Pathophysiology of hypercapnic and hypoxic respiratory failure and V/Q relationships
[Link] Nath Department of Pulmonary Medicine PGIMER Chandigarh
Jan 2006
Respiratory Failure
A syndrome rather than a disease
inadequate blood oxygenation or CO2 removal
Hypoxemic
PaO2 < 60 mmHg
Hypercapnic
PaCO2 > 45 mmHg
These two types of respiratory failure always coexist
Acute
Chronic
Respiratory function
Two main categories
Ventilation
Removal of waste CO2
Oxygenation
Transfer of O2 from air in blood
Ventilation
CNS Efferents PNS Respiratory Muscles Chest Wall Airways
CNS Afferents/ Integration
Alveoli
Chemoreceptors
PaO2 PaCO2
Alveolar Ventilation
Minute Ventilation
Dysfunction of any of the component leads to ventilatory failure
Chemical 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 Stimuli
Hypoxia peripheral receptors Hypercapnia central receptors
Response to respiratory acidosis is always greater than metabolic acidosis
Hypercapnic Respiratory Failure
Partial pressures of CO2 in blood depends on: Co2 production Dead space Minute ventilation
VA = VCO2 / PACO2 x K
CO2 Production Dead Space Ratio Minute Ventilation
Hypercapnic Respiratory Failure
Hypercapnic respiratory failure
Decreased minute ventilation
VT= VD + VA (multiplying by respiratory frequency) VE = VD + VA OR VA = VE VD Acc. To alveolar ventilation equation: VA x FaCO2= VA So VCO2 = VA x PACO2 x K Now, VA = VCO2 / PACO2 x K Paco2 is inversely proportional to minute ventilation
Hypercapnic respiratory failure
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
Hypercapnic respiratory failure
Chest wall abnormalities Scoliosis, kyphosis, obesity Metabolic abnormalities Myxedema, hypokalemia Airway obstruction Upper airway obstruction, Asthma, COPD
Pathophsiology in Asthma and COPD more complex
Hypercapnic respiratory failure
Increase dead space
Airway obstruction Upper airway obstruction Asthma, COPD Foreign body aspiration (check-valve) Chest wall disorder Kyphoscliosis, thoracoplasty etc
Hypercapnic respiratory failure
Increase CO2 production
Fever, sepsis, seizure, obesity, anxiety Increase work of breathing (asthma, COPD) High carbohydrate diet with underlying lung disease (high RQ)
Ventilatory Demand
Ventilatory Supply
Ventilatory Demand > Ventilatory Supply Ventilatory Failure Ventilatory demand depends on O2 demand CO2 production dead space and minute ventilation Ventilatory supply depends on Respiratory drive Muscle /neuron function Respiratory mechanics
This is responsible for MSV
CAUSES OF VENTILATORY FAILURE
[Link] centre [Link] [Link] cell [Link] [Link] [Link] muscles [Link] elasticity [Link] of structural integrity [Link] airway resistance
Respiratory Failure in a patient with Asthma
Airway obstruction Decreased FEV1 Work of breathing Increased dead space Hyperventilation Altered pulmonary mechanics
Ventilatory Supply
Ventilatory Demand
Ventilatory Demand > Ventilatory Supply Ventilatory Failure
Respiratory failure in COPD
Decreased FEV1
Relationship is curvilinear; CO2 retention does not occur unless FEV1 < 20 30 % of normal
Altered lung mechanics Increased dead space ventilation Expiratory air trapping due to obstructive physiology Respiratory muscle fatigue Decreased muscle blood flow Increased CO2 production
Hypoxic Respiratory Failure
PaO2 = [ FiO2 (PATM-PH2O) PaCO2/R ] [ A-a gradient]
Low Inspired Oxygen
Shunt V-Q mismatch Diffusion impairment
Hypoxemic Respiratory Failure
Hypoxic Respiratory Failure
Shunt:
Blood pathway which does not allow contact between alveolar gas and red cells PHYSIOLOGICAL PATHOLOGICAL Pulmonary Non-pulmonary
Hypoxic Respiratory Failure
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(with reversal), Pulmonary AVM
Lung atelectasis or consolidation
Pneumonia, Cardiogenic or Non-cardiogenic pulmonary edema
Hypoxic Respiratory Failure
Shunt (right-to-left shunt)
Resistant to O2 supplementation when shunt fraction of CO > 30%
Hypoxic Respiratory Failure
Etiologies of Shunt physiology
Diffuse alveolar filling Collapse / Consolidation Abnormal arteriovenous channels Intracardiac shunts
Hallmark of shunt is poor or no response to O2 therapy Usually causes hypoxemic respiratory failure
Hypoxic Respiratory Failure
Shunt can lead to hypercapnia when more than 60% of the cardiac output
Ventilatory compensation fails RR Increased dead space total alveolar ventilation Respiratory muscle fatigue
Hypoxic Respiratory Failure
Ventilation-Perfusion mismatch
Gas exchange depends on
V/Q ratio Composition of inspired gas Slopes and position of relevant blood gas dissociation curves
Hypoxic Respiratory Failure
CO2 lost in alveolar gas from capillary: VCO2 = Q(Cvco2-Ccco2) CO2 lost from exhaled gas into air VCO2 = VA x PACO2 xK In steady state CO2 lost from capillary and alveoli is same So Vax Paco2 xK = Q(Cvco2-Ccco2) i.e. VA/Q= (Cvco2-ccco2/ PAco2)x K.(1)
Hypoxic Respiratory Failure
Similarly for O2: VO2= VI x Fio2 Va x FAO2 And.. Now,as So, VO2= Q( Cco2 CvO2) Inspired VA = Expired VA
VA/Q = CcO2 - CvO2 / FIO2- FAO2.....(2)
Hypoxic Respiratory Failure
In normal lungs 5-10 mm difference in alveolar and arterial blood is due to physiological inequality
Gravitationally based inequality Fractally based inequality Longitudinally based inequality Collateral ventilation Reactive vaso- and broncho-constriction
Hypoxic Respiratory Failure
Ventilation-Perfusion Mismatch
Vascular obstruction
Pulmonary embolism
Air-space consolidation
Pneumonia, Pulmonary edema
Airway obstruction
Asthma, COPD etc.
Diffuse parenchymal lung diseases
ILDs, DAD etc
Models for V/Q relationship
Both the obstructive models result in hypoxemia and hypercapnia But the effects on O2 and alveolar arterial gradient exceed greatly those for CO2 Airway obstruction cause more hypoxemia and less hypercapnia than identical degrees of vascular obstruction
Hypoxic Respiratory Failure
Principal effects of V/Q inequality on O2 and CO2 exchange are:
Affects both gases no matter what the pathological basis of inequality Causes hypoxia and hypercapnia Causes more severe hypoxia than hypercapnia Impairs total O2 and CO2 exchange by lungs
Hypoxic Respiratory Failure
Affects O2 more than CO2 in very low V/Q areas Affects CO2 more than O2 in very high V/Q areas Creates alveolar arterial difference for both the gases
Response to V/Q mismatch
Physiologically the response to V/Q mismatch is primarily by:
Changes in mixed venous saturation Increase in ventilation Changes in cardiac output
In low V/Q areas
in ventilation leads to significant drop in CO2 But O2 is barely affected if at all
Response to V/Q mismatch
In high V/Q areas:
Both O2 and CO2 usually come to nearly normal levels
Changes in cardiac output have starkly contrast effects
In low V/Q areas O2 improves to some extent but, In high V/Q areas there is no significant effect
Hypoxic Respiratory Failure
Diffusion Impairment
Interstitial lung disease Pulmonary fibrosis, Connective tissue disease, Interstitial pneumonia, interstitial pulmonary edema ARDS Obstructive lung disease
Emphysema, Asthma
Hypoxic Respiratory Failure
Diffusion capacity of a gas depends on:
Thickness of the alveolar basement membrane. Avidity of the gas to bind to hemoglobin Hemoglobin concentration Alveolar partial pressures of O2 Capillary transit time Lung volumes
The capillary transit time of RBC is 0.75 seconds. With normal DL, it takes < 0.25 seconds to equilibration. Only when the DL is severely limited (<0.25 normal) or the transit time is markedly shorten (<0.25 seconds) is it possible to have a PaO2 less than PAO2.
Hypoxic respiratory failure
Acute lung injury:
Maldistribution of ventilation Shunt physiology Alveolar hypoventilation Diffusion limitation
Predominantly hypoxic respiratory failure Hypercapnia may appear in late phases
Mechanisms of hypercapnia in acute lung injury
Increased O2 consumption by lungs
Increased dead space Decreased total alveolar ventilation
Increasd lung compliance
Decreased FRC
Increased air flow resistance Respiratory muscle fatigue
Ventilatory Supply Ventilatory Demand
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