Homeostatic gaseous exchange involves a well-regulated cardiorespiratory system and two sets of capillary webs. Understanding the processes involved in oxygen transport from the environment to the tissues and the transport of carbon dioxide in the opposite direction is fundamental. This abstract would provide a thorough comprehension of the physiologic and physiopathologic mechanisms to enable accurate diagnosis and therapeutic intervention.
Hypoxemia is the relative deficiency in arterial oxygen pressure, PaO2 < 80 mm Hg and results from low alveolar oxygen pressures PAO2 as a result of FiO2 < 21%, hypoventilation or sub-ventilation. Sub-ventilation or derivation effect is observed with lung diseases (pneumonia, asthmatic crisis, etc.). Hypoxemia due to low alveolar oxygen pressure is highly responsive to oxygen therapy.
Decreased V/Q, or increased portion of collapsed alveoli. Blood is driven through alveoli that are not ventilated. The exchange of gases is already to the highest in the functional units and a further increase in FiO2 do not improve hematosis. This is called refractory hypoxemia and requires positive end expiratory pressure (PEEP) for alveolar recruitment.
Decreased mixed venous oxygen content or increased systemic oxygen extraction would reduce CvO2. Although increased cardio-respiratory work would normally compensate this situation, it could aggravate any degree of intrapulmonary derivation. The lower the saturation of deviated venous blood, the lower the level of oxygen in arterial blood.
Decreased CvO2 results from:
Increased metabolic index in the absence of compensatory cardiovascular response.
Decreased cardiac output.
Decreased arterial oxygen content (severe anemia, metahemoglobinemia, carboxyhemoglobinemia or preexisting hypoxemia).
Hypoxemia and Oxygen Therapy
In the clinical setting there is always some degree of derivation effect and some degree of pulmonary derivation. Very often the clinician faces hypoxemic patients that are only partially responsible to oxygen therapy.
Refractory hypoxemia should be diagnosed when:
PaO2 < 55 mm Hg at a FiO2 > 35%
PaO2 < 55 mm Hg at FiO2 < 35% that doesn't increase more than 10 mm Hg in response to an FiO2 increase of 20%
Refractory hypoxemia is seen when the primary disease causes an increase of physiologic derivation near to 30% or more.
Hypoxic pulmonary vasoconstriction HPV is the reduction of pulmonary blood flow through pulmonary diseased areas as a physiologic response to low oxygen partial tension at the pulmonary capillary web PcO2.
HPV minimizes the effect of reduced V/Q, as more blood is being driven to lung areas that are well ventilated. FiO2 between 50 and 100% would reduce HPV, thus increasing true derivation as more blood flows through diseased lung areas.
FiO2 > 50% increases in true derivation by producing denitrogenation absorption atelectasis DAA. These changes may be observed as soon as 15 minutes after oxygen therapy at high FiO2 and tend to be more remarkable in the diseased lung.
Due to the possible detrimental effects of oxygen therapy long term therapeutic range for oxygen supplementation is limited to FiO2 lower than 50%.
Tissue oxygen delivery DO2 depends on blood oxygen content and tissue perfusion. Local tissular blood flow is dictated by a complex series of systemic and local events.
The product of blood oxygen content and cardiac output can estimate DO2.
DO2 = Q x CaO2
CaO2 = (1.34 x [Hb] g/dl x SaO2) + (0.003 x PaO2)
Q: cardiac output (L/min); CaO2: arterial oxygen content; SaO2: hemoglobin saturation; PaO2: arterial oxygen pressure.
The impact of intrapulmonary derivation over arterial oxygenation is directly dependent upon the degree of desaturation of derived blood. By reducing the amount of oxygen extracted by the system on each pump thus increasing venous oxygen content, increased cardiac output is the most important compensatory response to hypoxemia.
Oxygen extraction is the amount of oxygen extracted from systemic blood at each pump; it is the difference between the amount of oxygen in arterial blood and the venous admixture (measured at the pulmonary artery) C(a-v)O2, it can be expressed in ml/dl or volume percent (vol%). The normal rest value is 5 vol% (4.5–6 vol%).
Oxygen consumption VO2 is the amount of oxygen in ml consumed by the patient per minute and can be calculated by the Fick equation.
VO2 = C(a-v)O2 x Q x 10
Aerobic metabolism is dependent of a steady stream of oxygen. Oxygen demands may change with many factors including metabolic rate, body temperature, age, diseases, and organ dysfunction. Oxygen extraction ratio (OER = VO2/DO2) is variable during normal daily activity but in normal healthy patients OER is never high enough to tax the oxygen reserves.
Some pathological conditions like anemia, metahemoglobin, poor perfusion, reduced cardiac output or increased metabolic demands may increase oxygen extraction ratio OER to the extent of limiting VO2 by oxygen delivery DO2. This point is referred as supply-dependent VO2.
However, energetic tissular requirements cannot be halted by reduced oxygen availability. Consequently cellular metabolism must be kept by anaerobic respiration, which is far less efficient than aerobic respiration.
Tissular hypoxia and hypoxemia are not synonymous; tissular hypoxia can be present without hypoxemia and hypoxemia can be present in the absence of tissular hypoxia.
Ventilatory problems relate only to CO2 homeostasis, the grade of systemic oxygenation is an independent variable and it must be evaluated separately!
Ventilation refers to the exchange of CO2 in the respiratory system and should keep arterial carbon dioxide pressure PaCO2 within 35–45 mm Hg independently of metabolic rate.
Ventilation requires the integrity of several interrelated systems, including the lungs, thoracic cavity and the neuromuscular system.
Clinical diagnosis of ventilatory insufficiency or hyperventilation based on observations of the respiratory pattern may be totally inadequate, blood gas analysis to measure PaCO2 is required.
CO2 rapidly diffuses through the alveolar-capillary membrane; PaCO2 should be equal to alveolar carbon dioxide tension PACO2. With a normal capnogram ETCO2 should be 2–3 mm Hg lower than PaCO2. The same conclusions cannot be taken from an abnormal capnogram.
Acute ventilatory insufficiency refers to the presence of high PaCO2 in association with acidosis. Sudden changes in the internal environment are far more harmful to normal biochemical cellular processes than gradual changes. Gradual changes allow the array of compensatory mechanisms, whereas abrupt variations arrest cellular function in greater degree and may be life threatening. Adequate ventilatory support would generally correct acidosis and hypoxemia.
Chronic ventilatory insufficiency is increased PaCO2 in association with almost normal pH as a result of metabolic compensation. The most important stimulus for ventilation in this patient is peripheral chemoreceptors' response to hypoxemia. Oxygen therapy at FiO2 higher than 25% may produce a profound drop in ventilation.
Alveolar hyperventilation results from a relative excess in the rate of CO2 excretion if compared to metabolic production. Some pathologic states like hypoxemia, metabolic acidosis and abnormal stimuli to the respiratory centers may affect cardiopulmonary homeostasis in such a way that normal exchange of gases is insufficient to meet metabolic demands; the patient is stimulated to increase the rate of gas exchange.
Acute alveolar hyperventilation is diagnosed when the drop in PaCO2 presents with alkalosis, whereas chronic alveolar hyperventilation presents with normal pH due to metabolic compensation.
Hyperventilation with hypoxemia will respond to oxygen therapy, whereas metabolic acidosis and central nervous system causes would require specific therapy.
Respiratory gas homeostasis is essential in maintaining normal cellular metabolism and systemic homeostasis. Thorough comprehension of oxygen and carbon dioxide dynamics is very important to completely understand the physiopathologic factors involved on each patient. Accurate utilization of diagnostic tools as well as correct interpretation may be of crucial importance for timely therapeutic intervention.
1. Davis H. Arterial and venous blood gases. In: Wingfield W, Raffe M, eds. The Veterinary ICU Book. 1st ed. Jackson, WY: Teton NewMedia; 2002:258–265.
2. Orton EC. Respiratory system. In: Wingfield W, Raffe M, eds. The Veterinary ICU Book. 1st ed. Jackson, WY: Teton NewMedia; 2002:280–297.
3. Raffe MR. Respiratory gas transport. In: Wingfield W, Raffe M, ed. The Veterinary ICU Book. 1st ed. Jackson, WY: Teton NewMedia; 2002:15–23.
4. Shapiro BA, Harrison RA, Cane RD, Templin R. Differential analysis of arterial and mixed venous blood oxygen content. Section II. Blood gas analysis applied to patient care. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:130–137.
5. Shapiro BA, Harrison RA, Cane RD, Templin R. Application of physiologic derivation. Section II. Blood gas analysis applied to patient care. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:138–153.
6. Shapiro BA, Harrison RA, Cane RD, Templin R. Physiologic dead space evaluation. Section II. Blood gas analysis applied to patient care. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:154–163.
7. Shapiro BA, Harrison RA, Cane RD, Templin R. Metabolic abnormalities and blood gas interpretation. Section II. Blood gas analysis applied to patient care. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:175–181.
8. Shapiro BA, Harrison RA, Cane RD, Templin R. Capnography. Section III. Point of care testing of blood gases. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:199–203.
9. Shapiro BA, Harrison RA, Cane RD, Templin R. Pulmonary artery oxymetry. Section III. Point of care testing of blood gases. In: Clinical Application of Blood Gases. 4th ed. Editorial Médica Panamericana; 1990:199–203.