction: Hypoxemia

 Hypoxemia is an important and potentially

avoidable cause of morbidity and mortality

 Rapid & accurate detection of hypoxemia is

critical to prevent serious complications

 Physically, it can be detected by cyanosis

Frank cyanosis does not develop until the level
of deoxyhemoglobin reaches 5 g/dl
Early and late signs of hypoxemia

 The threshold is affected by peripheral perfusion,

skin pigmentation and hemoglobin concentration
 Steps of oxygen utilization
 Three steps in O2 utilization to maintain aerobic
cellular metabolism throughout the body

 Oxygenation: the process of oxygen diffusing

passively from the alveolus to pulmonary capillary
Where it binds to the hemoglobin in RBCs or
dissolves into the plasma

 Oxygen delivery: the rate of 02 transport from the

blood to the peripheral tissues

 Oxygen consumption: the rate of oxygen

utilization by the tissues
Measurements of oxygenation

 There are numerous ways to measure oxygenation

 Arterial oxygen saturation (SaO2)

 Arterial oxygen tension (PaO2)

 A-a oxygen gradient (AaG)

 PaO2/FiO2 ratio

 a-A oxygen ratio

 Oxygen index (OI)

 Arterial oxygen saturation (SaO2)

 Proportion of red blood cells whose hemoglobin is

bound to oxygen (O2 saturated hemoglobin)

 ABG analysis (SaO2)

 Pulse oximetry (SpO2)

 Normal: 95-98% at rest, 88-92% in COPD, asthma

 Abnormal:
 A resting SaO2 ≤95 percent or exercise desaturation
by ≥5 percent
 A drop from baseline is abnormal (e.g. 99% to 95%)
Pulse oximetry
 Non-invasive technique of assessing arterial O2 level
 Called the "fifth vital sign“
 Consists of a photodetector & two light-emitting diodes
 One emitting at 660 nm & the other at 940 nm
 Oxyhemoglobin absorbs light maximally in the red band
of the spectrum (600 to 750 nm)
 While deoxyhemoglobin absorbs maximally in the
infrared band (850 to 1000 nm)

 80% SaO2 usually reflects a PaO2 of approximately 50

mmHg at a pH of 7.4

 However, changes in pH, temperature and the

concentration of 2,3-diphosphoglycerate
 Alter the PaO2-SaO2 relationship
Limitations of pulse oximetry
 Digital injury when continuously used

 Inability to measure ventilation (PCO2)

 Delay in detection of acute hypoxemia

Factors affecting pulse oximetry

 Improper probe placement, anemia, abnormal
hemoglobin, carboxyhemoglobin, methemoglobin,
sulfhemoglobin, poor peripheral perfusion

 Hypothermia, venous congestion, skin pigmentation,

nail polish, excessive motion etc. affect pulse oximetry
Arterial oxygen tension (PaO2)

 The amount of oxygen dissolved in the plasma

 Measured by ABG analysis

 PaO2 <80 mmHg is abnormal

 A normal PaO2 ranges 80-100 mmHg

 Varies with age and altitude

 Rule of thumb: PaO2 = 105-half of age

 Doesn’t include patients with chronic lung disease

 A low PaO2 and no symptoms of hypoxia may
indicate a chronic lung condition as in COPD
 A-a oxygen gradient = PAO2 - PaO2
 PaO2 is directly measured from ABG analysis

 PAO2 is the alveolar oxygen tension calculated as:

 PAO2= (FiO2  x  [Patm - PH2O]) - (PaCO2 ÷ R)

 FiO2 is the fraction of inspired oxygen (0.21 at room air)

 Patm is the atmospheric pressure (760 mmHg at sea
level)
 PH2O is the partial pressure of water (47 mmHg at 37ºC)
 PaCO2 is the arterial carbon dioxide tension
 R is the respiratory quotient which is approximately 0.8

 The normal A-a gradient varies with age and

calculated as = 2.5 + (0.21 x age in years) or
 PaO2/FiO2 ratio
 Most often employed in intubated patients
 A normal PaO2 /FiO2 ratio is 300 to 500 mmHg
 <300 indicates abnormal gas exchange
 <200 shows severe hypoxemia as in ARDS

 a-A oxygen ratio = PaO2 ÷ PAO2

 Used to predict the change in PaO2 that will result
when the FiO2 is changed. Normal: 0.77-0.82

 Oxygenation index (OI)

 Most commonly used in neonates with PPHN
 OI= (Mean airway pressure x FiO2/PaO2) x 100
 A high OI (e.g. >25) indicates severe hypoxemia
Causes of hypoxia

 Four main categories:

(1) Hypoxic (anoxic) E.g. High altitude

(2) Stagnant (ischemia) E.g. Shock

(3) Anemic (actual or relative anemia)

 E.g. Heavy smokers, carboxyhemoglobin,
methemoglobin & sulfhemoglobin

(4) Histotoxic (hypoxia without hypoxemia)

 E.g. Cyanide toxicity, narcotics, alcohol
Stages of hypoxia
1. Asymptomatic or Indifferent (SaO2: 90-95%)
 Loss of night vision and a loss of color vision
2. Compensatory (SaO2: 80-90%)
 Increasing the rate and depth of breathing & ↑CO

3. Deterioration or Disturbance (SaO2: 70-80%)

 Shortness of breath/air hunger, incoordination,
cyanosis, difficulty with simple tasks, drowsiness,
diminished vision, headache, tingling & numbness

4. Critical stage (SaO2<70%)

 Completely incapacitated both physically and mentally
 Lose consciousness, convulsions, may stop breathing
and finally die
Effects of hypoxia
 Hypoxia can adversely affect every tissue in the body

 Cellular mechanisms that contribute to hypoxic cell injury

 Depletion of ATP, development of intracellular acidosis
 Increased level of metabolic byproducts (e.g. lactate)
 Generation of oxygen free radicals
 Destruction of membrane phospholipids

 Dramatic increased in intracellular calcium level

Direct damage to the cytoskeleton
Induction of genes that contribute to apoptosis

 Induces an inflammatory reaction (neutrophilic

infiltration) via cytokines and oxygen free radicals
 Mechanisms of hypoxia
 Decrease in the partial pressure of oxygen in the blood
 Caused by;
 Hypoventilation

 V/Q mismatch

 Shunt defect

 Diffusion defect

 Reduced inspired oxygen tension

 Hemoglobin defect that affects Hgb-O2 affinity

Mechanisms of hypoxia
 Hypoventilation
 PaCO2 & PACO2↑ ► PAO2 ↓ ►hypoxemia & hypercapnia

 Pure hypoventilation is characterized by;

 Corrected with a small increase in FiO 2
 A-a oxygen gradient is usually normal
 Causes
 CNS depression such as drug overdose e.g. opioids
 CNS structural or ischemic lesions►Respiratory center
 Obesity hypoventilation (Pickwickian) syndrome
 Impaired neural conduction (ALS, GBS, high cervical
injury, phrenic nerve paralysis etc.)
 Muscular weakness (MG, polymyositis, severe
hypothyroidism, diaphragmatic paralysis etc.)
 Poor chest wall elasticity (flail chest, kyphoscoliosis)
Hypoventilation
Possible sites of hypoventilation
 V/Q mismatch
 In normal lung, there is V/Q mismatch because ventilation and
perfusion are heterogeneous.

 V/Q mismatch is helpful for the normal physiologic

occurring A-a gradient under normal conditions.

 In upright position, both ventilation & perfusion are greater in

the bases than in the apices.

 The difference in ventilation at apex & base is smaller unlike the

huge difference in perfusion at apex and base of the lungs.

 Thus, the V/Q ratio is higher in the apices than the bases

 Causes: Obstructive lung diseases, pulmonary vascular

diseases, ILDs worsen V/Q mismatch ► hypoxemia
Right-to-left shunt
 Shunting: blood passes from the right to the left side
of the heart without being oxygenated.
 There are two types right to left shunts.

 Anatomic shunts exist when the ventilated

alveoli are bypassed e.g. Intracardiac shunts,
AVMs & hepatopulmonary syndrome etc.

 Physiologic shunts exist when non-ventilated

alveoli are perfused e.g. Atelectasis, pneumonia,
ARDS etc.

 When 100% O2 is inspired, the PaO2 does not rise to the

expected level ► a useful diagnostic test
 Diffusion limitation
 Occurs when movement of O2 from the alveolus to the
pulmonary capillary is impaired

 A consequence of alveolar and/or interstitial inflammation and

fibrosis as in ILD

 Characterized by exercise-induced hypoxemia

 During rest, blood traverses the lung slowly ► There is
sufficient time for oxygenation
 During exercise, cardiac output increases and blood
traverses the lung quickly ► Less time for oxygenation

 In the healthy individuals, several compensatory

mechanisms occur like capillary dilatation

 If parenchyma destructed, it renders compensation

Diffusion limitation
 Fick's law of diffusion

 Rate of diffusion of a gas through a tissue slice is

proportional to the surface area but inversely
proportional to the thickness

 Diffusion rate is proportional to the partial pressure

difference

 Diffusion rate is proportional to the solubility of the

gas in the tissue

 But inversely proportional to the square root of the

molecular weight (CO2, 20x > O2)
 Reduced inspired oxygen tension (↓PiO2)

 PiO2 =FiO2 x (Patm-PH2O)=0.21 (760-47) = 150 mmHg

 Reduction of the PiO2 will decrease the PAO2

 PAO2= (FiO2  x  [Patm - PH2O]) - (PaCO2 ÷ R)

↓PAO2 ► impairs oxygen diffusion by decreasing the

oxygen gradient from the alveolus to the artery

 The net effect is hypoxemia

 A reduced PiO2 is most commonly associated with

high altitude
Respiratory Failure
 Introduction: Respiratory failure
 A syndrome in which the respiratory system fails in
one or both of its gas exchange functions.
 Oxygenation and CO2 elimination
 Hypoxemic(Pao2<60 mmHg)
 Hypercapnic (Paco2> 50 mmHg)

 Respiratory failure is one of the most common

reasons for ICU admissions.

 In some settings, up to 75% of patients require

mechanical ventilation.

 Four types of respiratory failure can be described.

Respiratory failure: Pathophysiology
Type-I: Hypoxemic respiratory failure

 Occurs when alveolar flooding and subsequent

intrapulmonary shunt physiology occur.

 Alveolar flooding may be because of pulmonary

edema, pneumonia or alveolar hemorrhage.

 Pulmonary edema can be categorized as

 Elevated pulmonary microvascular pressures as
seen in heart failure and intravascular volume
overload or

 ARDS ("low-pressure pulmonary edema") and

represents an extreme degree of lung injury
 Acute respiratory distress syndrome (ARDS)


Defined by diffuse bilateral airspace edema seen on chest
radiography in the absence of left atrial hypertension and
profound shunt physiology


In a clinical setting in which this syndrome is known to occur due to
the following reasons.


Sepsis, gastric aspiration, pneumonia, near-drowning, multiple blood
transfusions and acute pancreatitis


MR from ARDS was traditionally very high (50–70%)


Although recent changes in ventilator management strategy have led
to reports of MR closer to 30%
Type-II: Hypercapnic respiratory failure

 Occurs as a result of alveolar hypoventilation and

results in the inability to eliminate carbon dioxide
effectively.

 Mechanisms by which this occurs are categorized by:

 Impaired CNS (respiratory center) drive to breathe

 Failure of neuromuscular function in the

respiratory system

 Increased load(s) on the respiratory system

Type-II: Hypercapnic respiratory failure

 Reasons for diminished CNS drive to breathe

include:
 Drug overdose, brainstem injury, sleep-disordered
breathing and severe hypothyroidism

 Impaired neuromuscular transmission

 Myasthenia gravis, Guillain-Barré syndrome,
amyotrophic lateral sclerosis, phrenic nerve injury

 Respiratory muscle weakness

 Myopathy, electrolyte derangements (hypokalemic
paralysis)
Type-III: Perioperative respiratory failure

 Occurs as a result of lung atelectasis

 After general anesthesia, decreases in functional
residual capacity lead to collapse of dependent
lung units.

 Such atelectasis can be treated by

-Frequent changes in position
-Chest physiotherapy
-Upright positioning
-Aggressive control of incisional pain

 Noninvasive positive-pressure ventilation may

also be used to reverse regional atelectasis.
 Type-IV respiratory failure

Results from hypo-perfusion of respiratory muscles in patients

with shock.

Normally, respiratory muscles consume <5% of the total cardiac

output and O2 delivery.

Up to 40% of the cardiac output may be distributed to the

respiratory muscles in these conditions.

Causes: Cardiogenic shock, lactic acidosis and anemia will

increase the work of breathing

Intubation (MV) can allow redistribution of the cardiac output

away from the respiratory muscles and back to vital organs
while the shock is treated.
Diagnosis: Respiratory failure

 Only way to diagnose RF is to do ABG analysis

 It is a laboratory diagnosis, not a clinical diagnosis

 At least 2 of the 4 criteria should be fulfilled

1. Patient is in respiratory distress

2. Hypoxemia (PaO2 < 60 mmHg)

3. Hypercapnia (PaCO2 > 50 mmHg)

4. Arterial pH shows significant acidemia

RF: Principles of treatment

 Maintain adequate oxygenation

 Support ventilation with machine

 Treat underlying illness

 Maintain fluid and electrolyte balance

 Provide adequate nutrition

 Routine nursing care

 Avoid complications
Respiratory failure: Management
Care of the mechanically ventilated patient
 Pain control: opiates are the main stay of therapy

 Sedation & neuromuscular blockers if the patient

has profound dysynchrony with the ventilator

 Elevation of the head to >30 degree

 Use ulcer and DVT prophylaxes

 Nursing care and pulmonary rehabilitation

 Lung protective ventilation strategy and ECMO

Respiratory failure: Treatment
References