Carriage of Gases Flashcards
What is the equation for pressure?
Pressure = Force/Area
What units can be used for pressure?
- kPa (kiloPascal)
- N/m²
- mmHg (millimetres of mercury)
What is partial pressure?
- In a mixture of gases, each one exerts an individual pressure- partial pressure
- Partial pressure of any gas is independent of other gases in a mixture
- If other gases were removed, the partial pressure would equal total pressure
What is Dalton’s law?
- Total pressure is equivalent to sum of component partial pressures
- E.g. Atmospheric pressure is 100kPa and oxygen constitutes 21% of air, there oxygen partial pressure = 21kPa
- In lower altitude oxygen partial pressure is also lower
What is the relationship between partial pressure and solubility?
- Gases dissolve in aqueous solutions
- At equilibrium, partial pressure of a gas in solution is equal to that of gaseous form
What is Henry’s Law?
[Gas]= partial pressure x solubility coefficient
- Each gas has its own solubility coefficient
- Also dependent on factors like temperature
How is oxygen carried in the blood?
- Dissolved in plasma
- Bound to haemoglobin (found in erythrocytes)
What is the normal range of haemoglobin in females?
- 11.5-16.0g/100 ml
What is the normal range of haemoglobin in males?
- 13.5-18.0g/100ml
What is the importance of haemoglobin?
- Haemoglobin is important because otherwise we would need a large cardiac output
- 99% of oxygen carriage comes from haemoglobin
How does oxygen enter the blood from the lungs?
- Diffusion from alveoli to the blood
- High pressure to low pressure
How is oxygen delivered to tissue?
- Oxygen travels from blood into interstitium
- From interstitial into cells
- From cells into mitochondria for oxidative phosphorylation
- Partial pressure from blood to mitochondria is decreasing so oxygen moves down a gradient
Describe the structure of haemoglobin
- 4 sub- units each with global chain (peptide) and haem group (porphyrin ring)
- Each subunit will bind to 1 molecule of oxygen
- Saturated haemoglobin therefore will bind to 4 oxygen molecules
How much oxygen does 1g of haemoglobin bind to?
- 1.36ml of oxygen at body temperature and pressure
- Hb is then saturated
What is anaemia?
- Anaemia is the lack of Hb in the blood
- Less haemoglobin means less total oxygen content regardless of saturation
What does anaemia result from?
- Impaired production (iron deficiency etc.)
- Increased breakdown (haemolysis)
- Blood loss (haemorrhage)
- Fluid overload (haemodilution)
Describe the structure of adult haemoglobin (HbA)
- 2 alpha chains of 141 amino acids
- 2 beta chains of 146 amino acids
What percentage of adult haemoglobin in HbA₂?
2%
Describe the structure of HbA₂
- 2 alpha chains
- 2 delta chains replace the beta chains
What percentage of adult Hb is HbF (foetal haemoglobin)?
1%
Describe the structure of foetal haemoglobin
- 2 alpha chains
- 2 gamma chains replace beta chains
What is foetal haemoglobin?
- Embryonic forms replaced by HbF from 13 weeks of gestation
- At birth, majority of Hb is still HbF (80%)
- Switched to adult forms occurs between 3-6 months of age
- HbF not fully replaced and is approximately 1% adult Hb
What are some genetic defects that can occur in globin chains?
- Commonest of all genetic disorders
- Thalassaemia- defect in synthesis of globin chains
- Sickle cell disease- defect in structure of globin chains
What is Thalassaemia?
- Inherited defects in globin chain synthesis
- Can either be alpha or beta thalassaemia depending on chain affected, Hb not made properly
- Leads to imbalance of chains result in decreased erythropoiesis and increased haemolysis of mature cells
What causes sickle cell disease?
- Specific mutation in the beta chain
- A to T- valine for glutamine at codon 6
What are the two types of sickle cell disease?
- Heterozygous (HbAS)- leads to sickle cell trait
- Homozygous (HbSS)- leads to sickle cell anaemia
Describe heterozygous sickle cell disease (HbAS)
- Generally asymptomatic
- Anoxia manifesting in stress (e.g. air travel)
- Confers protection against malaria
What does sickle shaped cell mean for the circulation?
- Decreases flexibility of the cell leading to characteristic sickle shape
- Sickling leads to shortened erythrocyte survival and impaired flow through microcirculation
- Impaired blood flow and infarctions
Describe homozygous sickle cell disease (HbSS)
- Symptoms variable from asymptomatic to death
- Increased turnover of cells can lead to severe haemolytic anaemia
- Severe pain (bone and spleen common) due to vast-occlusive crises and infarction
How long do sickle cell abnormalities take to manifest?
- around 6 months
- Due absence of beta globin chains
How does oxygen bind to haem?
- Haem group has 4 pyrrole groups arranged in porphyrin ring, centre is Fe²⁺
- Oxygen binds to Fe²⁺ and interacts with iron
- Fe³⁺ is unable to do this
Describe how haemoglobin saturation works
- Each haemoglobin can carry 4O₂
- Saturation 50\5 means half haemoglobin in the blood is fully saturated
- Haemoglobin only exists in two states
Describe cooperative binding of oxygen
- Each oxygen increases haemoglobin affinity for oxygen
- Cooperative binding means that once oxygen has bound, more likely for oxygen to continue to bind
- Increasing affinity of Hb to bind to oxygen
What are the relative oxygen affinities for two Hb sub-species?
- Haemoglobin with three oxygens bound to it has 100x more affinity for oxygen than Hb with no oxygen bound to it
- Haemoglobin with less bound oxygen makes blood appear blue
Describe a normal oxygen-haemoglobin dissociation curve
- Sigmoidal curve
- Loading in lungs
- Unloading in tissues
Describe oxygen-haemoglobin dissociation in the heart
- Heart extracts most oxygen available
- As there is little functional reserve
- To increase oxygen delivery, blood flow must increase
- Cardiac muscle is sensitive to ischaemic stress
Describe oxygen-haemoglobin dissociation in the kidneys
- Kidney receives ~25% of cardiac output due to its excretory role rather than demand
- Therefore, renal outflow has high Hb saturation
What factors affect the dissociation curve?
- Factors that affect haemoglobin affinity
E.g. Hb affinity to bind to oxygen decreases - Dissociation curve shifts to right
- At any given PO₂ now, Hb saturation is lower
- Increased O₂ delivery to tissues
What factors affect Hb affinity?
- Temperature
- [H+]- Bohr effect
- 2,3 Biphosphoglyceric Acid (BPG)
How does temperature affect oxygen-haemoglobin dissociation?
- Increased temperature decreases the affinity for oxygen
- Reduced affinity can occur during exercise (metabolism)
What is the Bohr Effect?
- Related to pH changes- H+ and CO₂
- H+ stabilises deoxy-Hb, decreasing affinity for O₂ and increasing tissue delivery- binds protein and change conformation shape
- Chronic change in Ph from 7.4 to 7.2 can increase O₂ delivery by approx. 15%
- Acute pH changes occur often and change O₂ delivery
- Metabolically active tissue produces CO₂ and require more O₂ to respire aerobically
- Anaerobic respiration will also increase pH
What is BPG?
- 2,3 Bisphosphoglyceric Acid
- 1,3 BPG in glycolysis converted to 2,3 BPG (enzyme BPG maltase increases [H+])
- 2,3BPG can be converted to 3-phosphoglycerate in glycolysis (enzyme BPG phosphate- decreases [H+])
What factors increase BPG production?
- High altitude
- Chronic hypoxia states
- -> Lung disease, heart disease and anaemia
How does BPG stabilises Deoxy-Hb?
- BPG stabilises the deoxy-Hb
- BPG binds between lysine and histidine residues of B-globin chains
- Oxygenated Hb has a different conformation and prevents binding
- Does not stabilises Oxy-Hb
Describe BPG and Foetal Haemoglobin
- As BPG binds to beta chains it does not affect HbF, which has gamma chains
- As such HbF has a greater affinity for O₂ than HbA in the presence of BPG
- Without increased affinity, foetal haemoglobin has a higher affinity for any given PaO₂
