Respiratory System Physiology: Mechanisms, Volumes, and Acid-Base Balance

Course Learning Objectives and Overview

• Primary Objectives:     * Explain the detailed physiological process of inhalation (inspiration).     * Explain the detailed physiological process of exhalation (expiration).     * Describe and define all lung volumes and lung capacities.     * Explain term definitions and disturbances related to metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis.

Cellular Anatomy of the Lungs: Pneumocytes

• Lungs contain two primary types of cells:     * Type 1 Pneumocytes:         * The epithelium is composed of squamous epithelium.         * Function: Responsible for gas exchange.     * Type 2 Pneumocytes:         * Function: Responsible for producing a substance called surfactant.

Surfactant: Composition, Function, and Gestational Development

• Definition and Composition: Surfactant is a fluid composed of lipids and proteins that lines the inner surface of the alveoli.
• Physiological Function: Its role is to decrease surface tension. This ensures that the lungs do not collapse during exhalation.
• Gestation and Secretion:     * Type 2 pneumocytes begin producing surfactant after $24$ weeks of gestation.     * Surfactant does not line the alveoli while the fetus is in utero because the baby does not breathe air.     * The First Breath: During delivery through the birth canal, the stress of birth causes the hormone cortisol to be released.     * Cortisol Role: Cortisol triggers the Type 2 pneumocytes to secrete the surfactant to line the alveoli, allowing for the reduction of surface tension when the baby takes its first breath.

Mechanics and Principles of Respiration

• Definition of Respiration: The movement of gases between the atmosphere and the body cells.
• Types of Respiration:     * External Respiration (Ventilation): The gas exchange occurring between the atmosphere and the lungs (the movement of air in and out).     * Internal Respiration: The gas exchange occurring at the cellular level between the cell and the capillary, and between the capillary and the alveoli.
• The Flow Gradient: Air always flows due to pressure or gradient differences. It moves from an area of high pressure to an area of low pressure.
• Atmospheric Pressure Metrics:     * A barometer is used to measure atmospheric pressure.     * At sea level, atmospheric pressure is $760\,mmHg$.
• Boyle’s Law: States that pressure and volume are inversely proportional. As volume increases, pressure decreases, and vice versa.

The State of Rest

• Description: The brief moment between an inhale and an exhale.
• Pressure Equilibrium:     * Atmospheric Pressure: $760\,mmHg$.     * Intrapulmonary Pressure (pressure inside the lungs): $760\,mmHg$.     * Because pressures are equal, there is no gradient, and air does not move into or out of the lungs.
• Resting Physiological Values:     * Blood Oxygen Levels: Low.     * Blood Carbon Dioxide ($CO_2$) Levels: High.     * Lung Volume: Approximately $400\,ml$ of air.

The Step-by-Step Process of Inhalation (Inspiration)

• Condition Required: Intrapulmonary pressure must be less than atmospheric pressure (P_{intrapulmonary} < 760\,mmHg).
• Sequential Mechanism:     1. At rest, blood levels feature low oxygen and high $CO_2$.     2. This chemical state stimulates chemoreceptors.     3. Chemoreceptors stimulate the medulla oblongata (the respiratory center).     4. The respiratory center activates the phrenic nerve.     5. The phrenic nerve innervates and stimulates the diaphragm and respiratory muscles.     6. Muscle Action: The diaphragm moves down; respiratory muscles move outward.     7. Negative Pressure Creation: The lungs are pulled in every direction, creating negative pressure within the lungs, acting like a vacuum.     8. Thoracic Vein Reaction: Negative pressure causes thoracic veins to drain blood into the lungs.     9. Volume/Pressure Change: The influx of blood increases intrapulmonary volume. Per Boyle's Law, increased volume causes intrapulmonary pressure to decrease.     10. Result: The intrapulmonary pressure drops by $4\,mmHg$, reaching $756\,mmHg$. Since $760\,mmHg$ (atmosphere) is higher than $756\,mmHg$, air enters the lungs.

Chemoreceptors and Regulatory Hierarchy

• Central Chemoreceptors (Type 1):     * Location: Found around the medulla oblongata.     * Function: Monitor hydrogen ($H^+$) concentration in the Cerebrospinal Fluid (CSF).     * Activation: An increase in $H^+$ in the CSF indicates high $CO_2$ levels, signaling the body to take a breath.
• Peripheral Chemoreceptors (Type 2):     * Location: Found in the carotid artery and the aortic bodies.     * Function: Detect decreased levels of oxygen ($O_2$) in the blood.
• Regulatory Hierarchy:     * The Central Chemoreceptor is "The Boss": It can override information from peripheral chemoreceptors if they provide conflicting data to the respiratory center.     * Higher Brain Centers Control: The cerebral cortex (higher brain center) can override both central and peripheral receptors. This allows a person to voluntarily increase their breathing rate even if oxygen and $CO_2$ levels are normal.

The Step-by-Step Process of Exhalation (Expiration)

• Condition Required: Intrapulmonary pressure must be higher than atmospheric pressure ($P_{intrapulmonary} \approx 764\,mmHg$).
• Sequential Mechanism:     1. Inhalation causes the lungs to stretch.     2. Lung expansion stimulates stretch receptors within the medulla oblongata.     3. Activation of stretch receptors inhibits the phrenic nerve.     4. The diaphragm and respiratory muscles stop receiving signals and relax.     5. The diaphragm moves back up; respiratory muscles move inward.     6. Recoil: Because the lung contains elastic fibers (similar to a rubber band), it falls back on itself and returns to its original shape/size.     7. Blood Ejection: Lung recoil pushes blood out of the lungs via the arteries.     8. Volume/Pressure Change: This decrease in intrapulmonary volume causes an increase in intrapulmonary pressure.     9. Result: Intrapulmonary pressure rises from $756\,mmHg$ to $764\,mmHg$ (an increase of $8\,mmHg$). Since intrapulmonary pressure ($764\,mmHg$) is higher than atmosphere ($760\,mmHg$), air leaves the lungs.

Lung Volumes and Capacities: Definitions

• Tidal Volume (TV): One normal breath (normal inhale and normal exhale).
• Inspiratory Reserve Volume (IRV): A deep breath in. The amount of air that can be inhaled after a normal inhale.
• Expiratory Reserve Volume (ERV): A deep exhale. The extra amount of air that can be exhaled after a normal exhale is finished.
• Residual Volume (RV): The amount of air always left in the lungs. It can never be exhaled or manipulated.
• Inspiratory Capacity (IC): Total air that can be inhaled ($IC = TV + IRV$).
• Expiratory Capacity (EC): Total air that can be exhaled ($EC = TV + ERV$).
• Functional Residual Capacity (FRC): The amount of air remaining in the lungs after a normal exhale ($FRC = ERV + RV$).
• Vital Capacity (VC): The total amount of air a person can manipulate or change ($VC = ERV + TV + IRV$).
• Total Lung Capacity (TLC): The total amount of air the lungs can hold ($TLC = VC + RV$).

Lung Calculation Formulas

• IC Calculations:     * $IC = TV + IRV$     * $IRV = IC - TV$
• EC Calculations:     * $EC = TV + ERV$     * $ERV = EC - TV$
• FRC and RV Calculations:     * $FRC = RV + ERV$     * $RV = FRC - ERV$
• Vital Capacity Calculations:     * $VC = ERV + TV + IRV$     * $VC = IC + ERV$     * $VC = EC + IRV$
• Total Lung Capacity Calculations:     * $TLC = VC + RV$

Gas Transport in Blood

• Oxygen Transport:     * $97\% - 98\%$ of oxygen in arterial blood is bound to hemoglobin, forming oxyhemoglobin.     * Approximately $2\%$ is transported dissolved in the plasma.
• Carbon Dioxide Transport in Venous Blood (Three Pathways):     1. Bicarbonate ($70\%$): $CO_2$ enters red blood cells, combines with water via the enzyme carbonic anhydrase to form carbonic acid ($H_2CO_3$), which dissociates into $H^+$ and bicarbonate ($HCO_3^-$). Bicarbonate leaves the cell via an alkaline tide pump (alkaline pump/transport protein) in exchange for chloride ($Cl^-$).     2. Hemoglobin Bound ($20\%$): $CO_2$ binds to hemoglobin to form carboamino hemoglobin.     3. Dissolved in Plasma ($10\%$): Dissolves directly in the plasma.
• Releasing $CO_2$ in Lungs: The process reverses. Bicarbonate re-enters the cell via the alkaline tide pump (exchanging for chloride), binds with hydrogen, turns back into $CO_2$ and water via carbonic anhydrase, and diffuses into the alveoli.

Acid-Base Disturbances

• pH Scale Review:     * Range: $0$ (acidic) to $14$ (basic/alkaline).     * Neutral: $7$.     * pH and Hydrogen ($H^+$) are inversely proportional: As $H^+$ increases, pH decreases.
• Condition Terminology:     * Acidosis: pH is too acidic (excess acid/$H^+$).     * Alkalosis: pH is too basic/alkaline (excess base/low acid).
• The Two Systems:     1. Respiratory System: Specifically deals with $CO_2$ (a volatile acid).     2. Metabolic System: Deals with bicarbonate ($HCO_3^-$) and non-volatile acids.
• The Four Disturbances:     * Respiratory Acidosis: Excess acid Due to excess $CO_2$.     * Metabolic Acidosis: Excess acid (non-$CO_2$) or insufficient base ($HCO_3^-$).     * Respiratory Alkalosis: Alkaline state due to insufficient $CO_2$.     * Metabolic Alkalosis: Alkaline state due to excess base ($HCO_3^-$) or insufficient non-$CO_2$ acid.

Compensation Strategies

• Principle: The opposite system compensates to bring pH back to normal.
• Disturbance: Metabolic Acidosis:     * Compensatory System: Respiratory.     * Mechanism: Hyperventilation to release $CO_2$ (acid) and raise pH.
• Disturbance: Respiratory Acidosis:     * Compensatory System: Metabolic (Kidneys).     * Mechanism: Increased reabsorption of bicarbonate ($HCO_3^-$) to raise pH.
• Disturbance: Metabolic Alkalosis:     * Compensatory System: Respiratory.     * Mechanism: Hypoventilation to retain $CO_2$ (acid) and lower pH.
• Disturbance: Respiratory Alkalosis:     * Compensatory System: Metabolic (Kidneys).     * Mechanism: Increased secretion of bicarbonate ($HCO_3^-$) into urine to lower pH.

Laboratory Range Reference

• Normal pH: $7.35 - 7.45$
• Normal $CO_2$: $35 - 45\,mmHg$
• Normal $HCO_3^-$: $22 - 26\,mEq/L$

Questions & Discussion

• Question 1: Where would a probe go to look for central chemoreceptors?     * Response: By the medulla oblongata.
• Question 2: How would one stimulate central chemoreceptors?     * Response: Add hydrogen ($H^+$) to the CSF.
• Question 3: If $TV = 300$ and $IRV = 200$, what is $IC$?     * Calculation: $IC = 300 + 200 = 500$.
• Question 4: If $IRV = 200$, $TV = 300$, $FRC = 600$, and $RV = 200$, what is $VC$?     * Step 1: Calculate $ERV$: $FRC - RV = 600 - 200 = 400$.     * Step 2: Calculate $VC$: $IRV + TV + ERV = 200 + 300 + 400 = 900$.
• Question 5: A person is prescribed a drug where a byproduct is the formation of phosphoric acid. What is the disorder?     * Response: Metabolic acidosis (Acidosis because of acid; metabolic because phosphoric acid is not $CO_2$/respiratory).
• Question 6: If a person starts hyperventilating, what condition develops?     * Response: Respiratory alkalosis (Hyperventilating releases $CO_2$ [acid], making the body basic; it is a respiratory cause).