The mammalian respiratory system consists of a pair of lungs situated in the thoracic cavity, protected by the rib cage. The key structures include:

• Trachea (windpipe): Connects the larynx to the bronchi; lined with ciliated epithelium and goblet cells that trap dust and bacteria
• Bronchi: Two branches from the trachea, each leading to a lung
• Bronchioles: Smaller tubes that branch from the bronchi
• Alveoli: Tiny air-filled sacs (approximately 700 million in humans) with a total surface area of over 80 square metres—the main functional units for gas exchange

The alveoli are thin, moist, and richly supplied with blood capillaries. They contain special features including elastic collagen fibres for expansion and recoil, surfactant (a phospholipid-protein mixture) that lowers surface tension to prevent alveolar collapse, and macrophages that phagocytose debris and microbes.

Gas exchange occurs by diffusion across the alveolar wall (the air-blood barrier). Oxygen from the alveoli diffuses into the blood capillaries, while carbon dioxide from the blood diffuses into the alveoli to be exhaled.

Factors Governing Efficient Gas Exchange

For effective gas exchange, the respiratory surface must have:

1. Large surface area – More area allows higher rates of gas exchange
2. Pressure gradient – Gases move from high to low partial pressure
3. Thin membrane – Short diffusion distance speeds up gas exchange
4. Moist surface – Gases must dissolve in liquid for transport
5. Good blood supply – Dense capillary networks maintain concentration gradients
6. Permeable membrane – Allows gases to pass through

Oxygen Transport

Oxygen is transported in two ways:

• Dissolved in plasma (~2%)
• Bound to haemoglobin in red blood cells (~98%)

Haemoglobin consists of four iron-containing haem groups, each capable of binding one oxygen molecule. The reversible reaction is:

$\text{Hb} + 4\text{O}_2 \rightleftharpoons \text{Hb}.4\text{O}_2$

At high oxygen concentration (in the lungs), oxyhaemoglobin forms; at low oxygen concentration (in tissues), oxyhaemoglobin dissociates releasing oxygen.

The Oxygen Dissociation Curve

The oxygen-haemoglobin dissociation curve is S-shaped (sigmoid):

• At low O₂ partial pressure: Little oxyhaemoglobin (in tissues)
• At high O₂ partial pressure: Haemoglobin becomes saturated with oxygen (in lungs)

The Bohr Effect

Increased carbon dioxide lowers haemoglobin's affinity for oxygen, shifting the curve to the right. This promotes oxygen unloading in tissues where CO₂ is high. The reaction:

$\text{Hb}.4\text{O}_2 + \text{H}^+ \rightleftharpoons \text{HHb}^+ + 4\text{O}_2$

This allows oxygen release where it is most needed.

Carbon Dioxide Transport

Carbon dioxide is transported in three ways:

1. Dissolved in plasma (~5%)
2. As carbaminohaemoglobin (10-20%) – binds to amine groups of haemoglobin
3. As hydrogen bicarbonate ions (HCO₃⁻) (~85%) – the major form

The formation of bicarbonate ions involves the enzyme carbonic anhydrase:

$\text{CO}_2 + \text{H}_2\text{O} \xrightarrow{\text{Carbonic anhydrase}} \text{H}_2\text{CO}_3 \rightleftharpoons \text{HCO}_3^- + \text{H}^+$

The Chloride Shift

When bicarbonate ions diffuse from red blood cells into plasma, chloride ions (Cl⁻) diffuse inward to maintain electrical balance—this is called the chloride shift or Hamburger shift.

Aerobic respiration occurs in the presence of oxygen and takes place in the mitochondria. It involves three main stages:

1. Glycolysis (in cytoplasm)

Glucose is broken down into two molecules of pyruvate. The net yield is:

• 2 ATP (by substrate-level phosphorylation)
• 2 NADH

Steps:

1. Phosphorylation: Glucose → Glucose-6-phosphate → Fructose-1,6-bisphosphate (uses 2 ATP)
2. Lysis: Fructose-1,6-bisphosphate → 2 triose phosphates
3. Oxidation: Triose phosphates → Pyruvate (produces 2 NADH and 2 ATP)

2. Link Reaction

Pyruvate enters the mitochondrion and is converted to acetyl-CoA:

$\text{Pyruvate} + \text{CoA} + \text{NAD}^+ \rightarrow \text{Acetyl-CoA} + \text{CO}_2 + \text{NADH}$

3. The Kreb's Cycle (Citric Acid Cycle)

Takes place in the mitochondrial matrix. For each glucose molecule:

• Produces: 6 NADH, 2 FADH₂, 2 ATP, 4 CO₂

4. Electron Transport Chain (ETC)

Located on the inner mitochondrial membrane. NADH and FADH₂ donate electrons that pass through a chain of carriers (NAD → FAD → CoQ → Cytochromes). Energy released pumps protons to create a gradient used to produce ATP via oxidative phosphorylation.

ATP Yield from One Glucose Molecule:

The overall equation:

$\text{C}_6\text{H}_{12}\text{O}_6 + 6\text{O}_2 \rightarrow 6\text{CO}_2 + 6\text{H}_2\text{O} + 38\text{ATP}$

Worked Example: Calculating RQ for Lipids

The respiratory quotient (RQ) is calculated as:

$RQ = \frac{\text{Volume of CO}_2 \text{ evolved}}{\text{Volume of O}_2 \text{ consumed}}$

For tripalmitin (a fat):

$2\text{C}_{51}\text{H}_{98}\text{O}_6 + 145\text{O}_2 \rightarrow 102\text{CO}_2 + 98\text{H}_2\text{O}$

$RQ = \frac{102}{145} = 0.7$

This RQ of 0.7 indicates fat is being oxidised.

Occurs in the absence of oxygen. Only 2 ATP are produced per glucose molecule.

Lactic Acid Fermentation

Occurs in animal muscles (including human muscle cells) during intense exercise when oxygen is insufficient:

$\text{Pyruvate} + \text{NADH} \rightarrow \text{Lactate} + \text{NAD}^+$

Alcoholic Fermentation

Occurs in yeast and some plants:

$\text{Pyruvate} \rightarrow \text{Acetaldehyde} + \text{CO}_2$ $\text{Acetaldehyde} + \text{NADH} \rightarrow \text{Ethanol} + \text{NAD}^+$

High-Altitude Adaptations

• Increased red blood cell production
• Haemoglobin with higher oxygen affinity
• Larger lung capacity
• Deep, slow breathing

Diving Mammals

• High blood volume with more haemoglobin and myoglobin
• Collapse of lungs at depth to prevent nitrogen absorption
• Slow heart rate (bradycardia)
• High tolerance to lactic acid

Foetal Haemoglobin

Foetal haemoglobin (HbF) has higher affinity for oxygen than adult haemoglobin, allowing the foetus to extract oxygen from maternal blood. This is due to gamma subunits replacing beta subunits in the haemoglobin structure.

Understanding gas exchange and respiration is crucial for healthcare practice in Tanzania. For example, when patients suffer from respiratory conditions like pneumonia or asthma, doctors may prescribe oxygen therapy—concentrated oxygen is administered to increase the partial pressure of oxygen in the alveoli, enhancing diffusion into the blood. Additionally, knowledge of anaerobic respiration explains why yeast is used in local brewing of traditional beverages like kisumu and kangara, where fermentation converts sugars to alcohol and carbon dioxide, producing the characteristic bubbles and alcohol content in these drinks.