Filter, warm & moisten air Nose, (mouth), trachea, bronchi & bronchioles Huge increase in cross sectional

al area

Figure 17-4: Branching of the airways

Figure 18-1: Overview of oxygen and exchange and Transport CO2

 The

steps by which po2 decreases from air to mitochondria, ultimate site of o2 consumption, enabling transport of o2 along pres. Gradient to known as o2 cascade.

The air (atmosphere) around us has a total pressure of 760 mmHg (1 atmosphere of pressure = 760mmHg = 101kPa = 15lbs/sq. in). The pressure of oxygen (PO2) of dry air at sea level is therefore 159 mmHg (21/100 x 760=159). Inspired air on reaching the trachea becomes warmed and humidified by the upper respiratory tract. At 37oC the water vapour pressure in the trachea is 47 mmHg. PO2in the trachea when breathing air is (760-47) x 21/100 = 150 mmHg. In alveoli the PO2 has fallen to about 100 mmHg. This is because the PO2 of the gas in the alveoli (PAO2) is a balance between two processes: the removal of oxygen by the pulmonary capillaries and its continual supply by alveolar ventilation (breathing).

Blood returning to the heart from the tissues has a low PO2 (40 mmHg),to lungs via pulm art, to pulm vein to left heart to systemic circulatn. In a 'perfect lung' the PO2 of pulmonary venous blood would be equal to the PO2 in the alveolus. Three factors may cause the PO2 in the pulmonary veins to be less than the PAO2: 1. ventilation/perfusion mismatch 2.shunt 3.slow diffusion

In a 'perfect lung ventilation and perfusion would be perfectly matched. At rest both ventilation and perfusion increase down the lung, perfusion increases more than ventilation. Well ventilated alveoli (high PO2 in capillary blood) cannot make up for the oxygen not transferred in the underventilated alveoli with a low PO2 in the capillary blood. This is because there is a maximum amount of oxygen which can combine with haemoglobin.

 LOW

V/Q or VENOUS ADMIXTURE Ventilation is unable to saturate the blood PAO2 PaO2 gradient increases Causes hypoxemia Eg.obstructive ds, severe asthma, airways obstructed with edema,mucous plug,spasm.

 HIGH

V/Q or WASTED VENTILATION or mimics dead space ventilation Impedes CO2 elimination Eg.pulm vessel ds, pulm emboli, pneumonia, acute resp failure(atelectasis,fluid filling,consolidation)

 Shunt

is caused by complete cessation of ventilation in a region, as a result of collapse(atelectasis) or consolidation (pneumonia, edema, obliterative process). Blood passes through the lung without coming in contact with ventilated alveoli The effect of moderate shunt can be reduced but not eliminated. With a shunt of 30% or greater, almost no effect of added O2 can be seen.

Oxygen diffuses from the alveolus to the capillary until the PO2 in the capillary is equal to that in the alveolus, that is one third of the way along the pulmonary capillary. In high cardiac output and fibrosis, diffusion is impaired

Diffusion barrier may not cause hypoxia as long as there is enough time and capillary distance to allow equilibrium.
HYPOXIC PULMONARY VASOCONSTRICTION reduces blood flow in hypoxic lung regions.strenghth of constriction stronger,smaller the region. MAJOR STIMULUS IS LOW ALVEOLAR OXYGEN TENSION.

 Gas

flow by convection in larger and medium sized airways, By diffusion in peripheral airways and alveoli DIFFUSION ACROSS ALVEOLAR CAPILLARY MEMBRANES DETERMINED BY 1.Surface area available 2.Membrane thickness 3.Pressure gradient 4.Molecular wt of gas (inv to sq root of wt) 5.solubility

 Oxygen

carrying capacity of blood Gas content of blood Hb Oxygen Hb dissociation curve Factors affecting affinity of Hb for Oxygen

Hb bound O2 [g/dl] 1.34xHbxSo2 Dissolved O2 Solubility in plasma: 0.03mL/L/mm Hg Partial pressure of O2 [PO2] in blood eg. If PO2 is 100,1 L blood will have 3mL dissolved O2

Contd

 Arterial

O2 content [CaO2]

[1.34xHbxSaO2]+0.003XPaO2] Approx. 200mL O2/L of arterial blood[only 3 ml dissolved in plasma,if we were to rely on this then a cardiac output of 89 l/min will be needed for aerobic metabolism,so the importance of Hb in Oxygen transport] Venous O2 content [1.34xHbxSvO2X]+0.003XPvO2]

Comparative influence of Hb & PaO2 on O2 level:50% reduction in Hb causes 50% reduction in CaO2 while 50% reduction in PaO2 LEADS TO ONLY 18% fall in CaO2 This implies anaemia has more profound effect on blood oxygenation than hypoxemia & so PaO2 should be avoided to assess arterial oxygenation

Parameters
po2 sao2 Hbo2 Dissolved o2 Total O2 content Volume of O2

Arterial blood
90 mm Hg 0.98 197 ml/l 2.7 ml/l 200 ml/l 250ml

Venous blood
40mm hg 0.73 147ml/l 1.2ml/l 148ml /l 555 ml

The amount of oxygen leaving left ventricle/min in arterial blood Oxygen flux=QxSO2xHbx1.34 5000 ml/minx0.98x15x1.34 =1000 ml/min Oxygen that enters blood stream in lungs is carried to vital organs by cardiac output, rate at which this occurs is DO2

 On

reaching systemic capillaries,oxygen dissociates frm Hb& moves into tissues,the rate at which this occurs is called VO2[in ml/min] It is also a measure of O2 consumption as O2 is not stored in tissues VO2=Qx[CaO2-CvO2] VO2=Qx1.34xHbx[SaO2-SvO2]=200300ml/min

Fraction of oxygen delivered to capillaries that is taken up into tissues is an index of efficiency of oxygen transport O2ER=VO2/DO2 OR O2ER=[SaO2-SvO2]/ SaO2 When SaO2~1;O2ER approx.=SaO2-SvO2, which is normally 0.25..this implies 25% of O2 delivered to capillaries is taken up by tissues

contd.

Although O2 extraction is usually low, it is adjustable when O2 delivery is low Oxygen transport system operates to maintain a constant flow of O2 in tissues, in face of changes in O2 flux, this is made possible by ability O2ER to adjust to changes in DO2

VO2=DO2xO2ER

The DO2-VO2 RELATION Maximum OER Supply dependant Dysoxia Critical DO2 Impaired cell function Clinical shock & MOD

It is the ratio in the steady state of the volume of CO2 produced to the volume of O2 consumed per unit time. It is used to identify the predominant type of nutrient substrate being metabolised. For glucose 1.00 lipid 0.70 protein 0.80

Parameter Cardiac output O2 delivery

RANGE 5-6 L/min 900-1100 ml/min

O2 uptake O2 ER CO2 elimination Respiratory quotient

200-270 ml/min 0.20-0.30s 160-220ml/min 0.75-o.85

Hb is a protein made of 4 subunits,each with a HEME moitey attatched to polypeptide chain Heme: Porphyrin +1 Ferrous Iron Each Iron atom binds reversibly with one O2 molecule Hb4 + O2Hb2O2 Hb4O2+O2.Hb4O4 Hb4O4 +O2.Hb4O6 Hb4O6 +O2.Hb4O8 The reaction is rapid needing less than 0.01 sec

contd.

 Quaternary

structure of Hb determines its affinity to Oxygen When Hb takes up O2 ,two beta chains move close together,this movement favours a relaxed state or R state that favours O2 binding When O2 is given up two chains move away,assuming tense or T state that decreases O2 binding

The curve relating percentage saturation of the O2-carrying power of hemoglobin to the PO2 Has a characteristic sigmoid shape due to the TR interconversion. Combination of the first heme in the Hb molecule with O2 increases the affinity of the second heme for O2, and oxygenation of the second increases the affinity of the third, etc, so that the affinity of Hb for the fourth O2 molecule is many times that for first

100%

Plateau: % saturation of haemoglobin Steep slope: small drop of O2 partial pressure leads to a rapid decrease in % saturation of haemoglobin partial pressure of O2 (mmHg) highly effective in the uptake large amount of O2 from environment but release it so easily to the tissue cells ! favour the release of O2 in tissue cells haemoglobin highly saturated with O2 at relatively low O2 partial pressure favour the loading of O2 in lung

When blood is equilibrated with 100% oxygen(760 mmHg), the normal hemoglobin becomes 100% saturated. When fully saturated, each gram of normal hemoglobin contains 1.39 mL of O2. However, blood normally contains small amounts of inactive hemoglobin derivatives, and the measured value in vivo is lower. The traditional figure is 1.34 mL of O2. The hemoglobin concentration in normal blood is about 15 g/Dl. Therefore, 1 dL of blood contains 20.1 mL (1.34 mL x 15) of O2 bound to hemoglobin when the hemoglobin is 100% saturated. The amount of dissolved O2 is a linear function of the PO2 (0.003 mL/dL blood/mm Hg PO2). In vivo, the hemoglobin in the blood at the ends of the pulmonary capillaries is about 97.5% saturated with O2 (PO2 = 97 mm Hg

Because of a slight admixture with venous blood that bypasses the pulmonary capillaries, the hemoglobin in systemic arterial blood is only 97% saturated and that in venous systemArterial Blood is 75% saturated Parameter Venous blood
Total O2 Hb O2 Dissolved O2 Tissues remove 19.8 19.5 0.3 4.6 ml of O2 frm each dl 15.2 15.1 0.12

In this way 250ml O2 per minute is transported frm blood to tissues at rest

Three important conditions affect the oxygenhemoglobin dissociation curve: ph temperature 2,3biphosphoglycerate (BPG; 2,3-BPG)

convenient index of shifts is the P50, the PO2 at which hemoglobin is half saturated with O2. The higher the P50, the lower the affinity of hemoglobin for O2.

The decrease in O2 affinity of hemoglobin when the pH of blood falls is called the Bohr effect and is closely related to the fact that deoxygenated hemoglobin (deoxyhemoglobin) binds H+ more actively than does oxyhemoglobin. The pH of blood falls as its CO2 content increases, so that when the PCO2 rises, the curve shifts to the right and the P50 rises. Most of the unsaturation of hemoglobin that occurs in the tissues is secondary to the decline in the PO2, but an extra 12% unsaturation is due to the rise in PCO2 and the consequent shift in curve to right

2,3-BPG is very plentiful in red cells. It is formed in glycolysis via the Embden Meyerhof pathway. It is a highly charged anion that binds to the chains of deoxyhemoglobin. One mole of deoxyhemoglobin binds 1 mol of 2,3-BPG. In effect, HbO2 + 2,3-DPG Hb-2,3DPG+ O2

In this equilibrium, an increase in the concentration of 2,3-BPG shifts the reaction to the right, causing more O2 to be liberated. Thyroid hormones, growth hormone, and androgens increase the concentration of 2,3-BPG and the P50 The P50 is also increased during exercise, because the temperature rises in active tissues and CO2 and metabolites accumulate, lowering the pH. In addition, much more O2 is removed from each unit of blood flowing through active tissues because the tissues' PO2 declines. Finally, at low PO2 values, the oxygenhemoglobin dissociation curve is steep, and large amounts of O2 are liberated per unit drop in PO2.

The increase in CO2 content that results from oxyhemoglobin desaturation is known as HALDANE EFFECT. i.e. there is reciprocal binding of O2 and CO2 in lungs i.e. at same Pco2 , CO2 content will be more for deoxygenated blood as compare to oxygenated blood. Consequently , venous blood carries more CO2 than arterial blood, CO2 uptake is facilitated in the tissues and CO2 release is facilitated in the lungs. clinical significance In patients with lung disease, lungs may not be able to increase alveolar ventilation in the face of increased amounts of dissolved CO2. This partially explains the observation that some patients with emphysema might have an increase in PaCO2 (partial pressure of arterial dissolved carbon dioxide) following administration of supplemental oxygen even if content of CO2 stays equal.

Hypoventilation may occur during anaesthesia due to airway obstruction, the effects of volatile anaesthetic agents, opioids and other sedatives. Alveolar PO2 is a balance between the oxygen supplied by breathing and that used by metabolic processes in the body. Hypoventilation and a decreased inspired oxygen concentration will therefore cause a reduction in alveolar PO2(PAO2). The increased utilisation of oxygen when metabolic rate is raised such as with postoperative shivering or malignant hyperpyrexia also causes a reduction in alveolar PO2. If the PaO2 falls to less than 60mmHg the aortic and carotid body chemoreceptors respond by causing hyperventilation and increasing cardiac output through sympathetic nervous system stimulation. This normal protective response to hypoxia is reduced by anaesthetic drugs and this effect extends into the postoperative period

Following induction of anaesthesia there is a rapid reduction in FRC that results in airway closure - small airways, particularl in dependant parts of the lung, collapse and remain closed throughout the respiratory cycle. This results in some alveoli not being ventilated at all (true shunt). Ventilation/perfusion (V/Q) mismatch is also increased. Anaesthesia causes a 15% reduction in metabolic rate and therefore a reduction in oxygen requirements. Artificial ventilation causes a further 6% reduction in oxygen requirements as the work of breathing is removed. Anaesthetic agents do not affect the carriage of oxygen by haemoglobin.

 Static

compliance of lungs and chest wall reduced 15-20% lung is regularly collapsed (atelectasis) at the base of lung during uneventful anaesthesia, can be preventd by PEEP,inc ms tone (ketamine),pacing of diaphragm,double tidal vol,use moderate fraction of O2. Airway closure more prominent in anaesthetized patient. Inhibit hypoxic pulmonary vasoconstriction.

Inspired

oxygen concentration
30% is usually effective in restoring the PaO2 to normal when hypoxaemia is due to hypoventilation.

- An inspired oxygen in the range of 25%-

The small volume of the oxygen stores in the FRC of a patient breathing air means that there will be a rapid fall in oxygen saturation during apnoea (e.g. following induction of anaesthesia, during laryngospasm or during upper airway obstruction). Pre-oxygenation involves the breathing of 100% oxygen for three minutes through an anaesthetic circuit with a face mask firmly applied to the face.. Patients with a small FRC (infants, pregnancy, obesity) or a low haemoglobin concentration and therefore smaller oxygen stores desaturate more rapidly and preoxygenation is especially indicated in these patients

 Resorption

atelectasis appeared in patients given 100% O2. Almost absent in 60% O2 group in a study. By applying CPAP 10 cm H2O,induction of anaesthesia could be done with 100%O2 without substantial atelectasis.

If, during the course of an anaesthetic 100% nitrous oxide is given to the patient in error, the fall in alveolar PO2 will be much more rapid than during apnoea. The alveolar PO2 can fall to dangerously low levels in as little as 10 seconds. This is because the oxygen in the patient's lungs and blood (oxygen stores) is being actively washed out with each breath that contains no oxygen. The fall in PO2 is therefore more rapid than would occur if it was only being used up by the metabolic needs of the body (250ml/min).

 When

managing emergencies during anaesthesia consideration should always be given to the immediate administration of 100% oxygen while the cause is found and rectified. It is the most appropriate treatment for acute deterioration in cardiorespiratory function.

Nitrous oxide is forty times more soluble in blood than nitrogen. When nitrous oxide is discontinued at the end of anaesthesia, nitrous oxide diffuses out of the blood into the alveoli in large volumes during the next 2 - 3 minutes. If the patient is allowed to breathe air at this time the combination of nitrous oxide and nitrogen in the alveoli reduces the alveolar PO2. This is called diffusion hypoxia and is avoided by increasing the inspired concentration of oxygen by the administration of 100% oxygen for 2 - 3 minutes after discontinuing nitrous oxide

Postoperative hypoventilation is common and may be due to the residual effect of anaesthesia, the use of opioid analgesia, pain or airway obstruction. Shivering in the immediate postoperative period causes an increase in oxygen consumption. Additional oxygen should therefore be given to all unconscious patients in recovery and to those awake patients who either shiver, hypoventilate, desaturate or who are considered to be at special risk (eg. ishaemic heart disease).

Thank you