1. Learning Objectives:
- Be able to compare alveolar ventilation vs. dead space ventilation. Relate alveolar ventilation to PaCO2.
- Be able to define the various lung volumes and indicate how they can be measured.
- Be able to define compliance, explain decreased and increased compliance, and give an example of a disease process causing each.
- Explain the force of surface tension and why it causes alveoli to tend to collapse.
- Be able to explain the factors that affect the rate of gas diffusion at the air-blood barrier.
- Explain two mechanisms of oxygen transport in blood and how changes in Hb affinity affect oxygen delivery to tissues.
- Explain how carbon dioxide is transported in blood.
- Define low and high ventilation/perfusion ratios and list pathologic situations that lead to each.
- Define hypoxemia and list 5 causes.
- Define hypercapnia and list the most frequent cause.
2. The Respiratory System
- Respiration is the process of gas exchange between an animal's environment and the individual cells for the purpose of energy metabolism.
- Mammalian lungs are internalized structures that allow gas exchange between the environment and venous blood.
- Respiratory functions of the lungs include bulk gas transport and gas diffusion.
3. Ventilation: Moving Air from the Environment to the Gas Exchange Surface
3.1. Alveolar Ventilation:
- Alveolar Ventilation ( ) : Volume of fresh air entering or leaving the alveoli/min (i.e., the ventilation participating in gas exchange).
- Dead Space Ventilation
(D): Ventilation of lung regions that do not
participate in gas exchange.
- E = + D (E = minute ventilation)
- is Related to Clearance of Metabolically Produced CO2: PaCO2 (as an estimate of PaCO2) is a good indicator of whether is adequate for the animal’s metabolic needs.
3.2. Lung Volumes:
- Total lung capacity (TLC) = volume of gas that can be contained within the maximally inflated lung; it is subdivided into component volumes that are functionally important.
- Tidal volume (VT) = volume of a single expired breath.
- Vital capacity (VC) = maximal volume that can be expelled from the lungs after a maximal inspiration.
- Residual volume (RV) = volume of gas that remains in the lungs after a maximal expiration.
- Functional residual capacity (FRC) = volume remaining in the lungs at the end of a normal expiration.
4.1. Pulmonary Tissue Forces
- The lung is primarily passive and will collapse if force is not applied to expand it.
- Compliance = the change in volume as expanding pressure is applied (either negative or positive pressure).
The slide shows histology of normal sheep lung. This lung would correspond with the normal compliance curve in the first slide.
This slide shows a lung with increased collagen (blue stain) consistent with pulmonary fibrosis. This lung would correspond with the center compliance curve in the first slide. The compliance is decreased, and there is less volume increase with the pressure that would easily inflate the normal lung.
|Lung with Emphysema|
This slide shows lung tissue with severe destruction of elastin and loss of many alveolar septae. The clinical disease is called emphysema, and is the only pulmonary disease that results in increased compliance. There are large bullous air spaces and few intact alveolar septae. This would correspond to the curve on the right in the first slide. The lung has lost tissue, has poor recoil, and the compliance is increased.
4.2. Surface Tension Forces
- Surface tension also contributes to passive recoil of the lung.
- Alveoli tend to collapse in response to forces acting to reduce the surface area of the air-liquid interface - the pressure required to maintain alveoli in the open state is related to the surface tension and radius
- Pulmonary surfactant reduces surface tension and allows it to vary with alveolar radius.
4.3. Airway Resistance
- Friction with airway walls causes resistance to gas flow.
- A pressure difference from the mouth to the alveoli is required to move gas against this resistance
- Air flow may be turbulent or laminar: turbulent flow
generates greater resistance.
- Flow characteristics depend on air velocity and airway size.
- As the total cross-sectional area increases from trachea to the bronchioles, velocity decreases, and flow becomes laminar at the periphery.
- The total cross-sectional area of all the peripheral airway branches results in minimal resistance in small airways.
5. Diffusion: The Exchange of O2 AND CO2 at Pulmonary and Tissue Capillaries
5.1. Principles of Gas Diffusion Through Tissue
- CO2 has a higher solubility than O2 (20x greater) and diffuses more rapidly through tissue even though slightly heavier.
- Partial pressure differences drive gas diffusion. The partial P difference between alveolar gas and mixed venous blood is much greater for O2 (60 mmHg) than CO2 (6 mmHg).
5.2. Pulmonary Capillary Gas Equilibration
- Capillary transit time for RBC's is approximately 0.7 seconds; equilibration of O2 and CO2 is complete within 0.3 seconds.
- Exercise reduces the time available for equilibration, but there is ample reserve in the normal individual.
6. Gas Transport
6.1. O2 is Transported in Blood Via Two Mechanisms
- Dissolved O2 (minor) [0.003ml / 100ml
- arterial blood (PaO2 = 100 mmHg) has 0.3ml O2 / 100ml
- Chemical combination with hemoglobin (major) [1.34 ml
- 15 g Hb/100 ml blood (at normal hematocrit) x 1.34ml O2/gHb = 20 ml O2/100 ml blood
- PO2 of plasma determines the amount of O2 that binds Hb
- if the red cell mass (g Hb) is decreased, PaO2 may be normal, but O2 content will be less
6.2. Hemoglobin-Oxygen Binding and Dissociation
- At high PO2 the curve is nearly flat, and large changes in PO2 correspond with only minor changes in saturation, facilitating a large PO2 gradient at the alveolus to drive diffusion without severe compromise of arterial O2 content.
- In the steep portion of the curve, small changes in PO2 are accompanied by large changes in O2 content, favoring unloading to the tissues.
- Shifts in the curve left or right affect oxygen affinity and thus delivery to the tissues; muscular activity, fever, and acidosis decrease oxygen affinity favoring tissue oxygenation (right shift).
- There are species differences in Hb-oxygen affinity, and these are related to variation in metabolic need for oxygen with body size.
6.3. CO2 is Transported in Blood by Three Mechanisms
- Dissolved in plasma (minor): [0.06ml / 100ml plasma/mm Hg
- arterial blood (PaO2 40 mm Hg) has 2.4 ml CO2/100 ml plasma dissolved
- As bicarbonate (major) 85%: CO2 +
H2O ↔ H2CO3↔ HCO + H+
- reaction occurs within erythrocytes (carbonic anhydrase present)
- As carbamino-Hb (minor): combination of CO2 with terminal amine groups on hemoglobin
- The CO2 content of whole blood has a linear relationship with PCO2
7. Ventilation-perfusion Relationships
7.1. Normal Distribution of Blood Flow and Ventilation
- Ventilation increases from apex to base at normal lung volumes in upright humans, is uniform from dorsal to ventral in the standing dog, and increases from dorsal to ventral in the standing horse.
- Perfusion increases from apex to base in the upright human, is uniformly distributed in the standing dog, and increases from dorsal to ventral in the standing horse.
- In the clinically normal human, the gradients for ventilation and perfusion are not equivalent; the inequality in blood flow from apex to base is greater than that for ventilation, and the ratio of ventilation/perfusion varies.
- Both ventilation and perfusion are uniformly distributed in the dog, and the / ratio is nearly uniform throughout.
- A vertical gradient of both ventilation and perfusion exists in the standing horse, but matching is better than in humans, and the / ratio is nearly uniform throughout.
7.2. Pathologic / Inequalities
An extreme / inequality is complete obstruction or collapse of an airway ( / = 0), equivalent to an anatomic shunt.
The opposite extreme is the alveolus whose capillary supply is occluded ( / = 4), which contributes to dead space.
A considerable A-a gradient can develop due to / mismatch:
|PAO2= PIO2||- [PaCO2]||A-a gradient = PAO2-PaO2|
Many disease states are characterized by large areas of mild-moderate mismatch:
- low / (poorly ventilated areas) pneumonia, partial airway obstruction
- high / (under-perfused areas) emphysema, heart-worm disease
If the inspired PO2 is raised, the PaO2 and tissue oxygenation improve, however the A-a gradient due to complete shunt will not improve.
8.2. Causes of Hypoxia
- Decreased inspired PO2: For example, high altitude or anesthetic mismanagement
- Alveolar hypoventilation: PaO2 reduced and
- inadequate ventilation due to pulmonary or neuromuscular disease
- severe CNS depression (metabolic or depressant drugs) - inadequate ventilation during anesthesia
- Venous admixture, or right-to-left shunt:
- 3-5% cardiac output is normally shunted (example, bronchial circ.)
- congenital heart disease (puppies, kittens and calves)
- atelectasis (alveolar collapse) with continued blood flow
- Ventilation/perfusion mismatch:
- the most common cause and a major factor in development of hypoxia in nearly all forms of pulmonary disease
- hypercapnia (increased PCO2) will develop only in severe cases
- Diffusion impairment (diagrammed as a subcategory of /
- minor contribution in most cases
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