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373 Cards in this Set

  • Front
  • Back

Functions of the Respiratory System:

Gas Exchange


Acid-Base Balance (CO2)


Phonation


Pulmonary Defense


Metabolism & Bioactive materials

What is the difference between the conducting zone and respiratory zone?

Conducting zone is just a pathway, no gas exchange. The respiratory zone is where gas exchange occurs.

Cross-sectional area (increases/decreases) as you go down the respiratory generations.

Increases

Which zone has a higher cross-sectional area?

Respiratory Zone - favors gas exchange

What generations of the bronchial tree have cartilaginous support?

4-9


No cartilage starting at the bronchioles

What protein works with the microtubules to cause the cilia to stroke?

Nexin

How fast do cilia move mucus?

2 cm/min

Which cells produce mucus?

Goblet cells (100 ml/day)

What type of innervation do Goblet cells have?

Parasympathetic - Vagus nerve

What cell type dominates in the conducting zone?

Ciliated Pseudostratified Columnar Epithelium





Where are Clara cells and what do they do?

Bronchioles and beyond


Secrete proteins and inflammatory modulators

What do Mast cells contain?

Inflammatory mediators: Histamine, lysosomal enzymes, metabolites of arachidonic acid

What cell type dominates the respiratory zone?

Squamous cells (some ciliated)


No goblet cells or smooth muscle

What zone do alveoli start to be seen? Where?

Respiratory Zone; bronchioles

How many alveoli are usually on the end of a duct?

10-15

How many alveoli are in the adult human?

Approximately 300 million

What is the surface area for gas exchange?

70 m2; 280 billion pulmonary capillaries

Which type of alveolar cell manufactures and stores surfactant?

Type 2


What is the function of surfactant?

Decrease surface tension of the alveoli to help keep them open

What are pores of Kohn?

openings in the alveolar septa allowing air to move between alveoli

What are the canals of Lambert?

openings to a secondary bronchiole

Why do we have muscles to inhale?

They generate negative pressure to initiate breath

What is the primary muscle of inhalation?

Diaphragm

What are some accessory muscle to inhalation?

External intercostals


Sternocleidomastoid


Scalenes


Pectoralis

What does the diaphragm look like when it is contracted?

Flat; to allow an increased thoracic volume

What are some muscle of exhalation?

Abdominals


Internal intercostals

Exhalation is ____________ and generates a ____________ pressure.

Passive; Positive

When do we use muscles of exhalation?

To increase tidal volume or respiratory rate


Forced exhalation (cough)

What 2 types of rib/thorax motion help to enlarge the thorax?

Elevation of lateral shaft of rib (bucket handle)


Superior & Anterior movement of sternum (pump handle)

What is the function of the pleural space?

Negative pressure inside links motion of the chest wall and lungs



Events of inhalation

Intrapleural pressure becomes more negative


Alveolar transmural pressure gradient increases


Alveolar pressure falls below atmospheric pressure so air flows in

Events of Exhalation

Intrapleural pressure becomes less negative


Alveolar transmural pressure gradient decreases


Alveolar pressure is greater than atmospheric pressure so air flows out

Chest wall has the natural tendency to (expand/collapse).

Expand

If removed from the body, the lungs tend to expand/collapse).

Collapse

Why is inhalation active?

Force must be exerted to overcome the natural collapsing force of the lung (it naturally wants to be collapsed and is always stretched when in the body).

What keeps the chest wall from expanding infinitely?

Negative pressure of the pleural space

Mechanical ventilation is also known as:

Positive pressure ventilation (because the pleural pressure is being made positive)

What is driving pressure?

The difference between 2 points in a tube.




ex. one side is 20 mmHg and the other is 5 mmHg, driving pressure = 15 mmHg.

What is the formula for transmural pressure?

Pressure inside - Pressure outside

What happens when transmural pressure is positive? Negative?

Positive: expand


Negative: collapse

What is normal lung compliance?

150 ml/cmH20 or 1.5 L/kPa

What is normal chest wall compliance?

200 ml/cmH20 or 2 L/kPa

Which one has the greater compliance: lung or chest wall?

Chest wall

The lung is more compliant when it has (low/high) volumes?

Low

The dynamic compliance/recoil of the lung depends on:

Connective tissue make up of the lung


Surface tension of the lung

On a compliance curve of the lung, more compliance would be a _____________ slope.

Steeper

According to LaPlace's law, how would alveoli get filled if they didn't have surfactant?

All alveoli would have the same surface tension, so Small alveoli (small radius) would have the higher pressure inside, so the gas would empty into the larger alveoli




P=2T/r

What is surfactant?

Surface Active Agent


90% lipid, 10% protein


Hydrophilic and Hydrophobic ends

Why does surfactant effect smaller alveoli more than larger alveoli?

Surfactant is pack more densely in the smaller alveoli than the larger alveoli, so it exerts a greater effect

What is LaPlace's law?

P=2T/r

If there is a surfactant deficiency, you would see these effects in the lungs:

Decreased compliance


Areas of atelectasis


Fluid filled alveoli

What is the definition of FRC?

The point at the end of normal tidal volume where forces of lung recoil are balanced with the chest wall




When both = 0




Also, the volume where gas exchange occurs

What things affect lung compliance?

Lung volume (low volume = increased complnc.)


Pulmonary blood volume (venous congestion can decrease compliance)


Bronchial smooth muscle tone (constriction reduces compliance)


Pulmonary Diseases




NOT Posture

What things affect chest wall compliance?

Ossification of cartilage


Obesity


Scarring

Diaphragm compliance is mainly affected by ______________.

Posture




Also can be increased by obesity

Which has the higher FRC, emphysema or asthma?

Emphysema (needs higher lung volumes)


Asthma (needs higher transmural pressure)

What makes up total pulmonary resistance?

Tissue resistance (friction) - 20%


Resistance to airflow - 80%

Where is the major site of resistance in the tracheobronchial tree?

The first 6 generations

Where is the tracheobronchial tree has the highest total resistance?

5-7 generation

In small airways, what determines resistance?

Volume (high volume decreases resistance)


Pressure gradient (helps keep alveoli open)

In large/medium airways, what determines resistance?

Smooth muscle tone


---PSNS causes bronchoconstriction & secretions


---SNS causes bronchodilation & less secretions

Bronchoconstriction

PSNS


ACh


Histamine


Leukotrienes


Thromboxane


Serotonin


a-agonists


Decreased PCO2 in small airways

Bronchodilation

SNS


B2 agonists


Nitric Oxide


Increased PCO2 in small airways


Decreased PO2 in small airways

During forced exhalation, what causes dynamic airway compression?

The greatly increased intrathoracic pressure caused by the muscles exceeds airway pressure which causes collapse of the airway

During forced exhalation, the airway collapses at a certain point which causes what effect?

Flow limitation - the amount able to be forced out is independent of effort




If the airway didn't collapse, a high rate of flow could be generated.

What part of the lung gets the highest volume?

Apex

What is the closing volume?

The volume the lung can hold when airway closure occurs




Normally 10% of lung volume

What happens to closing volume when you age?

Alveolar elasticity decreases and compliance increases, so closing capacity increases, meaning earlier airway closure


Usually around 40% of lung volume




This can actually start to occur during regular ventilation, which can cause problems with gas exchange

What are other disease state similar to increased age that increase the closing volume?

Asthma - bronchoconstriction without forced exhalation causes airway closure


COPD - Each breath seems like a forced exhalation, can't get all the air out

What volume is total lung capacity?

6 L

What volume is inspiratory capacity?

3 L

What volume is FRC?

3 L

What is the inspiratory reserve volume?

2.5 L

What is normal tidal volume?

0.5 L

What is the expiratory reserve volume?

1.5 L

What is the residual volume?

1.5 L

How large is a vital capacity breath, usually?

4.5 L

What lung volumes can be measured with Spirometry?

Tidal volume


Inspiratory reserve volume


Expiratory reserve volume


Inspiratory capacity


Vital capacity




Residual volume cannot be calculated, that is why we can't get FRC or total lung capacity.

How does a pneumotachometer measure lung volumes?

The pressure differential across a resistor is proportional to flow




Also cannot measure FRC, TLC, or RV

How can FRC be measured?

Helium Dilution Technique


Body Plethysmography

What is the Helium Dilution technique?

The patient uses a spirometer filled with a known volume and concentration of Helium until the concentration reaches equilibrium throughout their system and lungs.




Use C1xV1 = C2xV2 to solve for V2


FRC = V2-V1 (usually overestimated because it only measures central airways and directly communicating volumes

What is Body Plethysmography?

Patient sits in an airtight box and breathes normally until the shutter closes. They are then asked to breath against the closed mouthpiece.




Use P1xV1 = P2x(V1-deltaV) to solve for delta V


Use P3(FRC) = P4(FRC + delta V)

What is the physiologic dead space?

Anatomical dead space + Alveolar dead space

What is the formula for tidal volume?

Alveolar ventilation + Physiologic dead space

How can you decrease dead space?

Decrease tidal volume or respiratory rate

If you have alveolar dead space (air is passing but gas exchange is not occurring) it could be a problem with:

Low cardiac output


Pulmonary embolism


Posture

How can you measure physiologic dead space?

The Bohr Method

What is the Bohr Method?

Collect exhaled gas from a subject over time to get mixed expired gas.




Normal Vd/Vt is about 0.3

How does the apex differ from the base of the lung?

Apex: less compliant, more air at the end of exhalation, pleural pressure is more negative, more ventilation ONLY at low lung volumes, negative transmural pressure




Base: more compliant, less air at the end of exhalation, pleural pressure is less negative, more ventilation, positive transmural pressure, closure of airways occurs here first

Normally, which lung receives more ventilation?

Right Lung

What is the closing capacity?

Residual volume + Closing capacity

What happens to closing capacity with age?

Increases


CC>FRC at age 70 (upright), 45 (supine), 30 (supine under anesthesia)

What is gas trapping?

Caused when CC > FRC or when transmural pressure is more positive (above atmospheric)




Gas becoming trapped distal to the airway collapse (cannot leave the lungs) and does not participate in gas exchange




Results in increased FRC and RV

What are some ways to prevent gas trapping in a patient who's CC is greater than their FRC?

PEEP or CPAP

What is the time constant formula?

Resistance x Compliance

What is 1 time constant equal to?

The amount of time required to fill 63% of the final lung volume

In COPD there is _____________ compliance and the time constant is ______________.

Decreased compliance and shorter time constant, but less volume gets in.

In asthma there is _______________ compliance and the time constant is ________________.

Increased compliance and longer time constant. Alveoli may or may not fill which could lead to shunt.

If alveoli have equal time constants:

Pressure build up will be the same and there will be no redistribution of gases

If alveoli have different time constants:

Depends on rate, duration, and frequency of breathing and redistribution of gases occurs




Compliance decreases with increased frequency

If inflation pressure is sustained indefinitely, volume change in different units depends on __________________.

Compliance

What does an upsloping ETCO2 indicate about time constants of alveoli?

They are different, maldistribution with both fast and slow alveoli

How do you calculate work of breathing?

Pressure x Volume

Ventilatory efficiency is greater when:

You minimize dead space

What happens to resistance, tidal volume, and RR in obstructive disorders?

Resistance increases


Tidal volume increases


RR decreases

What happens to compliance, tidal volume, and RR in restrictive disorders?

Decreased Compliance


Tidal volume decreases


RR increases

Obstructive disorders are more due to changes in _____________ whereas restrictive disorders and more due to changes in ________________.

Resistance; Compliance

What are the 2 routes of venous return from the lungs?

Pulmonary vein


SVC via azygous vein

Pulmonary circulation gets what percentage of blood volume?

10-12%

What influences pulmonary blood volume?

Posture


SVR - constriction increases blood flow


Left heart function - failure causes pulmonary venous engorgement




PBV reacts similarly to venous return

What is the difference in blood flow in the apex compared to the base of the lung?

More blood flow at the base

How do you calculate pulmonary vascular resistance?

PA pressure - Left atrial pressure/ CO




or driving pressure/CO

Why is resistance not as simple as Ohm's law in the pulmonary system?

Laminar/Turbulent combination of flow


Blood in non-Newtonian


Vessels are not rigid tubes (they vasodilate in response to increased flow to decrease resistance)

Resistance in the capillaries depends on:

Alveolar pressure


Pulmonary blood flow

When alveolar volume increases, capillary resistance:

Increases because the alveoli presses on the capillaries, squeezing them

Zone of West 1

Pa > PA > Pv


Apex of lung


Capillaries are flattened by large volumes, alveoli are a part of dead space

Zone of West 2

PA > Pa > Pv


Some blood flow - alveoli will act like a Starling resistor

What is a Starling resistor in the alveoli?

Alveoli fill slightly, increasing the resistance and blocking flow, however the pressure will build at the site of blockage and overcome the resistance to cause flow to return

Zone of West 3

PA > Pv > Pa


Base of the lung


Flow is determined by the A-v pressure difference, not alveolar pressure

Which lung volume has the lowest overall resistance?

FRC - why it is so good for gas exchange

How does the lung respond to increased blood flow?

Recruitment of previously under-perfused BVs


Distension (largest change in capillaries)


---Most important adaptation

PVR ___________ with increased flow.

Decreases

What is the pulmonary system's response to hypoxia?

vasoconstriction (HPV)

HPV responds to:

PAO2 and Mixed venous PO2


Non-linear response

Prolonged HPV -->

Pulmonary HTN --> Right heart failure --> overall heart failure

Most pulmonary HTN is (primary/secondary).

Secondary -- to chronic hypoxia or lung disease

Why are there few drugs to treat pulmonary HTN?

Non-specificity for pulmonary receptors


Drugs would also decrease the HPV response

What are some prostacyclin derivatives to treat pulmonary HTN?

Inhaled NO


--inactivated by Hb


Epoprostenol (IV infusion)


Treprostinil (subQ infusion)


Iloprost, Cisaprost (IV, subQ, inhalation)


--affect platelet aggregation




Vasodilation by increasing cAMP

How do Phosphodiesterase inhibitors (milrinone) help treat pulmonary HTN?

Slow the breakdown of cAMP to increase muscle relaxation

How do ACE inhibitors help treat pulmonary HTN?

They prevent angiotensin II formation, which is a potent vasoconstrictor

Ambrisentan

Endothelin receptor antagonist to treat pulmonary HTN

Inhaled drugs only effect the ____________ circulation, whereas IV drugs effect ____________.

Pulmonary; both

Normal pulmonary artery pressure:

25/8

Alveolar ventilation

Brings in O2 and removes CO2

Venous blood or Perfusion:

Brings in CO2 and sends O2 to tissues

What is the normal V/Q ratio?

0.8

In the supine patient, V/Q is better matched in the (anterior/posterior) section.

Anterior

With increased ventilation what happens to O2 and CO2?

O2 increases in the alveoli and more in the blood


More CO2 gets cleared out of the lungs (lower levels in the alveoli and blood)




Seen in the apex

With decreased ventilation what happens to O2 and CO2?

O2 decreases in the alveoli and in the blood


Less CO2 gets cleared out of the lung (higher levels in the alveoli and blood)

Mixed venous has V/Q =

0 (perfused but not ventilated)

Inspired air has V/Q =

infinite (ventilated and not perfused)

More ________________ at the apex and more ______________ at the base.




Choose either shunt or dead space.

Dead space; shunt

Right to Left shunt

Mixes less oxygenated blood with fully oxygenated blood (shunt)




More physiologic (2-5% normally from the Thebesian circulation)

Absolute shunts vs Shuntlike states

Absolute: venous blood flow to non-ventilated alveoli (one lung ventilation)




Shuntlike: V/Q<1 relatively less ventilation than perfusion (base of the lung)

How can we measure V/Q?

Multiple Inert Gas Elimination Technique (MIGET)

How does MIGET measure V/Q?

It compares the retention and elimination of 6 tracer gases of different solubilities to compute graphs of ventilation and blood flow.

If the shunt is greater than _____%, increasing the FiO2 will likely have little effect on PaO2.

40%

Gas moves by _____________ until it reaches the terminal bronchioles, where afterwards it moves by _______________.

Bulk flow; Diffusion

What is diffusion?

Movement of gas particles down their partial pressure gradient

What does the random movement of molecules have to do with diffusion of gases?

More random movement = more diffusion


(Increased temperature, blood flow, HR)

What determines the partial pressure of a gas?

The dissolved portion in the plasma is equal to the partial pressure. If the gas is attached to hemoglobin it does not contribute to the partial pressure.

What things increase the ability of a gas to diffuse?

Large surface area for diffusion


Large concentration gradient


High solubility


Low molecular weight


Thin membrane

How does carbon dioxide diffuse compared to oxygen?

CO2 diffuses 20 times faster

What is a perfusion-limited gas? Give an example.

Diffusion occurs readily and the amount taken up depends entirely on blood flow.


Ex. N2O

What is a diffusion-limited gas? Give an example.

Blood flow is plenty, but the amount of gas that gets to the blood is limited by the diffusion properties of the gas. This type of gas may never reach equilibrium in the plasma no matter how much blood flow you get.


Ex. CO

How does oxygen normally behave? Perfusion-limited or Diffusion-limited?

Perfusion limited*



When would the alveolar capillary be thickened, impeding normal diffusion?

Pulmonary edema


Pulmonary fibrosis (Sarcoidosis/Scleroderma)

When does oxygen become diffusion-limited?

If the alveolar capillary is thickened


Decreased FiO2


Increased cardiac output states (Exercise)

What are some outside factors that increase diffusion?

Increased pulmonary blood volume


Polycythemia


Supine position


Exercise (slow down time for diffusion, but overall increases the amount of diffusion)

How can we measure diffusion capacity?

Carbon monoxide diffusion test


D = Vco/P1-P2

Why is CO good for a diffusion test?

It is primarily diffusion limited


We don't normally have CO in our bodies


High affinity for hemoglobin


Similar to oxygen

What is a limitation of the CO diffusion test?

We must account for the CO diluted by residual gas in the lungs. We do this by measuring residual volume using the helium dilution test we learned about.

A restrictive disorder results in decreased _____________, whereas an obstruction disorder results in decreased _______________.

Compliance, Resistance

Pulmonary function test data must be compared to:

A PFT of a healthy person of same height, weight, age, sex and race.

What 2 ways is oxygen transported?

Dissolved in plasma


Bound to hemoglobin

How does oxygen "decide" that it will bind to hemoglobin?

When enough oxygen is dissolved in the blood, the PO2 increases to a point where the gradient favors binding to hemoglobin.




When dissolved oxygen leaves into tissues, the PO2 decreases and makes it favorable for hemoglobin to release O2 back into the plasma.

What is hemoglobin made up of?

4 polypeptide chains (2 alpha, 2 beta)


Iron-porphyrin heme compound


--- Fe++ (ferrous state) and porphyrin ring

Most oxygen is found in the __________ state.

Bound (99% to hemoglobin)


1% dissolved in plasma

How many ml of O2 bind to 1 g of hemoglobin?

1.39 ml

What factors cause shifts in the O2Hb dissociation curve?

Temperature


pH


2,3 DPG


PCO2

What does a shift to the left do to oxygen binding to hemoglobin. To the right?

Left shift: Better loading, More tightly bound, harder to release


Right shift: Less loading, Less tightly bound, easier to release

What happens to cause a left shift? Right shift?

Left: Decrease in acidity (pH ^), temp, 2,3 DPG, PCO2




Right: Increase in acidity (pH lower), temp, 2,3 DPG, PCO2

How does 2,3 DPG cause a shift in O2Hb curve?

Binds to hemoglobin, stabilizing the tense conformation to make it hard for oxygen to bind. Causes a right shift.




Depleted levels in stored blood, which may cause a left shift.

What is the Bohr effect?

Alterations in Hb O2 affinity that arises from changes in pH/CO2.

What is the oxygen content equation?

CaO2 = (1.39*Hgb*SaO2) + (0.0031*PaO2)

What is the PaO2 predicted by age?

102 - (Age/3)

Carboxyhemoglobin

CO binds to hemoglobin better than O2


Causes a left shift in O2Hb curve


---Less O2 delivery to tissues


Causes tachy, then VTach and death (40-60%)


Treat with hyperbaric O2 chamber

Methemoglobin

-Fe++ is oxidized to Fe+++ which causes O2 not to be able to bind or be released to tissues. No compensatory increase in cardiac output.


-Decreases O2 content and delivery.


-Treat with Methylene Blue (1-2 mg/kg, don't exceed 15 mg/kg = hemolysis)

Sulfhemoglobin

-Sulfer atom incorporated into porphyrin ring making O2 incapable of binding, causing green blood, and favors sickling if you have that trait.


-Decreases O2 content and delivery with no compensatory increase in cardiac output.


-Cyanosis


-Untreatable, must wait for RBCs to die

Sickle Cell Anemia

Valine replaces glutamic acid


More prone to hemolysis, cells have sickle shape


Sickling occurs at low PaO2


Orthopedic procedures have most risk


Avoid dehydration, hypothermia, acidosis

Fetal Hemoglobin

2 alpha chains, 2 gamma chains


Causes a left shift, greater affinity for O2, P50 is lower

What is P50?

Normal PO2 necessary to obtain a Hb saturation of 50% (27 mmHg)




In Fetal Hb is 19-20 mmHg

What is Perflubron?

Blood substitute that can improve O2 content




Used to help O2 delivery in people with partially occluded circulation after MI

Carbon dioxide has a _____________ solubility than oxygen.

Greater

What three ways is CO2 transported?

Dissolved (10%)


Bicarbonate (60%)


Carbamino compounds (30%)

What is the most common way that CO2 is transported?

As bicarbonate in the red blood cell

How do you solve for CO2 concentration in solution?

PCO2 * solubility coefficient (.03)

What catalyzes the reaction of CO2 to bicarb?

Carbonic anhydrase

What is a carbamino compound?

When CO2 binds to hemoglobin


-- deoxyhemoglobin has a higher affinity which is the opposite of oxygen

CO2 content is altered by:

PCO2


Temperature


Amount & function of carbonic anhydrase


SaO2

What is the Haldane effect?

O2 content effects affinity of CO2 for Hb




At the tissues, O2 is released from Hb and CO2 binds (it has higher affinity for deoxyHb). Then deoxyHb travels to the blood where is releases CO2 as a buffer and picks up O2 again.




Increased PCO2 with Increased PO2

PCO2 is higher in tissues with high __________________.

Metabolic Activity

CO2 has a __________ storage capacity than O2, thus changes in ventilation alter CO2 levels __________ than O2.

Greater, Slower

What are some causes of hypercapnia?

Hypoventilation


Fever/Sepsis


Shivering


MH


CO2 insufflation


Rebreathing

What 3 things cause decreased O2 delivery/Hypoxia?

Decreased PaO2 (hypoxemic hypoxia)


Decreased carrying capacity of blood (anemic hypoxia)


--- CO poisoning or anemia


Decreased tissue blood flow (circulatory hypoxia)


--- Decreased cardiac output, Shock

What are 5 causes of hypoxemia?

Hypoventilation


Low PiO2


Diffusion abnormality


V/Q mismatch


Pure Shunt

What is the primary site of afferent fibers from cranial nerves of the respiratory system?

Dorsal respiratory group located in the nucleus tractus solitarius

What 2 areas are considered in control of expiratory functions/inhibiting inspiratory functions?

Nucleus Retroambigualis


Botzinger complex

What is the hypothesis for how respirations are controlled?

Group Pacemaker Hypothesis: neurons in certain areas depolarize in distinctive firing patterns to influence respiratory muscle function.

What are the 2 main neurotransmitters in control of ventilation?

Glutamate (NMDA receptors) - excitatory


GABA - inhibitory

What does the pontine respiratory group do?

Fine control of respiratory rhythm




Sets lung volume for termination of inspiration




Modulates the response to hypoxia/hypercapnia

What part of the brain gives us voluntary control over our own breathing?

Cerebral cortex

What is Ondine's curse?

Primary Alveolar Hypoventilation: Disease where the only control over breathing is voluntary.

What are the three phases of a cough?

Inspiratory phase


Compressive phase


Expulsive phase

What are the receptors in the lung that collect information to send back to the brain?

Slowly adapting receptors (SARs) - in airways


Rapidly adapting receptors (RARs) - in mucosa

What are SARs activated by?

Changes in lung volume

What are RARs activated by?

Changes in Vt, RR, lung compliance


Irritants

What do "J" receptors do?

Sense tissue damage or PE and cause reflex tachypnea and dyspnea

What nerve senses the breaking point when breath holding?

Phrenic nerve

Which reflex is involved with spontaneous "sighs" to prevent atelectasis?

Hering-Breuer Deflation Reflex

Which reflex may be a part of the gasp reflex?

Paradoxical Reflex of Head

What receptors are responsible for 80% of total respiratory response?

Central chemoreceptors


--Monitor steady state PCO2

What are the main peripheral chemoreceptors and what do they do?

Carotid bodies > Aortic bodies


Detect changes in PO2, PCO2, H+


Undergo hypertrophy in prolonged hypoxia

What are the two different types of responses to hypoxia?

Isocapnic - continued response to prolonged hypoxia and continued increase in minute ventilation, CO2 controlled


Poikilocapnic - increased minute ventilation to a steady state, CO2 not controlled

What is the normal breaking point for breath holding?

50 mmHg

What can you do to give you the max duration of breath hold until breaking point?

Hyperventilation and 100% O2

What drugs that we normally use cause respiratory depression?

Opioids


Benzodiazepines (GABA agonists)

What is doxapram?

Respiratory stimulant - doubles minute volume and increases response to hypoxia and hypercapnia

What is normal VO2 max?

3 L/min

What is VO2 max?

Oxygen consumption when exercising as hard as possible

What structural adaptations does the respiratory system make for exercise?

None, only functional adaptations like muscle endurance and strength, increased VO2 and physiological like increased delivery and extraction


Is the 'weak link' limiting performance

If you have pulmonary disease, how is your response to exercise different?

Higher minute ventilation for the same VO2


Max breathing capacity is lower


--Hypercapnia and Hypoxia may occur


Lower anaerobic threshold

What is the anaerobic threshold?

Point at which you are working above the ability of the body to meet oxygen delivery needs




Lactate production increases with anaerobic metabolism

What is the breaking point?

Inability to keep exercising because of shortness of breath


Usually around 60% of max breathing capacity

What effect do cold gases have on the airways?

Not good for alveolar function -- thickens secretions and can trigger asthma

What are some non-specific pulmonary defenses?

Humidification


Olfaction


Filtration & Clearance (by capillaries into lymph)


Inflammation


Cellular defense (macrophages)

What are the types of aerosol deposition?

Impaction: particles in the nasopharynx > 10-15 mcm


Sedimentation/Gravity: particles in the small airways, 2-5 mcm


Small particles can diffuse in alveoli (Brownian motion) -- leukocytes fight off this type

What are the 2 airway reflexes?

Sneezing


Coughing

What is the ciliary escalator?

Moves debris up towards the glottis at 1-20 mm/min

What innervates the goblet cells?

PSNS - Vagus nerve

What are the chemical mediators of the inflammatory response of the lungs?

Histamine


Complement proteins


Prostaglandins

What is the first line of cellular defense?

Epithelia, then neutrophils & monocytes, then macrophages

What are the specific defenses of the lung?

Antigen/Antibody response


Humoral immunity


Cell mediated immunity

What is the antigen/antibody response?

Antigen are recognized by a histocompatability complex, antibodies are created that bind to that antigen. The antibody-antigen complex is then eliminated.

What is humoral immunity?

B-lymphocytes secrete antibodies

What is cell-mediated immunity?

T-lymphocytes recognize and destroy foreign cells

Why are drugs rapidly uptaken from the lungs?

The lung capillaries have a higher colloid oncotic pressure, so there is more absorption from the interstitial

Why are the pulmonary capillaries a good filter?

They have the highest surface area and all blood pass through there before going into systemic circulation.

When you increase altitude what happens to barometric pressure and inspired PO2?

Barometric pressure decreases as well as PO2

Up _____________ ft we can increase our FiO2 to compensate for the decrease in partial pressure of oxygen.

33,000 ft

What are the 3 main challenges to the respiratory system at high altitude?

Extreme cold


Low humidity


Hypoxia from reduced PO2

What happens with acute exposure to altitude?

Decreased PaO2 and PAO2 -- signs of hypoxia


Hyperventilation (initial: 30 min) -- alkalosis


Left shift in the curve


Polycythemia

How long does it take to acclimatize to a higher altitude?

1 week

After acclimatization to altitude, what changes in respiration do we see?

Increased ventilation


Decreased PaO2


Decreased PaCO2


Increased pulmonary artery pressure equivalent to pulmonary HTN

What is the difference between a high altitude resident and an acclimatized low-lander?

High altitude residents have a decreased hypoxic drive - ventilate less and have higher PaCO2 with the same PaO2 as the low-lander.




Increased vascularity of the heart and muscles.

Hemoglobin levels ____________ in high altitude?

Increase (up to 22 g/dL in Andes residents)

What happens with exercise at high altitude?

VO2 max declines -- can't perform as much work


PCO2 decreases and PO2 increases


The A-a gradient widens


---Diffusion limited oxygenation

What are the 2 main contributing factors to mountain sickness? Who is most likely to get it?

Rate of ascent


Degree of exertion




Young males are more likely to push these limits

What are the symptoms of mountain sickness?

Start at 6600 ft


-headache, fatigue, anorexia, dyspnea, difficulty sleeping


@16000 ft


-feelings of unreality, amnesia

What is High Altitude Pulmonary Edema? Who can get it?

Extreme pulmonary HTN due to hypoxia, possibly due to genetics (excessive response to hypoxia), impaired NO release, increased endothelin




High altitude residents who come back from low-land vacations or overambitious climbers

What is High Altitude Cerebral Edema?

All people at high altitudes have some degree of this. Made worse by hyperventilation response (decreased CO2 decreases blood flow to the brain)




Ataxia, irritability, irrational behavior, hallucinations, somnolence, coma

What is the treatment for high altitude pulmonary edema?

Nifedipine

What is the treatment for mountain sickness?

Acetazolamide

In-flight oxygen is indicated for what individuals?

Normal SaO2 < 92%


Normal PaO2 < 50 mmHg

Cabins are pressurized to ____________ ft so there aren't problems with altitude sicknesses.

8000 ft

What is near drowning?

Initial survival of a drowning accident that leads to secondary, possibly fatal, outcomes

What is secondary drowning?

Death due to the chemical and biological changes in the lungs after a near drowning incident.

When you are immersed in water, what are some changes that your body experiences?

Increased venous return, pulmonary blood volume, cardiac output




Increased work of breathing -- increased compression of the chest

What happens when you aspirate water?

Stimulates swallowing, coughing, glottic closure and larygnospasm




If the water gets to the vocal folds - bronchospasm

What is the diving reflex?

Cold water just on the face:


-bradycardia


-vasoconstriction


-apnea

What happens when you immerse the body in water colder than 25 C?

Potent stimulus for ventilation


- large gasp


- hyperventilation


- breath holding time is severely reduced

What level of PaO2 causes loss of consciousness?

30-45 mmHg

How can someone dry drown?

Laryngospasm continues until cardiac arrest

How do you "wet drown"?

Laryngospasm relaxes when you lose consciousness and water fills the lungs.

Aspiration of how much fluid leads to significant impairments in gas exchange?

1-3 ml/kg

What is the treatment for drowning?

Remove from water in prone position


Perform CPR and ventilate at higher pressures

What is the major determinant of subsequent outcomes of near drowning?

CNS injury

When does secondary drowning occur?

Usually 4 hours after incident, due to acute lung injury, neurological insult, and multiple system failure

What are the contents of a cigarette?

Water, nicotine, tar

What is the most destructive component of the cigarette in chronic smoking?

Tar - accumulates in the lungs

How do you calculate pack years?

packs/day x years

What are the respiratory effects of smoking?

Increased sensitivity of airway reflexes


Inhibited ciliary function


Increased mucous production


Decreased airway diameter -- increased CC


Decreased FEV1

What are the mechanisms of smoke related damage to the lungs?

Oxidative stress (free radicals, increased neutrophil and macrophage activity)


Increased alveolar permeability


Carcinogenesis


Immunologic activation (^IgE, oxidative damage, T-leukocytes -- allergic mechanism to chemicals)

Secondhand smoke increases your risk for:

CAD


Lung disease

What physiological differences are children of smokers born with?

60% increased chance for congenital heart dz


Decreased lung volume


Increased risk of asthma


Increased COHb

Worries with smokers in the preoperative area:

Increased risk for laryngospasm and breath holding on induction


Increased number of desats in the PACU


Increased incidence of post-op resp. compl.

At what length of smoking cessation does it take to get back to normal levels?

8 weeks

What is the half-life of nicotine?

30 minutes

What do volatile gases do to minute ventilation?

Decreased response to building CO2, less minute ventilation




Dose dependent -- effect increases with increased MAC

What is the normal response to hypoxia?

Acute Hypoxic response: increased min.vent.


Hypoxic ventilatory decline: due to decreased CO2 from the acute hyperventilation

What is the response to hypoxia when under anesthesia?

Low oxygen causes no response to increase ventilation!

What are the effects of anesthesia on the airway anatomy?

Posterior movement of the tongue and epiglottis, but not to occlusion until negative pressure ventilation implemented

What are the effects of anesthesia on the airway muscles?

Diaphragm action is preserved


Intercostal muscles have varying degrees of depression


Exaggerated expirations (more muscle activation than when awake)




Looks like abnormal breathing, disturbed coordination

What happens to FRC under anesthesia?

FRC decreases after all anesthetic drugs except ketamine (and possibly precedex)




Possibly due to the change in shape of the chest wall and diaphragm (cephalad)

What happens to respiratory system resistance under anesthesia?

FRC decreasing causes an increased resistance, but volatile agents are bronchodilators so the overall resistance is similar to the awake supine person.

How do volatile anesthetics cause bronchodilation?

Indirect: Inhibit ACh release (bronchoconstrictors)




Ketamine is a direct stimulator of B2.

In addition to decreased FRC, what are some other sources of increased resistance to the airway under anesthesia?

Circuit, connectors, ETT, obstruction/laryngospasm

What happens to compliance of the respiratory system under anesthesia?

Both static and dynamic compliance decreases




Possibly due to atelectasis/reduced FRC

What causes atelectasis under anesthesia?

Decreased FRC


Possibly high FiO2


Compression

How can you prevent the majority of atelectasis?

Use 100% O2 and good mask seal for preoxygenation




or




Preserve spontaneous ventilation (Ketamine)

What hyperinflation?

A recruitment maneuver to re-expand atelectasis




Give vital capacity breaths to at least 30 cmH20, if you use 100% O2 you get a shorter relief. :(

PEEP helps reduce ____________ but does not increase _______________.

Atelectasis; Oxygenation

Use PEEP on:

One lung ventilation


Lung disease


Obese


Small children

What are the major changes in gas exchange under anesthesia?

Increased dead space


Increased shunt


Reduced minute volume


Altered distribution of ventilation

Under anesthesia, alveolar dead space:

Increases proportional to tidal volume

What is the venous admixture/shunt fraction under anesthesia?

10% (this is increased from normal 1-2%)


A-a gradient increases because of this

What causes the increased shunt fraction in anesthesia?

Atelectasis and V/Q mismatch (more ventilation to under perfused areas when laying down)

What is the major cause of gas exchange impairment when younger than 50 vs. older?

younger: shunt


older: V/Q mismatch

The effect of HPV can be inhibited by:

High inspired oxygen (no hypoxia)


Volatile anesthetics

The patient can overcome how much of an increased resistance put on them to continue to breath on their own (overpowering the vent)?

8 cmH20

What do lithotomy and beach chair position do to breathing during anesthesia?

Lithotomy: increased shunt & atelectasis




Beach chair: Increased FRC, but perfusion is in more ventilated areas (oxygenation is not better)

How does obesity affect the pulmonary system under anesthesia?

Decreased FRC -- more prone to hypoxia


Increased BMI correlates with more atelectasis


More V/Q mismatch (decreased ratios)

CO2 absorption during laparoscopy can cause:

Acidosis -- arrythmias


Enhance HPV -- decreased shunt fraction

How does regional anesthesia affect breathing?

Decreased tidal volumes, but no decrease in oxygenation

Which surgery has the largest amount of atelectasis postoperatively?

Cardiac surgery

How should ventilation be changed in one lung ventilation?

Smaller Vt, Increased RR


Lung has decreased compliance b/c of cmprssn.




Collapse of left lung causes less hypoxia than collapse of the right

How is perfusion different in one lung ventilation?

Large shunt (30-50%)


Worse if they are supine with OLV




Recruitment maneuvers can improve this

How does decreased mucociliary function (caused by anesthesia) cause pulmonary complications?

Mucous pooling


Bacterial infections

What drugs can decrease mucociliary function?

Inhaled anesthetics


Atropine


Beta blockers


Poorly humidified air


High FiO2

What happens to the lung volumes of a parturient?

TLC changes little, but FRC decreases (both residual and expiratory reserve volumes decrease)

How does oxygen consumption change in pregnancy?

Oxygen consumption increases


-Increased response to PaCO2 and PaO2


-Increased tidal volume (no change in RR)


-Hyperventilation

What does decreased FRC and increased o2 consumption of the parturient indicate about them?

They are extremely prone to hypoxia!

Why do 60-70% parturients have dyspnea?

Believed to have more sensitive chest wall proprioceptors ...or




possibly due to increased levels of progesterone

What risks does asthma during pregnancy pose to the fetus?

Pre-term delivery


Chorioamnionitis


Pre-eclampsia

Mortality during labor is much higher with ___________ anesthesia.

General

When do the respiratory bronchioles form?

Canalicular phase - 24 weeks

When does most alveolar formation take place?

Postnatally, during the first 12-18 months

When does surfactant appear in the fetus' lungs?

24-26 weeks

What is the purpose of lung liquid in the fetus?

To flush debri and maintain positive pressure to keep the alveoli open

What is the volume of lung liquid in the fetus?

Equal to the fetus' FRC

How often does the fetus practice breath?

20 breaths/hour starting in the 3rd trimester

What 2 hormones can be given to the mother to speed up the development of her fetus' lungs?

Cortisol & Thyroxin

What carries the most oxygenated blood in the fetus?

Umbilical vein

What stimulates the neonate to breath after birth?

Cold stimulus


Mechanical stimulus

What happens to the lung liquid after birth and what trigger it to happen?

The lung liquid gets reabsorbed and drained into the lymph




This is stimulated by oxygen and epinephrine

Upon birth, what happens to PVR and SVR?

PVR decreases (negative pleural pressure is established causing vasodilation of the PAs, oxygen stimulus decreases HPV)




SVR increases (PFO an PDA close, vasoconstriction occurs)

What do neonates have to use their respiratory muscles more to maintain FRC?

They have very high compliance of their chest wall and lungs (5 ml/cmH2O) -- prone to collapse

Where is airway resistance the highest in the neonate?

The bronchial tree -- this causes an increased work of breathing and susceptibility to URI




Neonates tire out easily and consume a large amount of oxygen in respiratory effort

Neonates have a dynamically determined FRC. What does this mean?

They involuntarily terminate their expiration before reaching their actual FRC, resulting in intrinsic PEEP and higher FRC values




This stops around 6-12 months

Adding PEEP significantly helps the neonates compliance, especially at age:

< 8 months

What is different about the distribution of ventilation in a neonate compared to an adult?

The dependent lung, even when awake, gets less ventilation that the independent lung. This is due to their inefficient diaphragmatic contractions.

When does hypoxia actually begin to stimulate breathing in the neonate?

After 3 weeks post-gestational age. Otherwise, they just go apnea. If they are warm, they show hyperventilation first.

What is notable about neonatal airway reflexes?

They are extremely sensitive and any stimulus can cause apnea/laryngospasm

What is periodic breathing in the neonate?

Healthy! The neonate will have up to 200 periodic apneic spells per day, each lasting 5-10 seconds

There is an increased risk of postoperative apnea at what age?

< 41 weeks post-conception




Keep all neonates under this age for 23 hours post-op for observation

What medications can you give to the neonate post-operatively to stimulate respiration if they experience post-operative apnea?

Caffeine


Theophylline

What is the minute volume of a neonate? How does it compare to an adults?

6 ml/kg/min (this is double that of an adult)

Neonates are born with a ____% shunt.

10%, this is larger than in adulthood

Neonatal dead space is ________ of tidal volume.

1/2

What does the OxyHb curve look like compared to an adult for a neonate? An infant?

Neonate: shifted to the left


Infant: shifted to the right

What is the average hemoglobin and hematocrit of the neonate?

Hgb: 18 g/dL


Hct: 53%




For surgery, maintain at least 12-13 g/dL and 40% Hct

Premature babies experience a much ___________ dilutional anemia of childhood than term neonates.

Greater

What is respiratory distress syndrome?

Deficiency of surfactant in the neonate causing and extremely decreased compliance and severe atelectasis, hypoxia, and respiratory and metabolic acidosis

How do we detect respiratory distress syndrome?

Amniocentesis: get a lecithin:sphingomyelin ratio

How do we treat respiratory distress syndrome?

Mechanical ventilation using high inflation pressures with ETT or nasal CPAP




Also possible to do liquid ventilation

What is persistent pulmonary HTN of the newborn?

The PVR remains elevated after birth causing a right to left shunt; no O2 stimulated vasodilation




Possibly caused by meconium aspiration

Which 2 major neonatal diagnoses require the use of ECMO?

Persistent pulmonary HTN of the newborn


Congenital diaphragmatic hernia

Describe liquid ventilation.

Perflubron (carries 20x the O2 of saline) is instilled to the volume of FRC to the neonate's lungs. This allows positive pressure to be maintained, washing out of debris, and decreased inflammation. It then evaporates.




Used to treat RDS sometimes.

What sleeping position should be avoided in order to avoid SIDS?

Prone position

What is the primary response to hypoxia in the neonate?

Bradycardia

Why are neonates heart rate dependent?

Their myocardium is very non-compliant - non-developed SNS, low catecholamine stores

What nerve is stimulated to cause laryngospasm?

Superior laryngeal nerve

What things stimulate increased risk for laryngospasm in neonates?

Hyperventilation


Hypocapnia


Light anesthesia


Increased sensitivity of adductor neurons (reflexes)

What should you do if, during inhalation induction, the neonate laryngospasms?

Provide 5-6 cmH20 PPV

What is the normal PaO2:FiO2 ratio?

4:5

What is the dead space formula?

VD/VT = PaCO2-PetCO2 // PaCO2

What is the normal dead space?

< 0.33 or 33%

What disease states would create a large difference between PaCO2 and ETCO2?

Embolism


Hypovolemic Shock

Can PaCO2 be less than ETCO2?

No, not unless there is a mechanical error due to improperly calibrated machines (wrong atmospheric pressures)

What are some causes of acidosis?

COPD


Extreme V/Q mismatch


Neuromuscular Disorders


Inadequate mechanical ventilation


Neurological Disorders


Excessive CO2 production (MH, Thyroid storm)

What drugs can cause respiratory acidosis?

Barbiturates


Anesthetics


Narcotics


Sedatives


NaHCO3

If you patient is acidotic and hypernatremic, so you cannot give NaHCO3, what can you give to reverse the acidemia?

THAM




But it's expensive and can cause spasms, phlebitis, or thrombosis at the site of injection because of it's alkalotic pH.

What can cause respiratory alkalosis?

Hypoxemia


Overzealous mechanical ventilation


Restrictive lung disorders


Fever


Anxiety


Trauma/Shock

What is the formula to calculate anion gap?

Na - (Cl + Total CO2)

What is the normal anion gap?

12-16 mEq/L

What does an increased anion gap mean?

An increase in fixed acids

What does a decreased anion gap mean?

Could have hypoalbuminemia

What can cause metabolic acidosis with a high anion gap?

TALK




Toxins (ASA, methanol, ethylene glycol)


Azotemic Renal Failure


Lactic acidosis


Ketoacidosis

What is the most common cause of metabolic acidosis?

Lactic acidosis due to increased anaerobic metabolism.

What is the number one cause of lactic acidosis or excessive need for anaerobic metabolism?

Hypotension/Hypovolemia

What can cause metabolic acidosis with a normal anion gap?

Loss of bicarbonate ions


- Diarrhea


- Overuse of carbonic anhydrase inhibitors (acetazolamide)


- Dilution: giving too much NS


- Eucapnic ventilation post-hypocapnia (corrected hyperventilation)

What can cause metabolic alkalosis?

Hypokalemia


Vomiting


Hyperaldosteronism (Increased RAAS)


Diuretics (especially loop)


Eucapnic ventilation post-hypercapnia (corrected COPD)

What can you look at on the BMP to tell you how bad somebody's COPD is?

Total CO2 - correlates to bicarb levels




Really high may be a pretty bad COPD