Haemaglobin and oxygen transport

Dalton’s Law

The total atmospheric pressure exerted by a gas is equal to the sum of the partial pressures of the individual gases 

Henry’s Law

The amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid

Fick’s Law

V’gas = D*A* ΔP/T

• V’gas = Rate of gas diffusion across permeable membrane

• D = Diffusion coefficient of that gas for that membrane

• A = Surface Areas of the membrane

• ΔP = difference in partial pressure of gas across the membrane

• T = Thickness of the membrane

What are the types of shunting of blood at the lungs

1. Anatomical shunt: Blood bypasses the alveoli entirely, such as through the bronchial circulation or thebesian veins.

2. Physiological shunt: Blood flows through poorly ventilated alveoli, resulting in incomplete oxygenation.

Describe the oxygen cascade

The progressive decrease in oxygen partial pressure (PO2) as oxygen moves from the atmosphere to the mitochondria in cells

Describe the structure of Haemoglobin

• Tetrametric

  • 2 alpha chains

  • 2 Beta chains

• Binds a total of 4 oxygen molecules

• Carries O₂ from lungs to tissues

• Co-operative binding of O₂

• Required to increase the solubility of O₂ in blood

Describe co-operative binding of oxygen in haemoglobin

As oxygen binds to one subunit, it increases the affinity of the remaining subunits for oxygen. This means that binding of subsequent oxygen molecules becomes easier.

Oxygen binding causes a structural change in haemoglobin from the tense (T) state to the relaxed (R) state. This conformational shift is key to the cooperative mechanism.

Describe how changes in pO2 affect the state of haemoglobin

Low pO2 in tissues favours T state: Oxygen unloading

High pO2 in lungs favours R state: Oxygen loading

What equation represents the binding of oxygen to haemoglobin

O2 + HHb = O2Hb + H+

• O2 is oxygen

• HHb is deoxyhemoglobin (also called reduced hemoglobin)

• O2Hb is oxyhemoglobin

• H+ is a hydrogen ion (proton)

Describe the effects of oxygen binding to haemoglobin

1. Oxygen binding: When oxygen binds to deoxyhemoglobin (HHb), it forms oxyhemoglobin (O2Hb).

2. Proton release: The binding of oxygen causes the hemoglobin molecule to release a proton (H+).

3. Bohr effect: The release of protons during oxygen binding is the basis of the Bohr effect. As pH decreases (more H+ ions), the affinity of hemoglobin for oxygen decreases, facilitating oxygen release in tissues.

O2 + HHb = O2Hb + H+

What are the methods of CO2 transport

•Dissolved

•Bicarbanate and H+ ( Via carbonic acid)

•carbaminohemoglobin

Describe the importance of the Bohr effect in terms of oxygen binding to haemoglobin

The release of protons during oxygen binding to haemoglobin is the basis of the Bohr effect.

As pH decreases (more H+ ions), the affinity of hemoglobin for oxygen decreases, facilitating oxygen release in tissues.

O2 + HHb = O2Hb + H+

Draw a diagram of gas exchange in the alveoli

Draw a diagram of gas exchange in respiring tissues

Describe the effects of 2-3 DPG (aka 2,3-Bisphosphoglycerate)

• An intermediate product of glycolysis

• Interacts with deoxygenated haemoglobin beta subunits

• Stabilises the low oxygen affinity state (T state)

• Decreases the affinity for oxygen

• Promotes the release of the remaining bound oxygen molecules

• Enhances the ability of RBCs to release oxygen near tissues 

What are the signs of carbon monoxide poisoning

• Sickness

• Headache

• Dizziness

• Tiredness

Describe the effect of carbon monoxide on haemoglobin

• Hemoglobin binds carbon monoxide (CO) 200 to 300 times more than with oxygen

• Forms carboxyhemoglobin

• The binding of one CO molecule to haemoglobin increases the affinity of the other binding spots for oxygen

• Prevents oxygen unloading in peripheral tissue

• Can have severe tissue hypoxia while maintaining a normal PaO2

Why does carbon monoxide prevent oxygen unloading at peripheral tissues

Stabilization of the R-state of hemoglobin: Carbon monoxide stabilizes hemoglobin in its relaxed (R) state, which has a higher affinity for oxygen. This makes the hemoglobin resistant to conformational changes that would normally allow oxygen unloading.

What causes a left shift in the oxygen haemoglobin dissociation curve

• Decreased Temp

• Decreased 2-3 DPG

• Decreased [H⁺]

• Carbon Monoxide

What causes a right shift in the oxygen haemoglobin dissociation curve

• Increased Temp

• Increased 2-3 DPG

• Increased [H⁺]

Describe the Bohr effect in haemoglobin

• Carbon dioxide reacts with water to form carbonic acid

• An increase in CO₂ results in a decrease in blood pH (more free H+)

• Hemoglobin proteins releasing their load of oxygen

• A decrease in carbon dioxide provokes an increase in pH (less free H+)

• Haemoglobin picks up more oxygen.

Define respiratory acidosis

Respiratory acidosis is a condition that occurs when the lungs cannot remove all of the carbon dioxide the body produces.

Define respiratory alkalosis

Respiratory alkalosis is a condition marked by a low level of carbon dioxide in the blood due to breathing excessively.

List the causes of respiratory acidosis

• asthma and COPD

• pulmonary fibrosis

• scoliosis

• narcotics (opioids)

• benzodiazepines

• Severe obesity

• Obstructive sleep apnea

List the causes of respiratory alkalosis

• Anxiety or panic

• Fever

• Overbreathing (hyperventilation)

• Pregnancy (this is normal)

• Pain

• Tumor

• Trauma

• Severe anemia

• Liver disease

• Overdose of certain medicines, such as salicylates, progesterone

• Shortness of breath (lung disease)