By Adam Hollingworth 7.Gas Transport - 1 7.Gas Transport Table of Contents Oxygen Transport ................................................................................................................................................ 2 O2 Dissociation Curve ........................................................................................................................................ 2 The Curve ...............................................................................................................................................................................................3 Position of the Curve.........................................................................................................................................................................3 2,3 Diphosphoglycerate..................................................................................................................................... 4 Nb Extreme Altitude..........................................................................................................................................................................5 Carbon Monoxide (CO) effect on O2 Dissociation Curve .................................................................................... 5 Cyanosis .............................................................................................................................................................................. 5 Anaemia .............................................................................................................................................................................. 5 Calculations ....................................................................................................................................................................... 5 Henry’s Solubility Law ....................................................................................................................................... 6 Oxygen Flux Equation ........................................................................................................................................ 6 Carbon Dioxide ..................................................................................................................................................... 7 CO2 Movement At Tissue Level ................................................................................................................................... 8 Co2 & O2 Movement in Pulmonary Capillaries...................................................................................................... 9 CO2 Dissociation Curve ............................................................................................................................................... 10 CO2 Stores in Blood ...................................................................................................................................................... 11 O2 Stores in body .......................................................................................................................................................... 11 Acid Base Status .................................................................................................................................................11 Respiratory Acidosis.................................................................................................................................................... 12 Respiratory Alkalosis .................................................................................................................................................. 12 Metabolic Acidosis ........................................................................................................................................................ 12 Metabolic Alkalosis ...................................................................................................................................................... 12 BloodTissue Gas Exchange ............................................................................................................................13 Tissue Hypoxia ...................................................................................................................................................13 Hypoxaemic Hypoxia ................................................................................................................................................... 13 Anaesthetic Causes of Severe Hypoxia .......................................................................................................14 Summary ..............................................................................................................................................................15
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By Adam Hollingworth
7.Gas Transport - 1
7.Gas Transport Table of Contents
Oxygen Transport ................................................................................................................................................ 2 O2 Dissociation Curve ........................................................................................................................................ 2
The Curve ............................................................................................................................................................................................... 3 Position of the Curve ......................................................................................................................................................................... 3
2,3 Diphosphoglycerate ..................................................................................................................................... 4 Nb Extreme Altitude .......................................................................................................................................................................... 5
Henry’s Solubility Law ....................................................................................................................................... 6 Oxygen Flux Equation ........................................................................................................................................ 6
Carbon Dioxide ..................................................................................................................................................... 7 CO2 Movement At Tissue Level ................................................................................................................................... 8 Co2 & O2 Movement in Pulmonary Capillaries ...................................................................................................... 9 CO2 Dissociation Curve ............................................................................................................................................... 10 CO2 Stores in Blood ...................................................................................................................................................... 11 O2 Stores in body .......................................................................................................................................................... 11
Anaesthetic Causes of Severe Hypoxia ....................................................................................................... 14 Summary .............................................................................................................................................................. 15
By Adam Hollingworth
7.Gas Transport - 2
Oxygen Transport • O2 carried in 2 forms: O Dissolved 1-2% (small amount but functionally v impt)
• Combined with Hb 98-99% • Dissolved O2 • Obeys Henry’s Law = amount dissolved ∝ to partial pressure
! 1mmHg PO2 contains 0.003ml O2/100mls ! ∴ norm arterial blood with PaO2 of 100mHg contains 0.3ml dissolved O2/100mls
• ∴ 0.003ml O2 will be desolved in each 100ml blood/mmHg PO2 Combined with Haemoglobin • Normal Hb = A • Hb F & HbS also exist ! causes curve shift to R & unstable Hb in deoxygenated form ⇒ sickle ↳ causes L shift • Follows classic O2 dissociation curve
O2 Dissociation Curve • OHDC relates PO2 with % Spo2 (and O2 content) • 1 Haem group can bind reversibly with 1 O2 molecule ⇒ 1 Hb can bind 4 O2 molecules • relationship between PO2 & SPo2 is S shaped:
o reaction of each of the 4 subunits of Hb with O2 occurs sequentially o each reaction facilitates the next:
! 1st O2 binding is difficult but this then facilitates binding of molecules 2 then 3 ! = positive cooperativity ! is why myoglobin does not have S shaped curve
! 4th molecule binding is more difficult again due to crowding of molecule & natural tendency of O2 to dissociate
o O2 continues to combine with Hb as PO2 increases ! As limit of O2 which can be bound is reached curve flattens out as little binding occurring
• Change in Hb from oxygenated to deoxygenated state involves conformational change in molecule • Oxygenated state = R state (relaxed) • Deoxygenated state = T (tense)
By Adam Hollingworth
7.Gas Transport - 3
• Useful points on curve: o Arterial point = PO2 100mg with SaO2 97.5 (CaO2 = 20mlO2/dl) o Mixed venous point= 40mmHg with SaO2 75% (CvO2 = 15mlO2/dl) o P50 = PO2 26.6mmHg with Sao2 50% o ICU Point = PO2 ∼60mmHg with SpO2 low 90’s
! slippery slope of the curve • NB venous point never actually lies on the normal OHDC
! will be R shifted due to ↑PCO2 & ↑H+ ie the Bohr Effect
The Curve • Several physiological advantages:
o Top plateau = ! A buffer: even if Po2 falls, small effect on loading of Hb
! useful in lungs to keep arterial Hb Sats high ! maintenance of large partial pressure gradient exists to drive O2 diffusion out of alveolar
space ⇒ blood ! blood has a high affinity for O2 & will thus tend to drop PO2 (∴ helping to maintain diffusion gradient)
o steep lower part: ! periph tisues can withdraw large amounts of O2 for only small drop in capillary PO2
! ∴ pressure gradient for diffusion capillary ⇒ cell maintained despite O2 extraction from blood Position of the Curve P50 • = PO2 which oxygen carrying protein (Hb or myoglobin) is 50% saturated • most sensitive point to detect a curve shift • p50 values:
o HbA = 26.6 o HbF = 18 o Myoglobin = 2.75
• Right shift of curve = o Results in
! ↓ed O2 affinity of Hb AND ! ↑unloading of O2 in capillary at any given PO2
o Causes: ! ↓pH ie ↑PCO2 or ↑H+:
By Adam Hollingworth
7.Gas Transport - 4
• PCO2 acts on H+ ⇒ change in pH ! called Bohr Effect
! ↑temp ! ↑conc of 2-3DPG:
! occurs in chronic hypoxia eg lung disease or high altitude ! to remember exercising mm is acid, hypercarbic & hot and needs O2 to unload into mm
• Left shift of curve: (↑affinity for O2, better loading of O2) o ↓temp o ↓PCO2 & ↓H o ↓2,3 DPG o HbF o ↑CO (carbon monoxide)
2,3 Diphosphoglycerate • Produced by a side shunt (Rapoport-Leubering shunt) from the glycolytic pathway • Present in large quantities in rbcs • Binds with ß chains of Hb ⇒ change in protein conformation ⇒ ↓O2 affinity • ∴ ↑2,3 DPG ⇒ ↑ unloading of O2 form Hb • binds poorly to gamma chains of HbF (hence L shift f HbF) • factors ↑ing 2,3DPG:
o anaemia o chronic hypoxia o altitude o alkalosis o exercise o pregnancy o hyperthyroidism o some rbc enzyme abnormalities
• factors ↓ing 2,3 DPG: o acidosis eg stored blood (12-24 hrs for levels to restore) o hypothyroid o hypopituitarism o phyophosphataemia
By Adam Hollingworth
7.Gas Transport - 5
Nb Extreme Altitude • competing forces on OHDC:
o altitude ⇒ ↑ 2,3 DPG ⇒ R shift ie more unloading of O2 o hypoxic environment ⇒ hyperventilation ⇒ ↓CO2 ⇒ L shift ie more loading
! overwhelming hypocarbia higher force than ↑2,3DPG ⇒ NET L shift ! beneficial to prevent hypoxaemia
Carbon Monoxide (CO) effect on O2 Dissociation Curve • CO x240 higher affinity for Hb than O2
! need PaCO2 x240 lower for CO & O2 to combine with same amount of Hb • CO dissociation curve same shape as O2 except x axis (PaCO2) greatly compressed
! at physiological values curve generally linear • Small amounts of CO can tie up large proportion of Hb in blood causing:
o Less Hb available for O2 carraige o PO2 blood normal o O2 concentration greatly reduced as capacity of Hb ↓’ed o O2 curve shift to L ⇒ ↓unloading of O2 at tissues
Cyanosis • Deoxygenated Hb looks purple ⇒cyanosis
! anaemia – often no cyanosis polycythaemia – marked cyanosis Anaemia • If plotting O2 content & Hb Saturations on OHDC then need to take into account anaemia • The same PO2 in with different levels of Hb will obviously give you different O2 concentrations BUT
the same saturation:
Calculations • O2 + Hb ⇒ HbO2 reversible • Max amount of O2 which can be combined wih Hb = O2 capacity
! reached when all the Hb binding sites are occupied by O2 • O2 capacity =
o 1g of Hb can combine with 1.39ml O2 o ∴ to calculate 1.39 x 15g of Hb = 20.8ml O2/100ml blood
! ∴ if anaemia of 10g Hb capacity = 1.39 x 10 = 13.9
• O2 saturation of Hb = percentage of available binding sites which have O2 attached ! calculated by:
By Adam Hollingworth
7.Gas Transport - 6
SpO2= O2 combined with Hb
O2 capacity x100
• Impt to distinguish difference between: o PO2 = amount dissolved in plasma (Henrys Law) o O2 saturation = % binding sites on Hb which have O2 attached o O2 concentration = total amount of O2/100mls of blood
(! = Spo2 + dissolved) • Oxygen concentration (or content) of blood: (ml O2/100ml blood) CBO2 (mlO2/100ml blood) (1.39 x Hb x SpO2) + (0.003 x PO2)
100 Where: • Hb – gm/100ml • Po2 mmHg] • B = content in Blood - but can be more specific ie arterial, venous, mixed venous Henry’s Solubility Law O2 is dissolved in plasma according to Henry’s Law: • At a given temp, the amount of given gas dissolved in a given liquid is directly proportional to partial
pressure of the gas in quilibrium with the liquid • Amount of O2 dissolved = 0.003ml O2/mmHg x PO2/100mls of blood • ∴ at atmospheric pressures = around 0.3mlO2/100ml or 3ml O2/litre ↳ (20.93/100) x 713 = 149 (equation to account for pressure) ↳ 149 x 0.003 = 0.44 ie around 0.3) ↳ = 1.5% of total O2 in body • Small amount physiologically very impt:
o Its the dissolved O2 which difuses through interstitial & intracellular fluid � mitochondria o This dissolved fraction exerts tension for diffusion
• @Fio2 100% need to work out dissolved O2: o 100/100 x 713 = 713 o 0.003 x 713 (ie pressure) = 2.139mlo2/100ml
• @Fio2 100% and 3 atmospheres: o 100/100 x (713 x3) = 2139 pressures o 0.003 x 2139 = 6.417 ml O2/100mls
↳ this is sufficient for a-v extraction (= around 5ml O2/100mls)
Oxygen Flux Equation • O2 flux equation:
DO2 = CaO2 x CO
CaO2 = O2 content/100mls CO = Cardiac output • Normal DO2 = 1000ml O2/min • =x4 resting VO2 (O2 consumption) of 250ml O2/min
By Adam Hollingworth
7.Gas Transport - 7
Carbon Dioxide • CO2 produced in mitochondria • Exists a series of tension gradients as it moves mitchon ⇒ cytoplasm ⇒ ECF ⇒ blood ⇒ lungs • Arterial blood CO2 content = 48mlCO2/100ml • Mixed venous blood = 52ml Co2/100ml Arterial Content • Carried in arterial blood in 3 forms:
o Bicarbonate – majority ~45ml/dl o carbamino compounds - in combination with proteins ~2.5ml/dl o Dissolved – least ~2.5ml/dl o Carbonic acid <1%)
Venous Content • Content in venous:
o Bicarbonate ~ 47.5ml/dl o Carbamino compounds 3.5ml/dl o Dissolved 10% - ~3ml CO2/dl
Dissolved CO2 • Obeys Henry’s law but CO2 x20 more soluble than O2
! ∴ 0.066 Co2/100mls (ie 0.003 x20) • ↑solubility means dissolved gas plays ↑ed role in transport
! 10% gas extruded from lung in dissolved form in blood
By Adam Hollingworth
7.Gas Transport - 8
CO2 Movement At Tissue Level Bicarbonate • bicarbonate formed by CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3- Carbonic anhydrase
• CO2 from mitochondria diffuse by partial pressure gradient: o ⇒ interstial fluid ⇒ across capillary wall ⇒ blood plasma o different pathways:
! dissolve in plasma ! dissolve in rbc ! [MOST]:
• carbamino compounds OR • bicarbonate – (can occur in plasma or rbc)
• 1st reaction (creation of H2CO3)= o slow in plasma o fast in rbc with help of carbonic anyhdrase
• 2nd reaction (dissociation of H2CO3) = fast without enzyme ! = ionic dissociation of carbonic acid
• chloride shift: o occur when ions H+ & H2CO3
- accumulate in rbc o HCO3- diffuses out o H+ unable to diffuse out as membrane blocks this cation
! must be buffered in cell o To maintain elec neutral Cl- moves into cell
! chloride shift o events assoc with uptake of CO2 by blood ⇒ ↑osmolar content of rbc ⇒ water influx to rbc ⇒ ↑volume or rbc
! in lungs rbcs loose water and shrink • due to chloride shift venous blood has higher
o HCT o MCV o Cl
• Some H+ ions are bound to Hb ⇒ reduced Hb & release of O2: H+ + HbO2 ↔ H+ ·Hb + O2
o This occurs as reduced Hb is less acid than oxygenated form !ie a better proton acceptor
o ∴ presence of reduced Hb in periph blood aids with loading of Co2 ! and opposite in lungs try – oxygenation of Hb assists with CO2 unloading
o = Haldane effect ie deoxygenation of blood aids ability to carry CO2 Carbamino Compounds • in blood: carbamates made by CO2 & terminal amide groups of blood proteins
! also with amino gps in side chains of arginine & lysine • Hb is more important than plasma proteins in formation of carbaminos due to:
o numbers: ! Hb 15g/dl ! Plasma proteins 7g/dl
o Haldane effect: As Hb is reduced (deoxygenated) it can bind more CO2 in the form of carbamino-Hb than oxygenated Hb
! ∴ again unloading of O2 in perpih tissues facilitates loading of CO2
By Adam Hollingworth
7.Gas Transport - 9
o Structure of plasma proteins allows less carbamino formation • most impt protein is the globin of Hb:
Hb ·NH2 + CO2 ↔ Hb · NH · COOH • result is carbamino-Hb • reaction rapid with no enzyme Haldane Effect • = ↑ed capacity of deoxygenated blood for CO2 transport compared with oxygenated blood • effect due to:
o 70% - deoxy-Hb = x3.5 more effective in forming carbamino compounds (as above) o 30% - deoxy-Hb better buffer than oxy-Hb:
! dexoy-Hb better at ‘mopping up’ of H+ from dissociation of H2CO3 ! this improves carriage of CO2 as bicarbonate
! at physiological pH: imidazole gps in 38 histidine residues in Hb which account for ↑ed buffering
Co2 & O2 Movement in Pulmonary Capillaries • reverse of process in capillaries • PCO2 of venous blood > alveolar PCO2 (46mmHg : 40mmHg) • CO2 diffusion from rbc ⇒ alveolus ! ∴ is a partial pressure gradient all way from tissue mitochondrium to alveoli • Equilibrium achieved between CO2 creation and need for lungs to ventilate to change alveolar PCO2
to drive partial pressure gradient. This defined as:
Alveolar PCO2 = VCO2 / alveolar ventilation
VCO2 = creation of CO2 or output of CO2 from blood • @ end of pulmonary capillary blood PCO2 ~ PCO2 or alveolar gas
! due to rapid diffusability of CO2 ! ie PaCO2 ~ PACO2
• O2 diffuses in opposite direction ⇒ rbc • Loss of CO2 from rbc enhances O2 uptake (Bohr Effect – L shift of OHDC)
By Adam Hollingworth
7.Gas Transport - 10
CO2 Dissociation Curve
• CO2 curve more linear than O2 curve • different saturations of O2 effect CO2 concentration – the Haldane effect
! eg venous blood can carry more CO2 than arterial blood o lower O2 ⇒ L shift of CO2 curve ie ↑uptake of CO2
! explained by Haldane effect & ↑ed for CO2 carriage as carbamino-Hb • curve allows this to be quantifiable:
• figures:
o @arterial point (PCO2 40mmHg & SpO2 97%) CO2 content = 48mlCO2/dl o @mixed venous point (PCO2 46mmHg & Spo2 75%) CO2 content = 52mlCO2/dl
• Haldane effect also quantifiable: o @PCO2 46mmHg 50% of CO2 carriage is due to Haldane effect
! CO2 content falls from 52 ⇒ 50 on SvO2 75% line (arterial point lying at 48) o if Haldane effect not present would have to follow 97% line:
! mixed venous pCO2 would have to rise to 55mHg to carry same amount of CO2 ! or at PCO2 46mmHg content would be less at 50mls
By Adam Hollingworth
7.Gas Transport - 11
• diagram shows CO2 curve compared to O2 curve. CO2 curve is much more:
o steep: ! why - PO2 difference between arterial & venous blood is big (~60mmHg) AND
- PCO2 diff is small (~5mmHg) o linear – why V/Q scatter has less of an impact on PaCO2
• In range 40-50mmHg: o Co2 content changes ~4.7mlCO2/dl per mmHg o O2 content changes ~1.7mlO2/dl per mmHg
CO2 Stores in Blood • Total body store >100 litres:
o [most] bone or dissolved fat ! bone has slow equilibrium = reason eventual plateau in rise of PCO2 during long laproscopic procedures
o [small] blood: ! ~ 2.5 litres (although is x2.5 more than O2 in blood)
• VCO2 ~3ml CO2/kg/min O2 Stores in body • total store ~ 1.5 litres:
o blood = 1000mls O2/min o alveoli [FRC] ~ 290ml
! although can be very large store if denitrogenised ie ~ 1800mls o myoglobin ~ 200ml o dissolved in tissue fluid ~ 50mls
• VO2 ~ 3.5ml O2/kg/min
Acid Base Status • pH resulting from solution of CO2 in blood & dissociation of carbonic acid given by Henderson-
Hasselbalch equation:
H2CO3 ↔ H+ + HCO3-
Or: pH = pK + log HCO3
- pK value = 6.1
0.03PCO2 • bicarbonate concentration determined by kidney • PCO2 by lung
By Adam Hollingworth
7.Gas Transport - 12
Respiratory Acidosis • Caused by ↑PCO2 ⇒ ↓ed HCO3-/PCO2 ratio ⇒ ↓pH • Whenever ↑PCO2 must also see some ↑bicarbonate
! due to dissociation of carbonic acid produced ! only mitigates; not reverses ↓HCO3-/PCO2 ratio
• Causes of CO2 retention: o Hypoventilation o VQ mismatch
• If resp acidosis persists see kidney response: o Senses ↑PCO2 in renal tubular cells ⇒
-/PCO2 ratio ⇒ ↑pH • causes eg hyperventilation – psychogenic or high altitude • renal compensation:
o ↑excretion of HCO3- ⇒ returning HCO3
-/PCO2 ratio back to normal o see –ve base excess aka base deficit
Metabolic Acidosis • see ↓in plasma HCO3
- ⇒ ↓ed ratio of HCO3-/PCO2 ⇒ ↓pH
• ↓ in HCO3- by:
o accumulation of acids in blood • compensation by resp system:
o ↑H+ ions sensed by periph chemoreceptors ⇒ o ↑ventilation ⇒ ↓PCO2 ⇒ normalise HCO3
-/PCO2 ratio o see –ve BE
Metabolic Alkalosis • ↑ HCO3
- ⇒ ↑ed ratio HCO3-/PCO2 ⇒ ↑pH
• causes: o excessive ingestion of alkalis o loss of gastric acid by vomiting
• compensation: o limited & may be absent
Davenport Diagram
By Adam Hollingworth
7.Gas Transport - 13
! ↓alveolar ventilation ⇒ ↑PCO2
Blood-Tissue Gas Exchange • transfer of gas follows Ficks Law:
o ∝ tissue area & inversely ∝ to thickness of barrier o ∝ difference in gas partial pressure between 2 sides o ∝ to solubility and inversely ∝ to square root of molecular weight
• blood gas barrier = 0.5um • blood-tissue barrier ~ 50um resting mm; less in active mm
! ∴ delivery of O2 more of a problem ! Elimination of CO2 easier as moves x20 faster than O2 through tissue
• As O2 diffuses away from capillary it is consumed • Picture A = balance between O2 consumption and & delivery adequate
! determined by Cap PaO2 & intercap distance) • Picture B =
o critical situation o PO2 at midpoint minimal by ↓in cap PaO2 or ↑intercap distance
• Picture C = anoxic midpoint region ⇒ anaerobic glycolysis
• PO2 muscle cells may be very low ~1-3mmHg ! why need myoglobin in cell to act as reservoir for O2 and enhance diffusion in cell
• O2 consumption in cell continues at same rate until PO2 falls to ~3mmHg ! ∴ high PaO2 in cap blood exists to drive diffusion of O2 to mitochondria
• Abnormally low PO2 in tissue = tissue hypoxia
Tissue Hypoxia • Factors determining low O2 delivery to tissue:
! Cardiac Output x arterial O2 concentration • Tissue hypoxia can be caused by:
o hypoxaemic hypoxia: ie↓PaO2 ! eg pulmonary disease
o hypaemic hypoxia: ↓ability of blood to carry O2 ! anaemia ! CO poisioning
o ischaemic or circulatory hypoxia: ↓tissue blood flow ! shock ! local obstuction
o low inspired partial pressure of O2: ! ↓delivery of O2 to alveoli ! low FiO2 or high altitude ! inspired O2 content is imp rather than atmospheric conc as person may not be breathing
atmospheric gas eg semi-closed anaesthetic circuit o alveolar hypoventilation
! can cause hypoxaemia even in normal lungs ! eg airway obstruction, ↓central RR drive, mm weakness
o impairment of diffusion across blood-gas membrane ! very rare but consider dense consolidation/ARDS/pulmon oedema ! generally actually VQ problem
o VQ inequality: ! areas with VQ <1. ! VQ of zero = shunt
o shunt
Anaesthetic Causes of Severe Hypoxia • Anaesthetic Causes:
o Gas mixture: ! Incorrect flowmeter settings ! Second gas effect - NO (especially on extubation) ! O2 failure ! Machine error
o Failure to ventilate: ! Vent depression or narcosis ! Inadequate IPPV ! Disconnection ! Misplaced ETT - oesophageal/endobronchial ! Airway obstrution - patient to machine ! ↑airway resistance eg bronchospasm/laryngospasm ! ↓FRC - Ptx, ↑intra-abdominal pressure, morbid obesity
o Poor o2 delivery in body: ! Systemic hypoperfusion - hypovolaemia/sepsis ! Embolus ! Regional problems - Raynauds/vascular problems
o ↑O2 demand - ! Sepsis ! Malignant hyperthermia
• Rx: o 100% o2 o Check Fio2 o Expose pt & check for central cyanosis o Check vent bilaterally o Hand ventilate on simple system - 4 large breaths for recruitment o Secure airway
By Adam Hollingworth
7.Gas Transport - 15
o Endotracheal suction o Initially remove PEEP (consider brief disconnection of circuit) then trial more o Adrenaline if losing pulses
Summary • most O2 transported in blood bound to Hb • max amount which can be bound = O2 capacity • O2 sats = amount combined with Hb / by O2 capacity
! = to proportion of Hb binding sites occupied by O2 • Acid-base status of blood is determined by HH equation
! closely related to HCO3-/PCO2 ratio
• PO2 in tissues <5mmHg • Purpose of high PaO2 is to ↑pressure gradient