Respiratory Flashcards
What are the conducting airways?
From trachea, main bronchi (R and L), then lobar bronchi then segmental bronchi.
This process continues down until terminal bronchioles - smallest airways without alveoli
Function of conducting airways
o To lead inspired air to the gas exchanging regions of the lung
o As the airways become smaller, the amount of cartilage decreases and smooth muscle increases - the very small distal airways are composer mostly of smooth muscle.
o Because there is no gas exchange, they constitute the anatomic dead space - areas with ventilation but no blood flow.
Anatomical dead space
Space of conducting airways where there is no gas exchange
About 150mL
What is the respiratory zone?
o The terminal bronchioles divide into respiratory bronchioles, which have occasional alveoli budding from their walls
o Then alveolar ducts, completely lined with alveoli
What is an acinus
Portion of the lung distal to a terminal bronchiole, forms an anatomical unit called acinus
Airways zones
Blood-gas interface
o Extremely thin (0.2-0.3um) over much of its area
o Big surface area of 50-100m2
What are the main 4 lung volumes?
Tidal volume
Inspiratory reserve volume
Expiratory reserve volume
Residual volume
Tidal volume
Volume inspired or expired with each breath
Inspiratory reserve volume (IRV)
o Is the volume that can be inspired over and above the tidal volume.
o Is used during exercise.
Expiratory reserve volume (ERV)
The volume that can be expired after the expiration of a tidal volume.
Residual volume (RV)
The volume that remains in the lungs after a maximal expiration. cannot be measured by spirometry.
What are the main lung capacities?
Inspiratory capacity
Functional residual capacity
Vital capacity
Total lung capacity
Inspiratory capacity (IC)
Sum of tidal volume and inspiratory residual volume
Functional residual capacity (FRC)
o Sum of expiratory reserve volume and residual volume
o Is the volume remaining in the lungs after a tidal volume is expired.
o Includes the RV, so it cannot be measured by spirometry.
Vital capacity (VC) (aka forced vital capacity - FVC)
o Is the sun of tidal volume, IRV, and ERV.
o Is the volume of air that can be forcibly expired after a maximal inspiration.
Total lung capacity (TLC)
o Is the sum of all four lung volumes.
o Is the volume in the lungs after a maximal inspiration.
o Includes RV, so it cannot be measured by spirometry.
Graph of lung capacities / volumes - draw
Physiologic dead space
o Is a functional measurement.
o Is defined as the volume of the lungs that does not participate in gas exchange.
o Is approximately equal to the anatomic dead space in normal lungs.
o May be greater than the anatomic dead space in lung diseases in which there are ventilation/perfusion (V/Q) defects.
Equation to calculate physiological dead space
Minute ventilation
Volume of gas inhaled or exhaled per minute
Minute ventilation = Vt x RR (bpm)
Alveolar ventilation - VA
VA = (VT - VD) x RR (bpm)
VT = tidal volume
VD = physiological dead space
A person with a tidal volume (VT) of 0.5 L is breathing at a rate of 15breaths/min. The PCO2 of his arterial blood is 40mmHg, and the PCO2 of his expired air is 36 mm Hg. What is his rate of alveolar ventilation?
Muscles of inspiration
- Diaphragm
o Is the most important muscle for inspiration.
o When the diaphragm contracts, the abdominal contents are pushed downward, and the ribs are lifted upward and outward, increasing the volume of the thoracic cavity.
- External intercostal and accessory muscles
o Not used for inspiration during normal quiet breathing.
o Used during exercise and in respiratory distress.
Muscles of expiration
o Expiration is normally passive.
o Because the lung-chest wall system is elastic, it returns to its resting position after inspiration.
o Expiratory muscles are used during exercise or when airway resistance is increased because of disease (e.g., asthma)
o Abdominal muscles -> compress the abdominal cavity, push the diaphragm up, and push air out of the lungs.
o Internal intercostal muscles -> pull the ribs downward and inward.
Compliance of the respiratory system
o Describes the distensibility of the lungs and chest wall.
o Is inversely related to elastance, which depends on the amount of elastic tissue
o Is inversely related to stiffness.
o Is the slope of the pressure-volume curve
o Is the change in volume for a given change in pressure. Pressure can refer to the pressure inside the lungs and airways or to transpulmonary pressure (i.e., the pressure difference across pulmonary structures).
Compliance equation
C = V / P
C = compliance (mL/mmHg)
V = volume (mL)
P = pressure (mmHg)
Transmural pressure
Alveolar pressure - intrapleural pressure
Compliance of the lungs
o When the pressure outside of the lungs (i.e., intrapleural pressure) is negative, the lungs expand and lung volume increases.
o When the pressure outside of the lungs is positive, the lungs collapse and lung volume decreases.
o In the air-filled lung, inflation (inspiration) follows a different curve than deflation
(expiration);
o This difference is called hysteresis and is due to the need to overcome surface tension forces at the air-liquid interface when inflating the lungs.
o In the middle range of pressures, compliance is greatest and the lungs are most distensible.
o At high expanding pressures, compliance is lowest, the lungs are least distensible, and the curve flattens.
Airway pressure Paw
Pressure in the upper airways
Unless pressure is applied at the airway opening, Paw is 0mmHg or 760mmHg (same as atmospheric pressure)
Intrapleural pressure (aka intrathoracic pressure)
o Pressure in the pleural space
o Normally about -4mmHg at the end of expiration - we compare all pressures with atmospheric, so if we consider atmospheric pressure 0mmHg, then intrapleural is -4mmHg
How can we measure intrapleural pressure?
Using the esophageal pressure, obtained placing a specially designed balloon in the esophagus
Intrapulmonary pressure (aka intraalveolar pressure)
o Pressure at the alveoli level
o Changes as the intrapleural pressure changes
How many pressure gradients do we normally use to describe normal ventilation?
Four
o Transairway pressure
o Transthoracic pressure
o Transpulmonary pressure
o Transrespiratory pressure
Transairway pressure - Pta
o Pressure difference between the airway opening and the alveolus
o Pta = Paw - Palv
o The pressure gradient required to produce airflow in the conductive airways.
o Pressure that must be generated to overcome airway resistance
Transthoracic pressure (Pw or Ptt)
o Pressure difference between the pleural space and the body surface (Pbs) (same as atmospheric)
o It represents the pressure required to expand or contract the lungs and the chest wall at the same time
o Ptt = Pintrapleural - Pbs = (-4mmHg - (0mmHg)) = -4mmHg
Transpulmonary pressure (PL or Ptp)
o AKA transalveolar pressure
o Pressure between alveolar space and pleural space
o Pressure required to maintain alveolar inflation and is sometimes called the alveolar distending pressure
o Ptp = Palveolar - Ppleural = (0mmHg - (-4mmHg)) = +4mmHg
Why is intrapleural pressure negative?
o Natural elasticity of the lungs - recoil, wanting to go back when stretched.
o Surface tension - tension due to water / air interaction, tries to collapse lung
o Elasticity of the chest wall
o The overall result of the interaction of these 3 factors is increasing thoracic cavity volume and maintain negative intrapleural pressure - based on Boyle’s law
Boyle’s law
o Pressure x volume is constant (at a constant temperature)
o As volume increases, the pressure of the gas decreases in proportion
o P1 x V1 = P2 x V2
Transrespiratory pressure
o Pressure difference between the alveolar pressure and the atmospheric pressure
o Ptr = Palv - Patm = 0 - 0 = 0
Summary of pressure gradients at rest
T/F During inspiration the thoracic cavity will increase in volume - same as the pleural space, therefore based in Boyle’s law, the intrapleural pressure will decrease. It decreases from -4mmHg at rest to -6mmHg during inspiration.
TRUE
T/F During inspiration, intrapulmonary pressure (or alveolar pressure) will also decrease as the lungs increase volume. It will decrease from 0mmHg at rest, to -1mmHg during inspiration
TRUE
Explain how will pressure gradients change with inspiration
o Transpulmonary pressure = alveolar - intrapleural = ((-1) - (-6)) = 5mmHg -> increases from +4 to +5 during inspiration.
o Transthoracic pressure = intrapleural - atmospheric = ((-6) - (0)) = -6mmHg -> chest is pulling outwards. It has decreased from -4mmHg at rest to -6mmHg during inspiration
o Transrespiratory pressure = intraalveolar - atmospheric = ((-1) - (0)) = -1mmHg -> has decreased from 0 to -1mmHg -> means that air is going from the atmospheric to the alveoli.
T/F During inspiration, the intrapulmonary pressure will decrease to -1mmHg, compared to 0mmHg of the atmospheric. The goal is to move air in from high pressure to low pressure, until it equals again the intrapulmonary with atmospheric.
TRUE
T/F Expiration is passive, no muscles involved. The stretch receptors will send signals to the respiratory centers to inhibit stimulus and muscles will relax.
TRUE
T/F During expiration, thoracic cavity volume decreases, therefore pressures increase
TRUE
Summary of pressure changes during inspiration and expiration
T/F During expiration, intrapulmonary pressure raises to +1mmHg, therefore air goes out as it is higher than atmospheric at 0mmHg
TRUE
T/F Forced expiration does involve muscles
TRUE - abdominal muscles and internal intercostals
Upper airways include
Nasal chambers
Larynx
Pharynx
Cranial trachea
Walls of nasal chambers and turbinates are covered in what?
Layer of ciliated columnar mucous membranes
Rich in capillaries and branches of olfactory nerve
Purpose: warm humidify and filter
Pharynx structure
o Muscular tube lined with mucous membranes
o Crossover point between respiratory and digestive system
How does the air moves through the nostrils when a dog breathes ?
Air comes in through the middle of their nose
Comes out through the alar fold
Can we affect that when we place nasal cannulas, HFO?? We don’t know
Vomeronasal organ
Sensory organ that detects pheromones picked up by a dog’s wet nose
Olfactory bulb
Brain region that processes signals from the olfactory epithelium
3 times larger than in humans
Structure of larynx
o Rigid box-like structure (cartilage and smooth muscle)
o Arytenoids, cricoid, thyroid and epiglottis
o Vocal folds, ventricles, saccules
Describe upper trachea
o Permanently open, flexible tube
o C-shaped rings of hyaline cartilage linked by smooth muscle and fibrous connective tissue
o Each rings open onto dorsal aspect of trachea
Lower respiratory tract
o Intrathoracic trachea - slightly right to the esophagus. Lined with ciliary columnar mucous membrane to trap dust/dirt, particles -> pharynx -> coughed out or swallowed and destroyed by stomach acid
o Bronchi - right and left main bronchi branch from trachea. Rings of cartilage are complete and smaller than trachea
o Each bronchus enters the root of each associated lung and divides into smaller secondary bronchi -> bronchioles.
o About 16 divisions before becoming respiratory zone
Describe anatomy of dog lungs
o Right: cranial, middle, caudal and accessory
o Left: cranial and caudal.
o Left: cranial LL has 2 portions -> cranial and caudal portions of the left cranial LL.
Describe cat lungs
o Right: cranial, middle, caudal and accessory
o Left: cranial, middle and caudal
Once we are in the bronchioles, how do the airways continue to divide?
Terminal bronchioles -> respiratory bronchioles -> each divides to form 2-11smaller alveolar ducts -> end in alveolar sacs with 2-4 alveoli.
Globet cells and club cells
o Globet cells and cilia along the respiratory tract from the trachea, but as we go down they decrease in number.
o Globet cells - secrete mucus and bring unwanted particles up from lower airways. No longer found in bronchioles.
o Club cells - important in making glycosaminoglycans to protect the bronchioles and also serve as stem cells to make more bronchial epithelium.
Is there muscle in the lungs?
No.
The ability to contract or expand is due to the presence of collagen and elastin from fibroblasts.
Alveoli structure
o 700 million alveoli in human lung
o 0.1-1.5 um thick
o 50-100 um radius -> tendency to collapse
o Pores of Kohn - allow for colateral ventilation between alveoli but also a bit of fluid, bacteria, cells to come in and out of alveoli. Tent to be next to cells that don’t actively participates in gas exchange.
o Three major type cells: pneumocystis type I, type II and macrophages
o Nitrogen skeleton, poorly soluble gas. Helps maintain the alveoli open.
o Pulmonary artery leads to the net of capillaries that surround the alveoli - covers about 70% of the surface area.
o Capillaries leave the alveoli and form pulmonary vein that goes to the left atrium
Describe function of the 3 major type of cells we can find in the alveoli
o Pneumocytes type I - thin, flat and make the structure of the alveoli, helps with functionality of gas exchange.
o Pneumocytes type II - cuboidal, responsible for making the surfactant to lower surface tension. Surfactant within lamellar bodies.
o Macrophages - clean up debris.
Arteries in the pulmonary vasculature are about ______ of the pressure compared to systemic circulation
1/6 th
Low pressure system
T/F The arteries within the pulmonary vasculature have a tunica media hall as thick as the arteries in the systemic circulation and have elastic / muscular tissue
TRUE
Arterioles in the pulmonary circulation have a diameter of ________ microns with no muscular tissue, similar to venues.
< 100 microns
T/F There are arteriovenous anastomosis in the pulmonary circulatory system that can open when CO decreases
FALSE - open only when CO increases - exercises, higher demands of O2 - body adjusts.
Capillaries in the pulmonary circulation
o They arise from metarterioles
o They create a dense network over alveoli that traverse multiple alveoli -> venule
Bronchial circulation
o Supplies conducting airways
o Provides heat to warm and humidify inspired air
Are there lymphatics in the lungs?
o Yes
o At junction between alveolar and extra alveolar spaces -> when they get dilated -> peribronchial coughing
What do the met arterioles pre capillary sphincters do?
o They open or close based on need for O2 / CO2 and potentially on what happens inside the alveoli itself
o Hypoxic vasoconstriction -> this sphincters are closed -> blood goes from terminal arteriole to the venule -> shunting blood
T/F The alveolar epithelium and capillary endothelium fuses their basement membranes in the areas of gas exchange, to facilitate it.
TRUE
Alveolar surface tension
o Forces of attraction between molecules of liquid lining the alveoli causing a centripetal pressure, therefore alveoli tend to collapse - the smaller the higher pressure for collapse.
o Elastic recoil of lungs largely due to surface tension of air-water interface.
o Pressure inside a bubble is always higher than the pressure of the surrounding gas, but the alveoli are connected with the atmospheric pressure.
o Surfactant will create repulsing forces that will opposing those of surface tension -> surfactant reduces surface tension, although radius of bubble is also important based on the Law of Laplace
Law of Laplace
P = 2T / r
P = collapsing pressure
T = surface tension
r = radius
Because of the collapsing pressures, air would tend to move from smaller to bigger alveoli.
When there is surfactant present, it reduces the surface tension therefore radius becomes a little less important and there is less tendency for air to move from small alveoli to larger alveoli.
Surfactant
o Produced in the lamellar bodies of the type II pneumocytes to decrease surface tension (by 28% compared to having only air/water interface)
o Surface tension tends to collapse alveoli and suck fluid into alveolar space from capillaries
o By reducing surface tension:
- Prevent transudation of fluid, small alveoli emptying, collapse of alveoli, decreases WOB, increases lung compliance.
o Made up of 90% lipid with a hydrophilic and hydrophobic ends - polar head + nonpolar tail.
o Remainder of surfactant made of proteins - A, B, C and D - immunologic function
What is the partial pressure of a gas?
o Pressure exerted independently by a gas within a mixture of gases.
o Partial pressure of each gas = total P x fractional composition of the gas in the mixture
Composition of dry air
Partial pressure of O2 and CO2 in the body
Diffusion of O2 and CO2 across concentration gradients is according ___________
Fick’s law
Fick’s law
o Diffusion of a gas is inversely proportional to the thickness and proportional to surface area
o A large, thin alveolar wall will enable more gas exchange than a short thick sheet
Diffusion = SA x D x (P1-P2) / T
SA = surface area
D = diffusion constant (different for each gas)
P1 - P2 = pressures at each side of the membrane
T = thickness of the membrane
Boyle’s law
P1 V1 = P2 V2
Dalton’s law
P total = P1 + P2 + P3 …
If partial pressure of one gas increases, another has to decrease to compensate
Henry’s law
o At a constant temperature, the concentration of a gas will be proportional to the pressure of the gas -> the amount of gas that dissolves in a liquid is directly proportional to the partial pressure -> more pressure, more concentration.
o Soda bottle - pressurized system - high concentration. If we open - pressure decrease as concentration decreases.
o Animal with SQ emphysema and we give 100% oxygen - trying to push out the nitrogen and put oxygen -> it will then move into the blood stream and be exhaled
How much oxygen contains each gram of hemoglobin when it is 100% saturated?
1.36mL O2 / gram of Hb
Normal Hb is about ________, therefore 1dL of blood contains approximately ________ of O2 bound to Hb
15 grams / dL of blood
20mL (1.36 x 15)
T/F Amount of dissolved O2 is a linear function of PaO2
TRUE
0.003 mL / dL / mmHg PaO2
There is always a small physiologic shunt due to venous blood that bypasses pulmonary capillaries, therefore PaO2 is normally ______ mmHg and SpO2 ________%
97mmHg
97.5%
How much oxygen is normally removed in a resting state?
About 25%
Venous blood normally saturated to 75%, total O2 content of 15.2mL/dL
T/F - P50 is at what PaO2 the Hb is saturated 50% and it is species dependent
TRUE
Dogs 28.8mmHg
Cats 36mmHg - less affinity for Hb, more released to go into the tissues
Things that will shift Hb-O2 dissociation curve to the right
o Increased P50 (cats - decreased affinity)
o Increased temperature
o Increased CO2
o Increased 2,3-DGP
o Decreased pH
Things that will shift Hb-O2 dissociation curve to the left
o Decreased P50 (increased affinity for O2)
o Decreased temperature
o Decreased CO2
o Decreased 2,3-DGP
o Increased pH
Causes of hypoxemia
o Low FiO2
o Hypoventilation -> Dalton’s law (Total = P1 + P2 + P3…)
o Venous admixture: Low V/Q, no V/Q, diffusion impairment, shunt
Summary of partial pressures of gases in dead space, alveoli and blood
Causes of hypoxemia, PaO2, A-a gradient and responsiveness to O2
T/F - Breathing is controlled with respiratory centers in the medulla, but we can also control it voluntarily (cerebral cortex)
TRUE
Control of breathing
MEDULLA
o Ventral respiratory group (VRG) -> both inspiratory and expiratory neurons
- Pre-Botzinger complex -> central pattern generator (recently recognized as kind of the SA node for breathing, the pacemaker)
- Botzinger complex -> expiratory neurons
o Dorsal respiratory group (DRG) -> inspiratory neurons
PONS
o Apneustic center -> stimulate inspiratory neurons of DRG and VRG -> role in gasping breathing
o Pneumotaxic center -> regulates volume and rate, is like the off switch. For fine tunning
CORTEX, LIMBIC SYSTEM -> voluntary control, emotions
Central chemoreceptors in the medulla
o Retrotrapezoid nucleus in the brainstem
o Has pH sensors -> blood CO2 will diffuse into CSF and increase the concentration of protons, decreasing pH -> central mediated hyperventilation to eliminate CO2.
Peripheral chemoreceptors
o Bilaterally paired in carotid bodies (glomus type I cells), less in aortic bodies
o Hypoxemia (via oxygen sensitive K channels), hypercapnia, acidemia, or decreased in perfusion -> increased ventilation via glossopharyngeal nerve
o We also have baroreceptors -> mostly concerned with circulation, but severe hypotension will lead to hyperventilation.
Receptors within the lungs to control breathing
o Stretch receptors (usually inactive)
- Within airway smooth muscle -> stretch -> vagus nerve -> inhibits apneustic center
- Inhibits respiration / prevents overdistension (Hering Breuer reflex)
o Irritant receptors
- Between airway epithelial cells (noxious gases, cigarette smoke, dust, cold air)
- Causes bronchoconstriction and hyperpnea
o J receptors (juxtacapillary and in alveolar walls; aka C-fibers)
- Interstitial fluid or engorged pulmonary capillaries (PTE) -> stimulate rapid, shallow breathing
- Also in bronchi, larynx and nose
Summary control of respiration
T/F - Phrenic nerve controls diaphragmatic muscles and intercostal nerves travel from the spinal cord (C2-C3) to the intercostal muscles
TRUE
Why a patient that comes with cervical spinal cord injury might have breathing difficulties?
Interrupted connections between CNS and phrenic / intercostal nerves
T/F Atmospheric pressure increases with altitude
FALSE - decreases
760mmHg at sea level
T/F Intrapleural pressure changes from top to bottom of the lungs
TRUE
The lung is distorted by its own weight -> alveoli are stretched and expanded in the dorsal aspect, while they are compressed at the bottom by lung above
What makes air flow in and out of the lungs?
o Contraction and relaxation of diaphragm and intercostal muscles
o Lungs are passive participants -> due to adhesive nature of pleural fluid, lungs are pulled outward when thoracic wall expands
o Recoil of thoracic wall during exhalation causes compression of lungs
o Resistance -> force that will slow motion, slow flow of gases -> primarily dependent on diameter / size of airways -> ΔP / Flow
o Compliance -> ability to stretch while under pressure; aka distensibility. C = ΔV/ΔP
Compliance
o Varies with lung size -> decreases at high lung volumes
o When abnormally low -> lung is stiff. Difficult inhalation but easy exhalation.
o Increased compliance -> filling is easy, exhalation is difficult
Equation of motion
What is pendelluft
Movement of air within small airways; air pendulum
Why is it important to have an adequate inspiratory time and pause?
o Because we have fast and slow alveoli.
o If we deliver a very fast high velocity air into the airways we might be only filling the fast alveoli.
o Adequate inspiratory time and pause to allow equilibration of gases in the airways
T/F Lung compliance is the same during inspiration and exhalation
FALSE - at any given pressure, the lung volume will be less during inhalation than during exhalation
What is hysteresis? What causes the differences in compliance during inspiration and exhalation?
o The reluctance or delay of elastic structures to accept the deformation imposed by an applied stress.
o Is due to the surfactant - will change surface tension more rapidly during expansion than during compression
o Inhalation -> the lung becomes soon less compliant -> probably to avoid overdistension
o Exhalation -> the lung, as the volume decreases, becomes more compliant -> probably to allow collapsing of airways
How can we calculate resistance in a ventilated patient?
(PIP - Pplateau) / flow
Dynamic Compliance
Cdyn = ΔV / PIP - PEEP = mL/cmH2O
ΔV = tidal volume
PIP = peak inspiratory pressure
PEEP = positive end expiratory pressure
Static compliance
Cstat = ΔV / PIP - Pplateau = mL/cmH2O
ΔV = tidal volume
PIP = peak inspiratory pressure
Pplateau = plateau pressure
Relationship between tidal volume, inspiratory time and flow rate
Flow rate = Vt / Tins
Vt = tidal volume
Tins = inspiratory time
Changing things around we can also say:
Tins = Vt / Flow
Vt = Flow x Tins
Based on Bradbrook et al., 2013, which formulas did they come up with to calculate compliance and resistance based on body weight?
Crs = BW + 9
Rrs = (BW x (-0.1)) + 7
Crs = compliance of the respiratory system
Rrs = resistance of the respiratory system
T/F - There is more laminar flow within the small airways than within the trachea
TRUE
T/F Turbulent flow is more difficult to calculate as we don’t know exactly which gas with go from point A to point B, whereas with laminar flow it is easier, we just apply the formula
TRUE
T/F Due to gravity, the distribution of tidal volume is not the same between dorsal and ventral alveoli
TRUE
At FRC, dorsal alveoli are _______ and ________ to the plateau of their pressure/volume curve (cannot accept much more V) due to gravity pull
Large
Closer
Alveoli at the bottom are ________ on pressure/volume curve due to weight of lungs above and ______ accept more volume/change in pressure
lower
can
Why is there greater perfusion than ventilation in the bottom of the lungs?
Because blood is heavier compared to lungs, but both perfusion and ventilation increases in dependent regions of the lungs
T/F Increasing pressure ventrally distends vessels -> increases resistance to flow
FALSE - decreases resistance to flow
Ventilation (V) / Perfusion (Q)
o Non-dependent regions -> higher V/Q
o Dependent regions -> lower V/Q
o Pulmonary capillaries in non-dependent regions have increased O2 and decreased CO2
o Dependent regions suffer from atelectasis / edema + most greater influence on net blood ABG since they receive more blood flow -> prone position preferred if under GA.
West lung zones
In diseased lungs we have a zone 4 with increased interstitial pressure and reducing flow
TRUE
How is ventilation / perfusion normally controlled?
o Autoregulatory controls
o If low PAO2 -> constriction of terminal arteries -> shunt blood -> hypoxic pulmonary vasoconstriction
o If high PAO2 -> dilation of arterioles to increase blood flow
o If PaCO2 is high -> bronchioles will dilate to eliminate CO2
o End result: poorly ventilated areas with low PAO2 and high PaCO2 have vasoconstriction and bronchodilation to correct.
Dead space
How will the following diseases affect C / R?
Aspiration pneumonia
Feline asthma
Severe ascites
Tracheal collapse
Mainstem bronchus intubation
ARDS
Aspiration pneumonia -> decreased compliance
Feline asthma -> increased resistance
Severe ascites -> decreased compliance
Tracheal collapse -> increased resistance
Mainstem bronchus intubation -> decreased compliance - less volume per unit of change in pressure
ARDS -> decreased compliance
Pickwickian syndrome
Obesity hypoventilation syndrome, happens there is obesity and have hypoxemia and hypercapnia
Explain why with diseases that have decreased compliance we tend to see fast shallow breathing
o Lungs cannot expand well, needs higher pressures -> to get same minute ventilation as tidal volume is reduced, therefore they need to increase RR
o Also, J receptors in lungs activated -> will stimulate a rapid shallow breathing
Explain why with diseases that have increased resistance we tend to see slow deep breaths
We need to maintain a good minute ventilation -> takes longer to get an adequate tidal volume due to increased resistance -> we have to generate greater pressures to get air from point A to point B.
In which animals would we use the pulmonary function tests?
o In not very sick ones - exercise intolerance, cough or shortness of breath
o Or in patients that are on the vent
How would be a different way to classify respiratory diseases?
o Obstructive diseases (like COPD, air trapping) - big lungs
o Restrictive diseases (fibrosis) - small lungs
o In dogs / cats add upper airway / cervical obstruction
Forced expiratory volume / capacity
How much air you can breath out
o In 1 second - FEV
o Or completely (until getting to the residual volume) - forced vital capacity (FVC)
FVC / FEV in obstructive disease
o Hard to get the air out
o Small airway disease, inflammation, mucus plugs
FVC / FEV for restrictive disease
o Flow is not a problem, easy to get air out but capacity is reduced, they do not have more air to exhale
o Stiff lungs, they cannot inflate as much
If there is a patient with reversible obstruction to air flow and we give bronchodilators, what would we expect to occur to FEV/FVC?
Both would increase
Can be measured pre and post bronchodilator
T/F Dogs do not have airway reactivity and bronchoconstriction
TRUE
Causes of reduction of forced vital capacity
o Thoracic cage disease
o Neuromuscular disease
o Pleural space disease (pneumonia/effusion)
o Fibrosis
o Pulmonary edema
T/F Expiratory flow rates are limited by dynamic compression of airways during forced expiration, at some point you cannot increase anymore the rate
TRUE
What are challenges with pulmonary function testing in dogs?
o Cooperation
o Not possible to do effort breathing (maximal inspiration or exhalation)
Abnormalities in lung function testing
Rationale for lung function testing
What are veterinary options for pulmonary lung testing?
o TBFVL - tidal breathing flow volume loops
o Compliance and resistance
o 6 minute walk test
Tidal breathing flow volume loops
o Facemask connected to a pneumotachograph
o Measures flow, rate, and integrates to volume
o Changes in wave forms support obstructive diseases
Tidal breathing flow volume loops - upper airway obstruction
Tidal breathing flow volume loops - lower airway (feline asthma)
o Similar inspiratory flow
o Marked change in expiratory flow due to bronchoconstriction and mucus plug
T/F With tracheal collapse, if it is extrathoracic collapse they will have more inspiratory flow limitation vs intrathoracic collapse will curse with expiratory flow limitation
TRUE
Given this loop, what is the most likely disease?
o Most consistent with a fixed obstruction (tracheal mass)
o Light grey abnormal
What are lung mechanics governed by?
Flow rate - mL/sec
Driving pressure - cmH2O
Inspiratory time (occasionally expiratory time)
Resulting volume of air moved
T/F Higher flow rates require more pressure to generate
TRUE
For a given tidal volume, higher flow rates will result in _______ peak pressures over a short time
Higher
- Plateau pressure should be the same
T/F If there is a big difference between PIP and P-plateau it can be due to increased airway resistance but also due to a short inspiratory time (or both)
TRUE
Causes of increased lung resistance
o Primarily the upper / larger airways
o Lar par, BOAS
o Bronchoconstriction / lower airway dz
o Tracheal collapse
How can static compliance be measured under anesthesia?
o Having an anesthesia machine with pressure gauge and a hand held spirometer
o Inflate the lungs to 20cmH2O then measure exhaled volume
o Inflate the lungs to 10cmH2O then measure exhaled volume
o Measure static compliance (change in V / change in P)
Example of measuring static compliance in dogs under anesthesia
What is dynamic hyperinflation?
o Air trapping
o Intrinsic (auto) PEEP
o Most common in patients with intrinsic airway disease, with lower airway diseases
o Breathing without fully getting rid of the air -> chest cavity just expands and it becomes more difficult to move air.
Intrinsic (auto) PEEP
o Typically in ventilated patients
o Inadequate time for exhalation (may or may not be pathologic)
o Small airway disease /mucus
Negative effects of autoPEEP
o Worsening of cardiac pressure
o Barotrauma or hypoventilation if pressure limited ventilation
o Increased mean airway pressure
What is time constant?
o When pressure is applied to the lung, there is a time lag (very short, millisecond), until the volume change occurs
o The time point at which to inflate or deflate to 63% of tidal volume is called time constant
o Given also by compliance x resistance
Which disease would have the longest time constant?
ARDS
COPD
Pulmonary edema
Pneumonia
COPD - having hard time getting air out
What is an entrapped lung? and a trapped lung?
o Entrapped lung - unexpandable lung due to active process (like a pyothorax)
o Trapped lung - unexpandable lung due to long resolved process (resolved pyothorax 5 years later)
Six minutes walk test
PCO2 depends on?
Alveolar minute ventilation - Vt x RR
When we have a patient intubated, what properties of the respiratory system determines how much pressure reaches the alveoli?
Several factors:
o Resistance of the ET tube and airways
o Flow
o Airway pressure (at mouth point)
Palv = (Paw - (Ret + Raw)) x flow
In a patient in the vet, what property of the respiratory system determines how much volume reaches the alveoli?
Static compliance
What is static compliance?
o Overall compliance of the lungs and chest wall when there is no air flow
o Represents changes in compliance at the alveolar level
What is dynamic compliance?
o Compliance of the lungs during breathing
o Represents both airway and alveoli compliance
Name for each of these conditions which compliance would be affected, if static or dynamic
Asthma
Pneumonia
Pneumothorax
Tachypnea
ARDS
Pulmonary fibrosis
Pulmonary edema
Lung lobectomy
Emphysema
Bronchitis
Mucus plug/FB
o As dynamic compliance includes static compliance, secondarily it will also be affected
Driving pressure
Plateau pressure - PEEP
What processes can affect static compliance?
Parenchymal disease, chest wall stiffness (Pickwickian syndrome), pleural space disease, abdominal compartment syndrome
T/F - Dynamic compliance describes the overall effects of resistance of the airways and compliance of the lung and chest wall on the relationship between airway pressure and tidal volume
TRUE
How can we separate resistance and compliance effects?
o Stop flow
o With no flow, Paw an Palv become the same, so the pressure we measure at the airway would be the same as the driving pressure.
o On a ventilator -> do an inspiratory hold
T/F - The overall relationship between the pressure at the airway and the tidal volume delivered by the ventilator is summarized by dynamic compliance
TRUE
The dynamic compliance reflects two separate components
o The pressure drop from the airway to the level of the alveolus is due to the overall resistance and the inspiratory flow.
o The pressure available to provide alveolar ventilation is the driving pressure, which is the difference between the plateau pressure (the pressure in the alveolus after the tidal volume has been delivered and flow has stopped) and PEEP. This pressure is related to the tidal volume by the static compliance, which is the overall compliance of the lung and chest wall in the patient.
What is the equation of motion?
o The pressure available to generate a tidal volume is the sum of the the muscle pressure generated by the patient and the pressure applied by the vent.
o As the patient inspires, alveolar pressure decreases, so the net pressure applied to the alveolus and allows it to expand is the positive pressure from the vent PLUS the negative pressure generated by the muscles.
o Part of that net pressure is taken up from the resistive parts of the respiratory system multiplied by the inspiratory flow
o The rest of the pressure drop is from the static compliance of the respiratory system. The equation of motion is traditionally written using elastance which is just the inverse of compliance. Elastance as how much the lung wants to spring back when it’s stretched.
o The final term in the equation of motion is the residual pressure in the system, namely PEEP.
What are the control variables?
The physical variables that we can control on the vent
Volume, pressure, flow and time
What are phase variables?
Different phases of the breath governed by control variables
Trigger, limit, cycle and baseline
Trigger variable
Determines how inspiration is initiated
Time, flow, pressure and volume
Time triggered breath
Normally on mandatory modes where we decide an inspiration / expiration time and RR and the vent will deliver breaths.
Flow triggered breath
Patient will try to take a breath a cause a decrease in flow and trigger a breath
T/F In human medicine there is evidence that flow triggered breaths cause less work of breathing than pressure triggered breaths
TRUE.
Pressure triggered breath
Patient will try to take a breath and the vent will detect that drop in pressure and deliver a breath
Volume triggered breath
Same concept, vent will detect decrease in volume and deliver a breath
What is the limit variable
o A variable that cannot be exceeded during a breathing delivery. It does not stop the breath, that is the cycle variable.
o It can be flow, pressure or volume.
Flow limited scalar
Looks like a square
Volume control ventilation
o We set up a Tv and normally a flow limit
o The variable that will change is pressure - if there is a change in compliance and / or resistance
Pressure limited ventilation
o We set up a pressure that cannot be exceeded
o Typically associated with pressure control ventilation
Cycle variable
o Determines when the ventilator cycles into exhalation
o It can be time (after x seconds the breath stops), flow (after delivering x flow), volume (delivering a preset volume) or pressure (normally by setting the peak pressure alarm -> once the PIP reaches what we set up, the breath stops
Flow cycled breath
o Normally associated with pressure support
o We establish a specific level at which we want the breath to cycle off.
o Will reach a peak flow, then set a percentage at what point we want that breath to cycle off.
o Normally machines will automatically default to 25%
T/F Volume controlled ventilation is typically pressure limited and time cycled
TRUE
Ventilator modes
Pressure or volume control (control variable)
What determines the rest of the mode is how that breath is triggered
Controlled mandatory ventilation
o Time triggered - we decide, patient not doing anything
o Limit variable - pressure in PCV or flow in VCV
o Cycle - time (in PCV) or volume (in VCV)
Assist/controlled (A/C)
o Trigger can be time if it is controlled, or if it is assisted the patient can trigger (flow or pressure)
o Limit: pressure (PCV) or flow (VCV)
o Cycle - time (PCV) or volume (VCV)
Pressure support ventilation
o Trigger - always patient: flow or pressure
o Limit: pressure
o Cycle: flow
o Probably the most comfortable mode as the patient is determining how long, how much volume, small or bigger breath and the ventilator will give them what they want
Synchronized Intermittent Mandatory Ventilation (SIMV)
o Combined assisted control (PCV or VCV) and pressure support modes
o We set a RR - time triggered
o In between those breaths the patient can breath with pressure support breaths
What is patient ventilator asynchrony (PVA)?
When the ventilator gas delivery does not match the patient demands
It can be too much or too little
Indications for MV
Benefits of PEEP
PEEP and alveolar distension - at what PEEP there is increase in alveolar pressure but no more distension?
15cmH2O
What is auto-PEEP?
What is High Frequency Oscillatory Ventilation (HFOV)?
What is ventilator induced lung injury (VILI)?
PEEP and permissive hypercapnia
Contraindications for permissive hypercapnia
What is the normal spontaneous Tv
7-9mL/kg
T/F A breath in which the ventilator determines either the start or the end of inspiration is an assisted breath
FALSE - it is a mandatory breath
Decreased cardiac output is a potential detrimental effect of PEEP. Which mechanism is thought to be responsible?
The term “control” variable refers to
A
Fluffy is on a new mode of ventilation. Your mentor tells you this mode is time triggered. What does that mean?
A
What is the cycle variable in PSV?
Pressure
Your patient is on VCV-SIMV with PS. What type of breaths are possible?
Mainly A and C, but D would be correct too
a. CPAP
b. Pressure Support
c. SIMV
d. Assist/control
D - Assist/Control
A patient is on VCV-SIMV with PEEP. The clinician adds pressure support. What is the purpose of adding pressure support in this scenario?
a. Improve oxygenation
b. Decrease WOB
c. Prevent auto-PEEP
d. Protect against lung injury
B - Decrease WOB
Which of the following is thought to be most detrimental in a patient, an FiO2> 0.6 or a
PIP > 30cmH2O
PIP > 30cmH20
Define oxygen toxicity
Oxygen itself is a stable molecule with an indefinite Hal-life. However, excessive tissue oxygen can result in transformation of the stable O2 molecule to highly toxic substances, which is known as oxygen toxicity
Hyperoxia
An excess of oxygen supply
Hyperoxemia
A condition in which the PaO2 rises about normal values
Free radical
An especially reactive atom or group of atoms that has one or more unpaired electrons
Reactive oxygen species (ROS)
Chemically reactive chemical species containing oxygen
Reactive nitrogen species (RNS)
Chemically reactive chemical species containing nitrogen
Antioxidant
Compound that inhibits oxydation
What can be sources for oxygen toxicity?
Endogenous or exogenous
What are endogenous sources of oxygen toxicity?
Ionizing radiation procures
Environmental background radiation
UV radiation
Pollution
What are endogenous sources of oxygen toxicity?
Aerobic respiration
Excessive O2 in tissues compared to antioxidant defense mechanisms
Free electron production from NAPDH in neutrophils and macrophages during phagocytosis
Ischemic repercussion injury
Iron and copper
Oxidation of Hb to metHb
Toxicities including paraquat and bleomycin
T/F - ROS are natural by-products of normal oxygen metabolism and have important roles in cell signaling and homeostasis
TRUE
Why does ROS accumulation happens?
Because there is a limited capacity of the body to convert ROS into stable molecules via antioxidants.
T/F ROS does not contribute to RNS production
FALSE - ROS production can also contribute to RNS production which can be just as deleterious as ROS
What are the 3 stage reduction of O2?
Stage 1: reduction of molecular oxygen (O2) produces superoxide anion (O2-) -> precursor of most other ROS -> O2 + e- -> O2-
Stage 2: superoxide anion is stable itself but rapidly metabolized due to the presence of superoxide dismutase or glutathione peroxidase.
- Dismutation of O2- produces H2O2 -> not a ROS but it is a highly toxic molecule
2O2- + 2H+ -> H2O2 + O2
Stage 3: H2O2 can be reduced to water by the enzyme catalase
What is the Fenton / Haber-Weiss reaction?
o During the final stage of reducing H2O2 to water, hydrogen might be partially reduced to hydroxyl free radical (OH), which is the most toxic of ROS.
o Can be also reduced to hydroxyl anion (OH-) and singlet oxygen molecule (1O2)
o This reaction is canalized by iron or Cooper (pro-oxidants) -> that’s why they need to be tightly regulated in cells.
Myeloperoxidase reaction
o H2O2 can react with Cl to make hypochlorus acid (HOCl)
o It occurs in the phagocytic vesicle of the neutrophil
o Important in killing bacteria
Reactive nitrogen species
o NO can be beneficial in causing vasodilation
o In large quantities (like ischemic repercussion injury) can have cytotoxic effects and cause severe non-responsive vasodilation.
o NO can react with O2- (superoxide anion) to produce peroxynitrite (ONO2-) which can have deleterious effects to cells
With which molecules can free radicals interact and cause damage?
Lipids, proteins and nucleic acids
What can happen when free radicals interact with lipids?
o Lipid peroxidation
o Most susceptible to oxidation and free radical formation
o ROS reacts with lipids causing disruption of the lipid particles, and they also generate other ROS
o Lipid radical, peroxyl radical, lipid peroxide and ocoxyl radical
o Lipid peroxide is not a free radical but is damaging to the lipid membrane.
o Ocoxyl radical can lead to more radical formation.
What can happen when free radicals interact with proteins?
o Free radicals will interact with sulfhydryl-containing proteins
o Results in formation of disulphide bridges that will inactivate a whole range of proteins
What can happen when free radicals interact with nucleic acids?
o ROS can cause damage to DNA and RNA.
o If hydroxyl radical reacts with the base component -> DNA mutation
o If it reacts with the sugar component (ribose/desoxyribose) -> strand breakage, chromosome damage and mutation
What other effects can ROS cause?
o Can initiate the release of DAMPs - initiates inflammatory response.
o Release of cytokines and recruitment of neutrophils and monocytes will occur
o Vicious cycle of oxidative injury
T/F Hyperoxia during critical illness is associated with worse outcomes in people
TRUE
Which organ is the first target of oxidative injury and why?
o Lungs, due to continuous exposure to oxygen and its by-products.
o With prolonged exposure to O2 and during hyperbaric oxygen therapy (where partial pressure of O2 increases), there is increased O2 dissolved in plasma resulting in injury to other tissues and organs
What can oxygen toxicity lead to in the lungs?
Pulmonary parenchyma injury leading to pulmonary edema and impaired gas exchange.
What can happen when we administer 100% oxygen?
o Nitrogen displacement and wash out (maintains alveoli open) -> alveolar collapse
o Increased alveolar O2 concentration -> rapid diffusion of O2 in pulmonary circulation -> decreased alveolar volume, partial alveolar collapse and V/Q mismatch.
o Obstructive and adhesive atelectasis from poor mucociliary clearance and surfactant impairment
o Decreased immune response
o Alterations in microbial flora increasing the risk of secondary infections.
Name of the syndrome of oxygen toxicity in lungs in people
Lorrain Smith effect
Is there clear evidence that hyperemic therapies have positive benefits in outcomes of TBI?
No.
There are some proposed benefits of hyperopia including delayed cerebral ischemia and increased cerebral excitotoxcity after CVA, but no clear evidence
CNS and oxygen toxicity
o CNA is one of the first organs to be affected by O2 toxicity
o Syndrome in people is called Paul Bert effect
o Nausea, dizziness, headache, vision disturbances (retinal damage), neuropathies, paralysis and convulsions.
Oxygen toxicity and cardiovascular system
o Arterial hyperoxemia -> vasoconstriction -> increases SVR -> can impair perfusion, particularly coronary and cerebral circulation.
o Decreased HR, SV and CO have been documented with hyperoxia
o Potential beneficial effects of the vasoconstriction -> hemodynamic stabilization during shock and decrease ICP
Hyperoxia during MV
o High FiO2 associated with poor outcomes, due to all mechanisms discussed + VILI
o Even low levels of FiO2 40-60% -> linear association with pulmonary injury
o Imperative to decrease FiO2 asap.
o Target recommendations by ARDSnet group are SpO2 88-95%, PaO2 55-80mmHg
o The international consensus on MV -> minimum SaO2 of 90%
o Lower SpO2 targets (90-95%) associated with decreased pulmonary atelectasis, increased ventilator free days and lower mortality rates.
Shunt equation 1 - terms for flow and oxygen content
Shunt equation 2 - origin of the equation
Hemoglobin extinction curves and SpO2
Nasal oxygen flow rates and associated tracheal FiO2
Berlin Definition of ARDS
Risk factors for ARDS
ARDS phases
Exudative phase of ARDS
Picture damaged alveoli in ARDS
Pathogenesis of exudative phase of ARDS
Proliferative phase of ARDS
o From day 7 to 21 - most patients recover during this phase
o Some will progress into fibroproliferative phase
o Gradual clinical & radiographic resolution of ARDS
Findings of this paper
o Most substantial mortality benefit ever demonstrated for any therapeutic intervention in ARDS patients
Permissive hypercapnia in ARDS
Is there anything we can do to improve hypercapnia before accepting increased values in an ARDS patient?
Beneficial effects of PEEP
Detrimental effects of PEEP
Use of PEEP in ARDS patients
How do we perform a recruitment maneuver?
What factors do we have to consider when adjusting PEEP and looking at our PV loops?
Another method to guide PEEP?
ARDS Netwrok PEEP / FiO2
Indications for prone position in humans
Neuromuscular blockers
ARDS recommendations on NM blockade
T/F ARDS patients are at high risk for fluid overload
TRUE
Lung protective strategies ARDS net
Risk factors to develop ARDS in vet medicine
Definition of VetALI / VetARDS
Veterinary clinical signs of ARDS
How should we treat veterinary ARDS patients?
