lecture 4 Respiratory System Physiology MSc. Dr. Abdalrida Al-Asady

lecture 4 Respiratory System Physiology MSc. Dr. Abdalrida Al-Asady

Physiology of Respiratory system

The study of respiratory physiology is important to medicine, because many of the respiratory diseases (e.g., cystic fibrosis, asthma, emphysema, pulmonary hypertension, and pneumonia) impact many of the subspecialties.

The human lungs are so efficiently designed that gas exchange can increase >20-fold to remove carbon dioxide and to supply oxygen to tissues in order to meet the body’s energy demands.

Functional anatomy

The respiratory system is composed of the conducting airways and the respiratory airways.

Figure: respiratory system

Conducting and Respiratory Airways

The conducting airways include the nose, mouth, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. As their name suggests, these airways conduct air to the respiratory airways; they do not participate in gas exchange.

The bronchi are > 1 mm in diameter and have cartilaginous rings that protect them from collapsing during expiration. They are not embedded in the lung parenchyma, so their diameter is not dependent on lung volume.

The bronchi branch to form bronchioles that are smaller in diameter and have no supporting cartilage. They are embedded within lung parenchyma, and their diameter expands and contracts with lung volume.

Innervation:

Smooth muscles innervated by autonomic nervous system:

- parasympathetic – muscarinic receptors - bronchoconstriction

- sympathetic - beta2 receptors – bronchodilation -mainly to adrenalin

The respiratory airways include the respiratory bronchioles (i.e., bronchioles with alveoli in their walls; and alveolar ducts.

Alveoli: There are ~300 million alveoli in adult lungs, each being ~250μm in diameter. Their walls are composed of a simple squamous epithelium, primarily type I pneumocytes. Each alveolus is encased by pulmonary capillaries, which are sandwiched between the lumens of adjacent alveoli.

The total surface area available for gas exchange is ~150 m2.

Alveoli first begin to appear on the respiratory bronchioles, marking the start of the respiratory portion of the lung. These alveoli are isolated initially, then become more numerous and are collected into sacs. Each sac has a central open space, or alveolar duct, that is continuous with the lumen of its respiratory bronchiole. The alveolar walls are composed of squamous epithelium and are in direct contact with the pulmonary capillaries for gas exchange to occur. Connective tissue with abundant elastic fibers is found throughout the branches of the bronchial tree and the alveoli. These contribute substantially to the elastic recoil of the lungs during expiration.

Figure: respiratory zone

Removal of Inhaled Particles

With its surface area of 50 to 100 square meters, the lung presents the largest

surface of the body to an increasingly hostile environment. Various mechanisms for dealing with inhaled particles have been developed.

Large particles are filtered out in the nose. Smaller particles that deposit in the conducting airways are removed by a moving staircase of mucus that continually sweeps debris up to the epiglottis, where it is swallowed. The mucus, secreted by mucous glands and also by goblet cells in the bronchial walls, is propelled by millions of tiny cilia, which move rhythmically under normal conditions but are paralyzed by some inhaled toxins.

The alveoli have no cilia, and particles that deposit there are engulfed by large wandering cells called macrophages. The foreign material is then removed from the lung via the lymphatics or the blood flow. Blood cells such as leukocytes also participate in the defense reaction to foreign material.

Pressures in the lungs

To understand the mechanics of ventilation and airflow during breathing, it is necessary to review the pressure in the lungs.

– Intra-pleural pressure is the pressure in the intra-pleural space.

– Alveolar pressure is the pressure within the alveoli.

– Trans-pulmonary pressure is alveolar pressure minus intra-pleural pressure.

Alveolar Pressure

Alveolar pressure is the pressure of the air inside the lung alveoli. When the glottis is open and no air is flowing into or out of the lungs, the pressures in all parts of the respiratory tree, all the way to the alveoli, are equal to atmospheric pressure, which is considered to be zero reference pressure in the airways—that is, 0 centimeters water pressure. To cause inward flow of air into the alveoli during inspiration, the pressure in the alveoli must fall to a value slightly below atmospheric pressure (below 0). during normal inspiration, alveolar pressure decreases to about –1 centimeter of water. This slight negative pressure is enough to pull 0.5 liter of air into the lungs in the 2 seconds required for normal quiet inspiration.

During expiration, opposite pressures occur: The alveolar pressure rises to about +1 centimeter of water, and this forces the 0.5 liter of inspired air out of the lungs during the 2 to 3 seconds of expiration.

Trans-pulmonary Pressure: It is the pressure difference between that in the alveoli and that on the outer surfaces of the lungs, and it is a measure of the elastic forces in the lungs that tend to collapse the lungs at each instant of respiration, called the recoil pressure.

Figure: change in pressure during inspiration and expiration

Ventilation

Ventilation (breathing) is the process by which air enters and exits the lungs. Respiration is theoverall term for ventilation, gas exchange, and utilization in cells.

Mechanics of Ventilation

Ventilation occurs in a cyclical manner with alternating inspiratory and expiratory phases.

Inspiration

Inspiration is an active process and is principally mediated by the diaphragm during quiet breathing.

– Contraction of the diaphragm enlarges the chest cavity, reducing intra-pleural pressure. This increases the trans-pulmonary pressure and expands the lungs . Minimal movement of the diaphragm (a few centimeters) is sufficient to move several liters of gas.

– The external intercostal and accessory muscles are not necessary for resting respiration, but they contribute substantially to deep respiration during exercise and respiratory distress.

When the diaphragm moves to the inspiratory position, the ribs are elevated by the intercostal muscles (chiefly the external intercostals) and scalene muscles. Because the ribs are curved and directed obliquely downward, elevation of the ribs expands the chest transversely (toward the flanks) and anteriorly. Meanwhile, the diaphragm leaflets are lowered bymuscle contraction causing the chest to expand inferiorly. These processes result in overall expansion of the thoracicvolume.

Expiration

Expiration is a passive process during quiet breathing. When the diaphragm relaxes, air is expelledfrom the lungs due to the elastic recoil of the lung–chest wall system. Active expiration (usingmuscles of expiration) occurs during exercise or in obstructive lung disease.When the diaphragm moves to the expiratory position , the chest becomes smaller in all dimensions, andthe thoracic volume is decreased. This process does not require additional muscular energy. The muscles that are activeduring inspiration are relaxed, and the lung contracts as the elastic fibers in the lung tissue that were stretched oninspiration release their stored energy, causing elastic recoil. For forcible expiration, however, the muscles that assistexpiration (mainly the internal intercostal muscles) can actively lower the rib cage more rapidly and to a greater extent thanis possible by passive recoil alone.

During heavy breathing, however, the elastic forces are not powerful enough to cause the necessary rapid expiration, so that extra force is achieved mainly by contraction of the abdominal muscles, which pushes the abdominal contents upward against the bottom of the diaphragm, thereby compressing the lungs.

Muscles of respiration:

All the muscles that elevate the chest cage are classified as muscles of inspiration, and those muscles that depress the chest cage are classified as muscles of expiration. The most important muscles that raise the rib cage are the external intercostals, but others that help are the (1) sternocleidomastoid muscles, which lift upward on the sternum; (2) anterior serrati, which lift many of the ribs; and (3) scaleni, which lift the first two ribs.

The muscles that pull the rib cage downward during expiration are mainly

the (1) abdominal recti, which have the powerful effect of pulling downward on the lower ribs at the same time that they and other abdominal muscles also compress the abdominal contents upward against the diaphragm, and (2) internal intercostals.

(Internal Respiration) (External Respiration)

Surfactant

Surfactant is a complex substance, consisting of proteins and phospholipids (mainly dipalmitoyllecithin), that is produced in type II pneumocytes. It lines alveoli and lowers surface tension by the same mechanism as detergents and soaps (i.e., it coats the water surface and reduces cohesive interactions between water molecules).

As an extension of its role in lowering surface tension, surfactant also produces the following effects:

– It increases compliance at all lung volumes, which allows for easier lung inflation and greatly decreases the work of breathing.

– It reduces the otherwise highly negative pressure in the interstitial space, which reduces the rate of filtration from pulmonary capillaries. This assists in maintaining lungs without excessive water.

Airway Resistance

A small changes in diameter cause large changes in resistance.

– The large airways offer little resistance to airflow. The small airways individually have highresistance, but their enormous number in parallel reduces their combined resistance to a smallvalue. Therefore, the sites of highest resistance in the bronchial tree are normally in the medium airways.

Regulation of Airway Resistance:

Airway resistance is primarily regulated by modulation of airwayradius by the parasympathetic and sympathetic nervous systems.

–Parasympathetic nervous system: Vagal stimulation releases acetylcholine that acts on muscarinic (M3) receptors in the lungs, leading to broncho-constriction. This increases the resistance to airflow.

– Sympathetic nervous system: Post-ganglionic sympathetic nerves release norepinephrine that act on β2-receptors, leading to broncho-dilation. This decreases the resistance to airflow

Lung Volumes and Capacities

Lung volumes are a way to functionally divide volumes of air that occur during different phases of the breathing cycle. They are all measured by spirometry, except for residual volume.They vary with height, sex, and age.

Lung Volumes

– Tidal volume (TV) is the volume of air that moves in or out of the lungs during one normal, rest inginspiration or expiration.

– Inspiratory reserve volume (IRV) is the volume of air that can be inspired beyond a normal inspiration.

– Expiratory reserve volume (ERV) is the volume of air that can be expired beyond a normal expiration.

– Residual volume (RV) is the volume of air left in the lungs and airways after maximal expiration.

Lung Capacities

– Inspirational capacity (IC) is the maximum volume of air that can be inspired with a deep breath following a normal expiration. It is the sum of TV and IRV.

– Functional residual capacity (FRC) is the volume of the lungs after passive expiration with relaxed respiratory muscles. It is the sum of ERV and RV.

– Vital capacity (VC) or forced vital capacity (FVC): is the maximum volume of air that can be expired in one breath after deep inspiration. It is the sum of TV, IRV, and ERV.

– Total lung capacity (TLC) is the total volume of air that can be contained in the lungs and airways after a deep inspiration. It is the sum of all four lung volumes: TV, IRV, ERV, and RV.

Note: TLC and FRC cannot be measured by spirometry because residual volume is needed for their calculation.

Figure: lung volumes and capacities

Gas Exchange

Diffusion of Gases

O2 and carbon dioxide (CO2) diffuse between alveolar gas and pulmonary capillary blood according to standard physical principles

– The total amount moved per unit of time is proportional to the area available for diffusion and to the difference in partial pressure between alveolar gas and pulmonary capillary blood, and inversely proportional to the thickness of the diffusion barrier.

– Gas will diffuse from the alveoli (higher partial pressures) to the pulmonary capillaries (lower partial pressures) until they equilibrate and no partial pressure gradient exists. As a result, blood entering the pulmonary veins from the pulmonary capillaries has virtually the same partial pressures as gases in the alveoli.

The diffusion barrier (respiratory membrane)

Is very thin, which ensures that the diffusion distance between alveolar gas and pulmonary capillary blood is very short. This allows blood in the pulmonary capillaries to equilibrate with alveolar gas during the short time (< 1 sec) that the blood is in the capillaries.

Structure of respiratory membrane

Respiratory membrane is 0.2 micrometer thickness and composed of: 1) fluid (surfactant), 2) epithelium, 3) epithelial basement membrane, 4) interstitial fluid, 5) capillary basement membrane, 6) endothelial cells.

The total surface area is 70 m2 and contain 60-140ml blood. The diameter of the capillary is 5micrometers (RBC is 7 micrometers), so RBC squeeze inside.

Figure . Ultra structure of the respiratory membrane where diffusion occurs.

Partial Pressure Changes of Oxygen and Carbon Dioxide

Partial Pressure Changes of Oxygen

– The PO2 of humidified inspired air is 150 mm Hg.

– The PO2 of alveolar air is 100 mm Hg. This is due to the diffusion of O2 from alveolar air into pulmonary capillary blood.

– The PO2 of systemic arterial blood is 95 mm Hg. It is almost the same as the PO2 of alveolar air because the partial pressure of pulmonary capillary blood equilibrates with alveolar air.

– The PO2 of venous blood is 40 mm Hg because O2 has diffused from arterial blood into the tissues.

Partial Pressure Changes of Carbon Dioxide

– The PCO2 of humidified inspired air is almost zero.

– The PCO2 of alveolar air is 40 mm Hg because CO2from venous blood entering the pulmonary capillaries diffuses into alveolar air.

– The PCO2 of systemic arterial blood is 40 mm Hg because pulmonary capillary blood equilibrateswith alveolar air.

– The PCO2 of venous blood is 46 mm Hg. It is higher than systemic arterial blood due to the diffusionof CO2from the tissues into venous blood following cellular respiration.

Factors Affecting Diffusion through the Respiratory Membrane

1. Thickness of the membrane.

2. Surface area of the membrane.

3. Diffusion coefficient.

4. Difference in partial pressure.

Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids

Once oxygen has diffused from the alveoli into the pulmonary blood, it is transported to the peripheral tissue capillaries almost entirely in combination with hemoglobin. The presence of hemoglobin in the red blood cells allows the blood to transport 30 to 100 times as much oxygen as could be transported in the form of dissolved oxygen in the water of the blood.

In the body’s tissue cells, oxygen reacts with various food stuffs to form large quantities of carbon dioxide. This carbon dioxide enters the tissue capillaries and is transported back to the lungs. Carbon dioxide, like oxygen, also combines with chemical substances in the blood that increase carbon dioxide transport 15- to 20-fold.

Nervous and Chemical Control of Respiration

Nervous Control

Inspiratory muscles, diaphragm and intercostal muscles, composed of skeletal muscle and must be stimulated to contract, two phrenic nerves responsible for diaphragm contraction originate at the 3rd, 4th, and 5th cervical spinal nerves,11 pairs of intercostal nerves originate 1- 11th thoracic spinal nerves.

Respiratory Areas in Brainstem

These centers are responsible for automatic basic rhythm of respiration, located bilaterally in the reticular formation of the brain stem (which consists from medullaoblongata, pons and midbrain). The primary portions of the brainstem that control ventilation are the medulla oblongata and the pons.

A.Medullary respiratory center: consists of dorsal groups which stimulate the diaphragm (inspiratory center) and ventral groups (expiratory center) which stimulate the intercostal and abdominal muscles.

B.Pontine respiratory group

It is involved with switching between inspiration and expiration, it consists of

pneumotaxic and apneustic centers.

Medullary respiratory centers:

The medulla oblongata is the primary respiratory control center. Its main function is to send signals to the muscles that control respiration to cause breathing to occur. There are two regions in the medulla that control respiration:

· The dorsal respiratory group stimulates inspiratory movements.

· The ventral respiratory group stimulates expiratory movements.

The medulla also controls the reflexes for non-respiratory air movements, such as coughing and sneezing reflexes.

Inspiratory Center or Dorsal Respiratory Group (DRG)

- Basic rhythmic breathing, it sends signal to the Phrenic nerve ----> Intercostal nerves ---> Diaphragm + external inter-costalsit containing inspiratoryneurons

It sets the basic respiratory rate, stimulates the inspiratory muscles to contract (diaphragm).The signals it sends for inspiration start weakly and steadily increase for ~ 2 sec. This is called a ramp and produces a gradual inspiration.

The ramp then stops abruptly for ~ 3 sec and the diaphragm relaxes.

Ventral respiratory group (VRG):   The neurons in the VRG remain almost inactive during normal quiet respiration. There is no evidence that VRG participates in the basic rhythmical oscillation that controls respiration.

When the respiratory drive for increased pulmonary ventilation becomes more than normal as in exercise, respiratory signals spill over into VRG from the basic oscillatory mechanisms of the DRG area. Then the VRG contribute to the respiratory drive.VRG area is very important in providing powerful expiratory signals to abdominal muscles during expiration. The VRG area operates as an overdrive mechanism when high levels of pulmonary ventilation are required.

Pontine respiratory groups

The pons is the other respiratory center and is located above the medulla. Its main function is to control the rate or speed of involuntary respiration. It has two main functional regions that perform this role:1.Pneumotaxic center

It is located in upper part of the pons, slightly inhibits medulla, it has inhibitory effect on inspiration causes shorter, shallower, quicker breaths.

The pnuemotaxic center sends signals to inhibit inspiration that allows it to finely control the respiratory rate. Its signals limit the activity of the phrenic nerve and inhibits the signals of the apneustic center. It decreases tidal volume.when activity of inspiratory center stops, inhibitory impulses cease from pneumotaxic center and inspiratory impulses initiated.

2.Apneustic center

It is located in lower portion of pons,stimulates the medulla, causes longer, deeper, slower breaths (prevent switch off),it has stimulatory effect on inspiratory center and inhibitory on expiratorycenter.Its activity is modulated on and off by pneumotaxic center.It is intermittently inhibited by vagal discharge arise from lung which appear during inflation of the lung and disappear during deflation of the lung.

The apneustic and pnuemotaxic centers work against each other together to control the respiratory rate. 

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