Organization of the Respiratory System
Each lung is composed of air sacs called alveoli - the sites of gas exchange with blood. Airways are tubes through which air flows between external environment and alveoli. A respiratory cycle consists of an inspiration (inhalation) movement of air from the external environment into alveoli, and an expiration (exhalation) - movement of air from alveoli to external environment.
Airways and Blood Vessels
During inspiration, air passes through nose/mouth, pharynx (throat) and larynx. These constitute the upper airways. Airways beyond the larynx are divided into 2 zones:
(1) The conducting zone where there is no gas exchange. This consists of the tracheal tube, which branches into two bronchi, one of which enters each lung and makes further branching. Walls of trachea and bronchi contain cartilage for support. The first branches without cartilage are called terminal bronchioles.
(2) The respiratory zone where gas exchange occurs. Consists of respiratory bronchioles with alveoli attached to them.
Epithelial surfaces of airways up to respiratory bronchioles have cells that secrete mucus to trap particulate matter in air, which is then moved by cilia present on these cells and swallowed. Macrophages, which engulf pathogens, are also present.
Alveoli: The Site of Gas Exchange
Alveoli are hollow sacs having open ends continuous with lumens of airways. Inner walls lined by a single layer of flat epithelial cells called type I alveolar cells, interspersed by thicker, specialized cells called type II alveolar cells. Alveolar walls contain capillaries and a small interstitial space with interstitial fluid and connective tissue. Blood within an alveolar wall capillary is separated from air within alveolus by a very thin barrier. There are also pores in the walls that permit flow of air. The extensive surface area and the thin barrier permit rapid exchange of large quantities of oxygen and carbon dioxide by diffusion.
Lungs and the Thoracic Wall
Lungs are situated in thorax - the body compartment between neck and abdomen. Thorax is a closed compartment, bound at the neck by muscles and separated from the abdomen by a sheet of skeletal muscle, the diaphragm. Wall of thorax is composed of ribs, breastbone (sternum) and intercostal muscles between ribs.
A closed sac, the pleural sac, consisting of a thin sheet of cells, called pleura, surrounds each lung. The pleural surface coating the lung (visceral pleura) is attached to lung by connective tissue. The outer layer (parietal pleura) is attached to the thoracic wall and diaphragm. A thin layer of intrapleural fluid separates the two layers of pleura. Changes in hydrostatic pressure of the intrapleural fluid - the intrapleural pressure (Pip) or the intrathoracic pressure cause lungs and thoracic wall to move in and together during breathing.
Ventilation and Lung Mechanics
Ventilation is exchange of air between atmosphere and alveoli. Air moves by bulk flow, from a high pressure to a low pressure region. Flow rate can be found with:
F = (Patm - Palv)/R
where, Patm, is the atmospheric pressure and Palv is the alveolar pressure.
During ventilation, air is moved in and out of lungs by changing alveolar pressure through changes in lung dimensions.
Volume of lungs depends on (1) difference in pressure between inside and outside of lungs, called transpulmonary pressure and (2) stretchability of the lungs, called lung compliance.
Muscles used in respiration are attached to chest wall. When they contract or relax, they change the chest dimensions, which in turn changes transpulmonary pressure, which in turn changes lung volume, which in turn changes alveolar pressure, causing air to flow in or out of lungs.
Stable Balance between Breaths
Transpulmonary pressure = Palv - Pip
Palv is zero, which means it is same as atmospheric pressure. Pip is negative, or less than atmospheric pressure because the elastic recoil of the lung inwards and the elastic recoil of chest wall outwards increases volume of intrapleural space between them and decreases the pressure within.. Therefore, transpulmonary pressure is greater than zero and this pressure puts an expanding force equal to the force of elastic recoil of lung and keeps it from collapsing. Volume of lungs is kept stable and there is air inside lungs. By a similar phenomenon, the pressure difference across chest (Patm- Pip) directed inward keeps the elastic chest wall from moving outward excessively.
Inspiration is initiated by neurally induced contractions. The diaphragm moves down and intercostal, muscles moves rib cage out. The size of the thorax increases and Pip drops even further. This increases transpulmonary pressure, thus expanding the lungs. This increases size of alveoli, decreasing pressure within them. When Patmalv, it causes a bulk flow of air from the external environment through airways and into the lungs. When Patm = Palv, air flow ceases.
The diaphragm and intercostal muscles relax during expiration. The chest recoils, becoming smaller. Pip increases, thus decreasing transpulmonary pressure. Lungs recoil, compressing air in alveoli and increasing Palv. Air passively flows out from alveoli to the external environment. Under certain conditions, air can also be expired actively by contracting a set of intercostal and abdominal muscles that decrease thoracic dimensions.
Lung compliance is a measure of elasticity or the magnitude of change in lung volume (ΔVL) that can be produced by a given change in transpulmonary pressure.
CL = ΔVL / Δ (Palv - Pip)
When lung compliance is low, Pip must be made lower to achieve lung expansion. This requires more vigorous contractions of diaphragm and intercostal muscles.
Determinants of Lung Compliance
Since the surface of alveolar cells is moist, surface tension between water molecules resists stretching of lung tissue. Type II alveolar cells secrete a substance called pulmonary surfactant that decreases surface tension and increases lung compliance. Respiratory distress syndrome of newborns is a result of low lung compliance.
Resistance is determined mainly by radius. Transpulmonary pressure exerts a distending force and keeps airways from collapsing, makes them larger during expiration and smaller during inspiration.
Asthma is a disease in which airway smooth muscle contracts and increases airway
Chronic Obstructive Pulmonary Disease (COPD) is chronic bronchitis or the production of excessive mucus in bronchi that obstructs the airways.
This maneuver is the manual application of an upward pressure applied to the abdomen of a person, who is choking on an object caught in the airways. This maneuver can force the diaphragm to move up, reducing thoracic size and increasing alveolar pressure. The forceful expiration that is produced can expel the lodged object.
Lung Volumes and Capacities
Tidal volume is the volume of air entering lungs during a single inspiration or leaving the lungs in a single expiration. Maximal amount of air that can be increased ABOVE this value during the deepest inspiration is called inspiratory reserve volume. After expiration of a resting tidal volume, volume of air still remaining in lungs is called functional residual capacity. Additional volume of air that can be expired (by active contraction of expiratory muscles) after expiration of resting tidal volume is called expiratory reserve volume. Air still remaining in lungs after a maximal expiration is called residual volume. Vital capacity is maximal volume of air that can be expired after a maximal inspiration.
Minute ventilation = Tidal volume x Respiratory rate
Units: (ml/min) = (ml/breath) x (breaths/minute)
Anatomic dead space is space within the airways that does not permit gas exchange with blood. Total volume of fresh air entering the alveoli per minute is called alveolar ventilation.
Ventilation = (Tidal volume - anatomic dead space) x respiratory rate
Units: (ml/min) = (ml/breath) – (ml/breath) x (breaths/min)
Since a fixed volume of each tidal volume goes to dead space, increased depth of breathing is more effective in elevating alveolar ventilation than increased breathing rate.
The volume of inspired air that is not used for gas exchange as a result of reaching alveoli with no blood supply is called alveolar dead space. The sum of anatomic and alveolar dead space is called physiologic dead space.
Gas Exchange in Alveoli and Tissues
In steady state, volume of oxygen consumed by body cells per unit time is equal to volume of oxygen added to blood in lungs, and volume of carbon dioxide produced by cells is. identical to rate at which it is expired.
The ratio of CO2 produced / O2 consumed is called respiratory quotient (RQ), which depends on type of nutrients being used for energy.
Alveolar Gas Pressures
Alveolar P02 is lower than atmospheric P02 because oxygen in alveolar air keeps entering pulmonary capillaries. Alveolar Pool is higher than atmospheric PCO2 because carbon dioxide enters alveoli from pulmonary capillaries. P02 is positively correlated with (1) PO2, of atmospheric air, (2) rate of alveolar ventilation and inversely correlated with
(3) rate of oxygen consumption. PCO2 is inversely correlated with (1) rate of alveolar ventilation and (2) positively correlated with rate of oxygen consumption.
Hypoventilation is an increase in the ratio of carbon dioxide production to alveolar ventilation while hyperventilation is a decrease in this ratio.
Alveolar-Blood Gas Exchange
Blood entering pulmonary capillaries is systemic venous blood having a high PCO2 and a low P02. Differences in partial pressures of oxygen and carbon dioxide on two sides of alveolar-capillary membrane result in net diffusion of oxygen from alveoli to blood and of carbon dioxide from blood to alveoli. With this diffusion, capillary blood P02 rises and its PCO2 falls and net diffusion of these gases ceases when capillary partial pressures become equal to those in alveoli.
In diffuse interstitial fibrosis, alveolar walls thicken with connective tissue reducing gas exchange. Ventilation-perfusion inequality can result from:
(1) ventilated alveoli with no blood supply
(2) blood flow through alveoli with no ventilation, reducing gas exchange.
Gas Exchange in Tissues
Metabolic reactions within cells consume oxygen and produce carbon dioxide. Intracellular PO2 is lower and PCO2 is higher than in blood. As a result, there is a net diffusion of oxygen from blood into cells, and a net diffusion of carbon dioxide from cells into blood.
Transport of Oxygen in Blood
Oxygen is carried in 2 forms:
(1) dissolved in plasma
(2) reversibly combined with hemoglobin (Hb) molecules in erythrocytes. Each Hb molecule is a globin protein with four iron containing hemegroups attached to it. Each heme group binds one molecule of oxygen. Hb exist in two forms: deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2). Fraction of all Hb in form of Hb02 is called percent Hb saturation.
O2 bound to Hb x 100
Percent saturation = -----------------------------------
Maximal capacity of Hb to bind O2
(Oxygen carrying capacity)
Effect of P02 on Hemoglobin Saturation
Raising blood PO2 increases combination of oxygen with Hb and binding of one oxygen molecule to Hb increases the affinity of the remaining sites on the same molecule. Therefore, extent to which oxygen combines with Hb increases rapidly as P O2 increases and this relationship between the two variables is called the oxygen-hemoglobin dissociation curve. The plateau of the curve at higher P O2 provides a safety factor for oxygen supply at low alveolar P O2.
Diffusion gradient favoring oxygen movement from alveoli to blood is maintained because oxygen binds to Hb and keeps the plasma PO2, low and only dissolved oxygen contributes to P O2. In tissues the procedure is reversed.
Carbon Monoxide and Oxygen Carriage
CO competes for the oxygen binding sites on Hb and also decreases the unbinding of oxygen from Hb.
Effects of Blood PC02, H+ concentration, Temperature and DPG on Hb Saturation
The more active a tissue is, the greater is its PCO2, H+ concentration and temperature. CO2, H+ ions and DPG (2, 3-diphosphoglycerate) combine with Hb and modify it allosterically, thereby shifting the dissociation curve to the right. This shift causes Hb to release more oxygen to the tissues.
Transport of Carbon Dioxide in Blood
Some fraction of carbon dioxide is dissolved and carried in blood. Some reacts reversibly with Hb to form carbamino Hb.
CO2 + Hb ↔ HbC02
Some carbon dioxide is converted to bicarbonate.
CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+
The enzyme, carbonic anyhydrase, is present in erythrocytes where the reaction takes place after which the bicarbonate moves out into the plasma.
Transport of H+ ions between Tissues and Lungs
If a person is hypoventilating, arterial H+ concentration rises due to increased PCO2 and this is called respiratory acidosis. Hyperventilation lowers H+ and this is called respiratory alkalosis. Deoxyhemoglobin has a higher affinity for H+ ions than oxy-hemoglobin and binds most of H+ produced. In the lungs, when deoxyhemoglobin is converted to oxyhemoglobin, H+ ions are released.
Control of Respiration
Diaphragm and intercostal muscles are skeletal muscles and therefore breathing depends upon cyclical excitation of these muscles. Control of this neural activity resides in neurons called medullary inspiratory neurons in medulla oblongata. These neurons receive inputs from apneustic and pneumotaxics center in pons. Negative feedback from pulmonary stretch receptors is also involved in controlling respiration (Hering Breur reflex).
Control of Ventilation by PO2, PCO2, and H+ Concentration
Control by P02 and PC02
Peripheral chemoreceptors called carotid bodies and aortic bodies are in close contact with arterial blood and are stimulated by a steep decrease in arterial PO2 and an increase in H+ concentration. They give inputs to medulla.
Control by H+ not due to CO2
Lactic acid in exercising muscles can cause metabolic acidosis or metabolic alkalosis, changing H+ concentration and stimulating peripheral chemoreceptors.
Control of Ventilation during Exercise
Blood PCO2, PO2, and H+ concentration due to CO2 do no change much during exercise due to compensatory hyperventilation. Change in H+ concentration due to lactic acid, input from mechanoreceptors in joints and muscles, increase in body temperature, increase in plasma epinephrine, etc. play important roles in stimulating ventilation.
Other Ventilatory Responses
Protective reflexes such as cough and sneeze reflexes, protecting the respiratory system from irritants. Receptors for sneeze located in nose or pharynx, while those for cough are located in the larynx, trachea and bronchi. The reflexes are characterized by a deep inspiration followed by a violent expiration.
Voluntary control of breathing is accomplished by descending pathways from the cerebral cortex. Cannot be maintained when involuntary stimuli are very high.
Reflex from J receptors, which are located in lungs, are stimulated by increase in lung interstitial pressure due to occlusion of a pulmonary vessel (pulmonary embolus), left ventricle failure etc. Reflex effect is tachypnea (rapid breathing).
Deficiency of oxygen at tissue level. There are four types:
(1) Hypoxic hypoxia (hypoxemia) which is characterized by reduced arterial PO2.
(2) Anemic hypoxia occurs when total oxygen content of blood is reduced due to inadequate number of erythrocytes, deficient or abnormal Hb, or binding of CO to Hb. Arterial PO2 remains normal.
(3) Ischemic hypoxia (hypoperfusion hypoxia) occurs when blood flow to tissues is low.
(4) Histotoxic hypoxia occurs when tissue is unable to utilize the oxygen due to interference from a toxic agent. However, the quantity of oxygen reaching the tissue is normal.
Retention of carbon dioxide and increased arterial PCO2, is called hypercapnea.
Disease characterized by increased airway resistance, decreased surface area for ventilation due to alveolar fusion, and ventilation-perfusion inequalities.
Nonrespiratory Functions of the Lungs
Lungs (1) concentrate a large number of biologically active substances in the bloodstream and also remove them, (2) produce and add new substances to blood and (3) trap and dissolve small blood clots.