Gas Exchange And Disorders:

Study Objectives

· To define cardiac output, diffusion, diffusion- and perfusion-limited gas exchange, hypercapnia, hypocapnia, hypoxia, respiratory quotient (RQ), ventilatory exchange ratio(R) , and the ventilation-perfusion ratio (V°A / Q° -ratio) .

· To describe Henry’s and Dalton’s laws, factors of importance for the lung diffusion capacity and pulmonary perfusion, and its measurements, describe the PO2-PCO2-diagram, hypo-and hyperventilation, pulmonary water balance, and mixed venous blood composition.

· To calculate the pulmonary perfusion, use the alveolar gas equation, the alveolar ventilation equation, the final V°A / Q° -equation, and the law of mass balance in calculations.

· To explain the alveolar oxygen uptake and carbon dioxide output, pulmonary vascular resistance and pressures. To explain the alveolar dead space, veno-arterial shunts, uneven regional ventilation-perfusion ratio in health and disease, and peripheral gas exchange.

· To use the concepts in problem solving and case histories.

Principles

· Bernoulli’s principle or equations (see Eq. 13-6).

Definitions

· Alveolar oxygen uptake per min is the uptake of oxygen molecules into the passing pulmonary blood - into the cardiac output.

· Cardiac output is the volume of blood leaving the left (or the right) ventricle each min.

· Diffusion is a transport of atoms or molecules caused by their random thermal motion.

· Diffusion capacity for the lung (DL ) is defined as the volume of gas diffusing through the lung barrier per min and per unit of pressure gradient (DL = V°O2/ DP).

· Diffusion-limitation of gas exchange is a condition where equilibration does not occur between the gas tension in the pulmonary capillaries and the alveolar lumen. When the distance between the capillary blood and the cells is large, diffusion becomes a limiting factor even at high bloodflow.

· Hypercapnia refers to a resting condition with hypoventilation, where PaCO2 is higher than 6.4 kPa (48 mmHg).

· Hypocapnia is a hyperventilation disorder with abnormally reduced PaCO2 at rest (below 33 mmHg or 4.4 kPa).

· Hypoxia denotes oxygen deficiency in tissues due to insufficient delivery of oxygen or inability to utilize oxygen. Hypoxia may be present both with low PaO2 and with normal PaO2.

· Hypotonic or hypobaric hypoxia is characterised by a PaO2 less than 7.3 kPa (55 mmHg). This is the threshold, below which the ventilation starts to increase by carotid body stimulation. As the altitude increases, the barometric pressure decreases and the partial pressure of oxygen in the alveolar air falls.

· Hypoxic pulmonary vasoconstriction is a compensatory mechanism in alveoli with low ventilation and low oxygen partial pressure. The mechanism is triggered directly by smooth muscle contraction in the vessel walls at a PaO2 less than 7.3 kPa (55 mmHg).

· Multiple inert gas technique is a procedure, where multiple inert gases of different air—to-blood solubility ratios are infused intravenously until steady state of pulmonary gas elimination is reached. The partial pressure of each gas is measured inthe infused fluid and in the expired air. The V°A / Q° -equation (Eq. 14-5) and the law of mass balance is used to compute the most likely regional V°A / Q° -distribution. - Clinically, the alveolar-arterial oxygen tension gradient is measured instead of this complicated reseach procedure.

· Perfusion-limited or flow-limited gas exchange is limited by the bloodflow. The only limitation to net movement of small molecules across the capillary wall is the rate at which bloodflow transports the molecules to the capillaries.

· Peripheral Resistance Unit (PRU) is measured as driving pressure per bloodflow unit (eg, mmHg*s*ml-1).

· Pulmonary hypertension is a condition with a mean pulmonary artery pressure above normal - a pressure above 2 kPa or 15 mmHg.

· Pulmonary vascular resistance (PVR) is the ratio between the pressure gradient and the bloodflow. The basic equation is: PVR (PRU) = DP / bloodflow (PRU in mmHg*s*ml-1).

· Pulmonary oedema is an emergency caused by filtration of fluid out of the pulmonary capillaries into the interstitial space (interstitial oedema), and eventually in the alveolar spaces (alveolar oedema).

· Respiratory Quotient (RQ) is a metabolic ratio between the carbon dioxide output and the oxygen uptake of all cells of the body.

· Standard affinity is the binding force between two molecules, when half of the binding sites are occupied (at 50% saturation). In the case of oxyhaemoglobin the P50 is used. Here, standard affinity is equal to 1/P50.

· Ventilatory exchange ratio (R) is the ratio between the carbon dioxide output and the oxygen uptake measurable with gas exchange equipment at the mouth.

Essentials

This paragraph deals with

1. Gas exchange, 2. A key to lung disorders, 3. Uneven distribution of tidal volume and perfusion, 4. Blood gasses, 5. The PO2 - PCO2 diagram, 6. The V°A / Q° - curve, 7. Blood-R-curves, 8. Dead space, 9. Anatomic venous-to-arterial shunt, 10. Ficks law of diffusion, 11. Single -breath diffusing capacity, 12. Compensation of V°A /Q ° - mismatch, 13. Pulmonary bloodflow, and 14. Regional ventilation.

1. Gas exchange

Gasses are exchanged between the atmosphere and the alveolar air, and gasses diffuse between the alveolar air and the blood flowing through the pulmonary capillaries.

Oxygen is transported from the atmosphere, via the alveolar ventilation and then carried by the pulmonary bloodflow (equal to the cardiac output), into the cells and their mitochondria for metabolic purposes. Carbon dioxide, the final end-product of metabolism, migrates from the cells to the atmosphere.

A healthy normal person at rest, ventilates his lungs with 5 litres (l) min-1 of fresh air (V°A). The Respiratory Quotient (RQ) is a metabolic ratio between the carbon dioxide output

(V°CO2) and the oxygen uptake (V°O2) defined for all body cells as a whole. In respiratory steady state, RQ can be measured as the ventilatory exchange ratio (R) (Fig. 14-1).

On a diet dominated by carbohydrate the metabolic RQ for all cells of the body is approaching 1, and in a respiratory steady state, identical to the ventilatory exchange ratio, R, which is measured in the expired air (Fig. 14-1).

Fig. 14-1: The respiratory quotient (RQ) is compared to the measurable ventilatory exchange ratio (R).

The normal resting carbon dioxide output is 10 mmol or 224 ml STPD per min from an adult person, and the cardiac output is typically 5 l min-1. The blood volume of 5 l carries each min about 10 mmol (or 224 ml STPD) of oxygen towards the mitochondria. Following passage of the capillary system, the same amount of CO2 is carried towards the lungs in the venous blood as long as RQ and R is 1.

Blood passing the pulmonary capillaries of a healthy person is rapidly equilibrating with the alveolar air. Oxygen from the air diffuses into the blood and binds reversibly with haemoglobin. The normal oxygen capacity is 200 ml STPD per l of blood (150 g haemoglobin per l carrying 1.34 ml STPD per g).

The six zones of the alveolar-capillary barrier are: 1) a fluid layer containing surfactant, 2) the alveolar epithelium; 3) a fluid-filled interstitial space ; 4) the capillary endothelium with basement membrane; 5) the blood plasma; and 6) the erythrocyte membrane. The six zones form an almost ideal gas exchanger for oxygen and carbon dioxide diffusion.

There are 300 million tiny blind end sacs (alveoli) in both lungs together. Fortunately, the alveoli are diluted continuously with fresh air as we breathe.

2. A key to lung disorders

The alveolar ventilation-perfusion ratio is presented as a straight line in Fig. 14-2.

Alveolar ventilation (V°A ) and pulmonary bloodflow (equal to the cardiac output, Q°) is considered in three extreme situations:

1. The normal condition in which V°A and Q° are matched ( ideal V°A / Q° -ratio = 5/5 = 1), is shown with the typical normal arterial gas tensions (Fig. 14-2).

2. Pulmonary embolism creates an alveolar dead space. The V°A is maintained, but there is no bloodflow (Q° regional), so the V°A / Q° -ratio of the lung region approaches infinity. In the alveolar dead space, alveolar gas pressures approach the levels in inspired air.

3. Occlusion of the airway represents an extreme mismatch of venous to arterial shunting of blood, namely perfusion with no ventilation at all (ie, the total ratio approaches zero). The arterial blood gas tensions approach those of venous blood (Fig. 14-2).

The straight line (or V°A / Q° -axis) of Fig. 14-2 represents an infinite row of ventilation-perfusion-values. Each value refers to an alveolus with equilibrated blood flowing by.

Two well-known equations are relevant here: the Fick cardiac output equation (Eq. 14-1) and the alveolar gas equation (Eq. 14-3).

The hyperbolic relationship between V°A and FACO2 is described in the alveolar ventilation equation (Eq 14-4).

These three equations can be combined to one equation, which can be expressed in several ways. The calculations are not shown here. The final equation reads as Eq. 14-5:

V°A / Q° = R( CaO2 - Cv¯CO2) / FACO2

Solutions of this equation provide values from zero to infinity for the ventilation-perfusion-ratio. These solutions can be plotted in a PO2 - PCO2 diagram (Fig. 14-6), where complicated calculations are performed and solved graphically at a glance by looking at the red V°A / Q° --curve. In the venous point the V°A / Q° -ratio is zero, and in the I-point on the abscissae the V°A / Q° -ratio is infinite.

The regional V°A / Q° -ratio is the all-important variable. In any cardio-pulmonary disease, the normal variation of the ratio for the entire system (Fig. 14-2) is exagerated.

Fig. 14-2: Three pulmonary regions or alveoli representing 3 V°A / Q° ratios from zero to infinity. Normally, the ventilation/perfusion-ratio is 0.8-1.2 for the entire system. Blood gas tensions are given in kPa (133.3 Pa equals 1 mmHg).

3. Uneven distribution of tidal volume and perfusion

can eventuate from uneven resistance to airflow within the lung (bronchoconstriction, collapse and compression of airways). Uneven distribution can also be caused by uneven regional lung compliance (insufficient surfactant, loss of elastic recoil as in destruction of alveolar tissue, and increase of elastic recoil as in connective tissue scarring or fibrosis with stiff lungs). Hypoperfusion can be caused by compression of pulmonary vessels, obliteration of vessels by fibrosis, or blockage by emboli or thrombosis.

Functional shunts arise with any consolidation of alveolar regions that continue to have bloodflow (pneumonia, oedema, haemorrhage, cell necrosis, lack of surfactant).

4. Blood gasses

Blood gases from an arterial blood sample of a healthy person typically show the values of Box 14-1:

Box 14-1: Blood gas values (ranges) from healthy persons at rest. - Normal mean tensions for mixed venous blood and for alveolar air are shown below.

PaO2 :
10-13 kPa (75-95 mmHg)

PaCO2:
4.8-6 kPa (36-45 mmHg),

Base Excess:
Zero (Chapter 17),

pHa :
7.35-7.45 (ie,[H+] = 35-44 nM)

PAO2 :
10 - 13.3 kPa (75-100 mmHg)

PACO2 :
4.8-6 kPa (36-45 mmHg). Mean: 5.3 kPa (40 mmHg),

Mean PvO2 :
6 kPa (45 mmHg)

Mean PvCO2 :
6.1 kPa (46 mmHg)

Chapter 14