Disturbances of the Ventilation to Perfusion Ratio

Respiratory failure represents the inability of the respiratory system to maintain adequate oxygenation (hypoxemia) and/or carbon dioxide elimination (hypercapnia). From a pathophysiological perspective, this failure results from disturbances in ventilation, distribution of inspired gas, diffusion across the alveolar–capillary membrane, or pulmonary perfusion, leading to:

• V/Q mismatch (ventilation–perfusion ratio);
• intrapulmonary right-to-left shunts (intrapulmonary shunt);
• hypoventilation;
• abnormal gas exchange across the alveolar–capillary membrane;
• reduced concentration of inspired oxygen;
• increased desaturation of venous blood due to cardiac dysfunction, in combination with one or more of the five factors listed above.

Ventilation

Adequate alveolar ventilation ensures physiological normocapnia (PaCO₂ 4.5–6 kPa). Hypoventilation leads to hypercapnia, whereas hyperventilation results in hypocapnia.

Hemoglobin Dissociation Curve

Hyperventilation-induced hypocapnia may, as a consequence of respiratory alkalosis, worsen oxygen delivery by shifting the hemoglobin dissociation curve to the left and may precipitate cardiac arrhythmias.

Hypercapnia is undesirable mainly because of its arrhythmogenic effects and other negative impacts on the cardiovascular system, including vasodilation followed by compensatory tachycardia. Rapid correction of long-standing hypercapnia by mechanical ventilation is also undesirable, as it can lead to post-hypercapnic metabolic alkalosis. The kidneys have a relatively slow capacity to correct excess bicarbonate.

Ventilation disorders

Ventilation disorders can be classified according to impairment of individual functional levels of the respiratory system:

Disorders of the Respiratory Center

• trauma/intracranial hemorrhage;
• neuroinfections;
• pharmacological depression;
• disorders of cerebral perfusion;
• apnea in premature infants.

Disorders of Innervation and Neuromuscular Transmission

Guillain-Barré Syndrome

• nerve and spinal cord damage;
  • Guillain-Barré syndrome;
  • trauma;
  • Werdnig-Hoffmann Disease (spinal muscular atrophy type I);
  • phrenic nerve paresis;
• neuromuscular blockade;
  • medications;
  • myasthenic syndrome ;
• systemic diseases;
  • cerebral palsy;
  • infection.

Pneumothorax

Peripheral Disorders of the Executive Organ

These are also distribution disorders:

• involvement of chest and pleural;
  • pneumothorax;
  • hemothorax;
  • chylothorax;
• respiratory muscle damage;
  • with excessive respiratory effort;
  • cachexia;
    

    Bronchial Asthma Pathology
• involvement of respiratory tract;
  • epiglottitis ;
  • acute laryngitis ;
  • aspiration ;
  • bronchial asthma ;
  • bronchiolitis.
    

    Pathophysiology of ARDS
• involvement of lung parenchyma;
  • pneumonia;
  • ALI/ARDS;
  • pulmonary edema .

Distribution

Distribution refers to the allocation of the inspired gas mixture to individual regions of the lungs. Distribution patterns can be influenced by the choice of ventilation mode and by other modifications of the respiratory cycle (such as an inspiratory pause or the introduction of a so-called sigh breath, etc.). Disorders of distribution concern the intrapulmonary distribution of inspired air. Gas exchange is affected differently in the two basic types of lung disease: obstructive and restrictive disorders.

Distribution disorders – obstruction

Obstruction is characterized by an increase in airway resistance (expiratory stridor, wheezing, mixed stridor). The pathogenesis is dominated by uneven ventilation and perfusion (V/Q mismatch), pulmonary shunt, and an increase in airway resistance. Spirometry demonstrates impaired gas exchange dynamics and an increase in functional residual capacity (FRC).

Obstructive disorders are the prototype of ventilatory failure, in which the primary problem is insufficient elimination of CO₂.

COPD

Typical causes include:

• bronchial asthma
• bronchitis
• bronchiolitis
• COPD

Obstructive disorders are characterized by normal lung compliance, increased resistance (predominantly airway resistance), increased residual volume (RV), increased FRC, and decreased FEV₁.

Distribution Disorders– Restriction

Restriction is characterized by reduced compliance of the chest wall and/or lungs. The pathogenesis involves an alveolar–capillary block, reduced diffusing capacity, pulmonary shunt, and ventilation–perfusion mismatch. Spirometry demonstrates reduced lung volumes and capacities.

Restrictive lung disorders are the prototype of hypoxic respiratory failure, i.e., failure of oxygenation. In severe cases, hypercapnia may also develop.

Pulomary Causes

• pulmonary fibrosis
• lung resection
• pulmonary edema
• pneumonia

Extrapulmonary Causes

• ascites
• kyphoscoliosis
• burns
• evaluated position of the diaphragm

Hypoxic pulmonary vasoconstriction, through the mechanism of pulmonary hypertension, leads to the development of cor pulmonale.

Restrictive disorders are characterized by reduced compliance, increased pulmonary resistance, increased work of breathing, decreased alveolar ventilation (V̇A), decreased RV, FRC, and tidal volume (TV), increased right-to-left (P–L) shunts, pulmonary hypertension, and low time constants (T), resulting in the predominance of fast lung units.

Distribution Disorders– Combined Disorders

Combined obstructive and restrictive disorders represent a combination of the above-mentioned pathophysiological mechanisms. A typical example is cystic fibrosis. These conditions are characterized by reduced compliance, increased resistance, increased work of breathing, increased right-to-left (P–L) shunts, and a time constant (T) that may be either low or high.

Diffusion

Lung Disease and Alveolar O2

Diffusion is an important component of gas exchange. The transfer of blood gases is very rapid (0.1 s) and is determined by the gradient of partial pressures across the alveolar–capillary membrane. The high solubility of carbon dioxide allows it to diffuse more rapidly than oxygen; therefore, in many pathological conditions hypoxemia precedes hypercapnia. Adequate diffusion of blood gases corresponds to a physiological value of the alveolar–arterial oxygen gradient (A–aDO₂).

Interpretation of A–aDO₂ values:

• hypoxemia with a normal A–aDO₂ indicates hypoventilation
• hypoxemia with an increased A–aDO₂ indicates a ventilation/perfusion disorder or impaired diffusion (alveolar–capillary transport).

Diffusion Disorders

Diffusion disorders affect the rate and extent of gas exchange. Oxygen transfer is always impaired, and in more severe disorders, carbon dioxide transfer is also affected. In diffusion disorders, the following pathophysiological mechanisms are primarily involved:

• changes in the partial pressure gradients of gases between alveolar air and blood,
• functional or morphological reduction of the diffusing surface area,
• alteration of the diffusion pathway (damage to the alveolar–capillary membrane),
• changes in pulmonary perfusion.

Extensive diffusion disorders are referred to as an alveolar–capillary block.

• pulmonary fibrosis
• Interstitial lung inflammation
• ARDS

Perfused

Ventilation-Perfusion Ratio and its Disorders

The distribution of perfusion in the lungs is determined by blood pressure. The patency of pulmonary capillaries is influenced by the low-pressure circulation in the pulmonary vascular bed and by alveolar pressure. In adults, alveolar ventilation normally reaches 4–5 liters per minute, while cardiac output is approximately 5 liters per minute. The normal V/Q ratio is therefore 0.8–1.0.

For more detailed information, see the page Pulmonary ventilation-perfusion ratio .

The result of a pathological V/Q ratio is either a decrease in the V/Q ratio (formation of a right-to-left shunt due to perfusion of hypoventilated alveoli) or an increase in the V/Q ratio (increase in alveolar dead space due to hypoperfusion of well-ventilated alveoli). Regionally, opposing disturbances may also occur simultaneously. In extreme cases, the V/Q ratio equals infinity (absence of perfusion, e.g. pulmonary embolism) or, conversely, equals zero in atelectasis (absence of ventilation).

Mild hypoxemia caused by a V/Q mismatch responds well to oxygen therapy, whereas in severe V/Q mismatch, increasing FiO₂ has only a minimal effect.

Pulmonary Shunting Due to Hypoventilation

Shunt Qs / Qt

A shunt can be defined as the percentage of venous blood within the total systemic blood flow that does not come into contact with a functional alveolar–capillary membrane. The shunt is calculated as the ratio of shunt flow (Qs) to total blood flow, i.e. cardiac output (Qt). Increasing FiO₂ has only a minimal effect on pO₂ when the shunt fraction exceeds 30%.

Cause

The most common cause of a shunt is perfusion of non-ventilated lung regions. The dynamics of changes in this parameter are characteristic of specific stages in the development of pulmonary pathology. An increase in the pulmonary shunt correlates with worsening of both the local pulmonary findings and the overall clinical condition of the patient, and it has prognostic significance. Optimal conditions for gas exchange are achieved when there is a proper ventilation–perfusion (V/Q) ratio.

Even in completely healthy lungs, a shunt must be taken into account. It consists of functional shunts (approximately 2% of cardiac output) and anatomical shunts (also approximately 2% of cardiac output). Functional shunts are caused by the presence of very small regions of non-ventilated lung that nonetheless retain perfusion. Anatomical shunts result from blood flow through the bronchial veins, pleural veins, Thebesian veins, and from intracardiac shunts.

• A ratio value fraction < 10% during mechanical ventilation represents normal cardiopulmonary system function.
• A ratio value of 20–30% represents the upper physiological limit—the patient may breathe spontaneously provided there is no other organ dysfunction.
• With a value > 30%, the patient can no longer tolerate spontaneous ventilation. Hypoxemia persists despite oxygen therapy, because blood flowing through the shunt does not come into contact with the high oxygen concentration in the alveoli. In this situation, increasing FiO₂ provides no benefit; instead, recruitment maneuvers should be employed and lung volume maximized by increasing positive pressures (PIP, PEEP). As the intrapulmonary shunt increases, PaO₂ decreases proportionally, while PaCO₂ remains constant due to increased minute ventilation, until the shunt exceeds 50%.
• An increase in the proportion of shunted blood to > 50% causes life-threatening hypoxemia.

Secondary perfusion disorders arise due to pulmonary vasoconstriction (caused by hypoxia and acidosis), through the mechanism of hypoxic pulmonary vasoconstriction in response to reduced ventilation.

Pathological Conditions Leading to an Increased Right-to-Left Shunt

• atelectasis
• pneumothorax
• pulmonary edema
• pneumonia
• ARDS
• neonatal respiratory distress syndrome (RDS of prematurity)

Alveolar Dead Space

When ventilation exceeds the capacity of capillary blood flow, the V/Q ratio is > 1. In this situation, alveolar dead space increases. Alveolar dead space together with anatomical dead space forms the so-called total ventilatory dead space, which under normal conditions accounts for up to 30% of total ventilation. An increase in dead space leads initially to hypoxemia and later also to hypercapnia.

Alveolar dead space is increased by disorders of pulmonary perfusion due to hypotension, pulmonary embolism, and especially by high pressures (PIP, PEEP) during mechanical ventilation, through the mechanism of alveolar overdistension. An increase in anatomical dead space is mainly caused by ventilator circuits during mechanical ventilation.

In a steady state, PaCO₂ is directly proportional to CO₂ production and inversely proportional to alveolar ventilation. It follows that hypercapnia results from a decrease in alveolar ventilation and/or an increase in CO₂ production.

Under pathological conditions, with excessive ventilation and inadequate perfusion, the proportion of dead-space ventilation increases. Conversely, insufficient ventilation of well-perfused regions leads to an increase in shunt.

For an approximate assessment of the relationship between functional dead space and tidal volume (Vd/Vt), the difference between arterial CO₂ tension and end-tidal CO₂ (etCO₂) is used. Under normal conditions, this difference is minimal (2–5 torr); under pathological conditions, it increases markedly (the rise is caused mainly by a decrease in etCO₂).

In healthy individuals, Vd/Vt ranges from 0.2 to 0.3. An increase in Vd/Vt is initially associated with hypoxemia; hypercapnia usually develops when Vd/Vt exceeds 0.5.

Classification of Respiratory Failure According to Blood Gas Values

1. Hypoxemic respiratory failure is caused by ventilation–perfusion mismatch with an increased pulmonary shunt or by diffusion impairment at the alveolar–capillary membrane (alveolar–capillary block). This type leads to intrapulmonary mixing of venous and arterial blood. The result is hypoxemia with normocapnia, because the solubility of CO₂ is substantially higher than that of O₂. With compensatory hyperventilation (in children particularly via increased respiratory rate), hypocapnia may initially be observed. As the disorder progresses, PaCO₂ gradually increases, and in severe cases global respiratory insufficiency develops.
2. The second type is hypoxemic–hypercapnic respiratory failure, which also occurs when alveolar ventilation is reduced relative to the physiological needs of the organism. The result is hypoxia accompanied by hypercapnia.

• Diseases affecting the pulmonary parenchyma and leading to a reduced V/Q ratio initially cause hypoxemic respiratory failure.
• Diseases affecting the airways and the respiratory control units lead to hypoxemic–hypercapnic respiratory failure. Hypercapnia is particularly characteristic of disorders affecting the respiratory pump.

References

Source

• Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021.
• Hall JE. Guyton and Hall Textbook of Medical Physiology. 14th ed. Philadelphia: Elsevier; 2021.