respiratory failure

Respiratory failureRespiratory failure

Inability to transfer oxygen and/or carbon dioxide between the atmosphere and the blood

The major function of the lung is to get oxygen into the body and carbon dioxide out.

DefinitionsDefinitions

acute respiratory failure occurs when: pulmonary system is no longer able to meet the

metabolic demands of the body

hypoxaemic respiratory failure: PaO2 50 mm Hg when breathing room air

hypercapnic respiratory failure: PaCO2 50 mm Hg.

Oxygen inOxygen in

Depends on PAO2

Diffusing capacity Perfusion Ventilation-perfusion matching

Carbon dioxide outCarbon dioxide out

Largely dependent on alveolar ventilation Anatomical deadspace constant but

physiological deadspace depends on ventilation-perfusion matching

•Respiratory rate•Tidal volume•Ventilation-perfusion matching

Respiratory FailureRespiratory Failure inadequate blood oxygenation or COinadequate blood oxygenation or CO22 removal removal

A syndrome rather than a disease

HypoxemicHypoxemic HypercapnicHypercapnic

Acute: develops in minutes to hours, pH < 7.30Chronic: develops over several days or longer

PaO2 < 55~60 mmHg or SaO2 < 90% with FiO2 >= 60%

PaCO2 > 45~50 mmHg

This two types of respiratory failure always coexist

PaO2 < 60 mmHg or PaCO2 > 50 mmHgPaO2 < 60 mmHg or PaCO2 > 50 mmHg

Transfer of oxygen of inhaled air into the blood and

of waste carbon dioxide of blood into the lungs

Ventilation

Gas Exchange

Hypoxemic respiratory failure

Hypercapnic respiratory failure

VentilationVentilation

CNSEfferents

PNS Respiratory MusclesChest Wall

Airways

Alveoli

MinuteVentilation

AlveolarVentilation

PaO2PaCO2

Chemoreceptors

CNSAfferents/Intergration

Dysfunction of any component of the ventilation system may result in ventilatory failureventilatory failure

Control of VentilationControl of Ventilation

Mechanical stimuli, Chemical stimuli, Higher CNS inputMechanical stimuli, Chemical stimuli, Higher CNS input

rhythm, rate, depth of breathingrhythm, rate, depth of breathing

Medulla

Dorsal respiratory groupVentral respiratory group

Ventral and Lateral columns of the spinal cord

Phrenic n. diaphragmIntercostal n. intercostal m.

Pneumotaxic center

Dorsolateral ponsNucleus parabrachialis medialis

Switching between the inspiratory and expiratory phase

Chemical StimuliChemical Stimuli

Peripheral chemoreceptors Carotid bodies, Aortic bodies Stimulus: PaO2, Acidemia (pH), PaCO2

Central chemoreceptors Near the ventrolateral surface of the medulla Stimulus: H+ of brain ECF (pH), PaCO2

Chemical StimuliChemical Stimuli

Hypoxia peripheral receptors Hypercapnea central receptors (80%)

For the same pH change, the ventilatory response to respiratory acidosis is greater than metabolic acidosis: CO2 (gas) readily crosses the BBB, but H+

and HCO3- (ion) cross the BBB more slowly.

Respiratory MusclesRespiratory Muscles

Inspiration: active Diaphragm:

phrenic n. (C3-5) Intercostal muscles:

T (their own level) Accessory muscles

Expiration: passive Abdominal muscles:

(active expiration) Lower T and L level

Intercostal muscles: T (their own level)

Ventilatory Demand Ventilatory Supply

Ventilatory Demand > Ventilatory Supply Ventilatory Failure

O2 demandCO2 productionDead space

Respiratory driveMotor neuron/nerve functionMuscle strengthRespiratory mechanics

Alveolar HypoventilationLow Inspired Oxygen ShuntV-Q mismatchDiffusion impairment

Hypoxemic Respiratory FailureHypoxemic Respiratory FailureResponse well to oxygen therapy

Hypoxic Respiratory FailureHypoxic Respiratory Failure

1. Low inspired oxygen High altitudes

2. Hypoventilation Conditions described in hypercapnic

respiratory failure Oxygen therapy improve hypoxemia but may

worsen the hypoventilation


3. Shunt (right-to-left shunt) Normal shunting: (2~3% of C.O.)

Some of the bronchial arterial blood Some of the coronary venous blood

Abnormal shunting: Congenital defects in the heart or vessels

ASD, VSD, Pulmonary AVM Lung atelectasis or consolidation

Pneumonia, Cardiogenic or Non-cardiogenic pulmonary edema Resistant to O2 supply when shunt fraction of CO > 30%

Hypercapnia develops when shunt fraction > 60%


4. Ventilation-Perfusion Mismatch Vascular obstruction

Pulmonary embolism Air-space consolidation

Pneumonia, Pulmonary edema


5. Diffusion Impairment Interstitial lung disease

Pulmonary fibrosis, Connective tissue disease, Interstitial pneumonia, interstitial pulmonary edema

ARDS. RDS Obstructive lung disease

Emphysema, Asthma

FIO2

Diffusion abnormality

Perfusion without

ventilation (shunting)

Hypoventilation

Normal

Ventilation without

perfusion(deadspace ventilation)

Hypercapnic Respiratory FailureHypercapnic Respiratory Failure

Increase carbon dioxide production Fever, sepsis, seizure, obesity, anxiety Increase work of breath (Asthma, COPD) high carbohydrate diet with underlying lung

disease (high RQ)

Decreased minute ventilation CNS disorders

stroke, brain tumor, spinal cord lesions, drug overdose Peripheral nerve disease

Guillain-Barre syndrome, botulism, myasthenia gravis Muscle disorders

muscular dystrophy, respiratory muscles fatigue Chest wall abnormalities

scoliosis, kyphosis, obesity Metabolic abnormalities

myxedema, hypokalemia Airway obstruction

Upper airway obstruction, Asthma, COPD



Increase dead space Airway obstruction

Upper airway obstruction Asthma, COPD Foreign body aspiration (check-valve)

ARDS, Pulmonary embolism Chest wall disorder

Brainstem

Spinal cordNerve rootAirway

Nerve

Neuromuscular junction

Respiratory muscle

Lung

Pleura

Chest wall

Sites at which disease may cause ventilatory disturbance

Respiratory Failure SymptomsRespiratory Failure Symptoms

Respiratory compensation Sympathetic stimulation Tissue hypoxia Haemoglobin desaturation

•Often nonspecific (and unrecognized)•Dyspnea•Cynosis

DyspneaDyspnea

Short of breath Abnormally uncomfortable awareness of

breathing subjectively Increased work of breath

CynosisCynosis

Cyanosis is a blue coloration of the skin and mucous membranes due to the presence of deoxygenated hemoglobin in blood vessels near the skin surface.

It occurs when the oxygen saturation of arterial blood falls below 85-90% (>5 g/dl deoxyhemoglobin).

AsthmaAsthma

Definition Chronic inflammatory disorder

of bronchi characterized by episodic, reversible bronchospasm resulting from an exaggerated bronchoconstrictor response to various stimuli

AsthmaAsthma

EtiologyEtiology

Allergens Occupational

chemical Viruses Genetic factors Prematurity Lack breast feeding Smoking

Fumes, smoke, sprays

Diurnal variation Exercise, cold air Fog Emotion Allergens,

anaphylaxis Viruses Drugs - NSAID, Beta

Types of asthmaTypes of asthma

Extrinsic (Allergic/Immune) Atopic - IgE Occupational – IgG

Intrinsic (Non immune) Aspirin induced Infections induced

Mechanisms of asthmaMechanisms of asthma

Risk Factors(for development of asthma)

AirwayHyperresponsiveness Airflow Limitation

SymptomsRisk Factors

(for exacerbation)

Mechanisms of asthmaMechanisms of asthma

Edema Excesive mucus Bronchospasm Obstructed

bronchiole

Factors in inflammatory Factors in inflammatory processprocess

MEDIATORS HISTAMINE LEUCOCYTE C F PROSTAGLANDINS LEUKOTRIENES PAF KININS

CELL TYPES MAST CELLS MACROPHAGES EOSINOPHILS T LYMPHOCYTES

Mast cell in asthmaMast cell in asthma

Eosinophils in asthmaEosinophils in asthma

AIRWAY HYPERRESPONSIVENESS

ChemotaxisEotaxin,

RANTES, MCP-4

CCR3

SurvivalIL-3, IL-5, GM-CSF

VCAM-1VLA4

Adhesion

Bonemarrow

IL-4

IL-5

Airwayvessel

Activation

Th2 cell

BasicproteinsMediators

EOSINOPHIL RECRUITMENT IN ASTHMA

T cell in asthmaT cell in asthma

Neural mechanismsNeural mechanisms

PARASYMPATHETIC

AFFERENT SENSORY

HISTAMINE

KININS

EFFERENT

BRONCHOCONSTRICTOR

MUCUS SECRETION

Eosinophil

Mast cell

Allergen

Th2 cell

PATHOPHYSIOLOGY OF ASTHMAPATHOPHYSIOLOGY OF ASTHMA

VasodilatationNew vessels

Plasma leak Oedema

Neutrophil

Mucushypersecretionhyperplasia

Mucus plug

Macrophage

BronchoconstrictionHypertrophy/hyperplasia

Cholinergic reflex

Epithelial shedding

Subepithelialfibrosis

Sensory nerve activation

Nerve activation

COPDCOPD

Definition COPD is a disease state characterised by

airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

Includes Emphysema Chronic bronchitis

Risk factors for COPDRisk factors for COPD

Endogenous factors Genes (e.g. alpha1-antitrypsin deficiency)

Hyperresponsiveness

Lung growth

Exogenous factors Tobacco smoke

Occupational dusts and chemicals

Infections

Socioeconomic status

Endogenous factors Genes (e.g. alpha1-antitrypsin deficiency)

Hyperresponsiveness

Lung growth

Exogenous factors Tobacco smoke

Occupational dusts and chemicals

Infections

Socioeconomic status

Chronic bronchitisChronic bronchitis

Persistent cough with sputum production for at least 3 months in ≥ consecutive years


Mucosa of the lower respiratory passages becomes severely inflamed

Mucus production increases

Pooled mucus impairs ventilation and gas exchange

Risk of lung infection increases

Pneumonia is common

Hypoxia and cyanosis occur early


Hypersecretion of mucus in large airways Submucosal gland hypertrophy Increase in goblet cells in small airways Excessive mucus → airway obstruction Cigarette smoke predisposes to infection

EmphysemaEmphysema

Emphysema is defined by destruction of airways distal to the terminal bronchiole.

EmphysemaEmphysema

Alveoli enlarge as adjacent chambers break through

Chronic inflammation promotes lung fibrosis

Airways collapse during expiration

Patients use a large amount of energy to exhale

Overinflation of the lungs leads to a permanently expanded barrel chest

Cyanosis appears late in the disease

Cigarette smoke

Alveolar macrophage

Neutrophil

PROTEASES

Alveolar wall destruction(Emphysema)

Mucus hypersecretion(Chronic bronchitis)

PROTEASEINHIBITORS

Neutrophil chemotactic factors

CELLULAR MECHANISMS OF COPDCELLULAR MECHANISMS OF COPD

Neutrophil elastaseCathepsins

Matrix metalloproteinases

Cytokines (IL-8)Mediators (LTB4)4 ))

?CD8+

lymphocyte

-

MCP-1

Neutrophil elastase Cathepsins MMP-1 Granzymes Perforins

PROTEASE-ANTIPROTEASE IMBALANCE IN COPDPROTEASE-ANTIPROTEASE IMBALANCE IN COPD

1-Antitrypsin SLPI

Alpha1-Antitrypsin Alpha1-Antitrypsin DeficiencyDeficiency

Enzyme prevents loss of lungs’ elastic fibers

Deficiency – Pan-lobular emphysema

Homozygous – PiZZ – 15-30% of normal AAT levels (PiMM) Earlier development of COPD Airflow obstruction in early 40s Accelerated by 10 to 15 years occurs in 1:5000

Heterozygous – PiMZ – 50-80% - smokers

Z allele – 3-5% population

SP

Mucus gland hyperplasia

Goblet cellhyperplasia

Mucus

Sensory nerveCholinergicnerve ACh

NE

Neutrophils

Epithelium

INFLAMMATION

CytokinesROS

• Acetylcholine• Tachykinins• Proteinases neutrophil elastase

• Cytokines (TNF-)

• Oxidants• Growth factors

• MUC genes MUC5a, MUC8

MUCUS HYPERSECRETION IN COPDMUCUS HYPERSECRETION IN COPD

COPD ASTHMA

Neutrophils

No AHR

No steroid response

Eosinophils

AHR

Steroid response

~10%

“Wheezy bronchitis”

OVERLAP BETWEEN COPD AND ASTHMAOVERLAP BETWEEN COPD AND ASTHMA

Asthma and COPDAsthma and COPD

Inflammation ASTHMA COPD

CELLS Mast cellsEosinophilsCD4 T cellsmacrophages

NeutrophilsCD8 T cellsMacrophages++

MEDIATORS LTD4,histamineIL-4,IL-5, ROS +

LTB4’IL-8, TNFa,ROS+++

EFFECTS All airwaysLittle fibrosisEp shedding

Periph airwaysLung destructionFibrosis +Sq metaplasia

Response steroids +++ ±

respiratory failure

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