Oxygen and Carbon dioxide Transport

Question 1

Describe the means by which oxygen is transported in the blood

Answer 1

1.) Through binding to the haem group of haemoglobin (98.5%)
[Hb] = 15 gm/dL
2.) In blood plasma (soluble) (1.5%)
- Advantage of not using transport proteins is that it decreases the viscosity of the blood, allowing for more efficient circulation.

Question 2

Describe the structure and function of oxygen-binding proteins

Answer 2

Haem - Fe2+ porphyrin molecule. Has multiple oxidation states.
Globin - Formed from 4 polypeptide chains
Adult HbA = Most prevalent. Formed from 2 alpha and 2 beta chains
Fetus Hb = Formed from 2 alpha and 2 gamma chains. Gamma is replaced by beta approx. 3 months after birth. Very small amounts are still seen.

Question 3

Key Terms

PaO2, Ca02, SaO2, oxygen capacity

Answer 3

PaO2: The amount of oxygen dissolved in plasma. Partial pressure is always related to solubility.
Oxygen capacity: Amount of oxygen bound to haemoglobin
CaO2: Oxygen content. Amount of oxygen bound to haemoglobin and dissolved O2
SaO2: Oxygen saturation. The % of available binding sites bound to O2. Stays constant with PaO2.
- Increasing ventilation rate will increase Pa02 but this has little effect in health as Hb is usually close to saturation.

Question 4

Explain the shape and significance of the oxygen and haemoglobin dissociation curves.

Answer 4

• Sigmoidal curve. Cooperative binding is seen between oxygen and the haem group. With binding of oxygen causing an allosteric change in the molecule, increasing binding ability. This then plateaus.

Question 5

Describe the factors that affect gas transport and cause right and left hand shifts of the oxygen-haemoglobin dissociation curve

Answer 5

• Right hand shift: Affinity for oxygen is decreased - more unloaded into the tissues. Increased acidity (Bohr effect), increased temperature, increased PaCO2, 2, 3 - BPG
• Left hand shift: Affinity for oxygen is increased - less unloaded into tissues. Decreased acidity, decreased PaCO2, decreased temperature, fetal haemoglobin

Question 6

Appreciate the nature of haemoglobinopathies

Answer 6

Anaemia: [Hb] is below normal for age and gender. Reduced ability of oxygen transport is seen.
- Sickle cell: V6G. Unable to travel well through blood vessels. Brittle, can lyse. Decreased solubility.
- Diet acquired anaemia: Too little iron in diet.
- Pernicious anaemia: Loss of intrinsic factor in the stomach for B12 absorption.
Haemoglobinopathy: A hematologic disorder - due to the alteration in genetically determined molecular structure of Hb e.g. sickle cell or thalassaemia.
- Methemoglobinema (MetHb): Heme group inaccessible to methaemoglobin reductase (His replacement)
- Thalassemias: Mutations alter processing and degradation of mRNA or proteolytic degradation of globin chains.

Question 7

Pulse oximetry and oxygen saturation (SaO2)

Answer 7

Pulse oximetry: Non-invasive. < 92 % = abnormal. ERRORS: Excess light, skin pigmentation, nail varnish

• SaO2: Sample from artery
• SpO2: From pulse oximetry (measured ratio of red light and infra red light absorbed)

Question 8

Describe the means by which carbon dioxide is transported in the blood

Answer 8

1.) As the bicarbonate ion (78 %)
Catalysed by carbonic anhydrase.
CO2 + H2O --> H2CO3 --> H+ + HCO3-
2.) As carbamino haemoglobin (13%)
CO2 + Hb --> HbCO2
3.) In blood plasma (9%)
CO2 is x20 more soluble than O2 - more seen dissolved.

Question 9

CO2 in RBCs - Systemic circulation

Answer 9

CO2 produced in the tissues into RBCs –> Hydration of CO2 (CO2 +H2O) –> Carbonic acid (H2CO3) produced through a reaction catalysed by carbonic anhydrase –> Dissociates into H+ and HCO3-.
Hb acts as a buffer for H+. HCO3- diffuses into the plasma. Chloride shift sees Cl- move into the cell, compensates for the loss of the negative ion.
- THIS IS REVERSED IN PULMONARY CIRCULATION

Question 10

Explain the shape and significance of the oxygen and haemoglobin dissociation curves.

Answer 10

Dissociation of CO2 from the blood (venous and arteriole) is linear.
SaO2 has a major effect on the curve.
DeoxyHb has a greater affinity for CO2.
Venous blood transports CO2 more readily than arteriole blood.

Question 11

Myoglobin

Answer 11

• Has a single oxygen binding site, therefore binding is not cooperative.
• Shuttles oxygen from the cell membrane to mitochondria.
• Has a very high affinity for oxygen (higher than haem), only releases it when it really has to. Oxygen provided for working muscles.
• During crushing injuries it may be released. Can be very toxic (liver)

Question 12

Describe the functions of the conducting and respiratory zones and relate these to their anatomical and histological features.

Answer 12

Conducting zones allow the passage of air into the respiratory system. They moisten and warm the air, allowing for optimum gas exchange. Hence, the airway is patent.
Respiratory zones allow for the exchange of oxygen and carbon dioxide. The respiratory zone has a large surface area and is thin, allowing for maximum exchange.

Question 13

Define the terms ‘anatomical’ and ‘physiological’ dead space and explain influential factors on the volumes of each

Answer 13

Anatomical: Areas within the conducting zone where air is not expelled from, becoming stagnant.
Physiological dead space: Functional. Areas within conducting and respiratory zones (whole system) that do participate in gas exchange.
- Can be increased in pathology, e.g. COPD. Can be changed by position, age, size of breath, anatomy

Question 14

Explain the principles underlying gas flow and exchange across the alveolar-capillary walls, how factors in health and disease can affect this process and how pulmonary diffusion can be measured.

Answer 14

Fick’s law outlines the rate of diffusion. Proportional to surface area, inversely proportional to the thickness of the surface and proportional to the partial pressure gradients.
In disease the alveoli may be destroyed, decreasing SA, or may undergo fibrosis, increasing the diffusion distance.
Measuring pulmonary diffusion: Transfer capacity. DL gas. Tests transfer across the air:blood barrier Individuals breathe in air containing a small amount of CO. The rate of disappearance is measured through measurements of inhaled and expired air. Tests the integrity of the alveoli.

Question 15

Describe the partial pressure gradients for oxygen and carbon dioxide exchange, and the normal values for their partial pressures.

Answer 15

Partial pressure of oxygen decreases through the system as it is used by tissues. Oxygen has a greater partial pressure gradient but the increased solubility of carbon dioxide increases its exchange.
Oxygen:
PIO2 160 mmHg –> PAO2 100 mmHg –> PaO2 95 mmHg —> PvO2 40mmHg
Carbon dioxide:
PvCO2 46 mmHg –> PACO2 40 mmHg –> PEO2 32 mmHg

Question 16

Explain the clinical relevance of ventilation-perfusion matching and explain how respiratory dysfunctions can disrupt this process

Answer 16

Airflow and blood flow are governed by Poiseulle’s Law (flow, pressure and resistance). Resistance to flow in inversely proportional to the diameter of the vessel.
VQ matching ensures that sufficient oxygen is available for binding to haem and transport to tissues. Allows the metabolic demands of tissues to be met. Oxygen is essential. VQ matching maximises exchange within the alveoli.
VQ mismatch is the most common cause of lowered PaO2. Increases the area that is not used for gas exchange.
Lack of ventilation: Capillaries constrict, diverting blood to a better perfused area.
Raised PaCO2: Bronchioles dilate to improve airflow.

Question 17

Hypoxia

Answer 17

Insufficient oxygen to carryout normal metabolic functions

Question 18

Arterial hypoxemia

Answer 18

PaO2 is below normal range