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PULMONARY
CIRCULATION,
HPV
PULMONARY EDEMA
PULMONARY HTN
PLEURAL FLUID.
Comparison of the Pulmonary & Systemic Circulation
PULMONARY
CIRCULATION
 LOW PRESSURE
- because it only needs to pump bl...
Pulmonary Circulation
 P. circulation contain 10% of total blood volume but can easily
altered as much as 50% which is se...
PRESSURES IN THE PULMONARY
SYSTEM
 Right Ventricle:
Systolic= 25 mmHg
Diastolic= 0-1 mmHg,
 Pulmonary artery:
Systolic= ...
Measurement
of pulmonary
blood flow :
FOUR
METHOD
Radio active gases1.
Direct Fick method2.
Indicator –Dilution Method3.
B...
 HYPOXIC pulmonary vasoconstriction (HPV) is a
reflex contraction of vascular smooth muscle small
pulmonary arteries in t...
HPV:-
 Most of response occur locally
 Due to this reflex blood diverted in pulmonary circulation from
less perfuse or c...
The mechanism of
hypoxic pulmonary
vasoconstriction.
Hypoxia causes closure
of voltage-gated
potassium channel,
leading to...
Effects of anesthetics
 The general view is that the inhalational agents inhibit HPV and
intravenous agents do not.
 The...
Other factors
 Inhibition:
 Trauma, vasodialator drugs( nitroprusside, nitroglycerin, nitric oxide,
isoprenaline).
 Vas...
Blood supply of the lungs:
Lungs supplied by:-
Two Circulatory channels:-
 1. Pulmonary vessels(convey deO2 blood to alveolar wall and drain
O2 bloo...
2.Bronchial vessels-
 Bronchial artery :-supplies the lung parenchyma, bronchial glands and
tissue.
 Rt side :- 1 BA ari...
LUNG RECEIVES 2 BLOOD SUPPLIES
From the Left
Ventricle
BRONCHIAL
ARTERIES
Carry oxygenated blood
Blood supplied to the
con...
Ventilation
and
Perfusion
KEY
POINTS
 ALVEOLAR VENTILATION–
(VA)
 ALVEOLAR PERFUSION-
PULMONARY CIRCULATION
(Q)
 VENTILATION – PERFUSION
RATIO (V...
 Normal alveolar ventilation(VA)=4lit/min
 Normal total perfusion=5lit/min.
 V/Q=0.8

 At the base of lung .Blood Flo...
 Def:- Usually measured as a sum of all exhaled gas
volume in one min.(minute ventilation)
Minute Ventilation V = RR x VT...
Ventilation
Dead space ventilation - wasted ventilation
ventilation of unperfused alveoli
Dead space VD = 2ml/kg (Normally...
 Ventilation is unevenly distributed in the lungs.
 Rt lung more ventilated than Lt lung [53% & 47%]
 Due to gravitatio...
Ventilation
-6
-3
-1
Intra pleural pr
Ventilation pattern - VA
•Pleural pressure [Ppl]
increased towards lower zone
•Constricted alveoli in lower
zones & disten...
•Upper zone:
less pleural pressure,
distended more
& hence less compliant
•Lower zone:
more pleural pressure,
less distend...
Pulmonary Perfusion
Due to gravitational influence the lower – dependent areas
receive more blood
Pulmonary blood flow 5l/...
ZONE-I: Only exist if Ppa very low in
hypovolemia / PA in PEEP
ZONE-II: Perfusion α Ppa-PA
arterial-alveolar gradient
ZONE...
VENTILATION PERFUSION
RATIO
Wasted
ventilation
V=normal
Q=0
V/Q=∞
DEAD SPACE
Wasted
Perfusion
V=o
Q= normal
V/Q=0
SHUNT
No...
Respiratory Quotient
 The relationship between the oxygen consumption and the carbon dioxide
production is the Respirator...
Pathophysiology of the ZONES of
the Lungs
 Effect of Exercise:
The blood flow in all parts of the lungs may increase duri...
 MEANS – WASTED PERFUSION
 SHUNT – 1. ABSOLUTE SHUNT : ANATOMICAL SHUNTS – V/Q = 0
2. RELATIVE SHUNT : UNDER VENTILATED ...
 Anatomical shunt-true shunt
 Pathological shunt
 Physiological shunt
 Atelectic shunt
TYPE OF SHUNT
• SHUNTS have different effects on arterial PCO2 (PaCO2 ) than on arterial PO2 (PaO2
).
• Blood passing through under vent...
SHUNT
QUANTIFICATION - SHUNT
1. SHUNT RATIO QS = CCO2-CAO2
QT CCO2-CVO2
• CAO2 = O2 CARRIED BY HB + DISSOLVED O2 IN PLASMA
= 1.3...
DEAD SPACE ( Wasted Ventilation)
 Part of respiratory system which is not taking part in alveolar gas
exchange K/as DEAD ...
Physiological Dead space
 Normal :- 2 ml/kg
 In Intubated pt :- 1.25 ml/kg
Vd(ana)=Vd(phy) –Vd(alv)
Due to Exercise (inc...
Factor affecting Vd(ana)
1. Age and Sex: at infancy 3.3ml/kg and Old age higher
male >female(can be up to 100)
avg 2.2ml/k...
Factor affecting Vd(alv)
 INCRESE BY
1. IPPV
2. Lateral posture in mechanically ventilated patient
3. Decrease pulmonary ...
2. Apparatus Dead Space
 D/t Use of Anaesthetic mask and anaesthetic circuit added in Conduction
zone
 Avg mask and circ...
DEAD
SPACE
DEAD SPACE ESTIMATED AS RATIO VD/VT
1. (BOHR EQ.) VD = PACO2-PECO2
VT PACO2
NORMAL DEAD SPACE RATIO < 33%(20-40...
BLOOD GAS TRANSPOT
General consideration
Ambient Air
O2 = 20.93% = ~ 159 mm Hg PO2
CO2 = 0.03% = ~ 0.23 mm Hg PCO2
N2 = 79.04% = ~ 600 mm Hg ...
Solubility
CO2 is about 25 times more soluble than O2.
CO2 and O2 are both more soluble than N2
Gas Exchange in the Lungs
...
*
 Concentration and Partial Pressure of Respired
Gases
 Partial pressure = Percentage of concentration of specific gas ...
Pressure Differential
 The difference in the pressure of specific gases from the capillary blood to
the alveoli dictates ...
*
Physical Principles of Gas Exchange
 Diffusion of gases through the respiratory membrane
 Depends on membrane’s thickn...
Gas Exchange
External Respiration
 The exchange of gases
 Diffusion between the alveolar air and pulmonary capillary blo...
 The exchange membrane components and organization
Gas Exchange
External Respiration
Gas Exchange
External Respiration
alveolus
pulmonary
capillary
arteriole
end
venule end
PO2 = 40 mm Hg
PCO2 = 46 mm Hg
PO2...
O2 DIFFUSION FROM
INTERSTITIUM TO CELLS
Intracellular PO2 < Interstitial fluid PO2
• O2 constantly utilized by the cells
•...
Gas Exchange
Internal Respiration
systemic
cell
systemic
capillary
arteriole
end
venule end
PO2 = 100 mm Hg
PCO2 = 40 mm H...
Gas Exchange
 What happens when alveolar PO2 drops?
 Solubility rules indicate that
 If PO2 drops, then the amount diss...
Gas Exchange
Hypoxia classifications
Hypoxic
hypoxia
Low arterial PO2
altitude, hypoventilation, lung
diffusion capacity...
Gas Exchange
Hypoxia Problems
1. Not enough O2 in alveoli…
 High elevation
 What about top of Mt. Everest at 29,029 ft A...
Gas Exchange
Hypoxia Problems
2. Interference with alveolar capillary
exchange
 Alveolar air is normal but the exchange
i...
Gas Exchange
Hypoxia Problems
2. Not enough O2 transported in blood (anemia)
• Review causes from prior notes (table 16-3)
23-
63
Oxygen and Carbon Dioxide
Diffusion Gradients
 Oxygen
 Moves from alveoli into
blood. Blood is almost
completely ...
Changes in
Partial
Pressures
Gas Transport
General Process
 Oxygen once in blood
will
 A. remain as dissolved
oxygen
 B. Bind to hemoglobin
(Hb) to ...
Gas Transport
General Process
 TOTAL blood O2 content = quantity dissolved in plasma +
amount bound to Hb (HbO2)
 Why ha...
Gas Transport
Oxygen Summary
Gas Transport
General Process
 O2 in blood quickly associates with hemoglobin (Hb),
forming oxyhemoglobin (HbO2)
 allows...
OXYGEN DELIVERY IN CRITICAL
ILLNESS
• Tissue hypoxia is due to disordered regional
distribution of blood flow • often caus...
THE EFFECTS OF ANAESTHESIA
• The normal protective response to hypoxia is reduced by anaesthetic drugs and this effect ext...
Gas Transport
Carbon Dioxide
 Why be concerned with CO2 transport?
 Transported three ways:
 Dissolved in blood (~7%)
...
INTRODUCTION TO PHSYIOLOGY OF CO2
TRANSPORT
• end-product of aerobic metabolism. – production averages
200 ml/min in resti...
Dissolved carbon dioxide
• Carbon dioxide is 20 times more soluble than oxygen;
• obeys HENRY’S LAW, which states that the...
CO2 Transport as Bicarbonate
 CO2 in solution combines with water to form carbonic acid.
 Carbonic anhydrase
 Zinc-cont...
CO2 BOUND AS HCO3
•Dissolved CO2 in blood reacts with water to form
Carbonic Acid
•CO2 + H2O H2CO3
Carbonic acid dissociat...
CO2 Transport as Carbamino
Compounds
 CO2 reacts directly with amino acid to form carbamino compounds.
 Haldane Effect: ...
Gas Transport
Carbon Dioxide
Important things to
consider!
1. The H+ created
during
bicarbonate ion
formation
2. The trans...
 OXYGEN CASCADE
OXYGEN FLUX
OXYGEN DISSOCIATION CURVE
OXYGEN CARRIAGE BY BLOOD
 In two ways
 Dissolved in plasma.(5%)
 Combination with Hb(95%)
Hemoglobin
 Why is hemoglobin so effective?
 Each subunit of the quaternary
structure has a binding site for
oxygen
 Th...
Gas Transport
Hemoglobin
 Hb structure can vary
 Adult Hb
 The subunits are alpha, beta, gamma, delta
 Most common arr...
OXYHEMOGLOBIN
 One Hb molecule with its 4 heme group is capable of binding 4
molecules of O2.
 1gm of fully oxygenated H...
DISSOLVED OXYGEN
• Henry’s law :states that the concentration of any gas in a
solution is proportional to its partial pres...
 Venous blood have an O2 partial pressure of 40mmHg and Hb is
75% saturated.thus it contains about 15ml of O2/100ml
 1.3...
OXYGEN
CONTEN
T
 Total O2 content of blood is the sum of O2 in the
solution & that carried by Hb.
O2 content
OXYGEN FLUX
 Amount of O2 leaving the left ventricle per minute in the arterial blood .
 O2 content of arterial blood X ...
 Hb : Anaemic Hypoxia
 O2 saturation : Hypoxic Hypoxia
 Cardiac output : Stagnant Hypoxia
Three factors can decrease O2...
 Relates saturation of Hemoglobin (Y axis) to
partial pressure of O2 (X axis)
 It’s a sigmoid shaped curve with a steep ...
 Ferrous iron in each heme binds with one O2
 One Hb molecule can bind 4 molecules of O2
 Deoxy Hb : globin units are t...
CHARACTERISTICS OF
THE CURVE
SHAPE OF THE CURVE
 Characteristic sigmoid shape which offers many physiological advantages
 It reflects the physiologic...
 The flat upper portion means that even if PO2 falls somewhat,
loading of O2 wont be affected much.
 Even when red cells...
The characteristic points on the curve are:
 1) The arterial point
PO2=100mmHg and SO2=97.5%
 2) The mixed venous point
...
The oxygen saturation curve for fetal
hemoglobin (blue) appears left-shifted when
compared to adult hemoglobin (red) since...
 It is the partial pressure at which 50% of Hb is saturated.
 At a pH of 7.4 , temp 37C , the PO2 at which the Hb is 50...
Shift Of ODC
Right shift - High P50 (>27mmHg)
 Hb has decreased affinity for O2
 O2 delivery facilitated at tissue level
Causes:
 In...
Left shift - Low P50 (<27mmHg)
 Hb has ↑ed affinity for O2
 O2 delivery at tissues is decreased
Causes:
 Low H+
 Low t...
Temperature
 Increase in temperature decreases Hb-O2 affinity and curve is
shifted to right
 Decrease in temperature inc...
Hydrogen ions
 Acidosis decreases Hb-O2 affinity and curve is shifted to right
 Deoxy Hb binds with H+ more actively tha...
Carbon dioxide
 Effects attributed to changes in pH
 CO2 + H2O  H2CO3 H + HCO3
 Increase in CO2 shifts curve to right...
2,3 DPG
 Produced in red cells by Embden meyerhof shunt pathway of
glycolysis
 Normal concentration : 4mmol/l
 Binds to...
FACTORS INCREASING 2,3 DPG
 Anaemia
 Hypoxemia
 Cardiac failure
 Chronic acidosis
 Hyperthyroidism
 Uremia
 Cirrhos...
FACTORS DECREASING 2,3 DPG
 Polycythemia
 Hyperoxia
 Chronic alkalosis
 Hypothyroidism
 Blood storage
NB: blood store...
Physiological situations
(1) Exercise
 ODC for skeletal muscles shifted to right
 This ensures max O2 delivery for exerc...
(2) High Altitude
 A s distance from sea level increases , partial pressure of gases in
atmosphere decreases
 But, volum...
 Increased alveolar ventilation
 Increased Hb production
 Increase in 2,3 DPG
 Increase in diffusing capacity of lungs...
Congenital Abnormalities
 Hemoglobinopathies: ODC shifted to right or left depending on affinity of
abnormal Hb to O2
 D...
Carbon Monoxide Poisoning
 Hb has 200 times higher affinity for CO than O2  50% saturated at
0.4mmhg
 Displaces O2 from...
 A/c MI: right shift with an elevated P50
 Hypophosphataemia as occurs in starvation, vomiting, malabsorption etc
causes...
Bohr Effect
• By Christian Bohr in 1904
• The effect of CO2 on the OHDC is known as the
Bohr Effect
• High PCO2 levels and...
 Occurs at feto-maternal interface.
 CO2 & other metabolic products from
the fetal blood diffuses into maternal
blood ma...
DOUBLE BOHR EFFECT
• Reciprocal changes in acid - base balance that occur in maternal & fetal blood in
transit through the...
ODC AND THE ANAESTHESIOLOGIST
 ODC helps us to relate PO2 and Hb saturation
 A left shift gives a warning that tissue oxygen delivery may be
compromis...
 Among other drugs : propranalol , steroids have been found to be
associated with shift to right and improved tissue oxyg...
Diss. Curve - Myoglobin vs. Hemoglobin
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
Ventilation and perfusion
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Ventilation and perfusion

PULMONARY CIRCULATION
DISTRIBUTION OF VENTILATION
BLOOD GAS TRANSPORT

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Ventilation and perfusion

  1. 1. PULMONARY CIRCULATION, HPV PULMONARY EDEMA PULMONARY HTN PLEURAL FLUID.
  2. 2. Comparison of the Pulmonary & Systemic Circulation PULMONARY CIRCULATION  LOW PRESSURE - because it only needs to pump blood to the top of the lungs. - if it is HI pressure, then following Starling forces, the fluid would flood the lungs.  LOW RESISTANCE - only 1/10th of the resistance of the systemic circ. - arterioles have less smooth muscle, veins are wider & shorter & pulmonary vessel walls are thinner.  HIGH COMPLIANCE - accommodates 5 L of blood (same as the systemic circulation) - Accommodates shifts of blood more quickly e.g. when a person shifts from a standing to a lying position SYSTEMIC CIRCULATION  HIGH PRESSURE - B/c it needs to send blood to the brain even when standing & to the tip of en elevated fingertip.  HIGH RESISTANCE - because of increased smooth muscle in the arterioles & the arterial capillary  LOW COMPLIANCE - because of resistance offered by the arterioles and the metarterioles.
  3. 3. Pulmonary Circulation  P. circulation contain 10% of total blood volume but can easily altered as much as 50% which is seen in..  -ve pressure breathing  Supine pressure as compared with up right position  LVF  Any cause of Sys vasoconstriction  Over transfusion
  4. 4. PRESSURES IN THE PULMONARY SYSTEM  Right Ventricle: Systolic= 25 mmHg Diastolic= 0-1 mmHg,  Pulmonary artery: Systolic= 25 mmHg(20-30) Diastolic= 8 mmHg(8-12) Mean Pulmonary arterial pressure= 15 mmHg(12-15)  Pulmonary Vein: Averages about 5 mmHg  Pulmonary capillaries: 7 mm Hg  Left atrium: Mean left atrial pressure 8-15mmHg
  5. 5. Measurement of pulmonary blood flow : FOUR METHOD Radio active gases1. Direct Fick method2. Indicator –Dilution Method3. Body Plethysmography(to measure pul capillary flow) 4.
  6. 6.  HYPOXIC pulmonary vasoconstriction (HPV) is a reflex contraction of vascular smooth muscle small pulmonary arteries in the pulmonary circulation in response to low regional partial pressure of oxygen (PO2). Hypoxic pulmonary vasoconstriction ( Euler-Liljestrand mechanism)
  7. 7. HPV:-  Most of response occur locally  Due to this reflex blood diverted in pulmonary circulation from less perfuse or collapse area to well perfused area to maintain arterial saturation  In normal person 50% of total shift occur with in 2 min and complete after 7 min after occurrence of alveolar hypoxia.  Reflex accentuated by H+ ions concentration.
  8. 8. The mechanism of hypoxic pulmonary vasoconstriction. Hypoxia causes closure of voltage-gated potassium channel, leading to K+ accumulation intracellularly. It leads to depolarization of the cells, opening of voltage-gated calcium channel and calcium- mediated pulmonary vasoconstriction
  9. 9. Effects of anesthetics  The general view is that the inhalational agents inhibit HPV and intravenous agents do not.  The studies done on the same, none are with consistent results.  But it is evident from these studies that both inhalational and intravenous agents inhibit, but inhibition is less in intravenous agents than in inhalational.  Effect of Halothane on HPV is conflicting
  10. 10. Other factors  Inhibition:  Trauma, vasodialator drugs( nitroprusside, nitroglycerin, nitric oxide, isoprenaline).  Vasoconstrictors: which constrict the pulmonary vasculature (noradr, dopamine, histamine) reduces the effectiveness of HPV.  Indirect inhibitors: mitral stenosis, volume overload, hypothermia, thromboembolism, large hypoxic lung segment.
  11. 11. Blood supply of the lungs:
  12. 12. Lungs supplied by:- Two Circulatory channels:-  1. Pulmonary vessels(convey deO2 blood to alveolar wall and drain O2 blood to left side of heart )  The Pulmonary artery (Intrasegmental)emerges from the Right Ventricle, follows the bronchial tree, bifurcates with it and enters the lung. When it reaches the alveoli, it forms a dense network of capillaries like a flowing sheet surrounding the alveoli so that efficient oxygenation of the blood can take place.  The veins that arise carry the oxygenated blood and form the Pulmonary Veins (intersegmental)that take the blood to the Left Atrium.  Pul. Veins use as a landmark to resect a particular segment of lung
  13. 13. 2.Bronchial vessels-  Bronchial artery :-supplies the lung parenchyma, bronchial glands and tissue.  Rt side :- 1 BA arise indirectly from DTA(aorta) either from 3rd posterior intercostal artery(mostly)  Lf side :- 2 BA arise directly from DTA(aorta)  Bronchial veins:-Don’t drain all blood supplied by P. arteries some drain into P. veins.  Superficial Bronchial Veins:-  RT side:- drain in Azygous Vein  LF side :- drain in superior intercostal or ass. Hemi azygous veins  Deep Bronchial Veins:-  Aries as intra pulmonary bronchial plexus and end in main P. vein or Rt atrium
  14. 14. LUNG RECEIVES 2 BLOOD SUPPLIES From the Left Ventricle BRONCHIAL ARTERIES Carry oxygenated blood Blood supplied to the conducting airways, lung interstitium & tissue. From the Right ventricle PULMONARY ARTERIES Carry deoxygenated mixed - venous blood Blood circulates the alveoli to get oxygenated.
  15. 15. Ventilation and Perfusion
  16. 16. KEY POINTS  ALVEOLAR VENTILATION– (VA)  ALVEOLAR PERFUSION- PULMONARY CIRCULATION (Q)  VENTILATION – PERFUSION RATIO (VA/Q)  VENTILATION PERFUSION MISMATCH  SHUNT  DEAD SPACE
  17. 17.  Normal alveolar ventilation(VA)=4lit/min  Normal total perfusion=5lit/min.  V/Q=0.8   At the base of lung .Blood Flow > Ventilation. V/Q=0.63 because ventilation is proportionally low. S/O Shunted Blood  At the top of lung. Blood Flow <Ventilation V/Q=3.3 because here perfusion is about nil. S/O Dead space ventilation  Ventilation and perfusion are both missing S/O Silent Unit REALTION BETWEEN VENTILATION AND PERFUSION IN LUNG
  18. 18.  Def:- Usually measured as a sum of all exhaled gas volume in one min.(minute ventilation) Minute Ventilation V = RR x VT Volume of the inspired gas participating in alveolar gas exchange /minute is called ALVEOLAR VENTILATION-VA  VA = RR x VT-VD Not all inspired gas participating in alveolar gas exchange  DEAD SPACE – VD Ventilation
  19. 19. Ventilation Dead space ventilation - wasted ventilation ventilation of unperfused alveoli Dead space VD = 2ml/kg (Normally 150) Dead space ratio VD/ VT = 33% {BOHR EQUATION} VD = PACO2 – PECO2 VT PACO2 VD = Dead space VT = Tidal volume PaCO2 = Arterial CO2 PETCO2 = End tidal CO2  USE FOR:-approximate alveolar concentration and Co2 tension in expired gases.
  20. 20.  Ventilation is unevenly distributed in the lungs.  Rt lung more ventilated than Lt lung [53% & 47%]  Due to gravitational influence on intra plural pr [decreased 1cm/H2O per 3cm decrease in lung height] lower zones better ventilated
  21. 21. Ventilation -6 -3 -1 Intra pleural pr
  22. 22. Ventilation pattern - VA •Pleural pressure [Ppl] increased towards lower zone •Constricted alveoli in lower zones & distended alveoli in upper zones •More compliant alveoli towards lower zone •Ventilation: distributed more towards lower zone
  23. 23. •Upper zone: less pleural pressure, distended more & hence less compliant •Lower zone: more pleural pressure, less distended, & hence more compliant Ventilation pattern - VA
  24. 24. Pulmonary Perfusion Due to gravitational influence the lower – dependent areas receive more blood Pulmonary blood flow 5l/min Total pulmonary blood volume -500ml to 1000ml These volume going to be spreaded all along the alveolar capillary membrane which has 50 to 100 m² surface area
  25. 25. ZONE-I: Only exist if Ppa very low in hypovolemia / PA in PEEP ZONE-II: Perfusion α Ppa-PA arterial-alveolar gradient ZONE-III: Perfusion α Ppa-Ppv arterial-venous gradient ZONE-IV: Perfusion α Ppa-Pist arterial-interstitial gradient Pulmonary circulation – Alveolar Perfusion Q
  26. 26. VENTILATION PERFUSION RATIO Wasted ventilation V=normal Q=0 V/Q=∞ DEAD SPACE Wasted Perfusion V=o Q= normal V/Q=0 SHUNT Normal V&Q V/Q=1 IDEAL ALVEOLI V VV Q Q Q
  27. 27. Respiratory Quotient  The relationship between the oxygen consumption and the carbon dioxide production is the Respiratory Quotient (RQ).  Normal VCO2: 200 ml/min  Normal VO2: 250 ml/min  RQ is VCO2/VO2  (200 ml/min)/(250 ml/min) or 0.8
  28. 28. Pathophysiology of the ZONES of the Lungs  Effect of Exercise: The blood flow in all parts of the lungs may increase during exercise. In the top of the lungs, the increase may be 700-800% while in the lower parts may be 200-300%. This is because during exercise pulmonary vascular pressures rise enough during the exercise to convert the lung apices from zone 2 to zone 3 pattern of flow.  Zone 1 Blood flow occurs only during Abnormal conditions. Usually this is not seen unless there are 2 condition: - if an upright person is breathing against a positive air pressure and the intra-alveolar air pressure is higher than normal. - in an upright person, pulmonary circulatory pressure is very low as seen after severe blood loss.
  29. 29.  MEANS – WASTED PERFUSION  SHUNT – 1. ABSOLUTE SHUNT : ANATOMICAL SHUNTS – V/Q = 0 2. RELATIVE SHUNT : UNDER VENTILATED LUNGS –V/Q ≤ 1  SHUNT ESTIMATED AS VENOUS ADMIXTURE  VENOUS ADMIXTURE EXPRESSED AS A FRACTION OF TOTAL CARDIAC OUTPUT QS/QT QS = CCO2-CAO2 QT CCO2-CVO2 NORMAL SHUNT- PHYSIOLOGIC SHUNT < 5%(NORMAL SHUNT: 3 TO 5% • SHUNTS ABOVE 15% ARE ASSOCIATED WITH SIGNIFICANT HYPOXEMIA) Q V V/Q<1 SHUNT
  30. 30.  Anatomical shunt-true shunt  Pathological shunt  Physiological shunt  Atelectic shunt TYPE OF SHUNT
  31. 31. • SHUNTS have different effects on arterial PCO2 (PaCO2 ) than on arterial PO2 (PaO2 ). • Blood passing through under ventilated alveoli tends to retain its CO2 and does not take up enough O2. • Blood traversing over ventilated alveoli gives off an excessive amount of CO2, but cannot take up increased amount of O2 because of the shape of the oxygen- hemoglobin (oxy-Hb) dissociation curve. • Hence, a lung with uneven V̇ /q relationships can eliminate CO2 from the over ventilated alveoli to compensate for the under ventilated alveoli. • Thus, with Shunt, PACO2 -to-PaCO2 gradients are small, and PAO2 -to-PaO2 gradients are usually large.  SHUNT
  32. 32. SHUNT
  33. 33. QUANTIFICATION - SHUNT 1. SHUNT RATIO QS = CCO2-CAO2 QT CCO2-CVO2 • CAO2 = O2 CARRIED BY HB + DISSOLVED O2 IN PLASMA = 1.34 X HB% X SAO2 + 0.003 X PAO2 •CcO2-Pulmonary end capillary O2 content •CaO2-Arterial O2 content •CvO2-Mixed venous O2 content
  34. 34. DEAD SPACE ( Wasted Ventilation)  Part of respiratory system which is not taking part in alveolar gas exchange K/as DEAD SPACE (Vd)  TWO TYPE:-  1.Physiological dead space OR Function dead space Some gas remains in the non respiratory airways  ANATOMIC DEAD SPACE Some gas in the non per fused /low per fused alveoli  PHYSIOLOGIC DEAD SPACE 2. Apparatus Dead space
  35. 35. Physiological Dead space  Normal :- 2 ml/kg  In Intubated pt :- 1.25 ml/kg Vd(ana)=Vd(phy) –Vd(alv) Due to Exercise (increase CO) –decrease Vd(phy)-D/t decrease in Vd(alv)
  36. 36. Factor affecting Vd(ana) 1. Age and Sex: at infancy 3.3ml/kg and Old age higher male >female(can be up to 100) avg 2.2ml/kg 2. Depression of lower jaw and flexion of Head : Decreasd by 30 ml 3. Protrusion of jaw and extension of Head: Increased by 40 ml 4. Intubation reduce : 70 ml and tracheostomy 90ml 5. Pneumaectomy ↓ 6. Decreased TV
  37. 37. Factor affecting Vd(alv)  INCRESE BY 1. IPPV 2. Lateral posture in mechanically ventilated patient 3. Decrease pulmonary perfusion 4. Improper Ventilator Setting  Large TV  High Ventilatory Rate  Reduce inspiratory time
  38. 38. 2. Apparatus Dead Space  D/t Use of Anaesthetic mask and anaesthetic circuit added in Conduction zone  Avg mask and circuit volume up to expiatory valve 125 ml .  So always add this dead space to achieve desired TV.
  39. 39. DEAD SPACE DEAD SPACE ESTIMATED AS RATIO VD/VT 1. (BOHR EQ.) VD = PACO2-PECO2 VT PACO2 NORMAL DEAD SPACE RATIO < 33%(20-40%) DRING ANAESTHESIA WITH PASSIVE VENTILATION VD(PHY) CAN BE ROUGHFLY CALCULATED BY COOPER’S FORMULA:- VD/VT=33+AGE/3 % Q V V/Q= ∞
  40. 40. BLOOD GAS TRANSPOT
  41. 41. General consideration Ambient Air O2 = 20.93% = ~ 159 mm Hg PO2 CO2 = 0.03% = ~ 0.23 mm Hg PCO2 N2 = 79.04% = ~ 600 mm Hg PN2 Tracheal Air Water vapor reduces the PO2 in the trachea about 10 mm Hg to 149 mm Hg. Alveolar Air Alveolar air is altered by entry of CO2. Average alveolar PO2 = 103 mm Hg
  42. 42. Solubility CO2 is about 25 times more soluble than O2. CO2 and O2 are both more soluble than N2 Gas Exchange in the Lungs PO2 in alveoli ~ 100 mm Hg PO2 in pulmonary capillaries ~ 40 mm Hg Result: O2 moves into pulmonary capillaries PCO2 in pulmonary capillaries ~ 46 mm Hg Average arterial blood gases equal PO2 100 mm Hg PCO2 40 mm Hg
  43. 43. *  Concentration and Partial Pressure of Respired Gases  Partial pressure = Percentage of concentration of specific gas × Total pressure of a gas  Dalton’s law  Total pressure = Sum of partial pressure of all gases in a mixture Movement of Gas in Air and Fluids  Henry’s law  Gases diffuse from high pressure to low pressure.  Diffusion rate depends upon  Pressure differential  Solubility of the gas in the fluid
  44. 44. Pressure Differential  The difference in the pressure of specific gases from the capillary blood to the alveoli dictates the direction of diffusion.
  45. 45. * Physical Principles of Gas Exchange  Diffusion of gases through the respiratory membrane  Depends on membrane’s thickness, the diffusion coefficient of gas, surface areas of membrane, partial pressure of gases in alveoli and blood  Relationship between ventilation and pulmonary capillary flow  Increased ventilation or increased pulmonary capillary blood flow increases gas exchange  Physiologic shunt is deoxygenated blood returning from lungs
  46. 46. Gas Exchange External Respiration  The exchange of gases  Diffusion between the alveolar air and pulmonary capillary blood  Driven by  partial pressure (P) gradients for O2 and CO2  Solubility of gas which is affected by  Pressure gradient  Solubility coefficient for the particular gas  Temperature  Given the same pressure gradients and temp, O2 will reach equilibrium at a lower dissolved content than will CO2…. Why?
  47. 47.  The exchange membrane components and organization Gas Exchange External Respiration
  48. 48. Gas Exchange External Respiration alveolus pulmonary capillary arteriole end venule end PO2 = 40 mm Hg PCO2 = 46 mm Hg PO2 = 100 mm Hg PCO2 = 40 mm Hg PO2 = 100 mm Hg PCO2 = 40 mm Hg PO2 = 40 mm Hg PCO2 = 46 mm Hg O2 CO2 inspired air expired air
  49. 49. O2 DIFFUSION FROM INTERSTITIUM TO CELLS Intracellular PO2 < Interstitial fluid PO2 • O2 constantly utilized by the cells • Cellular metabolic rate determines overall O2 consumption N intracellular req for optimal maintenance of metabolic pathways ~ 3 mm Hg Pasteur point – critical mitochondrial PO2 below which aerobic metabolism cannot occur 0.15 – 0.3 kPa = 1.4 – 2.3mmHg
  50. 50. Gas Exchange Internal Respiration systemic cell systemic capillary arteriole end venule end PO2 = 100 mm Hg PCO2 = 40 mm Hg PO2 = 40 mm Hg PCO2 = 46 mm Hg PO2 = 40 mm Hg PCO2 = 46 mm Hg PO2 = 100 mm Hg PCO2 = 40 mm Hg O2 CO2
  51. 51. Gas Exchange  What happens when alveolar PO2 drops?  Solubility rules indicate that  If PO2 drops, then the amount dissolved in blood also drops!  Creating a hypoxic condition  Factors that may cause low arterial PO2 1. Not enough O2 reaching alveoli 2. Exchange between alveoli and pulmonary capillaries has a problem 3. Not enough O2 transported in blood
  52. 52. Gas Exchange Hypoxia classifications Hypoxic hypoxia Low arterial PO2 altitude, hypoventilation, lung diffusion capacity, altered ventilation-perfusion ratio, asthma Ischemic hypoxia Hypoxia from reduction in blood flow heart failure (systemic anemia), shock (peripheral hypoxia), thrombosis (single organ hypoxia) Anemic hypoxia Total O2 bound to Hb hemorrhage, low Hb, CO poisoning, altered Hb binding Histotoxic hypoxia cells being poisoned, and can’t use O2 Cyanide, H2S, alcohol, narcotics
  53. 53. Gas Exchange Hypoxia Problems 1. Not enough O2 in alveoli…  High elevation  What about top of Mt. Everest at 29,029 ft Atmospheric pressure = 30kPa or 225 mm Hg  PO2 then must be 47.25 mm Hg  A nearly 71% decrease in available oxygen in the blood!  To compensate ventilations increase from 15 per minute to between 80-90 ventilations per minute
  54. 54. Gas Exchange Hypoxia Problems 2. Interference with alveolar capillary exchange  Alveolar air is normal but the exchange isn’t  Caused by  Less surface area for exchange (b)  Increased thickness of alveolar membrane (c)  Increased distance between alveolar membrane and capillary membrane (d)
  55. 55. Gas Exchange Hypoxia Problems 2. Not enough O2 transported in blood (anemia) • Review causes from prior notes (table 16-3)
  56. 56. 23- 63 Oxygen and Carbon Dioxide Diffusion Gradients  Oxygen  Moves from alveoli into blood. Blood is almost completely saturated with oxygen when it leaves the capillary  P02 in blood decreases because of mixing with deoxygenated blood  Oxygen moves from tissue capillaries into the tissues  Carbon dioxide  Moves from tissues into tissue capillaries  Moves from pulmonary capillaries into the alveoli
  57. 57. Changes in Partial Pressures
  58. 58. Gas Transport General Process  Oxygen once in blood will  A. remain as dissolved oxygen  B. Bind to hemoglobin (Hb) to make HbO2
  59. 59. Gas Transport General Process  TOTAL blood O2 content = quantity dissolved in plasma + amount bound to Hb (HbO2)  Why have hemoglobin?  To ensure enough systemic O2!  Dissolved oxygen content in blood volume  15 ml O2/min reaching the systemic tissues  O2 requirement at rest = ~250 ml O2/min  Oxygen bound to hemoglobin, allows the total amount of oxygen in the blood to exceed 250 ml O2/min
  60. 60. Gas Transport Oxygen Summary
  61. 61. Gas Transport General Process  O2 in blood quickly associates with hemoglobin (Hb), forming oxyhemoglobin (HbO2)  allows for blood to carry an extra 985 ml of oxygen/min in an average blood volume of 5L  Dissolved = 15ml O2/min transported  Associated with Hb = 985 ml O2/min  Total Oxygen carrying capacity = 1000ml/min or 1L/min  4x’s greater than “at rest” demand
  62. 62. OXYGEN DELIVERY IN CRITICAL ILLNESS • Tissue hypoxia is due to disordered regional distribution of blood flow • often caused by capillary microthrombosis after endothelial damage and neutrophil activation rather than by arterial hypoxaemia OXYGEN STORES • o2 stores are limited to lung and blood. • The amount of O2 in the lung is dependent on the FRC and the alveolar concentration of oxygen. • Breathing 100% oxygen causes a large increase in the total stores as the FRC fills with oxygen • This is the reason why pre-oxygenation is so effective.
  63. 63. THE EFFECTS OF ANAESTHESIA • The normal protective response to hypoxia is reduced by anaesthetic drugs and this effect extends into the post- operative period. Following induction of anaesthesia : • FRC ↓ • V/Q mismatch is ↑ed • Atelectasis develops rapidly • This 'venous admixture' increases from N 1% to around 10% following induction of anaesthesia. Volatile anaesthetic agents suppress hypoxic pulmonary vasoconstriction. • Many anaesthetic agents depress CO and therefore ↓ O2 delivery. • Anaesthesia causes a 15% ↓ in metabolic rate and therefore a reduction in oxygen requirements. • Artificial ventilation causes a further 6% ↓ in oxygen requirements as the work of breathing is removed.
  64. 64. Gas Transport Carbon Dioxide  Why be concerned with CO2 transport?  Transported three ways:  Dissolved in blood (~7%)  Converted to bicarbonate ions (~70%)  Attaches to Hb (~23%)  CO2 + Hb ↔ Hb·CO2(carbaminohemoglobin)
  65. 65. INTRODUCTION TO PHSYIOLOGY OF CO2 TRANSPORT • end-product of aerobic metabolism. – production averages 200 ml/min in resting adult – During exercise this amount may increase 6x • Produced almost entirely in the mitochondria. • Importance of co2 elimination lies in the fact that -Ventilatory control system is more responsive to PaCO2 changes.
  66. 66. Dissolved carbon dioxide • Carbon dioxide is 20 times more soluble than oxygen; • obeys HENRY’S LAW, which states that the number of molecules in solution is proportional to the partial pressure at the liquid surface. PCO2 x S = CO2 conc in sol S = Solubility Coefficient Value dependant upon temp (inversely proportional) more temp lesser amount of CO2 dissolved. • The carbon dioxide solubility coefficient is 0.69 ml/L/mm Hg at 37C. • In absolute terms only 0.3 ml of CO2/dL transported in dissolved form • During heavy exercise contribution of dissolved CO2 can 7 fold 1/3 of total CO2 exchange
  67. 67. CO2 Transport as Bicarbonate  CO2 in solution combines with water to form carbonic acid.  Carbonic anhydrase  Zinc-containing enzyme within red blood cell  Carbonic acid ionizes into hydrogen ions and bicarbonate ions.
  68. 68. CO2 BOUND AS HCO3 •Dissolved CO2 in blood reacts with water to form Carbonic Acid •CO2 + H2O H2CO3 Carbonic acid dissociates into H+ & HCO3 When conc of these ions increase in RBCs, HCO3 diffuses out but H+ can’t easily do this because cell memb is relatively impermeable to cations. Thus to maintain electrical neutrality, Cl ions move into cell from plasma CHLORIDE SHIFT
  69. 69. CO2 Transport as Carbamino Compounds  CO2 reacts directly with amino acid to form carbamino compounds.  Haldane Effect: Hb interaction with O2 reduces its ability to combine with CO2.  This aids in releasing CO2 in the lungs.
  70. 70. Gas Transport Carbon Dioxide Important things to consider! 1. The H+ created during bicarbonate ion formation 2. The transport of HCO3 - out of the cell occurs with the movement of Cl- into the cell called the chloride shift Both must reverse in the lungs!
  71. 71.  OXYGEN CASCADE OXYGEN FLUX OXYGEN DISSOCIATION CURVE
  72. 72. OXYGEN CARRIAGE BY BLOOD  In two ways  Dissolved in plasma.(5%)  Combination with Hb(95%)
  73. 73. Hemoglobin  Why is hemoglobin so effective?  Each subunit of the quaternary structure has a binding site for oxygen  The heme group of each subunit contains a prophyrin ring with an iron atom (Fe2+) a the center  This Fe2+ reversibly binds O2 in accordance with the law of mass action  Typically PO2 drives this reaction
  74. 74. Gas Transport Hemoglobin  Hb structure can vary  Adult Hb  The subunits are alpha, beta, gamma, delta  Most common arrangement is 2 alpha, and 2 beta units (HbA) >95%  Also some where:  2 alpha & 2 delta subunits present (HbA2) ~2.5%  2 alpha & 2 gamma subunits present (HbF) rare  Fetal Hb (HbF)  Gamma chains in place of the beta chains.  Creates Hb molecules with a higher affinity for oxygen Hydroxyurea treatment in adults with sickle cell anemia stimulates development of more HbF than HbA
  75. 75. OXYHEMOGLOBIN  One Hb molecule with its 4 heme group is capable of binding 4 molecules of O2.  1gm of fully oxygenated Hb contains 1.34ml of O2 (vary depending on Fe content)  At an arterial PO2 of 100mmHg,Hb is 98% saturated,thus 15gm of Hb in 100ml blood will carry about 20ml of O2  =1.34ml x 15gm x 98/100=20
  76. 76. DISSOLVED OXYGEN • Henry’s law :states that the concentration of any gas in a solution is proportional to its partial pressure • Gas concentration= x partial pressure  is the gas solubility coefficient =0.003ml/dl(100ml of blood)/mmHg for O2 • Dissolved O2 in arterial blood is thus 0.3ml/dl (0.003ml/dl x100mmHg).
  77. 77.  Venous blood have an O2 partial pressure of 40mmHg and Hb is 75% saturated.thus it contains about 15ml of O2/100ml  1.34x15x75/100=15  Thus every 100ml of blood passing through the lungs will take up 5ml of O2
  78. 78. OXYGEN CONTEN T  Total O2 content of blood is the sum of O2 in the solution & that carried by Hb. O2 content
  79. 79. OXYGEN FLUX  Amount of O2 leaving the left ventricle per minute in the arterial blood .  O2 content of arterial blood X cardiac output  O2 content of arterial blood = (O2 bound to Hb + dissolved O2)  i.e 20ml+0.3ml=20.3ml/dl(20.3ml/100ml)  So O2 flux=20.3ml/100ml X 5000ml=1000ml
  80. 80.  Hb : Anaemic Hypoxia  O2 saturation : Hypoxic Hypoxia  Cardiac output : Stagnant Hypoxia Three factors can decrease O2 Flux
  81. 81.  Relates saturation of Hemoglobin (Y axis) to partial pressure of O2 (X axis)  It’s a sigmoid shaped curve with a steep lower portion and flat upper portion  Describes the nonlinear tendency for O2 to bind to Hb. O2 DISSOCIATION CURVE(ODC)
  82. 82.  Ferrous iron in each heme binds with one O2  One Hb molecule can bind 4 molecules of O2  Deoxy Hb : globin units are tightly bound in a tense configuration (T state)  As first molecule of O2 binds, it goes into a relaxed configuration (R state) thus exposing more O2 binding sites  500 times increase in 02 affinity  characteristic sigmoid shape of ODC
  83. 83. CHARACTERISTICS OF THE CURVE
  84. 84. SHAPE OF THE CURVE  Characteristic sigmoid shape which offers many physiological advantages  It reflects the physiological adaptation of Hb to take up O2 at higher partial pressures (alveoli) and release oxygen at lower partial pressures (tissues )
  85. 85.  The flat upper portion means that even if PO2 falls somewhat, loading of O2 wont be affected much.  Even when red cells take up most of the O2 from alveoli , PO2 drop is less compared to gain in saturation  a large PO2 difference still exists for diffusion of O2 to continue  The steep lower part of the curve means peripheral tissues can withdraw large amounts of 02 for only a small drop in capillary PO2.  This maintenance of blood PO2 assists diffusion of 02 into tissue cells
  86. 86. The characteristic points on the curve are:  1) The arterial point PO2=100mmHg and SO2=97.5%  2) The mixed venous point PO2=40mmHg and SO2=75%  3) The P50 PO2=27mmHg and SO2=50% ANCHOR POINTS IN THE CURVE
  87. 87. The oxygen saturation curve for fetal hemoglobin (blue) appears left-shifted when compared to adult hemoglobin (red) since fetal hemoglobin has a greater affinity for oxygen
  88. 88.  It is the partial pressure at which 50% of Hb is saturated.  At a pH of 7.4 , temp 37C , the PO2 at which the Hb is 50% saturated (P50) is 27mmHg  When affinity of Hb for 02 is increased , P50 decreases : shift to left in ODC  When affinity is reduced , P50 increases : shift to right in ODC P50
  89. 89. Shift Of ODC
  90. 90. Right shift - High P50 (>27mmHg)  Hb has decreased affinity for O2  O2 delivery facilitated at tissue level Causes:  Increase in H+  Increase in temperature  Increase in 2,3 DPG  Increase in PCO2  Exercise  Anaemia  Drugs : propranalol , digoxin etc
  91. 91. Left shift - Low P50 (<27mmHg)  Hb has ↑ed affinity for O2  O2 delivery at tissues is decreased Causes:  Low H+  Low temperature  Low 2,3 DPG  Low PCO2  Variants of normal Hb (fetal Hb, carboxy Hb, met Hb)
  92. 92. Temperature  Increase in temperature decreases Hb-O2 affinity and curve is shifted to right  Decrease in temperature increases affinity and curve shifted to left  decreased release of O2  But this wont cause hypoxia because in hypothermia body O2 demand is also less FACTORS AFFECTING ODC
  93. 93. Hydrogen ions  Acidosis decreases Hb-O2 affinity and curve is shifted to right  Deoxy Hb binds with H+ more actively than does oxy Hb  H+ + HbO2  H.Hb +O2  Advantageous at tissue level
  94. 94. Carbon dioxide  Effects attributed to changes in pH  CO2 + H2O  H2CO3 H + HCO3  Increase in CO2 shifts curve to right causing more release of O2  BOHR EFFECT
  95. 95. 2,3 DPG  Produced in red cells by Embden meyerhof shunt pathway of glycolysis  Normal concentration : 4mmol/l  Binds to deoxyHb and reduces its affinity for O2  ODC is shifted to right  Fetal erythrocytes have lower concn of 2,3 DPG and hence HbF has a higher affinity for O2
  96. 96. FACTORS INCREASING 2,3 DPG  Anaemia  Hypoxemia  Cardiac failure  Chronic acidosis  Hyperthyroidism  Uremia  Cirrhosis liver
  97. 97. FACTORS DECREASING 2,3 DPG  Polycythemia  Hyperoxia  Chronic alkalosis  Hypothyroidism  Blood storage NB: blood stored with ACD anticoagulant loses 2,3 DPG faster (6-7 days) than CPD blood. Effect starts immediately after transfusion and may last for 2-3 days
  98. 98. Physiological situations (1) Exercise  ODC for skeletal muscles shifted to right  This ensures max O2 delivery for exercising muscles  Factors : Increased CO2 production Increased Temperature Presence of myoglobin (higher O2 affnity) Other conditions affecting ODC
  99. 99. (2) High Altitude  A s distance from sea level increases , partial pressure of gases in atmosphere decreases  But, volume remains constant eg: 21% for O2  Leads to a progressive reduction in ambient O2  Hypoxia  Compensatory mechanisms  net effect is right shift of ODC
  100. 100.  Increased alveolar ventilation  Increased Hb production  Increase in 2,3 DPG  Increase in diffusing capacity of lungs  Increase in vascularity of tissues  Increase cellullar use of 02
  101. 101. Congenital Abnormalities  Hemoglobinopathies: ODC shifted to right or left depending on affinity of abnormal Hb to O2  Deficiency of red cell metabolism Pyruvate kinase deficiency : shift to right d/t elevated 2,3 DPG levels
  102. 102. Carbon Monoxide Poisoning  Hb has 200 times higher affinity for CO than O2  50% saturated at 0.4mmhg  Displaces O2 from Hb  Increases O2 affinity of those hemoglobin unbound to CO  Together it produces a shift to left in ODC and over all decrease in 02 delivery
  103. 103.  A/c MI: right shift with an elevated P50  Hypophosphataemia as occurs in starvation, vomiting, malabsorption etc causes increased Hb-O2 affinity and shift ODC to left
  104. 104. Bohr Effect • By Christian Bohr in 1904 • The effect of CO2 on the OHDC is known as the Bohr Effect • High PCO2 levels and low pH decrease affinity of hemoglobin for oxygen (a right-ward shift). • This occurs at the tissues where a high level of PCO2 and acidemia contribute to the unloading of oxygen.
  105. 105.  Occurs at feto-maternal interface.  CO2 & other metabolic products from the fetal blood diffuses into maternal blood making maternal blood more acidic & fetal blood more alkaline. DOUBLE BOHR EFFECT
  106. 106. DOUBLE BOHR EFFECT • Reciprocal changes in acid - base balance that occur in maternal & fetal blood in transit through the placenta FETAL BLOOD MATERNAL BLOOD Loss of CO2 Gain of CO2 Rise in pH Fall in pH Leftward shift of ODC Rightward shift of ODC
  107. 107. ODC AND THE ANAESTHESIOLOGIST
  108. 108.  ODC helps us to relate PO2 and Hb saturation  A left shift gives a warning that tissue oxygen delivery may be compromised even when there is not much drop in PO2  All inhalational agents including N2O causes shift to right  Intravenous agents have no demonstrable effect on ODC
  109. 109.  Among other drugs : propranalol , steroids have been found to be associated with shift to right and improved tissue oxygenation  Blood transfusion : whenever possible, ACD anticoagulated fresh blood (<5-7 days old) should be used and avoid massive transfusions.
  110. 110. Diss. Curve - Myoglobin vs. Hemoglobin

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