Gaseous diffusion and transport Flashcards
what does FO2 mean
fractional concentration
what does PO2 mean
partial pressure
what does PB mean
barometric pressure
what does PIO2, FIO2 mean
inspired
what does PAO2, FAO2 mean
alveolar
what does PaO2, FaO2 mean
arterial
what does mmHg mean
common pressure unit
(0.133 kPa)
what is SI measured in
kPa
(7.5 mmHg)
What does Daltonβs Law state about partial pressures?
In a mixture of non-reacting gases, the total pressure exerted is equal to the sum of the partial pressures of the individual gases.
What are the components of barometric pressure PB?
- includes all inert gases
How is the partial pressure of oxygen calculated?
What is the fractional concentration of oxygen in dry air?
0.209 (21%).
What is the approximate barometric pressure at sea level?
PB β101kPa (760 mmHg).
What is the dry partial pressure of oxygen (PO2) at sea level?
21kPa (159 mmHg).
How does the fractional concentration of oxygen (πΉπ2 ) change with altitude?
remains unchanged at 0.209, regardless of altitude.
What is the approximate barometric pressure at the top of Mount Everest?
33 kPa (250 mmHg).
What happens to ππΌπ2 with increasing altitude?
How did climbers like Hillary and Tenzing compensate for low ππ΅ at high altitudes?
They used a high πΉπΌπ2 (fraction of inspired oxygen) to compensate for the low barometric pressure.
What is the formula for Henryβs Law?
How does the partial pressure of a gas above a liquid affect the gas dissolved in the liquid?
The higher the partial pressure, the more gas will dissolve in the liquid.
What happens if the pressure above a liquid is released?
Less gas will stay dissolved, and bubbles of gas will rise from the liquid.
What happens when a gas comes in contact with a pure liquid?
Some gas molecules collide with the liquidβs surface and dissolve. A dynamic equilibrium is established when the rate of gas dissolution equals the rate of gas escape into the gas phase.
What happens when the pressure of a gas above a liquid is increased?
The number of gas molecules per unit volume increases, leading to more collisions with the liquid surface and a higher rate of gas dissolution.
What happens to equilibrium when the gas pressure above a liquid increases?
A higher concentration of dissolved gas is achieved until a new dynamic equilibrium is established at the higher pressure.
What does the concentration of a dissolved gas in a solvent at a given pressure depend on?
The concentration of a dissolved gas in solvent at a given pressure, i.e. solubility, depends strongly on its physical properties.
What factors determine water vapour pressure (PH2O)?
Water vapour pressure depends on temperature and saturation.
How does temperature affect saturated water vapour pressure?
Saturated water vapour pressure increases as temperature increases.
What happens to air as it enters the lungs?
Air passes over moist surfaces in the lungs and becomes 100% saturated.
Why is the water vapour pressure in the lungs constant?
Alveolar air is maintained at a constant temperature of 37Β°C, resulting in a constant water vapour pressure of 6.3 kPa (47 mmHg).
What is ππΌπ2 (Partial pressure of inspired oxygen)?
Why is the ππ΄π2
(Partial pressure of alveolar oxygen) not measurable directly?
Because πΆπ2 diffuses into the alveolus to replace π2 diffusing into the pulmonary capillary.
What is the partial pressure of oxygen (ππ2) in atmospheric air?
21 kPa.
What is the ππ2 in the trachea during inspiration?
20 kPa
What is the ππ2 in alveolar gas?
13.5 kPa.
What is the partial pressure of carbon dioxide (ππΆπ2) in alveolar gas?
5.3 kPa.
What is the water vapour pressure in the trachea and alveoli?
6.3 kPa
How does the pulmonary capillary ππ2 change as blood flows through it?
Pulmonary capillary ππ2 rises to match alveolar ππ2 (13.5 kPa) about 1/3 of the way along the capillary.
which is higher, alveolar PO2 or blood PO2 entering the pulmonary capillary, what does this achieve
Alveolar PO2 is higher than the PO2 in the blood entering the pulmonary capillary. This partial pressure gradient drives diffusion of O2 through the large area of thin alveolar-capillary membrane.
In which direction does CO2 move across the alveolar-capillary exchange surface?
CO2 moves down its partial pressure gradient, from the pulmonary capillary blood to the alveolar air, from where CO2 is expelled to the atmosphere during expiration
How does the rate of CO2 diffusion compare to O2?
NB: CO2 diffuses at approx. 85% of the rate of O2 ( due to its higher molecular weight).
Why does CO2 diffuse faster despite its lower diffusion rate?
CO2 is 23 times more soluble in plasma (0.7 mL/L/mmHg) compared to O2 (0.03mL/L/mmHg).
How much faster does CO2 diffuse compared to O2 when solubility and diffusion rates are considered?
CO2 diffuses 20 times faster than O2 (23Γ 0.85).
Why does CO2 equilibrate rapidly across the alveolar-capillary surface?
Due to its high solubility, CO2 equilibrates rapidly despite having a lower partial pressure gradient.
What determines gas transfer between alveolar gas and pulmonary capillary blood?
Gas transfer is determined by the partial pressure gradient, not the concentration gradient (e.g., ml/L or mmol/L).
What determines gas transfer between alveolar gas and pulmonary capillary blood?
Gas transfer is determined by the partial pressure gradient, not the concentration gradient (e.g., ml/L or mmol/L).
How does gas move in terms of partial pressure gradients?
Gas moves down a partial pressure gradient from high to low partial pressure (πgas) until a new dynamic equilibrium is reached.
How do O2 and CO2 diffuse in a normal lung?
A normal lung has more than adequate diffusion reserve, allowing O2 and CO2 to diffuse rapidly down their partial pressure gradients.
When does diffusion limitation occur?
Diffusion limitation occurs if alveolar-capillary units are disrupted by respiratory disease, especially when pulmonary blood flow increases (e.g., during exercise).
What factors affect the rate of gas diffusion across a membrane?
what drives diffusion across the alveolar-capillary membrane?
How is the rate of gas transfer calculated?
how to work out constant of proportionality
the oxygen diffusing capacity of the lungs, representing the ability of oxygen to transfer from the alveoli to the blood.
What is the equation for the rate of oxygen transfer?
It measures the carbon monoxide diffusing capacity of the lungs, representing the transfer of CO from the alveoli to the blood.
Why can pulmonary capillary
PπΆπΆπ be assumed to be zero?
Because CO is rapidly bound by haemoglobin as it crosses the alveolar-capillary membrane, leaving negligible free CO in the blood.
How does haemoglobinβs affinity for CO compare to oxygen?
Haemoglobin has approximately 240 times the affinity for CO compared to oxygen.
How is π·πΏπΆπ clinically measured?
A patient inhales a breath containing a very low concentration of CO and a tracer gas. The composition of the exhaled gas is then analyzed.
What is another term for π·πΏπΆπ?
what 3 factors reduce π·πΏπΆπ
- reduction in alveolar capillary membrane
- increased thickness of alveolar capillary membrane
- anaemia
What 3 things causes a reduction in alveolar-capillary membrane area, leading to decreased π·πΏπΆπ?
emphysema
pulmonary emboli
lung resection.
How does increased alveolar-capillary membrane thickness affect π·πΏπΆπ
Increased thickness, as in pulmonary oedema or pulmonary fibrosis, reduces diffusion due to:
- Thickened membrane.
- Reduced membrane area caused by smaller lung volume.
what 2 things can increase π·πΏπΆπ
Increased pulmonary blood volume, as occurs in⨠exercise (increases the effective area)
polycythaemia
What is the minimum ππ2 needed by mitochondria in tissues?
What is the ππ2 gradient from the capillaries to the tissues?
β5.3kPa.
What happens if capillary ππ2 becomes too low?
Diffusion becomes too slow to meet tissue needs, resulting in tissue hypoxia.
At the site of production, i.e., mitochondria.
What cardiac output would be required to meet resting oxygen consumption using dissolved π2 alone?
What is the normal basal cardiac output?
Approximately 5L/min, which is far less than required for dissolved oxygen alone.
What is hemoglobin composed of?
Four subunits, each containing a protein chain (globin) and a haem group.
What is the structure of normal adult hemoglobin (HbA)?
HbA contains two identical Ξ±-chains (141 amino acids each) and two Ξ²-chains (146 amino acids each).
What is the haem group, and where is it attached?
The haem group is an iron porphyrin compound attached to each globin chain at a histidine residue.
In what form is the iron atom in the haem group, and what is its role?
The iron atom is in the ferrous (Fe2+) form and binds to one oxygen molecule.
How many oxygen molecules can one hemoglobin molecule bind?
Each hemoglobin molecule can bind up to 4 oxygen molecules.
How much oxygen does 100 mL of blood contain without hemoglobin?
How much oxygen can 1 gram of hemoglobin combine with?
What is the normal concentration of hemoglobin in blood?
What is the oxygen capacity of normal blood?
What is the oxygen saturation and content of blood entering pulmonary capillaries at rest?
What is the oxygen saturation and content of blood leaving pulmonary capillaries at rest?
What happens when the first oxygen molecule binds to hemoglobin?
Binding of the first O2 to a haem group causes a conformational change in the globin sub-unit.
it increases the affinity of adjacent globin moleculesβ haem groups for O2, enhancing subsequent oxygen binding.
What gives the oxyhaemoglobin dissociation curve its sigmoid shape?
Co-operative binding of oxygen to hemoglobin.
Why is the plateau region of the dissociation curve significant?
blue text
At what Pπ2 does a precipitous drop in saturation occur, and why is this significant?
A precipitous drop occurs below 8 kPa, indicating a critical threshold where oxygen delivery to tissues may become compromised.
What factors increase hemoglobinβs affinity for π2, causing a leftward shift in the dissociation curve?
β pH (alkalosis)
β ππΆπ2
β Temperature
β 2,3-DPG (e.g., in alveoli).
What factors decrease hemoglobinβs affinity for π2 , causing a rightward shift in the dissociation curve?
β pH (acidosis)
β ππΆπ2
β Temperature
β 2,3-DPG (e.g., in chronic hypoxia or exercise).
(THE BOHR SHIFT)
What is the Bohr shift, and how does it assist oxygen unloading?
What is anaemia?
Anaemia is a condition characterized by a reduced content of functional haemoglobin in the blood due to defects in haemoglobin production or red cell numbers.
What are some causes of anaemia?
Defect in haemoglobin synthesis.
Genetic mutations.
Reduced production or loss of red blood cells.
How does anaemia affect oxygen transport?
Anaemia causes a reduction in the bloodβs oxygen-carrying capacity.
How does the oxygen dissociation curve differ in anaemia compared to normal conditions?
In anaemia, the oxygen content is significantly reduced due to lower haemoglobin levels ([Hb] = 75 g/L vs. normal 150 g/L), but tissues still metabolize oxygen at the same rate.
What happens to venous and tissue PO2 in anaemia?
Venous PO2 is lower (3.6 kPa), causing tissue PO2 to also drop, leading to hypoxia.
How does anaemia affect oxygen extraction and exercise tolerance?
Anaemia limits oxygen extraction during exercise, leading to fatigue and poor exercise tolerance.
How much oxygen do tissues extract from the blood in anaemia compared to normal conditions?
Tissues still extract 5 ml/dL of oxygen, but due to reduced haemoglobin, the oxygen reserve is less, resulting in hypoxia.
How do maternal and fetal hemoglobin differ in composition?
Maternal HbA has 2 Ξ± and 2 Ξ² protein chains, whereas fetal HbF has 2 Ξ± and 2 Ξ³ globin subunits.
Why does fetal hemoglobin have a higher affinity for oxygen compared to maternal hemoglobin?
The Ξ³ globin subunits in HbF increase the affinity of the haem group for oxygen and bind 2,3-DPG less effectively.
What is the functional significance of HbFβs higher oxygen affinity?
It facilitates the transfer of oxygen from the motherβs blood to the fetal blood across the placenta.
How is the oxygen dissociation curve for HbF positioned relative to HbA?
The HbF curve is shifted to the left compared to HbA, indicating a higher oxygen affinity.
How is carbon monoxide (CO) generated?
CO is produced during the incomplete combustion of hydrocarbon fuels.
How does the affinity of CO for hemoglobin compare to that of oxygen?
CO has 240 times the affinity for hemoglobin compared to oxygen, binding to the same site in the haem group.
What is the form of hemoglobin bound to CO called, and what is its appearance?
Hemoglobin bound to CO is called carbaminohaemoglobin
What are the two negative effects of CO binding to hemoglobin?
- Reduces the amount of oxygen bound to hemoglobin.
- Shifts the oxygen binding curve to the left, increasing the oxygen affinity of remaining binding sites and reducing oxygen unloading in tissues.
What happens to hemoglobin in CO poisoning?
In CO poisoning, 50% of hemoglobin is bound to CO, forming carboxyhemoglobin (COHb), which reduces oxygen binding and transport.
How much oxygen do tissues still remove in CO poisoning?
Tissues still remove 5 mlΒ·dlβ»ΒΉ of oxygen from the blood.
What happens to venous and tissue POβ in CO poisoning?
Venous POβ drops to 2 kPa, causing tissue POβ to also decrease to 2 kPa, leading to hypoxia.
What are the severe symptoms caused by CO poisoning?
Headache, convulsions, coma, and death can result from severe hypoxia caused by CO poisoning.
What causes cyanosis?
Cyanosis occurs when the supply of Oβ to tissues is deficient, leading to an increase in deoxyhemoglobin (deoxyHb), which has a bluish tinge and discolors tissues.
What are the two types of cyanosis?
Peripheral cyanosis and central cyanosis.
What is peripheral cyanosis?
Peripheral cyanosis is reduced blood flow to specific regions, causing hypoxic tissue and a bluish-grey tinge in extremities like hands and feet.
What are the 4 causes of peripheral cyanosis?
Cardiovascular shock
Low temperature
Reduced cardiac output
Poor arterial supply
What happens to respiration and arterial Oβ content in peripheral cyanosis?
Respiration is normal, and arterial Oβ content is likely also normal.
What is central cyanosis?
Central cyanosis occurs due to arterial hypoxaemia (reduction in Oβ content). It is best observed in the buccal mucosa and lips.
At what concentration of deoxygenated hemoglobin does cyanosis become observable?
Cyanosis is observable when arterial blood contains >1.5β2 g/dL of deoxygenated hemoglobin, even in well-perfused tissues.
At what oxygen saturation level does central cyanosis occur with normal hemoglobin concentration?
: Central cyanosis occurs when Oβ saturation falls below 85%, assuming normal hemoglobin concentration (15 g/dL).
How does cyanosis presentation differ in polycythaemic and anaemic patients?
In polycythaemic patients: Cyanosis appears at higher oxygen saturations.
In severe anaemia: Central cyanosis may be impossible as it would require an Oβ saturation incompatible with life.
What are the 2 causes of low POβ in arterial blood leading to hypoxia?
What 2 conditions reduce the bloodβs ability to carry oxygen?
Anaemia and carbon monoxide (CO) poisoning.
What are the two types of reduction in tissue blood flow?
Global: Circulatory shock.
Regional: Local obstruction (e.g., arterial blood clot or embolus).
What causes tissues to be unable to utilize oxygen?
Histotoxic hypoxia (e.g., cyanide poisoning).
In what three forms is COβ carried in the blood?
60% as HCOββ» (bicarbonate) in plasma and inside red blood cells (RBCs).
30% as Hb-COβ (carbaminohaemoglobin).
10% as dissolved COβ in plasma.
What is the solubility of COβ in blood?
0.52 mlΒ·dlβ»ΒΉΒ·kPaβ»ΒΉ.
How much dissolved COβ is present in normal arterial blood at PCOβ = 5.3 kPa?
: 2.74 mlΒ·dlβ»ΒΉ, which accounts for approximately 10% of the added COβ.
What is the reaction converting COβ to bicarbonate?
What buffers the HβΊ ions produced during bicarbonate formation?
Imidazole groups of histidine in haemoglobin.
Haemoglobin acts as a good buffer with 38 histidine residues per molecule.
What is the chloride shift?
Bicarbonate (HCOββ») formed in red blood cells diffuses into the plasma down its concentration gradient.
Chloride ions (Clβ») move into red blood cells to maintain electrical neutrality.
How are carbamino compounds formed?
Why is deoxyhemoglobin important for carbamino compound formation?
Carbamino compounds are mostly formed with deoxy-Hb in red blood cells.
A smaller amount is formed with plasma proteins
How is dissolved COβ removed in the lungs?
COβ dissolved in blood plasma diffuses down the partial pressure gradient into the alveoli very rapidly.
What happens to COβ reversibly bound as carbamino compounds to hemoglobin in the lungs?
COβ comes off hemoglobin, assisted by the oxygenation of Hb, and diffuses into the alveoli.
How is bicarbonate (HCOββ») handled during COβ unloading?
HCOββ» from plasma is taken back into red blood cells, combines with HβΊ to form carbonic acid.
What happens to carbonic acid during COβ unloading?
Carbonic acid dissociates into COβ and HβO via carbonic anhydrase, with COβ diffusing into the alveoli.
What is the Haldane effect?
At any given PCOβ, the quantity of COβ carried is greater in partially deoxygenated blood (venous) than in oxygenated blood (arterial).
what 2 things is the haldane effect due to
Due to:
1. Hb forms carbamino compounds more readily when deoxygenated so can carry more CO2.
- Hb binds to H+ better when deoxygenated this favours formation of HCO3-, increasing CO2
What does the CO2 binding curve in the blood look like?
The curve shape:
- not sigmoid
- no plateau
- approx linear over physiological range
How does the COβ carrying capacity compare to Oβ?
The total COβ carrying capacity is greater than that for Oβ.
For a given PCOβ, how does COβ content differ between venous and arterial blood?
Venous blood has more COβ content than arterial blood due to the Haldane Effect.
How much COβ do tissues produce at rest for every 100 ml of blood?
Tissues produce 4 ml of COβ for every 100 ml of blood passing through.
What happens when ventilation does not match metabolic requirements?
It results in either hyperventilation or hypoventilation, measured with respect to arterial PCOβ.
What is hyperventilation?
Over-ventilation in proportion to metabolism, leading to a lowering of arterial PCOβ below normal values.
What is hypoventilation?
Under-ventilation in proportion to metabolism, resulting in higher arterial PCOβ levels.
Does hyperventilation mean just increased ventilation?
No. In exercise, ventilation increases but is matched to metabolic rate, so arterial PCOβ (and POβ) remains relatively constant. This is not hyperventilation.
What is the formula for alveolar ventilation (ππ΄ )?
Because COβ rapidly equilibrates across the alveolar-capillary gas exchange surface.
What is hyperventilation?
Over-ventilation in proportion to metabolism, leading to low arterial ππΆπ2 (<5.3 kPa) and respiratory alkalosis.
How does alkalosis due to hyperventilation affect plasma calcium levels?
Alkalosis reduces free plasma calcium as more calcium binds to proteins, increasing cell excitability.
What are the symptoms of alkalosis due to hyperventilation?
Disturbed sensations like βpins and needles,β especially in hands and feet, and unwanted tetanic muscle contractions (spasms).
What are the possible causes of hyperventilation?
Anxiety, pain, or excessive mechanical ventilation.
Diseases contributing to metabolic acidosis, e.g., renal failure or diabetes.
What is hypoventilation?
Under-ventilation in proportion to metabolism, leading to hypercapnia (high arterial ππΆπ2 > 6 kPa) and respiratory acidosis.
What are the possible causes of hypoventilation?
Head injury impairing respiration.
Use of anaesthetics or drugs.
Chronic lung disease.
What happens as arterial ππΆπ2 increases?
It causes peripheral vasodilation, flushed skin, a full pulse, and extra systoles.
What are the effects of very high ππΆπ2 (> 10 kPa)?
It depresses central nervous system (CNS) function, causing confusion, drowsiness, coma, and potentially death.
What are the partial pressures of oxygen (POβ) and carbon dioxide (PCOβ) in inhaled air?
POβ = 21 kPa
PCOβ = 0 kPa.
What are the partial pressures of oxygen (POβ) and carbon dioxide (PCOβ) in inspired air in the airways?
POβ = 20 kPa
PCOβ = 0 kPa
PHβO = 6.3 kPa.
What are the partial pressures of oxygen (POβ) and carbon dioxide (PCOβ) in the alveoli?
POβ = 13.3 kPa
PCOβ = 5.3 kPa.
What are the partial pressures of oxygen (POβ) and carbon dioxide (PCOβ) in arterial blood?
POβ = 12.5 kPa
PCOβ = 5.3 kPa.
What are the partial pressures of oxygen (POβ) and carbon dioxide (PCOβ) in mixed venous blood (resting)?
POβ = 5.3 kPa
PCOβ = 6.1 kPa.
What is the oxygen content of arterial blood?
200 ml per liter.
What is the oxygen saturation of arterial hemoglobin (Hb) at rest?
> 97%.
What is the oxygen content of mixed venous blood?
150 ml per liter.
What is the oxygen saturation of hemoglobin (Hb) in mixed venous blood?
~75%.
What is the range of alveolar PCOβ (PACOβ) at rest?
4.7β6.1 kPa (35β45 mmHg).
What is the arterial COβ content at rest?
480 ml per liter.
What is the mixed venous COβ content at rest?
520 ml per liter.
What is the normal range of arterial pH?
7.36β7.44 (36β44 nmol H+/liter).
What is the normal range for arterial bicarbonate ([HCOββ»]) levels?
21β27 mmol/liter.
these question were on the slides, look at lecture capture for the answers
FREQUENTLY ASKED QUESTION: Does oxygen bound to haemoglobin contribute to PO2 or is PO2 just related to the dissolved oxygen?
The PO2 of blood is dependent on the amount of dissolved oxygen in the blood (the constant relating PO2 and content is the solubility of oxygen in the plasma/blood)). The oxygen bound to haemoglobin does not contribute directly to the PO2. However, it acts as a reservoir of oxygen, which can top the dissolved oxygen as this diffuses to the tissues.
If we could instantaneously replace the blood in the circulation by plasma, arterial PO2 would be unaffected but mean tissue capillary PO2 would fall and oxygen delivery would be inadequate to sustain life. The following diagrams show how PO2 falls (values in kPa) along the tissue capillary with different PaO2s and different [Hb]s.
What happens to oxygen delivery if hemoglobin concentration is 0 g/L?
Arterial POβ equilibrates with alveolar gas, reaching about 13 kPa.
Oxygen content in plasma is very low (approx. 3 ml/L).
Oxygen quickly diffuses out of capillaries to tissues, dropping POβ to zero after the first cell or two.
Most tissue remains hypoxic (dark blue cells).
How does normal hemoglobin maintain oxygen delivery to tissues?
Dissolved oxygen diffuses to tissue cells.
Oxygen bound to hemoglobin replenishes dissolved oxygen.
POβ remains high enough along the capillary to ensure adequate oxygen diffusion.
Reserve oxygen is available for exercise.
what is the effect of polycythaemia in chronic respiratory failure?
Increased hemoglobin compensates for low arterial POβ.
Higher oxygen reservoir reduces the steep fall in POβ along the capillary.
Tissue oxygen delivery may remain acceptable, but vulnerability to further POβ drops increases.
Cyanosis is likely due to high deoxygenated hemoglobin levels.
How does anemia affect tissue oxygen delivery?
Average tissue capillary POβ is reduced due to lower bound oxygen levels.
The oxygen delivery at rest may suffice but is inadequate during exercise.
Reduced hemoglobin limits the ability to meet increased oxygen demand.
