The Pathophysiology of Respiratory Failure 万用卡 The Pathophysiology of Respiratory Failure Jianzhong Sheng MD PhD Department of pathophysiology

O2 CO2 O2 CO2 External respiration circulation Internal respiration

What is respiratory failure Respiratory failure is a pathological process in which the external respiratory dysfunction leads to an abnormal decrease of arterial partial pressure of oxygen with or without carbon dioxide retention.

How to judge respiratory failure （1）PaO2< 8kpa（60mmHg） （2）PaCO2> 6.6 kpa（50mmHg） Classification of RF： Hypoxemic (Group I, Type 1) RF—(1) Hypercapnic (Group I, Type 2) RF—(1)＋(2)

Etiology and pathogenesis of RF Ventilatory disorders Diffusion disorders Ventilation-perfusion imbalance Anatomic shunt

Etiology and Pathogenesis of RF (1) Ventilatory disorder 1. Restrictive ventilatory disorders 2. Obstructive ventilatory disorders

Etiology and pathogenesis of RF (1) Restrictive ventilatory disorders Paralysis of the respiratory muscles Decreased compliance of chest wall Decreased compliance of lungs Hydrothorax or pneumothorax

Etiology and pathogenesis of RF (1) Obstructive Ventilatory disorders 1. Central airway obstruction 2. Peripheral airway obstruction

Central airway obstruction Trachea Central airway obstruction Iso-pressure Bronchia Peripheral airway obstruction

Extrathoracic variable obstruction Iso-pressure expiration inspiration

Intrathoracic variable obstruction expiration inspiration

Chronic bronchitis emphysema Peripheral airway obstruction ＋10 ＋20 ＋10 ＋20 ＋30 ＋20 ＋20 ＋20 ＋20 ＋25 ＋35 ＋20 ＋20 ＋20 ＋20 Normal Chronic bronchitis emphysema

Ventilatory disorders Blood gas Low PaO2 and High PaCO2

Etiology and pathogenesis of RF (2) Area of alveolar-capillary membrane↓ Thickness of alveolar-capillary membrane ↑ Diffusion disorders Exchenge time ↓

Alveolar-capillary membrane Surfactant O2 CO2 Alveolar epithelium Capillary endothelial cells

Diffusion disorders Blood gas Low PaO2 and Normal PaCO2

Etiology and Pathogenesis of RF (3) Local hypoventilation VA/Q ↓(Ventilation/perfusion) Functional shunt Ventilation- perfusion imbalance Local hypoperfusion VA/Q ↑ Dead space-like ventilation

Ventilation-perfusion imbalance Nomal or low or high PaCO2 Blood gas Low PaO2 and Nomal or low or high PaCO2

Ventilation-perfusion imbalance Functional shunt Blood gas Damaged lung Normal Whole lung V/Q <0.8 >0.8 =0.8 PaO2 ↓ ↓ ↑ ↑ ↓ CaO2 ↑ PaCO2 N CaCO2

Ventilation-perfusion imbalance Dead space-like ventilation Blood gas Damaged lung Normal Whole lung V/Q >0.8 <0.8 =0.8 PaO2 ↑ ↑ ↓ ↓ ↓ CaO2 ↑ PaCO2 N CaCO2

Etiology and pathogenesis of RF (4) Anatomic shunt Abnormal anatomic shunt Be not ventilated at all Pulmonary arterio-venous fistulas Pulmonary edema Atelectasis

Functional shunt and Anatomic shunt No blood –gas exchange Applying O2 can’t increase PaO2 Functional shunt Blood –gas exchange decrease Applying O2 can increase PaO2

Anatomic shunt Blood gas Low PaO2

Adult/acute respiratory distress syndrome ARDS Adult/acute respiratory distress syndrome

What is ARDS? ARDS is a common form of acute respiratory failure in adult that is characterized by dyspnea, hypoxia.

Recognition of ARDS History: Systemic or pulmonary insult Chest radiograph: Diffuse pulmonary infiltrates Respiratory distress: Labored breathing, tachypnea Severe hypoxemia: Refractory to treatment with supplement of oxygen

Sequential development of ARDS

Pulmonary hypoperfusion Trauma, shock, infection and other causative factors Pulmonary hypoperfusion and hypoxemia Platelet aggregation Damage to epithelium Mechanical obstruction Increased vascular permeability Release of vasoactive substances Leakage of fluid and plasma into lungs Stagnation of blood Noncardiogenic pulmonary edema or hemorrhage Decreased surfactant Alveolar filling Atelectasis Hypoxemia

Pathogenesis of ARDS

Complement activation Stimulus Complement activation C5a Sequestration of neutrophils in lungs Arachidonic acid metabolites Lysosomal proteinase Active oxygen Epithelial and endothelial Cell damage Pulmonary vasoconstriction Increased pulmonary permeability Pulmonary hypertension Pulmonary edema

Pathophysiology of ARDS

alveolar-capillary membrane damage Causative factors alveolar-capillary membrane damage inflammation Pulmonary edema Bronchia constriction Atelectasis Pulmonary vasoconstriction Microvascular thrombus Diffusion disorders Dead space ventilation Pulmonary shunt Hypoxemia

Chronic obstructive pulmonary disease COPD Chronic obstructive pulmonary disease

What is COPD? COPD is a kind of chronic obstructive ventilatory disorders caused by chronic bronchitis and emphysema

Pathophysiology of RF in COPD

COPD Respiratory Failure surfactant ↓ diffusion membrane↓ respiratory muscles failure Peripheral airway obstructed and convulsion diffusion membrane↓ underventilated or poor perfusion Obstructive ventilatory disorders Ventilation-Perfusion mismatching Restrictive ventilatory disorders Diffusion disorders Respiratory Failure

Functional and Metabolic Alterations in Respiratory Failure (1) 1. Metabolic acidosis K＋↑ 、Cl－ ↑ 2. Respiratory acidosis K＋↑ 、Cl－↓or normal 3. Respiratory alkalosis K＋ ↓ 、Cl－ ↑ Acid-base disturbance

Functional and Metabolic Alterations in Respiratory Failure (2) Ventilation increase 60mmHg 50mmHg carotid medulla PaCO2 80mmHg PaO2 30mmHg medulla medulla 90mmHg Ventilation depression 20mmHg Respiratory system 1

Functional and Metabolic Alterations in Respiratory Failure (2) Cheyne-stokes respiration PaCO2↑ Central depression Central excitement PaCO2↓ Respiratory system 2

Functional and Metabolic Alterations in Respiratory Failure (3) Hypoxia、Hypercapnia ↓ 【H＋】↑ Pulmonary embolism、Pulmonary arteriolitis Pulmonary arteriolosclerosis Pulmonary hypertension chronic polycythemia Blood viscidity↑ right ventricle Afterload ↑ Dyspnea R Hypoxia acidosis Heart failure Heart extrusion Cardiovascular system

Functional and Metabolic Alterations in Respiratory Failure (4) Neurons Cerebral vessels Activity of Glutamate decarboxylase↑ Activity of phospholipase↑ Acidosis Cerebrovascular Vasodilation Damage endothelium Membrane potential↓ neurotransmitters↓ ATP ↓ Intracellular Ca2＋ ↑ Hypoxia ATP ↓ ↓ Na＋－K＋bump Nervous system

Principles of treatment of respiratory failure Correcting the causes Relieving the hypoxemia and hypercapnia

Quiz What is respiratory failure? What is ARDS? What is V/Q?

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