Session 3 Flashcards

1
Q

How do you calculate total pressure from partial pressures?

A

In a mixture of gases, gas mixtures follow Dalton’s Law that the total pressure of the gases = the sum of the partial pressures of the individual gases.

E.g Partial pressure of O2 = 1/3 of Total pressure

Partial pressure of N2 = 2/3 of Total pressure

Total pressure = Partial pressure of O2 + Partial pressure of N2

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2
Q

What is atmospheric pressure?

A

Atmospheric pressure – the sum of the partial pressures of the gases in the atmosphere

  • Pressure exerted by the weight of the air above the earth in the atmosphere
  • At sea level: 101 kilopascals (kPa) = 1 atmosphere = 760 mm Hg of pressure
  • At high altitudes atmospheric pressure is lower (weight of air pressing down is less)
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3
Q

Gas partial pressures in the air we breath in, and in air in our lungs

A
  • Ambient air is a gas mixture of mostly nitrogen (79%) and oxygen (21%) and a bit of carbon dioxide (0.04%)
  • Remembering Dalton’s Law (sum of the partial pressures of gases = total pressure)
  • Atmospheric pressure (at sea level) = 101 kPa – sum of atmospheric partial pressures
  • Partial Pressure of Oxygen (PO2) = Fraction of Oxygen in the air (FiO2)×Atmospheric pressure (Patm)
  • PO2 = FiO2 ×Patm= (0.21 ×101 kPa) = 21 kPa - partial pressure of O2 in the air we breath
  • BUT Inspired gas (air) is warmed and humidified in the upper respiratory tract - that is we add water to the air we breath in, in the form of water vapour - so need to subtract the water vapour pressure from the atmospheric pressure 101 kPa- 6.3 kPa = 94.7 kPa
  • Therefore, PO2 of air once inspired and moistened (i.e. in our conducting part of Resp Tract) is 0.21 ×94.7kPa= 20 kPa
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4
Q

Alveolar gas pressure

A

ALVEOLARGAS PRESSURES determine SYSTEMIC ARTERIAL BLOOD GAS PRESSURES

  • Atmosphere PO2 = 21.3 kPa; PCO2 = 0.04 kPa
  • Remember PO2 in conducting airways of our Respiratory Tract = 20 kPa ; PCO2 = 0.04 kPa
  • Alveolar partial pressure oxygen is 13.3 kPa
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5
Q

Describe alveolar ventilation

A
  • Typical amount of air inspired/exhaled at rest = 450 ml (called the Tidal Volume) Typically 30% of the normal tidal volume fills Anatomical dead space ~30% of 450 ml = 150 ml
  • Anatomical dead space is Air conducting space of our respiratory tract
  • Conducting airways extend from the nostrils/nose, nasopharynx, trachea, bronchi, to the distal end of terminal bronchiole (or the start of/proximal end of respiratory bronchiole – No gas exchange occurs here
  • Therefore, 300 ml of air reaches the respiratory portion of our lung – this is alveolar ventilation
  • Typical total air volume in our lung is 3 litres – 3000 ml
  • Therefore that 300 ml of NEW (fresh) air represents about 10% of all the air in our lungs
  • Fresh air is DILUTED by old air in lung –old air is having O2 continually extracted by blood exchange, and CO2 constantly being added

Conducting airways, alveolar, arterial and vein partial gas pressures:

  • Conducting airways partial pressures – PO2 = 20 kPa; PCO2 = 0.04 kPa
  • Alveoli partial pressure O2(denoted PAO2) = 13.3 kPa; • Alveoli partial pressure CO2 (denoted PACO2) = 5.3 kPa
  • Arteries partial pressure of O2 (denoted PaO2 or pO2) =13.3 kPa
  • Arteries partial pressure of CO2 (denoted PaCO2 or pCO2) = 5.3 kPa
  • Veins partial pressure O2 (denoted PvO2 ) = 5.3 kPa • Veins partial pressure CO2 (denoted PvCO2)= 6.1 kPa
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6
Q

How does gas exchange occur?

A

In the body gases diffuse down their partial pressure gradient – from area of high partial pressure – to low partial pressure

e. g. movement of oxygen from alveolar air to blood
e. g. movement of carbon dioxide from blood to alveoli

  • Partial pressures (rather than concentrations) used to describe gases in the body
  • Denoted by ‘p’ - as in pO2, pCO2, pN2

When inspired gases come in contact with body fluids (made up mostly of water) - gas molecules will enter fluid and dissolve in the liquid

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7
Q

Gas dissolves in body fluids

A

Dissolved gas molecules also exert pressure in the liquid –i.e. water

• Equilibrium is reached when: rate of gas entering water = rate of gas leaving the water. At equilibrium, the partial pressure of the gas dissolved in the liquid = partial pressure of the gas in the air above it

– This occurs at the alveoluscapillary border

  • Blood oxygen and CO2 partial pressures equilibrate to the alveolar levels because “the partial pressure of the gas in the liquid = partial pressure of the gas in the air above it.”
  • –NB:another term used for partial pressure of a gas in the liquid is ‘tension’ (e.g. oxygen tension in blood)
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8
Q

Summary alveolar gas partial pressures

A
  • Alveolar air pO2 =13.3 kPa (lower than inhaled air)
  • pCO2 =5.3 kPa (higher than in inhaled air)
  • Because pO2 in inhaled air lower because it mixes with residual volume
  • Effect of O2 diffusing OUT across the alveolar wall
  • Effect of CO2 entering INTO the alveoli
  • Alveolar air composition stays constant around this level;
  • Blood equilibrates to this level –because “the partial pressure of the gas in the liquid = partial pressure of the gas in the air above it.”
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9
Q

How is partial pressure different form the amount of gas dissolved?

A

Amount of a gas dissolved (mmol/L) = partial pressure (kPa) x solubility coefficient of gas

Solubility coefficient – is a constant for the individual gas and the solvent (the substance in which it is dissolved) – which in our body is blood, plasma, ECF – i.e. mostly water!

Solubility coefficient of O2 in plasma = 0.01 mmol/ L /kPa (at 37°C) \When exposed to a pO2 of 13.3 kPa (as in alveolar air) the equation is: 0.01mmol/L/kPa x 13.3 kPa = 0.13 mmol/L of O2 will dissolve

Plasma has 0.13 mmol dissolved oxygen /per litre BUT –need to remember O2 binding to haemoglobin (Hb)

If a gas reacts with a substance within a liquid -e.g. O2 binding to haemoglobin (Hb) -in addition to dissolving, then this reaction must complete before equilibrium is reached and partial pressure is established –the oxygen binding to Hb does NOT contribute to pO2 in the blood

  • O2 enters plasma and dissolves in plasma, dissolved O2 enters RBC to bind to Hb
  • Process continues till Hb fully saturated (each Hb molecules binds 4 O2 molecules)
  • After Hb is fully saturated, O2 continues to dissolve till equilibrium is reached • At equilibrium, pO2 of plasma = pO2 of alveolar air
  • Blood contains both dissolved and Hb bound oxygen
  • The pO2 is a measure of dissolved O2 in the blood.
  • Dissolved O2 is available to diffuse into tissues down its partial pressure gradient
  • As dissolved O2 leaves the blood, it will be replaced by O2 bound to Hb.
  • In this way, the oxygen bound to Hb will be downloaded and diffuse into tissues
  • 98-99% oxygen bound to haemoglobin, 1-2% oxygen dissolved in the blood
  • In this way we very significantly increase the total available oxygen in our blood

Total content of gas = dissolved gas + gas bound to or reacted with a component ( e.g. O2 dissolved plasma + O2 bound to Hb)

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10
Q

What do we mean by “MIXED” venous blood? Mixed from what?

A

In mixed venous blood

  • PO2 typically ~6.0 kPa
  • PCO2 typically ~6.1 kPa
  • but varies with metabolism ratio of carbohydrates to fats eaten –respiratory quotient

Mixed venous blood is blood from IVC SVC and coronary vessels

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11
Q

Gradients of partial pressure of gases in the lung alveoli

A

PO2=~6.0 PCO2=~6.1 kPa in mixed venous blood and kPa PO2=13.3 kPa PCO2=5.3 kPa in alveolar gas

  • Alveolar PO2 > PO2 in mixed venous blood
  • Alveolar PCO2 < PCO2 in mixed venous blood
  • Therefore oxygen will diffuse into blood and carbon dioxide out
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12
Q

Factors affecting rate of diffusion

A
  • Partial pressure difference (gradient) across membrane (P1–P2) AND
  • A -the surface area available for diffusion
  • T –(thickness) i.e. distance molecules must diffuse
  • Diffusion coefficient of the individual gas Diffusion also depends on properties of the individual gas:
  • The solubility of the gas in the liquid : greater the solubility, faster the rate of diffusion
  • Molecular weight of gas: – Higher the molecular weight slower the rate of diffusion

Diffusion coefficient (D) - used to determine the relative rates at which different gases will diffuse across the same membrane at the same pressures;

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13
Q

Diffusion of CO2versus diffusion of O2

A
  • Solubility: CO2 much more soluble than O2 -so diffuses faster than O2
  • Molecular weight: molecular weight of CO2 > O2 -molecular weight slows down CO2

Combine the two factors Oxygen is small and thus fast, but CO2 is more soluble

Overall, the effect of solubility is greater CO2 diffuses 20 times faster than O2

  • Larger difference in partial pressures (ΔP) compensates for slower diffusion of O2
  • In a diseased lung with lower oxygen levels, O2 gas exchange is more impaired than CO2 because of O2 slower diffusion rate
  • HOWEVER, in order to exhale CO2, air needs to be delivered to the lungs for gas exchange to occur – therefore in HYPOVENTILATION (reduced amount of air entering alveoli 2º to either too few breathes or too shallow or both) pCO2 in the blood goes up as well as pO2 in blood decreasing
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14
Q

0Diffusion barriers between alveolar lumen and blood

A

Diffusion from alveolar air to RBC in capillary must cross:

– Fluid film lining alveolus

– epithelial cell of alveolus

– Interstitial space

– endothelial cell of capillary

– plasma

– red cell membrane

  • 5 cell membranes • 3 layers of cytoplasm • 2 layers of tissue fluid +plasma
  • The surface area of the alveolar capillary membrane about 100 m2
  • Barrier < 0.4 μM thick
  • Oxygen exchange complete in 1/3 of time blood spends in the lung capillary bed
  • So plenty of reserve – needed for when we exercise
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15
Q

Factors affecting rate of gas diffusion –in disease

A
  • Thickness of the membrane/space – Increase as a result of oedema fluid in the interstitial space and in alveoli – Lung fibrosis -increased thickness of alveolar and capillary membranes and interstium
  • Surface area of the membrane – Decreased by removal of an entire lung – Emphysema -decreased surface area
  • Diffusion coefficient of the gas: – CO2 always diffuses much faster than O2 – So, diffusion of O2 affected pO2 is low – Diffusion of CO2 not affected àpCO2 normal until late stage disease Diffusion impairment problems with alveolar capillary membrane

slide 26

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16
Q

Decompression sickness in divers

A
  • Pressure below sea level = atmospheric pressure + weight of water Therefore much higher
  • The air inspired (from a scuba tank) during a dive is at higher pressure than on dry land –has important safety implications
17
Q

O2 at Everest

A

At the summit of Everest Atmospheric pressure = 31.1 kPa pO2 = 31.1 kPa x 21% = 6.5 kPa

1/3 of pO2 at sea level (21 kPa)

Need oxygen to breath

18
Q

Carriage of gasses in blood

A
  • Cellular respiration requires oxygen and produces carbon dioxide • Oxygen is carried in the blood from the lungs to tissues
  • Carbon dioxide is carried away from the tissues to the lungs

Oxygen Transport

  • Oxygen is not very soluble in water – Solubility factor for O2 = 0.01 mmol.l-1.kPa-1 – Less soluble than CO2
  • [O2]dissolved = solubility x pO2 • At pO2 of 13.3 kPa only 0.13 mmol.l-1 is dissolved
  • At rest we need around 12 mmol O2 per minute
  • Would need 92 l.min-1 to meet needs

Cardiac output at rest – about 5 l.min-1

• Maximum cardiac output – about 25 l.min-1 • Even if all the O2 could be extracted cardiac output would be impossibly high • We need a chemical reaction to transport oxygen

Oxygen binding

  • The reaction needs to be reversible
  • The oxygen must dissociate at the tissues to supply them
  • Many substances will bind oxygen but only some are useful
  • Respiratory pigments contain haem group • Oxygen combines reversibly

Oxygen binding pigments

  • Haemoglobin – present in blood – Tetramer – binds 4 oxygen molecules
  • Myoglobin – present in muscle cells – Monomer – binds 1 oxygen molecule First consider myoglobin • Pigment found in muscles • Contains haem • Similar to haemoglobin but only a single subunit
19
Q

dissociation curves

A
  • Using myoglobin as an example
  • Can show reversibility of O2 binding as a dissociation curve
  • Plot of O2 bound vs pO2
  • Total content = bound + dissolved
  • Saturates because the amount of pigment is limited
  • Binding saturates above a given pO2
  • Amountof O2 bound therefore depends on amount of pigment when represented this way
  • Can overcome this issue by expressing saturation as a percentage – Independent of pigment concentration
  • So dissociation curves normally expressed as a percentage of amount bound at saturation
  • This is independent of pigment concentration
  • We can see how much O2 will be bound or given up when moving from one partial pressure to another
  • Work out difference in percentage saturations between the two pO2 values
  • Take amount bound at full saturation and use percentage to calculate how much given up
20
Q

Haemoglobin

A
  • Molecule of haemoglobin consists of 4 subunits – Tetramer– 2 alpha and 2 beta subunits
  • Each subunit has one haem and one globin
  • 4 oxygen molecules can bind to each molecule of haemoglobin
  • Low affinity for oxygen in T state (tense) – Difficult for oxygen to bind
  • High affinity for oxygen in R state (relaxed) – Easier for oxygen to bind
  • When pPO2 is low Hb is tense
  • So it is hard for the first O2 molecule to bind
  • As each O2 binds the molecule becomes more relaxed and binding of the next O2 molecule is easier

Haemoglobin dissociation curve

  • Initially the relationship between pO2 and binding is shallow
  • But as some O2 binds it facilitates further binding
  • Curve steepens as pO2 rises
  • Then flattens as saturation is reached
  • This gives a sigmoidal curve
  • Hb saturated above 9-10kPa
  • Virtually unsaturated below 1kPa
  • Half saturated at 3.5 – 4 kPa
  • Saturation changes greatly over a narrow range (steep part of curve)
  • Reaction is highly reversible and depends on pO2 levels saturation of venous blood
21
Q

Haemoglobin changes as it flows through the circulatory system

A

Haemoglobin in arterial blood leaving the lungs

  • Alveolar pO2 ≈ 13.3kPa, therefore Hb is well saturated
  • Can calculate oxygen contentof arterial blood
  • If Hb concentration is normal ≈ 2.2 mmol.l-1
  • Each Hb molecule binds four O2 molecules • Therefore oxygen content = 8.8 mmol.l-1 – If the patient’s lungs are functioning OK, but they are anaemic, pO2 will be normal, but oxygen content will be lower

Haemoglobin in the tissues

  • Tissue pO2 depends on how metabolically active the tissue is – typically 5 kPa
  • Hb saturation drops to ≈ 65%
  • 35% given up (fraction given up = 0.35)
  • Can calculate amount of O2 given up • 8.8 mmol.l-1 x 0.35 ≈ 3 mmol.l-1 Haemoglobin in venous blood
  • Mixed venous blood – mixture of blood returning from various tissues
  • Over half the oxygen is still bound
  • Could the tissues remove more?
  • The lower the tissue pO2, the more O2 will dissociate from Hb – lower
22
Q

How low can tissue pO2 get?

A
  • Tissue pO2 must be high enough to drive diffusion of O2 to cells
  • It cannot fall below 3 kPa in most tissues
  • However the higher the capillary density, the lower the pO2 can fall (doesn’t have so far to diffuse)
  • Very metabolically active tissue will have a higher capillary density (eg heart muscle)
23
Q

The Bohr shift

A
  • pH effects the affinity of haemoglobin
  • Acid condition shift dissociation curve to right (higher pO2 values)
  • ↓pH promotes T-state of Hb (tense state)
  • ↑pH (alkaline) promotes R-state (relaxed)
  • Bohr shift – ↓pH shifts dissociation curve to right – Hb has lower affinity for O2 In the Tissues • pH is lower in the most metabolically active tissues
  • So extra O2 is given up In the Tissues
  • Increased temperature also shifts the dissociation curve
  • Metabolically active tissues have slightly higher temperature
  • So extra O2 is given up
24
Q

Maximum unloading of oxygen

A
  • Maximum unloading occurs in tissues where pO2 can fall to low level
  • Also in conditions where increased metabolic activity result in more acidic environment and higher temperature
  • Under these conditions about 70% bound oxygen can be given up
25
Q

Mixed venous blood

A
  • Over the whole body about 27% of oxygen from arterial blood is given up • This can increase in exercise
  • There is an oxygen reserve
  • In extreme exercise can increase metabolism by 10x, but cardiac output only goes up by 5x
  • Improved extraction of O2 by the tissues
26
Q

2,3-Bisphosphoglycerate

A
  • Red blood cells normally contain ~ 5mM 2,3-BPG
  • 2,3-BPG levels increase with anaemia or at altitude
  • Increased 2,3-BPG shifts Hb dissociation curve for O2 to right
  • Allows more O2 to be given up to tissues because of shift in curve
  • 2,3-BPG levels drop in stored blood due to refrigeration – Limits how much O2 can be given up at tissues – Not usually a problem clinically
27
Q

Carbon monoxide poisoning

A
  • Reacts with Hb to form COHb
  • Increases affinity of unaffected subunits for O2
  • Therefore won’t give up O2 at the tissues
  • Fatal if HbCO is > 50%
28
Q

Hypoxemia or hypoxia

A
  • Hypoxemia -low pO2 in arterial blood
  • Hypoxia –low oxygen levels in body or tissues
  • If pO2 levels are low, not all the Hb will be saturated
  • If Hb levels are low, not enough O2 will be present in the blood
  • Conditions such as shock can reduce blood flow – Peripheral vasoconstriction can cause peripheral hypoxia
  • Tissues using O2 faster than it is delivered

– Peripheral arterial disease

– Raynaud’s

29
Q

Cyanosis

A
  • Bluish colouration due to unsaturated haemoglobin
  • Deoxygenated haemoglobin is less red than oxygenated haemoglobin
  • Can be peripheral (hands or feet) due to poor local circulation
  • Or central (mouth, tongue, lips, mucous membranes) due to poorly saturated blood in systemic circulation
  • Can be difficult to detect – Poor lighting – Skin colouration
30
Q

Pulse oximetry compared with Arterial blood gas and electrolyte analysis

A

Light detector

Red and infrared light emitted

  • Detects level of Hb saturation – Detects difference in absorption of light between oxygenated and deoxygenated Hb
  • Only detects pulsatile arterial blood
  • Ignores levels in tissues and non-pulsatile venous blood
  • Doesn’t say how much Hb present - only oxygen saturation o the haemoglobin - could have high saturation of a small amount of Hb so can’t detect anaemia.

Arerial blood gas and electrolyte analysis

can be used to detect acid base balance, oxygen sat, electrolytes.