Respiratory System Flashcards

Respiratory System: Ventilation and Respiration

• Main functions of respiration:
  • Deliver oxygen to tissues.
  • Remove carbon dioxide.
• Four major components:
  1. Pulmonary ventilation: Inflow/outflow of air between the atmosphere and alveoli.
  2. Diffusion of oxygen and carbon dioxide between alveoli and blood.
  3. Transport of oxygen and carbon dioxide in the blood/fluids to and from tissues/cells.
  4. Regulation of ventilation and other facets of respiration.

Mechanics of Pulmonary Ventilation

• Lungs are expanded/contracted in two ways:
  • Upward and downward movement of the diaphragm (elongates/shortens chest cavity).
  • Elevation and depression of the ribs (anteroposterior diameter).
• Muscles involved:
  • Raise the ribcage: External intercostals, sternocleidomastoid, anterior serrati, and scaleni.
  • Lower the ribcage: Abdominal rectus and internal intercostals.

Pressures

• The lung is elastic and collapses, expelling air through the trachea when no force keeps it inflated.
• It floats in the cavity attached by the mediastinum at its helium, surrounded by pleural fluid, which lubricates movement.
• The lung is "sucked" into the thoracic wall by continuous suction of excess fluid into lymphatic channels.
• Suction exists between the visceral surface of lung pleura and parietal surface of the thoracic wall, allowing free movement during expansion/contraction.

Pleural Pressure

• Pressure of the fluid in the pleural space.
• Slight suction (i.e., slightly negative pressure).
  • Beginning of inspiration: -5 cm of H2O (required to hold lungs open at resting level).
  • During normal inspiration: Expansion of rib cage pulls outwards on lungs, creating more negative pressure.
  • Change from -5 to -7.5 cm H2O during inspiration, increasing lung volume by approximately 0.5 L.
  • Expiration reverses this process.

Alveolar Pressure

• With the glottis open and no air flowing, pressure throughout the respiratory tree equals atmospheric pressure (0 cm H2O reference airways).
• For air to flow inward into alveoli, alveolar pressure must fall below atmospheric pressure (0).
  • Inspiration: Alveolar pressure drops to about -1 cm H2O, drawing + 0.5 L of air into lungs.
  • Expiration: Alveolar pressure rises to +1 cm H2O, pushing 0.5 L of air out of the lungs.

Surface Tension

• Water molecules attract one another when water forms a surface with air, causing the water surface to contract.
• Raindrops retain their shape because of this tight contractile water membrane.
• Alveoli experience a similar principle where water surface tension tries to contract the alveoli, forcing air out through the bronchi.
• This surface tension acts as an elastic force, contributing to the overall elastic contractile force of the lungs.

Surfactant

• Secreted by Type II alveolar epithelial cells (pneumocytes II).
• Contains dipalmitoyl phosphatidylcholine.
• It is a surface-active agent in water that reduces surface tension.
• Composition: Phospholipids, proteins, and ions (phospholipids are most important).
• Does not dissolve uniformly; part spreads over the surface of water in alveoli reducing surface tension to 1/12 to ½ of pure water surface:
  • Pure water: 72 \frac{dynes}{cm}
  • Alveolar fluid without surfactant: 50 \frac{dynes}{cm}
  • Alveolar fluid with surfactant: 5-30 \frac{dynes}{cm}
• Includes surfactant apoproteins and calcium.

Pulmonary Volumes and Capacities

• Spirometry records the volume movements of air into and out of the lungs.
• There are four volumes and four capacities.

Pulmonary Volumes

• Four volumes that, when added together, equal the maximum volume to which the lungs can be expanded.
• Volumes vary considerably based on:
  • Fitness
  • Age
  • Sex
  • Height
  • Altitude
• Most volumes and capacities are 20-30% less in women than in men.
• Greater in large/athletic people than in small/asthenic people.

1. Tidal Volume (TV): Volume of air inspired/expired with each normal breath (500 ml).
2. Inspiratory Reserve Volume (IRV): Extra volume of air that can be inspired over and above the normal tidal volume when the person inspires with full force (3000 ml).
3. Expiratory Reserve Volume (ERV): Maximum extra volume of air that can be expired forcefully after the end of a normal tidal expiration (1100 ml).
4. Residual Volume (RV): Volume of air remaining in lungs after most forceful expiration (1200 ml).

Pulmonary Capacities

1. Inspiratory Capacity (IC) = Tidal Volume + Inspiratory Reserve Volume = 3500 ml
   • The amount of air a person can breathe in.
2. Functional Residual Capacity (FRC) = Expiratory Reserve Volume + Residual Volume = 2300 ml
   • Amount of air remaining in lungs at the end of normal expiration.
3. Vital Capacity (VC) = Inspiratory Reserve Volume + Tidal Volume + Expiratory Reserve Volume = 4600 ml
   • Maximum amount of air a person can expel after filling lungs to max extent and expiring to max extent.
4. Total Lung Capacity (TLC) = Vital Capacity + Residual Volume = 5800 ml
   • Maximum volume to which lungs can be expanded with the most effort.

Restrictive and Obstructive Lung Diseases

• Obstructive and restrictive lung diseases affect airflow and lung volumes differently.

Obstructive Lung Diseases

• Airflow is blocked or restricted, making it harder for air to flow out of the lungs.
• Examples: Chronic Obstructive Pulmonary Disease (COPD), asthma, bronchitis, emphysema.
• Increased airway resistance due to mucus, inflammation, or narrowing.
• Symptoms: Shortness of breath, wheezing, chronic coughing.

Restrictive Lung Diseases

• Lung expansion is limited, leading to a reduction in lung volume, making it hard for the lungs to fill with air.
• Examples: Pulmonary fibrosis, interstitial lung diseases, obesity, chest wall deformities, or neuromuscular disorders.
• Symptoms: Shortness of breath (especially with exertion), rapid breathing, fatigue.

Spirometry Measurements

1. Forced Expiratory Volume in 1 second (FEV1): The volume exhaled in the first second after deep inspiration and forced expiration.
2. Forced Vital Capacity (FVC): The total volume of air that the patient can forcibly exhale in one breath.
3. FEV1/FVC Ratio: The ratio of FEV1 to FVC, expressed as a percentage.
   • Values of FEV1 and FVC are expressed as a percentage of the predicted normal for a person of the same sex, age, and height.
   • FEV1: >80% predicted
   • FVC: >80% predicted
   • FEV1/FVC ratio: >0.7

Spirometry Findings

• Obstructive Lung Disease:
  • Reduced FEV1 (<80% of the predicted normal).
  • Reduced FVC (but to a lesser extent than FEV1).
  • FEV1/FVC ratio reduced (<0.7).
• Restrictive Lung Disease:
  • Reduced FEV1 (<80% of the predicted normal).
  • Reduced FVC (<80% of the predicted normal).
  • FEV1/FVC ratio normal (>0.7).

Other Clinical Signs

• Obstructive: Barrel Chest
• Restrictive: Pectus excavatum

Reversibility and Asthma

• Assess reversibility with a bronchodilator (e.g., 400 micrograms of salbutamol) and repeat spirometry after 15 minutes if considering asthma.
  • Presence of reversibility suggests asthma.
  • Absence of reversibility suggests fixed obstructive respiratory pathology such as COPD.
  • Partial reversibility may suggest coexisting asthma and another obstructive airway disease (e.g., COPD).

Diffusion of O2 and CO2

• After alveoli are ventilated, the next step is diffusion of O2 from the alveoli into the pulmonary blood and diffusion of CO2 in the opposite direction.
• Diffusion is the random motion of molecules in all directions through the respiratory membrane and adjacent fluids.
• In respiratory physiology, we care about the rate of diffusion.

Physics of Gas Diffusion

• All the gases in respiratory physiology are simple molecules free to move amongst themselves by diffusion.
• This also applies to gases dissolved in the fluids and tissues of water.

Motion

• Diffusion requires a source of energy, which is the kinetic motion of molecules.
• Except at absolute 0 temperature, all molecules of all matter are continually in motion.
• Free molecules that are not physically attached to others exhibit linear movement at high velocity until they collide, bounding away in new directions.
• This movement is rapid and random.

Concentration

• Diffusion of a gas occurs from high to low concentration chambers.

Gas Pressures / Partial Pressures

• Pressure = multiple impacts of moving molecules against a surface.
• Pressures of gases on the surfaces of the respiratory tract are proportional to the sum of impacts of all the molecules of that gas striking the surface.
• Pressure is directly proportional to the concentration of gas molecules.
• In respiratory physiology, we deal with mixtures of gases (oxygen, nitrogen, carbon dioxide).
• The rate of diffusion of gases is proportional to the pressure caused by that gas alone (partial pressure).

Partial Pressure

• Air composition: 79% nitrogen, 21% oxygen.
• Total pressure of mixture at sea level: 760 mmHg.
  • PN2 = + 79% (600 mmHg)
  • PO2 = 21% (160 mmHg)

Partial Pressure in Water and Tissues

• Gas dissolved in water/body fluids also exerts pressure (kinetic energy).
• When gas dissolved in fluid meets a surface (cell membrane), it exerts partial pressure like in the gas phase (PO2, PCO2, PN2, etc.).

Gas Phase in Alveoli and Dissolved Phase in Pulmonary Blood

• The partial pressure of each gas in the alveolar mixture tends to force that gas into solution in the blood of alveolar capillaries.
• Molecules of that gas already dissolved in the blood bounce around.
• Some escape back into the alveoli depending on the partial pressure of the blood.
• Net diffusion of the gas is determined by the difference of the two partial pressures (PP).
  • If PP in the gas phase in alveoli is greater, it will diffuse into blood (e.g., Oxygen from air to blood).
  • If PP of the gas is greater in dissolved state in blood, net diffusion will be toward the has phase in alveoli (e.g., CO2 from blood to air).

Water Vapour

• Air is humidified by the respiratory passageways.
• Partial pressure at which this happens is vapor pressure of water.
• At normal temperature (37°C), PH2O = 47 mmHg.

Alveolar Air and Atmospheric Air

• They are not the same.
• Alveolar air is partially replaced with atmospheric air with each breath.
• Functional residual capacity is 2300 ml.
• 350 ml of new air is brought into alveoli with each breath.
• Also:
  • O2 is constantly being absorbed into the pulmonary blood, lowering the concentration in the alveoli.
  • Conversely the more rapid it is breathed into the atmosphere the higher its concentration becomes.
• O2 concentration/ PP in alveoli is controlled by:
  • Rate of absorption of O2 into blood
  • Rate of entry of new O2 into lungs by ventilation
• CO2 constantly diffuses from pulmonary blood into alveoli and is continually removed from the alveoli by ventilation.
• Alveolar PCO2 increases directly in proportion to the rate of excretion and decreases inversely proportional to alveolar ventilation.
• Dry atmospheric air is humidified as it enters the air passages, therefore PH2O = 47 mmHg, so total atmospheric pressure @ sea level cannot be >760 mmHg.

Respiratory Membrane

• Respiratory unit: Composed of about 300 million units - Respiratory bronchiole, Alveolar ducts, Atria, Alveoli in both lungs.
• The alveolar walls are extremely thin with an almost solid network of interconnecting capillaries allowing a sheet of flowing blood.
• Gas exchange occurs through the membranes of all the terminal portions of the lungs, not merely in the alveoli themselves.
• Composition of the respiratory membrane (or pulmonary membrane):
  • Layer of watery fluid, containing surfactant
  • Alveolar epithelium
  • Epithelial basement membrane
  • Thin interstitial space between alveolar epithelium and capillary endothelial membrane
  • Capillary basement membrane
  • Capillary endothelial membrane
• Optimized for gas exchange.
• The characteristics are:
  • Thickness of 0.6 micrometers
  • Surface area of 70 m2
  • Capillary blood volume of 60-140 ml
  • Capillary diameter of 5 micrometers

Factors Determining Gas Passage Rate Through the Respiratory Membrane

• Thickness of membrane:
  • Rate of diffusion is inversely proportional to thickness
  • Edema (fluid buildup) and fibrosis can increase the thickness
• Surface area:
  • Emphysema (alveolar coalescence, dissolution of walls) decreases area fivefold.
• Diffusion efficient.
  • Dependent upon each gases solubility in the membrane.
• Pressure difference across membrane:
  • Difference in PP in alveoli/capillary blood is directly proportional to the rate of gas transfer through the membrane in either direction.

Transport of Gases

• Gases move by diffusion due to differences in partial pressures.
• O2 diffuses from alveoli into blood because alveolar PO2 > pulmonary capillary blood PO2.
• Capillary blood PO2 > other tissues, so O2 diffuses into surrounding cells where it is metabolized into CO2, causing intracellular PCO2 to rise.
• CO2 diffuses into tissue capillaries where blood flows to lungs.
• Pulmonary capillary PCO2 > Alveolar PCO2.

Arterial Blood O2 Transport

• 98% of blood that enters left atrium is oxygenated.
  • PO2 = 104 mm Hg
• 2% shunted blood
  • PO2 = 40 mmHg
• Venous admixture of blood @ pulmonary veins causes PO2 of blood entering left heart/pumped to aorta to fall to 95 mmHg.

1. Peripheral tissue PO2 is 95 mmHg, while interstitial fluid PO2 is 40 mmHg, facilitating rapid O2 diffusion from capillary blood to the tissue, dropping to 40 mmHg as blood leaves tissue into systemic veins.
2. Oxygen is always used by the cells.
3. Two factors affect PO2 in tissues:
   • Rate of blood flow: Increased blood flow = increased PO2.
   • Rate of tissue metabolism: More metabolism = reduced interstitial fluid PO2.

• O2 BECOMES CO2 AS IT IS USED BY THE CELLS
• CO2 diffuses in the OPPOSITE DIRECTION each point in the chain is 20x rapid as O2
• Pressure differences for diffusion are far less than O2.

Hemoglobin and O2

• 97% of O2 is transported from lungs to the tissues in combination with hemoglobin (Hb) in the RBCs, while 3% is transported in dissolved state in the water of the plasma/blood cells.
• O2 combines loosely and reversibly with the heme portion.
  • High PO2 in pulmonary capillaries allows O2 to bind to Hb.
  • Low PO2 in tissue capillaries allows O2 to be released from Hb.
  • Each Hb molecule can bind with 4 O2 molecules.
• Quaternary structure consisting of four protein subunits which each have a heme group containing an iron atom that binds to oxygen. The two types of chains are 2 alpha and 2 beta

O2-Hb Dissociation Curve

• Progressive increase in the % of Hb bound with O2 as blood PO2 increases.
• Blood leaving lungs and entering systemic arteries has a PO2 of 95 mmHg and SatO2 of 97%.
• Venous blood returning from tissues has a PO2 of 40 mmHg and SatO2 of 75%.
• 15 g of Hb per 100 ml of blood, where each gram of Hb binds with a max of 1.34 ml of O2. In which case, 15 \times 1.34 = 20.1.
• Average15 g of Hb in 100 ml of blood can combine in total with 20 ml of O2 if the hemoglobin is 100\% saturated, or 20 volume \, percent.

O2-Hb Release Curve

1. Tissue capillaries have lower PO2 (40 mmHg, 75% SatO2), resulting in 5 ml O2 transported from the lungs to the tissues per 100 ml of blood flow.
2. Utilization coefficient: % of blood that gives up its O2 as it passes through tissue capillaries, the normal is 25% of Oxyhemoglobin gives O2 to tissues.
3. Tissue oxygen buffer system: Stabilizes PO2 in tissues through a PO2 of 40 mmHg (15-40 mmHg). If it rises above that threshold, O2 would not be released by Hb. This also enables Hb to still maintains almost constant tissue even if atmospheric O2 concentration were to change drastically or change locations such as:
   • Mountains (PO2 falls ½ 104 mmHg)
   • Deep sea (PO2 rises x10)

Shifts in the O2-Hb Dissociation Curve

• Several factors can displace the curve in either direction:
  • pH: 7.4 (normal), 7.2 (acidic), 7.6 (alkali)
  • CO2 concentration
  • Temperature
  • 2,3-diphosphoglycerate (BPG)

Bohr Effect

• A shift in the O2-Hb dissociation curve to the right and down.
  • Enhances O2 release from blood in the tissues.
  • Enhances oxygenation of blood in the lungs.
• As blood passes through the tissues:
  • CO2 diffuses from tissue cells into blood, raising PCO2.
  • PCO2 rises raising H2CO3 (carbonic acid)
  • H+ concentration
  • SHIFT IN THE CURVE
  • O2 is forced away from Hb delivering vast amounts to the tissues
• The opposite occurs in the lungs:
  • Diffusion CO2 from blood into alveoli
  • Less PCO2 and H+
  • Curve shifts left and upward
  • O2 binds to HB with more affinity resulting in More O2 transport to tissues

CO2 Transport in Blood

• CO2 is easier to transport than O2; acid-base balance is where it is more relevant.
• 4 ml of CO2 are transported from tissue to lungs per 100 ml of blood.
• CO2 is transported as:
  1. Dissolved CO2 = 7%
  2. Carbaminohemoglobin (Hgb-CO2) = 23%
  3. Bicarbonate (HCO3) = 70% (most important).

CO2 Transportation

• 7%, 0.3 ml per 100ml 70% 23% HCO3 ( BICARBONATE) CHLORIDE SHIFT, venous RBC have more chloride than arterial RBC
• dissolved
  • Small portion of CO2 transported this way into the lungs.
    • ACIDO
    • Produce bicarbonato dentro del
• Reaction With water.
• Hemoglobin and plasma proteins
  • CO2 reacts with amine radicals of Hb molecule, forming Carbaminohemoglobin, also a reversible and loose bond reaction
  • CO2 is released into the alveoli
  • Slow reaction in comparison to water reaction 20% of total CO2 transport
• Dissolved CO2 reacts with water 70%, however if it was not for Carbonic anhydrase inside the red blood cells, this process WOULD BE SLOW taking seconds and minutes. But because of it, Fraction of a second are only necessary and large amounts of CO2 react with the RBC water before it even leaves the capillaries with this step QUICKLY occurring
• H2CO3 dissociates into H+ and HCO3 with both the results having their respective actions:
  • H+ combines with Hb (buffer).
  • HCO3 ions diffuse into the RBC for which Chloride carrier protein in the RBC membrane then in return, Shuttles the 2 (HCO3/H+) in opposite directions

Haldane Effect

• Bohr effect: CO2 increases, O2 is displaced from Hb more O2 transport; the Haldane effect is the reverse.
• O2 binding with hemoglobin tends to displace CO2 from the blood.
• O2-Hb combining in the lung causes Hb to become more acid, so CO2 is displaced
• High acidity Hb does not want to combine with CO2 to form carbaminohemoglobin resulting in an Increased acidity also causes release of excess H+
  • H+ binds with HCO3 = carbonic acid.
  • Dissociates into water and C02. CO2 is released from blood to alveoli to air
• The Haldane effect approximately double the amount of CO2 released from the blood in the lungs and doubles the amount of CO2 in the tissues and its more impactful in CO2 transport than the Bohr effects is for O2 transport.

Ventilatory Regulation

• Rate of alveolar ventilation is regulated by the nervous system to maintain arterial blood gases (PO2/PC2) at relatively constant levels under various conditions.
• Three main groups of neurons:
  • Dorsal respiratory group in the nucleus tractus solitarius.
  • Ventral respiratory group in the medulla.
  • Pontine respiratory group in the pons.

Dorsal Respiratory Group

• Inspiratory action potentials.
• Ramp-link.
• Basic rhythm of respiration.
• Distal portion of the medullae.
• Receives input from the vagus and glossopharyngeal nerves.
• Most of its neurons are located in NTS (nucleus of the tractus solitarius).
• The NTS is the sensory termination of both the vagal and the glossopharyngeal nerves, which transmit sensory signals into the respiratory center from:
  1. Peripheral chemoreceptors
  2. Laringe
  3. Bronquios, senales.

Inspiratory Ramp

• Signal to the diaphragm is very slow, increasing like a ramp in 2 seconds, because of what happens next:
• Weak and steadily increasing action potentials which ceases abruptly for 3 seconds
• ELASTIC RECOIL OF LUNGS AND CHEST = EXPIRATION after said cease is over
• New inspiratory signal and new cycle and so forth
• This action produces a Steady increase in lung volume instead of gasp of inspiration because of rate and limit controls:
• Rate of increase of ramp signal
• During heavy respiration, ramp increases rapidly
• Limiting point at which the ramp suddenly ceases
• Earlier the ramp stops, the shorter the inspiration
• = higher frequency of respiration
• Prevents over inflation of the lungs; initiated by nerves receptors in the walls of bronchi and bronchioles (Hering Breuer Reflex).
• Lungs are overinflated and a signal is sent through the vagi into the dorsal resp group, switching off the respiratory ramp which leads to no more inspiration.

Pneumotaxic Center

• Dorsally in the superior portion of the pons.
• Controls rate and pattern of breathing.
• Inhibitory signals to the dorsal respiratory group.
• Controls filling phase of the respiratory cycle.
• Inhibits inspiration resulting to 2ry effect of increasing respiratory rate

Ventral Respiratory Group

• Ventrolateral part of the medulla.
• Inspiration/expiration - depending on specific neuron activation.
• Inactive during normal quiet breathing.
• Stimulates abdominal expiratory muscles when higher respiration levels are required.

Chemical Control of Respiration

• Respiratory stimulation is greatest in the first few hours of increased CO2 in blood where after Excitation declines within 1-2 days
• Ultimate goal of respiration is to maintain physiological concentrations of O2, H+, and CO2 in tissues.
• Excess carbon dioxide or hydrogen mainly stimulates the respiratory center, increasing the strength of inspiratory/expiratory signals to the respiration muscles.
• Oxygen, acts on peripheral chemoreceptors in the carotid and aortic bodies which then signals the respiratory center for control of respiration

Central Chemoreceptors

• PCO2/H+ stimulates chemosensitive area of the central respiratory center as the neurons are Very SENSITIVE TO HYDROGEN
• Hydrogen does not cross the blood-brain barrier, changes in blood H+ concentrations have little acute effect on stimulation of the chemosensitive neurons in contrast to CO2.
• CO2 stimulates secondarily by increasing hydrogen concentration given that it diffuses into the brain and reacts with water to form carbonic acid then dissociates into the hydrogen and bicarbonate ions for which now, the Hydrogen has a potent DIRECT stimulatory effect
• CO2 stimulation is potent acutely but weak in chronically stimulating the respiratory drive, as the kidneys facilitate hydrogen return to normal levels.
• They increase blood bicarbonate, which binds to H+ in blood and CSF which Lowers H+ concentration.
• Bicarbonate ions diffuse through the blood-brain barrier and directly combine with the hydrogen ions near respiratory neurological

Peripheral Chemoreceptors

• 02 is not important for direct control of the central respiratory center unless arterial oxygen levels decrease greatly.
• When this happens, the peripheral chemoreceptor mechanism kicks in
• They detect changes in PO2 (they also respond to PCO2 and H+).
  • Carotid bodies (Glossopharyngeal CP 9)
    • Bifurcations of the common carotid arteries
    • Afferent nerve fibers innervate the dorsal respiratory area of the medulla
  • Aortic bodies (Vagus CP 10)
    • Along the arch of the aorta
    • Afferent nerve fibers also innervate the dorsal respiratory area
    • MECHANISM:
• Glomus cells in both bodies synapse with the nerve endings. They contain O2 sensitive potassium channels inactivated when blood PO2 decreases markedly leading to Depolarization through which activation ● Voltage gated calcium channels ● then INTRACELLULAR CALCIUM +++
• Even though O2 lack stimulates is counteracted by decrease in PCO2 and H+ in blood, due to the Lack of 02 excites the carotid/aortic receptors increased respiration which equals a Low PCO2 and H+
• Depression of the respiratory center causing the final effect of increased respiration in response to low 02 to be mostly negated, however the effect is greater on some conditions:
  • Pulmonary disease
    • Pneumonia/emphysema cause no adequate gas exchange allowing: Little 02 to blood and PCO2 and H+ to remain normal/increased