The Respiratory System Part II. Dr. Adelina Vlad

Transcription

1 The Respiratory System Part II Dr. Adelina Vlad

2 Pulmonary Ventilation Pulmonary mechanics - is the physics of the lungs, airways and chest wall - explains how the body moves air in (inspiration) and out (expiration) of the lungs

3 The Respiratory Passageways As generation number (or branching level) increases, the amount of cilia, the number of mucus-secreting cells, the presence of submucosal glands, and the amount of cartilage in the airway walls gradually decrease

4 Conducting Airways Airways maintain some cartilage to about the 10th generation, up to which point they are referred to as bronchi At about the 11th and succeeding generations, the now cartilagefree airways are called bronchioles Without cartilage, they can maintain a patent lumen because - of the outward pull (radial traction or tethering) of surrounding tissues - the pressure surrounding them may be more negative than the pressure inside Thus, bronchioles are especially susceptible to collapse during expiration

5 Alveolar Air Spaces Up until generation approximately 16, no alveoli are present, and the air cannot exchange with the pulmonary-capillary blood Alveoli first appear budding off bronchioles, called respiratory bronchioles that are branches of a terminal bronchiole The alveolar ducts terminate blindly as alveolar sacs The airways arising from a single terminal bronchiole (i.e., the respiratory bronchioles, alveolar ducts, and alveolar sacs), along with their associated blood and lymphatic vessels, is a terminal respiratory unit or primary lobule The primary lobule is the functional unit of the lung

6 Mucus Lining the Respiratory Passageways The air is conditioned in the upper respiratory airways by warming, moisturizing and filtering The mucus is involved in moisturizing and filtering processes It is secreted partly by individual mucous goblet cells in the epithelial lining of the passages and partly by small submucosal glands The mucus traps small particles out of the inspired air and keeps most of these from reaching the alveoli; the mucus is pushed towards oropharynx by the work of cilia from the ciliated epithelium that coats the surface of the respiratory passages down as far as the terminal bronchioles

7 Particles with diameters below 0.5 μm tend to reach the alveoli suspended in the air as aerosols, but most of these aerosols are expelled in the exhaled air The particles that remain on the surface of the alveoli or penetrate into the interstitial space are: - phagocytized by alveolar macrophages (on the surface) or interstitial macrophages - carried away by lymphatics Coughing and sneezing reflexes triggered by airway irritation, accelerate the movement of particulates up the conducting airways and out of the body These processes are part of the nonspecific defense system of the body

8 Resistance to Airflow in the Bronchial Tree Airflow is proportional to driving pressure (ΔP), but inversely proportional to airway resistance (R): For the lung, the driving pressure is the difference between the alveolar pressure (P A ) and the barometric pressure (P B ) Poiseuille's law states that airway resistance is proportional to the viscosity of the gas (η) and the length of the tube (l), but is inversely proportional to the fourth power of airway radius (r): Resistance to airflow is highly sensitive to changes in airway radius (a 10% decrease in r causes a 52% increase in R)

9 Airflow Patterns Influence the resistance to airflow: All particles have the same speed and direction The branches set up small eddies Vortices develop randomly Laminar airflow - the subject invests relatively little energy in airflow; characteristic to the small airways that are distal to terminal bronchioles Transitional airflow - it takes extra energy to produce vortices the resistance increases; airflow is transitional throughout most of the tracheo-bronchial tree Turbulent airflow - the effective resistance to airflow is the highest; only in the trachea, where the airway radius is large and linear air velocities may be extremely high

10 The Raynold s Number Turbulence can be predicted by the following equation: Re=2rvr/h Re - Raynold s number, r tube radius, v velocity, r gas density, h - gas viscosity The Reynolds number gives a measure of the ratio of inertial forces to viscous forces: at low Re, viscous forces (2r/h) are dominant laminar flow characterized by smooth, constant fluid motion; at high Re, inertial forces (vr) are dominant, which tend to produce random eddies, vortices and other flow instabilities turbulent flow In ideal tubes the airflow is laminar for Re < 2000; in the branched and bumped respiratory airways, the lung airflow is laminar for Re<1, condition fulfilled distal from terminal bronchioles with low r and v.

11 Airway Resistance Along the Respiratory Tract From the total airway resistance in healthy subjects, that is 1.5 cm H2O/(l/s) 0.6 is in the upper air passages, 0.6 in the large airways, and only 0.3 in the small airways R is inversely proportional with the 4 th power of airway radius each small airway has a high individual resistance However, the approximately 65,000 terminal bronchioles aligned in parallel have a much lower aggregated resistance compared to the only few large airways

12 In disease conditions, the small airways often play a far greater role in determining airflow resistance than the large airways, because they are easily occluded by: (1) muscle contraction in their walls, (2) edema occurring in the walls, or (3) mucus collecting in the lumens of the bronchioles AGGREGATE AIRWAY RESISTANCE* LOCUS NORMAL COPD Pharynx-Larynx Airways > 2 mm diameter Airways < 2 mm diameter Total airway resistance * Units of resistance, cm H 2 O/(liters/sec); COPD, chronic obstructive pulmonary disease

13 The AIRWAY CALIBER, and thus the resistance to airflow (R), is affected by three factors: 1. NEURO-HUMORAL INFLUENCES 2. LUNG VOLUME 3. FLOW OF AIR THROUGH THE AIRWAY

14 1. Effects of Neuro-Humoral Factors on Airways The vagus nerve releases acetylcholine, which acts on a muscarinic receptor on bronchial smooth muscle producing bronchoconstriction and an increase in R The muscarinic antagonist atropine blocks this action The sympathetic division of the ANS releases norepinephrine which dilates the bronchi and bronchioles and reduces glandular secretions These effects are weak because norepinephrine is a poor agonist of the β 2 adrenergic receptors that mediate this effect via cyclic adenosine monophosphate (camp)

15 Humoral factors include epinephrine, released by the adrenal medulla Circulating epinephrine is a far better β 2 agonist than is norepinephrine and, therefore, a more potent bronchodilator During allergic reactions, especially those caused by pollen in the air, inflammatory cells rush into the airways releasing histamine, slow reactive substance of anaphylaxis (SRSA), cytokines, leucotrienes and other substances with a bronchoconstrictor effect

16 2. Effects of Lung Volume (V L ) on Airway Resistance Airway resistance is extremely high at low V L, but decreases steeply at higher volumes because: all of pulmonary airways expand at high V L, and resistance falls steeply as radius increases of the principle of interdependence - alveoli have a higher compliance than conducting airways at high VL they expand more and tend to hold open their neighbors by exerting radial traction or mechanical tethering

17 3. Dilation and Collapse of Airways with Airflow The transmural pressure (P TM ) is the pressure difference across the walls of airways (AW) Can cause AW to dilate (P TM > 0) or collapse (P TM < 0) to the extent that their compliance permits: PTM = PAW PIP

18 When there is no air flowing in the AW (panel B), a constant PAW all along the respiratory tract keeps the PTM constant and the AW uniformly dilated When airflow occurs (inspiration, expiration) PTM is not constant along the AW due to variation in pressure along the AW, inherent to airflow the AW caliber is not constant from alveoli to the mouth = AW resistance varies along the bronchial tract

19 PTM when there is no airflow: PAW = PB PTP = PA - PIP PIP = PA PTP = 0 5 = - 5 cm H2O PTM = 0 - (- 5) = + 5 cm H2O constant all along the AW, which are uniformly distended

20 Pressure gradients inside AW between alveoli and the mouth determine: an increase in PTM towards the mouth in inspiration (panel A), dilating the airways

21 PTM in Inspiration At a VL equal to FRC, PTP is assumed to be +5 cm H2O. During a forced inspiration started at RV, in the moment when VL becomes equal to FRC and PA is 15 cm H2O, PIP is: PAW decreases from 0 cm H2O at the mouth to 15 cm H2O in the alveoli; at the point along the AW where PAW = - 8 cm H2O, PTM is +12 cm H2O: A similar calculation shows that at the mouth PTM would be meant to be Due to the decreased compliance of the upper AW, the increase in PTM will be under this value, inducing a discrete dilation. From the alveoli to the mouth PTM increases substantially the airflow generated in inspiration dilates the AW and decreases AW resistance

22 Pressure gradients inside AW between alveoli and the mouth determine: a decrease of PTM from periphery to the center during expiration (panel C), tending to collapse the airways total airway resistance is greater during expiration

23 PTM in Expiration During a forced expiration, in the moment when VL becomes equal to FRC and PA is + 15 cm H2O, PIP is: PAW decreases from + 15 cm H2O in the alveoli to 0 cm H2O at the mouth. At the point along the AW where PAW = + 8 cm H2O, PTM is - 2 cm H2O: A similar calculation shows that at the mouth PTM would be meant to be 10 cm H2O. Due to the decreased compliance of the upper AW, the decrease in PTM will be under this value, causing a milder collapse of the central AW From the alveoli to the mouth PTM decreases substantially the airflow generated during expiration tends to collapse the AW and to increase resistance to airflow

24 Equal Pressure Point During a forced expiration the intrathoracic airways can be divided into three sections: A peripheral section nearest the alveoli where bronchial pressure exceeds outside pressure: PAW > PIP, the airways are expanded A point where intra- and extrabronchial pressures are equal ( equal pressure point ): PAW = PIP, the borderline A more central section toward the mouth where PAW < PIP, the airway will be compressed

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26 The equal pressure point moves more distal as the lung volume decreases Airway compression occurs first in the trachea and moves more distal as the lung volume decreases Why? Because at lower lung volumes PTP (transpulmonary pressure) decreases PIP increases (PIP = PA PTP) a higher PAW is needed to equal PIP the equal pressure point moves more distal, closer to the alveoli

27 Maximum Expiratory Flow Decreases at Low Lung Volumes A, Collapse of the respiratory passageway during maximum expiratory effort, an effect that limits expiratory flow rate B, Effect of lung volume on the maximum expiratory air flow, showing decreasing maximum expiratory air flow as the lung volume becomes smaller and the equal pressures point moves toward the more collapsible peripheral airways

28 Dependence of Expiratory Flow From Effort We study the dependence of expiratory flow from effort at different lung volumes PA reflects the expiratory effort:

29 Flow is effort dependent at high V L (5 liters) At a V L of 3 liters, the four V / V L curves (max, high, med and low effort) have merged is approximately 3.5 liters/sec regardless of effort

30 At low lung volumes flow becomes effort independent because the mechanical tethering decreases and cannot oppose the tendency toward airway collapse that occurs during expiration An increase in effort (i.e., in P A ) is matched by a proportional increase in the airway resistance (R) because of expiration-induced airway collapse (flow = P A /R remains constant)

31 Clinical relevance: Flows measured at low lung volumes are more sensitive to small airways obstruction Why? - obstruction induces a decreased airflow through the airways - at high lung volumes, a powerful contraction of the expiratory muscles can increase the flow and compensate (mask) a mild obstruction (flow rate values may appear normal) - at low lung volumes, the flow rates reflect only on the permeability of the airways, since they are independent from effort even a mild obstruction becomes evident = flow rates are lower than normal

32 Flow Rates Most common respiratory disorders are categorized as obstructive or restrictive on the basis of flow rates and lung volumes Flow rate and lung volume measurements are used - to differentiate obstructive from restrictive pulmonary disorders - to characterize disease severity - to measure responses to therapy Flow rates can be determined on a spirogram and on a flowvolume loop

33 Normal Spirogram - Displays lung volume (in L) over time (in sec) FEV1 = forced expiratory volume in the 1st second of forced vital capacity maneuver FEF25 75% = forced expiratory flow during expiration of 25 to 75% of the FVC FVC = forced vital capacity: the maximum amount of air forcibly expired after maximum inspiration

34 FEV1 is the most reproducible flow parameter and is especially useful in diagnosing and monitoring patients with obstructive pulmonary disease FEF25 75%, FEF50-75%, FEF75-85% are more sensitive markers of mild small airway obstruction than the FEV1 due to flow independence of effort (and dependence of AW caliber) at small lung volumes

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36 OBSTRUCTIVE DISEASE: a reduction in flow rates, particularly the FEV1 and the FEV1 as a percentage of the FVC (FEV1/FVC, the Tiffeneau index) Obstructive defects are caused by increased resistance to flow from: abnormalities within the airway lumen (eg, tumors, secretions, mucosal thickening); changes in the wall of the airway (eg, contraction of smooth muscle, edema); modified elastic recoil (eg, the parenchymal destruction that occurs in emphysema) With decreased flow rates, expiratory times are longer than usual, and air may become trapped in the lungs from incomplete emptying, increasing lung volumes (eg, TLC, RV)

37 RESTRICTIVE DISEASE: a reduction in lung volume, TLC < 80% of the predicted value The decrease in lung volumes produces a decrease in flow rates (reduced FEV1 and FVC) Restrictive defects are caused by a loss in lung volume (eg, lobectomy), abnormalities of structures surrounding the lung (eg, pleural disease, kyphosis, obesity), weakness of the inspiratory muscles (eg, neuromuscular disease), abnormalities of the lung parenchyma (eg, pulmonary fibrosis) The feature common to all is a decrease in the compliance of the lungs, the chest wall, or both

38 CHANGES IN FLOW RATES AND VOLUMES ASSOCIATED WITH PULMONARY DISORDERS

39 SEVERITY OF OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

40 Flow-Volume Loop - Displays flow (in L/sec) as it relates to lung volume (in L) during maximal inspiration from complete exhalation (residual volume [RV]) and during maximum expiration from complete inhalation (TLC) - The flow-volume loop shows whether flows are appropriate for a particular lung volume The peak expiratory flow (PEF) is the peak flow occurring during exhalation; it is used primarily for home monitoring of patients with asthma and for determining diurnal variations in airflows

41 Normal Flow-Volume Loop Flow rates at the midpoint of the inspiratory and expiratory capacity are often measured. Maximal inspiratory flow at 50% of forced vital capacity (MIF 50%FVC) is greater than maximal expiratory flow at 50% FVC (MEF 50%FVC) because dynamic compression of the airways occurs during exhalation.

42 Obstructive Disease All flow rates are diminished. Peak expiratory flow is sometimes used to estimate the degree of airway obstruction but is dependent on patient effort. MEF 50%FVC and MEF 25%FVC are more sensitive for diagnosing mild peripheral obstructions.

43 Flows measured at low lung volumes are more sensitive to small airways obstruction Why? - obstruction induces a decreased airflow through the airways; - at high lung volumes, a powerful contraction of the expiratory muscles can increase the flow and compensate (mask) a mild obstruction (flow rate values may appear normal); - at low lung volumes, the flow rates reflect only on the permeability of the airways, since they are independent from effort even a mild obstruction becomes evident = flow rates are lower than normal

44 Restrictive Disease The loop is narrowed because of diminished lung volumes, but the shape is generally the same as in normal volume. Flow rates are greater than normal at comparable lung volumes because the increased elastic recoil of lungs holds the airways open.

45 Pneumotachometer Flow (V') is derived from the pressure difference over a small, fixed resistance, offered by a fine metal mesh The pressure drop across the resistance relates linearly to flow, when the flow pattern is laminar The trumpet-like configuration of the pneumotachometer head is designed to achieve laminar flow over a wide range of flows

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47 Pulmonary Circulatory System O 2 CO 2 O 2 CO 2 RV LA ATP CO 2 O 2 Normal anatomic right-to-left-shunt: after passing through capillaries, about half of the bronchial blood anastomoses with oxygenated blood in the pulmonary venules

48 Characteristics of Pulmonary Circulation Low pressure system - it needs to pump blood only to the top of the lung - important for avoiding the flooding of lung with edema fluid Low resistance system, less than 1/10 that of systemic circulation due to: - shorter and wider vessels ( ) - higher number of less muscular arterioles with a low resting tone High compliance vessels - due to the thin walls and the paucity of smooth muscle - can accept large amounts of blood - can dilate in response to modest increases in PA pressure - the pulse pressure is low

49 Pressures in the Pulmonary System Pressure pulse contours Pressures in the pulmonary system D, diastolic; M, mean; S, systolic

50 Pulmonary Capillaries Pulmonary blood volume = 450 ml ( ml) Capillary blood volume = 75 ml at rest, up to 200 ml during exercise There are 280 billion highly anasomosing capillary segments = nearly 1000/ alveolus, creating a gas exchange surface of 100 square meters Blood passes through the pulmonary capillaries in about 0.8 s at rest and can shorten to 0.3 s when the cardiac output increases Alveolar capillaries are collapsible: If capillary pressure falls below alveolar pressure, the capillaries close off, diverting blood to other pulmonary capillary beds with higher pressures.

51 Influence of Gravity on Regional Perfusion

52 At rest and in orthostatic position, hydrostatic pressure gradient is about 15 mm Hg at the apex, resulting in a = + 10 mm Hg systolic Pa and an 8 15 = 7 mm Hg diastolic Pa the capillary beds located at more than 10 cm above the midlevel of the heart are closed during RV diastole (zone 2) Ppc < PAlv because the diastolic value (8 mm Hg) cannot overcome the hydrostatic pressure gradient In the lower regions of the lung, capillaries remain continuously open (zone 3) because Ppc remains greater than zero during both systole and diastole Blood is directed toward the base of the lung. Zone 1 occurs only under abnormal conditions: very high PAlv or exceedingly low systolic Ppc

53 Influence of Gravity on Regional Perfusion In an upright subject, perfusion is greatest near the base of the lung and falls towards the apex

54 Influence of Gravity on Regional Ventilation Because of the action of gravity, for an upright subject PIP is lower at the apex (- 7.5 cm H2O) compared to the base of the lung (- 2.5 cm H2O) alveoli at the top of the lung are more distended compared to the alveoli at the base the alveoli at the base are more compliant = during inspiration, the same DPIP produces a grater DVL near the base than near the apex for an upright subject, regional ventilation is greater at the base than at the apex of the lungs

55 Matching Ventilation and Perfusion The local ventilation-perfusion ratio (VA/Q) determines the local alveolar concentration of O2 and CO2 In the lungs of an upright subject VA/Q varies with height: Is lowest near the base where Q exceeds VA (VA/Q < 1) Gradually increases to 1 (VA/Q = 1) at the level of the 3 rd rib, where Q = VA Further increases toward the apex, where Q falls more than VA (VA/Q > 1)

56 When alveoli are ventilated but not perfused = alveolar dead space ventilation, VA/Q ; although the alveoli are ventilated, they are not engaged in gas exchange Compensatory changes correct the mismatch: - blood flow is redirected toward the normal parts of the lung that become hyperperfused VA/Q decreases in these areas - alveolar dead space ventilation lowers local alveolar PCO2 and triggers compensatory bronchiolar constriction airflow diverts toward normally perfused areas - starved pneumocytes II in the hipoperfused alveoli produce less surfactant, resulting a local decrease in compliance with a further decrease of local ventilation the compensation tends to correct VA/Q in both hypoperfused and normal areas, improving gas exchange A natural cause is pulmonary embolism; as lungs are filtering small emboli, they deal will small regions of dead space ventilation on a recurring basis

57 When alveoli are perfused but not ventilated (shunt, VA/Q tends to zero) - airflow is redirected to normal parts of the lung, - the decrease in local alveolar O2 triggers a compensatory hypoxic pulmonary vasoconstriction blood is redirected towards normally ventilated areas The normal areas are better ventilated and perfused, whereas the shunt zone looses the blood flow the compensation tends to correct VA/Q in both hypoventilated and normal areas, improving the alveolar gas exchange Natural causes generating a functional shunt: atelectasis (collapse of the alveoli), foreign bodies or tumors inside the airway

58 Local Control of Arterioles and Bronchioles by O 2 and CO 2 Gas composition Bronchioles Pulmonary arterioles Systemic arterioles P CO2 Dilate Constrict Dilate P CO2 Constrict Dilate Constrict P O2 Constrict Dilate Constrict P O2 Dilate Constrict Dilate Strong effects are marked in bold

59 Local Control Compensates Ventilation - Perfusion Mismatches

60 Mechanisms for Keeping the Alveoli Dry The pulmonary capillaries and the pulmonary lymphatic system - maintain a slight negative pressure in the interstitial spaces - are able to carry away the excess interstitial fluid (20 ml/ hour)

61 Capillary Exchange of Fluid in the Lungs

62 Pulmonary edema safety factor - The protection mechanisms are overwhelmed when the capillary hydrostatic pressure (7) rises up to the plasma osmotic pressure (28) edema - In acute conditions the safety factor is 21 mmhg (7 28 mm Hg) - In chronic conditions, due to lymph vessels expansion, the safety factor rises to mm Hg Examples: acute conditions left-sided heart failure chronic conditions mitral stenosis