Unit 5: Human Physiology - Breathing and Exchange of Gases

Evolution of Biological Approaches: Reductionist vs. Systems Biology

• The Reductionist Approach:     * Historical focus on studying life forms through physico-chemical concepts and techniques.     * Common methods included using surviving tissue models or cell-free systems.     * This approach led to an "explosion of knowledge" in molecular biology.     * Molecular physiology became nearly synonymous with biochemistry and biophysics.

• The Systems Biology Approach:     * A reaction to the realization that neither a purely organismic approach nor a purely reductionistic molecular approach reveals the full truth of biological processes.     * Considers living phenomena as "emergent properties."     * These properties arise from interactions among components within a system.     * Hierarchical Emergence: Regulatory networks of molecules, supra-molecular assemblies, cells, tissues, organisms, populations, and communities each create unique emergent properties.

• Unit Overview: Human Physiology:     * Chapters cover processes like gas exchange, blood circulation, and locomotion in cellular and molecular terms.     * The unit also addresses coordination and regulation at the organismic level.     * Chapters included: Breathing and Exchange of Gases (Ch. 14), Body Fluids and Circulation (Ch. 15), Excretory Products and their Elimination (Ch. 16), Locomotion and Movement (Ch. 17), Neural Control and Coordination (Ch. 18), and Chemical Coordination and Integration (Ch. 19).

Biography: Alfonso Corti ($1822 - 1888$)

• Background: Italian anatomist born in $1822$.

• Scientific Career Phases:     * Initial research: Studied the cardiovascular systems of reptiles.     * Transition: Shifted focus to the mammalian auditory system.

• Major Achievement:     * In $1851$, he published a paper describing a specific structure on the basilar membrane of the cochlea.     * This structure, now known as the organ of Corti, contains hair cells that function to convert sound vibrations into nerve impulses.

• Death: He passed away in the year $1888$.

Fundamentals of Breathing and Respiration

• Metabolic Necessity of Oxygen ($O_2$):     * Organisms utilize $O_2$ to indirectly break down simple molecules, including glucose, amino acids, and fatty acids.     * The objective of this catabolic breakdown is to derive energy for various activities.

• Production of Carbon Dioxide ($CO_2$):     * $CO_2$ is released during catabolic reactions and is considered harmful to the system.

• Definition of Breathing (Respiration):     * The continuous process of exchanging atmospheric $O_2$ for the $CO_2$ produced by the cells.     * Phenomenological indicator: The upward and downward movement of the chest.

Comparative Respiratory Organs across Animal Groups

• Lower Invertebrates:     * Examples: Sponges, coelenterates, and flatworms.     * Mechanism: Simple diffusion over the entire body surface.

• Invertebrate Specialists:     * Earthworms: Utilize their moist cuticle.     * Insects: Utilize a network of tracheal tubes to transport atmospheric air throughout the body.

• Aquatic Specialists:     * Groups: Most aquatic arthropods and molluscs.     * Mechanism: Special vascularized structures called gills (Branchial Respiration).     * Vertebrates: Fishes.

• Terrestrial Forms:     * Mechanism: Vascularized bags called lungs (Pulmonary Respiration).     * Vertebrates: Reptiles, birds, and mammals.

• Amphibians:     * Frogs utilize lungs for respiration but can also respire through their moist skin (Cutaneous Respiration).

Human Respiratory System: Anatomy

• Upper Respiratory Tract:     * External nostrils (pair): Open above the upper lips.     * Nasal passage and Nasal chamber: Conduct air from nostrils to the pharynx.     * Pharynx: A common passage for both food and air.     * Larynx: A cartilaginous box located at the opening of the trachea. Known as the "sound box" because of its role in sound production.     * Epiglottis: A thin elastic cartilaginous flap that covers the glottis during swallowing to prevent food from entering the larynx.

• Lower Respiratory Tract:     * Trachea: A straight tube extending into the mid-thoracic cavity. It divides at the level of the $5^{th}$ thoracic vertebra into the right and left primary bronchi.     * Bronchial Tree: Primary bronchi branch into secondary and tertiary bronchi, then into bronchioles, and finally into very thin terminal bronchioles.     * Structural Support: The trachea, primary, secondary, and tertiary bronchi, and initial bronchioles are supported by incomplete cartilaginous rings.

• The Alveoli and Lungs:     * Alveoli: Very thin, irregular-walled, vascularized bag-like structures arising from terminal bronchioles.     * The Lungs: Structured by the network of bronchi, bronchioles, and alveoli.     * Pleura: A double-layered membrane covering the lungs. The outer pleural membrane is in contact with the thoracic lining, while the inner pleural membrane contact the lung surface.     * Pleural Fluid: Located between the pleural membranes; its function is to reduce friction on the lung surface.

Functional Divisions and Thoracic Anatomy

• Functional Parts:     * Conducting Part: Starts from external nostrils and ends at terminal bronchioles. Functions: Transports atmospheric air to alveoli, clears air of foreign particles, humidifies air, and brings air to body temperature.     * Respiratory (Exchange) Part: Consists of the alveoli and their ducts. Function: The site of actual diffusion of $O_2$ and $CO_2$ between blood and atmospheric air.

• The Thoracic Chamber:     * Characterized as an anatomically air-tight chamber.     * Boundaries:         * Dorsal boundary: Vertebral column.         * Ventral boundary: Sternum.         * Lateral boundary: Ribs.         * Lower boundary: Dome-shaped diaphragm.     * Mechanical Significance: This setup ensures any volume change in the thoracic cavity is reflected in the pulmonary cavity, which is essential for breathing because pulmonary volume cannot be altered directly.

Five Major Steps of Respiration

1. Breathing (Pulmonary Ventilation): Drawing in atmospheric air and releasing $CO_2$-rich alveolar air.

2. Alveolar Diffusion: Diffusion of gases ($O_2$ and $CO_2$) across the alveolar membrane.

3. Gas Transport: Transport of gases by the blood.

4. Tissue Diffusion: Diffusion of $O_2$ and $CO_2$ between blood and tissues.

5. Cellular Respiration: Utilization of $O_2$ for catabolic reactions and the subsequent release of $CO_2$.

Mechanism of Breathing

• Principles of Air Movement:     * Relies on a pressure gradient between the lungs and the atmosphere.     * Inspiration: Occurs when intra-pulmonary pressure is less than atmospheric pressure (negative pressure in lungs).     * Expiration: Occurs when intra-pulmonary pressure is higher than atmospheric pressure.

• Involved Muscles: Diaphragm and specialized intercostal muscles (external and internal).

• Process of Inspiration:     * Initiated by the contraction of the diaphragm, increasing thoracic volume in the antero-posterior axis.     * Contraction of external intercostal muscles lifts ribs and sternum, increasing volume in the dorso-ventral axis.     * Combined volume increase leads to a decrease in intra-pulmonary pressure, forcing air into the lungs.

• Process of Expiration:     * Diaphragm and intercostal muscles relax, returning the diaphragm and sternum to normal positions.     * Thoracic and pulmonary volume decreases, raising intra-pulmonary pressure above atmospheric pressure, expelling air.

• Vital Statistics:     * Additional muscles in the abdomen can increase the strength of breathing.     * Average healthy human breathing rate: $12 - 16$ times per minute.     * Spirometer: A clinical tool used to estimate the volume of air involved in breathing and assess pulmonary functions.

Respiratory Volumes and Capacities

• Tidal Volume (TV): Volume inspired or expired during normal respiration. Value: approx. $500 \, \text{mL}$ ($6000 - 8000 \, \text{mL}$ per minute).

• Inspiratory Reserve Volume (IRV): Volume a person can inspire by forcible inspiration. Value: $2500 - 3000 \, \text{mL}$.

• Expiratory Reserve Volume (ERV): Volume a person can expire by forcible expiration. Value: $1000 - 1100 \, \text{mL}$.

• Residual Volume (RV): Volume of air remaining in lungs after forcible expiration. Value: $1100 - 1200 \, \text{mL}$.

• Inspiratory Capacity (IC): $TV + IRV$. Total volume air one can inspire after a normal expiration.

• Expiratory Capacity (EC): $TV + ERV$. Total volume air one can expire after a normal inspiration.

• Functional Residual Capacity (FRC): $ERV + RV$. Volume air remaining after normal expiration.

• Vital Capacity (VC): $ERV + TV + IRV$. Maximum volume air one can breathe in after forced expiration (or breathe out after forced inspiration).

• Total Lung Capacity (TLC): $RV + ERV + TV + IRV$ (or $VC + RV$). Total air accommodated at end of forced inspiration.

Physiology of Gas Exchange

• Primary Site: Alveoli; secondary sites include blood and tissues.

• Mechanism: Simple diffusion based on pressure/concentration gradients, gas solubility, and membrane thickness.

• Partial Pressure (p): The pressure contribution of an individual gas in a mixture (represented as $pO_2$ and $pCO_2$).

• Gradient Data (in $\text{mm Hg}$):     * Atmospheric Air: $pO_2 = 159$; $pCO_2 = 0.3$.     * Alveoli: $pO_2 = 104$; $pCO_2 = 40$.     * Deoxygenated Blood: $pO_2 = 40$; $pCO_2 = 45$.     * Oxygenated Blood: $pO_2 = 95$; $pCO_2 = 40$.     * Tissues: $pO_2 = 40$; $pCO_2 = 45$.

• Solubility Factor: $CO_2$ solubility is $20 - 25$ times higher than $O_2$, meaning more $CO_2$ diffuses per unit pressure difference.

• Diffusion Membrane Layers:     1. Thin squamous epithelium of alveoli.     2. Endothelium of alveolar capillaries.     3. Basement substance (basement membrane of epithelium and surrounding capillary cells).     * Total thickness: Much less than a millimeter.

Gas Transport in Blood

• Oxygen Transport:     * $97\%$ transported by RBCs as oxyhaemoglobin (bound to iron-containing pigment haemoglobin); $3\%$ dissolved in plasma.     * Binding is reversible and depends primarily on $pO_2$.     * Each haemoglobin molecule can carry maximum $4$ molecules of $O_2$.     * Oxygen Dissociation Curve: A sigmoid curve plotting percentage saturation of haemoglobin against $pO_2$.     * Association factors (Alveoli): High $pO_2$, low $pCO_2$, low $H^+$ concentration, lower temperature.     * Dissociation factors (Tissues): Low $pO_2$, high $pCO_2$, high $H^+$ concentration, higher temperature.     * Efficiency: $100 \, \text{mL}$ of oxygenated blood delivers approx. $5 \, \text{mL}$ of $O_2$ to tissues.

• Carbon Dioxide Transport:     * $20 - 25\%$ as carbamino-haemoglobin (RBC binding); $70\%$ as bicarbonate ($HCO_3^-$); $7\%$ dissolved in plasma.     * Dissociation of $CO_2$ from haemoglobin occurs in alveoli where $pCO_2$ is low and $pO_2$ is high.     * Enzymatic Reaction (Facilitated by carbonic anhydrase):     $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons HCO_3^- + H^+$     * At tissues: High $pCO_2$ causes diffusion into RBCs/plasma to form $HCO_3^-$ and $H^+$.     * At alveoli: Low $pCO_2$ shifts reaction to release $CO_2$ and $H_2O$.     * Efficiency: $100 \, \text{mL}$ of deoxygenated blood delivers approx. $4 \, \text{mL}$ of $CO_2$ to alveoli.

Regulation and Disorders

• Neural Regulation:     * Respiratory Rhythm Centre: Located in the medulla; primary regulator.     * Pneumotaxic Centre: Located in the pons; moderates the rhythm centre and can reduce inspiration duration to alter respiratory rate.     * Chemosensitive Area: Located adjacent to the rhythm centre; highly sensitive to $CO_2$ and $H^+$ ions. Activation leads to elimination signaling.     * Peripheral Receptors: Found in aortic arch and carotid artery; detect $CO_2$ and $H^+$ changes.     * Note: The role of $O_2$ in regulation is insignificant.

• Respiratory Disorders:     * Asthma: Breathing difficulty and wheezing caused by inflammation of bronchi and bronchioles.     * Emphysema: Chronic disorder; alveolar walls are damaged, reducing respiratory surface. Primarily caused by cigarette smoking.     * Occupational Respiratory Disorders: Found in stone-breaking/grinding industries. Long-term dust exposure causes inflammation and fibrosis (proliferation of fibrous tissue), leading to lung damage. Workers must use protective masks.

Questions & Discussion

• Definitions:     * Vital Capacity (VC): The maximum air volume breathed in after forced expiration. It signifies an individual's maximum potential for gas exchange and lung power.     * Tidal Volume (TV): Normal volume inspired/expired. For a healthy human in one hour: $500 \, \text{mL} \times (12 \text{ to } 16 \text{ breaths/min}) \times 60 \text{ minutes} = 360,000 \text{ to } 480,000 \, \text{mL/hour}$.

• Anomalies and Effects:     * High Altitude: Going up a hill leads to lower atmospheric pressure and $pO_2$. The body usually compensates with increased breathing rate and RBC production to counter hypoxia.     * Hypoxia: A condition where tissues are deprived of adequate oxygen supply.

• Interspecies Observations:     * Insect site of exchange: Tracheoles (via tracheal tubes).

• Transport Comparisons:     * $pCO_2$ effect on $O_2$: High $pCO_2$ decreases haemoglobin's affinity for $O_2$, aiding dissociation in tissues (Bohr effect).     * Atmospheric air vs. Alveolar air: Atmospheric air has higher $pO_2$ ($159 \, \text{mm Hg}$ vs $104 \, \text{mm Hg}$) and lower $pCO_2$ ($0.3 \, \text{mm Hg}$ vs $40 \, \text{mm Hg}$)