Human Respiratory System Explained: Structure, Function, and Common Disorders

Objectives

This blog post provides readers with the following objectives. The reader will be able to:

o     Explain the concept respiration.
o     Explain the concept of gaseous exchange.
o     Outline the breathing mechanism in humans.
o     Cellular respiration

RESPIRATION

Respiration is a sum total of chemical reactions which result in the breakdown of food substance to release energy with or without the use of oxygen. All organisms require energy to sustain life. Respiration takes place in the mitochondria inside living cells.

Respiration involves:

1. External respiration: is the uptake of oxygen and simultaneous elimination of carbon dioxide and water. This is commonly referred to as breathing or gaseous exchange.

2. Internal respiration: is also known as cellular or tissue respiration. Internal respiration is a series of chemical reactions within the cell in which organic molecules are oxidized to release energy.

Structure of Respiratory System in human

Structure of the Respiratory System

The respiratory system is composed of the following parts.

o Nasal cavity: is divided into two portions by a cartilaginous septum. It is lined by fine hairs that filter the dust particles from the air. It opens into the region called the pharynx.

o Pharynx is common to both food and air. This allows passage of air in case the nose is blocked. Pharynx continues into glottis. Glottis is guarded by a flap of tissue called the epiglottis.

o Larynx is also called the voice box. The vocal cords stretch and vibrate when the air passes through them. Larynx continues as the trachea after the cords.

o Trachea is held open by C-shaped rings of cartilage. The cartilage keeps the trachea from collapsing. The trachea branch into two main branches called bronchi (sing: bronchus)

o Bronchus is also supported by the cartilaginous rings. The trachea and the bronchi are lined with ciliated cells and secretory cells (goblet cells). The goblets cells secrete mucus which trap fine particles of dust or bacteria. The cilia sweep trap particles along with the mucus toward buccal cavity for elimination.

The bronchus branches into several bronchioles. The bronchioles end as fine tubules which opens into a sac called alveolus or air sac.

o Lung is situated in the thoracic cavity. It’s a spongy and elastic organ that is broad at the bottom and taper at the top. It consists of air sacs, (the alveoli). Each lung is enclosed by two membranes called pleural membrane.

o Diaphragm: is a thick membranous structure present below the lungs. It separates the thoracic from the abdominal cavity.

Mechanism of Breathing

This is the process by which the lungs expand to take in air then contract to expel it. The cycle of respiration consists of two phases: Breathing in (Inspiration or Inhalation) and Breathing out (Expiration or exhalation)

Inspiration	Expiration
External intercostal muscles contract.	External intercostal muscles relax.
Ribs and sternum move up and out	Rib and sternum move down and in
Width of chest increases	Width of chest diminishes
Diaphragm contracts	Diaphragm relaxes
Depth of chest increases	Depth of chest diminishes
Capacity of thorax is increased	Capacity of thorax is decreased
Pressure between pleural surfaces is reduced	Pressure between pleural surfaces is increased
Elastic tissue of lungs is stretched	Elastic tissue of lungs recoils
Air is sucked into alveoli from atmosphere	Air is forced out of alveoli to atmosphere

Diagram illustration of breathing mechanism, Inhalation and Exhalation

Gaseous Exchange

The main respiratory surface in humans is the alveolus. Alveolus is one-cell thick, highly vascularized and provide a moist and extremely large surface area for gas exchange to occur.

Inhaled oxygen is able to diffuse into the blood capillaries from the alveoli, while carbon dioxide from the blood diffuses in the opposite direction into the alveoli. The oxygen combines with hemoglobin to form oxyhemoglobin which is transported in the plasma. Hemoglobin does not release all of its oxygen as it passes through the body tissues. It releases its oxygen when; the concentration of O₂ is low; high concentration of CO₂ and high temperature.

Carbon dioxide also dissolves in the plasma or combines with water to form bicarbonate ions (HCO₃⁻). This reaction is catalyzed by the carbonic anhydrase enzyme in red blood cells.

The hemoglobin picks up the H⁺, preventing the blood from becoming acidic. The bicarbonate ion diffuses into the plasma where it is transported.

In the lungs, bicarbonate ions enter red blood cells, hemoglobin releases its hydrogen ions, and CO₂ is released. As blood passes through the lungs, HCO₃^- + H⁺ form H₂CO₃ which then forms CO₂ + H₂O. The waste carbon dioxide can then be exhaled out of the body.

Composition of Air

Gas	Breathed In	Breathed Out
*Oxygen*	20.94%	17%
*Nitrogen*	78.08%	78%
*Carbon Dioxide*	0.04%	4%
*Tracer Gases*	0.94%	1%
*Water vapour*	Variable	Saturated

Cellular Respiration

There are two types of cellular respiration: Aerobic and Anaerobic respiration.

Aerobic Respiration

This is the breakdown of glucose in living cells to provide energy in the presence of oxygen. It’s carried out by the vast majority of organisms.

Aerobic respiration takes place in three stages glycolysis, Krebs cycle or tricarboxylic acid (TCA) cycle and electron transport chain.

Anaerobic Respiration

This occurs in some organisms when glucose is broken down to release energy in absence oxygen. In humans, muscle cells respire anaerobically and the by-product is lactic acid. Plant and yeast cells respire anaerobically, producing alcohol as a by-product. Lactic acid fermentation and alcoholic fermentation are two types of anaerobic fermentation.

Difference between Aerobic and Anaerobic Respiration

Aerobic respiration	Anaerobic respiration
Water is produced as waste product	Alcohol or Lactic acid is produced as waste product
Oxygen is used up	Oxygen is not required
Complete breakdown of glucose	Partially breakdown of glucose
More energy released	Less energy is released
Takes place in mitochondria	Takes place in cytoplasm
more efficient	less efficient

Respiratory Quotient

During aerobic respiration, O₂ is consumed and CO₂ is released. The ratio of the volume of CO₂ evolved to the volume of O₂ consumed in respiration is called the respiratory quotient (RQ) or respiratory ratio.

RQ = Volume of CO₂ evolved
Volume of O₂ consumed

The respiratory quotient depends upon the type of respiratory substrate used during respiration. When carbohydrates are used as substrate and are completely oxidized, the RQ will be 1, because equal amounts of CO₂ and O₂ are evolved and consumed, respectively, as shown in the equation below:

determine respiratory quotients on carbohydrates

When fats are used in respiration, the RQ is less than 1. Calculations for a fatty acid, oleic, tripalmitin, if used as a substrate is shown:

When proteins are respiratory substrates, the ratio would be about 0.9. In living organisms, respiratory substrates are often more than one; pure proteins or fats are not used as respiratory substrates.

Glycolysis: Overview, Steps, and Importance

Overview of Glycolysis

Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate, generating energy in the form of ATP. It is the first stage of cellular respiration and occurs in the cytoplasm of all cells. Glycolysis is anaerobic, meaning it does not require oxygen to proceed. It is crucial for both aerobic and anaerobic respiration and provides key intermediates for various metabolic processes. In the eukaryotic cells, it occurs in the cytosol. It yields a pyruvate molecule, four molecules of ATP and two NADP molecules. Both ATP and NADP molecules are energy-rich and are used in other cell reactions.

Steps of Glycolysis

Glycolysis consists of a series of ten enzyme-catalyzed reactions divided into two phases: the energy investment phase and the energy generation phase.

1. Energy Investment Phase

Step 1: Phosphorylation of Glucose

Enzyme: Hexokinase (or Glucokinase in the liver)

Reaction: Glucose is phosphorylated to form glucose-6-phosphate (G6P) using ATP.

Purpose: Traps glucose in the cell and prepares it for further breakdown.

Step 2: Isomerization of G6P

Enzyme: Phosphoglucose isomerase

Reaction: G6P is converted to fructose-6-phosphate (F6P).

Step 3: Phosphorylation of F6P

Enzyme: Phosphofructokinase-1 (PFK-1)

Reaction: F6P is phosphorylated to form fructose-1,6-bisphosphate (F1,6BP) using ATP.

Purpose: Committed step in glycolysis; key regulatory point.

Step 4: Cleavage of F1,6BP

Enzyme: Aldolase

Reaction: F1,6BP is split into two three-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).

Step 5: Isomerization of DHAP

Enzyme: Triose phosphate isomerase

Reaction: DHAP is converted to G3P.

Purpose: Ensures that both three-carbon molecules continue in the glycolytic pathway.

2. Energy Generation Phase

Step 6: Oxidation and Phosphorylation

Enzyme: Glyceraldehyde-3-phosphate dehydrogenase

Reaction: G3P is oxidized to 1,3-bisphosphoglycerate (1,3-BPG), reducing NAD⁺ to NADH and generating a high-energy phosphate bond.

Step 7: Formation of ATP

Enzyme: Phosphoglycerate kinase

Reaction: 1,3-BPG is converted to 3-phosphoglycerate (3-PG), producing ATP through substrate-level phosphorylation.

Step 8: Conversion to 2-PG

Enzyme: Phosphoglycerate mutase

Reaction: 3-PG is converted to 2-phosphoglycerate (2-PG).

Step 9: Dehydration to Phosphoenolpyruvate (PEP)

Enzyme: Enolase

Reaction: 2-PG is dehydrated to form PEP.

Step 10: Formation of Pyruvate

Enzyme: Pyruvate kinase

Reaction: PEP is converted to pyruvate, producing ATP.

Purpose: Final step that generates pyruvate, the end product of glycolysis.

Importance of Glycolysis

1. Energy Production

Glycolysis produces a net gain of 2 ATP molecules per glucose molecule through substrate-level phosphorylation, providing immediate energy to the cell.

2. Production of NADH

Glycolysis generates 2 NADH molecules per glucose, which are used in the Electron Transport Chain during aerobic respiration to produce additional ATP.

3. Intermediates for Other Pathways

Glycolysis produces intermediates like G3P and pyruvate, which are used in other metabolic pathways, including the Citric Acid Cycle, gluconeogenesis, and fatty acid synthesis.

4. Anaerobic Metabolism

In the absence of oxygen, glycolysis provides ATP through fermentation pathways, such as lactic acid fermentation in muscles or alcoholic fermentation in yeast.

Disorders Related to Glycolysis

Several metabolic disorders can affect glycolysis, including:

Glycogen Storage Diseases: Genetic disorders that affect the storage and utilization of glycogen, impacting glycolysis and overall energy metabolism.
Pyruvate Kinase Deficiency: A genetic condition that impairs the function of pyruvate kinase, leading to anemia and reduced ATP production.
Lactic Acidosis: A condition where lactic acid accumulates in the blood, often due to impaired glycolysis or mitochondrial dysfunction.

For more detailed information on glycolysis and its role in cellular metabolism, visit these resources:

Fate of Pyruvate

The fate of pyruvate depends on the following factors; the cell in which the pyruvate was produced (animal cell, plant cell or bacterial cell) and whether there is presence of oxygen or not.

1. Lactic Acid Fermentation: In this process, the pyruvate is converted to lactate. Formation of lactate is catalyzed by lactate dehydrogenase.

a. This process occurs in the bacteria and involved in making of yogurt.

b. In animal cells, during exercise (strenuous muscular activity), when oxygen is inadequate for cellular respiration, pyruvate is reduced to lactate by lactate dehydrogenase. The building up of lactate causes drop in pH which result in energy deprivation and cell death. The symptoms are muscle pain and fatigue. During recovery, lactate is transported to the liver where it can be reconverted to pyruvate or glucose.

2. Ethanol Fermentation: In this process, the pyruvate is converted to acetaldehyde and carbon dioxide, then to ethanol. It occurs in some organism such as yeast and plants. Formation of ethanol is catalyzed by two enzymes; Pyruvate decarboxylase catalyzes the first irreversible reaction to form acetaldehyde:

Ethanol fermentation is used during wine-making.

Lactic acid fermentation and ethanol fermentation can occur in the absence of oxygen.

3. Aerobic conditions: In the presence of O₂ pyruvate is converted to Acetyl-CoA which enters Citirc acid cycle and gets completely oxidized to CO₂, water, and 36 ATP.

The Citric Acid Cycle: Overview, Steps, and Importance

Overview of the Citric Acid Cycle

The Citric Acid Cycle, also known as the Krebs Cycle or the TCA Cycle (Tricarboxylic Acid Cycle), is a central metabolic pathway that plays a crucial role in cellular respiration. It takes place in the mitochondria of eukaryotic cells and is essential for the production of energy from carbohydrates, fats, and proteins. This cycle is vital for generating ATP (adenosine triphosphate), the primary energy currency of the cell.

Pyruvate is decarboxylated (a carboxyl group is removed) to form 2-C, acetate catalyzed by enzyme dehydrogenase. Two electrons are removed from pyruvate and accepted by NAD to form NADH₂.

The acetate is converted into Acetyl-CoA by combining with co-enzymes A (CoA) and enters the citric acid cycle.

Steps of the Citric Acid Cycle

The Citric Acid Cycle involves a series of enzyme-catalyzed reactions that convert acetyl-CoA into carbon dioxide and high-energy electron carriers. The cycle operates as follows:

1. Formation of Citrate: The unstable bond of acetyl CoA breaks and the 2-C acetyl group (acetate) combines to the four-carbon oxaloacetate to form citrate (6-C).

Reactants: Acetyl-CoA (a two-carbon molecule) and oxaloacetate (a four-carbon molecule).
Enzyme: Citrate synthase.
Product: Citrate (a six-carbon molecule).

2. Isomerization to Isocitrate: The citrate then goes through a series of chemical transformations to form isocitrate.

Reactant: Citrate.
Enzyme: Aconitase.
Product: Isocitrate (an isomer of citrate).

3. Oxidative Decarboxylation to α-Ketoglutarate: Isocitrate is oxidized to α-ketoglutarate (5-C). Electrons are released and accepted by NAD to form NADH.

Reactant: Isocitrate.
Enzyme: Isocitrate dehydrogenase.
Products: α-Ketoglutarate (a five-carbon molecule), NADH (high-energy electron carrier), and CO₂ (carbon dioxide).

4. Oxidative Decarboxylation to Succinyl-CoA

Reactant: α-Ketoglutarate.
Enzyme: α-Ketoglutarate dehydrogenase.
Products: Succinyl-CoA (a four-carbon molecule), NADH, and CO₂.

5. Conversion to Succinate

Reactant: Succinyl-CoA.
Enzyme: Succinyl-CoA synthetase.
Product: Succinate, GTP (or ATP, depending on the cell type).

6. Oxidation to Fumarate

Reactant: Succinate.
Enzyme: Succinate dehydrogenase.
Product: Fumarate, FADH₂ (another high-energy electron carrier).

7. Hydration to Malate

Reactant: Fumarate.
Enzyme: Fumarase.
Product: Malate.

8. Oxidation to Oxaloacetate: The malate molecule is oxidized by a NAD to form NADH. Oxaloacetate is regenerated to begin the cycle again.

Reactant: Malate.
Enzyme: Malate dehydrogenase.
Product: Oxaloacetate, NADH.

Importance of the Citric Acid Cycle

1. Energy Production

The Citric Acid Cycle generates high-energy electron carriers (NADH and FADH₂) that are crucial for the Electron Transport Chain, leading to the production of ATP through oxidative phosphorylation.

2. Metabolic Intermediates

The cycle provides intermediates that are used in various biosynthetic pathways. For example, α-Ketoglutarate and oxaloacetate are precursors for amino acid synthesis.

3. Integration of Metabolism

The Citric Acid Cycle integrates the metabolism of carbohydrates, fats, and proteins, allowing cells to efficiently utilize various nutrients for energy.

4. Removal of Carbon Dioxide

The cycle helps in the removal of carbon dioxide, a metabolic waste product, which is subsequently exhaled through respiration.

Disorders Related to the Citric Acid Cycle

Several metabolic disorders can affect the Citric Acid Cycle, including:

Citric Acid Cycle Enzyme Deficiencies: Genetic defects in enzymes like α-Ketoglutarate dehydrogenase can lead to metabolic dysfunction and energy production issues.
Mitochondrial Diseases: Conditions affecting mitochondrial function can impair the Citric Acid Cycle and overall energy metabolism.

Learn More About the Citric Acid Cycle

For more detailed information on the Citric Acid Cycle and its role in cellular metabolism, visit these resources:

Electron Transport Chain: How It Powers ATP Production

Overview of the Electron Transport Chain

The Electron Transport Chain (ETC) is a vital component of cellular respiration that takes place in the inner mitochondrial membrane. After the Krebs cycle, which generates high-energy coenzymes (NADH and FADH₂) from glucose, these coenzymes are used in the ETC to produce ATP, the primary energy currency of the cell. The ETC operates through a series of redox reactions that ultimately lead to the reduction of oxygen and the production of water.

How the Electron Transport Chain Works

Oxidation of NADH and FADH₂
- Process: NADH and FADH₂ are oxidized, releasing high-energy electrons and protons (H⁺). NADH transfers electrons to FAD, converting it to FADH₂.
- Link: NCBI: NADH and FADH₂ in Cellular Respiration
Electron Transfer Through Cytochromes
- Process: FADH₂ donates electrons to an iron-sulfur protein (cytochrome), which then passes these electrons to ubiquinone (CoQ10), another cytochrome.
- Link: Wikipedia: Cytochrome
Electron Transfer to Ubiquinone
- Process: Ubiquinone shuttles electrons to a series of electron carriers, primarily cytochromes, in the mitochondrial membrane.
- Link: Encyclopedia of Life Sciences: Ubiquinone
Reduction of Oxygen
- Process: The final cytochrome transfers electrons to molecular oxygen (O₂). Oxygen combines with protons to form water (H₂O).
- Link: Biochemistry and Molecular Biology: Oxygen in Cellular Respiration
Creation of Proton Gradient
- Process: As electrons move through the ETC, a proton gradient is established across the inner mitochondrial membrane. This gradient creates a potential energy difference used for ATP synthesis.
- Link: Khan Academy: Proton Gradient and ATP Synthesis
ATP Synthesis by ATP Synthase
- Process: The inner mitochondrial membrane houses ATP synthase complexes. This enzyme uses the energy from the proton gradient to convert ADP and inorganic phosphate into ATP through oxidative phosphorylation.
- Link: Molecular Cell Biology: ATP Synthase

Importance of the Electron Transport Chain

1. ATP Production

The ETC is crucial for generating ATP, which powers various cellular processes. This process of oxidative phosphorylation is highly efficient, producing up to 34 ATP molecules per glucose molecule.

2. Oxygen Utilization

The reduction of oxygen to water is a key step in preventing the accumulation of toxic reactive oxygen species (ROS) and maintaining cellular health.

3. Energy Efficiency

By creating a proton gradient, the ETC allows cells to convert energy stored in NADH and FADH₂ into a usable form (ATP) efficiently.

Disorders Related to the Electron Transport Chain

Disruptions in the Electron Transport Chain can lead to several conditions, including:

Mitochondrial Diseases: Genetic disorders affecting ETC components can impair ATP production, leading to muscle weakness, neurological issues, and other symptoms.
Leigh Syndrome: A severe neurological disorder linked to defects in the ETC.
Chronic Fatigue Syndrome: Often associated with impaired mitochondrial function and reduced ATP production.

For further reading and detailed explanations of the Electron Transport Chain, consider these resources:

Comparison between Photosynthesis and Cellular Respiration

Photosynthesis	Cellular Respiration
Requires energy	Releases energy as ATP molecules
Produce O₂	O₂is used up
Occurs only in the presence of sunlight.	Occurs at all times.
Occurs in Chloroplasts	Occurs in mitochondrial, cytoplasm.
6CO₂+12H₂O + light → C₆H₁₂O₆+6O₂+ 6H₂O	C₆H₁₂O_{6 +}6O₂→ 6CO₂+ 6H₂O + energy
Produces food and captures energy.	Breakdown of food, releases energy.
2 stages - Light dependent reaction and Light independent reaction.	4 stages - Glycolysis, Pyruvate oxidation, Kreb's cycle and Electron transport chain