Gas transport Flashcards
Points on Sofia.
1
Q
***What is the notation for gases and their locations? REVISE THE FOLLOWING TABLE!
A
These columns all go together: e.g. Pa = partial pressure in the arterioles; PA = partial pressure in the alveoli; PI = partial pressure in the inspired air.
2
Q
What does the symbol P mean? Measurement? (x2)
A
Partial pressure in kPa or mmHg.
3
Q
What do the following symbols mean: F, S, C, Hb?
A
Fraction (%). Hb Saturation. Content (mL). Volume bound to Hb.
4
Q
What is Dalton’s law?
A
Pressure of a gas mixture is equal to the sum of the partial pressure of all the gases in it.
5
Q
What is Fick’s law?
A
Molecules diffuse from regions of high concentration to lower concentration at a rate proportional to the concentration gradient, the exchange surface area, and the diffusion capacity of the gas; it is inversely proportional to the thickness of the exchange surface.
6
Q
What is Henry’s law?
A
At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas (and the solubility of the gas), in equilibrium with that liquid.
7
Q
What is Boyle’s law?
A
At a constant temperature, the volume of gas is inversely proportional to the pressure of that gas.
8
Q
What is Charles’ law?
A
At a constant pressure, the volume of a gas is proportional to the temperature of that gas.
9
Q
What are the proportions of each gas in atmospheric air?
A
78% N, 21% O2, rest Ar, CO2 and trace Ne, He, H2 and Kr.
10
Q
What changes to proportions of gases in air in house fires?
A
N2 stays the same. O2 is replaced by CO2 and CO.
11
Q
What changes to proportions of gases in air in high-altitude?
A
Stay the same, but ALL at lower pressures.
12
Q
What happens to the air and its proportions of H2O, O2 and CO2 as it travels down the respiratory tree?
A
The air is warmed, humidified, slowed and mixed as it moves down the respiratory tree. CONDUCTING PATHWAYS: PO2 decreases as PH2O increases. RESPIRATORY AIRWAYS: PO2 decreases as PCO2 increases.
13
Q
How is oxygen carried around the pulmonary and systemic circulations?
A
Look at photo.
14
Q
How much oxygen is capable of being carried dissolved in the blood during ventilation? Comparison to demand?
A
16mL min-1 at rest. YET, the volume of oxygen CONSUMED per minute is around 250mL min-1m. We therefore NEED haemoglobin.
15
Q
What is the structure of haemoglobin?
A
It is a tetrameric protein = four monomers, consist of Fe2+ ions at centre of tetrapyrrole porphyrin ring connected to globin protein chain, covalently bonded at proximal histamine residue. Has two Hb-alpha subunits, and two Hb-beta/sigma/gamma depending on type.
16
Q
What are the three types of haemoglobin?
A
Most of your haemoglobin is HbA (two B subunits), small amounts can be HbA2 (two delta subunits). Third type is HbF (two gamma subunits).
17
Q
Describe the conformational change to Hb when oxygen is binding. What is a name for this?
A
Initially, Hb does not have very strong affinity to oxygen. After the first one is bound, there is a small conformational change in the structure of Hb that gives Hb higher affinity for oxygen. Each time an O2 binds, affinity increases EXPONENTIALLY. Hb transitions from TENSE (tight structure), to RELAXED (willing to accept more O2). Called: COOPERATIVE BINDING.
18
Q
What does oxygen binding open-up on the Hb molecule? What is a name for this?
A
A binding site is produced in the middle between the four chains, which is where 2,3-DPG binds. 2,3-DPG pushes Hb into a more TENSE, tight state which causes some of the oxygen to be ejected out. This behaviour is allosteric behaviour – so Hb is an allosteric protein.
19
Q
What is methaemoglobin and presence in the blood? Relationship with normal Hb?
A
Methaemoglobin exists in a small amount 0/5-1%. It has Fe3+ rather than Fe2+ which DOES NOT BIND OXYGEN. It exists in equilibrium with Hb (Fe2+): other chemical pathways and enzymes (like the electron transport chain) take part in redox reactions which oxidise/reduce Hb which results in this change.
20
Q
What is it called when methaemoglobin is too high? What symptom does this have?
A
When in high volume, you get Methaemogloinaemia – skin turns blue – haemoglobin colours our skin and is why our skin turns white when our blood leaves the skin.
21
Q
What clinical intervention e.g. in surgery, reduces Methaemoglobin levels in the blood?
A
Methylene blue increases amount of Hb when MetHb is too high.
22
Q
Why is the oxygen dissociation curve not linear? Significance of elderly and exercise in relation to the sigmoid curve?
A
Not linear to ensure that high saturation is achieved when blood enters the lungs, but that systemic circuit can unload a lot of oxygen when really needed. Look at photo – pay attention to the green arrows. As you get older, the amount of air getting into the lungs decreases, but the sigmoid curve means that your blood can still get very saturated. When you are at rest, steepness means that you take 25% O2 from the blood, but able to quickly extract more during exercise when tissue O2 changes.
23
Q
How much oxygen is removed in the systemic circulation at rest?
A
25%.
24
Q
Is the oxygen dissociation curve the same everywhere in the body, and at all times? How can we measure this?
A
NO! The ODC can change. We can track these changes by looking at P50. It is the partial pressure of O2 in the blood at 50% saturation.
25
What must be controlled when studying P50 for the ODC?
The type of haemoglobin is the same levels in each blood sample.
26
What factors result in a rightward shift of the ODC? (x4)
Factors that cause a rightward shift are all to do with metabolic activity – 1: TEMPERATURE: metabolism is exothermic, so temperature goes up. 2: ACIDOSIS: accumulation of protons from lactic acid and because they exist in equilibrium with CO2, so when CO2 goes up, H+ goes up too. 3: HYPERCAPNIA = high CO2. 4: Increased 2,3-DPG means that unloading is promoted. P50 also shifts to the right.
27
What is the effect of a rightward and leftward shift of the ODC?
LEFTWARDS: Leftward shift means blood has greater affinity so is better at loading with oxygen, but not as good at unloading to tissues in need. RIGHTWARDS: better at unloading oxygen. LOOK AT PHOTO.
28
What is a rightward shift of the ODC called?
Bohr shift.
29
What factors result in a leftward shift of the ODC?
Factors that cause this are decreased temperature, alkalosis, hypocapnia and decreased 2,3-DPG. P50 also shifts to the left.
30
What affects P50? (x4)
Temperature, pH, CO2, 2,3-DPG.
31
What results in the ODC losing and gaining height? Cause for each? (x1 and x2)
LOSE HEIGHT: This occurs when you lose Hb in the blood = decreased oxygen carrying capacity. This is called ANAEMIA. May mean you have 100% saturation, but it also means you have lost loads of Hb (blood) and impaired oxygen-carrying capacity as a result. GAIN HEIGHT: POLYCYTHAEMIA = increased oxygen-carrying capacity. Can be caused by a tumour causing increased secretion of erythropoietin which increases erythropoiesis (RBC production and maturation); or blood doping.
32
What is the effect of CO poisoning on the ODC? Why? Effect of this new ODC on gas exchange in the body?
Downwards and leftwards. Decreased capacity for oxygen carriage causes ODC to go down, and increased affinity causes ODC to go left. This is because CO is binding to Hb instead of O = Carboxyhaemoglobin (HbCO). (Red highlighting in photo – much less tissue-based capacity for release, because PO2 crosses an area when saturation is very high).
33
What is the structural difference between fetal haemoglobin and adult haemoglobin?
More gamma chains.
34
How does the ODC differ for fetal haemoglobin? Functional consequences?
Because of the gamma chains, the ODC shifts to the left. SO, there is greater affinity than HbA to extract oxygen from placental blood.
35
What is the structure of myoglobin, and where is it found? Differs from Hb?
Myoglobin is found in the blood in muscle tissue. It is a MONOMERIC protein, so only one subunit. It still has a haem group surrounded by a globin protein.
36
What is the function of myoglobin?
Much greater affinity that HbA to extract oxygen from circulating blood for storage because it has a much higher ODC. Suited for use when muscle cells are in use for high intensity exercise – the ODC means that when PO2 is VERY low, O2 can be rapidly delivered.
37
How saturated does the blood return to pulmonary circulation?
RBCs arriving are about 75% saturated when they return to the lungs.
38
What happens in the lungs when blood passes alveoli? When does this process stop?
PAO2 (alveolar) diffuses into RBCs and occupies binding sites. When PaO2 = PAO2, diffusion stops.
39
Why does blood arriving in tissues have slightly less oxygen saturation that when they left the lungs?
Blood arriving tissues is slightly less than that which left the lungs, because of the drainage in the bronchial circulation – SOME of which drains into the pulmonary veins, so dilutes the blood in the left side of the heart slightly. (LUNG HAS DOUBLE CIRCULATION – pulmonary and bronchial circulation.)
40
What is oxygen flux, and what are the oxygen values at the arteriole and venule ends?
CaO2 (arterial content) = 20.3 mL dL-1 at the arteriole end, and 15.1 mL dL-1 at the venous end. This causes OXYGEN FLUX (movement). (NB: CaO2 combines HbO2 and CpO2 (20 and 0.32 ml dl-1 in the arterial end, and 15 and 0.14 ml dl-1 in the venous end respectively).) THEREFORE, oxygen flux is -5 ml dL-1 (meaning movement out of the blood vessels).
41
How can oxygen flux be used to calculate total amount of oxygen flux in circulatory system?
Cardiac output = 5L/min. So, multiply 5 ml dl-1 by 50 (there’s 50 decilitres of blood) = -250 mL O2.min-1. This is the value for RESTING VO2.
42
What are the three different ways CO2 can be transported in the blood?
1. Dissolves in solution. 2. As bicarbonate – most is transported this way. 3. Also binds to Hb.
43
How does CO2 bind to haemoglobin?
Bind to amine end of the globin chains in Hb (there are four globin chains). Therefore, 1Hb = 4O2 OR 4CO2. (Oxygen binds to haem molecule.) Forms CARBAMINOHAEMOGLOBIN (HbCO2).
44
How is CO2 transported as bicarbonate? (x2 ways)
FIRST MECHANISM: CO2 moves into blood plasma and reacts with water to form carbonic acid (H2CO3) – this is SLOW, NON-ENZYMATIC (look at photo in PPT). Carbonic acid dissociates into H+ and HCO3- (this explains the equilibrium with CO2 and acidosis). SECOND MECHANISM: CO2 also moves into the erythrocyte and does the same – though combines with water and IS ENZYMATIC – carbonic anhydrase. Bicarbonate moves out, and Cl- moved in to maintain resting membrane potential using AE1 transporter. H+ is not good for erythrocytes and enzymes: Some of the Hb has negative charges in the amino acid chains – proton acceptors – these mop up the H+.
45
What is the value for CO2 flux? Why is CO2 flux not as significant as O2 flux?
CO2 flux is much less significant than O2 flux because it doesn’t have the same sigmoid dissociation curve. +4 ml dL-1. +200 mL CO2 min-1 (for every 250 ml of oxygen consumed).
46
What happens to the proportions of CO2 carried by Hb, bicarbonate and dissolved as blood travels from the arterial to the venous end of the circulation? Why is this?
If you look at CO2 and how it is carried in the arterial and venous blood: In less oxygenated blood, carbacminohaemoglobin, and dissolved is more prevalent. This is because of the CO2 dissociation curve which for all intents and purposes is LINEAR, because the only bits we care about are between 4 and 7 kPa of PCO2.
Points A(rterial) and V(enule) are marked. Relative proportions differ slightly between these two points. The shifting is called the HALDANE EFFECT – this occurs when Hb is 100% O2 saturated – at this point, its globin chains will not bind ANY CO2. This is why in the oxygenated, arterial end, the proportions of HbCO2 are lower.
47
What is the pulmonary transit time and its value in the body?
Pulmonary transit time = amount of time the blood is in contact with the respiratory exchange surface. 0.75 seconds to participate in gaseous exchange. CO2 does this even quicker.
48
What happens to pulmonary transit time in exercise?
When you exercise, more pulmonary capillary beds are recruited, flow is not faster – unless exercise is REALLY intense. SO, pulmonary transit time otherwise remains the same!
49
What is the nature of ventilation from the apex to the base of the lung?
AT THE APEX: transmural pressure is MORE NEGATIVE (PPL is -8cmH2O). Alveolar walls are stretched and therefore under pressure because of gravity. This means greater pressure is required to inflate them – less scope to increase size because stretched. LESS VENTILATION. AT BASE: PPL is less negative (-2 cmH2O) so transmural pressure gradient is smaller. Alveolar are smaller and more compliant, so MORE VENTILATION. OVERALL: air coming in will preferentially inflate the bottom than the top.
50
What is the nature of perfusion from the apex to the base of the lung?
For the same reason as ventilation, perfusion changes from the apex to the base, all because of the fact that there’s LOWER INTRAVASCULAR PRESSURE at the apex than at the base, because of GRAVITY. APEX: Less recruitment (less perfusion), greater resistance, lower flow rate. BASE: More recruitment, less resistance, higher flow rate.
51
What is the ventilation:perfusion ratio from the apex to the base of the lung?
\*\*\*Perfusion is affected more greatly by gravity than ventilation because blood is denser. If you combine the effects of both ventilation and perfusion, you get an exponential graph modelling V/Q (ventilation/perfusion ratio from the base to the apex – exponential because perfusion is more greatly influenced by gravity – look at photo).
At the top = wasted ventilation. At the bottom = wasted perfusion.
52
When is V/Q equal across the entire lung?
When there is no gravity e.g. International Space Station.
53
What is an ABG report?
Arterial blood gases report.
54
How does temperature affect acid-base regulation in the blood?
Affects equilibrium – which affects things like pH and CO2.
55
What are typical values for PaO2, SaO2 and PaCO2 in the arterial and venous circulation?
ARTERIAL CIRCULATION: PaO2 = more than 10kPa; SaO2 = more than 95%; PaCo2 = 4.7-6.4kPa. VENOUS CIRCULATION: PaO2 = 5.3kPa; SaO2 = 75%; PaCO2 = 6.1kPa.
56
What is alkalaemia?
Refers to higher than normal pH in the BLOOD.
57
What is alkalosis?
Describes CIRCUMSTANCES that will decrease [H+] and increase pH.
58
What is acidaemia?
Refers to lower than normal pH in the blood.
59
What is acidosis?
Describes circumstances that will increase [H+] and decrease pH.
60
Why it is important to control pH of the blood?
Marked changes in pH will alter 3D structure of proteins (enzymes, hormones, protein channels).
61
What is a base?
An ANIONIC (negatively charged ion) molecule capable of reversibly binding protons (to reduce the amount that was ‘free’) – given by the equation.
62
What is the conjugate acid of a base, A-?
HA. In a conjugate acid-base pair, one species is typically a strong acid/base, and the other species is a weak acid/base.
63
What is the pH equilibrium set up in the blood? What property does this give blood?
Gives blood a huge buffering capacity that can react almost immediately to acid-base imbalances.
64
What is a healthy H+ concentration and pH?
0.00000004 Eq/L (Eq means counting charges per litre, rather than molecules) – very small, but has a big impact. pH = -log(H+) = 7.35 - 7.45pH.
65
How do you convert from pH to [H+]?
10 to the power of minus pH.
66
What are the two types of ACID in the blood? Examples of each? (x1 and x2)
RESPIRATORY = CO2 – because can convert into carbonic acid. METABOLIC = anything other than CO2 – lactic, HCl…
67
Relative proportions of respiratory and metabolic acids in terms of production?
Respiratory acids produced in 100:1 to metabolic acids, so affect overall pH much more.
68
What is the Sorensen equation?
pH = -log10[H+]. And vice versa.
69
What is the Handerson equation?
Calculate the dissociation constant – Ka.
70
What is the Henderson-Hasselbalch equation?
Combines the Sorensen and Handerson equation, to estimate the pH of a BUFFER solution given the concentrations of an acid and its conjugate base. BASE GOES ON TOP, ACID DOES ON BOTTOM.
71
What is cardiac output per minute?
5L/min. Don’t think we really need to know this.
72
What is CO2 flu per minute?
4 mL/dL/min. Don’t think we really need to know this.
73
Cardiac output = 5 L/min; CO2 flux is 4 mL/dL/min: Estimate the volume of respiratory acid (CO2) produced in a typical adult over a 24-hour period.
FLUX MEANS OUTFLOW. CO2 flux of 4 mL/dL/min means that for every 100ml (1dL) of blood that goes through the system capillaries, 4 mL/dL of CO2 is added on top of the CO2 already there. Using this 4 mL per dL of blood value, we can extrapolate to 5L cardiac output (there are 50 decilitres in 5L of blood) by multiplying by 50. This gives a CO2 production rate of 200 mL every minute. There are 60 minutes in an hour and 24 hours in a day, so if you multiply 200mL by 60 and by 24, you get 288L, which is the volume of CO2 produced per day.
74
Calculate the pH of an arterial blood gas sample if the [H+] is 48 nmol/L.
48 nmol/L (/1000); 0.048 umol/L (/1000); 0.000048 mmol/L (/1000); 0.000000048 mol/L. NOW, we use Sorenson’s equation = 7.32.
75
What is the hierarchy of L, milli, micro… measurements? (x6)
L, Milli-, Micro-, Nano-, Pico-, Femto-. Each increase by 1000 fold.
76
What is hypoxaemia?
Low levels of oxygen in the blood.
77
What does base excess/deficit refer to?
The amount of base present in the blood. Usually reported as mEq/L or mmol/L.
78
What are the categories of hypoxaemia, and the values they are defined by?
More than 10kPa is normal. 8-10kPa is MILD hypoxaemia. 6-8kPa is MODERATE hypoxaemia. Less than 6kPa is SEVERE hypoxaemia.
79
What are they two pH compensatory mechanism?
ACIDAEMIA NEEDS AN ALKALOSIS TO CORRECT; ALKALAEMIA NEEDS AN ACIDOSIS TO CORRECT. 1. Changes in ventilation can stimulate a RAPID compensatory response to change CO2 elimination and therefore alter pH. 2. Changes in HCO3- (base) and H+ retention/secretion in the kidneys can stimulate a SLOW compensatory response to increase/decrease pH.
80
What is the compensatory mechanism in RESPIRATORY ACIDOSIS? (x3 stages - UPF) Cause - how?
HYPOVENTILATION – causing reduced diffusion gradient for CO2, leading to increased PCO2 in post-alveolar blood, decreased pH (because more CO2 is available in blood for conversion to H+), and normal base excess (bicarbonate normal for pCO2) (look at equation in photo). Result = UNCOMPENSATED RESPIRATORY ACIDOSIS.
NEED TO REDUCE [H+]. PARTIAL COMPENSATED RESPIRATORY ACIDOSIS: Look at equation – split into two phases, an ACUTE PHASE (CO2 moves into erythrocytes, combines with H2O In presence of carbonic anhydrase to form bicarbonate, which moves out of cell by AE1 transporter; increased bicarbonate leads to raised base excess, shifting equilibrium to the left towards the (weaker) carbonic acid and reducing [H+]) and a CHRONIC PHASE (increases bicarbonate reabsorption in kidneys to stabilise pH). The effect of both INCREASES BASE EXCESS which maintains the supply of CO2 in the blood also).
FULLY COMPENSATED RESPIRATORY ACIDOSIS: eventually, because of these actions, the pH will stabilise. CO2 remains high, and B.E. is still high – this is the nature of the compensation (look at the graph at the bottom). UPF = uncompensated, partial, fully.
Just think, UNCOMPENSATED affects CO2 and pH, PARTIAL affects pH AND Base Excess.
81
What is the compensatory mechanism in RESPIRATORY ALKALOSIS? (x3 stages - UPF) Cause - how?
HYPERVENTILATION – causing increased gradient for CO2, leading to a lower PCO2 in post-alveolar blood (look at photo), increased pH because less is available to be converted into H+, and normal base excess = UNCOMPENSATED RESPIRATORY ALKALOSIS.
NEED TO INCREASE [H+]. PARTIAL COMPENSATED RESPIRATORY ALKALOSIS: There is no acute phase unlike during acidosis. CHRONIC PHASE (reduces bicarbonate reabsorption from nephrons and increases secretion in collecting duct, causing position of equilibrium to shift to favour carbonic acid dissociation. The effect decreases levels of BE, which maintains the lowered CO2 levels.
FULLY COMPENSATED RESPIRATORY ALKALOSIS: eventually, the pH will normalise with low pCO2 and BE.
Just think, UNCOMPENSATED affects CO2 and pH, PARTIAL affects pH AND Base Excess.
82
\*\*\*What is the compensatory mechanism in METABOLIC ACIDOSIS? (x3 stages - UPF) Causes (x1 +2) - how?
DIARRHOEA may cause metabolic acidosis because it results in loss of bicarbonate in faeces, leading to increased dissociation of carbonic acid, causing pH reduction with normal PCO2 and low BE (remember, BE is the bicarbonate) = UNCOMPENSATED METABOLIC ACIDOSIS. OTHER CAUSES: loss of HCO3- from other conditions, and H+ gaining conditions.
PARTIALLY COMPENSATED METABOLIC ACIDOSIS: NEED TO REDUCE [H+] – remember, pH levels are MUCH MORE IMPORTANT than base excess. Occurs by increasing ventilation rate to increase diffusion gradient and reduce PCO2. This causes shift of equilibrium to the left, favouring carbonic acid formation and reduced [H+] (and reduced BE still).
FULLY COMPENSATED METABOLIC ACIDOSIS: pH is normalised with low PCO2 and base excess as a result!
Just think, UNCOMPENSATED affects pH and BE, PARTIAL affects pH and PCO2 (different from respiratory – BE and CO2 are swapped around).
83
\*\*\*What is the compensatory mechanism in METABOLIC ALKALOSIS? (x3 stages - UPF) Causes (x1 +2) - how?
VOMITING will result in loss of protons in STOMACH ACID, leading to increased bicarbonate, leading to high pH, normal CO2 and high base excess = UNCOMPENSATED METABOLIC ALKALOSIS. OTHER CAUSES: loss of H+ through other mechanisms, and HCO3- gaining conditions.
PARTIALLY COMPENSATED METABOLIC ALKALOSIS: NEED TO INCREASE [H+] – remember, pH levels are more important than a high base excess. Occurs by reducing ventilation rate to increase arterial PCO2 (look at PHOTO!). This causes shift of equilibrium to the right to favour increased protons and high base excess.
FULLY COMPENSATED METABOLIC ALKALOSIS: will normalise pH with high PCO2 and base excess.
Just think, UNCOMPENSATED affects pH and BE, PARTIAL affects pH and PCO2 (different from respiratory – BE and CO2 are swapped around).
84
\*\*\*How should an ABG report be systematically reviewed!?
1. Acidosis/alkalosis or acidaemia/alkalaemia – assess the pH. Be realistic, if pH is TOO LOW/HIGH, patient is probably DEAD! 2. Assess the PaCO2 – tells us about the cause (respiratory, metabolic or both). More likely to be respiratory if this has changed. 3. Assess the BE – tells us about the cause (respiratory, metabolic or both). More likely to be metabolic if this has changed. 4. Assess the PaO2. High oxygen is rarely a problem. 5. Evaluate the acid-base status. LOOK AT PHOTO FOR WHAT pH, PaCO2 and BE mean for uncompensated/partially/fully compensated respiratory/metabolic acidosis/alkalosis. 6. Evaluate the oxygenation: hypoxaemia, normoxaemia or hyperoxaemia. This tells us about breathing – adds to what we know!!!
85
SUMMARY: metabolic and respiratory acidosis/alkalosis.
Really good for reference.
86
SUMMARY OF DETERMINING FULLY/PARTIALLY/UNCOMPENSATED ACIDOSIS/ALKALOSIS!
Pay attention especially to what constitutes fully compensated, partially compensated, or uncompensated.
87
What are typical values for [Hb]?
130 – 170 g/L.
88
What are typical values for pCO2? (x2)
4.7 – 6.4 kPa (35 – 48 mm Hg).
89
What are typical values for HCO3-?
22-26 mEq/L. If it is 24 mEq/L, BE is 0!
90
What are typical values for BE?
-2 to +2 mmol/L or mEq/L – this variable is CALCULATED.
91
What, out of hyperventilation and larger tidal volume is better for normoxaemia?
Larger tidal volume is better because hyperventilation means that O2 doesn’t even reach the alveoli for long, so cannot obtain maximum amount of oxygen in the lungs.
92
What is hypoxia?
Describes a specific environment – specifically PO2 in that environment i.e. conditions.
93
What is hypoxaemia?
Describes the blood environment – PaO2 – BLOOD.
94
What is ischaemia?
Tissues receiving inadequate oxygen – TISSUES.
95
What factors can put the body under hypoxic stress? (x3)
Can be brought on by altitude, exercise (this is something that the body can usually compensate for and maintain oxygen delivery) and disease e.g. COPD.
96
What happens to PO2 with age?
It declines with age.
97
What is the oxygen cascade (two things that it describes)? What law makes it happen?
Describes the decreasing oxygen tension from inspired air to respiring cells. Fick’s law is a key idea in the oxygen cascade – says flow rate is proportional to pressure gradient --\> oxygen gets from air to the respiring cells because of the pressure gradient that exist. It also describes the incremental delay in PO2 between the atmosphere and tissues.
98
In the oxygen phase, what are the proportions of oxygen and CO2 in each part of the circulation?
Oxygen is found in its highest partial pressure in the air – at 21.3kPa. It decreases to 13.5 in the alveoli, 13.3kPa in tissues, and 5.3kPa in the veins. The mixing phase (when air enters the lungs in ventilation) is when the most amount of oxygen is lost, because high-oxygen-inspiratory-air is mixing in with CO2 rich air leaving the lungs.
99
What physiological mechanisms affect the oxygen cascade? (x5)
1. ALVEOLAR VENTILATION: hypo/hyperventilation, supplemental oxygen. 2. VENTILATION/PERFUSION (V/Q) RATIO: if blockage in respiratory tree and are not ventilating but are perfusing, then will not gain oxygen and kPa will drop more in the blood. 3. DIFFUSION CAPACITY: thickness of exchange surface will reduce oxygen gain e.g. disease. 4. CARDIAC OUTPUT: need high perfusion to move blood to tissues and take new blood to alveoli to maintain concentration gradient. 5. INCREASED TISSUE O2 UTILISATION (describes O2 taken up by tissues from blood).
100
What happens to the oxygen cascade when in high altitude?
Becomes the altitude cascade. Reduced ambient pressure reduces oxygen and the oxygen gradient between the air and blood. Therefore, it is harder to maintain homeostasis. This is why it is dangerous to climb Everest without supplemental oxygen, and why airplanes are pressurised.
101
What are the challenges of high altitude? (x5)
1. Hypoxia: less oxygen in ambient air. 2. Thermal stress: -7degrees Celsius per 1000m; high wind-chill factor also. 3. Solar radiation: less atmospheric screening and reflection off snow. 4. Hydration: water loss humidifying inspired air and hypoxia induced diuresis. 5. Dangerous: windy, unstable terrain, hypoxia-induced confusion and miscoordination.
102
\*\*\*What is the bodies physiological compensatory response to high altitude? CREATE A PNEUMONIC.
1. Atmospheric oxygen is less, so there is decreased PA and PaO2 which activates peripheral chemoreceptors (as opposed to central control – which occurs in CO2). 2. There is increased SNS outflow which (i) increases VENTILATION to increase alveolar oxygen and OXYGEN LOADING; and (ii) increased heart rate and cardiac output (HR/Stroke Volume) which increases OXYGEN LOADING and tissue delivery. 3. Hyperventilation leads to hypocapnia (low blood CO2), reducing central drive to breathe, reducing ventilation and reducing OXYGEN LOADING. 4. CO2 loss increases pH, shifting oxygen dissociation curve to the LEFT, increasing oxygen affinity, but DECREASING OXYGEN UNLOADING. 5. Alkalosis produced by increased pH is detected by the carotid bodies, increasing bicarbonate secretion (and causing kidneys recover/save/manufacture acid) to normalise oxygen dissociation curve and increasing OXYGEN UNLOADING – this is a LONGER-TERM EFFECT (the rest of the above are ACUTE EFFECTS). 6. Low blood oxygen increases erythropoietin production, increasing RBC production and OXYGEN LOADING. 7. Increased oxidative enzymes, mitochondrial numbers also occur which increases aerobic respiration rate = increased OXYGEN UTILISATION. 8. There is a small increase in the amount of 2,3-DPG in RBCs, which controls oxygen unloading – hence increased OXYGEN UNLOADING.
103
What prophylaxis measures are used to tackle altitude sickness? (x2)
Prophylaxis = measure taken to prevent disease. ACCLIMATION: stimulated by artificial environments to lead to artificial acclimatisation (e.g. Hyperbaric chamber/breathing hypoxic gas). ACETAZOLAMIDE: carbonic anhydrase inhibitor, accelerates slow renal compensation to hypoxia-induced hyperventilation.
104
What are the anatomical and physiological adaptations of native highlanders?
BARREL CHEST: larger total lung capacity (TLC), more alveoli and greater capillarisation, so more O2 INTO THE BODY. INCREASE HAEMATOCRIT: greater oxygen carrying-capacity of the blood, so more O2 CARRIED IN BLOOD. LARGER HEART: to pump through vasoconstricted pulmonary circulation, so GREATER PULMONARY PERFUSION. INCRESAED MITOCHONDRIAL DENSITY: greater oxygen utilisation at cellular level, so MORE O2 UTILISED.
105
What are the causes of acute and chronic mountain sickness?
ACUTE: maladaptation to high altitude. CHRONIC: idiopathic – seen in people with long-term adaptations and acclimatisation.
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What is the pathophysiology of acute and chronic mountain sickness?
ACUTE: mild cerebral oedema. CHRONIC: secondary polycythaemia (abnormal increase in number of mature RBCs) increases blood viscosity (higher Hct), which sludges through the systemic capillary beds impeding oxygen delivery (despite more than adequate oxygenation) – is a maladaptation in established residents!
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What are the symptoms of acute and chronic mountain sickness?
ACUTE: nausea and vomiting, irritability, dizziness, insomnia, fatigue and dyspnoea – ‘hangover’. CHRONIC: cyanosis, fatigue.
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What are the consequences of acute and chronic mountain sickness?
ACUTE: development into HAPE or HACE (high altitude pulmonary/cerebral oedema). CHRONIC: ischaemic tissue damage, heart failure and eventual death.
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What is the treatment for acute mountain sickness? (x4)
Stop ascent, analgesia fluids (pain-relievers), medication (acetazolamide) or hyperbaric (greater pressure than normal) oxygen therapy.
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What is the treatment for chronic mountain sickness?
MUST stay at low altitude.
111
What are the causes, pathophysiology, symptoms and consequences of high-altitude pulmonary oedema (HAPE)?
CAUSES: rapid ascent or inability to acclimatise. PATHOPHYSIOLOGY: pulmonary vessel vasoconstriction in response to hypoxia. Leads to increased pulmonary pressure, permeability and fluid leakage – once the leakage exceeds lymph drainage, an oedema forms. SYMPTOMS: dyspnoea, dry cough, bloody sputum, crackling chest sounds. CONSEQUENCES: impaired gas exchange, impaired ventilatory mechanics.
112
What are the causes, pathophysiology, symptoms and consequences of high-altitude cerebral oedema (HACE)?
CAUSES: rapid ascent or inability to acclimatise. PATHOPHYSIOLOGY: vasodilation of vessels in response to hypoxaemia (to increase blood flow), so more blood going into capillaries and increased fluid leakage. Cranium is a ‘sealed box’, so no room to expand and intracranial pressure increases. SYMPTOMS: confusion, ataxia (the loss of full control of bodily movements), behavioural change, hallucinations and disorientation. CONSEQUENCES: irrational behaviour, irreversible neurological damage, coma and death.
113
How is HAPE treated? (x5)
Descent, hyperbaric O2 therapy, nifedipine (Calcium Channel Blocker – decrease blood pressure), salmeterol (long-acting B2 adrenergic receptor antagonists used in asthmatics – are long-acting), sildenafil (Viagra – antihypertensive).
114
How is HACE treated? (x4)
Immediate descent, O2 therapy, hyperbaric O2 therapy, dexamethasone (prevent release of inflammatory mediators).
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What is respiratory failure?
Failure to maintain adequate pulmonary gas exchange in the lungs leading to V/Q inequality.
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What are the two type of respiratory failure?
Type 1 and 2.
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What is Type 1 respiratory failure? Causes? (x3)
HYPOXIC respiratory failure with NOMRAL CO2 and LOW O2: Hypoventilation/diffusion issue – CO2 can still diffuse out easily, but OXYGEN MOVING IN IS IMPAIRED. Can be due to pneumonia, pulmonary oedema or atelectasis (collapsed lung).
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What is Type 2 respiratory failure? Causes? (x4)
HYPERCAPNIC respiratory failure – failure to get CO2 out of alveoli. Oxygen has a greater concentration gradient, so will still be able to exchange, but CO2 has a lower concentration gradient so cannot leave the alveoli (oxygen likely to be low as well). May be a V/Q mismatch if the pulmonary vessels are not well perfused. Hypercapnic failure is usually due to pulmonary fibrosis, neuromuscular disease, obesity or increased dead space (INCREASED CO2 PRODUCTION AND/OR DECREASED ELIMINATION).
