Physiology/Pathophysiology Flashcards
What cell types comprise the lining of the respiratory tract?
- Cuboidal (ciliated pseudostratified columnar) with goblet cells (mucous secreting) line the majority
- In bronchioles, club cells replace goblet cells
- In the alveoli:
- Type I (95% of surface area)=modified squamous epithelium
- Type II (~ 2x as many of these however)=cuboidal, produce surfactant
- Phagocytic alveolar macrophages
Define collateral ventilation.
What are 3 possible pathways for collateral ventilation?
- Ventilation of alveolar structures through passages that bypass the normal airways; without collateral ventilation, alveoli distal to obstructed airways (in disease) would become atelectatic
- Possible pathways:
- Interalveolar communications through the Pores of Kohn
- Between the bronchioles and the alveoli through the canals of Lambert
- Interbronchiolar communications of Martin
Describe the changes in breathing/respiratory pattern that occur with an upper airway obstruction.
- During inspiration, airways outside the thorax experience a transmural pressure gradient directed towards the lumen that tends to make them collapse (low pressure within, high pressure outside)
- Patients with upper airway obstruction present with inspiratory dyspnea
- Increasing respiratory effort worsen these conditions, since they augment the pressure gradient and cause a worsening of the collapse
-
Paradoxical abdominal movement (abdominal wall moves in instead of out during inspiration)
- URT obstruction, pleural effusion, reduced pulmonary compliance and diaphragmatic rupture/paralysis
Explain the principle responsible for the appearance of expiratory dyspnea with lower airway disease.
Durring passive exhalation with healthy lower airways, transmural pressure gradient that tends to collapse the small airways is resisted by the attachment of elastic tissue in the alveolar septa.
When lower airways are diseased, intima thickened by inflammation and the lumen reduced by mucus, the same transmural pressure will end up collapsing these airways.
When severe, leads to air trapping, some degree of active exhalation.
Increased transmural pressure during forced exhalation preciptates small airway collapse and manifests as an expiratory effort.
What is Poiseuille’s law?
Raw=8nl/πr4
n= viscosity, l=length, r= radius
Indicates that airway resistance is inversely proportional to the 4th power of the radius–airway narrowing profoundly increases airway resistance.
Where is the location of greatest pulmonary airway resistance?
-
Medium sized bronchi (diameters >2mm)
- One would think that as the airways become smaller, the resistance would increase, however, as the airways branch further and further down, the cross-sectional area of the tracheobronchial tree actually increases…
Define pulmonary compliance.
- Change in volume divided by change in pressure
- Lungs with high compliance can easily be distended such that a small increase in pressure causes a large increase in volume
- Steep slope on PV curve
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Less compliant lungs require a large distending pressure to effect a small change in volume
- Shallow slope on PV curve
Define hysteresis
- At any volume, the pressure on the expiratory curve is less than that of the inspiratory curve
- As tidal volume increases, the difference between the inspiratory/expiratory curve increases
- Occurs because the pressure generated by elastic recoil on expiration is always less than the distending transmural pressure gradient required to inflate the lung
- Hysteresis of the lung as a whole may be due to recruitment of new alveoli or small airways on inspriation and derecruitment/closing on expiration
What is the purpose of surfactant and where is it produced?
- Surfactant is produced by the type II pneumocytes
- 90% lipid–dipalmitoyl phosphatidylcholine;
- Surface protein B&C: hydrophobic; asociated with lipid film, regulate absorption of lipid to the surface
- Surface proteins A&D: hydrophilic. role in innate antimicrobial defense.
- Lines the alveolar surfaces, lowering the elastic recoil due to surface tension, even at high lung volumes
- Increases the compliance of lungs, decreasing inspiratory work of breathing
- Surface tension of different-sized alveoli unequal; smaller alveoli have lower surface tensions, equalizing alveolar pressures within the lungs
Discuss the concept of a lung unit (fast/slow alveoli) and how alterations in compliance and resistance affect the speed with which lung units fill and empty.
- The volume with which each lung unit fills depends upon its compliance and resistance
- Lung units with normal/low resistance, but low compliance fill rapidly
- Fast alveoli/short time constant
- Lung units with high resistance, but normal/high compliance fill slowly
- Slow alveoli/long time constant
- Flow applied to different lung units for same amount of time, will result in a difference in volume–units have different time constants!
What is the pendelluft effect?
- Refers to non-homogeneous filling; fast alveoli will fill quickly and transfer to the slow alveoli, filling over time
- In patients with airway disease/abnormal compliance, can be transient gas movement out of some alveoli and into others as a result of lung units with different time constants, even when flow has ceased at the mouth
- Filling of a lung region with a partially obstructed airway will lag behind the rest of the lung such that it may continue to fill even when the rest of the lung has begun to empty, with gas moving into it from adjoining lung units.
Compare static versus dynamic compliance
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Static compliance
- Compliance calculated after an inspiratory hold (inflate to full inspiration, hold so no air can enter/leave, pressure will fall)–estimate of the true compliance of the lung tissue
- Independent of airway effects (resistance)
-
Dynamic compliance
- Calculate without an inspiratory hold--gas is moving–using the pressure measured at peak inspiration, incorporates airway resistance
Static compliance will ALWAYS be higher than dynamic compliance
What are the equations for:
Static compliance
Dynamic compliance
- Static Compliance: Delta volume/(plateau pressure-PEEP)
- Dynamic Compliance: Delta volume/(peak pressure-PEEP)
What is alveolar ventilation?
- The volume of fresh gas entering the alveoli per minute
- (VT-VD)/f
- (have to remember how to calculate dead space!)
Define minute ventilation.
Volume of air breathed per minute
VT x f
Define anatomic dead space.
The volume of the conducting airways (150ml in people…)
Define physiologic dead space.
Encompasses anatomic+alveolar dead space
The volume of the lung that does not elimate CO2
**Physiologic and anatomic dead space are almost the same in normal patients, however, the physiologic dead space is increased in many lung diseases (because alveolar dead space is increased**
List conditions that can increase anatomic dead space.
- Increasing body size
- Increasing age
- Increasing lung volume
- Sitting posture
- Hypoxia (bronchoconstriction)
- Lung disease (emphysema)
- Endotracheal intubation
List conditions that can increase physiologic dead space.
- Increasing age
- Decreased pulmonary artery pressure
- IPPV (leads to increased pulmonary vascular resistance, decreased pulmonary blood flow)
- Increasing tidal volume
- Hyperoxic vasodilatation
- Anesthetic gases
- Lung disease (ALI/ARDS, PTE, atelectasis)
What is Fick’s law of diffusion?
Vgas= (As x D x deltaP)/T
Vgas=volume of gas diffusing per minute
As=membrane surface area (can be altered by changes in pulmonary capillary blood volume, CO, pulmonary artery pressure, changes in lung volume)
D=diffusion coefficient of gas (dependedn on gas and properties of alveolar/capillary membrane)
deltaP=partial pressure difference of gas
T=membrane thickness (can be altered by changes in pulmonary capillary blood volume, CO, pulmonary artery pressure, changes in lung volume)
What is the Bohr Equation for Dead Space?
VD/VT= (PaCO2-PECO2)/PaCO2
In people, if dead space is >0.6, weaning from the ventilator is considered to be unlikely….
Discuss diffusion versus perfusion limited gases.
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Diffusion limited
- Partial pressure of gas in pulmonary capillary blood equilibrates fully with the partial pressure of the gas in the alveoli while the blood is adjacent to the alveolus
- Properties of the barrier and the diffusivity of the gas limit its transfer
- CO–only increasing the available surface area for diffusion will increase its uptake
-
Perfusion limited
- Diffuse extremely rapidly
- Alveolar pressures of these gasess equilibrate completely with mixed venous blood before blood has left the alveolar-capillary unit
- Additional diffusion is only possible once new blood arrives at the alveolus
- **Nitrous oxide; under normal conditions, O2 and CO2 are perfusion limited, but some diffusion limitation may occur under some conditions**
List the potential causes for hypoxemia.
Which are the most common?
- Low FiO2
- Hypoventilation
- Venous admixture
- Low V/Q regions
- No V/Q regions
- Shunting
- Diffusion impairment
**hypoventilation, V/Q mismatch, shunt**
What may lead to diffusion impairment?
Is this O2 responsive or not?
- Processes that may thicken the barrier (interstitial/alveolar edema, fibrosis)
- Processes that decrease surface area (low cardiac output, tumors, emphysema)
- Processes that decrease RBC uptake of O2 (anemia, low pulmonary capillary blood volumes)
- In general, is a relatively uncommon cause of hypoxemia; the flat, type I pneumocytes have to be damaged enough that in the healing phase, thick cuboidal type II pneumocytes proliferate.
- Partially O2 responsive
What are some causes of hypoventilation and how does it lead to hypoxemia?
Is it oxygen responsive?
- Drugs (morphine, barbiturates) that depress drive to respiratory muscles, damage to the chest wall, paralysis of respiratory muscles…
- Always leads to an increase in PCO2; will decrease PO2 unless additional O2 is inspired
- Quite O2 responsive:
- Adding FiO2 has a substantial benefit on oxygenation even in the face of increased CO2 concentrations–increasing the FiO2 displaces nitrogen and allows more of the total partial pressure in the alveolus to equilibrate
How do you calculate the A-a gradient and what does it signify?
PAO2-PaO2
Where PAO2=(PB-PH2O)xFiO2 - (PaCO2/R)==the alveolar air equation!!
- PB=barometric pressure; 760mmHg at sea level
- PH2O=partial pressure of water vapor in air; typically 47mmHg
- FiO2=fractional inspired concentration of O2; 21% on room air
- PaCO2 comes from your blood gas
- R=respiratory quotient; use 0.8
And PaO2 comes from your arterial blood gas.
Typical A-a gradient is <10-15mmHg; calculated as a way to signify efficiency of gas exchange
- Values greater than this represent decreased oxygenating efficiency=venous admixture
**At sea level, breathing room air, the alveolar air equation can be shortened to PAO2=150-PaCO2**
What are the main capacitance vessels in the lungs?
The pulmonary capillaries (distend markedly with pressure, important for the capacitative effects)
Describe hypoxic pulmonary vasoconstriction.
Alveolar hypoxia/atelectasis causes active vasoconstriction in the pulmonary circulation, shunting blood away from hypoxic or poorly ventilated areas of the lung and redirecting it to better ventilated areas.
Mechanism is not well understood, but is a local respone, with hypoxia acting directly on pulmonary vascular smooth muscle to produce contraction and subsequent vasoconstriction.
Not a very strong response because of the small amounts of smooth muscle in the pulmonary vasculature.
Describe the PO2 and PCO2 levels in units with…
Low to no V/Q?–causes of low to no V/Q?
High V/Q?–causes of high V/Q?
-
Low V/Q: low PO2 and high PCO2
- Low V/Q regions caused by small airway narrowing d/t moderate edema, pneumonia, hemorrhage, etc
- No V/Q regions are full small airway obstructions
-
High V/Q: high PO2 and low PCO2
- Receives no blood flow but continues to ventilate
Describe the differences in ventilation/perfusion in a given lung unit based upon its position within the lung (i.e top to bottom)…
- There is a very HIGH V/Q ratio at the top of the lung, where there is minimal blood flow
- There is a LOWER V/Q ratio at the bottom of the lung, where there is much higher blood flow
Ventilation increases slowly from top to bottom of the lung, whereas blood flow increases more rapidly.
Describe the concept of a shunt and the 3 types of pulmonary shunting that can occur.
- Shunting refers to blood that enters the arterial system without going through ventilated areas of the lung.
- Types:
-
Anatomic (physiologic vs pathologic): systemic venous blood entering the left ventricle wihout having traversed the pulmonary vasculature.
- Physiologic: 1-2% of CO enters the left side of circulation without passing through pulmonary capillaries
- Pathologic: right-to-left intracardiac shunts (i.e. tetralogy of Fallot)
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True shunts/absolute intrapulmonary shunts
- Mixed venous blood perfuses pulmonary capillaries that are associated with totally unventilated or collapsed alveoli. No gas exchange occurs here as this blood passes through the lung.
-
Shunt-like states:
- Collections of alveolar-capillary units with low V/Q ratios that act to lower the arterial O2 content because blood draining these units has a lower PO2 than blood from units with a high V/Q ratio
-
Anatomic (physiologic vs pathologic): systemic venous blood entering the left ventricle wihout having traversed the pulmonary vasculature.
- Hypoxemia associated with shunting responds poorly to added inspired O2 (if 100% O2 is inspired, the arterial PO2 will not rise to the expected level)
How do you calculate the shunt fraction?
How do you interpret the values?
QS/QT= (CCO2-CaO2)/(CCO2-CvO2)
Where:
- QS=shunt flow
- QT=total cardiac output
- CcO2=calculated pulmonary capillary blood O2 content
- CaO2=arterial oxygen content
- CvO2=mixed venous oxygen content
Doesn’t necessarily indicate how the deviation away from normal oxygenation occurred, rather, it calculates what fraction of the CO would have to be “shunted” away from the gas exchange surfaces in order to account for the documented hypoxemia.
Venous admixture is usually <5%; values >10% considered to be increased and may increase to >50% in severe diffuse lung disease
What is the formula for calculating arterial oxygen content?
CaO2=(1.34 x [Hgb] x SaO2) +(0.003 x PaO2)
What is the Bohr effect?
Increases in the carbon dioxide partial pressure of blood or decreases in blood pH result in a lower affinity of hemoglobin for oxygen
(The effect pH and pCO2 have on HGb/O2 affinity)
Draw the oxyhemoglobin desaturation curve; what are the useful “anchor points”, and what causes a right or left shift (and what do these “shifts” mean?)
- Anchor Points: PO2 40=SO2 75%, PO2 100, SO2 97%
-
Right Shift:
- Increase in temperature
- Increase in PCO2
- Increase in H+ (and thus a decrease in pH)
- Increase in 2,3-DPG (end product of RBC metabolism, will occur in chronic hypoxia)
-
Left Shift:
- Decrease in temperature
- Decrease in PCO2
- Decrease in H+ (and thus an increase in pH)
- Decrease in 2,3 DPG
- Presence of CO (has 240x the affinity for Hgb than O2; interferes with the unloading of O2)
*May help to remember that an exercising muscle is acidic, hypercarbic, and hot and it benefits from increased unloading of O2 from its capillaries!**
A right shift means a reduced affinity of Hgb for O2–>more uloading of O2 at a given PO2 in a tissue capillary!!!!
Define the Haldane effect.
Describes the effect of oxygen on CO2 transport
Deoxygenated blood can carry increasing amounts of CO2, whereas oxygenated blood has a reduced CO2 capacity
Which lung volumes cannot be measured with a spirometer?
Total lung capacity, functional residual capacity and residual volume
Define tidal volume
Lung volume representing the normal volume of air displaced between normal inhalation and exhalation
(ml/kg)
“normal breathing/filling of lungs”
Define vital capacity.
The greatest volume of air that can be expelled from the lungs after taking the deepest possible breath
“max inhalation followed by max exhalation–>the exhaled volume”
Define residual volume
lung volume representing the amount of air left in the lungs after a forced exhalation; this volume cannot be measured, only calculated
Define functional residual capacity.
The volume of air present in the lungs at the end of passive expiration (normal expiration)
Define inspiratory reserve volume.
additional air that can be forcibly inhaled after the inspiration of a normal tidal volume
Define expiratory reserve volume.
the additional amount of air that can be expired from the lungs by determined effort after normal expiration
Define inspiratory capacity.
sum of the expiratory reserve volume, tidal volume, and inspiratory reserve volume. The inspiratory capacity (IC) is the amount of air that can be inhaled after the end of a normal expiration
Define hypoxia versus hypoxemia (and severe hypoxemia).
- Hypoxia: decrease in the level of oxygen supply to the tisues
-
Hypoxemia: inadequate oxygenation of arterial blood; defined as PaO2 <80mmHg of SaO2 (SpO2) of <95%
- Severe hypoxemia is PaO2 <60, SpO2 of <90%
When is supplemental oxygen administration indicated?
- When SaO2 is <93% on room air or if PaO2 is <70mmHg
What is the equation for oxygen delivery (DO2)?
DO2= Q x CaO2
Where Q is cardiac output and CaO2 is the arterial oxygen content (remember how to calculate!)
What FiO2 is provided via:
- Flow-By oxygen at 2-3L/min (nasal prongs similar)
- A tight fitting facemask with flow rates of 8-12L/min
- Oxygen hood (after flooding at 1-2L/min); flow rates of 0.5-1L/min
- Oxygen cage
- Nasal/nasopharyngeal catheters with 50-150ml/kg/min flow rate (patient discomfort likely above 100ml/kg/min)
- Transtracheal oxygen at 50ml/kg/min
- 25-40%
- 50-60% (rebreathing is highly possible; awake patient probably won’t tolerate!)
- 30%-40%
- 40-50%
- 30-70%
- 40-60%
Describe how hyperbaric oxygen functions.
- Provides 100% oxygen under supra-atmospheric pressures (>760mmHg) to increase the percent of dissolved oxygen in the patient’s bloodstream by 10-20%
- Dissolved oxygen can readily diffuse into damaged tissues that may not have adequate oxygen supply
- Recommended for treatment of severe soft tissue injuries
What possible risk may be associated with administration of supplemental oxygen to a chronically hypercapnic patient?
- Depression of the hypoxic respiratory drive and can result in severe hypoventialation and respiratory failure
- The hypoxic drive for ventilation is important in these patients–they have chronically increased CO2 levels, and therefore, a diminished central/peripheral O2 response. Arterial hypoxemia in these patients is the principle stimulus for ventilation.
Describe the 5 phases of pulmonary oxygen toxicity.
How long can an FiO2 of 50% be administered to avoid oxygen toxicity?
-
Initiation Phase
- O2 derived free radicals (superoxide anion, perioxide, hydroxyl radicals) cause direct damage to pulmonary epithelial cells as cellular antioxidant stores become damaged
- Occurs within 24-72 hours of exposure to 100% O2
-
Inflammatory Phase
- Massive release of inflammatory mediators leading to increased tissue permeability and development of pulmonary edema
-
Destruction Phase
- Severe local destruction occurs, most associated with patient mortality
- Accumulation of platelets and neutrophils in pulmonary tissue
-
Proliferation Phase
- If patient survives, type II pneumocytes/monocytes proliferate
-
Fibrosis Phase
- Collagen deposition and interstitial fibrosis; can result in permanent pulmonary damage
Administer an FiO2 of 50% for no longer than 24-72 hours (difficult to do without mechanical ventilation :) )
Describe 3 important clinical implications of the relationship of SO2/PO2 on the oxyhemoglobin dissociation curve.
-
Small changes in SpO2 represent large changes in PO2 on the sigmoidal curve
- Difference between normoxemia, hypoxemia, and severe hypoxemia minimal
-
Severe hypoxemia is defined at a level when the hemoglobin is still 90% saturated
- PO2 is the driving force for O2 diffusion down to the mitochondria
- SO2 is the reservoir that prevents the rapid decrease in PO2 that would otherwise occur when O2 diffuses out of the blood
-
Saturation measurements cannot detect the difference between a PaO2 of 100 and 500
- Important when monitoring/tracking patients receiving supplemental oxygen
- Give an example of a disease process that would lead to low V/Q regions (V/Q mismatching). Would this be responsive/non-responsive to oxygen therapy?
- Progression of this disease process may lead to atelectasis, which would represent which type of venous admixture/cause for hypoxemia? Would this be responsive/non-responsive to oxygen therapy?
- Moderate to severe diffuse lung disease–>edema, pneumonia, hemorrhage. Responsive to oxygen therapy
- Atelectasis is a representation of NO v/q units (airway collapse, but they are perfused); typically not responsive to oxygen therapy, requires PPV to open the airways up. Has been referred to as a “physiologic shunt”
What effect would the presence of a PTE (an example of ventilated, but unperfused lung units) have on the net PaO2?
No impact on the net PaO2--essentially there will be alveolar dead space ventilation, with no blood flow to or from these regions
Describe how pulmonary injury may progress to development of a diffusion impairment (which is an uncommon cause of hypoxemia)
- Results due to a thickened respiratory membrane.
- With pulmonary injury, fluid leak will ultimately build up enough pressure that they break into airways causing 1) airway narrowing (low V/Q) and then small airway and alveolar collapse (no V/Q), without a diffusion defect.
- In order for a diffusion defect to occur, flat type I alveolar pneumocytes must be damaged (inhalation/inflammatory injury)
- In the healing process, thick cubiodal type II pneumocytes proliferate across the surface of the gas exchange membrane
- **ARDS, O2 toxicity!**
- Substantial diffusion defect until the type II pneumocytes ultimately mature to type I pneumocytes
Describe the “120 rule” when estimating lung function.
- If a patient is breathing 21% oxygen at sea level, the PaCO2+PaO2 should equal 120mmHg (normal PaCO2 of 40, minimum PaO2 of 80)
- If the value is less than 120, suggests the presence of venous admixture; the greater the discrepancy, the worse the lung function
- ***Only appropriate at sea level and on room air!!!***
Describe how to interpret the PF ratio (PaO2:FiO2)
- Best to use if the patient is receiving supplemental oxygen (use A-a gradient or 120 rule if on room air)–on room air, elevated PaCO2 levels will have an impact on the PF ratio
- Normal values for PF >400mmHg
- <300mmHg=severe defects in gas exchange
- <200mmHg=ARDS suspected
What is Starling’s formula?
What is the Berlin definition for diagnosis of ARDS?
What is the Starling’s formula as it applies to the pleural space?
What are the four phases of the capnogram?
- Flat baseline segment; gas typically CO2 free
- Period of expiration where CO2 containing alveolar gas begins to be exhaled in a mixture of gas from the dead space
- Plateau; PCO2 is almost as constant as alveolar gas
- Rapid downstroke corresponding to inspiration
What are the causes of these abnormal capnograms?
