Respiratory - Johnson Flashcards
Don't Suck!
What do we mean by Respiration?
The transport of oxygen from the ambient air to the tissue cells and the transport of CO2 in the opposite direction
Surface to volume ratio!
The bigger you get, the bigger the problem of getting oxygen in and CO2 out!
The 4 phases of respiration
- Ventilation: ambient air <> airway <> alveolus
• Stage 1 Ventilation from the ambient air into the lung (pulmonary) alveoli - Diffusion: alveolar-capillary membrane (pulmonary capillaries)
• Stage 2 Pulmonary gas exchange from the alveoli into the pulmonary capillaries - Transport: Perfusion <> circulation
• Stage 3 Gas transport from the pulmonary capillaries to the peripheral (tissue) capillaries - Diffusion: peripheral capillaries <> interstitial fluid <> cell mitochondria
• Stage 4 Peripheral gas exchange from the tissue capillaries into the cells (mitochondria)
• Stage 5 …and CO2 back again, though this is not usually considered to be one of the stages…
Physiological respiration involves ________
GAS FLOW
Conducting Zone
Trachea = 0 generations
Bronchi (segmental bronchi 1-8) = 1-3 generations
Bronchioles (segmental bronchi 1-8) = 4-5 generations
Terminal bronchioles (segmental bronchi 1-8) = 6-16 generations
*see slides 13 & 14
Notes from handout: Conducting Zone takes no part in gas exchange, and constitute the anatomic Dead Space, with a volume of about 150 ml in each breath
Transitional and Respiratory Zones
Respiratory bronchioles (17-24) = 17-19 generations Alveolar ducts (25-26) = 20-22 generations Alveolar sacs = 23 generations *see slides 13 & 14
Notes from handout: The respiratory zone, is comprised of the respiratory bronchioles (which have occasional alveoli budding from their walls) and alveolar ducts are completely lined with alveoli. The respiratory zone makes up most of the lung volume, about 2.5 to 3 liters during rest.
1cm H2O =
0.736mm Hg
Although airway diameter goes down Cross-sectional area goes ___ __!
way up
?
What jobs does the lung do?
- Conduction of air
- Diffusion of gas
- Transport
- Metabolism
- Defense
Flow =
Volume/Time
or
deltaP/Resistance
*Flow moves down a pressure gradient (deltaP)
Pressure =
Force/Area
Flow is ____ in the conducting zone (trachea and bronchi).
As cross-sectional area increases in the respiratory zone deltaP _______ and so does Velocity of flow which facilitates gas exchange!
fast
decreases
*Cross sectional area increase so pressure gradient decreases so flow velocity decreases!
The velocity of airflow in the respiratory system:
A. Is highest in the peripheral airways
B. Is low in the central airways because the pressure gradient is lower
C. Increases with every generation of the airway
D. Is lowest in the alveoli
E. Is highest where deltaP is lowest
D. Is lowest in the alveoli
Diffusion of gas
The passive movement of molecules or particles along a concentration gradient, or from regions of higher to regions of lower concentration
Fick’s Law
The rate of diffusion of a gas across a permeable membrane depends on:
- The nature of the membrane
- The surface area of the membrane (A)
- The thickness of the membrane (T)
- the partial pressure gradient of the gas across the membrane (deltaP)
- The diffusion coefficient of the gas (D)
Vgas ≈
(A / T) * D * (P1-P2)
A= Surface Area T= Thickness of membrane D= Diffusion Coefficient P1 and P2 = Pressures on either side of membrane D ≈ Sol / MW = diffusion constant
Diffusion in the lung:
In the normal lung:
• 300 million alveoli
• Barrier between blood and air is less than 1mm
• Capillaries are very small so almost all RBC in contact
• CO2 diffuses about 20X faster than O2
Gas exchange occurs predominantly during _______.
expiration
*notes from handout
The alveolocapillary membrane:
- thin structure dividing air from blood
- 0.3-0.5µM thick (thicken in various disease states which can reduce oxygen diffusion)
- alveolar epithelium on the ‘air’ side
- endothelium on the ‘capillary’ side
- interstitium which lies between the two membranes
*notes from handout
The alveolar epithelium has 2 types of cells:
Type 1 cells (sunny side up, or pavement cells)
Type 2 pneumocytes which secrete a surface active material (or surfactant) into the alveoli (slide 22).
The application of Frick’s Law suggests that:
A. The Product of Pressure and Volume are constant
B. Diffusion of a gas across a membrane is inversely related to membrane area
C. Diffusion of gas is usually faster for a light gas
D. Diffusion does not occur when the membrane is thin because of equilibration
E. Diffusion is independent of pressure
C. Diffusion of gas is usually faster for a light gas
Vgas ≈ (A / T) * D * (P1-P2)
A= Surface Area T= Thickness of membrane D= Diffusion Coefficient P1 and P2 = Pressures on either side of membrane D ≈ Sol / MW = diffusion constant
Pulmonary capillaries are of very _____ caliber (_µM), squeezing the Red Blood Cells (RBCs) close to the vessel wall, and ________ the distance for diffusion.
small, 7
decreasing
Pulmonary Circulation
• The lung is a reservoir for ______
• Receives almost all __
• ___ resistance circuit
blood
CO
Low
Pressure =
since _________ is low, the pressure gradient can also be low to get good flow
Flow x resistance
resistance
F=deltaP/R
The pulmonary circulation is a ___ RESISTANCE circuit, as the walls of the pulmonary artery and its branches contain relatively little smooth muscle and are extremely thin.
LOW
As pulmonary vascular resistance is so low, a mean pulmonary arterial pressure of only __ cm water (__ mmHg) is needed for a flow of _L/min, which is the __, and also the RV output into the lung, as the 2 systems are in series. (Fig. 5.)
20, 15, 6, CO
As pulmonary vascular resistance is so low, a mean pulmonary arterial pressure of only __ cm water (__ mmHg) is needed for a flow of _L/min, which is the __, and also the RV output into the lung, as the 2 systems are in series. (slide 25)
20, 15, 6, CO
Although each red blood cell spends only _ second in the capillary network, and probably traverses only 2 or 3 alveoli, this brief time suffices for near complete equilibration of __ in the alveolus, and return of ___ to the alveolus.
¾, O2, CO2
*handout
Function of Extra alveolar vessels
As the lung expands, larger vessels are pulled open by the traction of expanding lung parenchyma.
Slide 26-28
Alveolar vessels are exposed to the alveolar pressures and so they are ___________ at higher lung volumes. Alveolar vessel resistance thus __________ at high lung volumes.
compressed
increases
F=deltaP/R
- handout
- *Slide 26-28
At low lung volumes, the extra alveolar vessel resistance _________ significantly.
increases
Slide 26-28
If a lung is completely collapsed, pulmonary artery pressure has to be raised to several cms. above downstream pressure before any flow will occur; this is called the _____ ______ ________.
critical opening pressure
Pulmonary vascular resistance may be reduced by increased blood flow, a phenomenon referred to as __________, and occurs due to capillary distention, and opening of capillaries which are normally ‘closed’: no blood flows through them at rest. This happens during exercise, when cardiac output, and thus, pulmonary blood flow is increased.
recruitment
F=deltaP/R
- handout
- **Slide 29
Pulmonary vascular resistance _________ with alveolar hypoxia, due to constriction of small pulmonary arteries
increases
*handout
Pulmonary vascular resistance can be _________ with _____ _____, which is a powerful selective pulmonary vasodilator, and is used to treat pulmonary hypertension. Useful in neonatal pulmonary hypertension due to prematurity.
decreased, Nitric Oxide
- handout
- **and see slide 36!!!
At low lung volumes
• Extra alveolar vessel resistance ________
• Alveolar (capillary) vessel resistance ________ (not squashed)
At high lung volumes
• Extra-alveolar resistance ________ (traction of surrounding expanding lung pulls vessels apart)
• Alveolar (capillary) vessel resistance ________ (squashed)
Clinical: Important to maintain OPTIMAL lung volume so that overall resistance is ___ and pulmonary blood flow is maximized
increases, decreases
decreases, increases
low
Factors that Affect Pulmonary Circulation
• Pressures around the vessels: Extra alveolar vessels vs ______ _______
• Increased blood flow - _________ which occurs during exercise: decreases resistance
• Vasoconstrictor – ________
• Vasodilator: _____ _____
• Acid base status: Alkalemia is a pulmonary vaso______
alveolar vessels recruitment Hypoxemia Nitric oxide dilator
Why don’t alveoli collapse at low lung volume?
Surfactant
Surface tension:
The elastic tendency of a fluid surface which makes it acquire the least surface area possible.
_______ _______ exerts a force that would tend to collapse the alveoli at low lung volume
Surface tension
Respiratory Distress Syndrome (RDS)
• Babies born before about __ weeks do not make enough surfactant resulting in RDS
• Surfactant _______ surface tension in the alveoli
• As the healthy lung Expands, surface tension _________
• As lung volume decreases, surface tension _________
• Surfactant most effective at ____ lung volume
32 reduces INCREASES DECREASES low
Pulmonary Circulation:
A. Is uniform all over the lung
B. Can be considered to be a high resistance circuit
C. Extra alveolar resistance decreases as the lung expands
D. Alveolar vessel resistance is uniformly low regardless of lung expansion
E. Hypoxemia decreases pulmonary vascular resistance
C. Extra alveolar resistance decreases as the lung expands
Metabolism of
Vasoactive substances: Produces Angiotensin Converting Enzyme (ACE), which generates vasoconstrictor Angiotensin II (SLIDE 39!)
Bronchoactive substances such as leukotrienes (which cause bronchospasm)
Xenobiotics (plays a role)
Is an important reservoir of several
cytochrome P450 enzymes (CYPs)
Contains mast cells which produce the anticoagulant ______
heparin
Defense:
• The mucociliary escalator protects the lung from ______ ______
• Can be _________ (as in black lung)
• Production of ___ (Important first line of defense)
• APUD cells in the lung secrete ________
inhaled particles
overcome
IgA
serotonin
Acts as a filter:
Filters small clots before they can reach the brain or other vital organs.
Applied Aspect: In right to left shunts, such as cyanotic heart disease with Tetralogy of Fallot, septic and other emboli are released into the circulation, as the blood bypasses the lungs, and flows directly from right to left: this leads to cerebrovascular occlusion, causing strokes, or infections causing cerebral abscesses.
*handout
- The nose has cilia which filter larger particles and generate a sneeze. Particles over 25 mm are filtered out in the nose and nasopharynx.
- The cough and gag reflexes prevent us from inhaling or aspirating nasopharyngeal secretions or food particles.
- The ciliated columnar epithelium of the bronchial tree has mucous glands and goblet cells, which secrete mucous. The cilia beat to propel this mucous towards the ____ _____, like an escalator, which carries debris from ___ _____ ______ to the trachea, to be coughed up, or swallowed. Particles greater than __ mm are cleared in this way.
- Particles reaching alveoli are removed by ____________ and end up in the regional lymph nodes.
- Cellular immune responses unique to the lung exist. When over-activated, these cause _______.
oral cavity
the lower airways
25
macrophages
asthma
*handout
Dalton’s law of Partial Pressures states that
The partial pressure of each gas is thus a fraction of ___ mm Hg, depending on its concentration in the mixture of gases.
in a mixture of gases, each gas exerts a partial pressure proportional to its concentration in the mixture.
760 (Barometric pressure of the atmosphere at sea level)
Pressure in Different Compartments of the Respiratory Tract (mm Hg):
GAS Room Trachea Alveolar Arterial blood PCO2 0 0 40 40 PO2 159 150 100 95 PH2O 0 47 47 - PN2 601 563 573 578 TOTAL 760 760 760 713
NOTE that the total pressure in arterial blood is only 713 mm Hg. That’s because the gas is saturated with water vapor as soon as it comes into contact with the moist respiratory mucosa of the trachea. PH2O is 47 mm Hg. Water vapor does not enter the blood, and hence partial pressure in the artery is 760-47 = 713 mm Hg.
*handout
Henry’s Law states that
the solubility of a gas in a liquid solution is proportional to the partial pressure of the gas and the solubility constant (a) of Bunsen.
This constant is different for each gas; eg: carbon dioxide is 20 times more soluble than oxygen, a fact which has great physiological implications
*handout
Lecture 2!
10/7/19
Boyle’s Law states that
the product of pressure and volume of a gas is constant at constant temperature
• Pressure (P) x Volume (V) = Constant (K)
• P1xV1 = P2xV2…..TEMP = CONSTANT!
so, V is inversely proportional to P, as V increases, P decreases.
Inspiration is _____:
• _ in the chest increases
• _ decreases
active
V
P
• The diaphragm moves down, the ribs move forward, upward and outward
• Air flows into the lung down a pressure gradient
Expiration is generally _______:
• _ in the chest decreases so _ increases
Expiration can be _______:
• Wind instrument
• Asthma
passive
V,P
• Due to elastic recoil of the chest wall
• Air flows out passively down the pressure gradient
active
• Uses the muscles of the abdomen and internal intercostal muscles
Types of flow:
Bulk Flow depends on pressure gradient, size and resistance of the conduit and the nature of the fluid
• Laminar: __________________
• Turbulent: Branch points, ________ airway resistance
– asthma
– velocity is reduced and more pressure is required to drive flow
• Transitional: ______ _____
Most flow most of the time is __________
Laminar: Smooth, high velocity, streamlined
Turbulent: Branch points, increased airway resistance
Transitional: Branch points
Most flow most of the time is transitional
POISEUILLE’S LAW FOR LAMINAR FLOW
Volume Flow Rate, Q = ΔPπr4 / 8ηL
ΔP = Driving Pressure (Pressure gradient or ΔP) r = Radius η = Viscosity L = Length
Ohm’s Law
Resistance =
Resistance = Driving Pressure / Flow
or
Pressure difference between the mouth and alveolus (ΔP) / Flow rate
R = η8L / πr4
Flow = ΔP / Resistance
Thus radius of a tube has a significant impact on resistance.
For example, if radius is halved, resistance increases 16 fold!
Airway constriction (ex: Infant with Croup or extubation ~ airway inflammation):
• Airway radius halved
• Resistance increased by sixteen fold!
How can we help?
- Reduce gas density
* Heliox: He:O2 - 80:20
Laminar vs Turbulent Flow:
Reynold’s Number =
Reynold’s Number = 2rVρ / μ r= Radius V = Velocity ρ = Fluid Density µ = Fluid Viscosity
Reynold’s Number > 2000 in a straight, smooth tube
= ?
Turbulence
Turbulent Flow:
• ____ axial velocity than laminar flow
• ____ work to drive flow
• Reducing the density of the gas can _______ work
• Heliox: Helium:Oxygen __:__ can convert _________ flow to ________ flow
• Used to treat upper airway __________: Croup and Asthm
Less More decrease 80:20, turbulent, laminar obstruction
Where, then is the site of maximum airway resistance?
Intuitively, by the application of Posuielle’s law, one would expect it to be the smallest airways, but in reality, most resistance occurs upto the 7th generation, that is the medium sized bronchi, when pressure gradients are actually measured at different points in the bronchial tree.
Q = ΔPπr4 / 8ηL R = η8L / πr4
*handout
Factors affecting airway resistance (AWR)
• Airway Generation: Most resistance occurs upto the _th generation (determined experimentally)
• Lung volume: Greater the volume, the ______ the AWR
• Similar to affect of lung volume on extra-alveolar vessels
• Airways pulled open as lung expands
• Conductance is ______ of AWR but increases linearly
7
less
inverse (slide 11)
Q = ΔPπr4 / 8ηL R = η8L / πr4
In the respiratory tract:
A. Airflow is mainly turbulent
B. Airflow is mainly laminar
C. Turbulent flow occurs when the radius is small
D. Airway resistance increases with a decrease in radius when flow is laminar
E. Flow is laminar at branch points
D. Airway resistance increases with a decrease in radius when flow is laminar ?
Other factors affecting AWR:
• Bronchial smooth muscle is controlled by the _________ nervous system
• Bronchial smooth muscle constriction _________ AWR
• b2-adrenergic _______ cause smooth muscle relaxation
• b2receptor agonists treat ________
• ________ gas density (diving at depth)
• ________ gas density (Heliox to reduce AWR)
• Forced expiration / Dynamic compression of the airways……………_______ point
autonomic increases agonists asthma (ex: Terbutaline, albuterol) Increased Decreased Choke (Flow during dynamic compression is determined by the gradient between alveolar pressure and pleural pressure, not mouth pressure, as the airway is compressed....*handout)-IMAGE ON PHONE
Bronchial Smooth Muscle contraction will ________ resistance.
Contraction occurs in response to
increase
β2 adrenergic blockers, parasympathetic activity, acetylcholine and histamine.
Airways Resistance (AWR)
A. Is maximum during expiration at the choke point
B. Is unrelated to the volume of lung expansion
C. Is increased by using low density gas
D. Depends on patient effort after the choke point
E. Is increased by stimulating airway adrenergic receptors
A. Is maximum during expiration at the choke point
Lung Compliance
Compliance = Change in volume for a given change in pressure = ∆V / ∆P
see and understand slide 17 & 18!
Maximal expiratory flow is said to be effort __________, and is used as an important clinical indicator of airways resistance to diagnose _______, a condition with increased airways resistance.
independent
asthma
*handout
Other factors that affect resistance to airflow include
- The dimensions and content of the airways
- The structure and quality of tissue
- The degree of vascular distension
- The composition (viscosity and density) of the inspired air
- The mechanical properties of the chest wall
*handout
FACTORS AFFECTING LUNG COMPLIANCE:
- Volume: Compliance increases with _________ lung volume.
- Hysteresis:
- Elasticity of the lung, or its tendency to return to resting position after inflation, leads to a _______ pressure surrounding the lung, compared to atmospheric pressure. This elasticity is attributed to fibers of elastin and collagen in the alveolar walls, around vessels and bronchi.
- __________
A saline filled lung is easier to distend than an air filled lung, because the surface tension, which tends to collapse alveoli, is reduced.
__________ reduces surface tension at low lung volumes, keeping the alveoli open.
It _________ compliance of the lung, promotes stability of alveoli, keeps alveoli dry. _________ prevents reduction of hydrostatic pressure in tissue around capillaries, prevents capillary transudation of fluid into alveoli.
__________ contributes to hysteresis (see above). - Vascular Distension: Engorgement of the lung causes _________ stiffness, ie _________ compliance
- decreasing
- The phenomenon by which the lung demonstrates different compliance curves during inspiration and expiration. Lung volume at any given pressure is higher during deflation than during inflation.
- negative
- Surfactant, Surfactant, increases, Surfactant, Surfactant
- increased, decreased
Aging results in a ____ elastic lung
less
Fibrosis makes the lung
stiffer
Aging & Emphysema =
Increased Compliance
- Pumonary Fibrisis
- Alveolar Edema
- Hypoventilated lung
- Increased pulmonary venous pressure, leading to pulmonary edema
- Atelectasis
Decrease Compliance
Functional Residual Capacity (FRC):
• The volume of the lung at which the elastic recoil of the lung pulling it inwards, and the tendency for the chest wall to spring out, are __________
• The volume in the lung, which stays there, keeps the lung _____ and acts as a bank to supply O2 when needed
• Keeps the lung ‘open’, keeps intrapleural pressure _________
• Applied : Incentive Spirometry __________ FRC, prevents lung collapse
balanced
open
negative
maximizes
At volumes above FRC, the airway pressure is ________. The chest wall tends to expand at volumes upto __% of vital capacity.
At volumes below FRC, airway pressure is ________, and hence air is sucked into the lung, to maintain FRC.
positive
75
negative
Pneumothorax
- Loss of negative pressure in the pleural space
- Loss of mechanical linkage between chest and lung
- Lung collapses
- Lung cannot be inflated by forced respiration
- Let air out of the pleural space with a chest tube and vacuum
- Stab wound allowing air to enter
A 45 year old man sustains a stab wound in the chest and develops difficulty in breathing
A. He is likely to have fully expanded lungs
B. He could have a pneumothorax
C. His functional residual capacity will be unaffected
D. He is best treated by pumping air into the damaged lung
E. He is best treated by sucking air out of his lungs
B. He could have a pneumothorax
Surfactant:
• Produced by ____________________
• Reduces _______________
• Effect is greatest at ___ lung volumes
• Contributes to ___________
• Lack of results in ___ in premature babies
type II pneumocytes surface tension low hysteresis RDS
Type I Pneumocytes:
• Large, flattened, non replicating
• Involved in ______________
• Diffiuse Alveolar Disease (DAD) seen in SARS epidemic • Type __ Pneumocytes can differentiate into Type __ but not vice versa
gas exchange
II,I
Surfactant in the lung:
A. Is produced by the Type I pneumocytes
B. Is only important in premature babies
C. Increases surface tension in the alveoli
D. Is not produced in sufficient amounts by babies born at less than 32 weeks
E. Is responsible for asthma
D. Is not produced in sufficient amounts by babies born at less than 32 weeks
Regional differences in ventilation: • Apex volume is \_\_\_\_\_\_ • Apex pressure is \_\_\_\_\_\_ • Base pressure is \_\_\_\_\_\_ • Base volume is \_\_\_\_\_\_\_\_\_ Thus ventilation/unit volume is \_\_\_\_\_\_\_\_\_\_ at the base vs apex
large low (Not much room for expansion) High decreased increased
Regional differences in ventilation:
• Apex is ______ better at baseline, as surrounding intrapleural pressure is more negative at the apex
• Its _________ is greater, compared to the compressed base (By Boyle’s Law) due to the effect of gravity
• Per unit volume, ventilation (or CHANGE in volume with inspiration) is greater at the ________ at normal lung volumes
• At very low lung volumes, there is reduced recoil at the base of the lung, pleural pressure may even be positive
• In this situation, ______ ventilates better
aerated
VOLUME
base
apex
Dalton’s Law states…..
the total pressure = sum of all pressers.
Example:
Oxygen (21%) has a partial pressure of 21/100 X 760 = 159.6
In the human body, all gas is saturated with water vapor which has a partial pressure of 47 mm Hg
Thus pO2 in the airway is 21/100 (760-47) = 149.73 or 150 mm Hg
At the alveolus, there is CO2 production with pCO2 of about 40 mm Hg
Alveolar Gas Equation (at sea level)
pAO2 = FiO2 x (760-47) – pACO2 / R
pAO2 = Partial pressure of alveolar O2
FiO2 = Fractional concentration of O2
760 = Total barometric pressure (local)
47 = Partial pressure water vapor in alveolus
pACO2 = Alveolar partial pressure of CO2
R = Respiratory Quotient (RQ) = amount of CO2 generated per O2 molecule used – typically 0.8 at BMR (I think he used 1 in class?)
pAO2~pACO2?
Gas levels along the respiratory tract: \_\_\_\_\_\_\_\_\_ is the major component and does not change much Room air (760 mmHg): N = \_\_\_\_, O2 = \_\_\_\_ Trachea (760 mmHg): pN2 = \_\_\_, pO2 = \_\_\_, pH2O = \_\_ Alveolus (760 mmHg): pN2 = \_\_\_, pO2 = \_\_\_, pH2O = \_\_, pCO2 = \_\_ Arteries (\_\_\_ mmHg): pN2 = \_\_\_, pO2 = \_\_, pH2O = _, pCO2 = \_\_\_
Nitrogen Room air (760 mmHg): pN2 = 601, pO2 = 160 Trachea (760 mmHg): pN2 = 563, pO2 = 150, pH2O = 47 Alveolus (760 mmHg): pN2 = 573, pO2 = 100, pH2O = 47, pCO2 = 40 Arteries (713 mmHg): pN2 = 578, pO2 = 95, pH2O = 0, pCO2 = 40
Arterial O2 (paO2):
• paO2 = about __ mm Hg in a healthy adult breathing room air at sea level
• The difference between pAO2 and paO2 is the _________________ Gradient – typically 5-10 mm Hg
*pAO2 = 100 –> paO2 = 95
• The alveolar-arterial gradient is _________ when there is a diffusion problem.
95
Alveolar-arterial
increased
The Partial Pressure of Oxygen
A. Is 21 mm Hg in atmospheric air at sea level
B. Is higher in the artery than the alveolus
C. Is proportional to it concentration in the mixture of gasses
D. Is independent of partial pressure of CO2
E. Is not influenced by the presence of water vapor
C. Is proportional to it concentration in the mixture of gasses
Healthy V/Q:~1 V: Frequency/RR ~ 15/min Anatomic dead space ~ \_\_\_ml Tidal volume ~ \_\_\_ml Minute ventilation ~ \_\_\_\_ml Alveolar gas volume ~ \_\_\_\_ml V: Alveolar ventilation ~ \_\_\_\_ml/min Q: HR ~ 70 bt/min Pulmonary capillary blood \_\_ml/bt Q: Pulmonary blood flow \_\_\_\_\_ ml/min
Anatomic dead space 150ml Tidal volume is 500ml Minute ventilation is 7500ml (TV x RR) Alveolar gas volume is 3000ml V: Alveolar ventilation is 5250ml/min (TV-DS x Rate) Pulmonary capillary blood 70ml/bt Q: Pulmonary blood flow 5000 ml/min (BV x HR) • Flows roughly match
Capacities and Volumes (mls): Tidal Volume (TV) ~ Inspiratory Reserve Volume (IRV) ~ Expiratory Reserve Volume (ERV) ~ Residual Volume (RV) ~ Total Lung Capacity (TLC) ~ Vital Capacity (VC) ~ Inspiratory Capacity (IC) ~ Functional Residual Capacity (FRC) ~
- Forced Vital Capacity (FVC) is the same as __ but a bit less (get less air out when forced)
- Anything that includes RV, cannot be measured by simple _________
Tidal Volume (TV) ~ 500
Inspiratory Reserve Volume (IRV) ~ 3000
Expiratory Reserve Volume (ERV) ~ 1100 (max expiration)
Residual Volume (RV) ~ 1200
Total Lung Capacity (TLC) ~ 5800
Vital Capacity (VC) ~ 4600
* IRV + TV + ERV = Everything you can move
Inspiratory Capacity (IC) ~ 3500
* IRV + TV = Everything from rest
Functional Residual Capacity (FRC) ~ 2300
* ERV + RV – Everything left
VC
spirometry
STATIC LUNG VOLUMES
____________: Normal Breathing
____________: Exhaled volume after maximal inspiration and maximal expiration
____________: Gas that remains in the lung after maximal expiration
____________: Volume of gas in the lung after a normal expiration
While tidal volume and vital capacity are easily measured using _________, __ and ___ can only be measured using a gas dilution technique. The gas used is _____, which is insoluble in blood, and is breathed in from a jar.
The amount of ______ in the jar = the amount of _____ in the lung after a few breaths (equilibrium).
V2 is the volume of gas in the lung = FRC.
C1 = Concentration of ______ in jar,
V1 = Volume of gas in jar
C2 = Concentration of ______ in lung
V2 = Volume in the lung = ___
C1 V1 = C2 (V1 + V2)
V2 = V1 (C1-C2)/ V2
Tidal Volume Vital Capacity Residual Volume Functional residual capacity spirometry RV and FRC Helium x5 V2 = Volume in the lung = FRC
The Functional Residual Capacity (FRC)
A. Represents the volume of the lung at which the tendency of the lung to spring out and the chest wall to recoil are balanced
B. Is measured by spirometry
C. Is the sum of tidal volume and residual volume
D. Is always composed of communicating gas, or gas that is easily breathed out
E. Ensures that the intra-pleural pressure outside the lung is negative
A. Represents the volume of the lung at which the tendency of the lung to spring out and the chest wall to recoil are balanced
Anatomic Dead Space is the volume of __________________, about ___ ml
Physiological Dead Space is the volume of _________________________
conducting airways, 150
gas that does not eliminate CO2
Tidal Ventilation (Tidal Vol) = Alveolar Ventilation + Anatomic Dead Space
V(T) = V(A) + V(D)
If n is RR
n (V (T)) = n (V(A)) + n (V(D))
Alveolar ventilation may be increased by increasing _, or increasing _____
Increasing ______ is more effective, as it reduces the relative proportion of Anatomic Dead Space (V(D)), which is a constant value. The Anatomic Dead Space is ______ to measure: its value is generally ________.
n, V(T)
V(T) or Tidal Volume
hard
assumed
MEASUREMENT OF ANATOMIC DEAD SPACE: FOWLER’S METHOD
Based on the fact that __, a significant component of inspired gas, does not participate in gas exchange and is present in expired alveolar gas. A single breath of 100% O2 displaces __ from alveolar gas, into the dead space, and __ concentration in the dead space increases: it is sampled continuously at the mouth.
Measures volume of conducting airways down to ________________ from dead space to alveolar gas.
N2x3
midpoint of transition
Assessment of alveolar ventilation:
• Total Ventilation = Tidal Volume x Rate
• Tidal Volume = Alveolar Volume + Dead Space
• Alveolar ventilation (VA) = Tidal Volume – Dead Space x Rate
• Volume of CO2 exhaled per unit time (VCO2)
• Fractional CO2 =%CO2 100 (FCO2)
• VCO2 = VA x FCO2 x K (Constant)
• CO2 (is or is not?) VERY soluble, so alveolar CO2 and arterial CO2 are virtually ________ in a healthy individual
• Measuring ___ is useful for monitoring patients with impending respiratory failure due to hypoventilation.
• If Ventilation is HALVED, CO2 is _________
• If lung is healthy, end tidal CO2 or Transcutaneous CO2 can be measured
is, identical
CO2
DOUBLED
Regarding dead space
A. Anatomic and Physiologic Dead Space are similar in healthy lungs
B. Physiologic Dead Space is best measured by Helium Dilution
C. Increased dead space leads to a difference between expired and arterial pCO2
D. Arterial CO2 and alveolar CO2 are different when dead space increases
E. A healthy person has no dead space ventilation
A. Anatomic and Physiologic Dead Space are similar in healthy lungs
C. Increased dead space leads to a difference between expired and arterial pCO2
MEASUREMENT OF PHYSIOLOGICAL DEAD SPACE BY BOHR’S METHOD
All expired CO2 comes from alveolar gas, and none from the dead space.
VD/VT = PA CO2 – PECO2 / PACO2
This is the BOHR EQUATION, where A refers to alveolar, and E to mixed expired gas
The normal ratio of dead space to tidal volume is in the range of 0.2 to 0.35 during resting breathing.
In healthy subjects, pCO2 in arterial blood and alveolar gas are virtually identical, so the equation is often written as
VD / VT= PaCO2 – PECO2 / PaCO2 where PaCO2 is arterial pCO2
**just see handout page 25
Important Features of Fick’s Law of Diffusion
- Rate of diffusion of a gas is proportional to the ____, and inversely proportional to _______
- Diffusion rate is ____________ to the difference in partial pressure
- Diffusion rate is ____________ to solubility of the gas, and ______________ to the square root of the molecular weight
- Diffusion of Oxygen is efficient. __________ of alveolar and arterial O2 occurs almost immediately. O2 transfer into the pulmonary capillary is dependent on blood flow, and is therefore, mainly _________ limited.
Partial Pressure of O2 in the capillary is __mm Hg, and that of alveolar air is ___mm Hg
O2 flows down this large pressure gradient, and pO2 in the cell rapidly rises.
5.CO2 has a much ___er solubility than O2. Hence diffusion of CO2 through tissue is about 20 times ____er than O2.
area, thickness proportional proportional, inversely proportional Equilibration, perfusion, 40, 100 high, fast
Which comes first: Hypoxemia or Hypercarbia: • At high altitude? • With interstitial lung disease? • During hypoventilation?
Hypoxemia
Hypoxemia
Hypercarbia
Carbon Monoxide
• Binds very tightly to __ which is why a poorly maintained gas heater can be a killer
• Useful (in small amounts) to measure _______ capacity because pCO does not rise since it binds to Hb as soon as it diffuses into the blood.
• Transfer is _______ limited
• Used to measure ________ capacity in cases of intestinal fibrosis, sarcoidosis, or asbestosis
Hb
diffusion
diffusion
diffusion
Applied Aspects
- At ____ altitudes, alveolar pO2 is reduced and the gradient between air and blood is ____, so rise in pO2 along the capillary is relatively slow
- In diseased states, where the blood-gas barrier is thickened, as in interstitial lung disease, ________ of O2, and more rarely, CO2 may be impaired
high, less
diffusion
Hypoxemia: Low ______
Causes of Hypoxemia =
paO2
- Low inspired O2 (Hypoventilation)
- Diffusion limitation (interstitial disease)
- Ventilation – perfusion inequality
- Shunt
Hypoxemia =
Hypoxia =
Low oxygen in the blood
Low oxygen in a tissue
Low inspired O2 - The effect of high altitude Barometric pressure = 600 mm Hg Ambient O2 = 21 / 100 x 600 = 132 mm Hg Inspired O2 = 21 / 100 x 553 = 116 mm Hg Climber has a pCO2 = 40 & RQ = 1 Alveolar O2 = 116 – 40 = 76 mm Hg
What could he do?
Use enriched air (extra O2)
25% O2
25 / 100 x 600 = 150 mm Hg
25 / 100 x 553 = 138 mm Hg
Alveolar O2 = 98 mm Hg
Causes of hypoxemia: Hypoventilation (reduced _)
• Drugs such as …….
• Damage to chest wall
• Weakness of respiratory muscles
• Increased __________ to airflow (deep sea diving)
Hypoventilation always increases ______ and ______ Alveolar O2 = inspired O2 – (pCO2 / R) x p
So as pCO2 increases, alveolar O2 levels fall
Treatment?
V Morphine, barbiturates resistance pACO2 and paCO2 Increase inspired pO2
The fall in pO2 due to hypoventilation can be countered by exogenous __ administration.
(Remember this)
O2
Causes of Hypoxemia: Diffusion Limitation
• Diffusion can be limited by _______ disease
• What do we know about diffusion?
• Vgas ≈ (A / T) x D x (P1-P2) = _____ law
• What can we change?
• _____ would be the easiest
• Increase the pO2 in the _______ will increase gradient and increase _______ pO2
interstitial
Fick’s
P1-P2
alveolus, arterial
Causes of Hypoxemia: V/Q mismatch
V/Q = 0 = mixed venous point = NO ________
*When blood bypasses the alveolus, there is no ventilation, venous blood flows directly to the arterial system, bypassing the lungs V/Q = 0 = ________
V/Q = α = inspired gas point = NO ________
ventilation (diffusion of O2)
*pO2 and pCO2 are identical with those of mixed venous gas, and no further oxygenation occurs.
SHUNT
perfusion (blood flow)
*When blood flow is completely obstructed, as in a pulmonary embolism, or in diseased states, there is normal ventilation but no perfusion, and V/Q = α. Here O2 rises and CO2 falls, approaching the composition of inspired gas, O2 = 150 and CO2 = 0 (DEAD SPACE)
V/Q Ratio • Normal V/Q is _ • V/Q = α = • V/Q = 0 = • V/Q < 1 leads to \_\_\_\_\_\_\_\_\_\_
1
PE
Airway obstruction, Shunt
hypoxemia
Causes of Hypoxemia: Shunt
Blood that enters the arterial system without going through ventilated areas of the _____.
• Does not _________ gas. No ___________
Anatomic: Bronchial circulation (conducting zone)
• Responsible for the difference between _________ and ________ pO2
• Know as the - gradient
• Normally = _____ mm Hg
Physiological shunt:
• Perfusion of a non-ventilated ______
Pathologic shunt:
• Atrial or ventricular septal defects
• Patent ductus arteriosus
• AV malformations
lung
exchange, ventilation
Alveolar (A), arterial (a)
A-a
5-10
alveoli
A-a Gradient in Hypoxemia:
Hypoxemia but A-a is Normal
• Low Inspired O2 - What helps?
• Hypoventilation - What helps?
Hypoxemia and A-a is Increased
• Diffusion Limitation - What helps?
• Ventilation-perfusion inequality - What helps?
• Shunt - What helps?
Oxygen helps
Oxygen helps
Oxygen helps
Oxygen helps
Oxygen does NOT help
A 34 year old woman has sudden breathlessness after traveling on a 14 hour flight. She was previously healthy. An arterial blood gas shows a paO2 of 68 mm Hg in room air.
A. There will not be an alveolo-arterial gradient
B. She will have a V/Q ratio of 1
C. The patient will have hypercarbia
D. She may be helped by oxygen
E. She has a shunt and should be given oxygen
D. She may be helped by oxygen
West’s Zones of the Lung….see slides 16-17 and handout page 31-33
West’s Zones of the Lung….see slides 16-17 and handout page 31-33
Regional differences in ventilation
• Apex volume is _____ , = Not much room for expansion
• Base volume is _______ , = More room for expansion
large
decreased
Thus ventilation/unit volume is increased at the base vs apex
Lecture 4, Slides 18-24 = know!!!!
Slides 18-20 = know!!!!
Regarding increased Alveolo-Arterial (A-a) Gradient
A. It indicates the difference between alveolar and arterial CO2
B. It can always be fixed by 100% O2
C. It can signify diffusion limitation of the transfer of O2 D. It may occur when there is a septal defect with from from Rt to Lt
E. It occurs when the V/Q ratio is infinite
C. It can signify diffusion limitation of the transfer of O2
D. It may occur when there is a septal defect with from from Rt to Lt
Lecture 4, Understand problem on slide 23
Understand problem on slide 23
Review Questions
- Which lung volumes cannot be measured by spirometry and why not ?
- Explain the hypoxia of diffusion limitation.
- 100% shunt cannot be treated with oxygen therapy. Explain why not.
- Explain why blood flow is higher at the base of the lung than at the apex
- What would the immediate effect on arterial blood gases be, if a patient had a sudden complete occlusion of the main pulmonary artery with a huge thrombus?
Answer these
Why do we even need a respiratory system?
To get Oxygen to the tissues
To breath the CO2 out
TRANSPORT OF O2
Once Oxygen gets into the blood, it needs to be transported to the different tissues where it is taken up by the ____________.
It is transported as dissolved O2 and bound to ____________.
A significant property of O2 is its ___ solubility. Applying Henry’s law, the dissolved O2 at a PaO2 of 100 mm Hg will equal ___ ml/100ml of blood. If cardiac output is 5000 ml/min, the flow of O2 into the pulmonary capillary blood would be only 50 X 0.3 = 15 ml/min (minimum amount required for survival is 250 ml/min). Therefore, an active transport mechanism is needed.
mitochondria
Hemoglobin
low
0.3 ml/100ml
HENRY’s LAW
States that the amount of gas dissolved is __________ to the partial pressure of the gas.
For every mm Hg of PO2, there is 0.003ml O2/100 ml of blood
If the paO2 is 100 mm Hg, the blood contains 100 X 0.003 = 0.3 mls O2/100 mls of blood
Clearly, this method is inadequate to carry the oxygen that is needed.
proportional
HEMOGLOBIN
____ is an iron-porphyrin compound, and this is joined to the protein ______, which consists of _ polypeptide chains. The chains are of two types, alpha and beta, and differences in their amino acid sequences give rise to various types of human hemoglobin.
Hemoglobin _ is adult Hb, Hemoglobin _ is fetal Hb, Hb _ is Sickle cell Hb, and there are several other types that have differing affinities for Oxygen.
Abnormal Hemoglobins such as Sulfhemoglobin and Methemoglobin are not useful for __ carriage
Heme globin 4 A F S O2
Hemoglobin = _ binding sites for O2
4
How much Oxygen can be carried by Hemoglobin?
• The Oxygen carrying capacity of Hemoglobin (Hb) is ___ ml O2/g of Hb
• Average Hb concentration in blood is __ g/100 ml
• O2 carrying capacity of Hb = 15 x 1.39 = 20.85 ml O2/100 ml blood
• Thus Oxygen delivery using Hb can be 1043 ml/min if Hb is saturated ««< ____ ml/min needed!
• Some use 1.34 or 1.36 ml O2/g as conversion factor
( Met Hb)?
• ___________ is a much bigger player in Oxygen transport than dissolved Oxygen
• 100% capillary saturation means that Hb is fully saturated with __ to its max carrying capacity
1.39 ml O2/g of Hb 15 g/100 ml 5000 Hemoglobin O2
Oxygen Saturation of Hemoglobin
• Percentage of available sites that have __ attached
• (O2 combined with Hb / O2 capacity) x 100
• O2 saturation of arterial blood with pO2 of 100 mm Hg is ___% or P___
• O2 saturation of mixed venous blood with a pO2 of 40 mm Hg is about __% or P__
• O2 saturation in blood with pO2 of 26.5 mm Hg is about __% and is called P__
O2
97.5
75
50
Arterial oxygen content and oxygen delivery: • Arterial O2 content: CaO2 = • Oxygen Delivery DO2 = DO2 : CaO2 : SaO2 : paO2 : CO:
CaO2 = (Hb x SaO2 x 1.34) + (paO2 x 0.003) (per 100ml) DO2 = CaO2 x CO x 10 (per L) DO2 : Oxygen Delivery CaO2 : Oxygen Content (g/100ml) SaO2 : Oxyhemoglobin Saturation paO2 : Arterial Oxygen Tension CO: Cardiac Output (L/min)
Arterial oxygen content and oxygen delivery: • Arterial O2 content: CaO2 = • Oxygen Delivery DO2 = DO2 : Oxygen Delivery CaO2 : Oxygen Content (g/100ml) SaO2 : Oxyhemoglobin Saturation paO2 : Arterial Oxygen Tension CO: Cardiac Output (L/min) Calculate the Oxygen delivery/min in a 35 year old healthy male, with Hb of 15 g/100ml, and Arterial PO2 =100 mm Hg Hb saturations are 98%
CaO2 = (Hb x SaO2 x 1.34) + (paO2 x 0.003) (per 100ml) DO2 = CaO2 x CO x 10 (per L)
Calculate the Oxygen delivery/min in a 35 year old healthy male, with Hb of 15 g/100ml, and Arterial PO2 =100 mm Hg Hb saturations are 98%
CaO2 = (15 g/100ml x 0.98 x 1.34) + (100 mmHg x 0.003) = 20 g/100ml DO2 = 20 g/100ml x 5 L/min x 10 = 1000 ml/L
Select the best answer Arterial Oxygen Content
A. Is the Partial Pressure of Oxygen in the artery
B. Is dependent on the concentration of inspired O2
C. Is dependent on Hemoglobin saturation with O2
D. B and C are correct E. Is dependent on cardiac output
B. Is dependent on the concentration of inspired O2
C. Is dependent on Hemoglobin saturation with O2
Oxygen dissociation curve:
Lecture 5, slides 16-25
KNOW THIS
Oxygen dissociation curve:
Shift to the left = Avid binding, less release
Avid binding, less release
Oxygen dissociation curve:
Shift to the right = Less binding, easier release
Less binding, easier release
Shift to the right = Less binding, easier release
Less binding, easier release
Oxygen dissociation curve:
SHIFT TO THE LEFT results in……
CAUSED BY:
INCREASED AFFINITY OF Hb FOR O2 Alkalosis Carbon Monoxide? Reduced CO2 Decreased temperature Decreased 2-3 DPG (end product of red cell metabolism)
Oxygen dissociation curve:
SHIFT TO THE RIGHT results in……
CAUSED BY:
REDUCED AFFINITY OF Hb FOR O2. (UNLOADS EASILY) Acidosis Increased pCO2 (the Bohr effect) Increased temperature Increased 2-3 DPG
2,3-diphosphoglyceric acid (2,3-DPG):
• _______ effector of Hb affinity for oxygen
• Binding ________ affinity promoting release
• Synthesis of 2,3-DPG is controlled by local __ as part of normal glycolytic pathway
• High levels of 2,3-DPG during pregnancy facilitate transfer of _______ to fetal blood as fetal Hb is much less sensitive
Allosteric
decreases
pH
oxygen
A six year old boy has been running a race for 10 minutes. His oxygen dissociation curve
A. Loses its sigmoidal shape
B. Shifts to enhance delivery of Oxygen to tissues
C. Binding of oxygen to Hemoglobin occurs at a lower paO2 compared to usual
D. The boy has adapted by increasing Hemoglobin to increase arterial oxygen content
E. Hemoglobin changes its configuration to carry more oxygen/gram of Hemoglobin
B. Shifts to enhance delivery of Oxygen to tissues
Lecture 5, slide 25…….Acclimatization
? Get it
Lecture 5, slide 26……, CO
? Get it
Transport of Carbon Dioxide
• CO2 is __ times more soluble than O2 and 10% of gas is carried as such:
• CO2 + H20——— H2CO3 ——- H+ + HCO3- (__% as bicarb)
• Carbamino compounds CO2 + amine groups in blood proteins, including Hb account for __%
- Formation of reduced Hb (HHb) helps load ___ in the tissues.
- The presence of oxygenated Hb in the lung helps unload ___, which can be breathed out
- This is called the _______ Effect
20
60
30
CO2
CO2
Haldane
SEE SLIDE 28. Lect 5 for diagram!!!!
CO2 dissociation curve is more _____ than the O2 dissociation curve……..for a smaller _______ change of CO2, there is a relatively larger change in CO2 ___________
linear
pressure
concentration
SEE slides 29 and 30, Lect 5 for diagrams!
Dissociation of Carbon Dioxide
A. From tissue to the blood is diminished in low oxygen states
B. Follows a sigmoidal curve
C. Is related to Hemoglobin concentration
D. Occurs in an oxygenated milieu
E. Depends on the solubility coefficient of CO2
D. Occurs in an oxygenated milieu
Review Questions
- In the absence of the Haldane effect, how could CO2 tension in arterial blood be decreased?
- Describe the effects on O2 dissociation curve during exercise
Answer these
