(everything from Watkins/Delaney’s notes is in here, but there’s some extra stuff from the physio for dummies text)
Lung respiratory and conducting zones
Respiratory zone – respiratory bronchioles, alveolar ducts & sacs
Conducting zone – bronchioles, bronchi, trachea
Alveoli have largest cross-sectional area
Bronchioles have smooth muscle & cartilage
23 divisions of branches into ever smaller conduits
Mucous-secreting, ciliated cells line conducting zone airways. Large particles stop at nose, smaller ones caught in cilia, finest particles (like asbestos) make it into alveoli
Gas exchange can be divided into four functional components:
Ventilation – movement of air into lungs (need pump to generate flow, pipes slow down flow – R)
Perfusion – movement and distribution of blood through pulmonary circulation
Diffusion – movement of O2 and CO2 across air-blood barrier or alveolar-capillary membrane
Control of breathing – process of regulation of gas exchange to meet metabolic needs of moment
Respiratory quotient, RQ = CO2 produced = 200 ml/min. = 0.8 (average)
CO2 consumed 250 ml/min.
Carb RQ = 1, fat RQ = 0.7, protein RQ = 0.8
A = alveolar
a = arterial blood
v = venous blood
Non-respiratory functions of respiratory system:
(upper airway includes nose, paranasal sinuses, naso- and oropharynx, larynx)
1) route for water loss, heat elimination (warms, moistens air so alveoli don’t dry out – oxygen and carbon dioxide can’t diffuse across a dry membrane)
2) enhances venous return (respiratory pump)
3) helps normalize pH by altering amount of CO2 (H+-producing) exhaled
4) enables speech, singing, other vocalization – larynx – vocal cords act as ‘vibrator’
5) defends against inhaled foreign matter (filters particulates or microbes via mucous coat propelled towards larynx by ciliary action, cough reflex, sneeze reflex, immunoglobulins – both locally produced and brought into lung from other sites)
6) removes, activates/deactivates various materials passing through pulmonary circulation (i.e., turns prostaglandins off, angiotensin II on)
7) nose – sense of smell
300 million alveoli in lungs – 0.3 mm in diameter
total surface area of lungs is about 75 m2 (size of tennis court)
collateral ventilation – airflow between adjacent alveoli (via pores of Kohn)
pleurisy – inflammation of pleural sac (painful “friction rub”)
atmospheric pressure = 760 mmHg at sea level, decreases as altitude increases
intra-alveolar pressure (intrapulmonary pressure) will equilibrate with atmospheric pressure
intrapleural pressure (intrathoracic pressure) = 756 mmHg – vacuum (called ‘-4’); closed cavity
**negative intra-alveolar, intrapleural pressures provide driving force for inhaling/exhaling
transmural pressure – pressure across surface of lungs, = Palveolus - Ppleural space
Two forces hold thoracic walls & lungs in close apposition
(can’t expand thorax without expanding lungs)
1) intrapleural fluid’s cohesiveness (like water between two slides)
2) transmural pressure gradient (most important)
intra-alveolar pressure = 760 mmHg, pushes out against intrapleural p. of 756 mmHg
atmospheric pressure = 760 mmHg, pushes in against intrapleural p.
Neither chest wall nor lungs are in their resting position (both are actively pushing against space)
Pleural space has slightly negative pressure because chest is pulling out, lungs are pulling in, and there’s no extra fluid to fill expanded space
Pneumothorax – air enters pleural cavity, pressure equalizes with atmospheric pressure, transmural pressure gradient is gone → lungs collapse, thoracic wall springs out
Before inspiration – respiratory muscles are relaxed, no air is flowing, intra-alveolar p. = atm. p.
Major inspiratory muscles (diaphragm, external intercostals) contract → thoracic cavity enlarges
[Diaphragm is innervated by phrenic nerve; dome-shaped at rest, contracts & pulls down. Responsible for 75% of enlargement of thoracic cavity during inspiration. Contraction of external intercostals enlarges cavity in lateral and AP dimensions (elevate ribs when contracting)]
As lungs expand, pressure decreases (to 759 mmHg) → air flows in
(alveolar pressure is negative during inhalation, positive during exhalation)
Intrapleural pressure drops to 754 mmHg (ensures that lungs will be fully expanded)
**Lung expansion is not caused by movement of air into lungs.
With deeper contractions, contract diaphragm and external intercostals more forcefully & contract accessory inspiratory muscles (SCM, scalenes, alae nasi, small muscles of neck/head) to raise sternum & first 2 ribs
At end of inspiration – inspiratory muscles relax, diaphragm is dome-shaped again, rib cage falls because of gravity once external intercostals relax, chest walls & stretched lungs recoil → volume decreases, pressure increases (to 761 mmHg) → air flows out
During quiet breathing, expiration is passive (due to elastic recoil of lungs – no muscular/energy expenditure), whereas inspiration is always active.
During heavy breathing – active expiration – contract abdominal muscles (increase intra-abdominal pressure → pushes diaphragm up → increases intrathoracic pressure), internal intercostal muscles (pull ribs downward, inward) → lungs are emptied more forcefully.
During forceful expiration, intrapleural pressure exceeds atmospheric pressure, but lungs don’t collapse because intra-alveolar pressure increases, too (4 mmHg pressure gradient stays same)
Paralysis of intercostal muscles doesn’t affect breathing much, but paralysis of diaphragm = can’t breathe. Phrenic nerve is C3-C5, so patients with paralysis from neck down can still breathe.
Flow, V = ∆P/R
∆P = pressure gradient between atmosphere and alveoli
R is primarily determined by radius
Resistance of total airways circuit depends on #, length, cross-sectional area of conducting airways. Each terminal bronchiole has greater resistance to flow than trachea, but because of vast cross-sectional area, their overall contribution to total R is less than that of central airways (since bronchioles are arranged in parallel).
In healthy patient, overall respiratory system has extremely low R
Laminar vs. turbulent flow
Flow can be laminar (low flow rate) or turbulent (fast flow rate)
In small airways, flow is usually laminar
For laminar flow, R = 8ηl (Poiseuille’s Law) η = viscosity, l = length
Turbulent flow has different properties – driving pressure is proportional to square of flow (V2)
Turbulence is most likely to occur with high velocity, large diameter.
Volume of inflation of lung has important effect on airway resistance
Pressure = (vol./compliance) + flow * resistance P = pressure required to breathe
Chronic obstructive pulmonary disease (COPD)
Narrowing of lumina of lower airways. When airway R increases, larger ∆P must be present to maintain same airflow. Expiration is more difficult than inspiration – “wheeze” as air is forced out through narrowed passages. In normal patients, smaller airways collapse – further outflow stops only if lung volume is very low (lungs can never be completely emptied)
Chronic bronchitis – triggered by frequent exposure to cigarette smoke, pollution, other allergens. Airway lining thickens, mucous production increases, ciliary mucous elevator is immobilized by irritants. Increased mucous → bacterial infections
Asthma – obstruction due to 1) thickening of walls b/c of inflammation, histamine-induced edema, 2) plugging of airways by very thick mucous, 3) airway hyperresponsiveness – trigger-induced spasms (allergens, irritants, infection). Most common chronic childhood disease.
Emphysema – collapse of smaller airways, breakdown of alveolar walls (irreversible). Can happen because of 1) excessive release of trypsin from alveolar macrophages as defense against cigarette smoke irritants (lungs normally protected by α1-antitrypsin, but can be overwhelmed), 2) genetic inability to produce α1-antitrypsin
(asthma and emphysema start in small airways – difficult to detect – ‘silent airways’)
Amount of inspired air that makes it to alveoli depends on:
**Strength of pump (muscles)
**Airway resistance (frictional resistance, 80% total R)
**Tissue resistance – frictional resistance of lungs and chest wall (20% total R)
**Inertance – energy must be expended to set system in motion
(Need to overcome stiff/elastic recoil, frictional resistance, and inertance)
1) elastic recoil – returning to preinspiratory volume at end of inspiration
2) compliance – measure of distensibility, magnitude of change in volume for given transmural ∆P Defined by slope of pressure-volume curve for lungs – curve is steep in normal operating range (only at very low/high volumes does curve flatten). Normal compliance is 200 cm/ml H2O. Different compliance for expiration/inspiration b/c of surfactant – hysteresis. Static compliance is measured without airflow; dynamic compliance is measured during airflow. (poor compliance = stiff lung, restrictive disease = more work to breathe)
Pulmonary elastic behavior depends on:
1) CT in lungs has lots of elastic fibers (arranged in meshwork)
2) alveolar surface tension
water molecules want to be close together – resist expansion of surface area (the greater the surface tension, the less compliant the lung). If alveoli were lined with water alone, surface tension would be so great, airways would collapse.
pulmonary surfactant (lipid-protein mixture) lowers surface tension because water-surfactant attraction is not as strong as water-water → increases pulmonary compliance, reduces lung’s tendency to recoil. Produced by type II pneumocytes
LaPlace’s Law P = 2T/r P = inward-directed collapsing pressure, T = surface tension
Smaller airways are more likely to collapse than large ones because of greater surface tension (smaller r), but surfactant is more effective at lowering surface tension in smaller airways (less spread out). Surfactant stabilizes small alveoli.
**Evidence of these two factors of lung elastic recoil is found in differing pressure-volume characteristics of saline-filled vs. air-filled lungs (saline-filled are easier to stretch than air-filled)
You can have separate pressure-volume curves for chest wall, lungs – combine to get one for total respiratory system. Two structures are in series, interdependent – force required to inflate lung equals sum of pressure difference across lung and across chest wall.
Interdependence of neighboring alveoli – surrounding alveoli resist collapse of another alveolus.
Respiratory Distress Syndrome (RDS) – not enough type II cells to make surfactant
Work of Breathing
Normally only required on inspiration
Subdivided into compliance work (to expand lungs against lung/chest wall elastic forces); tissue resistance work (to overcome viscosity of lung/chest wall); airway resistance work
Work = P * V
Measurements of Lung Volumes
3-5% of total energy expended by body goes to breathing (heavy exercise – can increase 50-fold)
in obstructive lung disease, up to 30% of body’s energy expenditure is for breathing – even at rest!
Quiet breathing – 2,200 ml (expiration) – 2,700 ml (inspiration) tidal volume = 500 ml
Tidal volume (TV or VT) – 500 ml at rest. Amount entering/leaving lungs during one breath. As tidal volume increases, intrapleural and intra-alveolar pressures decrease in direct proportion.
Inspiratory reserve volume (IRV) – 3,000 ml. extra air you can breathe in, using inspiratory muscles (beyond normal tidal volume)
Inspiratory capacity (IC) – 3,500 ml. IC = TV + IRV
Expiratory reserve volume (ERV) – 1,200 ml. extra air you can breathe out, using expiratory muscles (beyond normal tidal volume)
Residual volume (RV) – 1,400 ml. amount that can’t be expired from the lungs (can measure with tracer like helium)
Functional residual capacity (FRC) – 2,500 ml. Volume of lungs after normal passive expiration. FRC = ERV + RV
Vital capacity (VC) – 4,600 ml. Maximum volume change possible. VC = IRV + TV + ERV
Total lung capacity (TLC) – 6,000 ml. TLC = VC + RV
Forced vital capacity (FVC) – total volume expired from maximum inspiration to maximum expiration; normal range is 80-120% normal tidal volume.
Forced expiratory volume in 1 second (FEV1) – maximum volume that can be expired in one second. FEV1 = 80% VC (normal)
Maximum mid-expiratory flow rate (MMEFR) – FEF25-75 – forced expiratory flow over middle half of the FVC, gives us most information about small airways (<2mm diameter)
Peak expiratory flow rate (PEFR) – FEFmax – highest expiratory flow achieved. Can only be measured from flow/volume curve
Spirometer – air-filled drum floating in water. Breathe into drum – records volume changes on spirogram. Most lung volume subdivisions can be measured directly from spirogram
trapped gas within lung must be measured either by gas dilution method or by body plethysmography. Lung volumes can also be measured by x-ray – planimetry
Spirometry can measure TV, IRV, IC, ERV, VC (others measured indirectly, calculated)
Forced vital capacity (FVC) maneuver – take in deepest breath possible, breathe out as much as possible. Data can be displayed as volume vs. time or as flow vs. volume
if airways resistance is normal, FEV1 > 70%
Obstructive ventilatory defect – decreased air flow through tubes, normal tidal volume. Can be from 1) upper airways disease; 2) peripheral airways disease (from asthma, cystic fibrosis, chronic obstructive bronchitis, bronchiectasis); or 3) pulmonary parenchymal disease (emphysema).
Restrictive ventilatory defect – normal flow, normal R, but small vital capacity, FVC, FEV1 are reduced (in ratio to each other). Can be chest wall, pleural, space-occupying intra-thoracic lesion, extra-thoracic conditions (obesity, pregnancy, ascites), or interstitial lung disease. Reduction in lung volumes below 80% of predicted values.
Examples of lung volumes being smaller than predicted (restrictive defect):
Fibrosing (scarring) – increased elastic recoil
Diseases of chest wall (kyphoscoliosis) – increased elastic recoil
Diseases of the pleural space (pleural effusion) – compress lung
Tests of gas exchange function of lungs
Arterial blood gas determination (ABGs) – measurement of dissolved tensions of CO2 and O2 as well as pH of sample of arterial blood
Pulse oximetry – photometric measurement of saturation of hemoglobin with O2. (non-invasive)
DLCO – diffusing capacity of lung for carbon monoxide, usually done by ‘single breath’ method (DLCOsb). DLCO is affected by factors other than characteristics of gas exchange membrane; membrane thickness and increased surface area reduce DLCO.
Ventilation (V – ventilation, Q – perfusion)
Volume of air breathed in and out in one minute
Respiratory (minute) ventilation, V• = TV (ml/breath) * f, respiratory rate (breaths/min)
At rest: 6,000 ml = 500 * 12 (6 L air breathed in and out per min.)
With exercise, can increase 25-fold, to 150 L/min.
TV is more important than respiratory rate when minute ventilation increases
Dead space (VD) – volume of air-filled space incapable of gas exchange with blood
=Anatomical dead space – 150ml. volume of conducting airways (350ml used for gas exchange)
(equal to individual’s lean body weight in pounds)
Alveolar ventilation, VA• = (TV – VD, dead space) * f, respiratory rate
At rest: 4,200 ml = (500-150) * 12
Alveolar ventilation is about 5 L per minute = cardiac output (excellent transfer of gases)
Normal respiratory rate is 12-15 breaths/minute
**if you breathe deeply & slowly, respiratory ventilation can stay same but alveolar ventilation increases
**if you breathe shallowly & rapidly, respiratory ventilation can stay same but alveolar ventilation decreases (even to zero)
Each tidal breath does not completely fill/empty an alveolus – reservoir of gas ‘stored’ within alveoli that’s only gradually replenished. Volume = 3,000 ml – prevents fluctuation in alveolar gas tensions with each tidal breath.
(alveolar ventilation is more important measurement than respiratory ventilation, since that’s where gas exchange is done)
alveolar gas equation: PAO2 = FiO2 (PB – PH20) - (PACO2/R)
solving for conditions at sea level & R = 0.8: PAO2 = 0.21(760-47) – (40/0.8)
PAO2 = 100
obstructive lung disease – easy to fill lungs, hard to empty
TLC is normal
FRC, RV are increased
VC, FEV1, FEV1/VC% are decreased
restrictive lung disease – lungs are less compliant than normal
TLC, IC, VC are decreased
RV is normal
FEV1/VC% is normal or even increased
Increasing tidal volume is most efficient way to increase alveolar ventilation (increase respiratory rate and alveolar ventilation increases somewhat, but dead space is also increased)
Not all alveoli are equally ventilated with air, perfused with blood → alveolar dead space
(minimal in healthy patients, but can be lethal) ventilated, but don’t participate in gas transfer
physiologic dead space – sum of anatomical & alveolar dead space
lower regions of lung are better ventilated than upper zones.
gravity is largely responsible. pleural pressure is more negative at top of thoracic cavity – greater distending pressure for alveoli at top of lungs (top alveoli are larger in size). alveoli on bottom vs. top operate on different parts of a pressure-volume curve
lower regions of lung are better perfused than upper zones.
gravity is primary determinant. hydrostatic pressure gradient from top to bottom b/c lowest point in lung is 30 cm below highest point pressure gradient of 30 cm water = 23 mmHg (15 mmHg above heart, 8 mmHg below heart)
Perfusion conditions in lung divided into three zones (a=pulm.art, A=intra-alveolar, v-pulm.vein)
Zone 1: Pa < PA collapse of vessel before it crosses alveolus; no forward flow; doesn’t exist in normal lungs – might occur if person has hemorrhaged (BP, intravascular volume are low)
Zone 2: Pa > PA > Pv flow driven by difference between arterial/alveolar pressure; primary area of distension, recruitment of vessels during exercise
Zone 3: Pa > PA, Pv > PA continuous forward flow through distended vessels.
Matching of ventilation to perfusion
there is not perfect matching of ventilation to perfusion in most alveoli. non-uniform distribution of both results in alveolar units with varying ratios of ventilation to perfusion (V/Q)
alveoli at apex are overall poorly ventilated, perfused, but relatively better ventilated than perfused = high V/Q ratio
if no perfusion but good ventilation, alveolar gas tensions will be same as in trachea (PAO2 = 150, PACO2 = 0). No effect on downstream gas tensions – part of dead space. But if there is some degree of perfusion PAO2 will be high, PACO2 will be low
alveoli at base are well ventilated, perfused, but better perfused than ventilated = low V/Q ratio
if no ventilation, but some perfusion, alveolar gas tensions in unit will be same as those in mixed venous blood (no fresh air being added). PAO2 will be low, PACO2 will be high (blood exiting capillary will be low in O2, high in CO2)
units with low V/Q ratios have greater effect on overall gas exchange since they receive greater proportion of total pulmonary blood flow.
A high V/Q unit can’t compensate for impact of low V/Q unit because it’s at flat part of S-shaped oxygen-hemoglobin dissociation curve – raises PO2, which results in more dissolved O2, but not much more HbO2
Any rise in PCO2 in arterial blood stimulates respiratory centers to increase alveolar ventilation removal of CO2 through alveolar units with better V/Q ratios. Overventilation of these units can’t raise PaO2 since they are operating on flat upper portion of oxygen-Hb saturation curve
Measurement of V/Q mismatch